Case 1 was a 71-year-old man with a BMI of 29.7 kg/m2. Laparoscopic low anterior resection (LAR) and ileostomy was performed for rectal cancer in 2017 years. Postoperative fever and lower abdominal pain were noted, and colonoscopy was performed, and anastomotic leakage was noted with a correction of about 1/2 around the 6 o’clock direction of the anastomotic region, and fistula and formation of a large abscess cavity. After identification (Fig. ), a tube was inserted for drainage and conservative treatment was performed. The patient was discharged on POD 46. Four months after the operation, marked improvement in the abscess cavity was noted but still remained (Fig. a and b). Anastomotic leakage was almost improved by colonoscopy at 17 months after surgery, but at the preference of the patient we performed colostomy 22 months after surgery (Fig. ). It took a long time to improve intestinal movement of the colon because the large intestinal tract had not been used for a long time, and conservative treatment was performed using a nasogastric tube for paralytic ileus. Diet was initiated 7 days after surgery, and the patient was discharged from the hospital 14 days after surgery. The Wexner score [] was 19 points one month after closure, 17 points 3 months after the operation and 16 points after 6 months after the operation, and severe anal dysfunction was observed, but gradually improved.


Case 2 was a 58-year-old man with a BMI of 30.3 kg/m2. Robot-assisted LAR and ileostomy was performed for lower rectal cancer over the past 2017 years, and a 1/2 circumferential fistula around the 6 o’clock direction was recognized on postoperative colonoscopy (Fig. ). The patient was diagnosed as having a grade A anastomotic leakage without symptom because of the anastomotic leakage. He was discharged on POD 26 and was followed up on an outpatient basis. Contrast imaging performed simultaneously with endoscopic examination 6 months after the operation showed remarkable improvement of the abscess cavity, but it still remained (Fig. a and b). The anastomotic leakage improved 11 months after surgery (Fig. ), but a polyp was found on the anal side 2 cm from the anastomotic site and was resected. Adenocarcinoma, pTX, ly0, v0, pHMX, and pVMX were diagnosed. The tumor was followed up because the depth of penetration, the deep stump, and the horizontal stump remained unknown (Fig. ). Regarding the polypectomy site, no abnormality was found in the examination 8 months after resection of the polyp. Therefore, ileostomy closure was performed 18 months after the first operation (Fig. ). Postoperatively, it took some time to improve the intestinal movement with paralytic ileus, but the patient was discharged 18 days after surgery. The Wexner score one month after closure was 18 points and still showed high anal dysfunction but the patient was under observation at the outpatient department.


A 61-year-old woman (case 1 in ) complained of nasal congestion, nasal discharge and atypical genital bleeding. Laboratory testing revealed the following findings: hemoglobin, 8.5 g/dL; platelet count, 25.4×109/L; leukocyte count, 5.7×109/L without atypical cells; lymphocyte count, 0.60×109/L; lactase dehydrogenase, 550 U/L (high); soluble interleukin-2 receptor, 2,920 U/mL (high); immunoglobulin G (IgG), 371 mg/dl; immunoglobulin A (IgA), 51 mg/dl; immunoglobulin M (IgM), 48 mg/dl. The patient was negative for hepatitis B, hepatitis C, human immunodeficiency virus (HIV) and human T-cell leukemia virus type 1 (HTLV-1). Her Epstein-Barr virus (EBV) status was positive for EBV viral capsid antigen (VCA)-IgG, but negative for EBV VCA-IgM and EBV nuclear antigen (EBNA), suggesting that she was in the recovery phase from either initial or chronic EBV infection.
Nasal cavity biopsy demonstrated the infiltration of medium-sized lymphoma cells with constricted nuclei; the cells were CD 3 (+), CD 4 (-), CD 5 (-), CD 56 (-), TIA-1 (+) and EBV-encoded RNA (EBER) in situ hybridization (ISH) (+) ().
In order to observe the spread of the lesions, positron emission tomography-computed tomography (PET-CT) was performed after the biopsy, and the accumulation of 18F-fluorodeoxy glucose (FDG) was observed in the mediastinal nodes, pleura, mesenteric nodes, uterus (bulky mass) and pelvic nodes (). Bone marrow invasion was not noted by bone marrow biopsy.
Uterine cervix biopsy demonstrated the diffuse infiltration of medium to large-sized aberrant lymphoma cells. These cells were CD 10 (+), CD 20 (+), bcl-2 (+), bcl-6 (+), MUM-1 (-), EBER-ISH (-) and MIB-1 (+) (MIB-1 index; 90%) (). Lymphoma-like lesions in the cervix, which were benign lymphoid hyperplasia simulating malignant lymphoma, were excluded, as this patient had a bulky uterine mass.
The patient was finally diagnosed with composite lymphoma composed of ENKL in the nasal cavity and uterine DLBCL. Chromosomal analyses of the nasal cavity biopsy or uterine cervix biopsy were not performed.
Complete remission (CR) was achieved with 8 cycles of R-CHOP (rituximab, cyclophosphamide, adriamycin, vincristine and prednisolone). DLBCL but not ENKL relapsed at 7 months after achieving CR. Combination chemotherapy with 2 cycles of CHASER (rituximab, cyclophosphamide, cytarabine, etoposide and dexamethasone) and 1 cycle of etoposide were administered, resulting in 2nd CR. Autologous hematopoietic stem cells were unable to be harvested from her peripheral blood because of poor mobilization after etoposide treatment. She remained alive for 49 months from the diagnosis without a 2nd recurrence of either type of lymphoma.


A 35-year-old man was admitted to our hospital for evaluation of an intra-abdominal mass.
He had no remarkable medical history. He developed abdominal pain and visited a local clinic
in May 2014. Abdominal ultrasonography revealed a large mass on the right side of the
umbilical region. He was admitted to our hospital several days later. At that time, he did
not have any abdominal pain, but he noted discomfort around the upper area of the umbilical
region. Physical examinations revealed a palpable soft mass on the right side of the
umbilical region, which was consistent with the ultrasonography findings. Laboratory
examinations found no abnormalities, including in the levels of C-reactive protein, lactate
dehydrogenase, and soluble interleukin-2 receptor. He was also negative for the human
immunodeficiency virus (HIV). Contrast-enhanced computed tomography (CECT) demonstrated
thickening of the entire circumference of the wall of the small intestine on the right side
of the umbilical region and multiple soft tissue density nodules in the mesentery. On
positron emission tomography-computed tomography (PET-CT), abnormal accumulation of
fluorodeoxyglucose was localized in the small intestine and multiple nodules (). However, no abnormal accumulation of
fluorodeoxyglucose was observed outside of the abdominal region. Total double-balloon
endoscopy revealed multiple areas with small raised reddish mucosa in the lumen of the
entire circumference of the small intestine. To examine these abnormalities, laparoscopic
lymph node biopsy was performed one month later. Multiple lymph nodules were found in the
mesentery, and a tumor was also found in the small intestine. One lymph node in the
mesentery was removed. On histopathological examination, diffuse proliferation of
large-sized abnormal cells with irregular nuclei and scant cytoplasm in the biopsied lymph
node were observed (). Immunohistochemical
analysis revealed that these abnormal cells were positive for CD19, CD20 (), and Bcl-6, and negative for CD10, Bcl-2, Myc
(below 5%), and MUM-1, consistent with the germinal center (GC) origin according to Hans’
criteria. The Epstein-Barr virus encoded
small RNA (EBER) in situ hybridization was negative. The Ki-67 index was
very high (). According to immunohistochemical
analysis, abnormal cells did not express programmed cell death ligand 1 (PD-L1) (). Proliferation of many collagen fibers suggested
interstitial fibrosis, and apoptotic abnormal cells were also found. Both infiltrating CD4-
and CD8-positive T cells were found in the background of a lymph node, with CD8-positive T
cells being predominant (). According to
immunohistochemical analysis, the CD4- and CD8-positive T cells surrounding the abnormal
cells expressed programmed cell death-1 (PD-1) (). Flow cytometric analysis demonstrated that the abnormal cells were positive only
for CD19 and CD20, consistent with the immunohistochemical analysis. JH rearrangement
examined by Southern blotting exhibited a monoclonal band, suggesting clonal proliferation.
These findings led to the diagnosis of DLBCL, not otherwise specified according to the World
Health Organization (WHO) 2017 classification. Chromosomal analysis using G banding was unsuccessful. Bone marrow
examination revealed no abnormal cells. Thus, he was determined to be at clinical stage IIA.
The international prognostic index (IPI) was classified as low risk. After the laparoscopic
biopsy, the patient felt that his abdominal discomfort gradually improved, and approximately
one month later, he felt free from any symptoms. Of note, there was no abnormal accumulation
of fluorodeoxyglucose on PET-CT three months later (). He did not take any medications, such as anti-cancer agents or prednisolone,
nor did he receive radiotherapy. We considered that his DLBCL spontaneously regressed after
the laparoscopic biopsy. At the time of writing this report, the patient was free from any
symptoms. DLBCL has not recurred for over three years and no abnormal accumulation of
fluorodeoxyglucose has been observed by PET-CT ().


An 18-year-old male patient exhibited a 1-month history of neck pain, restricted neck mobility, and numbness and weakness of both upper limbs. The patient reported no pain at other sites, exhibited no fever or night sweats and was unable to recall any recent injury. A physical examination demonstrated localized tenderness over the C4 spinous process, restricted neck mobility, and numbness and weakness of both upper limbs. Laboratory tests, including full blood cell count, serum electrolytes, and renal and liver function tests did not reveal any abnormalities. Erythrocyte sedimentation rate and C-reactive protein were increased to varying degrees. Computed tomography (CT) revealed C4 vertebral bony destruction (Fig. A–C). Magnetic resonance imaging revealed C4 osteolytic destruction and corresponding flat spinal cord compression thinning (Fig. D). On the basis of the radiological features of the lesion, there was a high possibility that the patient had a tuberculosis lesion. Our department did an anterior approach operation. The position of the internal fixation was found to be satisfactory by X-ray after operation (Fig. E). Postoperative GeneXpert and Mycobacterium tuberculosis (MTB) culture results showed MTB negative. Postoperative pathological results showed: (Cervical 4 vertebrae) LCH. Immunohistochemistry showed tumor cells: CD1a (+++); S100 (+); LCA (+); CD68 (KP1) (+); Vimentin (++); Ki-67 (30%+); CD117 (−); CD21(−); CK(−); EMA(−); Lysozyme(+); MPO(−) (Fig. ). Immunohistochemical staining was positive for CD1a and S-100. No other LCH infiltration was identified in the patient and the patient was treated as suffering from a single-system disease. The patient was treated with prednisone combined with vincristine after operation. There were no serious side effects of the chemotherapy. The patient was discharged from the hospital with complete remission of cervical pain and rapid relief of neurological symptoms. Outside the hospital, the neck was fixed and oral prednisone was continued. Eight months after discharge, the patient returned to our hospital for re-examination. Cervical CT showed that the position of the cervical 3 to 5 vertebral body was satisfactory, and the bone graft area was not collapsed (Fig. F and G). The upper limb muscle strength and sensation were the same as those of discharge, and there was no progression in the state of illness.


A 57-year-old Indian male with HIV-positive status was admitted to our hospital with chief complaints of large-volume watery stools without blood or mucus, 3–4 times a day for 4 months with recent exacerbation for 1 week. This was also associated with nausea, loss of appetite, significant weight loss, generalized weakness, and dysphagia to solids. He denied personal or family history of allergies. He was diagnosed with HIV infection 17 years ago and was on treatment with antiretroviral drugs, namely raltegravir, lamivudine, and efavirenz. He was also diagnosed with pulmonary tuberculosis 5 months back for which he was on treatment with isoniazid, rifampicin, pyrazinamide, and ethambutol. He unintentionally lost 20 kg of weight over the past 4 months. He further denied the use of laxatives or any complementary or alternative medications. He had stable vital signs, was cachectic, and had a normal systemic examination. His workup for chronic diarrhea included a normal thyroid function test and no opportunistic infections or helminthic infestation. Stool analysis including culture was negative for Clostridium difficile toxin, Cryptosporidium, Vibrio cholerae, acid-fast bacteria, or any other parasites. Serum IgE concentration was also within the normal range. Other investigations revealed hemoglobin 11.4 g/dL (13–18 g/dL), platelets 244,000/uL (140,000–440,000/uL), and total leukocyte count 4880/mm3 (4000–10000/mm3) with neutrophils 78.5% (40%–75%), lymphocytes 16.2% (20%–45%), and eosinophils 0.8% (1%–6%). His total protein was 5.4 g/dL (6.60–8.70 g/dL), albumin 1.8 g/dL (3.97–4.94 g/dL), absolute CD4 count 89.91/mm3 of blood (400–1600/mm3 of blood), absolute CD8 count 427.68/mm3 of blood (280–1400/mm3 of blood), CD4 (helper T-cells)% 11.1% (28–58%), CD8 (suppressor T-cells)% 52.8% (19–49%), CD4/CD8 0.21 (1.2–3.3), and HIV-1 viral load by TaqMan plasma (quantitative) 12,59,309 copies/mL.
On further investigations, esophagogastro duodenoscopy revealed white mucosal plaques in the esophagus consistent with esophageal candidiasis. The mucosa of the duodenum showed focal erosions with blunting of the villi as seen in . Urease test was negative for Helicobacter pylori. Mucosal biopsies from the stomach and duodenum were taken. Histopathology study shown in revealed active inflammation in the gastric and duodenal mucosa with excess eosinophils (20 eosinophils/high-power field) and no microorganisms. This was consistent with EGE. He also had a colonoscopy which was normal. Rifampicin was stopped during this admission for a period of 2 weeks. However, the persistence of diarrhea ruled out drug-induced EGE. He was then started on oral prednisolone 40 mg once daily. The frequency of stools decreased and consistency improved. Prednisolone was gradually tapered over a period of 2 months. This was associated with an increase in the frequency of watery stools like before resulting in a readmission with dehydration and weight loss.
The patient was restarted on oral prednisolone 60 mg once daily. Along with cessation of diarrhea, his appetite and weight improved during follow-up after 30 days. On 6-month follow-up, he has regained 18 kg and has normal stools. He is currently on oral prednisolone 40 mg once daily.


A 35-year-old G1P0 woman was diagnosed with preeclampsia with severe features at 34 weeks of gestation and delivered a 1900 g infant. Her renal function worsened after parturition (Cre: 0.78md/dL, eGFR: 68.4 ml/min), and she was diagnosed with renal hypouricemia, with 2.0 mg/dL of serum uric acid and elevated clearance of uric acid
(UA) (17.0 ml/min) along with the exclusion of other disease in which uric acid excretion is accelerated, such as Fanconi syndrome, syndrome of inappropriate secretion of antidiuretic hormone (SIADH), DM, etc. Serum uric acid of her child was also below 2.0 mg/dL. However, she did not desire genetic testing for renal hypouricemia. At her second pregnancy, she was referred to our hospital at 19 weeks of gestation because of her previous pregnancy history. As renal hypouricemia causes acute renal failure due to severe exercise and dehydration, we advised her to drink sufficient water and avoid activities that cause fatigue. We advised her to urinate >5 times/day, excreting >1 litre of urine. We instructed her to measure home blood pressure so that she could respond early to the onset of preeclampsia.
Blood pressure during pregnancy was around 110/60 mmHg. The blood urea nitrogen (BUN)/creatimine (Cre) ratio was not affected during pregnancy and postpartum (Table ). At the first visit, clinical measurements were taken after she had adequate water. Thereafter, dehydration did not worsen, as estimated from the serum BUN/creatinine ratio.
At 38 weeks and 4 days’ gestation, rupture of membranes occurred, and delivery was uneventful (3240 g female infant, with Apgar score 8/9). We had considered administering epidural anaesthesia to reduce the stress during labour but could not implement it because of rapid delivery that happened in about one-and-a-half hours from onset of the active phase.
Her blood pressure during delivery was on the order of 120/70 mmHg, with an upper limit of 138/88 mmHg in the second term of labour. She was given sufficient infusions during labour. Considering dehydration via lactation after parturition, drinking of water after delivery was also encouraged and she was advised to urinate about five times/day. She was well conditioned and was discharged on the fourth day after delivery. Laboratory results at the outpatient clinic did not reveal abnormal findings, including kidney function parameters, 11 days after parturition.


A 70-year-old man was admitted to our hospital with fever and diffuse pain, mainly in cervical area and right shoulder initiated 4 days before the admission. Soon after the hospitalization, he presented with polyarthritis in elbows, wrists, hands, knees and ankles. Three weeks before the present hospitalization, he had a self-limited diarrhea secondary to rotavirus infection. He had no remarkable family history. At physical examination, the patient was bedridden because of pain. He had tachycardia, fever (38°C) and evident polyarthritis in the right wrist, knees, elbows, shoulders, right ankle and right midfoot. The rest of the physical examination was unremarkable. Laboratory tests revealed hemoglobin of 14 mg/dL, total white blood count of 26.690 cells/mm3 with no shift deviation, erythrocyte sedimentation rate of 120 mm and c-reactive protein of 5.14 mg/dL (normal range up to 0.5 mg/dL). He had negative serology for dengue, B and C hepatitis, human immunodeficiency virus and syphilis. Urine culture was negative. Serum uric acid was within the normal range, and the patient had no history of hyperuricemia. The renal function (cretinine = 0.7 mg/dL; creatinine clearance estimate by Cockcroft–Gault = 104.17 mL/min), electrolytes (calcium, phosphorus and magnesium) as well as thyroid function and parathyroid hormone were normal. Transesophageal echocardiography had no evidence of vegetation. Plane radiographs of the joints demonstrated chondrocalcinosis in meniscus of the knees, fibrocartilage of the wrists, metacarpophalangeal joints and elbows articular cartilage (Fig. ). The right shoulder had joint space narrowing and irregularity of the glenohumeral bone surface resembling the one observed in the Milwaukee shoulder syndrome (Fig. ). Unfortunately, we were not able to perform a study to define the type of crystal present in his joints because polarized light microscopy for crystal search was not available in this service.
A regimen of 20 mg/day prednisone was initiated for symptomatic relief of the pain, with only partial improvement. Assuming a presumptive diagnosis of CCPD, colchicine 1 mg/day was started. The patient presented rapid improvement of his arthritis and fever within 48 h of the introduction of colchicine even with the suspension of the corticosteroids. He was discharged in use of colchicine, walking normally without fever and no other complaints.


Chief complaints: A 50-year-old man presented with aggravating thirst, diuresis, blurred vision, and significant weight loss for 1 mo.
History of present illness: One month before admission, the patient suffered from aggravating thirst, diuresis, blurred vision, and significant weight loss of 5 kg in 1 mo. No fever and other symptoms were present during onset of the illness.
History of past illness: The patient had a history of hypertension. The patient has been smoking for 20 years at a rate of 15 cigarettes daily. He also had a family history of type 2 diabetes mellitus.
Physical examination: Physical examination found that blood pressure was 200/100 mmHg, heart rate was 86 beats/min, body temperature was 36.3 °C, and body mass index (BMI) was 25.93 kg/m2. Sporadic chromatosis and mild edema were found in the lower limbs. The rest of the physical examination was normal.
Laboratory testing: The laboratory tests showed elevated hemoglobin A1c (HbA1c) (8.2%), urine glucose (3+), 8-hr ACTH (36.89 pmol/L), 8-hr cortisol (1027.56 nmol/L) and 24-hr urinary free cortisol (12221 nmol). The laboratory results also showed decreased level of serum K+ (2.18 mmol/L), Na+ (135 mmol/L), Cl− (94.9 mmol/L) and Ca2+ (1.84 mmol/L). Concentrations of urine Na+ (339.5 mmol/24 hr) and Cl− (300 mmol/24 hr) were increased. Thyroid function results showed decreased levels of free tri-iodothyronine (2.4 pmol/L) and free thyroxine (10.21 pmol/L). Dexamethasone-suppression test showed that there was no suppression of ACTH and cortisol secretion. These results are shown in Table .
Imaging examination: Findings on laboratory evaluation raised the suspicion of ectopic ACTH secretion that may have originated from SCLC. The conjecture was confirmed by chest X-ray and biopsy (cT2aN3M0). X-rays showed the following: (1) right middle lobe: peripheral LC with lymph node metastasis and distal obstructive pneumonia; and (2) bilateral pleural effusion. Bronchoscopic biopsy showed SCLC. Immunohistochemistry showed: Ki-67 (+ 80%), thyroid transcription factor-1 (+), CD56 (+), Synaptophysin (+). These results are shown in Figure . Adrenal gland computed tomography (CT) showed bilateral adrenal stroma, and pituitary magnetic resonance imaging showed nothing abnormal.


Chief complaints: A 54-year-old woman presented with elevated blood glucose concentration for 3 d before physical examination.
History of present illness: Three days before admission, the patient showed blood glucose elevation at physical examination without obvious clinical manifestations. Her weight loss was 2 kg in 1 mo and she felt slight weakness.
History of past illness: Hypertension (140/100 mmHg) was found at physical examination. The patient had a family history of diabetes mellitus and was an active smoker of 40 cigarettes daily.
Physical examination: Physical examination showed body temperature was 36.5 °C, blood pressure 130/98 mmHg, heart rate 89 beats/min, and BMI 21.37 kg/m2. Systemic examination was normal.
Laboratory examination: The laboratory tests showed elevated hemoglobin A1c (9.4%), urine glucose (1 +), fasting glucose (11.2 mmol/L), 8-hr ACTH (167.1 pmol/L), 8-hr cortisol (> 1710.49 nmol/L) and 24-h urinary free cortisol (12762.25 nmol). The laboratory results also showed decreased level of serum K+ (2.45–3.25 mmol/L) and Ca2+ (1.72–1.94 mmol/L). Thyroid function results showed decreased levels of thyroid-stimulating hormone (0.039 μIU/mL), free tri-iodothyronine (2.8 pmol/L) and free thyroxine (11.72 pmol/L). These results are shown in Table .
Imaging examination: Pituitary punctate enhanced imaging showed nothing abnormal. Positron emission tomography-computed tomography-CT showed a hypermetabolic nodule in the left lingular lobe. An immunohistochemistry test for antibodies showed the presence of Ki-67, thyroid transcription factor-1, CD56, and Synaptophysin. These results are shown in Table and Figure .


A nine-week-old female infant, with an unremarkable birth-medical history, was admitted to the Pediatric Surgery Department for severe abdominal distension and rectal bleeding. Three days prior to admission the mother noted poor feeding, diarrhea and vomiting. The infant’s condition worsened one day before hospital admission, with the appearance of progressive abdominal distention and rectal bleeding. The infant was born at term (weight 3.200 kg) by cesarean section (CS) (due to a previous maternal CS). No antenatal concerns or postnatal medical problems were reported; however, the mother reported a family history of Mediterranean anemia and maternal diabetes.
Abdominal distension () and an enlarged spleen (more than 5 cm below the costal arch) were detected upon physical examination. The baby (weight 5.5 kg) looked markedly pale, and was afebrile (36°C); eupneic (54 breaths/minute) with good oxygen saturation at room air (99%), the heart rate was 160 beats/minute with hypertension (105/52 mmHg). Laboratory investigations revealed severe anemia (Hb 4.6 g/dL), thrombocytopenia (54×103/μL) and coagulation abnormalities: fibrinogen 50 mg/dL vn 150-45 and prothrombin time (PT) 15.7 sec vn 9-12.5; PT% 60 vn 70-120. Liver function tests were normal. A plain abdominal X-ray revealed multiple air fluid levels in the distended small intestine. Abdominal ultrasound showed ascites and splenomegaly (11 cm in longitudinal diameter) with a bossellated mass in the lower part of spleen. Computed tomography (CT) revealed corpuscolated liquid in the abdominal cavity, hepatomegaly and splenomegaly (longitudinal diameter 9.5 cm) with a large isodense mass, without intraparenchymal contrast enhancement, at the lower medial pole of the spleen ().
Based on the triad of pallor, anemia and abdominal distension, in addition to the imaging and biochemical findings a diagnosis of intra-abdominal hemorrhage was hypothesized. The infant received several blood transfusions and underwent monitoring for 24 hours in the Pediatric Intensive Care Unit. The subsequent increase in abdominal distension, appearance of respiratory distress, and persistent abdominal hemorrhage un-responsive to blood transfusions were then considered indications for an exploratory laparotomy. During surgery, a great amount of bloody ascites (more than 1.5 L) were aspirated. Considering the complete transformation of the spleen to bosselated masses of different dimensions (varying from 1 to 2 cm in diameter) and the multiple bleeding capsular ruptures without subcapsular hematoma an urgent splenectomy was performed.
At gross pathologic evaluation the lesion was composed of multiple red-brown nodules diffusely distributed, without a coalescent scar. At histological evaluation the mass showed a multinodular architecture composed of numerous, convoluted, congested vessels without significant atypia of the endothelium. Subtle sclerotic tissue surrounded the vascular structures and an abundant lymphoid infiltrate was intermingled among the vessels. By immunohistochemistry, endothelial cells expressed the vascular markers CD34 and CD31 and positivity for CD8, whereas podoplanin (D2 40), CD21, CD35 e CD 68 were negative. Smooth muscle actin (SMA) stained the perimeter of the vascular structures. No infection by HHV8/ORF73 or EBV/EBER and IGg4 were detected by immunohistochemistry and in situ hybridization, respectively (). The lymphoid infiltrate contained both CD20- positive B and CD3-positive T cell components with no evidence of lymphoproliferative disease.
Elevated polymorphonuclear leukocyte counts were detected after splenectomy; however, no infectious complications occurred and the monthly postoperative follow up has been uneventful. Vaccination against the most common pathogens that can cause post-splenectomy infection and antibiotic prophylaxis were prescribed, together with parental education on the consequences of splenectomy.


A 27-day-old newborn male was admitted in pediatric ward with chief complains of bleeding from the umbilicus and left ear since 1 day. The bleeding was profuse and light pink in color. Child was born at term, to parents with third-degree consanguineous marriage and was exclusively breastfed since birth. There was family history of hyperlipidemia in the mother and immediate maternal siblings.
Preabdominal examination revealed grade III hepatomegaly and grade II splenomegaly.
Ophthalmological evaluation was performed and revealed normal anterior segments of both eyes. Fundus examination revealed pale optic discs with peripapillary atrophy, salmon pink retinal background, and tortuous dilated milky white retinal blood vessels bilaterally, suggestive of lipemia retinalis [].
During sampling, his blood was found to be highly viscous and milky. Total serum cholesterol was 4,560 mg/dl (normal range 50--92 mg/dl), serum triglycerides were 10,350 mg/dl (normal range 30--105 mg/dl), serum LDL was 498 mg/dl (normal range 3--39 mg/dl), and serum HDL was 16 mg/dl (normal range 23--58 mg/dl). Serum Apo B was 171 mg/dl (normal range 55--140 mg/dl).[] Liver, kidney, and thyroid function tests were normal. Hb was 7.6 g/dl.
As genetic testing was not available, the neonate was clinically diagnosed to have lipemia retinalis secondary to familial-combined hyperlipidemia. Other causes of secondary hyperlipidemias, such as obesity, diabetes, liver disease, kidney disease, and hypothyroidism were ruled out in the newborn as well as family members.
The neonate was then weaned on skimmed milk and started on lipid lowering agents. Antibiotics, IV fluids, and blood transfusions were also given. However, the newborn succumbed to sepsis and passed away.
Google Scholar and PubMed databases were reviewed to ascertain the number of cases of lipemia retinalis which have been reported in newborns and infants less than 16 weeks, till the year 2018. To the best of our knowledge only 20 cases have been reported so far [].


A 71-year-old male patient presented with severe pain in the hypogastric region. Ultrasonography revealed anteroposterior abdominal wall defect (3.5 cm) with herniation of loops of the distal ileum and mesentery (SH compatible). A large right inguinal hernia (2.8 cm) was also diagnosed. A minimally invasive combined approach was performed.
A transumbilical incision was performed in the umbilical scar, and an 11 mm trocar was inserted under direct vision. The pneumoperitoneum was created using the open technique, with the visualization of the peritoneal cavity. A 3.5 mm trocar was introduced in the right periumbilical hypogastric region, and dissection of the preperitoneal space was performed with the CO2 and the dissector. The 11 mm trocar was removed and reintroduced into the newly created preperitoneal space. The laparoscopic view confirmed two defects on the right side: one in the inguinal region and the other lateral to the rectus abdominal muscle []. A mini-laparoscopic (3.5 mm) trocar was inserted to the left of the lower umbilical midline into the preperitoneal space under direct vision. Through the Luer-lock of this trocar, CO2 under pressure was injected, and a preperitoneal workspace was created. A 5 mm trocar was inserted in the right flank, also inside the newly created preperitoneal space, for the use of harmonic scalpel. Next, an 11 mm trocar was inserted blindly into the preperitoneal space through the same umbilical incision but through a subcutaneous tunnel in the aponeurotic region that was 2–3 cm below the umbilical orifice. A 3 mm trocar was used on the left flank for the mini grasping forceps. A harmonic scalpel was chosen in this surgery due to the underlying liver disease, cirrhotic (Child-A) patient. We chose to close the two herniary orifices to reduce the risk of recurrence, and the formation of seroma. Besides, we used a fish scale suture to close the defects [], with totally extraperitoneal (TEP) technique. As the two hernias were homolateral, a single mesh (28 cm × 16 cm) was used, which facilitates and reduces the cost of the procedure []. We used haemostatic tissue in the bladder region to decrease bleeding after dissection []. In addition to the use of tackers, a transfascial suture was used to fix the mesh. The 11 mm trocar was removed and reintroduced into the peritoneal cavity to evaluate the position of the mesh. The procedure was uneventful, with a total duration of 125 min. The patient had no further complications, being discharged in the 1st post-operatory day.


A 3-year-old male neutered domestic shorthair cat was referred to our institution for investigation into the cause of an acute onset of icterus. The patient reportedly had no past significant medical history, was previously retrovirus negative, and lived both indoors and outdoors. The cat was up to date on vaccinations but was not receiving any heartworm or flea or tick preventatives. In the 24 h preceding presentation, the patient developed acute vomiting, inappetence, lethargy and icterus. On presentation the patient had a dull mentation, but was responsive to stimuli and had normal vital parameters.
A complete blood count (CELL-DYN 3500; Abbott Diagnostics) was unremarkable. A serum chemistry panel (AU480; Beckman Coulter) and urinalysis (VetStix 11) revealed a marked hyperbilirubinemia (12.2 mg/dL; reference interval [RI] 0–0.9 mg/dL) with bilirubinuria (6 mg/dL), moderately increased alkaline phosphatase (ALP) activity (205 U/L [RI 0–60 U/L]), and moderate hypercholesterolemia (337 mg/dL [RI 80-250 mg/dL]) indicative of cholestasis. There was evidence of hepatocellular injury given the markedly increased alanine aminotransferase (ALT) activity (1863 U/L [RI 0–100U/L]), and moderately increased aspartate aminotransferase (AST) activity (586 U/L [RI 0–60 U/L]). There was a mild hyponatremia (144 mEq/L [RI 148–160 mEq/L]) with a disproportionate moderate hypochloremia (104 mmol/L [RI 115–126 mmol/L]) indicative of fluid losses and a hypochloremic metabolic alkalosis, which was attributed to the patient’s vomiting. A coagulation panel (Amelung KC4A; Sigma Diagnostics) revealed a mildly prolonged partial thromboplastin time (23.3 s [RI 10–17 s]) and normal prothrombin time. Serologic assessment of feline immunodeficiency virus (FIV) and feline leukemia virus (FeLV) were negative (SNAP FIV/FeLV/HW Triple Test; IDEXX).
Initial abdominal ultrasonography was performed within 24 h of admission and revealed variably organized anechoic-to-hyperechoic material within the gall bladder lumen (). The path of the common bile duct could not be followed to the duodenal papilla owing to interference caused by gastrointestinal gas shadowing, as well as inflammation of the surrounding mesentery resulting in attenuation of the ultrasound beam. The left limb of the pancreas was hypoechoic, with adjacent hyperechoic fat. No effusion or free gas was noted, and the remainder of the abdomen was unremarkable. Thoracic radiographs were within normal limits.
The patient was started on antimicrobial therapy consisting of ampicillin sulbactam (22 mg/kg IV q8h [Unasyn; Pfizer]) and enrofloxacin (5 mg/kg IV q24h [Baytril; Bayer DVM]), as well as ondansetron (0.5 mg/kg IV q12h [Ondansetron Accord; Accord Healthcare]) for antiemetic support. Buprenorphine (0.01 mg/kg IV q8–12h [Buprenex (buprenorphine hydrochloride) Injectable; Fresenius Kabi USA]) was also added for analgesia. Forty-eight hours after initial presentation, the patient’s hyperbilirubinemia worsened (23 mg/dL); however, clinical improvement was noted as the patient appeared brighter, comfortable on abdominal palpation and eating well. Continued hospitalization was recommended; however, the owners elected to take the patient home for continued monitoring.
Two days later, the patient was re-presented for repeat blood work and evaluation for anorexia. A serum chemistry panel revealed progressive hyperbilirubinemia (26.4 mg/dL) and a worsening hypochloremic metabolic alkalosis (chloride 99 mmol/l, sodium 143 mEq/l), and hypokalemia (3.2 mEq/L [RI 3.5–5.5 mEq/L]), likely due to anorexia. Repeat abdominal ultrasound revealed mostly hyperechoic, organized material against an interface of anechoic content within the gall bladder lumen (). The cystic duct was abnormally dilated at 2.9 mm, and the common bile duct was tortuous and difficult to follow. The distal portion of the common bile duct measured 5.0 mm at its termination, where normal feline common bile duct diameter is <4.0 mm. The previously noted pancreatic changes had resolved.
The following day the patient was sedated with butorphanol (0.2 mg/kg IV [Dolorex; Merck Animal Health]) and propofol (5 ml/kg IV [PropoThesia; Henry Schein Animal Health]), and general anesthesia was maintained with isoflurane and oxygen. Ultrasound-guided liver aspirates and cholecystocentesis were performed using a 22 G 1 ½ inch needle, followed by esophagostomy tube (e-tube) placement (14 Fr Mila). The fluid obtained from the cholecystocentesis was grossly white and opaque. Esophagostomy tube placement occurred without incident, and the patient was started on one-third of its resting energy requirement via the e-tube with Clinicare Nutritional Support (Abbott). The following morning, a nematode of unknown type (presumed Ollanulus tricuspis or Physaloptera species) was discovered in the lumen of the e-tube. A fecal sample was unable to be obtained for parasitic evaluation, and the patient was discharged with a 3 day course of fenbendazole (Panacur; Merck).
The Wright’s stained smear obtained from the cholecystocentesis lacked the typical cytologic appearance of bile, which is normally acellular to poorly cellular with a granular-to-amorphous purple/gray background. Instead, the background had a hazy proteinaceous-to-mucoid quality with a moderate amount of blood. Leukocytes consisting mostly of mildly degenerate neutrophils appeared increased over the expected contribution from blood. Low numbers of round-to-oval, approximately 2 x 5–7 µm, deep-blue yeast organisms with a thin clear halo were present extracellularly and rarely phagocytized within neutrophils (). No pseudohyphae or hyphal forms were observed. No biliary epithelial cells were present. Rare neutrophils appeared to contain phagocytized blue material, suggestive of mucin (). The cytologic interpretation was mild suppurative inflammation with intralesional yeast organisms. The morphologic appearance of the yeast organisms was suggestive of Candida species and fungal culture was recommended for confirmation.
The Wright’s stained smears of the liver aspirate were moderately cellular consisting of predominantly hepatocyte clusters, moderate numbers of small to moderately sized clusters of cuboidal-to-low columnar epithelial cells, interpreted as biliary in origin (), and moderate numbers of inflammatory cells. The hepatocytes ranged from well-differentiated cells to those that displayed higher nuclear-to-cytoplasmic ratios, increased cytoplasmic basophilia, binucleation and mild-to-moderate anisokaryosis. The atypical hepatocytes were often present in disorganized clusters with streaming noted, suggestive of fibrosis. The hepatocytes contained low numbers of clear, discrete vacuoles consistent with lipid, and small amounts of fine, granular, blue–green lipofuscin pigment. The biliary epithelial cells had a round nucleus with coarsely stippled chromatin and 1–2 indistinct nucleoli. They displayed minimal anisocytosis and anisokaryosis, and rare binucleation. The biliary epithelial cells frequently contained small-to-moderate amounts of pale blue cytoplasmic material, suggestive of mucin (). Elsewhere on the smear, there were loose streams and tight spirals of pale-to-dark-blue mucinous material, which occasionally contained entrapped hepatocytes and non-degenerate neutrophils (). In addition to neutrophils, few plasma cells and macrophages containing non-specific phagocytic debris were noted, supportive of tissue inflammation (not shown). No fungal organisms or other infectious agents were observed in the smears from the liver aspirates.
The cytologic interpretation was mild-to-moderate mixed (neutrophils, lymphocytes, plasma cells and macrophages) inflammation, mild lipid accumulation and probable biliary hyperplasia. While a biliary adenoma, cystadenoma or well-differentiated carcinoma could not be ruled out, this was considered unlikely given the lack of reported nodular and/or mass lesions in the liver. Biliary hyperplasia was favored given their well-differentiated appearance and the concurrent presence of inflammation. The cytologic atypia noted in the hepatocytes was interpreted as reactive, likely representative of a regenerative response in the liver secondary to the inflammation present. The abundant mucoid material in the sample is an abnormal finding for liver aspirates, and the possibility of ‘white bile’, as has been reported with gall bladder mucoceles and extrahepatic biliary obstruction, was raised. Histopathologic examination was recommended to confirm these findings.
The patient continued to tolerate e-tube feedings well, but started to decline systemically. Ten days after initial presentation the cat was found to be obtunded and hypotensive (systolic blood pressure 40–96 mmHg). Recheck packed cell volume revealed an anemia (20% [RI 24–45%]), and recheck chemistry revealed a progressive hyperbilirubinemia (33.8 mg/dL) and persistent liver enzyme increases (ALT 1486 U/L, AST 663 U/L, gamma-glutamyl transferase 17 U/L, ALP 241 U/L). There was also a newly documented mild fasted hyperammonemia (128 µmol/l [RI 0–100 µmol/l]), that in conjunction with the clinical presentation and chemistry results, was supportive of hepatic encephalopathy. Repeat ultrasound-guided cholecystocentesis was performed without sedation using a 22 G, 1 ½ inch needle in order to obtain a sample for fungal culture. Later that evening the patient experienced cardiorespiratory arrest. The fungal culture grew an isolate of C albicans (Cornell University Animal Health Diagnostic Center).


On 4 January 2016, a 48-year-old Chinese female patient was admitted to the Shaoxing People’s Hospital because of nausea, vomiting, dizziness, headache, crooked mouth, and slurred speech. Magnetic resonance imaging (MRI) showed multi-site metastatic brain tumors () and bilateral adrenal gland metastasis (data not shown). Chest computed tomography (CT) scans revealed multi-site metastatic lung tumors (). This patient was diagnosed with GBC via cholecystectomy that was performed because of cholecystitis and gallstones in 2010 (pT3N0M0; TNM staging: IIB; Nevin staging: III) (). Lung metastasis was found in 2014, and brain metastasis was detected in 2015. The patient’s medical history is shown in .
One month after admission, the patient underwent surgery to remove one of the largest metastatic tumors (longest diameter in the transverse plane, 38.96 mm) in the left frontal lobe. The biopsy showed that the metastatic tumor was adenocarcinoma (). The patient was diagnosed with the GBC brain metastasis after a comprehensive review. Genetic profiling of 416 cancer-relevant genes was performed using targeted next generation sequencing (NGS; see Materials and Methods) to develop potential molecular therapeutic approaches. GBC primary tumor and brain metastatic tissues, as well as the circulating tumor DNA (ctDNA) in the blood were collected from the patient for genetic profiling. The sequencing results showed a significant increase in the HER2 copy number in the GBC primary tumor (8.6×), brain metastasis (14.6×), and ctDNA (2.5×) (). Thus, dual-targeted therapy was initiated on 6 March, 2016 using trastuzumab (administered intravenously at an initial dose of 8 mg/kg, followed by subsequent doses of 6 mg/kg once per week for 3 weeks) and lapatinib (administered orally each day at a dose of 1000 mg per day in 21-day treatment cycles), based on previously published work in breast cancer (i.e., one dose of trastuzumab each week and one dose of oral lapatinib each day). No concurrent chemotherapy was administrated.
Three weeks after dual HER2 targeted therapy with trastuzumab and lapatinib, the follow-up chest and brain MRI revealed that the patient achieved a partial response in brain metastatic tumors () and lung metastatic tumors (), after three cycles of treatment based on the Response Criteria Evaluation in Solid Tumors (RECIST) version 1.1. The MRI results showed that the metastatic tumors had shrunk. A concurrent blood sample was collected for genetic testing of ctDNA using targeted NGS. The HER2 copy numbers did not increase at this time (), suggesting that the tumors were cleared after trastuzumab and lapatinib dual therapy. It was also accompanied by a carcinoembryonic antigen (CEA) response (CEA levels decreased from 4030 ng/mL to 660 ng/mL). The patient developed grade 3 adverse reactions including fatigue, skin rash, and increased bilirubin concentration, but no grade 4 or 5 adverse reactions were observed. In summary, dual-targeted therapy with trastuzumab and lapatinib offered a chemotherapy-free option and achieved tumor suppression with an acceptable safety profile for this patient with HER2 amplification in GBC.


A 14-year-old female patient, a known case of OI Type I, came with a closed fracture of the shaft of right femur after a history of fall at home. She was a known case of OI with history of earlier femur and tibia fracture, which were operated uneventfully under general anaesthesia. On general examination, patient weighed 40 kg with short stature of 140 cm, barrel-shaped chest, kyphoscoliosis, and was bedridden. Multisystem examination was normal except kyphoscoliosis. On airway assessment, she had poor dentition, short neck, and Mallampati class II. Her investigations revealed haemoglobin of 13.4 g%, white blood cell count of 10,000, platelet count 2.49 lacs, blood sugar 87 mg/dl, blood urea 17 mg/dl, serum creatinine 0.9 mg/dl, serum potassium 3.4 meq/l, serum sodium 137 meq/l, and serum calcium 8.7 meq/l. Preoperative coagulation profile was normal. 2D echo revealed no valvular abnormalities and a normal ejection fraction (60%). Pulmonary function tests revealed a moderate degree of restrictive lung disease.
The patient was accepted for surgery as American Society of Anesthesiologists physical status III for fixation of femur. The coagulation parameters were normal. Hence in presence of restrictive lung disease and increased chances of difficult intubation, the plan of anaesthesia decided was intrathecal regional anaesthetic technique using USG guidance. Pre-operative preparation included attaching monitors including ECG, Non invasive blood pressure (NIBP), SpO2, skin temperature monitoring and securing 22 G intravenous access in both upper limbs. Wide bore access was difficult to establish. Patient was preloaded with 500 ml Ringer's lactate. Her baseline blood pressure was 114/84 mmHg, heart rate was 72 beats/min, and SpO2 on room air was 98%. Patient was given sitting position with adequate care including padding of pressure points considering brittle bones. Sterile precautions were followed and the patients back was painted and prepared. Linear USG probe was selected and covered by sterile plastic drapes. Due to the kyphoscoliosis, there was extreme difficulty in finding the subarachnoid space as the intervertebral spaces were unequal in length and the tissue planes were distorted, but once clearly visualised with ultrasound [], using out-of-plane approach, 25-G Quincke spinal needle was inserted and 2.5 ml of bupivacaine heavy 0.5% was given in L3–L4. Patient was immediately placed in the supine position and the level of block was assessed using pinprick and motor block with modified Bromage scale. Sensory and motor block were achieved up to T8 level. The surgery lasted for 2 h and 15 min, in which vital parameters were maintained and the recovery was uneventful and adequate.


A 22-year-old African American female presents with juvenile dermatomyositis (diagnosed since the age of 6 years). On arrival at the emergency department (ED), her chief complaints were fatigue, inability to ambulate, and a nonhealing leg wound. Past medical histories include hypertension and a heart murmur.
Home medication regimens are hydroxychloroquine 200 mg by mouth twice daily, prednisone 50 mg by mouth daily, folate 3 mg by mouth daily, and methotrexate 7.5 mg by mouth weekly. All the home medications were continued at the hospital. In addition, the dermatologist ordered the following topical medications: hydrocortisone butyrate cream 0.1%, to apply to all affected areas of the face daily; triamcinolone acetonide lotion 0.1%, to apply to the affected skin or the trunk daily; and fluocinonide acetonide ointment 0.025%, to apply to scalp daily. Scalp oil was also applied nightly to the scalp. The patient was also encouraged to maintain moisturization with Eucerin or Aquaphor. The nutritionist added Boost and Juven supplements to her nutrition.
Her vital signs on admission were as follows: blood pressure 122/68 mmHg, pulse 77 beats per minute, temperature by oral source 97.6°F (36.4°C), respiratory rate 16 breaths per minute, height 1.575 m (5′2″), weight 45.13 kg (99 lb 8 oz), and Spo2 98%.
On physical examination, patient appeared sick and cachectic and stated that she had fatigue, right ear pain, and sore throat. She admitted experiencing shortness of breath (SOB), chest pain, and diarrhea. She had a splitting of the second heart sound and 2/6 systolic murmur. Other findings include rash, tingling, visual change, weakness, and headaches.
There were some facial skin rash and alopecia, which was of concern to the patient. There was a “box”-shaped rash on the chest. The rash was red and scaly covering the central chest region from right to left clavicle extending down below her right breast dissecting her right areola across the sternum to her mid left breast up to her clavicle. Other than tenderness in the suprapubic region, her abdominal exam was unremarkable. The patient displayed atrophy and exhibited abnormal muscle tone with worsening weakness to immobility mainly in the lower extremities.
She had a 3 cm × 7 cm, nonhealing, and nonpruritic ulcer on the dorsal left thigh. In addition, the patient presented with diffused xerosis, hypopigmentation periorally along with linear streaks of hypopigmentation on her face, and some areas of hyperpigmentation on her cheeks, periorbital heliotrope sign. Her scalp displayed erythema and some focal areas of alopecia. The patient’s chest demonstrated poikilodermatous changes, erythematous, and atrophic. Her hands had Gottron papules and dilated nail-fold capillary loops without clubbing.
Three years before this admission (see ), the patient had a calcium (calcinosis) deposit removed from her dorsal left thigh that produced a nonhealing wound and received wound care with multiple treatments without resolution. Three weeks before the admission, the patient coughed up a calcium deposit and was then taken to ED and later released. Intravenous antibiotics she received at that time resulted in the healing of the wound on her dorsal left thigh for the first time in 3 years, but it was inadvertently reopened due to the use of compression cuffs on her legs while in physical therapy. At that time she was issued walker for her mobility.
The patient stopped taking her medications due to pregnancy and at the recommendation of her rheumatologist. During this time, she was diagnosed with preeclampsia, underwent a Cesarean-section, and was intraoperatively transfused with platelets and blood. After she had her baby, she was then restarted on prednisone and hydroxychloroquine.
Four months before her current presentation in the ED, the patient began feeling weak and started experiencing SOB on exertion. She had also exhibited intermittent chest pain throughout the day which was not associated with exertion. She described the pain as paralyzing when lying on her back, and lasting roughly 15 minutes each time. Shortly after the chest pain subsided, she began experiencing episodes of muscle stiffness and cramping that lasted approximately 30 minutes in duration. She also began losing strength, having falls due to weakness, and SOB at rest. Eventually, the patient lost her ability to ambulate due to muscle weakness, and she began experiencing severe throbbing right ear pain. Three days before this admission, the patient was advised by her new rheumatologist to go to the ED for wound management. As she was leaving the ED, she fell and developed a large lump on her right hip.
Cancer is considered one of the common complications of dermatomyositis. During this hospital stay, the patient had a skin punch biopsy on the left axilla to rule out skin cancer which was negative. The patient experienced new onset pancytopenia, which the hematologist attributed to methotrexate and Plaquenil toxicities.


42-year old African American female with a past medical history of morbid obesity, heterozygous FVL mutation, DVT and PE, splenic infarction, descending aortic thrombi, insulin dependent diabetes and hypertension. Hypercoagulable workup was otherwise unremarkable except for FVL. Her family history is significant for a mother decreased at age 35 from PE and a father deceased from myocardial ischemia. Due to the patient’s prior history of thrombosis and hypercoagulable state, she was on lifelong anticoagulation with warfarin.
Patient was admitted with a sudden on-set of acute left-upper-quadrant (LUQ) abdominal and epigastric pain on the morning of admission. Pain was crampy, severe, constant, and non-radiating associated with nausea and two episodes of bilious vomiting. Pain was worse with movement and associated shortness of breath. On examination, patient was tachypneic and tachycardic, in acute distress from pain with dry mucous membranes. Abdominal exam was notable for tenderness on the LUQ and epigastric region with guarding. Blood pressure was well maintained. Patient was found to have a subtherapeutic International Normalized Ratio (INR) 1.6, white count of 19.6 K/UL, elevated d-dimer of 2889 NG/ML DDU, and a lactic acid of 3.4 MEQ/L.
The patient had a prior history of allergy to contrast dye where she developed desquamation after exposure.
She required pre-medications with IV methylprednisolone and diphenhydramine. CT angiogram was performed which revealed an abrupt occlusion of the SMA (distal to its origin) with associated small bowel dilatation consistent with ischemia. Fortunately, this was without associated bowel perforation.
Patient was placed on Intravenous (IV) heparin, IV hydration, IV board-spectrum antibiotics and taking to the operation room (OR). Patient underwent exploratory laparotomy with superficial mesenteric artery thrombectomy and temporary abdominal negative pressure wound therapy (VAC) placement, complicated with hypotension. Consequently, the patient was placed on norepinephrine for pressor support. She underwent a second look and re-exploratory laparotomy on day 2. Over the course of 2 weeks, she underwent multiple surgeries including exploratory with resections and wash out. The patient received multiple pack red blood cell transfusions throughout the course of her complicated surgeries and had a total of 119 cm of small and large bowel resection. She required total parenteral nutrition (TPN). She had an interventional radiology embolization of bleeding in the abdominal wall. After a one-month hospitalization, the patient was discharged to inpatient rehabilitation in stable condition.


A 63-year-old male with a past medical history of COPD, CVA with residual left-sided weakness, and hypertension presented with dyspnea on exertion, lower extremity swelling, abdominal distention, and weight gain over the course of six months. He was admitted for anasarca. Initial laboratory evaluation revealed nephrotic range proteinuria (urine protein creatinine ratio 5.14), progressive renal insufficiency (Creatinine 2.5 mg/dL increased from his baseline 0.9 mg/dL), and hypoalbuminemia (albumin 2.0 g/dL). On exam, he had diffuse anasarca and peripheral neuropathy. A renal biopsy showed AL amyloidosis, lambda related, involving the glomeruli, interstitium, and arterial walls. During this admission, the patient unfortunately left against medical advice.
He presented to the hospital three months later with the same complaints of dyspnea on exertion, abdominal distention, weight gain, and difficulty walking from the lower extremity swelling. His renal function worsened to creatinine of 3.4 mg/dL. Serum free light chains revealed elevated lambda light chains 11.50 mg/dL, elevated kappa light chains 5.12 mg/dL, but a normal kappa/lambda ratio 0.45. Hemoglobin and calcium were within normal limits at 14.4 g/dL and 8.8 mg/dL. Skeletal x-ray did not show bone lesions.
Hematology-Oncology was consulted who recommended a bone marrow biopsy. Bone marrow biopsy showed 30% plasma cells with lambda light chain predominance. A CD 138 immunohistochemical stain identified plasma cells (see ). The bone marrow touch imprints (see ) identify plasma cells. Congo red stain was performed and the apple green birefringence characteristic of amyloid was not identified. FISH analysis was positive for 13q deletion, monosomy 13, and additional copies of chromosomes 1q and 9. Cytogenetics revealed normal male karyotype.
In retrospective review of his chart, there were signs of cardiac amyloidosis on his admission for a stroke two years prior. ECG at that time showed low voltage criteria and an anterior pseudo-infarct pattern with Q waves in V1, V2, and V3 (see ). Echocardiogram showed mild concentric left ventricular hypertrophy. The patient was started on chemotherapy with Bortezomib but after one cycle, decided to go on home hospice.


Here we report the case of a 32-year-old man who died from a BRAF-mt K601E tumor. This patient, with no familial or personal history (apart from obesity, BMI = 37 kg/m2), had a cholecystectomy in March 2018 due to right upper quadrant pain and vomiting with enlarged gallbladder on US exam. Nothing was noted during laparoscopic cholecystectomy but pain persisted. Several weeks later a CT scan revealed multiple enlarged retroperitoneal and mediastinal lymph nodes with a right colon mass and regional adenomegalies. Biopsy of a supraclavicular node revealed a poorly differentiated adenocarcinoma; colonoscopy disclosed a large caecal tumor, tumor markers (CEA and CA 19–9) were normal. In May 2018 the patient underwent surgery (right colectomy) because of a subocclusion. A peritoneal carcinomatosis was found. Pathological exam of the right colectomy revealed a large (11 cm) caecal tumor which histologically corresponded to a poorly differentiated adenocarcinoma invading the serosa with a colloid component of 10%; 34 of the 35 resected lymph nodes were invaded. The tumor was classified pT4aN2b with nodal and peritoneal metastases. The tumor was MMR proficient, with no mutation of RAS, but a BRAF mutation on codon 601 (nucleotide substitution c.1801 A>G; BRAF-mt K601E) was identified; this mutation was considered as activating. Following the usual guidelines, a first-line chemotherapy combining 5FU, folinic acid, irinotecan and oxaliplatin associated with bevacizumab [] was introduced. After 6 cycles the general status improved and pain disappeared, but CT scan showed only a 10% decrease in tumor size. Therefore, the same regimen was proposed for 6 other cycles. After 9 cycles the patient presented mild neuropathy and oxaliplatin was stopped. A few days later a pulmonary embolism led to withdrawal of bevacizumab. In mid-December, after 12 cycles, the patient reported no pain. He was tired (PS 1), but physical examination was normal. The CT scan images remained stable. It was decided to give him time off from chemotherapy during the 2 last weeks of December but when he came back in early January, pain had recurred and his performance status had worsened to PS 2. Despite medical palliative care, PS worsened and the patient died in mid-February, 8 months after colonic surgery. He never developed liver or lung metastases.


A 77-year-old woman presented to the emergency room for treatment of oral tongue pain, odynophagia, and dehydration. She reported a 2-week history of progressively worsening tongue pain with ulceration and odynophagia. The patient stated that her tongue was blue in color before the onset of ulceration (). She denied having any associated fevers, chills, malaise, scalp or jaw tenderness, headaches, or vision changes. Initially, the patient was treated by her primary care physician for a presumed infection and was prescribed Bactrim, then Augmentin, with progression of her symptoms. Her odynophagia led to severe dehydration that required a short hospitalization at an outside facility 1 week prior to presentation. The patient was seen by an infectious disease physician and underwent continued antimicrobial treatment with addition of acyclovir and fluconazole as an outpatient.
Upon evaluation by the otolaryngology service, the patient was noted to have dry mucous membranes, and there was an extensive, but well-demarcated, area of necrosis involving the anterior one-third to half of the oral tongue (). The tongue was tender to palpation.
Laboratory studies revealed that the patient had a leukocytosis of 22 K/µL, thrombocytosis of 716 K/µL, and erythrocyte sedimentation rate (ESR) that was elevated to 65 mm/h. Computed tomography (CT) angiogram of the head and neck revealed an undulated-beaded appearance of the distal internal carotid arteries and vertebral arteries bilaterally. Biopsy of the tongue revealed marked acute inflammation and granulation tissue with focal loss of the squamous mucosa above the basal layer. No fungal elements were identified with staining, and no viruses (cytomegalovirus, herpes simplex virus, or varicella zoster virus) were identified with immunohistochemistry markers.
The rheumatology service was consulted due to concern for vasculitis and the patient was started on high-dose intravenous steroids. A transthoracic echocardiogram was not performed due to low suspicion for an emboligen cardiopathy in the absence of an arrhythmia or artificial valve. The patient was taken to the operating room for a left superficial temporal artery biopsy. Histology revealed reduction of the vessel lumen caliber due to intimal hyperplasia, fragmentation of the internal elastic lamina, and transmural mononuclear cell infiltrate, confirming the diagnosis of GCA. With long-term high-dose steroids, the patient’s pain resolved and the tongue necrosis stopped progressing. She eventually recovered and the anterior edge of the tongue was well-healed 6 months after presentation ().


Patient M was a 32-year-old male, shot through his left proximal tibia in Syria in 2012. He reached shelter and remained hidden and untreated for three months. All he had available were dressings.
Eventually, he attended a field hospital. An external fixator was applied and antibiotics given, although his tibial wound continued to discharge. The fixator was removed, a plaster back slab applied, and the patient crossed the border into Lebanon.
He was referred to our unit three years after wounding, in a plaster back slab, with an ununited fracture (Fig. a,b), and a discharging, 6 cms × 3 cms pretibial wound. Imaging and bacteriology for the period beforehand were not available.
Amputation was discussed but declined by the patient. A two-stage Masquelet procedure was thus selected. A first-stage excision of the ununited area, 8cms in length, was undertaken and an external fixator applied (Hoffmann II; Stryker Trauma AG Bohnackerweg 1, CH-2545, Switzerland) (Fig. ). A cement spacer (Hi-Fatigue Bone Cement, Zimmer Biomet, 1800 West Center St, Warsaw, Indiana 46 580, USA) was inserted, without antibiotic impregnation. Cultures revealed methicillin-sensitive and methicillin-resistant Staphylococcus aureus. Sensitivities were obtained, and intravenous vancomycin followed by oral clindamycin were given, for a total of ten weeks.
Wound cover was obtained with a tubularised cross-leg flap, and immobilization achieved with an external fixator (Hoffman II) (Fig. ).
The flap was next weaned from the donor site, the contralateral component of the fixator removed, and the patient discharged 6 weeks after admission, without antibiotic therapy.
The patient was readmitted 6 months later for the second stage with a dry wound (Fig. ). At surgery, a pseudosynovial membrane was found and preserved (Fig. ). Fracture stabilization was with an interlocked 9-mm intramedullary Sign nail (Surgical Implant Generation Network, 451 Hills Street, Suite B, Richland, WA 99 354, USA). Cancellous autograft, obtained using a Reamer-Irrigation-Aspirator (RIA) (DePuy Synthes, Synthes GmbH, Eimattstrasse 3, 4436 Oberdorf, Switzerland) from the contralateral femur, was inserted into the cavity (Figs and a,b).
The patient was discharged full-weight-bearing one month later, was subsequently readmitted for nail dynamization, then discharged, but sustained additional trauma. Radiographs revealed a broken intramedullary nail (Fig. ). This was exchanged for a 12-mm nail with bone autograft, the patient being discharged two weeks later. At final review, 59 months after wounding, he was walking painlessly and without sign of recurrent infection (Fig. a,b).


This 32-year-old G4P3A1 (three previous uncomplicated pregnancies delivered at term and one spontaneous miscarriage) presented with angina. She had a past medical history of rheumatoid arthritis and systemic lupus erythematous (SLE), treated with azathioprine 50 mg PO TID, plaquenil 200 mg PO BID and prednisone. On physical examination, vital signs were within normal range. Cardio-pulmonary auscultation and peripheral pulses were normal with no signs of volume overload. Coronary microvascular dysfunction diagnosed by CRT with two of four abnormal pathways (Table ). She underwent stress cardiac magnetic resonance imaging (CMRI) which showed stress-induced infero-lateral wall hypokinesis. She had an unplanned pregnancy approximately 1 year after diagnosis. Systemic lupus erythematous treatment was stopped upon confirmation of pregnancy and prednisone was restarted at 28 weeks’ given suspicion of SLE flare-up. Carvedilol was stopped at the beginning of pregnancy. Self-reported frequency of angina was stable throughout pregnancy, which was free of adverse cardiac outcomes. She experienced an APO, as her female child was small for gestational age, weighing 2265 g at 37 weeks’ gestation. Seattle Angina Questionnaire scores worsened and functional capacity remained stable at approximately 1-year follow-up (Tables and ).


This 32-year-old G3P2A1 (two uncomplicated pregnancies delivered at term and one spontaneous miscarriage) woman with a history of SLE treated with plaquenil 400 mg PO daily and prior stroke initially presented with angina. On physical examination, vital signs were within normal range. Cardio-pulmonary auscultation and peripheral pulses were normal with no signs of volume overload. She underwent stress CMRI which showed circumferential stress-induced hypoperfusion. Coronary microvascular dysfunction was evident with two of four abnormal pathways (Table ). Carvedilol was stopped prior to conception. Plaquenil was continued during pregnancy. She became pregnant 3 years after the CMD diagnosis. Self-reported frequency of angina remained stable throughout her pregnancy. She experienced medically indicated preterm delivery due to decreased foetal movements and non-reassuring biophysical profile, giving birth to a female child weighing 2665 grams at 35 weeks’ gestation. Both SAQ scores and functional capacity were improved at 5 year follow-up (Tables and ).


This 35-year-old G3P2A1 (three uncomplicated pregnancies delivered at term and one spontaneous miscarriage) woman with no previous medical history initially presented with angina. On physical examination, vital signs were within normal range. Cardio-pulmonary auscultation and peripheral pulses were normal with no signs of volume overload. She underwent exercise cardiac single photon emission computed tomography (SPECT) and was found to have 1.65 mm ST segment depression on exercise electrocardiogram (ECG). Coronary microvascular dysfunction was evident by one of four abnormal pathways (Table ). She was not on any beta-blockers prior to conceiving. She became pregnant 6 months after her CMD diagnosis. Self-reported frequency of angina was stable throughout pregnancy. There were no APO and she delivered a healthy female child weighing 3286 g at 40 weeks’ gestation. Both SAQ scores and functional capacity were improved at 1-year follow-up (Tables and ).


This 35-year-old G2P1A1 (one uncomplicated pregnancy delivered at term and one therapeutic abortion) woman with no previous medical history initially presented with persistent angina. On physical examination, vital signs were within normal range. Cardio-pulmonary auscultation and peripheral pulses were normal with no signs of volume overload. She underwent exercise cardiac SPECT which showed 12% reversible defect in the mid-distal anterior wall. Coronary microvascular dysfunction was diagnosed with three of four abnormal pathways (Table ). Carvedilol was switched to labetalol because she was planning to conceive, and she became pregnant 1 year after her CMD diagnosis. Self-reported frequency of angina improved during pregnancy and labetalol was stopped. She did not experience any APO and delivered a female infant weighing 3969 g at 39 weeks’ gestation. Four of five SAQ scores improved during pregnancy but deteriorated at last available 4 year follow-up, as did functional capacity (Tables and ).


In February 2019, a 56-year-old woman presented to our tertiary care hospital with a 1-year history of repeated episodes of generalized tonic–clonic seizures, irritability, involuntary body movements primarily of the upper limbs, dysphagia and insomnia. Her past medical history was insignificant except for subtotal thyroidectomy 25 years previously.
Symptoms had begun insidiously with involuntary movement of the upper limbs which was progressive in nature. The family had also noticed ongoing changes in her overall behaviour, including forgetfulness, irritability, disorientation and dysphoria. Later, she also developed dysarthric speech. The family visited a neurologist and the woman was prescribed anti-epileptics and anti-psychotics, with some improvement. However, during the 3 months before presentation at our hospital, the patient’s symptoms had worsened with advanced limitation of movement, so all medications were stopped. The family history was unremarkable for any neurological disease or similar disorder. Her examination showed normal vital signs and a normal neurological system without any focal deficits. Her mini-mental state score was 22/30 with mild confusion. A scar from the previous thyroidectomy was visible on her neck. There were no parkinsonian features. The biochemical laboratory findings are given in .
A non-contrast CT scan revealed massive calcifications involving the basal ganglia, thalamus and cerebellar nuclei ().
On the basis of clinical, laboratory and neurological findings, the patient was diagnosed with Fahr’s disease secondary to post-thyroidectomy hypoparathyroidism. Upon consultation with the neurology clinic, she was started on oral calcium and vitamin D which resulted in some improvement.


A 52-year-old male patient visited the emergency department with massive hematemesis and hypovolemic shock. After hemodynamic stabilization, emergent bedside upper gastrointestinal endoscopy was performed with no proof of upper gastrointestinal bleeding. Bronchoscopy revealed no abnormalities in the respiratory tract. The relatives of the patient reported a history of a cervical spine surgery 10 years prior. A portable X-ray showed a cervical laminoplasty plate (). The carotid arteries were evaluated by three-dimensional computed tomography angiography, which revealed a ruptured 4×10-mm left extracranial ICA pseudoaneurysm that was probably connected with the pharynx (). After a fast-track preparation, an emergent open surgical repair was performed. Under general anesthesia, a longitudinal incision was made from the anterior region of the sternocleidomastoid muscle. The ICA, external carotid artery, and common carotid artery (CCA) were explored and controlled by vascular slings. Systemic heparin 100 U/kg was injected intravenously and vascular clamps were placed. A 5×12-mm injured portion of the posterior wall of the ICA was evident. After a vertical arteriotomy was performed from the CCA to the ICA, a spine cervical laminoplasty plate tip penetrated the posterior wall of the left extracranial ICA segment (). The lesion was not suitable for primary repair. The tip of the laminoplasty plate may have easily injured either the native ICA segment or a saphenous graft after interposition. Therefore, we decided to perform polytetrafluoroethylene (PTFE) graft interposition that was more resistant to the laminoplasty tip injury. The ICA stump pressure was 50 mmHg; a carotid shunt was not used. After complete resection of the injured segment, interposition grafting with a 6-mm PTFE graft was performed. The total clamping time was 22 minutes. Ear-nose-throat surgeons repaired the 3×3 mm fistula tract to the pharynx. There was no gross sign of infection. The patient tolerated the surgery well and the postoperative course was uneventful. An intravenous antibiotic, cefazolin Na 1,000 mg, was given 3 times a day for 5 days. The patient was discharged on lifelong aspirin and clopidogrel on the 6th day after surgery. The patient’s case remained uneventful at the 1-, 3-, and 6-month follow-up visits. Duplex ultrasonography performed at 1 and 3 months postoperative revealed no abnormalities.


A 16-year-old boy was referred to our outpatient department. His chief complaints were loss of vision and redness in the right eye associated with headaches since 5 months. Patient also gave history of gradual increase in the size of right eye since 5 months. There was no gross anomaly detected on general examination. He had undergone a whole spectrum of systemic investigations including brain MRI and everything had turned out to be negative. There was one red flag sign in the battery of investigations that had been done. His triglyceride level was 679 mg/dl, which was abnormally high for his age group and he was taking lipid lowering treatment for the same (Tablet Lipaglin OD for 3 months) advised by the physician.
His ocular examination showed best corrected visual acuity of hand movement close to face in the right eye and 6/9 in the left eye. On slit lamp examinations, right eye had diffuse conjunctival congestion, mild corneal haze, normal anterior chamber depth, relative afferent pupillary defect, and small twigs of iris neovascularization in pupillary margin in 2’o clock hours. Left eye anterior segment was within normal limits, with a clear cornea and reacting pupil. Lens was clear in both the eyes. IOPby Goldmann's Applanation tonometer was 54 mmHg in right eye and 15 mmHg in left eye. Gonioscopy revealed open angles up to scleral spur in both eyes. Fundus examination with 90D lens showed glaucomatous optic atrophy with cup to disc ratio of 0.9:1 (disc pallor) in the right eye [] and 0.3:1 in the left eye, with normal blood vessels and bright foveal reflex. He was using following eye drops: brimonidine and brinzolamide combination BD, timolol BD and tablet acetazolamide SR BD, which was prescribed to him 2 days ago elsewhere. We added liquid glycerol 1 oz BD.
At 1 week follow-up, the pressure in right eye was 32 mmHg and left eye was 16 mmHg, and the neovascularization had resolved. He was intolerant to systemic antiglaucoma medications. The IOP was not under control with topical antiglaucoma treatment alone, we advised to go for right eye trabeculectomy with mitomycin C. The surgery in the right eye was done uneventfully. On first postoperative week, right eye IOP was 10 mmHg with a well-formed anterior chamber and good functioning bleb []. Because of discontinuation of systemic antiglaucoma medications, the left eye IOP had increased to 34 mmHg and he was prescribed eye drops: timolol BD, brimolol, and brimonidine combination BD and bimatoprost HS. Two weeks after giving maximum topical antiglaucoma treatment, the pressure of left eye was still 32 mmHg. This was a challenging situation for us as the left eye was the only seeing eye, IOP uncontrolled by topical antiglaucoma drugs, and the patient was intolerant to systemic medication.
Since trabeculectomy with MMC showed good response in the right eye, we performed the same procedure in the left eye. Seven days later, the inIOP in the right eye was 10 mmHg and in left eye was 8 mmHg. Patient had visual acuity of 6/18 in the left eye. Slit lamp examination of left eye revealed a well-formed anterior chamber with good functioning bleb []. His serum triglyceride levels had also come down to normal with systemic lipid lowering medications.


A 46-yr-old woman came to outpatient department at our referral center in South India with chief complains of pain in both eyes (OU) and dimness of vision since 10 months. She was seen elsewhere and was diagnosed as a case of VKH. She was investigated thoroughly and other causes of panuveitis were ruled out. Her best corrected visual activity was light perception with inaccurate projection of rays in the right eye (OD) and 6/15 in the left eye (OS). Her intraocular pressure was unrecordable in OD and 17 mmHg in OS. On slitlamp examination, OD had corneal edema with Descemets folds, shallow anterior chamber with iris bombe, posterior synechiae, peripheral anterior synechiae, patent peripheral iridectomy, and complicated cataract with festooned pupil. Gonioscopy showed 360° peripheral anterior synechiae with iris root closed. OS had clear cornea with anterior chamber cells++, flare++, patent peripheral iridectomy, posterior synechiae with posterior subcapsular cataract. Fundus examination had no view in OD, OS had lens haze with attached retina. A diagnosis of hypotonous eye secondary to chronic uveitis complicated cataract with seclusio papillae was made. She was put on tablet azathioprine 50 mg three times daily with oral predinisdone 40 mg/day. Patient was advised to undergo cataract surgery (extracapsular cataract extraction with intraocular lens implantation with iris hooks under steroid cover) in OS. Cataract surgery was done 6 months later. Postoperatively she was found to have sunset glow fundus. A diagnosis of VKH was confirmed. There was no systemic feature. A diagnosis of incomplete VKH was made according to revised diagnostic criteria of VKH. She was lost to follow-up. She came back after 1 year with dimness of vision left eye. Her best corrected visual acuity was 6/60 in OS. Slit lamp examination of OD status quo and OS showed anterior chamber flare1, + cells1, + vitreous cells1 + posterior chamber intraocular lens in situ. Fundus examination showed depigmented fundus with sunset glow in the OS with choroidal neovascular membrane (CNVM). Optical coherence tomography (OCT) in OS showed choroidal neovascular membrane with cystoid macular edema. Three intravitreal avastin injections were given and finally CNVM regressed after third injection. At final visit, OS had depigmented fundus with sunset glow, with scarred CNVM. A diagnosis of VKH disease was made and patient was on azathioprine oral prednisolone 10 mg/day and prednisolone eye drops. Patient had a regular follow-up every 2 months and oral prednisolone was tapered. At 6 months follow-up visit, her best corrected visual acuity was 6/18 in the OS. Oral steroid was continued 10 mg/day along with topical prednisolone eye drops 3 times a day. Fundus showed depigmentation with sunset glow. Best corrected visual acuity in OS was 6/12. Right eye was painful blind with phthisis bulbi. She was advised for enucleation of OD after obtaining the informed consent. Enucleation done was after 1 month. Fundus examination in OS showed typical sunset glow suggestive of VKH disease.
The enucleated eyeball (OD) on histopathology showed anterior segment including lens in the section studied. Vitreous cavity showed red blood cells (RBC) with occasional lymphocytes. Posterior segment showed diffuse choroidal thickness with congested choroidal stromal vessels and full thickness inflammation by chronic inflammatory cells which included lymphocytes and plasma cells [Figs. and ]. There were reducing numbers of choroidal melanocytes. In retina, there were photoreceptor degenerations with multiple pockets of fluids in outer retinal layers. Bone formations were noted with focal retinal pigment epithelium (RPE) undulations. Areas of retinal gliosis were seen. Portion of the choroid under the degenerated RPE showed choroidal neovascularization with outpouring of RBCs. Sclera was thickened posteriorly. Immunohistochemistry showed CD3 (T-cell marker, CELL MARQUE, USA): +++, CD20 (B-cell marker, CELL MARQUE, USA): + [Figs. and ], slides were compared with controls. Significance of CD3 positivity indicated that T-cells involvements were predominant.


A 49-year-old male complained of distending pain in his right upper abdomen for 2 weeks. He also complained of nausea and fatigue that began shortly before the onset of abdominal pain. He had a contrast-enhanced computed tomography (CT) and magnetic resonance imaging (MRI) of the upper abdomen that revealed multiple liver tumors on segments II, III, IV of left lobe and a huge lesion (12.4 cm) on segment VIII of right lobe, with thrombus in the left hepatic vein, middle hepatic vein, and the IVC which extended to the right atrium (). Imaging findings of hepatic cirrhosis, ascites, and splenomegaly were also evidenced. The patient had a history of hepatitis B, with a high level of hepatitis B virus (HBV) DNA copy number (1.63×103).
The patient’s liver function tests demonstrated: ALT 329 U/L, AST 231 U/L, total bilirubin 17.8 µmol/L, albumin 37.6 g/L, LDH 313 U/L, and an international normalized ratio of 1.14. Tumor markers were negative for Alpha-fetoprotein and CA 19–9. CEA was elevated (9.0 ng/mL). After multidisciplinary team (MDT) evaluation, the diagnosis of hepatic cancer was established with clinical and imaging evidence according to the Chinese standard (version 2017). The case was regarded as unresectable, and SBRT was recommended to shrink the tumor thrombus and preserve liver function, preventing further extension of thrombus and with the hope to pursue subsequent TACE.
The patient was immobilized in a stereotactic body frame with customized vacuum cushion (Karity, Guangzhou, China) and abdominal compression for control of respiratory motion. Four-dimensional contrast-enhanced computed tomography simulation (Light Speed RT, GE) was performed at 2.5 mm slice thickness. The gross tumor volume (GTV) was delineated as the tumor thrombus in the left hepatic vein, middle hepatic vein, IVC, and in the right atrium. Internal target volume (ITV) was defined as the volumetric sum of GTVs in the multiple phases. ITV margin was expanded by 3 mm to set the planning target volume (PTV). The volume of PTV was 262.31 cm3. The patient was treated under institutional review board guidelines of the Second Affiliated Hospital, Zhejiang University School of Medicine, with signed informed consent. Written informed consent for the publication of the case details and accompanying images was provided from the patient, institutional approval was not required. He received a radiation dose of 40 Gy/5 fractions administered over a week ().
The patient was relieved of his pain in 1 week. Contrast-enhanced MRI was done one month after SBRT, the thrombus in the left hepatic vein dramatically shrank, and no thrombus in the middle hepatic vein, IVC, and the right atrium be found. The ascites disappeared. Moreover, the huge lesion on segment VIII of right lobe shrank to 9.1 cm (). The liver function was improved, ALT and AST level decreased to 67 and 46 U/L, respectively. HBV DNA copy number came back to normal range after anti-virus therapy.
Another MDT meeting was held, and it was decided that TACE would be the best option for the patient at this period. We used TACE targeting at tumors on segments II, III, IV of left lobe and VIII of right lobe. The microcatheter was advanced into tumor feeding artery of each tumor. A total dose of pirarubicin (40 mg)-lipiodol (15 mL) emulsion, 5% bicarbonate 100 mL, oxaliplatin 150 mg, irinotecan 100 mg, PVA microsphere (300–500 µm and 700–900 µm), gelatin sponge particles (710–1,000 µm), were alternatively injected until the blood flow stopped. Microcoil was used to prevent recanalization of the embolized tumor feeding arteries with diameters larger than 2 mm. The patient tolerated TACE well. Thirty days after TACE, the patient had MRI examination, which demonstrated a 94% necrosis, leaving around 6% viable residue. Selective deposit of the lipiodol oil only on tumor was also confirmed by CT scan. His CEA was 6.8 ng/mL, CA 19–9 and Alpha-fetoprotein values were normal. The patient remained in stable condition with Child-Pugh A after SBRT and TACE. The patient received two TACE with more than 6 weeks interval, and had been doing well for more than half a year. Ten months after SBRT, the patient was hospitalized with a 1-week history of obstructive jaundice, an extrahepatic biliary obstruction was found in the procedure of percutaneous transhepatic cholangiography and drainage (PTCD) (). The patient died 11 months after SBRT.


A 70-year-old female, known case of gout, presented to our center through emergency department with 2 weeks history of right upper quadrate (RUQ) pain. The pain was sudden with no radiation, relieved by analgesia, not related to food. There was no fever, no vomiting, no change in bowel habit or stool color, and no jaundice. No history of trauma. No remarkable surgical history prior to her complaint. She was not a smoker. The physical examination disclosed only an abdominal tenderness in the RUQ.
Laboratory investigation revealed mild leukocytosis with normal liver enzymes, normal bilirubin level, and normal liver function panel. Also, the tumor marker tests were performed after awhile and revealed elevation in cancer antigen 19–9 (CA19-9) (291.6 U/mL).
Radiological studies and interventions were conducted. Abdominal ultrasound revealed distended gallbladder with stone and suspicion of soft tissue mass. Then, an enhanced computerized tomography (CT) scan of the chest, abdomen, and pelvis was performed and demonstrated an irregular enhancing diffuse wall thickening of the gallbladder mainly at the fundus with an exophytic mass lesion measuring about 5×6 cm abutting the hepatic flexure with fatty infiltration of the liver and hypodense hepatic lesions noted in the gallbladder bed with largest measuring about 1.3 cm in diameter. Also, the proximal transverse colon showed wall thickening with regional lymphadenopathy, ( and ). Then, the patient underwent positron emission tomography (PET) scan that also demonstrated intensely increased uptake involving the gallbladder wall as well as exophytic mass coming from the gallbladder strongly suspicious for primary malignancy. Also, there are multiple foci of increased uptake in the liver at the gallbladder bed representing direct invasion of the primary gallbladder tumor into liver. The multiple enlarged lymph nodes seen on CT images were hypermetabolic on PET scan which was consistent with metastatic lymphadenopathy, ).
While the lower gastrointestinal endoscopy was obtained, and it was unremarkable, the possibility of colon cancer was excluded. Also, she was offered magnetic cholangiopancreatography which yielded a diffuse wall thickening of dilated gallbladder mainly at the fundus with a heterogeneously enhancing soft tissue mass lesion arising from its wall measuring 4.7×6.7 cm. The mass extended downward and appears inseparable from the proximal transverse colon which appeared thickened and edematous with few enlarged regional lymph nodes in the porta hepatis and precaval nodes. The mass manifested invasion to segment VIb of the liver as well. Also, there were two large stones and multiple enhancing polyps inside the gallbladder. Moreover, few well-defined high T2 signal intensity lesions were seen in the liver at the gallbladder bed the largest of which measured about 1.3 cm, (). After that, percutaneous biopsy was taken from the mass which demonstrated invasive moderately differentiated adenocarcinoma consistent with gallbladder origin.
Multidisciplinary team was consulted, and the decision was to attempt radical surgery by an expert surgeon. Open cholecystectomy, partial hepatectomy with transverse colectomy, and lymph node dissection were performed. Microscopic examination revealed solid sheets of tumor cells invaded the gallbladder and liver tissue. The tumor cells were bizarre shape, hyperchromatic, high nuclear/cytoplasm ratio, prominent nucleoli, and high mitotic index. There is geographic necrosis detected. The tumor cells were immunoreactive for cytokeratin (CK)19, CK7 and CK5/6 and immunonegative for CK20, and hepatocyte-paraffin stain. The tumor was poorly differentiated (grade 3). The surgical margins were negative. The tumor exhibited lymphovascular and perineural invasion. The TNM stage for the cancer was 4B (T=3, N=2, M=0). The histopathological results confirmed the aforementioned diagnosis. Unfortunately, analysis of microsatellite instability was not available.
However, CT scan was performed 1 month postoperatively and disclosed a recurrent local cancer with relapse of the liver, colon metastasis, and lymph nodes. Other radiological examinations were not available and the clinical status of the patient did not allow us to take biopsy. Another CT scan two months postoperatively confirms the progression of the relapsed disease, ( and ). Consequently, and after obtaining the consent from the patient, she commenced a pembrolizumab regimen for the advanced tumor. The patient’s clinical performance was poor. In addition, she refused chemotherapy. For these two reasons we consulted the patients and offered the pembrolizumab. The pembrolizumab was administered in eight doses. The doses were 3 weeks apart. The total duration of treatment was 21 weeks. Each dose was 100 mg (half the complete dose due to financial issues as this drug is expensive for the patients). PET scan after the eighth cycle revealed a complete resolution of the tumor, (). The last PET scan was performed 2 years after the last dose of pembrolizumab and indicated no disease. The patient was clinically and radiologically free after 2 years follow-up, ().


A 51-year-old female, not known to have any medical illness, presented to our center with painless progressive yellowish discoloration of her face. Associated with prurities, dark urine, and pale stool. No previous history of biliary colic or similar episodes. The patient stated significant weight loss, anorexia, and asthenia. No history of contact with hepatitis patient. Neither blood transfusion nor drug abuse was reported. No travel history. No previous surgical history. No family history of malignancies. She was not a smoker. On examination, yellowish discoloration of whole body was noted. No abdominal tenderness or masses felt. Laboratory investigation was conducted and disclosed a direct hyperbilirubinemia with a total bilirubin of 200 umol/L and direct bilirubin of 196 umol/L. In addition, alkaline phosphatase and gamma-glutamyl transferase were significantly elevated (972 and 973 U/L, respectively). The aspartate aminotransferase and alanine aminotransferase were mildly elevated. The complete blood count revealed microcytic anemia that was found to be due to iron deficiency. Normal coagulation profile was yielded. Lipase and amylase levels were normal. The CA 19.9 was significantly elevated.
She underwent a series of radiological studies and interventions. Abdominal ultrasound revealed a severe dilation of the common bile duct with a diameter of 15 mm with intrahepatic and pancreatic duct dilatation. After that, endoscopic retrograde cholangiopancreatography (ERCP) was done and showed a completely invaded ampulla of vater by a vegetating mass with no visible orifice or bile flow. Subsequently, the biliary tree could not be visualized. Multiple biopsies were taken from the ampullary mass which demonstrated the presence of invasive moderately differentiated adenocarcinoma consistent with biliary origin. As the ERCP failed to relieve the obstructions, she underwent percutaneous transhepatic cholangiography that also demonstrated an intra- and extrahepatic biliary dilation. Internal and external drainage were achieved. Chest–abdomen–pelvis CT scan revealed the presence of periampullary mass lesion that invades the second part of duodenum with regional lymphadenopathy, ( and ). Also, PET scan was conducted, and a hypermetabolic mass measured 3.5×2.5 cm was located around ampulla of vater with perihepatic, celiac, retropancreatic, aortic, and precaval lymphadenopathy. These findings were consistent with distal cholangiocarcinoma with regional invasion.
Multidisciplinary team was informed, and the decision was to go for radical surgery by an experienced surgeon. Whipple procedure was performed with pancreaticoduodenectomy, distal gastrectomy, and a dissection of 20 regional lymph nodes were done. Microscopic examination demonstrated multiple fragments of duodenal and ampullary mucosa infiltrated by a tumor composed of moderately differentiated glands and tubules, lined by pleomorphic cells with hyperchromatic nuclei and prominent nucleoli. Areas of central necrosis are also detected. The tumor cells are immunoreactive for CK19, CK20, and CKX2 immunostains and immunonegative for CK7 immunostain. The tumor was moderately differentiated (grade 2). The surgical margins were negative. The tumor exhibited lymphovascular and perineural invasion. The TNM stage was 3B (T=3, N=1, M=0). The resultant histopathological examination confirmed the aforementioned diagnosis of distal cholangiocarcinoma with regional lymph nodes metastasis. Unfortunately, analysis of microsatellite instability was not available.
While the surgery was radical and achieved R0 resection, the decision was to commence the patient on gemcitabine-cisplatin chemotherapy. This decision was based on the results that the lymph nodes were invaded by the tumor. Shortly after the surgery, the patient started chemotherapy. After the second cycle, the gemcitabine-cisplatin regimen was stopped due to two main reasons. The follow-up CT scan revealed a progression of the disease as a hepatic metastasis, (). Also, the patient developed acute heart failure as a side effect of the chemotherapy. As a result, and after obtaining a consent from the patient, she started a pembrolizumab regimen. The pembrolizumab was administered in eight doses. The doses were 3 weeks apart. The total duration of treatment was 21 weeks. Each dose was 100 mg (half the complete dose due to financial issues as this drug is expensive for the patients). Whole body CT scan during and after the eighth cycle revealed decrease and complete resolution of the tumor, ( and ). The last CT scan was performed 2 years after the last dose of pembrolizumab and demonstrated no relapse.


A 30-year-old woman (twin 1) who had not previously been diagnosed with diabetes mellitus presented at a clinic of Kobe University Hospital, Kobe, Japan, because of the recent onset of thirst and polyuria. She had a plasma glucose concentration of 739 mg/dL, glycosylated hemoglobin level of 16.9% and ketonuria of ≥3, and she was admitted to the hospital. On admission, her height was 152.3 cm and bodyweight 41.8 kg. After her blood glucose level had been lowered sufficiently, various examinations were carried out. Glucagon challenge and meal challenge tests showed that her insulin secretion was markedly impaired (Table ). Her estimated glomerular filtration rate was within normal range (Table ). She showed hypomagnesemia and hyperuricemia, but her liver function was normal (Table ). Computed tomography and magnetic resonance imaging showed complete aplasia of the body and tail of the pancreas, as well as marked aplasia of the right kidney and multiple cysts in both kidneys (Figure ). Pancreatic volume calculated by a method described previously was 5.2 mL. A diagnosis of MODY5 was suspected on the basis of the clinical features.
Given that the proband had an identical twin sister, twin 2 was also examined for MODY5. Her height was 151.9 cm and bodyweight 40.3 kg. Although her glycosylated hemoglobin level was 5.8%, the results of a 75-g oral glucose tolerance test (fasting plasma glucose 135 mg/dL; 2-h postload 337 mg/dL) met the criteria for diabetes mellitus. She manifested renal dysfunction, hypomagnesemia, hyperuricemia and normal liver function (Table ). Her glucagon challenge and meal challenge test results showed preservation of insulin secretion (Table ). Computed tomography and magnetic resonance imaging showed hypoplasia of the body and tail of the pancreas, with a pancreatic volume of 14.6 mL, as well as marked aplasia of the right kidney, multiple cysts in both kidneys and hydronephrosis in the left kidney. Serum glucagon levels during an arginine challenge test of twin 1 and twin 2 were smaller and greater, respectively, than those observed with type 2 diabetes patients (Figure ).
The bodyweights of twin 1 and twin 2 at birth were 2,250 and 2,550 g, respectively, and those at 2 years and 20 years were 13.0 and 12.0 kg, as well as 40.1 and 40.4 kg, respectively. Although twin 2 underwent surgery for hydronephrosis immediately after birth, there was no other notable event in their medical history until this presentation. They had no family history of diabetes mellitus, multiple kidney cysts and aplasia of kidneys (Figure ).
All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national), and with the Helsinki Declaration of 1964 and later versions. Written informed consent was obtained from all patients before they were included in the report.
Array-based comparative genomic hybridization showed a heterozygous 857-kb deletion of a region at chromosome 17q12 (arr[GRCh37] 17q12 (34817422_36079369) x1) that contains the HNF1β locus, as well as LHX1, in both twins. They were therefore diagnosed with MODY5 associated with a deletion of 17q12 containing HNF1β (known as 17q12 deletion syndrome).