A 6-week-old Caucasian girl was admitted to a private hospital in South Africa with acute onset symptomatic cardiac failure secondary to anemia. Her parents reported a 1-day history of lethargy, poor feeding, shortness of breath, and irritability on a background history of progressive pallor.
There was no family history of note. Antenatal history included a low maternal pregnancy-associated plasma protein A (PAPP-A) level (0.376 IU/L) which resulted in a high-risk screening protocol for intrauterine growth restriction (IUGR) and fetal chromosomal anomalies. Cell-free fetal deoxyribonucleic acid testing from maternal blood excluded aneuploidies for the common trisomies [–] and subsequent fetal anomaly ultrasound and echocardiogram scans were all normal. A caesarean section was performed at 37 weeks for spontaneous labor, IUGR, and breech presentation. The delivery was uneventful and apart from a low birth weight of 2465 g, a healthy baby was discharged 3 days post caesarean section as per normal protocol.
On admission to hospital at 6 weeks of age, the baby under examination was severely anemic, tachycardic, and lethargic. There were no stigmata of immunocompromise, infection, or icterus. The baby weighed 3200 g with a head circumference of 38 cm.
There were no obvious craniofacial or skeletal abnormalities of note and examinations of her other systems were normal. The preliminary results with normal range for age in brackets showed a hemoglobin (Hb) level of 3.1 gm/dL (10–18 gm/dL) and a hematocrit of 9% (31–55%), mean corpuscular volume of 106 fl (85–123 fl), mean corpuscular Hb concentration 34 g/dL (32–37 g/dL), reticulocyte production index of 0.0, and an absolute reticulocyte count of 5.1 × 109/L (20–60 × 109/L). Her white cell count was low 4.0 × 109/L (5–19.5 × 109/L) but apart from a low neutrophil count of 0.32 × 109/L (1–9 × 109/L), the remaining differential count was normal. Her platelet count was increased 655 × 109/L (140–420 × 109/L). Her C-reactive protein was marginally raised at 7.7 mg/L (< 5 mg/L), and the infective work up was positive for Escherichia coli cultured from the urine. Tests for cytomegalovirus, human immunodeficiency virus (HIV), rubella, Epstein–Barr virus, toxoplasmosis, herpes simplex virus 1 and 2, and parvovirus B19 were all negative. A diagnosis of E. coli urosepsis was made. The baby was transfused with leukodepleted irradiated red cell concentrate to an Hb level of 10 g/dL and given goal-directed antibiotics and discharged 6 days later.
Readmission 14 days later with an anemia (Hb 7.7 g/dL) and associated reticulocytopenia of 7.0 × 109/L (20–60 × 109/L) prompted a provisional diagnosis of transient erythroblastopenia of childhood (TEC), which was made after infection, HIV, and tuberculosis were excluded. Three further admissions over the next 3 months for anemia requiring red cell transfusions and a persistent neutropenia prompted a bone marrow biopsy (Figs. and ).
Review of the bone marrow biopsy showed reactive features with markedly increased megakaryopoiesis and significant lymphocytic infiltrate. Flow cytometry demonstrated the infiltrate to consist of T cells, mature B cells, and hematogones. An absence of red cell precursors and immunohistochemical glycophorin stain on the bone marrow trephine confirmed a pure red cell aplasia.
Due to the unavailability of molecular and eADA testing in South Africa, specimens for molecular testing were sent to Oxford, UK, for identification of a possible heterozygous pathogenic variant in one of the genes associated with DBA. A multigene panel using the Multiplex Ligation-dependent Probe Amplification kit (MRC-Holland) confirmed a heterozygous whole gene deletion of RPL35A. In addition, dried plasma was sent to Duke University Medical Center, USA, to exclude adenosine deaminase 2 deficiency.
Once the diagnosis of DBA was made, the non-standardized management and limited experience in managing DBA in South Africa resulted in inconsistencies in opinion in the optimal early management of the case. Controversies around Hb transfusion threshold, optimal Hb target, frequency of transfusions, and timing and dosage of corticosteroid treatment and hematopoietic stem cell transplantation (HSCT) resulted in different opinions from different specialist practitioners.
Together with input from international DBA specialists managing large numbers of patients with DBA, the initial hematopoietic management in this case was directed toward correcting the anemia with transfusions every 3–5 weeks with irradiated leukodepleted RBC concentrate. A transfusion threshold of 8 g/dL was used and a volume of 10–15 ml/kg transfused on each visit. Planned iron chelation therapy to prevent transfusional hemosiderosis will be delayed until approximately 170–200 ml/kg of transfused red packed cells has been given. A planned trial of corticosteroids will be given at 1 year of age.
At follow-up at 6 months of age, the baby was stable requiring red cell concentrate infusion therapy every 3–4 weeks. Persistence in the neutropenia was noted, with no changes in the other cell lineages. Her current ferritin level is 573 μg/L and a total of 90 ml/kg of red packed cells has been transfused, thus, iron chelation therapy has not yet been instituted. Apart from a delay in gross motor development and growth (weight and height), all other parameters and development are within normal limits.


An 81-year-old Caucasian female, healthy weight (44 kg, or 97 pounds), without
systemic diseases, presented herself in a tertiary hospital ambulatory with a
complaint of bulge and pain in the right groin for 10months. The pain was mild and
usually appeared when she performed physical effort. No further symptoms were
recorded. The patient had no episode of acute cholecystitis previously. She had
urinary incontinence surgery 12 years ago and a Lichtenstein hernioplasty on the
left side 10 years ago with no signs of recurrence. She had a descending thoracic
aortic aneurysm measuring 7.1×6.3 cm on its major axial diameter and an
infrarenal abdominal aortic aneurysm measuring 6.4×6.1 cm on its axial
diameter and was planning to undergo an endovascular repair in two steps. She also
had a cystocele. The physical exam showed a bulge on the right inguinal region with
no expansion on coughing. The palpation showed a hard bulge and the hernia was not
reducible with pain on manipulation ().


A 46-year-old female underwent a health examination with no complaint. No remarkable family history was reported. Her vital signs and blood tests were normal. Examination of the abdomen revealed no pain. However, following an abdominal ultrasonography, a solid mass was observed in close approximation to the kidney. The mass did not involve the abdominal cavity’s wall (). A further evaluation by computed tomography showed the presence of a 38 × 25 mm heterogeneously enhancing mass, with mottled calcifications and a cystic portion arising from small bowel mesentery (a). A low intensity mass of small bowel mesentery was observed by magnetic resonance imaging (T2 WI) (b). We diagnosed either sarcoma of the mesentery or gastrointestinal stromal tumor. The patient underwent a single incisional laparoscopic curative resection of the tumor. During the operation, the tumor was identified in the small bowel mesentery. It did not involve the stomach, intestine and marginal vessel (). The resected tumor measured showed 38 × 25 × 13 mm. Externally, the tumor had a smooth surface. Histopathological findings revealed nests of round to oval cells. The focal area showed the presence of more atypical cells with surround osteoid formation (). The final histologic diagnosis was of primary extraskeletal osteosarcoma arising from the mesentery. The patient underwent an uneventful postoperative course. She did not receive chemotherapy during her follow-up and had no recurrence 10 months post-surgery.


A 55-year-old man came to our hospital with complaints of vague abdominal pain, burning micturition, hematuria, increased frequency and urgency of urine, more during night and pain during defecation since four months. He was referred to the urology department where the clinical examination was done including digital rectal examination which revealed an enlarged prostate. Further, more hematological investigations were done with no abnormal findings aside from prostate-specific antigen (PSA) which was mildly raised with a value of 12.4 ng/ml. He had no remarkable medical history.
The patient was further investigated in our radiology department where an abdominal ultrasonography and intravenous pyelography (IVP) was done. On ultrasonography, he was diagnosed with moderate hydroureteronephrosis with chronic cystitis with significant post void urine and increased volume of the prostate which measured approximately (75)cc with grade-III prostatomegaly and a large cystic swelling within prostatic parenchyma. On IVP it was diagnosed as moderate hydroureteronephrosis with significant residual post void urine.
Contrast-enhanced computed tomography (CECT) was done with axial images of delayed phase which showed well defined large cystic lesion measuring approximately 7.8 x 7.1 cm in the mid and left pelvis likely arising from the prostate. Lesion demonstrated multiple enhancing polypoid soft tissue components along the wall. The lesion abutted urinary bladder anteriorly, rectum medially and levator ani muscle posteroinferiorly with loss of fat planes as shown in Figure .
There was also mid circumferential wall thickening of the urinary bladder with few internal iliac lymph nodes as shown in Figure .
Bone scan and computed tomography (CT) of chest, abdomen, and pelvis were negative for metastasis.
Histological sections from the specimen, as seen in Figures -, consist of 19 out of 22 prostatic transurethral resection of prostate (TURP) chips which showed tumor composed of medium-sized glands with irregular outline and a smooth inner surface and scanty intervening stroma. Ducts were lined by pseudostratified columnar epithelium with abundant amphophilic cytoplasm and intraluminal eosinophilic secretion. Anisonucleosis was seen. On histopathological sections, diagnosis of ductal adenocarcinoma of the prostate was made with Gleason score 5+4=9, grade group V (WHO 2016 classification).
The patient underwent combination treatment open radical retropubic prostatectomy along with androgen blockade drugs, bicalutamide, and goserelin for six months. An 8-10 cm incision was made (well below the belt-line) in the skin between the umbilicus and the top of the pubic bone. The pelvis was then explored and the important structures such as the urinary bladder, prostate, urethra, blood vessels, and nerves were identified.
The prostate along with cyst was removed from the urethra below and the bladder above, and the bladder and urethra were reconnected. The yellowish color fluid was found in the cyst. The blood vessels leading to and from the prostate were divided and tied off. A catheter running through the penis into the bladder was typically required for at least a week after surgery. A surgical drain was left in the pelvis to allow drainage of blood and other fluid. Additional components of the operation include:
- Lymphadenectomy: Left sided internal iliac lymph nodes were removed. Prostate cancer often spreads to nearby lymph nodes in the early stages, especially the sentinel lymph node.
- Nerve-sparing surgery was attempted to protect the cavernous nerves of the penis, which control erection. These nerves are very thin and fragile and run next to the prostate and may be destroyed during surgery, leading to impotence.
- Bone scan and CT chest, abdomen, and pelvis were negative for metastasis; radiotherapy was not given to the patient. Serum PSA level was within normal range of 4 ng/ml and under follow up.


A 22-year-old woman came to our department with complaints of intermittent palpitation and shortness of breath for 6 months. Physical examination was unremarkable. Echocardiography revealed that there was an ASD with the diameter of 10 mm. Enhanced computed tomography (CT) demonstrated a huge well-defined and homogeneous cystic mass, in left superior anterior mediastinum and in close proximity to pulmonary trunk (Fig. a and b), no significant artery feeding were found. Cancer antigen 125 was higher than normal. The uniportal video-assisted thoracoscopic surgerywas performed with the preoperative diagnosis of cystic teratoma. The first striking intraoperative finding was the completely CAP. A large well-defined cystic lesion (9 cm × 9 cm × 10 cm) was visualized, which bulged through the aortopulmonary window (Fig. ). We performed a mini-incision to cystic lesion, from which large amounts of white viscous liquid was sucked. Finally the basal segment of mass was separated carefully from mediastinal pleura (Fig. c). Besides, we did not do surgical intervention to CAP and ASD. Histopathology revealed that grossly, the lesion had a smooth inner wall with gray gelatinous material. And cystic dilated bronchus, lung tissue and its own pleura could be seen under microscope (Fig. d). The final diagnosis of this patient was ELS, not cystic teratoma. We reassessed the enhanced CT, but we still could not found a significant feeding artery for ELS.The patient recovered well and in excellent condition during follow-up,with no intermittent palpitation and shortness of breath.


A 15-year-old girl visited the orthopedic service because of severe knee pain after a sudden fall while heading downstairs, and she was unable to stretch her leg. The patient had a history of dislocation of the patella 2 weeks ago. Physical examination showed tenderness on palpation over the upper pole of the patella and absence of active movement of the knee accompanied by swelling and joint effusion. A plain radiograph showed an avulsed fragment of the superior pole of the patella (Fig. ). Magnetic resonance imaging (MRI) confirmed a superior pole patellar avulsion fracture and dysfunction of the knee extensor mechanism (Fig. ). There were no signs of damage to the articular cartilage, meniscus, and cruciate ligament caused by previous dislocation.
Under general anesthesia, the patient underwent open surgery for reduction of the patellar fracture and reconstruction of the knee extension apparatus through an anterior approach. All of the above-mentioned imaging findings were further confirmed during surgery. Through a midline incision above the quadriceps tendon, careful dissection was performed to expose the injury site. Intraoperatively, a sleeve-like piece of bone was detected above the patella, and the proximal quadriceps tendon was attached to the bone piece (Fig. ). Then, complete removal of the blood clot and tissue debris was performed in the joint cavity and around the torn ends of the quadriceps tendon. Patellar retinaculum and quadriceps tendon with the patellar fracture piece was meticulously repaired and secured to the main patellar body by 2 Bio Composite suture anchors (Arthrex, Naples, FL) using a modified Mason–Allen stitch and was augmented by performing the figure-of-8 technique (Fig. ).
Postoperatively, the patient's knee was maintained in full extension using a knee brace, and weight-bearing was prohibited until 6 weeks after surgery. The passive range of motion exercise of the knee was started on the first day after surgery, and it was gradually progressed to full-scale motion as the tolerance improved. During the first 6 weeks of surgery, the patient's main activities included patellar mobility exercises, knee passive range of motion exercises, and quadriceps activation exercises. After 6 weeks, the patient was referred to the rehabilitation department for restoration of complete knee activity and initiation of muscle strength training. The patient was allowed to gradually resume sports when the normal strength, stability, and knee range of motion were comparable to those on the contralateral side.
Six months after the operation, the knee function was fully restored, there was absence of pain and swelling, and the patient was able to return to sports.


A 38-year-old nonsmoking female presented with left-sided chest pain and dyspnea for three consecutive days. The patient was admitted to Masih Daneshvari Hospital on September 19, 2016. She had no history of fever, weight loss, and arthralgia or skin rash. Her blood pressure was 110/70 mmHg, pulse rate was 85, temperature was 37.5°C, and respiratory rate was 28. The breath sound was decreased in the left lower zone of the lung, and other physical examinations were unremarkable.
Chest radiograph manifested two pulmonary nodules and basal atelectasis in the left lower lobe with pneumothorax (). Chest CT scan exhibited collapsed consolidation of the left lower lobe with pneumothorax and the presence of relatively two separated small-sized cystic lesions within the collapsed segment ().
The laboratory tests revealed the increase in WBC count with predominantly neutrophils; the erythrocyte sedimentation rate and C-reactive protein were elevated. The nitroblue tetrazolium (NTB) blood test was at the 99% accuracy level. Anti-nuclear antibodies (ANAs), anti-neutrophil cytoplasmic antibodies (C-ANCA and P-ANCA), and anti-double-stranded DNA (anti-dsDNA) were negative; in addition, the anti-HIV antibody test was negative. Transparently, the pulmonary function tests showed moderately restriction.
Lung lesion resection for two intraparenchymal pulmonary nodules and cavitary lung lesion in the left lower lobe was performed; furthermore, the histological examination showed some epithelioid and giant cell granulomas with necrotizing arteritis in conjunction of a large area of necrosis (Figures and ). Acid-fast staining, periodic acid-Schiff (PAS) staining, and Gomori methenamine-silver (GMS) staining were negative; therefore, the ultimate diagnosis was necrotizing sarcoid granulomatosis. The prognosis of NSG is favorable, and medical treatment is usually not required. As a matter of fact, in our case report, the patient recovery conspicuously occurred; nevertheless, in some cases, treatment with corticosteroids is quite essential.


A 12-year old boy, known case of hemophilia A, was brought to the emergency department (ED) of Dr. Ruth KM Pfau, Civil Hospital Karachi (CHK) in February 2019 with the complaint of swelling and pain in multiple joints along with intermittent fever for 13 days. Swelling initiated from the left elbow joint followed by a sudden, dull, aching pain, exacerbated by activity and associated with a limited range of movement. Seven days later, it was followed by a similar joint ache and swelling in the right elbow joint, then in the left knee joint, and, lastly, in the right shoulder joint. There was no history of any trauma to the joint. The patient also experienced high-grade fever, intermittent in nature, with severe joint ache, which was relieved by taking oral antipyretics.
Our patient had experienced similar episodes of joint ache occasionally since birth, and all of them were relieved by the injection of FVIII and transfusion of blood. He also had a history of occasional non-traumatic episodes of epistaxis and skin bruising since birth. Past surgical history revealed a difficulty in blood clotting after circumcision, which required medical management. The patient's vaccinations were up to date according to the expanded program of immunization (EPI). He is the first product of a consanguineous marriage, where the second product is a seven-year-old male with similar complaints as to our patient.
On examination (O/E), a young boy of average height and lean built was found oriented to time, place, and person with a Glasgow coma scale (GCS) of 15/15. His heart rate (HR) was 88 beats/min, blood pressure (BP) was 110/80 mmHg, respiratory rate (RR) was 20 breaths/min, and he was febrile (102°F), with no visible bruises. Upon locomotor examination (Table ), swelling with or without tenderness and restricted range of movement in the involved joints was noted (Figures -). All other systems were found unremarkable.
Upon history and physical examination, a diagnosis of hemophilia A with hemarthrosis and HA was suspected for which two pints of fresh frozen plasma (FFP) were transfused until FVIII was arranged. Injection Provas was given to relieve pain. Laboratory (lab) investigations were sent. Upon stabilization, the patient was transferred to the ward.
Lab investigations revealed hemoglobin (Hb) of 7.5 gm/dl, mean corpuscular volume (MCV) of 82 fl (Normal (N) = 76-96), mean corpuscular hemoglobin concentration (MCHC) of 33.2 gm/dl (N = 32-36), total leukocyte count (TLC) of 8.7 x 103/μL (N = 4-11), and platelet count (PLT) of 309 x 103/μL (N = 150-400). The level of C-reactive protein (CRP) was found to be 30.7 mg/L (N = <5). The clotting profile showed an international normalized ratio (INR) of 1.04, prothrombin time (PT) of 10.9 seconds and activated partial thromboplastin time (aPTT) of 29 seconds. FVIII levels were found to be less than 1%.
A radiologic examination of the right elbow, left elbow, and left knee showed Grades 1, 2, and 5 arthropathic changes, respectively, upon X-rays of the anteroposterior (AP) and lateral views. Therefore, a final diagnosis of severe hemophilia A with hemarthrosis and HA was made. FVIII was arranged and injected 1750 international units (IU) intravenous (I/V) on Day 1 followed by 700 IU I/V on Days 2, 3, and 5 with subsequent improvement in the patient’s condition. The further plan was to give FVIII on every alternate day till symptoms completely resolved.
The patient was counseled for regular follow-up after every three to four weeks, FVIII prophylaxis and at least 60 minutes of low-impact daily physical activity. He was also taught to immediately report to the emergency department (ED) in case of any joint swelling and pain, bruising, epistaxis, blood in urine or stool, severe headache, or weakness on any side of the body.


A 30-year-old Hispanic female referred to our clinic with the history of chronic low back pain for the last two years. She mentioned that she has been suffering from pain in her back during her second peripartum period which never resolved. During her first pregnancy, she had this pain, but it resolved after delivery. Both of her pregnancies were normal vaginal deliveries without any complications five years apart. Now her pain is mostly in the lower lumbosacral area, sharp in character, 10/10 in intensity intermittently. It gets aggravated by lifting heavy weights or doing household chores and relieved by taking rest. She was taking ibuprofen and cyclobenzaprine as needed, with symptomatic relief. She denied any joint stiffness, swelling, deformity, no skin rash, no eye, and bowel symptoms. She denied any weight loss. Physical examination was normal. Faber’s /Patrick’s test (flexion, abduction, external rotation of hip) was non-revealing. Straight leg raising test and Schober’s test were normal. X-ray of her back showed significant sclerosis at the iliac border of SIJs (Figure ). Several other tests were performed to exclude inflammatory and other pathologies (Table ). No other sources of inflammation were identified. She had physical therapy for six weeks and was recommended to continue exercises at home. She was also prescribed Ibuprofen and cyclobenzaprine as needed at the same time. She had significant improvement in her symptoms in three months with minimal usage of Ibuprofen and completely stopped cyclobenzaprine.


A 76-year-old Japanese man was referred to our department with a several-week history of right inguinal pain and discomfort in his right femur that worsened with movement. Laboratory tests showed a normal white blood cell count and C-reactive protein level. Ultrasound and computed tomography examinations indicated a vermiform appendix in an inguinal hernia sac, with no remarkable findings of inflammation in the appendix (Fig. a, b). He was clinically diagnosed as having an AH without appendicitis. Reduction of the hernia was attempted under ultrasound but was unsuccessful. Thus, we planned combined TEP with mesh repair and laparoscopic appendectomy after laparoscopic reduction.
He was placed in a supine position and underwent general anesthesia by tracheal intubation. A laparoscopic transabdominal approach was initially performed after establishment of pneumoperitoneum. A 5-mm direct umbilical trocar and a needle forceps (Endo Relief™; Hirata Precisions, Chiba, Japan) were introduced into the upper right abdominal quadrant to inspect the hernia canal for the absence of appendicitis and reduce the appendix laparoscopically (Fig. ). This inspection revealed a 3 × 2 cm right external inguinal hernia defect with the appendix; no other intra-abdominal pathology was identified. The vermiform appendix was pulled out and placed in the abdominal cavity without tearing the appendix (Fig. ). Next, the hernia sac was reduced into the abdomen via the laparoscopic TEP approach. Our patient was placed in the 30° Trendelenburg position. The rectus muscle was lateralized and a Covidien Balloon Dissector (Medtronic, Minneapolis, MN, USA) was inserted preperitoneally from the umbilical incision of the skin to the symphysis pubis. The balloon was insufflated to open the extraperitoneal area. Additional trocars were introduced as follows: a 12-mm trocar in the initial umbilical incision of the skin and anterior right fascia of the rectus, a 5-mm trocar at the symphysis pubis in the midline, and a 5-mm midline trocar between the symphysis pubis trocar and the umbilical trocar. To cover the myopectineal orifice, Hesselbach’s area, and the femoral canal orifice, a 7.9- × 13.4-cm mesh (3DMax™ mesh; Bard, Murray Hill, NJ, USA) was fixed to Cooper’s ligament and the rectus muscle with an absorbable fixation device (AbsorbaTack™; Medtronic). Finally, we removed the trocars and newly inserted two 5-mm trocars at the umbilical region for the intraperitoneal operation with the initial use of needle forceps. The appendectomy was completed via a laparoscopic approach, and the appendix was removed in a sterile bag via the umbilical region. The total estimated blood loss was 5 mL, and the total operation time was 111 minutes. Our patient was started on intravenously administered cefmetazole at 2.0 g intraoperatively. A histopathological examination confirmed chronic appendicitis with fibrosis and inflammatory cells. Postoperatively, he was discharged and had an uneventful recovery. He was followed up at 6 months postoperatively. He had no recurrence of the hernia, and the wound had healed without inflammatory signs.


We report a case of a 66-year-old male with minimal co-morbidities who presents with lower trunk flat back deformity, severe iatrogenic kyphosis and sagittal imbalance following 9 months postoperative lumbar decompression and fusion (L2-L5) with postero-lateral grafting, without inter-body implants from a different institute. He experienced significant pain due to L4 and L5 motor / sensory radiculopathy. Reflexes were absent in both lower limbs with a bilateral foot drop. Oswestry Disability Index was 74%, with Visual Analog Scale pain score of 10 in the standing position, 8 on lying flat.
Computed tomography (CT) scan revealed loosening and non-union of the inferior aspect of the fusion construct. There is pull-out of the inferior screws (Fig. A) with haloing around the body and distal aspect of the pedicle screws. (Fig. ). Standing EOS scan reveals gross sagittal imbalance. The kyphotic angle due to the construct failure at L3/4 level was approximately 45°. A flat back deformity can be seen along the vertebral levels above the level of screw pull-out. Bone mineral density was normal for his age. Figure A shows the pre-operative presentation, with significant sagittal plane deformity and bent-knees in order to maintain a gaze along the horizon while requiring a walking aid for ambulatory.
The haloing effect demonstrated by the pedicle screws is consistent with hardware failure, and also seen in the “PEEK-Halo” effect when PolyEther-Ether-Ketone (PEEK) is being used as an intervertebral implant which results in poor osseointegration. However, in this case, the poor osseointegration was a result of repetitive screw cranial-caudal micromotions and toggling which prevent consistent screw – bone contact but not due to hardware material.
A revision procedure utilizing both anterior and posterior approach was carried out (Fig. ). Lordosis was restored utilizing 2 anterior lumbar interbody fusion (ALIF) cages (L3/4 and L4/5 levels) and Posterior Smith-Peterson osteotomy at L3/4. Focal lordosis of approximately 22o was corrected resulting in a total correction of over 65 degrees at L3/4. The patient was able to stand up-right which enabled him to maintain his view on horizon when his spine was in a neutral position. Figure B shows patient post-op with a corrected posture requiring no walking aids to ambulate.


The patient is a 36-year-old male with no significant past medical history. He presented to a local hospital with a complaint of left-sided abdominal pain for several days. He was initially managed conservatively as a non-specific abdominal pain and discharged home. Two months later, he re-presented with severe abdominal pain associated with signs and symptoms of sepsis. Computed tomography (CT) scanning of the abdomen revealed a phlegmon in the LUQ and free fluid (A). A diagnostic laparoscopy was performed, and showed extensive peritoneal deposits of thick mucoid material. Biopsies were taken, washout was performed, and drains were inserted. Later, his sepsis resolved, and the biopsies showed LAMN.
He was then referred to our hospital for further management. Upon evaluation, upper and lower gastrointestinal scopes were performed and showed no evidence of pathology.
Reviewing the CT imaging identified the abnormal anatomy of the bowel where the right colon runs retroperitoneally behind the mesentery of the small bowel. The cecum with the appendicular mass was found in the left side of the abdomen joining the colon at the splenic flexure. The duodenojejunal (D–J) junction was found slightly to the right side of the midline, and the inferior mesenteric vein to its left side. In addition, a large right kidney, an atrophied left kidney, and two ureters were noted (B).
The case was discussed in a multidisciplinary meeting (Tumor Board), where the committee advised to proceed management with CRS/HIPEC.
Exploratory laparotomy revealed extensive deposits all over (A), giving a Peritoneal Cancer Index (PCI) of 39. The abnormal anatomy was clarified as described in the CT scan. The duodenum was partially intraperitoneal (B). There were congenital adhesions between the sigmoid colon and the small bowel mesentery. Severe adhesions were also apparent in the LUQ—phlegmon-like—involving the greater omentum, cecum, appendix, splenic flexure and spleen. This phlegmon was resected en-bloc to include the spleen, greater omentum, terminal ileum, and part of the ascending, distal transverse, and splenic flexure colon. However, most of the left colon, sigmoid, and the intraperitoneal rectum were also heavily diseased. Thus, the resection was extended to include the entire colon beyond the distal transverse with the upper two-thirds of the rectum (A and B). Complete cytoreduction was achieved through stripping the entire peritoneum, including the peritoneal lining of the diaphragm, burning the liver surface, and resecting both the greater and lesser omentum. In addition, small bowel mesentery and its surface were cleared from the disease.
Creating a tension-free anastomosis with good vascularity between the remaining transverse colon and the low rectum constituted a great challenge. The segment was dependent on the middle colic pedicle, and could not reach to the low rectum in the current anatomical position. Considering this unusual challenge, we aimed to preserve the transverse colon by rotating the colon along the axis of the middle colic pedicle from left to right after scoring the peritoneal surface of the mesentery. At this position, the distal end of the transverse colon reached the low rectum without tension through the right side (A and B).
Given this procedure has not been described before, we questioned the perfusion and tension in that new position. Therefore, the colon was left in the proposed position for 90 minutes, during which we performed the HIPEC by infusing heated intraperitoneal mitomycin C and doxorubicin, in addition to intravenous 5-fluorouracil and leucovorin.
Upon completion of HIPEC, the colon retained normal vascularity and viability in the new rotated position. Therefore, we proceeded with the anastomosis by connecting the low rectal stump to the rotated distal transverse colon, using the stapled technique (). After washing the abdominal cavity with warm water and re-inspecting the bowel, drains were placed intraabdominally and bilateral chest tubes were inserted. The midline laparotomy wound was closed, and a double-barrel stoma was created with the distal ileum as one end, and the proximal part of the remaining colon as the mucous fistula ().
The patient was extubated at the end of the procedure, and transferred to the intensive care unit (ICU), where he recovered gradually for several days, and was then transferred to the surgical ward. Heparin infusion was initiated eight hours postoperatively as an attempt to protect against a concerning risk of thrombosis in the rotated vascular pedicle, which could endanger the blood supply to the remaining colon. Unfortunately, during his early postoperative days, he developed a subsegmental pulmonary embolism despite being on mechanical venous thromboembolism (VTE) prophylaxis and heparin infusion. However, all other aspects of his postoperative course were uneventful. Postoperative abdominal CT scan was performed with barium injected through the stoma, which showed no leak or collection (). Four weeks following his surgery, he was discharged home in a good condition.
The final histopathology proved the diagnosis of LAMN in all resected specimens. He was regularly followed up in the clinic. His last visit was seven months after surgery, where he appeared well and had no complaints. Closure of the stoma is planned after one year and following reevaluation for any possible recurrence.


A 31-year-old female, gravida 2, para 2 (G2 P2), referred to the gynecologic clinic with a main complaint of secondary infertility during the last twelve months. Written informed consent was obtained from the patient for publication of this case report and any accompanying images. The patient had two previous C-sections. Her menstrual cycles were ovulatory. Spermogram was unremarkable and hormonal assay did not show any abnormality. HSG was performed and revealed a migrated copper IUD with its long tail out of the uterine cavity (Fig. ). Plain abdominopelvic radiography also indicated a rotated T-shaped IUD in the pelvis (Fig. ). A transvaginal ultrasound was also performed by a skilled radiologist who reported a copper IUD in the bladder lumen with a small portion of it within the bladder musculature. The patient had taken multiple courses of antibiotics for urinary tract infection (UTI), but her symptoms never disappeared. The patient also underwent cystoscopy for recurrent infection last year, but no pathological finding was detected. Eventually, the patient said that her symptoms were related to the possible adhesions following two previous operations. The patient had a history of IUD insertion following her last C-section about eight years ago. After three years, however, the patient decided to remove it due to recurrent vaginal secretions. Three years later, her IUD was expelled, and another copper IUD was inserted. The patient removed the other copper IUD for becoming pregnant about two years ago. The patient was very confident of its removal, but her recent HSG, interestingly, demonstrated a rotated copper IUD in the pelvic cavity. Physical examination was essentially normal. A baseline complete blood count, urea, and creatinine levels were normal. The patient was candidate for a hysteroscopic cystoscopy. Hysteroscopy was normal except for a small fibrotic defect at the lower segment of the uterus. During cystoscopy, the long tail of the copper IUD was found on the posterolateral border of the bladder far from ureteral offices (Fig. ). The two short arms adhered to each other were embedded in the mucosal and muscular layer (Fig. ). No calculus was observed within the bladder cavity. Using glycine as the media, a mono-polar loop entered the bladder. A gentle and brief cautery was applied on the mucosa where the shadow of a short arm of the device was observed. The copper IUD was safely removed through the urethra using a special grasper. There was no major defect in the place of the copper IUD in the bladder. The bleeding points were effectively cauterized (Fig. ). The patient was discharged the next day with an indwelling catheter. After catheter removal, the patient did not complain of any urinary symptoms.


A 57-year-old female patient presented with a chief complaint of abnormal findings upon medical examination. She had no significant lifestyle/family history or medical history. Regarding her history of present illness, the patient was referred to our department after undergoing a computed tomography (CT) scan in September 2017, which revealed a tumor in the descending colon.
Hematological analysis revealed the following results: White blood cell count, 7900/μl; hemoglobin level, 12.6 g/dL; platelet count, 28.4 × 104/μl; carcinoembryonic antigen level, 3.3 ng/mL; and CA 19–9 level, 11.1 U/mL. The results were not significant.
Lower gastrointestinal endoscopy findings revealed a 25-mm type 0-Is lesion observed in the ascending colon and a 30-mm type Is lesion in the descending colon. In the abdominal contrast-enhanced CT findings, the tumors could not be located, and lymph node, lung, or liver metastases were not observed. Regarding histopathological findings, biopsy results revealed that the tumor in the ascending colon was a high-grade adenoma and the tumor in the descending colon was a moderately differentiated adenocarcinoma. Endoscopic tumor resection was not possible due to the difficulty in maneuvering the endoscope in the ascending and descending colon. Thus, surgery was considered.
In the first round of surgery, surgery was initiated with five ports. No ascites, peritoneal dissemination, or liver metastases were observed. The ascending colon polyp was adenoma, but there was a polyp near the ileocecal valve. Therefore, it was difficult to resect the ascending colon and we chosed the right hemicolectomy. The descending colon polyp was adenocarcinoma on biopsy. However, we diagnosed intramucosal cancer and performed descending colon resection. Laparoscopic resection of the descending colon and right hemicolectomy was performed according to standard procedures. There were two functional end-to-end anastomoses. Regarding the clinical course after the first round of surgery, mechanical intestinal obstruction occurred on the 9th day postoperatively, and CT scan showed that intussusception occurred from the functional end-to-end anastomosis (Figs. and ). An attempt at endoscopic reduction was unsuccessful (Fig. ), and open surgery was considered on the 16th day after the first round of surgery.
In the second round of surgery, when midline laparotomy was performed, the site of the ileocolic anastomosis was found to be firmly adhered to the side wall and right retroperitoneum. Because the staple used for anastomosis may have adhered to the peritoneum. The intestines in the proximal side of the anastomosis were not fixed. Examination of the anastomosis revealed that the ileum had passed through the anastomosis and entered the transverse colon (Fig. ). Although manual reduction was attempted, manipulation was challenging. The ileocolic anastomosis was resected. End-to-end anastomosis was performed, and surgery was completed. Histopathological findings revealed no lesions in the resected intussusceptum (Fig. ). Regarding the clinical course after the second round of surgery, the postoperative clinical course was favorable, and the patient was discharged on the 10th day after the second surgery.


A 12-month-old Japanese boy born to nonconsanguineous parents was a second child with a healthy elder sister. He had grown and developed normally. No abnormalities were detected in a newborn screenings using tandem mass spectrometry. He presented with a fever, upper respiratory symptoms, and loss of oral intake. After 7 days of febrile illness, he was admitted to the hospital because of polypnea and cyanosis. Influenza A was detected in a rapid test. Laboratory investigation (Supporting Information Table ) revealed mild hyperammonemia (173 μg/dL), elevated aspartate aminotransferase (AST; 461 IU/L) and alanine aminotransferase (ALT; 142 IU/L) levels and severe metabolic acidosis (pH 6.985, pCO2 13.8 mmHg, HCO3 3.2 mmol/L, BE −26.5 mmol/L; and anion gap, 30.5 mmol/L). The creatine kinase, lactic acid, and pyruvic acid levels were normal. Hypoglycemia was not detected (9.39 mmol/L) before glucose infusion was started. While the level of FFA was elevated (1.31 mmol/L), that of acetoacetic acid did not increase (0.04 mmol/L) and that of 3-hydroxybutyrate was only mildly elevated (0.154 mmol/L).
Physical examination revealed marked hepatomegaly. Abdominal computed tomography (CT) revealed severe fatty liver and hepatomegaly without splenomegaly (Figure ).
After admission, the patient had a convulsion, which was immediately treated with diazepam (1 mg/kg). However, he did not regain consciousness and had no reaction to pain. Intravenous infusion including glucose was initiated after taking critical blood samples. Peramivir was also administered against the influenza A infection. Administration of carnitine and vitamin cocktail therapy including vitamin B1, B2, B12, C, and biotin was started, considering the possibility of mitochondrial dysfunction. At the second day of admission, his consciousness did not improve, and the severe metabolic acidosis lasted even after correction with sodium bicarbonate. Continuous electroencephalography monitoring revealed no high-amplitude slow wave. On the third day, his symptoms improved dramatically. The patient reacted to stimulation and could open his eyes. He could sit by himself on day 4, and his consciousness became completely normal on day 5. The fatty liver and hepatomegaly were improved somewhat on day 11 (Figure ). A brain MRI performed on day 10 revealed no abnormality. The patient was discharged without any complication on day 14.
After discharge, he was managed with a normal diet and avoidance of long fasting periods. Around 3 months after the onset, he had enteritis. He overcame it without metabolic crisis with intravenous glucose administration at the local hospital. However, his liver was enlarged and his AST and ALT levels spiked again (Figure ). In 7 months after the onset, his AST and ALT levels finally normalized. In 13 months after the onset, the fatty liver had mostly disappeared, but mild hepatomegaly was still detected on CT. After the first episode of metabolic crisis, the patient experienced no further episodes of metabolic crisis even with minor illnesses. At the age of 6 years, he had grown and developed normally.


Case 1. A 5-year-old boy was diagnosed with PDA and cardiac dilation. A clear diagonal line was seen in the main pulmonary artery. Its shape and length changed in the different echocardiographic views (Figures , , , and ). A linear line was seen in color Doppler imaging (). We also observed the artifact in the patient's video recording (). This patient's diagnosis was confirmed by CTPA (Figures and ) and surgery.


Case 2. A 1-year-old girl was diagnosed with an atrial septal defect (ASD) without pulmonary artery dilation or PAH. A horizontal line was seen in the main and left pulmonary arteries and varied in different echocardiographic views (Figures –). We also visualized the ASD flow from the left to right atrium (). The length of the linear artifact was short. The thymus gland was prominently seen. This patient's diagnosis was proven by surgery. The surgeon repaired the ASD and found no fibrous band or dissection in the pulmonary artery.


Case 3. A 2-year-old girl was diagnosed with PDA. A very long diagonal line was seen in the main pulmonary artery from the left high parasternal view and suprasternal aortic short-axis view (Figures –, and ), but not in the aortic short-axis view or pulmonary artery long-axis view (Figures and ). The long, thick artifact line was clear and could still be seen in color Doppler imaging (). The adjacent thymus gland was clearly visualized. This patient underwent PDA ligation without evidence of dissection in the pulmonary artery.


Case 4. A 38-year-old woman was diagnosed with systemic lupus erythematosus and PAH. Pulmonary artery dilation and a long diagonal line were seen from the left pulmonary artery to the main pulmonary artery (). CTPA showed pulmonary artery dilation without a luminal filling defect (). The right heart was significantly enlarged and hypertrophied. We also observed the artifact in the patient's video recording ().


The patient was an 82-year-old male who was scheduled for a robotic left lower lobectomy for the resection of a biopsy-proven squamous cell lung carcinoma. He had a medical history of hypertension controlled with multiple medications; a 40-pack-year history of tobacco abuse, with a 20-year history of abstinence; and a prior history of melanoma of his left upper extremity, which was successfully resected.
Standard American Society of Anesthesiology (ASA) monitors were placed and preoxygenation was performed; general anesthesia was induced with propofol, followed by the administration of muscle relaxant and the placement of a left-sided, double-lumen endotracheal tube. Additional venous access and arterial line placement occurred concurrently while the correct placement of the endotracheal tube was confirmed by bronchoscopy. The placement was then reconfirmed after the patient was situated in the right lateral decubitus position. The left lung was isolated and deflated, and the surgeon proceeded to place ports to facilitate the robotic resection as follows: the sixth intercostal space in the anterior axillary line, the third intercostal space in the anterior axillary line, and the ninth intercostal space in the posterior axillary line. The surgical procedure continued uneventfully from an anesthesia perspective with level 7 and 10 lymph node dissections, extensive lysis of adhesions and pericardial and pleural fat to facilitate visualization, and a left lower lobectomy. Surgical blood loss was estimated at less than 50 cc. Chest tubes were placed through the sixth and ninth intercostal port incisions. A bolus of 30 cc of 0.5% bupivacaine was administered via a catheter placed at the tenth intercostal space in the posterior axillary line for an elastomeric pump ball to infuse local anesthesia for post-operative pain management. Within 15 minutes of this, the patient began to experience hypotension, requiring incrementally increasing doses of vasopressors. Over the course of 10 minutes, escalating doses of phenylephrine were becoming ineffective at restoring the patient’s mean arterial pressures (MAP) to his intraoperative baseline (within 20% of the patient’s preoperative MAP). Vasopressin was administered, in 1-2 mg aliquots, as urgent assistance was summoned to the operating room. The hemodynamic instability was immediately reported to the surgeon. Based on the scant chest tube drainage, a thoracic source of bleeding was considered unlikely. A portable chest radiograph was ordered and point-of-care blood testing was performed. The hemoglobin was resulted at 6.5 g/dL, and transfusion was initiated while awaiting a confirmatory hemoglobin sent to the lab, which was resulted at 7.4 g/dL (preoperative hemoglobin 13. 5 g/dL). The chest radiograph did not show any areas suspicious for bleeding. The double-lumen endotracheal tube was removed and replaced with a single-lumen endotracheal tube to facilitate transport and the potential for prolonged mechanical ventilation, and the patient was transported urgently to the computed tomography (CT) scanner for chest, abdomen, and pelvis imaging. Upon review with the radiologist, the diagnosis was made of a subcapsular splenic hematoma with fluid extending to the diaphragm and tracking along the paracolic gutters, concerning for a splenic injury (Figure ).
The patient was then returned to the recovery room, where he continued to require ongoing blood transfusion and phenylephrine infusion to maintain satisfactory blood pressures. After receiving a total of four units of packed red blood cells, the phenylephrine infusion was able to be weaned significantly and serial hemoglobin values stabilized. Although both splenectomy and splenic embolization were considered in this patient, as his hemodynamic instability abated, the decision was made to observe him in the intensive care unit and to continue serial hemoglobin monitoring. On the first postoperative day (POD), he was weaned completely off of phenylephrine and was extubated. He was discharged to a rehabilitation facility on POD 15.


A 77-year-old male patient had a history of myocardial infarction for half a year, but without significant discomfort, lived a normal life at home. Two hours before seeing a doctor, he suddenly developed significant palpitations and shortness of breath and was admitted to the Second Hospital of Lanzhou University by ambulance. The patient’s expression was painful and a distinct murmur was heard in the precordium. Electrocardiogram showed old left ventricular anteroseptal myocardial infarction. X-ray showed enlarged heart shadow. Myocardial enzymes and other laboratory test results showed no significant abnormalities. Echocardiography showed that the interventricular septum was thinned near the apex and bulged toward the right ventricular side, exhibiting “paradoxical motion,” and a rupture opening of about 8 mm in diameter was visible on its top (Fig. ). CDFI: left ventricular blood shunted to right ventricle through rupture (Fig. ), the shunt velocity measured by CW is about 410 cm/s, PG:67 mmHg. Left ventricular enlargement (anteroposterior diameter about 61 mm), significantly reduced wall motion amplitude, left ventricular ejection fraction (EF) about 33%, moderate aortic and mitral regurgitation, pulmonary artery systolic pressure about 60 mmHg. Echocardiographic diagnosis: old myocardial infarction of ventricular septal apex with ventricular septal rupture. Due to the patient’s older age and reduced left ventricular function, surgical repair of the site of ventricular septal rupture was very difficult. After multidisciplinary discussion, it was agreed that the patient could not undergo thoracotomy and was not suitable for thoracotomy, and echocardiography guided interventional occlusion of the ruptured interventricular septum could be performed. Interventional occlusion was performed after obtaining the patient’s family’s consent and signing a written consent. Under the guidance of transesophageal echocardiography, the ventricular septal rupture was clearly displayed during the surgery. The size of the rupture was measured again. In order to prevent the occluder device from falling off, a VSD occluder device that is larger and can cover the normal myocardial tissue was selected. Under direct vision, the guide wire and sheath smoothly passed through the ventricular septal rupture (Fig. ). The left ventricular side of the occluder device was opened and the occluder device was gently pulled to determine the stability of the occluder device (Fig. ). Then the right ventricular side of the occluder device was opened (Fig. ), and then the occluder device was gently pushed to determine the stability of the occluder device again to ensure that the occluder device was stable and there was no residual shunt around the occluder device. The operation was completed. After repeated examinations within one year, the occluder device was in normal position without residual shunt(Fig. ), left ventricular diameter was gradually decreased (anteroposterior diameter was about 52 mm), left ventricular function was improved, and left ventricular EF reached 46%. The patient can live a normal life.


A 58-year-old male with KS, diagnosed at age 17, presented to our centre. Throughout adolescence and early adulthood, he identified as female; however, he later identified as male and used TRT periodically in adulthood for two to three decades. The patient tells us the dosing and frequency of TRT during this time period was variable and intermittent; however, we were unable to obtain further details. He was diagnosed with T1 Gleason Grade 3+3 prostate adenocarcinoma six years before presenting to our centre. At the time of diagnosis, prostate-specific antigen (PSA) measured 7.79 u/L. Due to a history of traumatic experiences with the healthcare system relating to his gender identity, he had not pursued prostate cancer treatment. A second biopsy was performed after our initial consultation with the patient and revealed progression to Gleason Grade 3+4. A repeat PSA had increased marginally to 8.22 u/L. The patient had stopped TRT for much of the time period between his diagnosis of prostate cancer and presentation to our centre. Ultrasound-guided biopsy demonstrated 4/12 cores positive with 4% of tissue positive for malignancy. Clinical staging found evidence for localized disease only. Past medical history included deep vein thrombosis (DVT) following a cycling accident, hypercholesterolemia, and hypertension.
During the ensuing discussions regarding prostate cancer treatment, the patient expressed concerns regarding his symptoms of hypogonadism including weight gain and gynecomastia. Accordingly, he wished to continue TRT. He was counseled by his urologist, radiation oncologist, and endocrinologist about the possible increased risk of cancer progression in the setting of exogenous testosterone administration. He felt he was at a turning point with regard to his gender identity and had recently become sexually active, thus continuing TRT to maintain virilization was important for his QOL. Ultimately, he decided to proceed with definitive treatment in view of his cancer progression, with the caveat that he would remain on TRT. He decided upon radiation therapy rather than surgical management as this option aligned best with his values. He received local radiation 11 months after his second biopsy to a dose of 76 Gy in 35 fractions.
Post radiation therapy, a total testosterone level of 6.7-25.7 nmol/L was targeted, falling in the low-normal range for his age. Figure illustrates a timeline of the patient’s diagnostic and treatment journey. Three months post radiation, his testosterone measured 27.5 nmol/L and PSA 2.4 u/L. Five months thereafter, this increased to testosterone of 34.5 nmol/L and PSA 4.87 u/L. The patient was advised that he likely has a residual disease with progression and a rapid PSA doubling time. After extensive discussion, he decreased his TRT dose by half. Around this time, he started tadalafil for erectile dysfunction and possibly due to its effectiveness, he eventually stopped TRT altogether. He attained good erectile function defined as function sufficient to complete sexual activity. At 14 months post-radiation, his testosterone dropped to 2.0 nmol/L, and PSA reached a peak of 5.6 u/L. He was advised to remain off TRT. Five months after discontinuing TRT, his PSA fell to 0.53 u/L. The responsiveness of his PSA to changes in TRT suggests that the prostate and possible residual disease remains sensitive to testosterone.
Since completing radiation therapy, the patient and his physicians have struggled to achieve a balance between adequate TRT to manage his hypogonadism symptoms and the risk of accelerating cancer progression. Long-term risk of hypogonadism includes osteoporosis; a bone mineral density showed a spine T-score of -1.4 and a femoral neck score of -0.3. After evaluating TRT risks and benefits, the patient has decided that the benefits of TRT outweigh the risk of prostate cancer progression. Under the supervision of his treatment team, the patient continues to use TRT variably four years after his initial presentation while adjusting for his PSA levels to optimize his QOL, gender identity, hypogonadism symptoms, and the risk of prostate cancer progression.


A 33-year-old man presented to our clinic with complaints of watering, redness, and purulent discharge in the right eye. The patient reported seeing a physician a year earlier in Georgia due to fatigue, nausea, vomiting, and diarrhea. After his diarrhea and vomiting had resolved, he had swelling of the lymph nodes on the right side of the neck. After returning to Turkey for treatment, he had received cephalosporin and penicillin for suspected pharyngitis. When night sweating and weight loss were added to his complaints, he had presented to another hospital where his treatment was changed to amoxicillin-clavulanic acid 1 g 3 times a day and ciprofloxacin 750 mg twice a day, and incisional drainage was performed on the lymph nodes of his neck. When his symptoms failed to resolve completely, he had presented to the department of infectious diseases of a different university hospital. Serum agglutination test was positive for F. tularensis at a titer of 1/1280 and he was prescribed streptomycin 1 g per day for 9 days followed by 1 g twice a day for 5 days for a total of 14 days, followed by doxycycline 100 mg twice a day for 1 week. Ultrasound examination of the neck had revealed multiple abscesses in the right submandibular region and pathological lymph nodes including multiple calcifications in the right cervical chain, while magnetic resonance imaging of the neck showed retropharyngeal abscess narrowing right nasopharynx and oropharynx and submandibular lymphadenopathies (LAP) including cystic and necrotic areas (). He reported that the LAPs had resolved after a few months with no recurrence, but complaints of watering, swelling in the lacrimal sac area, hyperemia, and pain in the right eye developed a few weeks later. The patient presented to our clinic with recurrent swelling around the lacrimal sac, hyperemia, and purulent discharge.
On examination his best corrected visual acuity was 20/20 in both eyes. Intraocular pressure measured by automatic tono-pneumometry was 15 mmHg in each eye. On slit-lamp examination, epiphora was noted in the right eye and the left eye was normal. There was swelling in the area of the right lacrimal sac (). Fundus examination was normal in both eyes. In nasolacrimal lavage, the patient’s right nasolacrimal duct was occluded and the common canaliculus was patent. Discharge of purulent material from the right lower punctum was noted after lavage. A sample of the purulent discharge was collected and sent to the microbiology laboratory for culturing and the patient was started on oral amoxicillin-clavulanic acid 1 g twice a day and topical ciprofloxacin drops 4 times a day. Antibiotherapy was discontinued because the culture was negative. Consultation from the otorhinolaryngology (ENT) department was requested to rule out any intranasal pathology. The patient underwent ENT examination, followed by nasal endoscopic examination. In addition, to rule out intranasal pathologies that may present an obstacle to surgery, the paranasal sinuses were examined using computed tomography. No intranasal pathologies were detected in ENT evaluation. Dacryocystorhinostomy surgery was recommended to the patient, but he refused the procedure.


A previously healthy, 72 year old man with a history of well-regulated hypertension was diagnosed with bladder cancer causing severe nephropathy due to bilateral obstruction of the ureter ostium. The patient was referred to an 18F-FDG PET/CT for staging. 18F-FDG PET/CT was acquired 60 min after injection of 280 MBq 18F-FDG on a Biograph mCT Flow 64 (Siemens Medical Solutions, Erlangen, Germany) with a flow table of 0.8 mm/s. The PET images were reconstructed using Ordered Subset Expectation Maximum, applying time-of-flight and point-spread-function. A CT (120 kV/10–150 mA) was performed without intravenous contrast due to the patient’s nephropathy.
Non-enhanced CT showed a large hollow process with a distinct calcified wall mimicking a porcelain gallbladder. However, the fused PET/CT demonstrated a discrete FDG uptake in the central part of the process, comparable to blood pool activity (SUVmax 3.5) with a surrounding mural thrombus () corresponding to a large HAA measuring approximately 107 × 105 mm with a thick calcified wall. Color Doppler ultrasound was performed to confirm the diagnosis. Ultrasound showed a giant aneurysm with perimural thrombus and intraluminal turbulent flow (). In addition, 18F-FDG PET/CT revealed lymph node metastases and peritoneal carcinosis.
The patient was discussed at the urological multi-disciplinary team conference and, based on the disseminated urothelial carcinoma, no treatment with curative intent was possible. The patient was offered palliative chemotherapy. For evaluation and potential treatment of the giant HAA, the patient was referred to the Department of Vascular Surgery. Based on the poor prognosis of the cancer, it was decided that there was no indication for either open or endovascular treatment of the aneurysm due to the high risk of such procedures. Palliative treatment was initiated for the bladder cancer, and the patient was followed with non-contrast enhanced CT.
A total of three CT scans were performed, showing minimal progression of the HAA from 107 × 105 mm to 110 × 106 mm. The patient did not experience any symptoms related to the aneurysm until his death 8 months later. The patient presented in this case report was identified during a quality assurance of our use of FDG PET/CT in bladder cancer. This study was approved by the Danish National Data Protection Agency and according to national legislation retrospective, observational studies do not require approval from the ethical committee.


A 45-year-old man presented to the hospital with complaints of rectal pain and bright red blood with each bowel movement for the past 6 months. He also described cramping rectal pain alleviated by bowel movements and aggravated by sitting and straining. He denied fevers or chills, but endorsed 15-pound weight loss in the last 3 weeks due to anorexia and fear of having a painful bowel movement. He admitted to have receptive anal intercourse, but had not been sexually active for the past 14 months due to pain. He also complained of dysuria and straining to urinate with incomplete voiding. The patient had a history of HIV infection and treated syphilis 6 months ago. His antiretroviral treatment consisted of dolutegravir and darunavir/cobicistat. A physical exam revealed a soft, nontender, and nondistended abdomen with normal bowel sounds. A rectal exam showed normal rectal tone, tenderness to palpation, external hemorrhoids, and a deep anal fissure. Laboratory studies were significant for hemoglobin of 12.6 g/dL, a white blood cell count of 5.6 K/uL, and creatinine of 1.15 mg/dL. His CD4 count was 283 cells/uL and his HIV viral load was undetectable. Urinalysis was normal. Computed tomography revealed prominent concentric thickening of the mid and lower rectum with associated mesorectal fat stranding and lymphadenopathy, highly concerning for an underlying rectal neoplasm or severe proctocolitis.
For this reason, the patient underwent a colonoscopy that showed a fungating and infiltrative partially obstructing medium-sized mass in the rectum, 10–15 cm from the anal verge (A). Discontinuous areas of nonbleeding ulcerated mucosa with no stigmata of recent bleeding were present in the rectum. Multiple biopsies were obtained. He was started empirically on doxycycline 100 mg every 12 hours for possible lymphogranuloma venereum or syphilis. Further infectious work-up revealed a negative gonorrhea/chlamydia PCR in urine and rectum. RPR (rapid plasma reagin) titer was 1:8; however, the patient had a titer of 1:32 6 months ago, consistent with history of adequately treated syphilis. Given the possibility of rectal cancer, magnetic resonance imaging (MRI) was ordered for staging, which demonstrated a polypoidal mass with a circumferential nodular border. More than 50% of the tumor had a very high T2 signal intensity compared with perirectal fat (B). Lymphadenopathies of ≥9 mm were identified in the mesorectal/superior rectal space. Histologic sections of the biopsy revealed colorectal mucosa with ulceration, epithelial cells with viral nuclear inclusion, exuberant granulation tissue, marked lymphoplasmacytic and eosinophilic infiltrate, and fibrinopurulent exudate (C). Immunohistochemistry for herpes simplex virus-1 was positive in epithelial cells demonstrating a viral cytopathic effect (D), supporting the diagnosis of HSV infection. Immunostain for Cytomegalovirus (CMV) and Adenovirus were negative. Warthin–Starry stain was negative for spirochetes. Gomori methenamine silver (GMS) stain and trichrome stain failed to demonstrate fungal organisms or parasites. The overall histologic changes were not suggestive of human herpes virus-8 (HHV-8) or HPV infection; therefore, testing for these viruses was not performed. Doxycycline was discontinued and the patient was started on valacyclovir (1 g) every 8 hours for 21 days. At 3-month follow-up, the patient reported complete resolution of rectal pain and denied any further episodes of bloody stools. Three months later, a sigmoidoscopy was performed and revealed a normal rectal mucosa and no evidence of masses.


A 77-year old female came to the department of oral medicine complaining about an ulceration on the left side of her tongue. A few days earlier, she had her lower left first molar non-surgically extracted. She reported that the tooth was very sharp and irritated her tongue. Now she was edentulous in the upper and lower jaw. Her medical history revealed hypertension and a penicillin allergy. She was taking nebivolol, lysinopril, and acetylsalicylic acid daily, and pantoprazolum occasionally. She did not smoke or consume alcohol. Clinical examination revealed an oblong ulceration on her left side of the tongue, the size of 1.5 × 4 cm. The extraction wound was healing fine. The patient was given a perilesional instillation of corticosteroid (methylprednisolone, 0.5 mL of 40 mg/mL,) around the tongue wound and local therapy, which included an antiseptic solution (chlorhexidine gluconate 2%) and corticosteroid ointment (betamethasone in orabase) to be applied four times a day.
At the control examination, after one week, the tongue lesion was enlarged (). The extraction wound healed, but an exposed area of bone was visible on the lingual side of the lower jaw, in the projection of the wound (). The patient did not wear dentures after the tooth extraction, so this was not a denture pressure sore, and also, this was not trauma from tooth extraction because it appeared a week after in the distal part of the mandible. Conventional radiographic analysis (orthopantomograph) had shown a healthy bone without osteolysis in that area (). An oral surgeon specialist smoothed the visible bone edges with a chisel without elevating the mucoperiosteal flap (to avoid ischaemia and further spreading of the wound). There was no bone sequestration and the exposed bone was not removed and histopathologically analyzed. The patient received local therapy, which included antiseptic solution (chlorhexidine gluconate 2%) and corticosteroid ointment (betamethasone in orabase) to be applied four times a day.
At the next control examination after one more week, the earlier lesions remained unchanged, but another area of exposed bone appeared in the edentulous ridge of the same jaw in the anterior region, and also on the lingual side of the jaw, with a diameter of 0.5 cm (). The sharp and protruding edges of the first lesion of exposed bone in the distal part of the mandible were manually reduced one more time, again without elevation of the mucoperiosteal flap. The patient was referred to make a complete blood count, blood glucose, and serum iron level to exclude anemia or diabetes mellitus as possible causes of slow healing, and all findings were within a normal range. The patient received local therapy for home, according to the previous protocol.
The control examination was after one week and there were no changes in the clinical appearance of the lesions. Since there was no improvement despite local therapy, a biopsy sample of mucosa was taken from the tongue ulceration to exclude possible malignant transformation. The histopathological finding was: “On most of the surface of the received sample, there is no preserved surface epithelium and there is a granulation tissue. At the edge of the sample, there is a multilayer squamous epithelium, which is degeneratively and reparatory transformed. The finding corresponds to the edges of an ulcer. There is no tumor tissue in the examined and received material”.
We decided to try the conservative treatment and the patient was then prescribed systemic antibiotic therapy of clindamycin 3 × 600 mg and metronidazole 3 × 400 mg for ten days.
At the control examination 7 weeks after the first clinical examination and 10 days after antibiotics were prescribed, all lesions healed.


A 65-years old previously fit and well Caucasian male patient presented to a small district general hospital with a 3 weeks history of recurrent rigors, fevers and night sweats. He was found to have kidney injury and thrombocytopenia. The whole-body CT (computed tomography) scan revealed in the retroperitoneal space a lesion measuring approx. 13x8x8cm (Fig. ). The patient was referred to our hospital for further evaluation and treatment. At presentation, blood biochemistry showed low platelets (55 × 109/L, reference range (ref.) 150–400), low white blood cells (3.2 × 109/L, ref. 4.0–10.0) with lymphocytopenia (0.47 × 109/l, ref. 0.8–4.0). The liver enzymes were elevated, too (Alanine Aminotransferase 1.16μkat/l, ref. < 0.73; Aspartate Aminotransferase 3.56μkat/l, ref. < 0.67) and albumin was low (21.9 g/l, ref. 35.0–53.0). The patient underwent explorative laparotomy, which revealed a tumor in mesocolon ascendens invading radix mesenterii. A surgical biopsy was performed. Few days later, he developed progressive pancytopenia, coagulopathy (fibrinogen 0,7 g/l) and his serum C-reactive protein concentration increased (140 mg/l). The patient was readmitted to the intensive care unit and treated with platelet transfusions, fibrinogen, prothrombin complex concentrates and broad-spectrum antibiotics. Despite all these measures, he developed multi-organ failure with dominant liver failure (Aspartate aminotransferase 18.64 μkat/l, ref. < 0.67; Bilirubin 158.4 μmol/l, ref. < 21.0) and refractory shock. He died 22 days after the initial presentation. At the time of death, the underlying disease leading to death was not known. An autopsy was performed.
Two formalin-fixed adipose tissue fragments with the size of 16x8x4 mm and 12x7x3 mm were sent to the Department of Pathology. Microscopically, we saw adult fat tissue with dense lymphocytic infiltration. The lymphocytic infiltration consisted mostly of small- to medium-sized cells with hyperchromatic irregular nuclei with little rim of pale cytoplasm. There was a pattern of isolated adipocytes surrounded by a dense rim of hyperchromatic lymphocytes (Fig. ). We also found necrotic adipocytes and reactive macrophages phagocytizing lymphocytes and erythrocytes. Immunohistochemically, the atypical cells rimming the adipocytes stained for CD45(LCA), CD2, CD3, CD5, CD7, CD8, granzyme B, perforin, TIA1 and TCRβF1 and did not stain for CD4, CD20, CD79a, CD56, CD30, EBER, CD1a, S100, myeloperoxidase, cytokeratin CAM5.2 and TCRγ. The proliferation index Ki67 varied between 10 and 50% (Fig. ).
Genomic deoxyribonucleic acid (DNA) from formalin-fixed paraffin-embedded (FFPE) tissue section was isolated using the QIAamp DNA FFPE Tissue Kit (Qiagen GmbH, Hilden, Germany). The clonality of the TCR rearrangements (TCR β, γ and δ) were tested using standardized multiplex polymerase chain reaction (PCR), as described by the BIOMED2 study group []. The clonality of the PCR products was assessed using an Agilent 2100 Bioanalyzer (Agilent Technologies, Santa Clara, CA, USA), with detection of clonal rearrangement of TCR-γ. Tests for clonal rearrangement in TCR-β and TCR-δ were negative.
Based on these morphological, immunohistochemical and molecular findings, we diagnosed panniculitic T-cell lymphoma with morphological and immunohistochemical features of SPTCL.
During outer inspection we found yellowish color of entire skin and cutaneous suffusions in the abdominal and genital regions. During the inner inspection, there was a thickened, firm, whitish area approx. 12x10x10 cm in the mesocolon ascendens. Intestine and mesenteric lymph nodes were unremarkable. Spleen was enlarged (470 g) and of soft consistency without focal lesions. Liver (2100 g) had a blunt margin, soft consistency and yellow cut surface. Other organs were unremarkable on gross examination. We collected samples for histopathological examination. We specifically and thoroughly examined subcutaneous adipose tissue and looked for any signs of a tumor. We have only found superficial reddish spots that were also sampled for microscopy.
Histopathological examination of mesenterial fat tissue revealed similar findings to those described above in the biopsy: adult fat tissue with atypical hyperchromatic lymphoid cells rimming the adipocytes, with macrophages engulfing whole lymphocytes and erythrocytes (Fig. c). In the spleen there was marked activation of red pulp with abundant histiocytes but no signs of infiltration by lymphoma. The bone marrow had cellularity about 50%, with trilinear hematopoiesis, with admixture of macrophages with signs of hemophagocytosis of lymphocytes and red blood cells (Fig. a). The immunohistochemistry of the vertebral bone marrow showed focal infiltration of CD8+ lymphocytes rimming the adipocytes; the finding is highly suspect from presence of lymphoma cells in the bone marrow (Fig. b). Liver tissue showed marked steatosis with cholestatic features (Fig. d), but no signs of lymphoma (Fig. e). Histopathological examination of the other organs, including abdominal skin and subcutaneous fat tissue (Fig. f), was unremarkable.
The autopsy determined the underlying disease as T-cell lymphoma with cytotoxic phenotype, with morphological and immunohistochemical features of SPTCL, associated with signs of hemophagocytic syndrome (clinical findings of fever, bicytopenia and hypofibrinogenemia, autoptic finding of enlarged liver and spleen and histiocytic hemophagocytosis of lymphocytes and red blood cells), probably leading to patients death due to multiorgan failure, in line with reported clinical features.


A 37-year-old Panamanian female patient without a pre-existing medical history, was diagnosed with a stage IIIB mammary ductal carcinoma (cT4N0M0), positive estrogen receptors (ER-positive), negative progesterone receptors (PR-negative) in her right breast in 2013, for which she received four cycles of doxorubicin (cumulative dose 240 mg/m2) and cyclophosphamide from January to March 2013, followed by paclitaxel from April to June. An electrocardiogram (Fig. ) and chest radiography done prior to chemotherapy revealed no cardiac alterations. In July 2013 the patient underwent mastectomy, with subsequent radiation therapy (45 Gy in 25 fractions).
Two years later, she was admitted to the hospital emergency department with 10 days history of orthopnea, swelling of her arms and legs, bendopnea, and fatigue. An echocardiogram was ordered, showing a reduced left ventricular systolic function (LVEF 25%). The diagnosis of anthracyclines induced cardiomyopathy was established. She was treated with a beta-blocker, diuretics and antihypertensives. After two weeks, she showed a significant improvement of her symptoms, with a LVEF of 45%. A year later, her 38-year-old brother was admitted to the hospital with a clinical presentation characterized by swelling of his legs, fatigue and minimum effort dyspnea, a left ventricular internal diameter in diastole (LVIDd) of 7.52 cm, with a LVEF of 20%. This clinical event prompted us to consider whether our patient had a genetic predisposition for DCM, and thus we performed a complete pedigree analysis of the proband (Fig. and Additional file : Figure S1) that showed the presence of several DCM cases in the family.
In order to establish the genetic mutation responsible for the familial DCM, genomic DNA was extracted from whole-blood samples of the proband, and her brother, using a Masterpure DNA purification kit following the manufacturer’s protocol, and untargeted whole exome sequencing (WES) assessment was performed. Briefly, DNA samples were amplified prior to exome library preparation by means of GenomiPhi V3 DNA Amplification Kit. Exome libraries of the selected individuals were prepared from amplified DNA using an Illumina Nextera Rapid Capture Exome kit (version 1.1, 37 Mb). Genomic DNA was then tagmented, and amplified using polymerase chain reaction amplification (PCR); regions of interest (exons) were captured by hybridization to specific probes followed by a cycle of PCR amplification. The sequencing step was performed on an Illumina HiSeq 2500 platform, targeting for 100 bp pair-end reads, and a mean sequencing coverage average above 80x. The clinically relevant variant was subsequently confirmed by means of Sanger sequencing. The genetic investigations revealed the presence of a LMNA-p.Arg190Trp (NM_170707.3:c.568C > T) missense variant.


A 70-year-old woman presented at the gynecology unit of our hospital complaining about a painful vulvar lesion in May 2017. She had no significant medical history. Physical examination revealed an exophytic and ulcerative vulvar mass, approximately 4 cm in diameter, localized on the right labium majus at less than 2 cm from the midline, without palpable inguinal lymph nodes bilaterally. An incisional biopsy was performed, and histology revealed an invasive poorly differentiated vulvar SCC. A total-body CT scan performed to stage the disease resulted negative for distant metastases.
The patient underwent right hemivulvectomy in order to obtain wide tumor-free pathological margins in June 2017. Concomitant inguinal lymph node dissection was not performed due to the patient's refusal (risk of lymphedema). Histopathologic findings confirmed a poorly differentiated vulvar SCC arising on a background of lichen sclerosus. The size of the invasive SCC lesion was 4.5 cm with a depth of invasion of 2.7 mm and no lymphovascular invasion. All surgical margins of the lesion were tumor-free (more than 1 cm).
She was addressed to our oncology unit in July 2017. We required a disease restaging by abdominal and pelvic MRI scan and chest CT scan. No evidence of distant metastases resulted from the imaging studies. Therefore, we suggested locoregional lymph node dissection in order to define the pathologic stage of the tumor and to plan postoperative adjuvant radiotherapy to the groin just in case of lymph node involvement.
In August 2017, a bilateral inguinofemoral lymph node dissection was performed with all nodes (twelve) resulting negative for metastatic spread on conventional hematoxylin-eosin staining. The tumor was staged as FIGO stage IB, and the patient was addressed to strict follow-up.
However, just one month later (September 2017), the patient developed a local recurrence with a 3 cm nodule in the right vulvar area and a 0.8 cm lesion in the clitoris. A wide local excision was performed and histopathology examination revealed a poorly differentiated vulvar SCC in both lesions.
A restaging CT scan of the chest, abdomen, and pelvis showed multiple bilateral pulmonary metastases and multiple inguinal and pelvic lymph node involvement.
Because of recurrence, systemic chemotherapy was started with carboplatin (AUC5 day 1 every 3 weeks) and paclitaxel (80 mg/m2 days 1 and 8 every 3 weeks). After 3 cycles, a total body CT scan showed progression of metastatic disease in the lungs, lymph nodes, and liver. Moreover, a painful erythematosus nodule appeared on the skin of the right groin () and right thigh ().
Because of disease progression, a second-line chemotherapy with capecitabine (1000 mg/m2 bid, days 1-14 every 21 days) was started (December 2017). After 3 cycles of treatment, the patient presented ulceration and fistulization of the groin lesion () and new skin nodules in the right thigh associated with extremities lymphedema. She complained of perineal pain and analgesic therapy was prescribed. Moreover, palliative radiotherapy to inguinal metastases (30 Gy in 10 fractions) was performed.
A reevaluation CT scan (February 2018) revealed further progression of the disease with multiple liver metastases, multiple excavated lesions in the lungs (), and matted metastatic iliac/inguinal lymph nodes ().
The patient died one month later, in March 2018, because of respiratory failure.


A 44-year-old female came to us with the complaint of gradual visual loss and metamorphopsia in the right eye since 6 months. At presentation, she had a BCVA of 20/40 N6 in the right and 20/30 N6 in the left eye, respectively. Anterior segment examination was normal. On fundus examination, the right eye showed multiple yellowish flecks over the posterior pole and a pale yellow confluent lesion with irregular borders nasal to the fovea with a speck of hemorrhage over it, while the left eye showed multiple yellow flecks over the posterior pole (Figure 1 ). Blue autofluorescence image of both eyes showed multiple hyperautofluorescent lesions corresponding to flecks and the right eye showed a hypoautofluorescent lesion corresponding to the CNVM (Figure 2 ). Fundus fluorescein angiography (FFA) of the right eye (Figure 3a ) showed an area of increasing hyperfluorescence in late phase suggestive of classic CNVM with small areas of hyperfluorescent staining corresponding to flecks; the left eye (Figure 3b ) showed small areas of hyperfluorescence staining corresponding to flecks. Spectral domain optical coherence tomography (SD OCT) of the right eye pre treatment (Figure 4a ) showed a juxta foveal CNVM with surrounding subretinal fluid. A full field electroretinogram was done which was found to be normal. In view of these findings, a diagnosis of PDSFF with classic CNVM was made. The patient was advised anti-VEGF injection. Subsequently, the patient went ahead with injections of Ranibizumab in her right eye. The patient came for a follow-up visit after one month. At this visit, her BCVA improved to 20/30 N6 with a significant decrease in her metamorphopsia. A repeat SD OCT was done (Figure 4b ) which showed minimal subretinal fluid with regressing CNVM and adjacent scarring. The patient was advised further anti-VEGF injections and the patient went ahead with injection of Ranibizumab in her right eye. Repeat OCT was done on follow-up visit after a month which showed a complete regression of the subretinal fluid and her vision was maintained (Figure 4c ).


A 65-year-old woman came to the clinic of the First Hospital of China Medical University in January 2015 with main complaints of moderate headache and mild nausea. Her medical history included hypertension and coronary disease for 10 years, which were under control with oral medications. She was a non-smoker and a non-drinker, and denied any family history of cancer.
Physical examination revealed a palpable nodule in the lower right cervical zone, which was about 1.0 cm in diameter, painless, hard, and fixed with surrounding structures. No other significant clinical findings were detected.
Multiple enlarged lymph nodes in the right lower cervical and bilateral supraclavicular zone were detected by ultrasound. A chest computed tomography (CT) scan with contrast revealed a 1.5-cm nodule in the left upper lobe of the lung, with multiple enlarged lymph nodes in the left hilum and bilateral mediastinum. Brain magnetic resonance imaging showed a 1.2-cm nodule in the right parietal lobe with mild surrounded swelling. F18-Fluorodeoxyglucose (FDG) positron emission tomography CT (PET-CT) scan confirmed multiple lesions with increased FDG uptake (Fig. a–e).
An ultrasound-guided core needle biopsy of the cervical lymph node was performed in January 2015. Pathological and immunohistochemical (IHC) examinations indicated metastatic adenocarcinoma of the lung. The IHC staining revealed the following: carbohydrate antigen (CA)125 (+), CA199 (+), cluster of differentiation (CD) 34 (blood vessels+), caudal type homeobox 2 (CDX2) (−), cell keratin (CK) 19 (+), galectin-3 (±), Ki-67 (40%+), mammaglobin (±), naspin-A (+), paired box gene 8 (PAX8) (±), thyroglobulin (−), and thyroid transcription factor-1 (TTF-1) (+). EGFR gene detection showed L858R mutation in exon 21.
The patient was diagnosed with non-small-cell lung adenocarcinoma with clinical staging of T1N3M1b, stage IV (with synchronic brain metastasis), according to the American Joint Committee on Cancer version 7.0 [].
From February 2015, the patient started treatment with icotinib (125 mg tid orally). A partial response was achieved after 1 month (Fig. a and b). In October 2015, she complained of severe headache and nausea, and leptomeningeal metastasis was confirmed by CSF cytopathology. No progression of primary lung tumor or metastatic brain lesion was found at that time (Fig. c). Intrathecal chemotherapy with methotrexate was given (methotrexate 10 mg, every other day), and liquid biopsy using plasma and CSF was performed. Next-generation sequencing (NGS) reported EGFR gene amplification, primitive L858R mutation, and a new T790 M mutation in CSF, but not in plasma. Osimertinib was then administered (80 mg/day orally) from November 2015. The disease was controlled well, and all symptoms disappeared. Repeated NGS using CSF after 2 months of osimertinib treatment showed EGFR gene amplification and L858R mutation only, while T790 M mutation was undetectable.
In July 2016, the patient developed disease progression and was admitted to the hospital in a critical condition. She presented with severe headache, dizziness, nausea, and vomiting, with persistent high intracranial pressure of 240 mm H2O. The Eastern Cooperative Oncology Group (ECOG) performance status was 3. Intense surveillance and life-supporting care were given. Liquid biopsy using CSF showed EGFR gene amplification, L858R mutation, and a new L718Q mutation. A b-rapidly accelerated fibrosarcoma (BRAF) G466R mutation was also found. Supportive care and exploring therapeutics were given sequentially after obtaining informed consent, including high-dose icotinib pulsatile therapy (375 mg every 3 days, followed by 625 mg every 5 days), temozolomide oral administration (200 mg/day for 5 days), and bevacizumab intrathecal injection (100 mg), as described in previous studies [–]. No treatment-related side effects were observed, and clinical evaluation showed no improvement in cancer-related symptoms, signs, or laboratory findings (Fig. a and b). The patient failed to respond to any of these treatments.
In August 2016, about 1 week after all the exploring therapeutics failed, afatinib was challenged (40 mg/day orally). The patient tolerated the treatment well with grade 1 diarrhea only. All the symptoms related to the disease improved gradually. After 1 month, she complained of only mild headache and nausea, and her ECOG performance status improved from 3 to 1. The dynamic changes in the allelic variations and clinical factors during treatments are shown in Fig. a and b.
In December 2016, her symptoms became worse with disease progression. The patient passed away in January 2017. She survived for 23 months in total and for 15 months after suffering from leptomeningeal metastasis. The treatment timeline is shown in Fig. .


A 4-year-old girl was brought to our emergency department with decreased level of consciousness since an hour before. She was the second child of the family whose father was an opium addict on MMT. The methadone had been kept in a bottle like pediatric syrup bottle and the girl was mistakenly given methadone instead of cough syrup by her mother. Upon arrival she had a Glasgow coma score (GCS) of 7/15, a heart rate of 145 bpm, a respiratory rate of 32 breaths/minute, blood pressure of 132/76 mmHg and a temperature of 36.8°C with an oxygen saturation of 85% in room air. Her pupils were myotic and responsive to light and other examinations were within normal limits, so treatment by naloxone (0.1 mg/kg) was started for her. Since there was no response to the initial therapy, she was admitted to the intensive care unit (ICU) and maintenance naloxone (0.16 mg/kg/h) was started. Her electrocardiogram showed tachycardia with QT interval of 440 milliseconds and ST segment elevation in aVR and T wave inversion V1, V2 and V3 (). Laboratory investigations revealed white blood cell (WBC) count of 31,800 /mm3, hemoglobin of 11.9 mg/dL, platelet count of 291,000/mm3, blood urea nitrogen (BUN) of 24 mg/dL, creatinine (Cr) of 1.7 mg/dL, sodium of 133 mEq/L, potassium of 6 mEq/L, blood sugar of 113 mg/dL, calcium of 8.9 mg/dl, creatine phosphokinase (CPK) of 32,000 IU/L, lactate dehydrogenase (LDH) of 6,030 IU/L, troponin of 6.18 U/L, prothrombin time (PT) of 24.4 sec, partial thromboplastin time (PTT) of 48 second, SGOT of 123 U/L and SGPT of 1545 U/L.
Transthoracic echocardiography revealed left ventricular ejection fraction of 25% with akinesia of posterior wall and hypokinesia of septum. She was diagnosed with stress cardiomyopathy and acute heart failure and thus the management of heart failure including diuretics and inotropes was stared for her. On the second day of admission, she developed respiratory arrest and thus was intubated and connected to the ventilator with GCS of 3/15. Brain CT-scan showed bilateral cerebellar infarction and edema and diffuse brain edema. Neurologist was consulted and medical management of intracranial hypertension was started. The patient received hypertonic saline (5mg/kg as bolus dosage and 3mg/kg every 6 hours) and mannitol (1 mg/kg/dose). However, unfortunately she died on the third day despite intensive care management.
An 18-month-girl was transferred to our center from a primary healthcare center due to decreased level of consciousness several hours prior to presentation. She was reported to be treated with 3cc of methadone solution by mistake instead of diphenhydramine because of coryza signs and symptoms. On admission to the primary center, she had a GCS of 14/15, a heart rate of 135 bpm, a respiratory rate of 26 breaths/minute, blood pressure of 127/67 mmHg and a temperature of 36.8°C with an oxygen saturation of 98% in room air. Her pupils were myotic with response to the light. With the primary impression of methadone poisoning, naloxone (0.1 mg/kg) had been administered in the primary center and then she was transferred here. She was also reported to have had 2 episodes of tonic-clonic convulsions in the ambulance during the transfer for which diazepam (0.1 mg/kg) was administered. On admission to our center, she had GCS of 8/15 and she had bradypnea with abdominal respiration and O2 saturation of 84% without oxygen supplement, blood pressure of 117/67 mmHg, a temperature of 37.5°C with myotic pupils that were reactive to light and upward plantar reflex (Babinski), so naloxone infusion was continued (0.16 mg/kg/h). She was intubated and transferred to ICU. She had two episodes of tonic clonic convulsion for which midazolam infusion was started (0.05 mg/kg/hr). Laboratory examination revealed WBC count of 18,000/mm3 (88%PMN, 11%Lymphocyte), hemoglobin of 8.6 mg/dL, platelet count of 390,000/mm3, BUN of 18 mg/dL, Cr of 0.7 mg/dL, sodium of 140 mEq/mL, potassium of 4.7 mEq/L, blood sugar of 102 mg/dL, CPK of 3,050 IU/L, LDH of 2,375 IU/L, PT of 20 second, PTT of 28 second, SGOT of 6220 U/L, SGPT of 5740 U/L and CRP of 73 mg/L. The ECG also showed sinus tachycardia and prolonged QT interval (). On the second day, she had another episode of convulsion with decrease in O2 saturation. She developed bilateral fine rales in lung examination in favor of pulmonary edema, so infusion of furosemide (1 mg/kg q2h) was started. Chest radiography revealed pulmonary edema. Brain CT scanning demonstrated a small area of ischemia and hydrocephaly.
In echocardiography, ejection fraction of 15% with diffuse hypokinesia and mild mitral valves regurgitation has been showed. She was diagnosed to suffer from stress cardiomyopathy for which management of heart failure was started. After 3 days of conservative management with naloxone (0.1 mg/kg/dose) and phenobarbital (0.15 mg/kg q12h) the patient developed spontaneous respiration and was extubated 2 days later. Her GCS increased to 14/15 and echocardiography revealed normal cardiac function. She was discharged from the hospital on the 12th day while she was completely awake with normal echocardiography. On the 6-month follow-up she had normal daily activity and normal echocardiography without signs of cardiac failure. She did not have any seizure so the anticonvulsants were tapered.