A 59-year-old man presented to our clinic in April 2014 with fatigue, anorexia, fever, and anemia. Clinical examination revealed splenomegaly and cervical lymphadenopathies. Laboratory tests were reported as hemoglobin 9.1 gr/dL, white blood cell 6.1 × 103/μL, and platelets 430 × 103/μL with normal other biochemical values. HIV test was negative. Spleen size was found as 160 × 90 mm and lymphadenopathies around portal hilus were detected by abdominal USG. Cervical lymph node biopsy revealed high grade B lymphoproliferative neoplasm. Conventional cytogenetic analysis was performed; however it resulted in no metaphases. The FISH investigation has resulted in BCL2−, BCL6−, and MYC−. Immunohistochemical study has resulted in CD20+, BCL2+, MUM1+, BCL6+, and Tdt−. Ki-67 proliferation index of the patient was 90%. No disease involvement was detected in the bone marrow biopsy investigation. PET-CT was performed for disease staging. Involvement in spleen, bone marrow, cervical lymph nodes, bilateral axillary lymph nodes, thoracal lymph nodes, portal, para-aortic, paracaval, and bilateral inguinal lymph nodes, sternum, C2 vertebra, clavicula, acromion, and left humerus was detected, with SUV max value above 4. The patient was diagnosed as stage 4 diffuse large B cell lymphoma and 4 cycles of R-CHOP (rituximab, cyclophosphamide, adriamycin, vincristine, and prednisolone) regimen were given. In August 2014, cervical, thoracal, and abdominal CT revealed regression. R-CHOP regimen was given for 3 more cycles. The patient responded to the treatment well with complete resolution of all lymphadenopathies. However, 2 months after the completion of chemotherapy cycles in November 2014, the patient had emerging skin lesions that cover nearly all of his body. The lesions were painless and different in diameter with the biggest lesion reaching 5-6 cm (). A control PET-CT revealed diffuse cutaneous involvement (SUV max 18.3) with axillary lymph node involvement (SUV max 14.8). Interestingly this time, spleen, inguinal nodes, and bone marrow involvement could not be detected. Biopsy was performed from skin lesion which was reported as CD20+, BCL2+, MUM1+, BCL6+ high grade B cell lymphoma infiltration. The patient also had foot drop which was considered to be secondary to vincristine. Electromyography revealed diffuse and severe axonal polyneuropathy and active myopathy in distal muscles. There was no involvement in cranial MR. He was diagnosed as relapsed lymphoma, so R-DHAP (rituximab, cisplatin, cytosine arabinoside, and dexamethasone) chemotherapy regimen was started. There was no treatment response after 2 cycles of R-DHAP; therefore, chemotherapy regimen has changed to R-ICE (rituximab, etoposide, carboplatin, and ifosfamide). With R-ICE treatment, the patient achieved second complete remission and his skin lesions were completely regressed (). Autologous peripheral blood stem cell transplantation (PBSCT) was planned for our patient.


A 10 year old girl initially presented to our dermatology clinic with an 8 month history of skin lesions developing on her right upper limb. The patient was otherwise healthy with an unremarkable family history and an unaffected twin sister. According to the patient, the lesions began as bruise-like discolorations. Physical exam revealed atrophic, non-sclerotic and band-like hyperpigmented plaques on her right forearm and upper arm. Linear atrophoderma of Moulin and linear scleroderma as well as atrophoderma of Pasini and Pierini were considered in the differential diagnosis.
An initial punch biopsy revealed an unremarkable epidermis save for prominent melanin deposition in the basal layer. Mild inflammatory changes were also noted in the specimen with perivascular and focally interstitial lymphoid infiltrates without any obvious signs of sclerosis. The patient was diagnosed with atrophoderma of Moulin. Over the next 5 years, month-long trials of topical steroids, vitamin D analogues, retinoid and hydroquinone were administered without any clinical improvement. At 15 years of age the lesions had coalesced to form band like hyperpigmented atrophic plaques with prominent veins and clear margins on her forearm, upper arm, shoulder and right inner thigh (Fig. ). The lesions were asymptomatic except for occasional pruritus and the patient reported no preceding inflammation or hardening of the skin. There was no joint involvement. Given the apparent progression of the disease a repeat biopsy was performed which revealed unremarkable mild dermal inflammatory changes with no evidence of dermal sclerosis or atrophic skin appendages that would support a diagnosis of localized scleroderma. All laboratory findings were normal including negative anti-nuclear antibodies. Correlating the clinical picture with the histological examination, a diagnosis of LAM was re-established.


A 38-year-old female patient with an incidentally found gastric submucosal tumor was referred to our hospital for the consultation of the possibility of NOTES gastrectomy. The patient herself wished to undergo NOTES as a surgical alternative, due to possible less pain and better cosmesis. Her body weight was 41 kg and height was 155 cm. The patient was asymptomatic and otherwise healthy without any gastrointestinal disorders. The lesion, 2.5 cm in size, was demonstrated on the posterior wall of the gastric fornix by preoperative abdominal computed tomography. Endoscopy revealed a SMT with intra-gastric growth, with the distance of 2.0 cm below the esophago-gastric junction (Fig. ). Biopsy was not attempted due to the size and location of the lesion. The patient experienced one childbirth with normal transvaginal delivery. After intensive discussion among the team, transvaginal NOTES partial gastrectomy was indicated as a surgical alternative. We informed the patient of its experimental nature, our previous clinical experience, the procedure’s short- and long-term outcomes, the possible risks/complications, and the details of the procedure itself. Surgery was conducted under the protocol approved by the University’s Institutional Review Board (IRB Folio No. 08063). Table demonstrates our inclusion/exclusion criteria for transvaginal NOTES gastrectomy, which was approved by the University’s Institutional Review Board.
The routine part of our transvaginal NOTES technique has been described elsewhere [, ]. Briefly, after placing two laparoscopic ports at the umbilicus (5 mm) and the left mid-abdomen (3 mm), the posterior vaginal sac was exposed and punctured under laparoscopic guidance. This entry site was secured with an extra-long endoscopic over-tube, and a standard flexible gastrointestinal endoscope was advanced into the abdomen. The peri-gastric ligaments were dissected with energy devices passed through the endoscope to mobilize the involved portion of the stomach. The endoscope was then replaced with a linear stapling device. EGD was advanced trans-orally into the stomach to calibrate the EGJ and to obtain adequate surgical margin during stapling (so-called gastric calibration). Stapled partial gastrectomy was accomplished under laparoscopic monitoring. The specimen was isolated in a plastic bag and was delivered via the vagina. The vaginal entry site was closed with sutures under direct vision.
In this particular patient, we employed new techniques and newly developed accessory devices.
The transvaginal over-tube was secured with a thin loop-retracting device (Mini Loop Retractor, Hakko, Nagano, Japan), which was introduced via the umbilical incision under retroflexed flexible endoscopic guidance. This technique enabled intentional “steering” of long and flexible over-tube in the abdominal cavity and greatly enhanced its stability while controlling the tip of the flexible endoscope (Fig. ).
Currently available over-tube has been designed to be used as a “guide” for flexible endoscope, and is not suitable to maintain pneumoperitoneum. Its distal orifice is not leak-proof; therefore, carbon dioxide, once fed through the trans-abdominal trocar, continuously leaks from the space between the over-tube and the endoscope. To solve this problem, we have developed a reinforced anti-leak adapter, and it was commercialized as an endoscopic accessory (Leak Cutter, Top Corporation, Tokyo, Japan) in 2012. With this simple device, pneumoperitoneum was successfully established and maintained all through the procedure without causing any major gas leakage (Fig. ).
This newly developed device (Endoshower, Yamashina Seiki Co., Ltd., Siga, Japan) is a flexible catheter which passes the standard biopsy channel of current flexible endoscopes. Endoshower enables “laparoscopy-like” irrigation and suction under sterile condition. With this device, the abdomen was diffusely irrigated, and the fluid in the sub-diaphragmatic space was safely drained without causing any mis-suction and injuries on the splenic capsule (Fig. ).
The procedure was successfully completed without any complications. No additional trocar was required, and no trans-abdominal energy device was used. The operative time was 260 min, and the blood loss was 20 ml. The patient showed uneventful and rapid postoperative recovery without any analgesic. She discharged from the hospital without any abdominal/gynecological complaints on the fifth postoperative day, which was determined by the IRB-approved clinical protocol. The postoperative pathology revealed leiomyoma of the stomach, 28 × 15 × 10 mm in size. Both umbilical and mid-abdominal scars are now well consolidated and virtually invisible.
One of the technical challenges in human NOTES is how to control and stabilize flexible endoscope in the abdominal cavity [, , , ]. Various commercially available/non-available over-tubes, i.e., platforms, have been attempted; however, virtually none of them have archived true clinical success [, ]. Our “over-tube steering technique” using loop-retracting device is simple, effective, and inexpensive; however, its true advantage in reducing operating time/blood loss was not shown in this single case report. This technique is applicable to any type of NOTES and practical since it is compatible with any kind of off-the-shelf endoscopic over-tubes. Further accumulation of clinical cases is definitely needed, to establish this technique as an attractive surgical option. The authors believe that future platform for pure NOTES should have at least “anchoring” mechanism that anchors the platform onto the abdominal lining.
How to maintain pneumoperitoneum is another fundamental but difficult problem in NOTES [, ]. Since commercially available endoscopic over-tubes are not designed to maintain a steady-pressure environment, they are not as leak-proof as laparoscopic trocars. Our newly developed “Leak Cutter,” now available in Japanese market as a reinforced anti-leak adapter for routine endoscopy, works perfect to prevent gas leakage during the case. The device has a Luer lock-type stopcock for emergent evacuation in case of over-insufflation. This stopcock can also be used as an insufflation inlet in future pure NOTES, where trans-abdominal insufflation via laparoscopic trocar will no longer be available.
The intra-abdominal irrigation via current flexible endoscope is feasible; however, it is technically demanding due to its one-direction spray from the tip of the endoscope. The use of sterile saline solution via built-in air/water channel requires specific and cumbersome preparation and setting. The suction from the tip of the endoscope is further challenging, since conventional technique requires “diving” of the endoscope beneath the fluid. While diving the endoscope, the visualization is temporally lost. This is acceptable in the gut lumen where no other organs exist; however, this is not acceptable in the abdominal cavity where blind mis-suction may lead to serious organ damage. Our new product, Endoshower, is one of the solutions. This device, 2.6 mm in outer diameter, has 24 side holes of 0.4 mm in size at its tip. With this device, sterile irrigation and safe suction under endoscopic visual control were feasible in the present case.


A 67-year-old woman was acutely admitted to the cardiological department presenting with angina, dyspnea (NYHA II), melena, hypotension and anemia (hemoglobin (Hgb) 3.2 mmol/L (reference: 7.3 - 9.5)). She had a history of paroxystic atrial fibrillation treated with amiodarone and an HOCM due to a displaced artificial mitral valve causing a subvalvular aortic stenosis diagnosed 6 months prior to the admission. An echocardiography had revealed a high left ventricular outflow tract (LVOT) obstruction with a gradient of 140 mm Hg (normal values < 30 mm Hg).
An acute gastroscopy revealed gastritis and hematin spots. Besides a few spots with slight bleeding were observed and warfarin therapy was discontinued (instead she was treated with low molecular heparin due to the artificial mitral valve). The patient continued having episodes of melena and the anemia persisted despite numerous blood transfusions. From the admission and during the next 34 days, she received 24 transfusions. Renewed gastroscopy, colonoscopy and CT angiography did not reveal any source of bleeding. A capsule endoscopy showed multiple angiodysplasias in the small intestine. During an oral spiral endoscopy, the bleeding elements were visualized from the Treitz ligament and in the proximal part of the jejunum. In the distal jejunum and proximal ileum, we did not disclose any angiodysplasias. They were treated with argon beaming. However, bleeding persisted and the patient received continuous blood transfusions. Two weeks treatment with thalidomide 50/100 mg per day was initiated with no significant effect on Hgb levels. Thalidomide was arrested for 4 weeks due to induction of bradycardia and QT prolongation. We considered it was a side effect of the thalidomide treatment. At an interdisciplinary conference, the possibility of Heyde’s syndrome was raised and cardiac surgery was considered, despite the patient’s severe physical condition, in order to cease GB. As a last resort, after an octreotide test-dosis of three times 50 μg (which were well tolerated), the patient was treated with Sandostatin® (octreotide) slow release formulation 20 mg injections every 4 weeks (). The demand for transfusion was reduced after the combined treatment with argon beaming and medical treatment. Still, a need for transfusion persisted, and further 11 transfusions were given during the next 42 days (). A renewed capsule endoscopy showed three uncharacteristic areas of bleeding but no signs of angiodysplasias. Still repeating blood transfusions were necessary in order to maintain stable Hgb levels. For this reason, treatment with thalidomide was resumed at a lower dose (50 mg per day) alongside with octreotide treatment (). After 2 weeks at combined treatment, the Hgb was normalized and no further transfusions were needed during an observation period of 1 year. After 3 months with normal Hgb, the subvalvular hypertrophy was treated with TACE (alcohol septal ablation) with a positive effect on the patient’s cardiac symptoms. Treatment with octreotide was continued until 1 month after the TACE treatment where the gradient was reduced from more than 100 mm Hg to 50 mm Hg. Thalidomide was slowly tapered (50 mg every second day → 50 mg twice a week). Five months after surgery, an echocardiography revealed a reduction of the LVOT gradient to a near normal level (40 mm Hg) and thalidomide was therefore halted. Twelve months following treatment, the patient has had no symptoms of GB and Hgb has stabilized (8.8 - 9 mm Hg) with no need for further blood transfusions.


A 72 years old man presented to the Outpatient Clinic of Otolarygology of Rouhani Teaching Hospital with complaints of hoarseness, low grade fever with decreased appetite for a duration of one month. He had no cough or expectoration. The patient was not a smoker and with no alcohol and drug abuse. His wife had pulmonary tuberculosis 14 years ago and was treated with anti tuberculosis agents. She died five years ago due to myocardial infarction. His 14 year old daughter had subcutaneous tuberculosis of the femur 16 years ago without involvement of her lung or spine.
In general physical examination, he was conscious. There was no cervical lymphadenopathy or clubbing. There were no scars or sinuses in the neck. Indirect laryngoscopy had shown a growth in the right ary-epiglottic fold (). Vocal cords were moving with no signs of infiltration. The respiratory system examination and chest x-ray were normal. PPD test showed 15 mm indurations after 48 hours. After a standard evaluation, the patient underwent laryngoscopy under local anesthesia and biopsy was taken from epiglottis.
The histopathological examination revealed biopsy tissue lined by stratified squamous epithelium showing focal dysplasia. Underlying stroma showed diffuse infiltration by lymphocytes, plasma cells, occasional polymorphs along with epitheloid granulomas, langhans giant cells and caseous necrosis (). Histopathologic findings confirmed tuberculosis as the cause of his hoarsness and he was treated with standard regimens of therapy.
A standard six month treatment with a combination of isoniazid, rifampicin, pyrazinamide, and ethambutol was started for two months followed by isoniazid and rifampicin for additional four months. The follow up after treatment showed resolution of the symptoms and improvement of the mass ().


A 62-year-old female patient was admitted for discomfort in the upper abdominal area as the chief complaint. The patient visited at “S” hospital for the symptom and diagnosed as cholangiocarcinoma. Although laparoscopic resection was attempted, surgery could not be performed because of the presence of peritoneal seeding. Then she was treated with 1cycle of gemcitabine and cisplatin combination chemotherapy (gemcitabine 1200 mg/m2 Day 1 and 8, cisplatin 60 mg/m2 Day 1, every 3 weeks), and transferred to our hospital. At the time of admission, vital signs were within normal ranges. In peripheral blood test, leukocyte was 4920/μL, hemoglobin was 10.0 g/dL, and platelet was 359,000/μL. In serum biochemistry test, they were also within normal ranges. At the time of admission, tumor marker tests were not performed.
After 2nd cycle of combination chemotherapy with gemcitabine and cisplatin, we performed abdominal computed tomography (CT) for the response evaluation. The abdominal CT revealed that the size of tumor increased as compare to baseline CT findings. For the next therapeutic plan, we performed immunohistochemical staining for TP with a surgical biopsy specimen, and the result, as shown in Figure , was positive immunohistochemical staining for TP.
Afterward, chemotherapeutic agents were switched to gemcitabine and doxifluridine regimen (gemcitabine 1200 mg/m2 Day 1 and 8, doxifluridine 1200 mg divided 3 times p.o. daily, every 3 weeks), and administered 4 cycles. The abdominal CT scan revealed that shrinkage of main mass indicating partial response (Figure ). The patient chose to terminate chemotherapy, and was observed at the outpatient clinic even though the adverse events were minimal. The CT scan performed during the follow-up revealed the progression of disease (remission duration: 9 months), and then combination chemotherapy was restarted with the previous gemcitabine and doxifluridine regimen. The abdominal CT scan performed after 2 cycle of chemotherapy showed the disease progression. Afterward, maintained with doxifluridine alone until the patient's condition was deteriorated and the patient died of sepsis (overall survival: 22 months).


A 32-year-old female patient was admitted for discomfort in the upper abdominal area as the chief complaint. The patient was diagnosed as cholangiocarcinoma. She was transferred to “A” hospital, treated with 4-cycle of gemcitabine and cisplatin combination chemotherapy (gemcitabine 1000 mg/m2 Day 1 and 8, cisplatin 60 mg/m2 Day 1, every 3 weeks), and then transferred back to our hospital due to disease progression after chemotherapy. On admission, vital signs were within normal ranges. In peripheral blood test, leukocyte was 4927/μL, hemoglobin was 9.1 g/dL, and platelet was reduced to 49,000/μL. In serum biochemistry test, they were within normal ranges except that alkaline phosphatase was mildly elevated to 174 IU/L. Abdominal CT scan revealed 12-cm sized huge mass invading portal vein (Figure A). For the next therapeutic plan, immunohistochemical staining for TP was also performed with a biopsy specimen, which revealed positive immunoreactivity to TP (Figure ).
On admission, gemcitabine and doxifluridine combination chemotherapy (gemcitabine 1000 mg/m2 Day 1 and 8, doxifluridine 1200 mg divided 3 times p.o. daily from Day 1 to 14, every 3 weeks) was initiated. For 11 months, the cancer lesion had been controlled as stable disease as shown in CT scan (Figure B). The abdominal CT scan performed at 11 months after treatment indicated the disease progression, and thus chemotherapeutic agents were switched to irinotecan and capecitabine combination chemotherapy. Nonetheless, the cancer was not responded to it, and she died due to disease progression (overall survival: 16 months).


A 50-year-old previously healthy male presented to the emergency room with severe abdominal pain. He denied use of any medications or allergies. He had a family history of breast cancer in his mother and ovarian cancer in his maternal grandmother. He was an ex-smoker and denied use of alcohol or illicit drugs. His physical exam was within normal limits except for diffuse abdominal tenderness. A computed tomography (CT) scan of the abdomen and pelvis showed acute appendicitis. Appendectomy was done and pathology showed mixed adenoneuroendocrine carcinoma (MANEC), most consistent with adenocarcinoma ex-goblet-cell carcinoid, signet ring cell tumor-type, with a maximum dimension of approximately 4.3 cm. He had features of both adenocarcinoma and carcinoid tumor. The patient subsequently underwent a colonoscopy that showed a 7 mm polyp in the descending colon. Biopsy showed a sessile tubular adenoma with no high grade dysplasia. Definitive surgical therapy, a right hemicolectomy, was performed. Lymph nodes showed metastatic goblet cell carcinoid tumor. In the presence of positive nodal disease, it was decided to proceed with adjuvant chemotherapy.
Adjuvant chemotherapy with Folinic acid, Fluorouracil, and Oxaliplatin (FOLFOX) was started. During the third cycle of FOLFOX, the patient developed a witnessed tonic-clonic seizure that lasted approximately 2-3 minutes. He was transferred to the hospital for further evaluation. He denied any previous personal or family history of seizures or strokes. Electrocardiogram (ECG), complete blood count (CBC), complete metabolic panel (CMP), thyroid stimulating hormone (TSH), and urine drug screen were within normal limits. Initial 24-hour urine 5-HIAA was 3.8 mg/24 hr (reference range 0.0–14.9 mg/24 hr) and Chromogranin-A was 3 nmol/L (reference range 0.0–5.0 mg/L). Magnetic Resonance Imaging (MRI) of the brain did not show any acute abnormality. An electroencephalogram (EEG) was normal. The patient was rechallenged with the FOLFOX chemotherapy, however, at the end of the fourth infusion, the patient became unresponsive, his eyes rolled back, and he had tonic-clonic seizures for the second time. Workup including CBC, CMP, and MRI of brain again was negative. His chemotherapy regimen was switched to Folinic acid, Fluorouracil, and Irinotecan (FOLFIRI), thus removing Oxaliplatin from his chemotherapy regimen. After 5 cycles of FOLFIRI chemotherapy, the patient did not develop any more seizures, making Oxaliplatin the most likely reason for his seizures.


A 17-year-old female without a history of smoking was admitted to our hospital for complaining of a right pulmonary nodule incidentally detected during routine examination. The patient was asymptomatic; physical examination and routine laboratory studies were all within normal values. X-ray demonstrated that there was a well-defined solid mass measuring 3.13 cm in the diameter at the right pulmonary hilar region (Fig.). In the current visit, the patient underwent wedge resection in our hospital. The postoperative course was uneventful, and there was no evidence of disease 12 months later.


In October 2010, a 45-year-old man presented to his local physician with pain in his right groin, which the patient attributed to a muscle strain from playing soccer. As his pain worsened, the patient went to an orthopedic surgeon who obtained a magnetic resonance imaging (MRI) study that showed a mass within the right anterior ilium. In December 2010, the patient was examined by physicians in the Department of Orthopaedic Oncology at The University of Texas MD Anderson Cancer Center, and a biopsy of the right ilium mass revealed a malignant epithelioid and spindle cell neoplasm most consistent with PMH. The patient was treated with two cycles of intra-arterial cisplatin (120 mg/m2) administered every 3 weeks. Due to hearing loss, administration was modified to intravenously with a slow infusion rate over 24 h for the next two cycles. Restaging positron emission tomography-computed tomography (PET-CT) studies revealed a minor tumor response to cisplatin.
Because the patient’s hearing loss worsened, therapy was switched to a combination of gemcitabine (900 mg/m2) and docetaxel (100 mg/m2) administered in 3 week cycles, beginning 3 weeks after cessation of cisplatin. Restaging PET-CT studies performed after completion of the third cycle revealed that the PMH had significantly responded to gemcitabine plus docetaxel (Fig. ). Unfortunately, despite this significant improvement, there was evidence of gemcitabine-induced pulmonary toxicity. Therefore, cytotoxic chemotherapy was halted, and a tapering dose of steroids was given to the patient to treat the pulmonary toxicity. The patient’s edema was managed with furosemide and amiloride.
During a follow-up visit 3 months after cessation of gemcitabine and docetaxel, the patient’s PET-CT scans showed mild progression of disease in the right iliac bone with enlarging lucencies. This finding suggested that the PMH progressed in the absence of gemcitabine and docetaxel treatment. Therapy with weekly paclitaxel (80 mg/m2) was therefore started. However, after 4 months of paclitaxel, therapy was discontinued because the patient experienced hearing loss, rhinitis, and neuropathy characterized by tingling of the hands and feet. Restaging studies performed 16 months following cessation of cytotoxic chemotherapy revealed stable disease.
The tumor response to the combination of gemcitabine and a taxane was clearly demonstrated on the PET-CT scans. PMH progressed once chemotherapy was stopped, and taxane treatment led to disease stability, suggesting that gemcitabine plus taxane could be an effective treatment for PMH.


In June 2011, a 22-year-old man presented to his local physician with a painless, dime-shaped nodule in his right lateral thigh. Approximately 1 year later, the mass began to enlarge and induce pain, and the patient saw a dermatologist who performed a punch biopsy that was inconclusive. In September 2012, an excisional biopsy was performed at MD Anderson Cancer Center, and the pathologist concluded that the mass was consistent with PMH originating from the right femur. Baseline imaging included MRI of the right thigh which showed multiple enhancing lesions in the distal right femur and lateral soft tissues, extending for a length of 6.8 cm and centered approximately 7 cm proximal to the articular surface of the lateral femoral condyle. A baseline PET-CT study revealed a hypermetabolic mass in the right distal femur (standardized uptake value, maximum of 15.2) and a 1.3 cm left acetabular lytic lesion (standardized uptake value, maximum of 7.9), suspicious for metastatic disease (Fig. ). After the patient was evaluated by physicians in the Department of Sarcoma Medical Oncology at MD Anderson, therapy with gemcitabine (900 mg/m2) and docetaxel (75 mg/m2) was started and given in 3 week cycles. The cytotoxic chemotherapy was well tolerated. However, imaging showed no evidence of tumor response after two cycles, and treatment was halted.
Therapy was then changed to doxorubicin (90 mg/m2 as a continuous infusion over 72 h) and cisplatin (120 mg/m2 as an intravenous infusion over 4 h), but the patient had mucositis, tinnitus, neutropenic fever, and ototoxicity during the first cycle. The cisplatin dose was reduced to 100 mg/m2 as a slow infusion over 24 h to prevent ototoxicity and doxorubicin was changed to bolus doxorubicin with dexrazoxane (90 mg/m2) in a 3 week cycle to reduce mucositis caused by continuous intravenous infusion of doxorubicin. The patient tolerated the regimen better during the second cycle, and the PMH remained stable.
In July 2013, the patient underwent surgical resection to remove the right distal femoral lesion. DNA sequencing of the tumor revealed the presence of a tuberous sclerosis 1 (TSC1):c.1760A >Gp.K587R mutation. Owing to the TSC1 mutation, therapy with everolimus (10 mg/day) was started. Two months later, the patient underwent MRI of the pelvis, which revealed mild interval healing of the small intramedullary metastases in the supra-acetabular region of the left iliac bone (Fig. ).
Restaging MRI studies of the pelvis were performed 5 months after the start of everolimus treatment and revealed generally stable disease and no evidence of recurrent disease in the thigh. Owing to the stability of the disease, the patient decided to cease everolimus therapy and pursue cryotherapy. Overall, the mTOR inhibitor provided a noticeable response in the tumor, which had not responded to doxorubicin and cisplatin. Thus, targeted therapy could serve as a viable treatment option for PMH.


A 39-year-old woman without underlying malignancy was previously treated with diazepam and remained ambulant.
The woman was admitted to an immunological department due to muscle hypertonia with episodic attacks of painful spasms, affecting predominantly axial muscles. Benzodiazepine monotherapy proved to be ineffective despite a high dose of diazepam (50 → 100 mg/24 hours gets out of control). Very high titer GADAbs (>1: 20,000) were observed (Figure ). Furthermore, an immunogenetic element was tested in individual susceptibility to SPS and in latent autoimmune diabetes of adults (LADA) (Table ).
Following the clinical manifestation and laboratory investigations (the patient satisfying M.C. Dalakas criteria), the diagnosis of autoimmune SPS was established and the patient was urgently treated with 2 courses of plasmapheresis [therapeutic plasma exchange (TPE)].
Since the IGT is a risk factor for the development of diabetes mellitus, the patient underwent a 75 g oral glucose tolerance test (OGTT) before, during and after plasmapheresis as well as rituximab therapy: the cut-off point was set at blood glucose of 140 mg/dL (7.8 mmol/L) as previously described and in accordance with the WHO criteria.
After the second course of TPE common complications—hypoalbuminemia and anemia—were observed as the result of large volume plasmapheresis (total volume > 4000 mL). Biochemical and laboratory investigations showed high muscle involvement: very high level of creatine kinase (CK) (brain CK-BB plus muscle type CK-MM, but not cardiac CK-MB isoenzyme). Unfortunately, the refractory status epilepticus-like symptoms were observed, continuing seizures despite adequate initial pharmacologic treatment and essential GADAb reduction after TPE. Immunosuppressive agents were added a single course of rituximab (375 mg/m2 on day 1, 8) followed by mycophenolat mofetil (1 g b.i.d.) (Figure ). Interestingly, the initial exteroception and spasm were confined to the muscles of the trunk followed by sleeplessness, anxiety, myoclonic jerks and further life-threatening seizures, tachycardia, sweating, and vegetative symptoms after TPE. Benzodiazepine withdrawal syndrome developed because the patient took benzodiazepines for a long time (at increasing dose, out of control), serum drug concentration was drastically reduced by plasmapheresis. Initially we did not notice IGT, but it was visible later, after diazepam withdrawal. We observed successful therapy of autoimmune phenomena: SPS and IGT/LADA—gradually the patient became able to walk, read books (GADAb was below 1:80 titer, rituximab therapy reestablished OGTT) (Figure ). Further on, after benzodiazepine withdrawal, the tonus and spasm attacks were successfully controlled by tizanidine, and the patient was discharged.
Unfortunately, after the reintroduction of benzodiazepine (out of control), rapid and high increase of GADAb and IGT (defined as 2-hour glucose levels of 140 to 199 mg/dL)—LADA and SPS relapse were observed.


An 18-year-old woman was referred to our hospital in July 2009 for a 1-year history of uncontrolled hypertension (BPmax 185/120 mmHg). The patient was treated with β-blocker, calcium channel blocker, and angiotensin II receptor blocker, however, without satisfactory effect. The patient also complained of episodes of severe headache and palpitation during micturition, without history of lower urinary tract symptoms or hematuria. The physical examination and routine laboratory investigations were normal. The patient's height is 163 cm while the weight is 53 kg. On ultrasound abdomen 9.2 × 3.9 cm low echo-level lesion was seen in the retroperitoneum next to aorta in front of spine and 4.1 × 2.3 cm low echo-level lesion was seen in right posterior wall of the bladder. Computed tomography (CT) abdomen revealed 8.5 × 6.1 × 3.7 cm well capsulated lesion in portocaval region with increased enhancement in arterial phase and relative washout in portovenous phase. Part of portal vein, abdominal aorta, and renal artery were wrapped by the lesion (Figure A, B). A 3.5 × 2.1 × 1.3 cm similar enhancing lesion in right posterior bladder wall was present (Figure C). Twenty-four hour urinary norepinephrine was 465.45 μg/24 hour (normal: 16.69–40.65 μg/24 hour), urine epinephrine 26.76 μg/24 hour (normal: 1.74–6.42 μg/24 hour), while dopamine 124.5 μg/24 hour (normal: 20.93–330.59 μg/24 hour) within normal limits. Then, 131I-MIBG scintigraphy was performed which revealed high uptake only in both of the retroperitoneum and urinary bladder mass, but not in the adrenal glands or elsewhere (Figure A). Then, the diagnosis of concurrent PGL of the retroperitoneum and urinary bladder was made.
As the patient and her parents refused to be surgically excised, she was given the intermediate-dose 131I-MIBG therapy for the young patient without any basic diseases. 131I-MIBG therapy was approved by the Institutional Review Board. Written informed consent was also obtained before therapy. The patient received 6 doses of high-specific activity 131I-MIBG from October 2009 to April 2015, each treatment dose was 400 mCi. 131I-MIBG was administered as a slow intravenous infusion over a period of 1 hour. Thyroid uptake of free radioiodine was blocked either by potassium iodide 200 mg/day plus levothyroxine 100 μg/day for 72 hours prior to and 14 days after therapy. Blood pressure and heart rate were monitored during 131I-MIBG infusion. Posttherapeutic 131I-MIBG imaging was performed 4 to 6 days after therapy. Toxicity was evaluated by extensive laboratory tests including complete blood count, liver function, and thyroid function tests. Twenty-four hour urinary catecholamines levels were measured 24 hours prior to and 7 days after each course therapy (Figure A–C). CT abdomen was used to assess the radiological tumor response within 3–6 months after the each dose of 131I-MIBG. The symptomatic, hormonal, and radiological tumor response, according to WHO criteria, assessed within 6 months after the each dose of 131I-MIBG. CR for symptomatic, hormonal, and radiographic tumor were defined as complete normalization for symptomatic response, catecholamine levels, and complete regression of radiological abnormalities and also a negative diagnostic 131I-MIBG scan. Partial response (PR) for symptomatic, hormonal, and radiographic tumor were defined as subjective decrease in intensity and frequency of symptoms, 50% or greater reduction from pretherapy level of hormones and 50% or greater reduction of all measurable tumor. After 4 course of 131I-MIBG therapy, the patient got symptomatic and hormonal CR. The lesion of urinary bladder was disappeared with CT (Figure E) and 131I-MIBG scan (Figure E), while the focus of retroperitoneum reduced more than 50% (PR) (CT scan: 2.3 × 1.8 × 1.3 cm) (Figure C, D). After 6 course intermediate-dose course of 131I-MIBG therapy, the patient got radiographic tumor CR (Figure G–I and Figure G). We monitor the myelosuppression and other toxicity closely by laboratory tests including complete blood count and liver function tests. The Supplemental Table 1, , contains complete blood count, liver function, and thyroid function tests before and after treatment. There are no life-threatening adverse events were observed.


A 60-year-old woman was referred to the Department of Oral and Maxillofacial Surgery of the University of Ribeirão Preto (UNAERP) because she had displacement of three dental implants into the maxillary sinus, two of which were in the right sinus and one was in the left sinus. According to the report, the patient underwent surgery for implant placement in the maxilla 8 months ago. Three months after the surgery, she began to report pain and felt pressure in the premolar region, particularly on the right side. The patient also had pain on palpation of the anterior wall of the right maxillary sinus, with no sign of oroantral fistula ().
After examination of panoramic radiography, two similar images of dental implants were noted in the right maxillary sinus with evidence of sinusitis, including opacification of the maxillary sinus. On the left sinus, the same image pattern, corresponding to a dental implant, was found; however, no sign of sinusitis was found. Computed tomography (CT) showed implants displaced into the maxillary sinus cavity with a significant opacification of the right maxillary sinus; however, the left sinus did not present the opacification; only the implant did (Figures and ).
Surgical Procedure. The patient was operated under local anesthesia (Figures and ). An oral antibiotic prophylaxis (amoxicillin + clavulanate, 2.0 g) was administered 1 h prior to start of the procedure. The surgical intervention began with the Caldwell-Luc access bilaterally and the elevation of a trapezoidal full-thickness mucoperiosteal flap. The buccal aspect of the flap was raised to access the maxillary sinus bony wall. A low-speed straight hand piece with a circular diamond bur was used to perform spherical osteotomy. The Schneiderian membrane was perforated and removed through the bone window to gain full access into the sinus cavity (Figures and ). Immediately thereafter, the implants were identified and removed with a surgical aspirator and a Kelly clamp (Figures and ). In the right maxillary sinus, the inflammatory tissue was removed and the surgical field was irrigated with sterile saline in both maxillary sinuses. After irrigation, a porcine collagen membrane (Geistlich Bio-Gide, Switzerland) was installed in the lateral bone window to protect the sinus cavity (Figures and ). After irrigation of the surgical field with sterile saline, the surgical flap was sutured (Figures and ), and an antibiotic therapy with amoxicillin and clavulanate (1.0 g) was prescribed in association with a nonsteroidal anti-inflammatory drug every 8 h for 7 days. Chlorhexidine mouthwashes were used along with usual oral hygiene for 7 days. The patient was instructed to avoid using a mucosupported prosthesis for 15 days to prevent suture dehiscence. The postoperative recovery was uneventful. After 7 days, the patient returned to the university for suture removal and clinical examination. Twelve months after the procedure, a CT scan showed the maxillary sinus without the opacification, with no sign of sinusitis (Figures –). The patient is being regularly monitored for future rehabilitation of the edentulous area. The Helsinki declaration was followed in this case report.


Our patient was a 27-year-old Japanese woman, gravida 1 para 0 (G1P0010). Her obstetric history was not significant except for a spontaneous abortion requiring curettage 10 years previously. There was no history of any other pelvic or abdominal surgical intervention.
She was admitted to our hospital with premature rupture of the membranes and had undergone induction of labor at 39 gestational weeks. Two days later, she had an uncomplicated vaginal delivery of a 3244-g male infant with a good Apgar score. However, her placenta was not delivered. We tried manual removal of the placenta, but felt resistance during traction of the umbilical cord. Subsequent Doppler ultrasonography (US) examinations showed a progressive vascular flow to the placental mass in her uterus. We suspected placenta accreta, so we left the whole placenta in her uterus. Fortunately, postpartum bleeding was not severe and the total amount of bleeding was 850mL, even though the umbilical cord was torn during delivery.
We cared for the bleeding and possible infections. At 7 days post-partum, her serum human chorionic gonadotropin (hCG) level was 12,656IU/L. Gadolinium-enhanced MRI also indicated deep myometrial invasion by placental tissues, and the whole placenta was strongly enhanced (Fig. ). A general physical examination revealed no abnormalities. Her medical and gynecological histories were unremarkable.
Our patient hoped to preserve her uterus for a future pregnancy so we decided to administer 50mg MTX by intravenous injection after obtaining informed consent relevant to surgical and other treatment strategies. Hematological, hepatic, and renal functions were evaluated and found to be normal before the MTX injections. Our patient experienced no untoward effects following MTX administration, and her vaginal bleeding diminished gradually over four weeks. To avoid intrauterine manipulation with surgical equipment and subsequent infection (that is, diagnostic hysteroscopy), follow-up MRI using an identical technique was performed every four weeks to assess the treatment response. MTX therapy (50mg/week) was administered 13 times. During the course of this therapy, our patient had an intrauterine infection and took three separate course of antibiotics. Complete resolution of the uterine lesion was confirmed by MRI scans (Fig. ). Her serum hCG level was undetectable (<5IU/L) 97 days after the first MTX injection (Fig. ). At 117 days post-partum, she had a labor-like pain every three minutes and delivered the remnant of the placenta with a little bleeding. The vestigial mass weighed 80g (10×6×4cm) and histopathology indicated placental tissue with necrosis. Her menses resumed 181 days after the first MTX injection, and a follow-up hysteroscopy showed no abnormal findings (Fig. ).
Two years later, our patient (G2P1011) became pregnant spontaneously. We did not detect any placental lacunae or clear spaces on transabdominal US, nor did we see any depletion of decidua in her uterus on MRI. She underwent an uncomplicated vaginal delivery of a 3304-g female infant with a good Apgar score. Postpartum bleeding was not active and the total bleeding was 910mL. We did not find any thinning of the posterior uterine muscular layer on transabdominal US, and there was no bleeding with the dislodging of the placenta. The placenta had histopathological features of marginal infarction and chorioamnionitis stage 2 by the Blanc category. Two independent pathologists did not note any deficiency in the decidua.


A 45-year-old female patient reported with the chief complaint of growth on the inner aspect of right cheek with one-year duration. History of presenting illness revealed that the growth was gradual in onset, initially small in size now increased to attain the present size. There was also a history of occasional bleeding from the growth during chewing. The patient’s medical history and family was insignificant. Extra oral examination showed no swelling or facial asymmetry. Intraoral examination revealed a solitary exophytic, pedunculated growth on the right side of buccal mucosa at the level of occlusal plane ().
The exophytic growth appears erythematous with grayish white borders with lobulated surface. The growth measured of about 2cm×1cm in diameter, which was soft to firm in consistency and bled on provocation. The cusp of the right upper premolars had sharp buccal edge corresponding to about the center of the swelling. There was no evidence of pus discharge from the lesion. Regional lymph nodes were not palpable. Based on the history and clinical appearance of the lesion, provisional diagnosis of benign exophytic growth of right buccal mucosa was considered. And the differential diagnosis included traumatic fibroma, pyogenic granuloma, and capillary hemangioma. The lesion was excised under local anesthesia and sent for histopathological examination.
shows the macroscopic appearance of the excised specimen in the formalin bottle. Histopathologically, hematoxylin-eosin (H&E) stained section confirmed the clinical diagnosis of pyogenic granuloma ().
The wound healing was completed and no recurrence was noted on 3-year follow up period ().


A 36-year-old Japanese male was referred to our hospital because of persistent chest pain and a subacutely progressive pulmonary nodule. Four weeks prior to his referral to our hospital, he began to experience chest pain that increased in severity on inspiration. He visited a private hospital the following day. He had no family or personal history of nontuberculous or pulmonary disease. Chest computed tomography (CT) showed an irregularly shaped solitary nodule in the periphery of the left lower lobe with microcalcifications and pleural indentation. On CT at a follow-up appointment 2 weeks after the initial consultation, the nodule was enlarged (Fig. , ). To diagnose the subacutely progressive pulmonary nodule, a CT-guided lung biopsy was performed in the private hospital. The histological examination of the biopsy specimens revealed granulomatous inflammation with atypical cells of various sizes. One week later, the patient was referred to our hospital. Although we intended to clarify the origin of the atypical cells and rule out malignancy, the specimen volume was insufficient for further investigation.
He reported no history of smoking, foreign travel, eating crab or boar or deer meat, or contact with patients with active pulmonary tuberculosis. The results of his physical examinations, including vital signs and consciousness, were normal. The laboratory data, including lymphocyte count, C-reactive protein, procalcitonin, gamma globulin, tumor markers, antineutrophil cytoplasmic antibodies, anti-HIV antibody, β-D-glucan, aspergillus antigen, cryptococcus antigen, Interferon-Gamma Release Assay (T-SPOT.TB®), and antibody to Paragonimus westermani or P. miyazaki, were unremarkable. Two weeks after the referral, positron emission tomography (PET)-CT showed intense FDG uptake in the nodules, with a maximum standard uptake value (SUV) of 13.94 (Fig. ).
Owing to his continuous chest pain and subacutely progressive nodules, which could not be diagnosed using CT-guided lung biopsy, wedge resection via video-assisted thoracoscopic surgery was performed in the left lower lobe. The histological examination revealed an epithelioid granuloma, with caseating necrosis and calcification, and pleurisy over the visceral pleurae (Fig. –). Although a smear test of the resected lung tissue was negative, the patient was initially diagnosed with tuberculosis based on the results of the histological examination. Antituberculous therapy was initiated with isoniazid, rifampicin, ethambutol, and pyrazinamide. Because the patient presented with severe skin eruptions and high fever 2 weeks after initiation of the antituberculous therapy, we paused the treatment. One week later, the lung tissue culture was positive for mycobacteria identified as Mycobacterium avium via DNA-DNA hybridization. His chest pain disappeared almost simultaneously. Anti-interferon-γ autoantibodies were negative. We plan to initiate anti-MAC chemotherapy (rifampicin, ethambutol, and clarithromycin) once these adverse effects have abated, for which the patient is being closely monitored.


A 3-year-old boy without any medical history presented with a headache and vomiting and was referred to our institute. Computed tomography (CT) images, which had incidentally been taken 2 years before at a local neurosurgical clinic for the assessment of a minor head injury, were available and showed no significant abnormality (Fig. a). The patient had no neurological deficit on admission. Magnetic resonance imaging (MRI) showed enlargement of all ventricular systems associated with the dilatation of the foramina of Magendie and Luschka, with no obstructive organic lesions (such as brain tumors) on contrast enhanced MRI (Fig. b–f). The patient underwent emergent ventricular drainage through the anterior horn of the right lateral ventricle to relieve his symptoms. We had initially considered this case might be a communicating hydrocephalus because the fourth ventricle outlets appeared to be patent on MRI. However, the highly expanded fourth ventricle and its outlets were inconsistent with communicating hydrocephalus. We thus conducted CT ventriculo-cisternography on the fifth day post-surgery by injecting contrast medium (Isovist®) via a ventricular catheter (Fig. ). On serial CT images, contrast medium was accumulated in the foramina of Magendie and Luschka 1 h after injection, with limited diffusion to the adjacent cisterns at 3 h after injection. These findings suggested a mechanical obstruction at the outlets of the fourth ventricle. We therefore diagnosed the patient with FVOO and chose to perform an ETV using a flexible neuro-endoscope (VEF-V, Olympus, Tokyo, Japan). The endoscope was inserted into the fourth ventricle through the dilated cerebral aqueduct and encountered the suspected cause of obstructive hydrocephalus—a thickened, arachnoid, membranous structure that enveloped the foramina of Magendie and Luschka (Fig. ). A standard third ventriculostomy in the tuber cinereum was performed without any additional surgical intervention to the membranous structures in the fourth ventricle outlets. On endoscopic observation of the lateral ventricle and pre-pontine cistern, no abnormalities suggestive of previous meningitis or intraventricular hemorrhage were found. The patient’s postoperative course was uneventful with no signs of neurological deficit. MR images obtained 1 month post-surgery revealed significant resolution of the hydrocephalus (Fig. a). However, after 1 year, the patient again presented with vomiting, and it was noted that the hydrocephalus had recurred (Fig. b). Re-exploration with the endoscope revealed severe stenosis of the fenestration site from the first surgical procedure and a second ETV was subsequently performed. Postoperative MRI confirmed that the hydrocephalus was resolved (Fig. c). The patient has remained in good condition without recurrence of hydrocephalus, as identified by MRI, since undergoing the second ETV for 20 months.


A 37-year-old previously healthy white woman was stung by an unknown Hymenoptera; an hour later a rash developed accompanied by breathing difficulties and impaired consciousness. At a nearby clinic she was found to be hypotensive and was immediately given intravenous adrenaline (0.9 mg) and promethazine, and transferred to our emergency room. On admission she was agitated, tachypneic without stridor (approximately 24 breaths/minute), desaturated (arterial oxygen saturation, SaO2, approximately 84 on oxygen mask) and hypotensive (blood pressure was 85/50 mmHg) with cool and moist extremities. Her ECG demonstrated lateral wall ST elevation, inferior and anterior ST depressions. Echocardiography demonstrated left ventricular (LV) global basal and mid akinesis with preserved apical contraction, with an estimated LV ejection fraction of 20 % (Fig. ), her right ventricular cavity size was normal and its systolic function was mildly reduced. Combined cardiogenic and anaphylactic shock was therefore suggested. She was then mechanically ventilated and transferred to the cardiac catheterization laboratory for a presumed acute myocardial infarction. Cardiac catheterization revealed normal coronary angiography, severely reduced LV function with hyperdynamic apical function. The LV end diastolic pressure was 25 mmHg. At this time her blood pH was 7.2, lactate level was 3.3 mg/dl with a combined metabolic and respiratory acidosis. Her troponin I level was 0.14 ng/dl (high). An intra-aortic balloon pump was inserted and set to 1:1 augmentation, and various intravenous high-dose inotropic agents including adrenaline, norepinephrine and dopamine were administered to achieve a central systolic blood pressure of approximately 100 mmHg and appropriate arterial oxygen saturation. She remained hemodynamically unstable under this aggressive pharmacological and mechanical support. Assuming a reversible cause of cardiomyopathy, venoarterial extracorporeal membrane oxygenation (VAECMO) was installed via the femoral vessels (21 F and 18 F for venous and arterial cannulas, respectively) with limb perfusion protection. A day later, she was extubated and as her cardiac systolic function improved she was gradually weaned off VAECMO support and inotropic agents over the following 48 hours. She was discharged with a near normal LV ejection fraction and gained a full complete recovery. Three weeks after the event she was asymptomatic with normal electrocardiographic and echocardiographic examinations (LV ejection fraction >65 %, Fig. ) and she returned to her previous healthy normal life. She continued with Hymenoptera venom sensitivity testing and started a desensitization program.


A 56-year old man presented to a regional hospital with acute gout of the right knee, on a background of 6 months of lethargy, easy bruising, epistaxis and recent episodes of macroscopic haematuria. On presentation, he was noted to have AKI, anaemia, thrombocytopaenia and abnormal liver function tests. His past medical history included gout, alcoholism (10 standard drinks daily), gastro-oesophageal reflux and previous gastric fundoplication. He was not on any regular medications. He lived alone and was an active smoker of 20 pack-years but denied intravenous or recreational drugs. He reported no fever, sweats or weight loss (body mass index, 22.9 kg/m2). He had no haemodynamic compromise and was transferred to our centre for further management.
On arrival, his blood pressure was 140/80 mmHg. He had a normal mental status and no focal neurological signs. Physical examination was notable for mild hepatomegaly, subcutaneous bruising and spider naevi. Macroscopic haematuria was evident when the patient voided. His vital signs were normal and the laboratory results on arrival are shown in Table . The blood film showed target cells, anisocytosis, stomatocytes, occasional myelocytes and confirmed thrombocytopaenia. In retrospect, thrombocytopaenia was first noted eight months prior to presentation (platelet count, 60 × 106/L; reference range [RR], 150–400 × 106/L). At this time, the patient’s serum creatinine was 100 μmol/L (RR, 60–110 μmol/L), with an estimated glomerular filtration rate (eGFR) of 73 ml/min. Kidney function was noted to be slightly impaired (serum creatinine, 113 umol/L (eGFR, 63 ml/min) four months ago, after the onset of haematuria was noted.
Autoimmune studies were negative including: anti-nuclear, anti-extractable nuclear antigens, anti-neutrophil cytoplasmic, anti-glomerular basement membrane, anti-double stranded DNA antibodies. The serum electrophoresis revealed neither serum paraprotein nor increased free light chains. Serology was negative for hepatitis B, C and HIV. Serum IgA level was elevated at 6.7 g/L (RR, 0.80–4.50 g/L) with normal IgG and IgM levels. Serum complement was low on presentation, with a C3 of 0.56 g/L (RR, 0.79–1.52 g/L) and C4 of 0.10 (RR, 0.16–0.38 g/L). Blood cultures were negative on two separate occasions.
Urinalysis of a sterile, mid-stream sample confirmed haematuria, with an erythrocyte count >999× 106/L (RR, <13 × 106/L) and leukocyte count of 10 × 106/L (RR, <10 × 106/L). Urine sediment analysis showed dysmorphic erythrocytes and casts, consistent with a glomerular origin. A 24-h urine collection showed a protein excretion of 1.8 g/24 h (protein:creatinine ratio 0.25 g/mmol; RR, 0.00–0.03 g/mmol). Abdominal ultrasound demonstrated mild hepatomegaly with diffuse echogenicity consistent with hepatic steatosis. The kidneys measured 11.1 cm and 11.4 cm, with no hydronephrosis. Urine cytology was negative for malignant cells.
Acute glomerulonephritis was suspected and he was treated with intravenous methylprednisolone. An urgent kidney biopsy was performed after platelet transfusion to a count of 102 × 109/L. A bone marrow biopsy was also performed. The kidney specimens demonstrated cortex with 27 glomeruli, of which 6 were globally sclerosed. The principal abnormality was extensive tubular intra-luminal erythrocyte cast formation associated with acute tubular necrosis (Fig. ). The presence of haemosiderin deposition within tubular cells was suggestive of recurrent glomerular bleeding. There was interstitial fibrosis and tubular atrophy (approximately 30 %), along with a mild inflammatory infiltrate without eosinophils or granulomas. Glomerular capillary loops appeared normal and there were no segmental necrotizing lesions or crescents. Immunoperoxidase stains showed weak, non-specific mesangial staining for IgM (1+) and no significant staining for IgA, IgG, C3, C1q and fibrinogen. Electron microscopy showed thinning of the glomerular basement membrane but no immune complexes. The average glomerular basement membrane thickness was 251 ± 70 nm (range, 125–439 nm), consistent with thin basement membrane disease. This was associated with incomplete pedicel effacement, indicating podocytopathy (Fig. ). Bone marrow examination showed moderately reduced megakarypoeisis but otherwise normal haemopoeitic function. Cytogenetics and immunophenotyping were unremarkable.
The patient’s macroscopic haematuria ceased after correction of platelet count and intravenous desmopressin given for biopsy. The serum creatinine peaked at 552 μmol/L and subsequently improved. He maintained a good urine output and was discharged for outpatient follow-up. He achieved a best serum creatinine of 250 μmol/L at 6 months, with significant chronic kidney disease (eGFR, 25 ml/min) with mild proteinuria (protein:creatinine ratio, 0.07–0.10 g/mmol). He continued to experience episodes of macroscopic haematuria and AKI although not to the extent experienced on initial admission. His platelet count continued to fluctuate at 26–53 × 109/L. A second bone marrow biopsy 4 months later only showed mildly reduced megakaryopoiesis. A reduced production of thrombopoeitin associated with liver disease and the direct toxic effects of alcohol may be potential factors contributing to the reduced platelet production. Repeat serum complement and autoimmune studies were normal on two separate occasions. After nine months of ongoing alcohol intake, repeat abdominal ultrasound noted hepatic nodularity and small volume ascites. The spleen was borderline enlarged, measuring 14.0 × 7.24 × 6.08 cm, giving a splenic volume of 323 cm3. Thus, splenic sequestration-destruction could also be contributing to the thrombocytopaenia. The follow-up ultrasound also noted a reduction in kidney size (right 9.4 cm, left 10.2 cm), associated with an eGFR of 15 ml/min. Due to progression of his chronic kidney disease, he has been worked up for long term haemodialysis with the creation of an arterio-venous fistula.


The patient is a 50-year-old white male, previous smoker (he smoked for 30 years, 45 pack-years, quitting 8 years ago), who worked in an underground emerald mine for 20 years, until 9 years ago, without proper use of personal protective equipment. He had a history of pulmonary tuberculosis treated with rifampin, isoniazid, and pyrazinamide for 2 months, followed by rifampin and isoniazid for 4 months, 11 years ago.
He attends a pneumology outpatient clinic due to silicosis and, as of 2013, a high-resolution computed tomography of the thorax already showed structural lung sequelae.
During follow-up, he developed a worsening of cough and expectoration pattern. Two sputum samples were positive for acid-fast bacilli [(+) and (++), resp.], and presumptive treatment for pulmonary tuberculosis was initiated with rifampin, isoniazid, pyrazinamide, and ethambutol. Mycobacteria culture was not performed at this moment. However, at month 5 of treatment, already in the continuation phase with rifampin and isoniazid, and despite correct medication intake and a slight improvement of symptoms, sputum bacilloscopy remained positive. A thorax computed tomography revealed large pulmonary opacities in the upper lobes of both lungs, with intermingled air bronchograms and calcifications, bilateral diffuse nodular infiltrates with areas of pleural thickening, and nodular interstitial infiltrate associated with ground glass opacities in the posterior segment of the inferior right lobe, as well as cavitations with thick walls, suggesting an active inflammatory process (). Blood tests revealed a normal hemogram and renal and liver functions, and HIV, hepatitis B, and hepatitis C serologies were negative.
Sputum cultures were then performed and two were positive for NTM; while awaiting the identification of the species, empiric treatment with streptomycin, ethambutol, clarithromycin, and rifampin was instituted for Mycobacterium avium, the most frequently NTM isolated in our community. The patient had a greater improvement of his symptoms.
The species identification was performed by the Tuberculosis Bacteriology Laboratory from the Professor Hélio Fraga Reference Center (Rio de Janeiro), the National Mycobacterium Reference Laboratory, using genetic sequencing of the 16S rRNA gene. The NTM species isolated was Mycobacterium sherrisii. The treatment regimen was once again adjusted, with the replacement of rifampin with rifabutin, inclusion of trimethoprim-sulfamethoxazole (TMP-SMX), and suspension of streptomycin after 2 months. A sensitivity test was not performed.
Currently, the patient is at month 9 of treatment, with only an occasional nonproductive cough, and with negative sputum bacilloscopies and cultures, which have been performed monthly, since month 2 of treatment.
It is our plan to complete 12 months of treatment with rifabutin, clarithromycin, ethambutol, and TMP-SMX, as of the first negative culture.


We present a 67-year-old female with high blood pressure and previous ictus with no sequelae. She was being treated with antiaggregant (acetyl salicylic acid). She complained of two-year evolution of intermittent dysphagia for solids, not associated with chest pain or significant weight loss. A high resolution esophageal manometry and 24-hour pH-metry were found to be normal. An oral panendoscopy showed multiple exudative ulcerations with fibrin () and webs in mid- and proximal esophagus () and a peeling mucosa (). Initially we suspected pill-induced esophagitis so that the acetyl salicylic acid (ASA) intake was stopped and antiacid was prescribed, but the patient did not improve. Several oral panendoscopies (OPE) were carried out with similar findings discarding peptic and viral esophagitis, candidiasis, and even HIV. An esophagogram did not show esophageal stenosis and a thoracic-cervical CT was also normal. We performed diagnosis of exclusion with the possibility of esophageal pemphigoid cause of esophageal ulcers. Therefore we performed a biopsy with direct immunofluorescence (DIF), demonstrating IgG and C3 complement deposition along the basement membrane (Figures -). There were no ocular or skin lesions, only vulvar erythema with no pemphigoid signs on the biopsy. As initial treatment the patient received prednisone at 1 mg/kg daily (60 mg) and 2 gr daily of MMF as a steroid-sparing agent. Six months later there was a significant clinical improvement: the patient had no dysphagia and had gained weight. Moreover the esophageal ulcerations had disappeared, developing cicatricial fibrous rings, although no stenosis was present (). This allowed us to use MMF maintenance dose of 500 mg daily. The control gastroscopies showed no evidence of reactivation of the disease. Four years later the patient continues asymptomatic, without other extraesophageal manifestations.


A 69-year-old man was admitted for treatment of a large, 12-cm hepatic tumor. He had chronic hepatitis C with a sustained virologic response to interferon treatment. Plain computed tomography (CT) showed a heterogeneous, hypodense tumor located in segments IV/V/VIII of the liver. The tumor showed contrast enhancement and washout in the arterial and late phases. The levels of alpha-fetoprotein, Lens culinaris agglutinin-reactive fraction of alpha-fetoprotein, and protein induced by vitamin K absence/antagonist-II were 13.7 ng/mL, <0.5 %, and 14,699 mAU/mL, respectively. The indocyanine green retention rate at 15 min was 6.6 %. The patient was classified as having Child-Pugh class A liver function based on the following parameters: total bilirubin, 0.9 mg/dL; albumin, 4.1 g/dL; prothrombin activity, 91 %; ascites, absent; and hepatic encephalopathy, absent. The ratio of 99mTc-galactosyl human serum albumin (GSA) scintigraphy uptake by the liver to that by the liver plus heart at 15 min was 0.97. Curative hepatectomy, in the form of mesohepatectomy, was initially planned.
However, an exercise stress test on a treadmill showed ST depression in leads II, III, aVF, V4, V5, and V6 at a double product of 13,500 in the Bruce protocol (Fig. ) despite no apparent findings on the electrocardiogram and echocardiogram. Then, coronary contrast CT and 201Tl myocardium scintigraphy revealed asymptomatic myocardial ischemia (inferioseptal ischemia). During coronary angiography, multiple stenoses were detected: 100 % of the #2 right coronary artery, 75 % of the left main trunk, and 90 and 50 % of the #6 and #7 left coronary arteries, respectively (Fig. ). A multidisciplinary discussion between the hepatic surgery, cardiovascular surgery, and cardiovascular medicine departments was conducted. The use of a bare metal stent in the left main trunk is unreliable, a DES requires oral administration of a dual antiplatelet agent for at least 6–12 months, and coronary artery bypass grafting (CABG) can be conducted 1 month after hepatectomy if everything goes smoothly [, ]. However, the risks with mesohepatectomy are high in the presence of oral anticoagulant and antiplatelet administration. Therefore, as an initial therapeutic strategy, the following sequential treatments were planned: TACE for local disease control, CABG, and mesohepatectomy without the use of an anticoagulant or antiplatelet agent.
One month following successful TACE to prevent aggressive disease progression, CABG (left internal thoracic artery-left anterior descending coronary artery [LITA-LAD], aorta-saphenous venous graft-right coronary artery [AO-SVG-RCA]) was performed. However, the coronary three-dimensional CT on day 7 post-CABG showed a poorly described LITA-LAD bypass, and myocardial scintigraphy revealed a re-distributed image in the middle reserve on the apex side, indicating remaining myocardial ischemia. Although the HCC was partially controlled by TACE, partial viability remained (Fig. ). Therefore, we finally decided to perform an IABP-assisted mesohepatectomy as curative treatment for HCC.
Eleven weeks after the TACE, the IABP-assisted mesohepatectomy was performed (Fig. ). The antiplatelet (aspirin) and anticoagulant (warfarin potassium) agents were stopped 9 and 7 days, respectively, before the hepatectomy. Heparin was continuously and intravenously administered for 6 h before the hepatectomy. First, the IAB was inserted from the left femoral artery under local anesthesia and perioperatively ran at a 1:1 ratio without a heparin cover. To avoid a cardiovascular event, intravenous nicorandil and isosorbide mononitrate were continuously administered. There was no apparent change in vital signs after the IABP was inserted. Conventional liver resection was performed through an exclusive abdominal incision. Liver transection was performed using the Pean clamp-crushing technique and TissueLink (TissueLink Medical Inc., Dover, DE) or a VIO soft coagulation system (ERBE, Elektromedizin GmbH, Germany). The Pringle maneuver or hemihepatic vascular occlusion was applied during parenchymal transection. In addition to the general vital signs, hemodynamics were monitored using a FloTrac Sensor®, and transesophageal echocardiography was monitored; the patient remained stable during the operation. During the mesohepatectomy, 998 mL blood was lost with transfusion of 6 units red cell concentrate, and the operative time was 5 h and 31 min. The IABP was removed the following morning without any problem.
Standard systemic antibiotic therapy using cefmetazole was routinely administered immediately before surgery and then twice daily for the first three postoperative days. Nicorandil and isosorbide mononitrate were also administered after surgery, and the route of administration was changed to oral and transdermal patches, respectively, on postoperative day 3. The antiplatelet agent (aspirin) was also resumed on postoperative day 3 without any sign of postoperative bleeding. The postoperative course was uneventful, and he was discharged on postoperative day 15 (Clavien-Dindo classification, grade 1). The liver tumor was pathologically diagnosed as poorly differentiated HCC. Then, PCI was successfully performed.


A 71-year-old man underwent PVP following a long history of lower urinary symptoms and failed drug treatment with tamsulosin. Preoperatively, the prostate had a volume of 44 cc as measured by transrectal ultrasound. Treatment was performed using the 180 W XPS GreenLight laser (American Medical Systems, Minnetonka, Minneapolis). The total operation time was 51 minutes and total lasing time was 25 minutes and 259 kJ of energy was expended. The operative procedure was uncomplicated and following surgery the duration of catheterisation and duration of hospital stay were 11 and 18 hours, respectively.
At one year following PVP, he presented with exercise related macroscopic haematuria. A urinary tract ultrasound and computerised tomography of the abdomen and pelvis failed to find an explanation for these symptoms. Rigid cystoscopic examination at that time appeared unremarkable. The patient also complained of perineal pain and bilateral groin pain on walking. A technetium 99 radionuclide bone scan revealed increased tracer uptake at the pubic symphysis with erosive changes likely related to symphysitis pubis and he was then referred for management by an orthopaedic surgeon.
Over the next 12 months, the patient continued to complain of urinary symptoms and haematuria. Over this time, he continued to experience bilateral groin pain on walking which was managed with analgesics. Empirical treatment with dutasteride failed to alleviate the urinary symptoms and a further rigid cystoscopic examination was performed. On this occasion, an actively bleeding ulcer was observed on the anterior aspect of the prostatic urethra and there appeared to be a calculus present within. Access and visibility were difficult due to the anterior location and the side firing Greenlight laser was therefore used to cauterise visible bleeding following extraction of the calculus.
Magnetic resonance imaging of the prostate was then undertaken and this revealed the presence of a communication between the anterior part of the prostate and the pubic symphysis with urine filling the space of completely eroded symphysis pubis cartilage (), confirming a diagnosis of a prostatosymphyseal fistula.
Following a review of the literature, the decision was made to undertake treatment with robotic assisted radical prostatectomy. Using the Da Vinci Si robotic platform, surgery was performed using a six-port transperitoneal approach. There was surprisingly little difficulty in accessing the retropubic space. The endopelvic fascia was opened on each side and the prostate was found to be adherent to the symphysis pubis. Upon disconnecting the prostate flush from the pubic bone, a large defect in the anterior aspect of the prostate was uncovered and a clean defect was observed in the space where cartilage of the symphysis pubis had been completely eroded ().
The patient made an uneventful recovery. Histopathology of the prostate specimen found incidental focal Gleason Score 3 + 3 = 6 adenocarcinoma.
At one month following procedure, the patient reported complete resolution of pain and had returned to playing golf. Urinary leakage was minor and necessitating a single pad per day.


A 24 year old female patient in 2002 at the age of 12 underwent a Ross procedure due to severe congenital aortic valve stenosis. During the follow-up, in the last year the aortic root dilated from 30 mm to 34 mm. Other findings were mild aortic regurgitation and mild pulmonary valve stenosis (mean gradient 15 mmHg) with no progression. The patient is still under surveillance and clinically is on NYHA class II.


A 29 year old female patient in 2002 at the age of 17 underwent a Ross procedure due to a congenital severe aortic valve stenosis combined with regurgitation. During the follow-up the aortic root and the ascending aorta gradually dilated to 52 mm and 50 mm respectively with also mild to moderate aortic regurgitation (Fig. ).
In 2014 she underwent a redo-Bentall operation with the replacement of the dilated aorta and aortic valve with a mechanical conduit ATS 22 mm/26 mm (Medtronic Inc MN USA). After the operation the patient is stable and is doing well.


A 29-year-old man was treated by percutaneous stabilization from L1 to L3 (pedicle screw diameter: 5.5 mm in L1 and 6.5 mm in L3) for a L2 burst fracture (type A3.1 according to Magerl’s classification []) caused by a car accident (Fig. a).
After 6 months of follow-up the fracture was healed but the patient reported local pain, presumably due to mechanical irritation. Nine months after the first surgery, the spinal fixation was removed. No sign of implant failure or loosening was found on preoperative radiographs and on the operative field.
There were no intraoperative complications. The patient began to walk on the first post-operative day.
One month after the second surgery, the patient, suffering from bronchopneumonia, experienced a sharp pain in the upper lumbar spine during an episode of forceful coughing.
X-ray, computed tomography (CT) scan and magnetic resonance imaging demonstrated an acute wedge fracture (A1.2) of the superior plate on L1 (Fig. b). No signs of spondylodiscitis were present.
Very precise peripheral measurements by quantitative CT for the evaluation of bone density showed normal cortical and cancellous bone density. The patient had never used steroids. Body mass index was below 25. Laboratory tests were in the normal range except for markers of inflammation (WBC and ESR). C-reactive protein was normal.
The fracture was treated conservatively by a 3-point brace and analgesics for 3 months and healed without further progression of the kyphotic deformity (Fig. c). The patient returned to his previous job after 4 months. At the time of last follow-up, 12 months after the second surgery, he was completely pain-free.


A 30-year-old female patient reported to the Department of Conservative Dentistry & Endodontics, Vasantdada Patil Dental College, with a chief complaint of food lodgement in maxillary left first premolar tooth (number 24). Patient gave history that the tooth was decayed for the past 5-6 years and denied any past or recent episode of trauma. Clinical examination revealed presence of distoocclusal caries in tooth number 24 () and absence of draining sinus, swelling, and tenderness to percussion. Medical history was noncontributory. Radiographic examination by an intraoral periapical radiograph revealed distoocclusal caries in tooth number 24 approaching pulp chamber (). An oval shaped radiolucency within the root periphery of tooth number 24 at the junction of coronal and middle one-third of the root was observed, suggestive of internal root resorption, which was confirmed by taking multiple angulated radiographs. It is worth highlighting that the patient had no pain, normal space on the periodontal ligament, and no mobility of the tooth. Vitality testing of the involved tooth with dry ice (R C Ice; Prime Dental Products India) and electronic pulp stimulation (Parkel Electronics Division, Farmingdale, NY) gave a positive response. From the clinical and radiographic findings, a diagnosis of inflammatory internal root resorption in tooth number 24 was made and endodontic treatment of tooth number 24 was suggested to the patient.
Local anesthesia (2% lignocaine with 1 : 80000 adrenaline) was administered and tooth number 24 was isolated under rubber dam. Removal of caries was done followed by access cavity preparation with high speed air turbine with careful attention to the direction of the diamond point to prevent accidental perforation. Canals were thoroughly irrigated with normal saline followed by 3% sodium hypochlorite. The working length of the tooth was measured first manually and then by Root ZX apex locator (J. Morita Mfg. corp., Kyoto, Japan) which was confirmed radiographically (). Biomechanical preparation was done of 24 using ProTaper nickel-titanium rotary instruments (Dentsply Maillefer) in a crown-down technique till F3 file. Root canals were copiously irrigated with 3% sodium hypochlorite solution using nontraumatic plastic tips of EndoActivator (Dentsply) for achieving a complete chemomechanical debridement. A calcium hydroxide dressing (RC CAL, Prime Dental Products, India) was placed for a period of 30 days, with change of the medication after 15 days. A small cotton pallet was placed and the access cavity was temporarily sealed with Cavit (3M ESPE, Saint Paul, MN). After 30-day interval, the root canal was reentered and irrigated with normal saline and hand filing with number 15 K file alternately to remove the calcium hydroxide medicament, followed by 3% NaOCl, 17% EDTA, and normal saline used as the final irrigant. As the internal resorption defect periphery was very thin radiographically, absence of any perforation during root canal instrumentation was confirmed with dried sterile absorbent paper points. Master cone selection was done and confirmed radiographically (). Biodentine capsule (Septodont, Saint-Maur-des-Fossés, France) () was mixed according to manufacturer's instructions and capsule material which had good creamy consistency was inserted into the resorption cavity using a nonsurgical MTA carrier (Micro Apical Placement System, Produits Dentaires, Vevey, Switzerland) and was condensed laterally against the walls of resorption cavity with root canal spreaders (Dentsply Maillefer) to reinforce the weakened tooth structure of the resorptive defect (). After ensuring complete set of the material (setting time 12 mins), the remaining resorptive defect was obturated using thermoplasticised gutta-percha technique. Obturation was done with a down pack of gutta-percha using E & Q pen (META BIOMED) () with AH plus sealer (Dentsply). The remainder of canal was backfilled with an E & Q gun using thermoplastic gutta-percha. Warm gutta-percha at the orifice was vertically compacted by using appropriate sized pluggers. After completion of root canal treatment, the tooth was restored using posterior resin composite (P60; 3M Dental Products, Saint Paul, MN). Immediate postoperative radiograph showed dense obturation in the resorptive defect (). After ten-month follow-up, the patient was asymptomatic demonstrating a functional tooth number 24. Radiographic examination revealed stoppage of resorptive process with intact dense obturation (). The patient was advised with full-coverage porcelain crown.


An 18-year-old male patient was referred to the Cardiology Emergency Department with dyspnea and progressive weakness accompanied by cough and edema of lower extremity. One month ago, he had been submitted to hepatectomy due to the primary adult hepatoblastoma at a local hospital. Clinical examination revealed distended jugular veins, systolic murmurs could be heard on tricuspid valve area, edema of lower extremity, and the sign of left side pleural effusion was positive. The serum levels of carcinoembryonic antigen (CEA) were elevated at 239.1U/mL, alpha fetoprotein (AFP) was elevated at 2 ng/mL. Arterial blood gas analysis showed PaO2 (arterial partial pressure of oxygen) was 61 mm Hg and PaCO2 (arterial partial pressure of carbon dioxide) was 38 mm Hg. Chest X-ray showed diffuse bilateral alveolar infiltrates and left-sided pleural effusion. Urgent echocardiography (Figure ) revealed the right ventricule was occupied by a dense sessile mass (43 mm × 30 mm) causing right ventricule and main pulmonary artery filling restriction, pulmonary artery hypertension (83 mm Hg), and tricuspid moderate regurgitation (Figure ). On August 30, 2013, the patient underwent surgical treatment due to worsening of his clinical condition. The large tumor was carefully and copiously dissected from the surrounding tissues due to its friability. The tumor originated mostly from the right ventricle and its terminal end was inside the main pulmonary artery. It was cautiously dissected from the tricuspid valve and the right ventricular endocardium ensuring that no remnants were left behind both on the tricuspid valvular cusps and within the vicinity of the right ventricle. Macroscopically, the tumor appeared sallow and the size was about 10 cm × 8 cm × 2 cm. The specimen was histopathologically investigated and eventually diagnosed as metastatic adult hepatoblastoma (Figure ). Immunohistochemistry findings showed AFP(−), CK7(−), CK8/18(+), Hepa(−), Vim(+), Syn(−), CD34(+), CD10(−), Ki67(+,80%), S-100(−), NF(−).
After operation, respiratory symptoms of the patient improved significantly, arterial blood gas analysis showed PaO2 was 89 mm Hg and PaCO2 was 41 mm Hg. Echocardiography revealed pulmonary artery pressure dropped to normal. Then, the boy was referred to the Oncology Department for further adjuvant therapy. Twelve months of follow-up, echocardiography and CT showed there were no signs of metastasis and recurrence. The patient provided written informed consent for the publication of these case details, and the consent procedure was approved by the Human Ethics and Research Ethics committees of The First Affiliated Hospital of Zhengzhou University, Henan, China.


A 22-year-old female, with no significant previous medical history, presented with a congenital painless left retroauricular swelling extending into the side of her neck. She consulted us due to recent onset dysphagia and headache. She had left sided cerebellar signs with left sided lower cranial nerve paresis on examination. She also had multiple subcutaneous neurofibromas over her body along with cafe au lait spots and a plexiform neurofibroma (PNF) of the left side of her neck ().
Magnetic Resonance (MR) images (Figures –) showed bony dysplasia of the left squamous occipital bone with herniation of the gliotic left cerebellar hemisphere and the tip of the left occipital lobe through the defect into the suboccipital region. Another meningocele was noted extending through the region of the left petrous apex into the left parapharyngeal region. There was dilation of the ventricular system also.
She was advised on duraplasty and cranioplasty along with excision of the redundant scalp. She refused to undergo the suggested procedure; however, she agreed to undergo a lumbar-peritoneal shunt. She had significant improvement in her symptoms as well as a reduction in the local swelling after the procedure. She has no recurrence of symptoms at follow-up of 3 years.


We report the case of a 56-year-old woman with personal history of smoking, dyslipidemia, hypertension, overweight (BMI 28), and amaurosis fugax episode whereby continued antiplatelet therapy with clopidogrel. The patient came to the emergency room for severe abdominal pain in the right lower quadrant with nausea and vomiting of 24-hour duration. The examination revealed abdominal distension, painful palpation in the right iliac fossa, and decreased bowel sounds.
The woman underwent abdominal ultrasound, which reported appendage of increased caliber with thickened wall, data compatible with uncomplicated acute appendicitis. She entered the surgery department, beginning antibiotic treatment with amoxicillin/clavulanic and deciding urgent open intervention. The preintervention clinical situation was stable from both respiratory and hemodynamic points of view. The laboratory exams and X-ray exams were also normal before the surgery.
It was decided to administer a pool of platelets, obtained by apheresis with a volume of 250 cc in 30 minutes, half an hour before intervention due to platelet dysfunction by clopidogrel. Pharmacological induction of anesthesia with propofol, fentanyl, and rocuronium was performed. Standard monitorization included SpO2, ECG, and noninvasive arterial pressure and neuromuscular block monitoring was applied. Intubation was performed without any problems including vomiting or aspiration. After induction elevated airway pressures were evident, without bronchospasm signs in the auscultation, improving after lung recruitment maneuvers. Subsequently she remained stable from both respiratory and hemodynamic points of view during the whole intervention. The surgery lasted 60 minutes. No general peritonitis was observed. Extubation was performed when the Train of Four ratio was higher than 0.9 and the conscious was recovered. After extubation, while staying at the postanesthesia care unit fifteen minutes after the extubation, she presented with progressive dyspnea, cyanosis, and severe agitation which may be related to the hypoxia and necessitated the administration of high-flow oxygen. A lung auscultation showed no rales, rhonchi, or wheezing. She was moved to the Resuscitation Unit where she persisted in need of high concentrations of oxygen. The patient remained hemodynamically stable without tachycardia and in sinus rhythm. No hypothermia and shivering were observed.
She underwent an urgent echocardiogram by an expert operator showing cardiac chambers of normal size, preserved systolic function, and normal pattern of relaxation filling mitral E/e′ = 6.2 (lateral measures) and the tissue Doppler shows a′ minor compared to e′ (see ). Also the presence of significant valvular and pericardial effusion was discarded. In the thoracic ultrasound the presence of B lines and areas of subpleural condensation in both hemithoraces were shown (see ). An urgent chest radiograph was requested showing the presence of bilateral pulmonary infiltrates, not present previously on admission. Noninvasive mechanical ventilation was established after the TEE and the results were observed. Arterial blood and gas analysis were repeated, confirming the existence of moderate respiratory failure (PaO2/FiO2 = 84/0.6 = 140).
Faced with the possibility of having platelet transfusion reaction, it was reported to the Hematology Department that dismissed the remaining blood components from the same donor. Procalcitonin and lactate were also requested, showing values within normal ranges. Diuretic therapy was initiated without improvement of pulmonary infiltrates in the following hours. In serial radiographs in 48 hours, the pulmonary infiltrates persisted. She remained hemodynamically stable during the next three days. The antibiotic treatment was discontinued on the third day of admission due to lack of fever and leukocytosis. From a respiratory point of view she needed noninvasive ventilation with pressure support of 15 cmH2O. The patient was discharged with supplemental oxygen by nasal cannula on the fifth day of admission in the Resuscitation Unit. X-ray and lung ultrasound at discharging were normal.


A 14 year old male of mixed Sephardic-Ashkenazi Jewish ancestry was referred to our Pediatric Rheumatology Clinic with “colchicine resistant FMF”. From early infancy he suffered from recurrent afebrile episodes of yellowish-greenish vomiting with abdominal pain. Episodes occurred every 1 to 2 weeks, lasting for 1–3 days. Exercise, stress and infections were precipitants of episodes. The patient did not develop rashes, joint/muscle or chest pain. He was hospitalized during several episodes due to dehydration, easily corrected by intravenous fluids. His school attendance was severely impaired, missing about 2 days every week. His father was diagnosed with FMF, after years of recurrent fever, abdominal pain and vomiting, with compound heterozygous mutations on the MEFV gene (M694V/E148Q). Following father’s diagnosis, our patient underwent genetic analysis at age 11 years and a heterozygote E148Q mutation was found. Colchicine was initiated and he received up to 1.5 mg/d for 2 years prior to his referral, with no clinical improvement. He underwent investigations by multiple pediatric gastroenterologists and metabolic diseases specialists, and his laboratory evaluation was normal including: acute phase reactants (even during episodes), blood counts, liver and muscle enzymes, fibrinogen, celiac profile, amino-acids, organic acids, acyl-carnitine and E3 mutation. Abdominal radiographs and ultrasound were normal. His physical examination was unremarkable except for low weight (7th percentile). Due to the history of bilious vomiting since his neonatal period he was referred by us for an upper gastrointestinal series (UGI). This demonstrated malposition of the ligament of Treitz and a corkscrew appearance of the duodenum, consistent with malrotation (Fig. ). After a successful Ladd procedure with classical findings of malrotation but no intestinal ischemia, the patient is feeling well, with no further vomiting episodes, a rapid catch up in the growth curves and full school attendance.


In early December 2009, a 71-year-old man presented to the Emergency Department with dyspnea as well as right-sided chest wall and upper quadrant abdominal pain. He was diagnosed with pulmonary embolus and started on anticoagulation. His imaging investigations revealed multiple coalesced masses in the liver with the largest measuring 6 cm x 9 cm x 9 cm in the right lobe of the liver. Multiple lesions were also noted in the lung with bilateral pleural plaques consistent with asbestos exposure (Figure ). Alpha-fetoprotein (AFP) was significantly elevated at 11 460 µg/L (normal less than 5). In late December, a liver biopsy was performed and pathology was diagnostic for primary HCC. He was diagnosed with Stage IV T3N0M1 disease. His past medical history was only significant for hypertension and Type 2 diabetes. He was an ex-smoker and quit in 1968. He was a retired boilermaker with asbestos exposure.
In late January 2010, he met with a liver surgeon. A repeat CT scan of the thorax and abdomen in early February revealed the liver lesions had increased in size with the primary lesion now measuring greater than 14 cm. Furthermore, there was evidence of worsening metastatic disease in the lungs with innumerable lesions between 0.5 and 2 cm in size. These were non-calcified and non-cavitary lesions. With this rapid doubling time, there was some debate within the Multidisciplinary Tumor Board about the role of medical treatment with sorafenib. The patient was ECOG 1 and had only mild hepatomegaly. He had no jaundice or stigmata of liver disease but was experiencing significant fatigue. Liver enzymes were minimally elevated with ALT 31 IU/L (normal less than 40), AST 73 IU/L (normal less than 41), ALP 95 IU/L (normal less than 129), and total bilirubin 8.1 µmol/L (normal less than 17). His albumin was 35 g/L and INR was normal. His Child-Pugh Score was A6. However, the combination of his hypertension and anticoagulation raised the concern of increased bleeding risk and potential difficulty controlling hypertension while on sorafenib. Therefore, in conjunction with the patient, it was decided to go ahead with radiotherapy alone.
The patient underwent 70 Gy treatment in 15 fractions to the liver, which was completed in April 2010 (Figure ). A follow-up CT abdomen in June 2010 showed the largest liver lesion had now shrunk from over 14 cm to 3 cm. The patient was clinically stable and asymptomatic. Biochemically, the AFP had decreased to 196.8 µg/L. In August 2010, the CT thorax and abdomen demonstrated stable disease in the liver. Furthermore, there was a dramatic complete resolution of the numerous pulmonary metastases with no new nodules or masses seen (Figure ). The patient received no other treatments up to this assessment point (August 2010), including no systemic treatments.
From August 2010 till March 2012, the man enjoyed stable disease with normal liver laboratory results (including an AFP of 3.1) and no imaging evidence of disease recurrence. In March of 2012, a small recurrent nodule was found in the right liver and he underwent hepatic artery embolization with doxorubicin and cisplatin in May of 2012. This resulted in a complete response at that location.


A 16-year-old Hispanic male presented to our emergency department (ED) with difficulty breathing that his mother first noted on the previous night. He had a history of muscular dystrophy (MD), frequent seizures and severe developmental delay causing him to be non-verbal at baseline. He also had a long-standing history of constipation. His mother had not noted any new symptoms until the previous night when he appeared to develop difficulty breathing. Upon arrival to the ED he was found to be in respiratory distress. His vital signs were significant for the following: heart rate 144 beats/minute; blood pressure of 43/22mmHg; temperature of 35.2ºC; and respiratory rate of 44 breaths/minute. Pulse oximetry waveform was initially undetectable. On initial exam we noted markedly but symmetrically diminished lung aeration, a tensely distended abdomen and mottled skin with cyanosis. When we attempted supplemental ventilation with bag valve mask we noted high airway pressures. Concurrent with obtaining intravenous access and placing the patient on continuous monitoring, we obtained portable supine chest () and left lateral decubitus abdominal () radiographs.
After noting massive pneumoperitoneum and elevation of the diaphragm we suspected tension pneumoperitoneum (TP) as the cause of shock. We positioned the patient in the right lateral decubitus position and placed three 14-gauge needles through the left abdominal wall, just lateral to the rectus musculature, and we advanced each needle until a rush of air was heard. As air was evacuated the patient’s abdominal distension visibly resolved. We soon noted decreased airway resistance and improved aeration. Within minutes the patient’s blood pressure improved to 93/47mmHg, and his pulse oximetry waveform became detectable at 93%. A repeat chest radiograph showed markedly improved pneumoperitoneum and diaphragmatic excursion with persistently dilated loops of bowel ().
The patient was then taken to the operating room where he was found to have purulent peritonitis, and a 1.5cm cecal perforation was identified and repaired. A large rectal scybalum was also noted, and as there was no other bowel pathology identified during laparotomy, the cause of our patient’s bowel perforation was determined to be obstipation. We suspect that his preexisting communication difficulties caused a delay in presentation, allowing his constipation to progress to bowel perforation.