Targeted high-throughput sequencing for genetic diagnostics of hemophagocytic lymphohistiocytosis

Background: Hemophagocytic lymphohistiocytosis (HLH) is a rapid-onset, potentially fatal hyperinflammatory syndrome. A prompt molecular diagnosis is crucial for appropriate clinical management. Here, we validated and prospectively evaluated a targeted high-throughput sequencing approach for HLH diagnostics. Methods: A high-throughput sequencing strategy of 12 genes linked to HLH was validated in 13 patients with previously identified HLH-associated mutations and prospectively evaluated in 58 HLH patients. Moreover, 2504 healthy individuals from the 1000 Genomes project were analyzed in silico for variants in the same genes. Results: Analyses revealed a mutation detection sensitivity of 97.3 %, an average coverage per gene of 98.0 %, and adequate coverage over 98.6 % of sites previously reported as mutated in these genes. In the prospective cohort, we achieved a diagnosis in 22 out of 58 patients (38 %). Genetically undiagnosed HLH patients had a later age at onset and manifested higher frequencies of known secondary HLH triggers. Rare, putatively pathogenic monoallelic variants were identified in nine patients. However, such monoallelic variants were not enriched compared with healthy individuals. Conclusions: We have established a comprehensive high-throughput platform for genetic screening of patients with HLH. Almost all cases with reduced natural killer cell function received a diagnosis, but the majority of the prospective cases remain genetically unexplained, highlighting genetic heterogeneity and environmental impact within HLH. Moreover, in silico analyses of the genetic variation affecting HLH-related genes in the general population suggest caution with respect to interpreting causality between monoallelic mutations and HLH. A complete understanding of the genetic susceptibility to HLH thus requires further in-depth investigations, including genome sequencing and detailed immunological characterization.Peer reviewe

Seprafilm may ease colostomy reversal

Hypothesis: In this study, we aimed to investigate whether the use of a sodium hyaluronate and carboxy-methylcellulose\u96based antiadhesive membrane (Seprafilm, Adhesion Barrier; Genzyme Corp, Cambridge, Mass) is associated with fewer adhesions around the pelvis and rectal pouch. Design, Interventions, and Main Outcome Measures Forty Wistar albino female rats were divided into 4 equal groups. Each rat underwent segmental left-sided colonic resection and end colostomy. The groups were as follows: group 1, colostomy alone (control group); group 2, colostomy and Seprafilm application around distal rectal pouch; group 3, colostomy and Seprafilm application beneath laparotomy incision; and group 4, colostomy and application of Seprafilm on both rectal pouch and laparotomy incision. All animals were operated on the 21st day and intra-abdominal adhesions were evaluated. Results: The results were assessed by analysis of variance and Tukey multiple comparison tests. Intra-abdominal adhesions were significantly (P<.05) reduced in groups 2 through 4 compared with the control group, whereas no statistically significant difference was observed between these 3 groups. Conclusions: The use of Seprafilm during the initial step of the Hartmann colostomy reduced intra-abdominal adhesions on the reversal. This result might be beneficial in the prevention of adhesion-related difficulties during second operation and its application beneath laparotomy incision seems to be sufficient to ensure this effect

Hepaticojejunostomy with the "Hand-Fan" technique

A standard hepaticojejunostomy technique might be difficult to perform, especially when the bile duct is small and located deep in the liver hilum. Herein we present a new procedure, the Hand-Fan technique, that was used to enhance the exposure and ease the performance of these challenging anastomoses. Thirty-one patients who had had hepaticojejunostomy with this technique for bile duct injury and other benign biliary pathologies from July 2004 to June 2011 were included into the study. Median postoperative hospital stay was 7 days (6-25 days) and median follow-up time was 33 months (2-84 months). Liver function tests revealed that the blood bilirubin levels of the patients were normalized after hepaticojejunostomy. Follow-up showed that there were no signs of clinical recurrence or impaired bile flow. The Hand-Fan technique considerably facilitates challenging hepaticojejunostomies. Surgeon's comfort is exceptional and the clinical results are satisfactory. (Hepatobiliary Pancreat Dis Int 2013;12:210-214

Intraoperative Doppler ultrasound: A reliable diagnostic method in insulinoma

A 44-year-old woman was admitted with obvious symptoms of hypoglycemia and Whipple's triad during a 6-month period. The glucose level was as low as 32mg/dL and insulin/glucose ratio greater than 0.5 after fasting. Abdominal magnetic resonance imaging (MRI) studies revealed a pancreatic mass at the head, 2cm in diameter that was not suggesting because of hypointensity. Selective angiography and somatostatin-receptor scintigraphy did not reveal insulinoma. During laparotomy the tumor was palpated on the ventral surface of pancreas and intraoperative ultrasound accurately localized it. Doppler ultrasound examination clearly revealed the hyper-vascularity of the tumor, which was suggesting an insulinoma. After the tumor enucleation, blood glucose level increased to normal ranges. Histopathological examination revealed benign, well differentiated neuroendocrine tumor, insulinoma. The postoperative recovery was uneventful and the patient is still symptom free during a follow-up period of 6 months. Doppler ultrasound may be a simple but efficient tool for the differential diagnosis of insuhnoma. If the clinical symptoms and findings suggest clearly an insulinoma, intraoperative Doppler ultrasound examination seems to be a simple but the most sensitive diagnostic method

A Splenic Marginal Zone Lymphoma Case Presenting with Cyanosis, Spider Angiomas, and Polycythemia

Splenic marginal zone lymphoma (SMZL) is an indolent cancer classified among low-grade B-cell lymphomas in the World Health Organization (WHO) classification. The major characteristics of SMZL are splenomegaly, villous cytoplasmic protrusions of the lymphocytes in peripheral blood, anemia, and/ or thrombocytopenia. The involvement of various organs, particularly the bone marrow or liver, can be frequently observed. SMZL has been reported to be associated with hepatitis C infection. The course of the disease is generally indolent, but aggressive behavior may be observed in a minority of patients. Here, we report a 43-year-old male hepatitis B virus carrier who presented with abdominal distension, multiple spider angiomas on the skin, and central cyanosis, leading to a diagnosis of SMZL

Laparoscopic cystogastrostomy for the management of pancreatic pseudocysts

Aims: To assess the value of laparoscopic cystogastrostomy in the treatment of pancreatic pseudocysts. Materials and Methods: Patients who underwent laparoscopic surgery for pancreatic pseudocysts were included in the study. All the cysts were non-resolving, symptomatic and large, as a result of acute pancreatitis. Laparoscopic cystogastrostomies were performed by either anterior transgastric or posterior techniques. Results: From February 2001 to November 2006, seven patients were included into the study. The etiology of pancreatitis was gallstone disease in six cases and hyperlipidemia in one. The mean age was 58.7 years (5269) and the mean pseudocyst size was 15.1 cm (7-20). Transgastric cystogastrostomy and posterior cystogastrostomy were carried out in three and four patients, respectively, with no conversion. Mean hospital stay was 13.4 days (6-30). Neither mortality nor procedure-related major complication was encountered, Follow-up computerized tomography studies confirmed complete resolution of the cyst in all cases, in the first month. Conclusions: Laparoscopic cystogastrostomy is an effective and safe treatment of pancreatic pseudocysts

A Splenic Marginal Zone Lymphoma Case Presenting with Cyanosis, Spider Angiomas, and Polycythemia

Splenic marginal zone lymphoma (SMZL) is an indolent cancer classified among low-grade B-cell lymphomas in the World Health Organization (WHO) classification. The major characteristics of SMZL are splenomegaly, villous cytoplasmic protrusions of the lymphocytes in peripheral blood, anemia, and/ or thrombocytopenia. The involvement of various organs, particularly the bone marrow or liver, can be frequently observed. SMZL has been reported to be associated with hepatitis C infection. The course of the disease is generally indolent, but aggressive behavior may be observed in a minority of patients. Here, we report a 43-year-old male hepatitis B virus carrier who presented with abdominal distension, multiple spider angiomas on the skin, and central cyanosis, leading to a diagnosis of SMZL

Late complication of diaphragmatic gunshot injury: appendix perforation due to colon incarceration

Missing the diaphragmatic injury on first admission is often associated with late complications. A 38 year-old male patient is presented here as a case of missed diaphragmatic injury due to gunshot injury resulted with fecal peritonitis. Celiotomy revealed a distended appendix perforation due to herniated left colon obstruction through the left pleural cavity. Left colon and stomach were reduced to peritoneal cavity and diaphragm was repaired with interrupted polypropylene sutures. After being sure about the viability of the colon and stomach, appendectomy with cecal exteriorization was performed. Postoperative period was uneventful. The patient was discharged on the 10th postoperative day. A thorough inspection of the diaphragm is essential in thoraco-abdominal trauma. Repair of the diaphragmatic defects should invariably carried out to avoid life-threatening complications