Total pancreatectomy with remnant stomach preservation in a patient with a history of proximal gastrectomy and interposed jejunal reconstruction with right gastroepiploic conduit preservation: a case report.

BACKGROUND: Pancreatic head resection following proximal gastrectomy jeopardizes the blood flow of the remnant stomach owing to right gastroepiploic conduit sacrifice, thereby necessitating total gastrectomy. However, owing to its high invasiveness, concomitant remnant total gastrectomy with pancreatectomy should be avoided as much as possible. Herein, we describe our experience of total pancreatectomy with right gastroepiploic conduit preservation in a patient with a history of proximal gastrectomy and reconstruction by jejunum interposition. CASE PRESENTATION: A 78-year-old woman with a history of gastric cancer was followed up at our institute for multiple intraductal papillary mucinous neoplasm, and main pancreatic duct stricture in the pancreatic head was newly detected. The cystic lesion was extended to the pancreatic body. Proximal gastrectomy and reconstruction by jejunal interposition were previously performed, and the mesenteric stalk of the interposed jejunum was approached through the retrocolic route. We planned total pancreatectomy with right gastroepiploic conduit preservation. Following adhesiolysis, the interposed jejunum and its mesentery lying in front of the pancreas were isolated. The arterial arcade from the common hepatic artery to the right gastroepiploic artery was detached from the pancreas. Furthermore, the right gastroepiploic vein was isolated from the pancreas. The pancreatic body and tail were pulled up in front of the remnant stomach, and the splenic artery and vein were resected. The pancreatic body and tail were pulled out to the right side, and the pancreatic head was divided from the pancreatic nerve plexus to the portal vein. The jejunal limb for entero-biliary anastomosis was passed through the hole behind the superior mesenteric artery and vein, and gastrointestinal anastomosis using the antecolic route and Braun anastomosis were performed. CONCLUSIONS: To avoid remnant total gastrectomy, right gastroepiploic conduit preservation is an optional procedure for pancreatic head resection in patients who have undergone proximal gastrectomy with reconstruction by jejunal interposition.

Pancreatic acinar cell carcinoma with pleomorphic and spindle cells: An autopsy-proven case.

Pancreatic acinar cell carcinomas are glandular and have amphophilic/eosinophilic cytoplasm, presenting acinar, solid, and trabecular structures. Unusual histological features of acinar cell carcinoma are known, such as oncocytic, pleomorphic, spindle, and clear cell variants, but their clinical significance has not been well described. A man in his 70s was referred to our hospital because of elevated serum pancreatic enzymes. Contrast-enhanced abdominal computed tomography revealed slight swelling of the pancreatic head and suspension of the main pancreatic duct in the pancreatic body. He died only 14 days after admission. Gross findings at autopsy showed an ill-defined tumor located in the pancreatic head, involving the gastric and duodenal walls. Peritoneal dissemination, liver metastases, and lymph node metastases were also observed. Microscopically, tumor cells had moderate-to-severe nuclear atypia and amphophilic cytoplasm showing pleomorphism, and diffusely proliferated in solid pattern without lumina, were admixed with spindle cells. Immunohistochemically, tumor cells including pleomorphic and spindle cells were positive for B-cell lymphoma/leukemia 10 and trypsin. Consequently, the diagnosis was pancreatic acinar cell carcinoma with pleomorphic and spindle cells. We encountered a rare variant of pancreatic acinar cell carcinoma with pleomorphic and spindle cells. Clinically, our case showed rapid progression.

Bi-glandular and persistent enterovirus infection and distinct changes of the pancreas in slowly progressive type 1 diabetes mellitus.

In slowly progressive type 1 diabetes mellitus (SPIDDM), the pancreas shows sustained islet inflammation, pancreatitis, pancreatic acinar cell metaplasia/dysplasia (ADM), and intraepithelial neoplasia (PanIN), a precancerous lesion. The mechanisms underlying these changes remain unclear. The presence of enterovirus (EV) encoded-capsid protein 1 (VP1) and -2A protease (2Apro) and the innate immune responses of the pancreas were studied using immunohistochemistry and in situ hybridization in 12 SPIDDM and 19 non-diabetic control pancreases. VP1, 2Apro, and EV-RNA were detected in islets and the exocrine pancreas in all SPIDDM pancreases. Innate immune receptor, melanoma differentiation-associated gene 5 (MDA5), and interferon (IFN)-beta1 were intensified in the islets of SPIDDM patients with short disease duration. However, expressions of MDA5 and IFN-beta1were suppressed in those with longer disease duration. CD3+ T cell infiltration was observed in the VP1- and insulin-positive islets (insulitis) and exocrine acinar cells. CD11c+ dendritic cells (DCs) in islets were scarce in long-term SPIDDM. This study showed the consistent presence of EV, suggesting an association with inflammatory changes in the endocrine and exocrine pancreas in SPIDDM. Suppressed expressions of MDA5 and IFN-beta1, as well as decreased numbers of DCs in the host cells, may contribute to persistent EV infection and induction of ADM/PanIN lesions, which may potentially provide a scaffold for pancreatic neoplasms.

A Case of Methimazole-Induced Acute Pancreatitis With an HLA Allele Causing Antithyroid Drug-Induced Agranulocytosis.

Among the side effects of methimazole (MMI) for the treatment of Graves' disease, MMI-induced acute pancreatitis (MIP) is a rare adverse reaction, with only 7 cases being reported to date. However, 2 large-scale population-based studies recently revealed that the risk of MIP was significantly higher, ranging from 0.02% to 0.56%. Although MIP is common in middle-aged and elderly Asian women, its pathogenesis remains largely unknown. We herein present a case of a 72-year-old Japanese woman with Graves' disease who developed MIP 12 days after the initiation of MMI. The MMI was discontinued, the patient was switched to propylthiouracil (PTU) therapy, and pancreatitis gradually resolved. Serological human leukocyte antigen (HLA) typing identified HLA-DRB1*08:03:02. This HLA allele was previously detected in a patient with MIP and is one of the major risk factors for agranulocytosis induced by antithyroid drugs, including PTU as well as MMI. In cases of MIP, PTU is being considered as an alternative to MMI; however, its safety needs further investigation and patients require close monitoring after the switch to PTU. Further studies are warranted, particularly on the relationship between MIP and the presence of HLA alleles causing antithyroid drug-induced agranulocytosis.

Leiomyosarcoma of the splenic vein with a history of bilateral retinoblastoma: A case report and review of the literature.

Diagnosing leiomyosarcomas of the splenic vein is challenging, and a treatment strategy has not yet been established for this condition. We herein report the case of a 45-year-old female patient with a history of retinoblastoma who underwent pancreatosplenectomy for a primary leiomyosarcoma originating from the splenic vein and transcatheter arterial chemoembolization for metastatic hepatic lesions observed 5 months postoperatively. An initial medical check-up using abdominal ultrasound revealed a 40-mm mass behind the pancreatic tail. Imaging tests revealed a well-circumscribed mass compressing the pancreas posteriorly, without invasion into the pancreatic duct. The splenic vein was torn, with the epiploic veins developed as collateral blood vessels, which was an atypical finding for carcinoma. The patient was followed up regularly. At 5 years after the first visit, an abdominal ultrasound showed that the mass had increased in size to 50 mm, and had developed into a tumor embolus within the splenic vein, causing an obstruction of the vessel. Pancreatosplenectomy was performed due to suspicion of malignancy. The final diagnosis was leiomyosarcoma arising from the splenic vein. The patient was discharged on postoperative day 15 and was followed up regularly thereafter. Imaging studies performed 5 months postoperatively revealed four hepatic lesions. The hepatic masses were histologically diagnosed as metastatic leiomyosarcomas, and transcatheter arterial chemoembolization was performed using epirubicin. Since then, regular follow-ups have been conducted without observed recurrence. Leiomyosarcoma of the splenic vein is exceedingly rare, and the number of reported cases is not sufficient to establish clinical guidelines. Therefore, it is crucial to collect more reports on the occurrence and treatment of this disease.

Solid pseudopapillary neoplasm of the pancreas in a young male with main pancreatic duct dilatation: A case report.

BACKGROUND: Solid pseudopapillary neoplasms (SPNs) are rare tumors of the pancreas. Typically, they occur in young females, often have characteristic imaging features, such as cystic components and calcification, and have few effects on the pancreatic duct. CASE SUMMARY: A 31-year-old man was admitted to our hospital with the chief complaint of epigastric pain. There was only mild tenderness in his upper abdomen, and blood tests showed only a slight increase in alkaline phosphatase. Contrast-enhanced computed tomography showed a 40-mm-diameter, hypovascular mass in the head of the pancreas, and the main pancreatic duct upstream of the mass was severely dilated. Magnetic resonance imaging showed low intensity on T1-weighted images, with high intensity on T2-weighted image in some parts. Pancreatic ductal adenocarcinoma was the primary differential diagnosis. Portal vein infiltration could not be ruled out, so this case was a candidate for neoadjuvant chemotherapy. Subsequently, endoscopic ultrasound-guided fine needle aspiration was performed, and pathological evaluation and immunostaining suggested a diagnosis of SPN. Thus, pancreatoduodenectomy was performed. One year after the operation, the patient is alive with no recurrence. CONCLUSION: Main pancreatic duct dilatation is usually a finding of suspected pancreatic cancer. However, pancreatic duct dilatation can occur in SPN depending on the location and growth speed. Therefore, SPN should be considered in the differential diagnosis of tumors with pancreatic duct dilatation, and pathological evaluation by endoscopic ultrasound-guided fine needle aspiration should be actively performed.

Pancreatic ductal adenocarcinoma with mismatch repair deficiency resected after long-term observation.

Pancreatic ductal adenocarcinoma (PDAC) with mismatch repair (MMR) deficiency is a rare subtype, clinicopathological features of which have not been fully understood. A 70-year-old woman was admitted for the investigation of a 20-mm pancreatic tumor in the pancreatic head, detected during the cause scrutiny of exacerbation of diabetes mellitus and panhypopituitarism. The tumor decreased in size after administration of hydrocortisone for panhypopituitarism. Autoimmune pancreatitis, complicated with hypophysitis, was suspected, and prednisolone treatment was administered. The tumor did not show enlargement for 3 years during which a dose of prednisolone was maintained. However, 1.5 years after the cessation of prednisolone administration, the tumor size increased again. On endoscopic ultrasonography, the tumor was found to be a 25.2-mm mass lesion with almost uniformly low echogenicity and blood flow signal, and anisonucleosis on cytodiagnosis was revealed. Pancreatoduodenectomy was performed, and on histological analysis, moderately differentiated tubular adenocarcinoma with massive lymphocytic infiltration was observed. Immunohistochemistry revealed a concomitant loss of MSH2 and MSH6 in the tumor cells, which implicated mutant MSH2 gene. She has remained well with no recurrence for 2.9 years since her surgery. We herein report a case of PDAC with MMR deficiency, resected after long-term observation.

Simultaneous macroamylasemia and macrolipasemia in a patient with mucosa-associated lymphoid tissue lymphoma.

We report a case of simultaneous macroamylasemia and macrolipasemia complicated with mucosa-associated lymphoid tissue (MALT) lymphoma. A 78-year-old man presented with hyperamylasemia and hyperlipasemia for 2 years and was misdiagnosed with chronic pancreatitis at another hospital. However, his other pancreatic enzymes were normal, his amylase-creatinine clearance ratio was low, and no definite findings of pancreatic disease were evident. Immunological analyses revealed that both amylase and lipase were bound to immunoglobulin (Ig) A-κ, and that serum IgA was high (827.1 mg/dL). He was diagnosed with simultaneous macroamylasemia and macrolipasemia. Since these diseases are associated with malignancy, an additional investigation was performed which revealed the complication of MALT lymphoma, and polymerase chain reaction analysis showed monoclonal immunoglobulin light chain gene rearrangement (κ >> λ). In this case, macroamylasemia and macrolipasemia may have developed due to the formation of macroenzymes resulting from excess IgA-κ secreted by the MALT lymphoma. Simultaneous macroamylasemia and macrolipasemia are very rare and difficult to diagnose and can lead to diagnostic and therapeutic errors. When encountering atypical clinical features associated with hyperamylasemia and hyperlipasemia, the possibility of macroenzymes and underlying diseases such as lymphoproliferative disorders should be considered.

Distinct Inflammatory Changes of the Pancreas of Slowly Progressive Insulin-dependent (Type 1) Diabetes.

OBJECTIVE: The aim of this study was to identify the distinct pathological changes on the endocrine and exocrine pancreas of slowly progressive insulin-dependent diabetes mellitus (SPIDDM) or latent autoimmune diabetes in adults. METHODS: The pancreases from 12 islet autoantibody-positive SPIDDM patients and 19 age-matched subjects with no diabetes were examined histologically for islet inflammation/insulitis, expressions of cytokines, and enterovirus VP1 protein, exocrine pancreatic inflammation, pancreatic ductal changes, major histocompatibility complex class I hyperexpression, and amylin-positive amyloid in the islets. RESULTS: Insulitis dominant for CD8 T-cells and CD68 macrophages was observed in all SPIDDM cases irrespective of duration of diabetes and weight of residual beta cells. Major histocompatibility complex class I hyperexpression on residual beta cells was observed in SPIDDM. All SPIDDM exocrine pancreases showed extensive inflammation, dilated pancreatic ducts, and periductal fibrosis. As many as 75% (9/12) of pancreases had pancreatic intraepithelial neoplasia, which is assumed to be associated with ductal obstruction/narrowing and exocrine pancreatic inflammation, in SPIDDM. Amylin-positive amyloid deposition was not detected in SPIDDM. CONCLUSIONS: Persistent insulitis with preserved beta cells and major histocompatibility complex class I hyperexpression and exocrine pancreatic inflammation with pancreatic intraepithelial neoplasia are distinct histological features of SPIDDM pancreas.

Treatment of biliary tract stones after gastrectomy in the era of laparoscopic cholecystectomy.

BACKGROUND: The incidence of biliary tract stones has widely been reported to be high after gastrectomy. Treatment of biliary tract stones in post-gastrectomy patients was examined retrospectively, particularly minimally invasive therapy with laparoscopic cholecystectomy for gallbladder stones and endoscopic bile duct lithotomy for common bile duct stones. METHODS: Treatment of 122 post-gastrectomy patients with biliary tract stones was examined retrospectively from 1995 to April 2015. RESULTS: Symptomatic biliary tract stones were found in 3.7% of post-gastrectomy patients. The frequency of bile duct stones was higher in post-gastrectomy patients with gallbladder stones (44%) than in the nongastrectomy patients (11%). Laparoscopic cholecystectomy was carried out in 84% of the patients with gallbladder stones. Endoscopic bile duct lithotomy was feasible in 89% of patients with common bile duct stones. CONCLUSIONS: Laparoscopic cholecystectomy was feasible for removing gallbladder stones after gastrectomy. Endoscopic bile duct lithotomy followed by laparoscopic cholecystectomy was a good option for patients in whom endoscopic intervention could be performed. On the other hand, choledochoenterostomy could be a good option for patients in whom endoscopic bile duct lithotomy cannot be performed, particularly considering the risk of recurrent bile duct stones.

Adrenal Metastasis and Hemorrhage Secondary to Hepatocellular Carcinoma.

A 66-year-old man was admitted to undergo treatment for the sudden onset of hypogastric pain radiating to the left flank. Based on the clinical presentation and radiological findings, left adrenal hemorrhage secondary to hepatocellular carcinoma was diagnosed. Although the patient was hemodynamically stable, anemia progressed over the first four days after admission and a blood transfusion was subsequently initiated, which was effective. According to the results of interval imaging with computed tomography, elective transcatheter embolization (TAE) was performed nine days after admission to treat the bleeding from the adrenal tumor. After TAE, the patient's abdominal pain resolved, with no further progression of anemia.

Recurrent common bile duct stones composed of ursodeoxycholic acid: a report of four cases.

Ursodeoxycholic acid (UDCA) is often used to treat cholesterol gallstones. UDCA makes cholesterol stones soluble, thereby improving biliary emptying. Conversely, however, UDCA can also form stones via an unknown mechanism, as shown in a few previous reports of cholangitis caused by the formation of UDCA stones in the common bile duct (CBD). We herein report four cases of recurrent cholangitis resulting from UDCA stones. The withdrawal of UDCA administration was highly effective in these patients. The details of these four cases suggest that clinicians must rethink the indications for UDCA treatment in cases in which cholangitis caused by CBD stones frequently recurs over a short period of time.

Ultrasonographic imaging of bile duct lesions in autoimmune pancreatitis.

OBJECTIVES: Patients with autoimmune pancreatitis (AIP) commonly have lesions in the bile duct itself and show stenosis of the bile duct system; however, no detailed study has evaluated the ultrasonographic findings of bile duct lesions in AIP. In this study, we monitored the clinical course and imaging findings, mainly ultrasonographic, of bile duct lesions in AIP. METHODS: We retrospectively analyzed the incidence of bile duct lesions, imaging findings, and clinical course in 37 patients with AIP. RESULTS: Characteristic bile duct and gallbladder wall thickening was recognized on ultrasound in 37.8% (14/37) of AIP patients. We divided the patients into 2 types according to the ultrasonographic findings of bile duct wall thickening: (1) 3-layer type (64.3%) and (2) parenchymal-echo type (35.7%). All 14 cases were treated with prednisolone, with immediate resolution of the bile duct lesions. CONCLUSION: Sclerosing cholangitis is one of the extrapancreatic lesions that are commonly detected in AIP patients; it is detected on ultrasonographic imaging as characteristic wall thickening. Our ultrasonographic findings reflect the fact that bile duct wall thickening in AIP is an inflammatory process that responds to prednisolone therapy. Ultrasonography is a useful tool in detecting biliary tract lesions in AIP.

Long-term outcome after interferon therapy in elderly patients with chronic hepatitis C.

OBJECTIVE: The purpose of this study was to elucidate the long-term outcome after interferon (IFN) therapy in chronic hepatitis C elderly patients. METHODS: We studied the incidence of hepatocellular carcinoma (HCC) and survival probability after the initiation of IFN therapy in 500 Japanese chronic hepatitis C patients >60 years. The mean age of initiation of IFN was 63 years and the mean follow-up period was 7.4 years. Cox proportional hazard regression analysis was used to evaluate the long-term outcome after initiation of IFN therapy. Sustained virological response (SVR) was defined as negative HCV-RNA by RT-nested PCR 6 months after the completion of long-term IFN therapy. Non-response (NR) was applied to patients who did not show SVR. Hepatic fibrosis was defined as the fibrosis score (score 0-4) according to Knodell et al. RESULTS: 140 patients (28%) had an SVR and 360 patients (72%) had an NR. 71 of 500 patients developed HCC during follow-up. The cumulative incidence of HCC was 9.6% at the 5th year, 17.4% at the 10th year, and 31.3% at the 15th year. HCC developed with significance when: (1) HCV was not cleared after IFN therapy (p < 0.0001), (2) sex was male (p < 0.0001), and (3) staging of liver fibrosis was >2 (p = 0.008). 53 of the patients died. The cumulative survival probability was 95.7% at the 5th year, 86.4% at the 10th year, and 78% at the 15th year. Patients achieved a long survival with significance when: (1) staging of liver fibrosis was 1 (p < 0.0001), (2) HCV was cleared after IFN therapy (p = 0.034), and (3) sex was female (p = 0.015). CONCLUSION: Chronic hepatitis C patients with clearance of HCV after IFN therapy had a significantly reduced risk of HCC appearance and achieved prolonged survival even if they are > or =60 years.

Hepatic injury following reduced intensity unrelated cord blood transplantation for adult patients with hematological diseases.

Liver injury is a common complication in allogeneic hematopoietic stem cell transplantation. Its major causes comprise graft-versus-host disease (GVHD), infection, and toxicities of preparative regimens and immunosuppressants; however, we have little information on liver injuries after reduced intensity cord blood transplantation (RICBT). We reviewed medical records of 104 recipients who underwent RICBT between March 2002 and May 2004 at Toranomon Hospital. Preparative regimen and GVHD prophylaxis comprised fludarabine/melphalan/total body irradiation and cyclosporine or tacrolimus. We assessed the etiology of liver injuries based on the clinical presentation, laboratory results, comorbid events, and imaging studies in 85 patients who achieved primary engraftment. The severity of liver dysfunction was assessed according to the National Cancer Institute Common Toxicity Criteria version 2.0. Hyperbilirubinemia was graded according to a report by Hogan et al (Blood. 2004;103:78-84). Moderate to very severe liver injuries were observed in 36 patients. Their causes included cholestatic liver disease (CLD) related to GVHD or sepsis (n = 15), GVHD (n = 7), cholangitis lenta (n = 5), and others (n = 9). Median onsets of CLD, GVHD, and cholangitis lenta were days 37, 40, and 22, respectively. Frequencies of grade 3-4 alanine aminotransferase elevation were comparable across the 3 types of hepatic injuries. Serum gamma-glutamil transpeptidase was not elevated in any patients with cholangitis lenta, whereas 27% and 40% of patients with CLD and GVHD, respectively, developed grade 3-4 gamma-glutamil transpeptidase elevation. Multivariate analysis identified 2 risk factors for hyperbilirubinemia; grade II-IV acute GVHD (relative risk, 2.23; 95% confidential interval, 1.11-4.47; P = .024) and blood stream infection (relative risk, 3.77; 95% confidential interval, 1.91-7.44; P = .00013). In conclusion, the present study has demonstrated that the hepatic injuries are significant problems after RICBT, and that GVHD and blood stream infection contribute to their pathogenesis.

Efficacy of interferon therapy in elderly patients with chronic hepatitis C.

OBJECTIVE: We assessed the efficacy and safety of interferon (IFN) monotherapy in 84 elderly patients aged > or =65 years with chronic hepatitis C in a retrospective cohort study. METHODS: Twenty-two of the 84 elderly patients were treated with IFN at a dose of 6 million units daily for 6-8 weeks, 18 patients were treated 2-3 times a week for 24 weeks and 44 patients were treated daily for 2-8 weeks and 2-3 times a week for 16-24 weeks. RESULTS: A sustained virological response (SVR) occurred in 35.7% (30/84) of the patients by intention-to-treat analysis. Multivariate analysis showed that patients achieved a significant SVR when: (1) serum HCV-RNA level before IFN therapy was <100 KIU/ml (p < 0.0001) and (2) staging of liver fibrosis was mild (p = 0.040). Eleven (13.1%) patients discontinued the IFN regimen due to adverse events. Regarding factors predicting discontinuation of IFN, univariate analysis showed that patients aged >70 years were prone to drop out of therapy due to adverse events in IFN therapy (p = 0.009). CONCLUSION: Our results suggest that IFN administration is suitable for 65- to 70-year-old patients with chronic hepatitis C without genotype 1b and high virus load.

Hypoglycemia and hyperglycemia due to insulin antibodies against therapeutic human insulin: treatment with double filtration plasmapheresis and prednisolone.

Two diabetic patients, who had been treated with human insulin, suffered from fasting hypoglycemia and postprandial hyperglycemia. The insulin-binding capacities of their sera were high, and a large amount of total insulin and prolonged presence of free insulin in the sera were shown. Scatchard analysis of these insulin antibodies revealed that high-affinity insulin antibodies had larger capacity and stronger affinity compared with commonly insulin-treated patients. Treatment with double filtration plasmapheresis and subsequent administration of prednisolone in the second patient reduced such antibodies and resulted in recovery of glycemic control by insulin. Hypoglycemia and hyperglycemia could be incurred when insulin antibodies with strong affinity and high capacity in high-affinity sites arise. This condition can be treated with double filtration plasmapheresis and subsequent administration of prednisolone.