A case of progressive xanthogranulomatous pancreatitis with splenic abscess.

Xanthogranulomatous inflammation is a chronic inflammatory reaction microscopically characterized by aggregation of foamy histiocytes, fibrous tissue, and infiltration of various inflammatory cells. In contrast to xanthogranulomatous inflammation in the gallbladder or kidney, xanthogranulomatous pancreatitis is rare. We herein present a case of xanthogranulomatous pancreatitis in a patient who underwent distal pancreatectomy with splenectomy under preoperative suspicion of a pancreatic pseudocyst or pancreatic tumor. A 77-year-old woman with a 1 month history of epigastric pain, anorexia, and general fatigue was admitted to our hospital. Contrast-enhanced computed tomography revealed a cystic mass with ill-defined margins at the pancreatic tail together with a splenic abscess. Contrast-enhanced endoscopic ultrasound detected a hyperechoic cystic lesion at the tail of the pancreas with heterogeneous internal echogenicity, and part of the intra-cystic content was enhanced by the contrast agent. Endoscopic retrograde cholangiopancreatography showed a cystic lesion at the tail of the pancreas that continued into the main pancreatic duct, and the main pancreatic duct was slightly narrowed downstream of the cystic lesion. Pancreatic juice cytology revealed suspicious cells, leading to the possibility of intraductal papillary mucinous carcinoma. Distal pancreatectomy with splenectomy was performed, and the histopathological diagnosis was xanthogranulomatous pancreatitis with no malignant findings.

A case of spindle and giant cell-type undifferentiated carcinoma of the extrahepatic bile duct.

Spindle and giant cell type undifferentiated carcinoma of the extrahepatic bile duct is an uncommon malignancy. We report a case involving the common bile duct in a 72-year-old male with jaundice who was admitted to our hospital. Diagnostic imaging, including abdominal computed tomography and magnetic resonance imaging, revealed a mass in the distal common bile duct, accompanied by dilatation of both intra- and extrahepatic bile ducts and regional lymph node enlargement. Endoscopic retrograde cholangiography demonstrated stenosis in the distal common bile duct, with a biopsy confirming adenocarcinoma. The patient underwent endoscopic retrograde biliary drainage followed by a subtotal stomach-preserving pancreaticoduodenectomy with regional lymphadenectomy. Microscopic examination revealed that the tumor predominantly comprised spindle and giant atypical cells within the stroma. Immunohistochemical analysis showed the tumor cells expressing cytokeratins and mesenchymal markers, confirming the diagnosis of spindle and giant cell type undifferentiated carcinoma of the common bile duct. Ki-67 labeling index was observed to be above 80%. Postoperatively, intra-abdominal lymph node recurrence was noted at two months, and multiple liver metastases were identified at three months. The patient died seven months post-surgery. The literature pertaining to this rare disease is reviewed and discussed.

Comparison of Oncological and Perioperative Outcomes Between Self-Expanding Metal Stents and Decompression Tubes for Stages II and III Obstructive Colorectal Cancer: A Retrospective Observational Study.

BACKGROUND: A bridge to surgery (BTS) using self-expandable metallic stents (SEMSs) is becoming the primary treatment for obstructive colorectal cancer (OCRC). In Japan, intestinal decompression was usually performed using decompression tubes (DTs). However, few reports have compared the outcomes of SEMS and DTs as BTS. Therefore, we compared the treatment outcomes of SEMS and DTs for OCRC. METHODS: Data of 80 patients who underwent radical resection after endoscopic decompression for stage II or III OCRC between 2007 and 2021 were retrospectively analyzed. Patients were divided into two groups based on whether they received SEMS (n = 53) or DTs (n = 27). RESULTS: The clinical success rate of decompression was 96.2% and 88.9% in the SEMS and DT groups, respectively. Additionally, 96.2% of patients who received SEMS were able to resume their routine diet without stricture symptoms. The rate of stoma construction and incidence of postoperative complications were lower in the SEMS group (p < 0.005 and p < 0.01, respectively). The 3-year relapse-free survival rates were 71.9% and 51.2% in the SEMS and DT groups, respectively, which were not significantly different (p = 0.10). CONCLUSION: BTS using SEMS might be an adequate treatment for stage II or III OCRC regardless of tumor location owing to the comparable oncological outcomes with DT and low perioperative complication rate.

Successful En Bloc Resection of Locally Advanced Pancreatic Tail Cancer with Colonic Perforation Following Neoadjuvant Chemotherapy: A Case Report.

BACKGROUND Distal pancreatic cancers may be unresectable at the time of diagnosis because these cancers are asymptomatic and readily infiltrate neighboring organs. Radical resection of a pancreatic tail cancer with colonic perforation is rare. We describe successful resection of a locally advanced pancreatic tail cancer with colonic perforation using a multidisciplinary approach. CASE REPORT A 66-year-old man presented to our hospital with a chief concern of high fever. Abdominal computed tomography revealed a pancreatic tail tumor infiltrating the neighboring organs and causing colonic obstruction with perforation, which resulted in an intra-abdominal abscess. Colonoscopy revealed obstruction of the descending colon by extramural invasion. Laboratory tests showed high tumor marker concentrations (carcinoembryonic antigen, 11.6 ng/dL; pancreatic cancer-associated antigen-2, >1600 U/mL). We clinically diagnosed locally advanced pancreatic tail cancer with an intra-abdominal abscess caused by colonic perforation. First, we performed transverse colostomy and percutaneous drainage. We then started neoadjuvant chemotherapy with FOLFIRINOX for tumor shrinkage and prevention of distant metastases. The therapeutic effect was a partial response, and no distant metastases was found. We therefore performed radical surgery comprising distal pancreatectomy with partial resection of neighboring organs. Although pathological examination revealed a pancreatic tail tubular adenocarcinoma with direct invasion of the neighboring organs, R0 resection was achieved. The patient was discharged with no perioperative complications. Tegafur/gimeracil/oteracil potassium were administered as adjuvant chemotherapy. The patient remained recurrence-free for 19 months after surgery. CONCLUSIONS We achieved successful en bloc resection of a locally advanced distal pancreatic cancer with colonic perforation by using a multidisciplinary approach.

Gallbladder cancer spreading into the aberrant cystic duct: First literature report.

INTRODUCTION AND IMPORTANCE: Although variations from the standard anatomy of the extrahepatic bile ducts are common, duplication of the cystic duct draining a single gallbladder is an extremely rare variant. We herein describe the first report of gallbladder cancer spreading into the aberrant cystic duct. CASE PRESENTATION: A 60-year-old female presented with upper abdominal pain, and she was diagnosed with gallbladder cancer. Intraoperatively, she was found to have a duplicated cystic duct draining a single gallbladder, and her cancer had spread into the aberrant cystic duct entering the anterior right hepatic duct. Right hepatectomy with extrahepatic bile duct resection was performed to achieve R0 resection. CLINICAL DISCUSSION: In the English literature, 28 cases of duplicated cystic duct draining a single gallbladder have been reported. However, no cases of gallbladder cancer have been described in these previous reports. CONCLUSION: We report the first case of gallbladder cancer spreading into the aberrant cystic duct. To perform an oncologically adequate operation, exact assessment of the biliary tree is essential not only preoperatively but also intraoperatively.

The Impact of a Nitric Oxide Synthase Inhibitor (L-NAME) on Ischemia⁻Reperfusion Injury of Cholestatic Livers by Pringle Maneuver and Liver Resection after Bile Duct Ligation in Rats.

The Pringle maneuver (PM) has been widely used to control blood loss during liver resection. However, hepatic inflow occlusion can also result in hepatic ischemia-reperfusion injury (IRI), especially in patients with a cholestatic, fibrotic, or cirrhotic liver. Here we investigate a nitric oxide synthase (NOS) inhibitor N-Nitroarginine methyl ester (L-NAME) on IRI after the PM and partial hepatectomy of cholestatic livers induced by bile duct ligation (BDL) in rats. Control group (non-BDL/no treatment), BDL + T group (BDL/L-NAME treatment) and BDL group (BDL/no treatment) were analyzed. Cholestasis was induced by BDL in the L-NAME and BDL group and a 50% partial hepatectomy with PM was performed. L-NAME was injected before PM in the BDL + T group. Hepatocellular damage, portal venous flow, microcirculation, endothelial lining, and eNOS, iNOS, interleukin (IL)-6, and transforming growth factor-ß (TGF-ß) were evaluated. Microcirculation of the liver in the BDL + T group tended to be higher. Liver damage and apoptotic index were significantly lower and Ki-67 labeling index was higher in the BDL + T group while iNOS and TGF-ß expression was decreased. This was corroborated by a better preserved endothelial lining. L-NAME attenuated IRI following PM and improved proliferation/regeneration of cholestatic livers. These positive effects were considered as the result of improved hepatic microcirculation, prevention of iNOS formation, and TGF-ß mRNA upregulation.

Optimal Timing for Venous Systemic Oxygen Persufflation Supplemented with Nitric Oxide Gas in Cold-Stored, Warm Ischemia-Damaged Experimental Liver Grafts.

BACKGROUND/AIM: Worldwide shortage of donor organs has increased the use of donation after cardiac death (DCD). The aim of this study was to analyze the best time point for venous systemic oxygen persufflation (VSOP) supplemented with nitric oxide (NO) gas during the 1st and 24th hour of cold storage (CS) in warm ischemia (WI)-damaged experimental liver grafts. MATERIALS AND METHODS: Liver grafts (n = 5) were retrieved after 30 min of WI induced by cardiac arrest and CS in histidine-tryptophan-ketoglutarate solution at 4°C. The 1st hour group was immediately persufflated with a VSOP plus NO (VSOP+NO) mixture for 1 h followed by 23 h of static CS (DCD+NO 1st hour). The 24th hour group entailed CS for 23 h followed by 1 h of VSOP+NO persufflation (DCD+NO 24th hour). CS livers without WI but with VSOP served as controls. CS livers with WI represented the fourth group (DCD). Viability of the liver grafts was assessed by normothermic isolated reperfusion for 45 min with oxygenated Krebs-Henseleit buffer. RESULTS: Data are presented as mean ± SEM (control vs. DCD vs. DCD+NO 1st hour vs. DCD+NO 24th hour). After 45 min of reperfusion, the DCD+NO 1st hour group showed significantly lower aspartate aminotransferase (13.4 ± 5.3, 63.2 ± 17.3, 25.6 ± 3.9, and 82.8 ± 27.3 U/l) and lactate dehydrogenase levels (289.4 ± 41.2, 2,139.4 ± 542.7, 577.2 ± 117.2, and 2,429 ± 221.6 U/l). Malondialdehyde levels were significantly abrogated (1.0 ± 0.3, 2.7 ± 1, 1.0 ± 0, and 3.9 ± 1.2 nmol/ml). Significantly higher levels of portal venous pressure were recorded in the DCD+NO 24th hour group (12.0 ± 1, 21.2 ± 3.1, 16.1 ± 1, and 23.2 ± 3.5 mm Hg). NO levels were recorded after 5 min of reperfusion (1.42 ± 0.17, 1.8 ± 0.2, 2.7 ± 0.2, and 2.6 ± 0.1 µmol/l). Bile production levels showed no statistical significance (23.2 ± 3.8, 27.3 ± 1.8, 43.5 ± 18, and 31 ± 2.5 µl/45 min). CONCLUSION: Our results present the beneficial effects of NO combined with VSOP during the 1st hour of CS of WI-damaged experimental liver grafts.

Improving Research Practice in Rat Orthotopic and Partial Orthotopic Liver Transplantation: A Review, Recommendation, and Publication Guide.

BACKGROUND: Due to a worldwide shortage of donor organs for liver transplantation, alternative approaches, such as split and living donor liver transplantations, were introduced to increase the donor pool and reduce mortality on liver transplant waiting lists. Numerous details concerning the mechanisms and pathophysiology of liver regeneration, small-for-size syndrome, rejection, and tolerance in partial liver transplantation facilitated the development of various animal models. The high number of preclinical animal studies contributed enormously to our understanding of many clinical aspects of living donor and partial liver transplantations. SUMMARY: Microsurgical rat models of partial orthotopic liver transplantation are well established and widely used. Nevertheless, several issues regarding this procedure are controversial, not clarified, or not yet properly standardized (graft rearterialization, size reduction techniques, etc.). The major aim of this literature review is to give the reader a current overview of rat orthotopic liver transplantation models with a special focus on partial liver transplantation. The aspects of model evolution, microsurgical training, and different technical problems are analyzed and discussed in detail. Our further aim in this paper is to elaborate a detailed publication guide in order to improve the quality of reporting in the field of rat liver transplantation according to the ARRIVE guidelines and the 3R principle. Key Messages: Partial orthotopic liver transplantation in rats is an indispensable, reliable, and cost-efficient model for transplantation research. A certain consensus on different technical issues and a significant improvement in scientific reporting are essential to improve transparency and comparability in this field as well as to foster refinement.

Portal vein reconstruction in adult living donor liver transplantation for patients with portal vein thrombosis in single center experience.

BACKGROUND: Liver transplantation (LT) used to be contraindicated in patients with portal vein thrombosis (PVT). In comparison to deceased donor LT, living donor LT (LDLT) still presents additional difficulties in determining appropriate vein grafts and overcoming small-for-size syndrome. Here, we introduce our LDLT strategies and assess their outcomes in adult patients with pre-existing PVT. METHODS: We performed 282 consecutive adult LDLTs between April 2006 and December 2011. Forty-eight patients (17%) had pre-existing PVT (grade I; 15, II; 20, III; 12, IV; 1). RESULTS: Our preferred treatments for PVT were thrombectomies/thromboendovenectomies in 30 patients, replaced grafts in seven, jump grafts in seven, renoportal anastomosis in one and no surgical intervention owing to minimal thrombosis in three. Post-transplant portal vein complications occurred in eight of 48 (17%) cases, which were treated by surgery, anticoagulation therapy, and/or interventional radiology. Post-transplant survival rates of patients with preexisting PVT at 1 year and 5 years were comparable to a PVT-free cohort (1 year; 81% vs. 77%, 5 years; 81% vs. 73%). CONCLUSIONS: The excellent survival rates in patients with PVT who underwent LDLT could be attributed to our strategies, which included surgical techniques and timely treatment of postoperative complications.

Donor morbidity in right and left hemiliver living donor liver transplantation: the impact of graft selection and surgical innovation on donor safety.

This study investigated adequate liver graft selection for donor safety by comparing postoperative donor liver function and morbidity between the right and left hemilivers (RL and LL, respectively) of living donors. Between April 2006 and March 2012, RL (n = 168) and LL (n = 140) donor operations were performed for liver transplantation at Kyoto University Hospital. Postoperative hyperbilirubinemia and coagulopathy persisted in RL donors, whereas the liver function of LL donors normalized more rapidly. The overall complication rate of the RL donors was significantly higher than that of the LL donors (59.5% vs. 30.7%; P < 0.001). There were no significant differences in severe complications worse than Clavien grade IIIa or in biliary complication rates between the two donor groups. In April 2006, we introduced an innovative surgical procedure: hilar dissection preserving the blood supply to the bile duct during donor hepatectomy. Compared with our previous outcomes (1990-2006), the biliary complication rate of the RL donors decreased from 12.2% to 7.2%, and the severity of these complications was significantly lower. In conclusion, LL donors demonstrated good recovery in postoperative liver function and lower morbidity, and our surgical innovations reduced the severity of biliary complications in living donors.

Portocaval shunt for hepatocyte package: challenging application of small intestinal graft in animal models.

In developing therapeutic alternatives to liver transplantation, we have used the strategy of applying a small intestinal segment as a scaffold for hepatocyte transplantation and also as a portocaval shunt (PCS) system to address both liver dysfunction and portal hypertension. The aim of this study was to investigate the feasibility of such an intestinal segment in animal models. Hepatocytes isolated from luciferase-transgenic Lewis rats were transplanted into jejunal segments of wild-type Lewis rats with mucosa removal without PCS application. Luciferase-derived luminescence from transplanted hepatocytes was stably detected for 30 days. Then, we performed autologous hepatocyte transplantation into the submucosal layer of an isolated and vascularized small intestinal segment in pigs. Transplanted hepatocytes were isolated from the resected left-lateral lobe of the liver. On day 7, hepatocyte clusters and bile duct-like structures were observed histologically. To create an intestinal PCS system in pigs, an auto-graft of the segmental ileum and interposing vessel graft were anastomosed to the portal vein trunk and inferior vena cava. However, thrombi were observed in vessels of the intestinal PCSs. We measured the correlation between infusion pressure and flow volume in whole intestines ex vivo in both species and found that the high pressure corresponding to portal hypertension was still insufficient to maintain the patency of the intestinal grafts. In conclusion, we demonstrated the feasibility of the small intestine as a scaffold for hepatocyte transplantation in rat and pig models, but PCS using an intestinal graft failed to maintain patency in a pig model.

Bone marrow-derived mesenchymal stem cells ameliorate hepatic ischemia reperfusion injury in a rat model.

BACKGROUND: Ischemia-reperfusion (I/R) injury associated with living donor liver transplantation impairs liver graft regeneration. Mesenchymal stem cells (MSCs) are potential cell therapeutic targets for liver disease. In this study, we demonstrate the impact of MSCs against hepatic I/R injury and hepatectomy. METHODOLOGY/PRINCIPAL FINDINGS: We used a new rat model in which major hepatectomy with I/R injury was performed. Male Lewis rats were separated into two groups: an MSC group given MSCs after reperfusion as treatment, and a Control group given phosphate-buffered saline after reperfusion as placebo. The results of liver function tests, pathologic changes in the liver, and the remnant liver regeneration rate were assessed. The fate of transplanted MSCs in the luciferase-expressing rats was examined by in vivo luminescent imaging. The MSC group showed peak luciferase activity of transplanted MSCs in the remnant liver 24 h after reperfusion, after which luciferase activity gradually declined. The elevation of serum alanine transaminase levels was significantly reduced by MSC injection. Histopathological findings showed that vacuolar change was lower in the MSC group compared to the Control group. In addition, a significantly lower percentage of TUNEL-positive cells was observed in the MSC group compared with the controls. Remnant liver regeneration rate was accelerated in the MSC group. CONCLUSIONS/SIGNIFICANCE: These data suggest that MSC transplantation provides trophic support to the I/R-injured liver by inhibiting hepatocellular apoptosis and by stimulating regeneration.

Luminescence technology in preservation and transplantation for rat islet.

The development of organ preservation solutions and associated technology has been a major effort in tissue transplantation recently. However, this research takes a great deal of time and resources. In this study, a novel method for the evaluation of preservation solutions was established by using islet cells. Primary islets were obtained by hand-picking method from the luciferase transgenic (Luc-Tg) rat pancreas. The viability rate and living condition of islets preserved with several solutions were evaluated by relative photon intensity. Preserved islets were transplanted to the renal capsule of streptozotocin (STZ)-induced type 1 diabetic NOD-scid mouse, and the intraperitoneal glucose tolerance test (IPGTT) and histology were analyzed. The Luc-Tg rat islet viability was increased in a relative photon intensity-dependent manner. In the recipients of ET-Kyoto (ET-K) or University of Wisconsin (UW) solution preserved Luc-Tg rat islet at 1 day, hyperglycemia induced by glucose injection declined to the normal range. In conclusion, this study demonstrates that the ET-K preservation method allowed tissue ATP synthesis and amelioration of cold ischemic tissues damage during extended 24 h isolated-islet preservation. This simple method will be adapted easily to the clinical setting and used to maximize the utilization of islet transplantation as well as for pancreas sharing with remote centers.

Use of rat segmental intestine for fetal pancreatic transplantation.

It is thought that the small intestine may provide a scaffold for pancreas regeneration. Herein, we investigated whether fetal pancreatic tissue could be transplanted into the segmental intestine in rats. Fetal pancreases from firefly luciferase transgenic Lewis rat embryos (embryonic day 14.5 and 15.5) were transplanted into streptozotocin (STZ)-induced diabetic wild-type Lewis rats. As a scaffold for pancreatic development, rat small intestinal segments were utilized after the removal of mucosa, and fetal pancreases were grafted into the luminal surface through the stoma. We also transplanted fetal pancreases into the omentum. The survival of transplanted fetal pancreases was monitored by luciferase-derived photons and blood glucose levels. Transplanted fetal pancreas-derived photons were stable for 28 days, suggesting that transplanted fetal pancreatic tissues survived and that their intestinal blood supply was maintained.

Development of a portocaval shunt using a small intestinal segment in rats.

The transjugular portosystemic shunt, widely used to treat portal hypertension today, may increase the risk of encephalopathy and reduce effective hepatic flow. To address these issues, a strategy to produce a portocaval shunt (PCS) with hepatic function using intestinal grafts was conceived, and rat models were developed. We transplanted ileal grafts from wild-type and luciferase transgenic Lewis rats to wild-type Lewis rats, anastomosing the graft mesenteric artery (SMA) and portal vein (PV) to the recipient PV trunk and inferior vena cava, respectively. Recipient survival was significantly longer in the partial PCS model, in which the graft SMA was anastomosed to the recipient PV trunk in an end-to-side fashion, than in the total PCS model, with the end-to-end anastomosis. In the partial PCS model, histological and luminescence analyses showed graft survival for 1 month. These results suggest that intestinal grafts can be maintained in the particular conditions required for our strategy.

Familial occurrence of congenital bile duct dilatation.

Congenital bile duct dilatation (CBD) that developed in a parent and son is presented. Familial occurrence of CBD is rare, with only a few male cases having been reported. Since the initial report of CBD occurring in siblings in 1981, a total of 20 cases (10 pairs) have been published as of 2007. Clinical and genetic features of CBD are discussed.

A case of histopathologically typical toxic epidermal necrolysis despite no visible blisters or erosive lesions.

Toxic epidermal necrolysis (TEN) is a rare life-threatening disease characterized by blister formation and erosion over the entire body surface resulting from extensive keratinocyte death. We reported a case of TEN that developed in a 68-year-old man with hepatitis C virus liver cirrhosis three weeks after treatment with allopurinol. Exanthema developed as multiple target-like lesions, and erythroderma within five days without forming visible erosive lesions or obvious mucous membrane involvement. Reactivation of human herpes virus-6 or other herpes virus was not detected by polymerase chain reaction or serologic studies, and drug-induced hypersensitivity syndrome was ruled out. The finding of panepidermal necrosis on histopathological examination led to a diagnosis of TEN. Exanthema, fever and renal dysfunction responded to oral prednisolone, but the patient died of liver failure. Cases of TEN with histopathologically proven panepidermal necrosis without apparent blisters or erosions have rarely been reported because they do not fulfill the previously proposed diagnostic criteria for TEN. This finding, the discrepancy between the clinical and the histopathological manifestations, should not be overlooked in a case suspicious of TEN, and the importance of the histopathological examination should be emphasized in the differential diagnosis of TEN.