Clinical features of extrahepatic portal vein obstruction: Myeloproliferative neoplasms eliminate hypersplenic hematologic changes in extrahepatic portal vein obstruction.

Extrahepatic portal vein obstruction (EHPVO) is a rare disease. Most EHPVO patients are usually referred to a gastroenterologist for intestinal bleeding and hypersplenic thrombocytopenia; however, hypercoagulative diseases may be occult in these patients and require anticoagulation. The purpose of this study was to elucidate the clinical characteristics of EHPVO. We conducted a retrospective analysis of the hospital database, evaluating the medical records of 15 patients (7 males, 8 females, mean age of onset 42.0 years, range 5-74 years). Thirteen of 15 EHPVO patients (86.7%) had intestinal varices. These included 10 esophageal (66.7%), 12 gastric (80.0%), and 6 ectopic varices (40.0%). Nine (60.0%) of 15 had a history of intestinal bleeding. Regarding comorbidities, 5 of 15 (33.3%) suffered from vascular diseases, including acute myocardial infarction, cerebral infarction, pulmonary embolism, Budd-Chiari syndrome, and mesenteric vein thrombosis. The former 3 vascular commodities manifested at less than 32 years of age. Four patients (26.7%) with JAK2V617F mutation were diagnosed as myeloproliferative neoplasm (MPN). 72.3% of EHPVO patients without MPN experienced thrombocytopenic state. No EHPVO patients with MPN experienced thrombo-leukocytopenia. The elevation of white blood cell and platelet counts, and decrease of protein S were seen in EHPVO with MPN, compared with EHPVO without MPN. EHPVO is frequently associated with underlying hypercoagulative factors, causing a dilemma between thrombotic complications and portal hypertensive bleeding. Most EHPVO patients experience an evident thrombocytopenic state due to severe hypersplenism; however, hypersplenic hematologic changes are eliminated in EHPVO with MPN. MPN should be suspected in EHPVO patients negative for thrombo-leukocytopenia.

Current Status of Robotic Hepatobiliary and Pancreatic Surgery.

Laparoscopic surgery is performed worldwide and has clear economic and social benefits in terms of patient recovery time. It is used for most gastrointestinal surgical procedures, but laparoscopic surgery for more complex procedures in the esophageal, hepatobiliary, and pancreatic regions remains challenging. Minimally invasive surgery that results in accurate tumor dissection is vital in surgical oncology, and development of surgical systems and instruments plays a key role in assisting surgeons to achieve this. A notable advance in the latter half of the 1990s was the da Vinci Surgical System, which involves master-slave surgical support robots. Featuring high-resolution three-dimensional (3D) imaging with magnification capabilities and forceps with multi-joint function, anti-shake function, and motion scaling, the system compensates for the drawbacks of conventional laparoscopic surgery. It is expected to be particularly useful in the field of hepato-biliary-pancreatic surgery, which requires delicate reconstruction involving complex liver anatomy with diverse vascular and biliary systems and anastomosis of the biliary tract, pancreas, and intestines. The learning curve is said to be short, and it is hoped that robotic surgery will be standardized in the near future. There is also a need for a standardized robotic surgery training system for young surgeons that can later be adapted to a wider range of surgeries. This systematic review describes trends and future prospects for robotic surgery in the hepatobiliary-pancreatic region.

Gallbladder strangulation caused by a fibrotic band due to chlamydia infection: A case report.

Acute cholecystitis, a very common disease, is usually caused by gallstone obstruction of the cystic duct. Meanwhile, strangulated cholecystitis is extremely rare, and it develops when the gallbladder is strangled by a band. It is very similar to gallbladder torsion in terms of imaging findings and obstruction of blood and biliary flow, and it requires emergency surgery. We herein report a case of a 90-year-old woman with gallbladder strangulation caused by a fibrotic band due to a chlamydia infection, and we also reviewed some literature on strangulated cholecystitis.

Stenting of inferior right hepatic vein in a patient with Budd-Chiari syndrome: a case report.

A Japanese man in his 20s was referred to our hospital with a two-month history of abdominal fullness and leg edema. Abdominal computed tomography revealing massive ascites and ostial blockage of the main hepatic veins, and angiographic evaluation demonstrating obstruction of the main hepatic veins yielded a diagnosis of Budd-Chiari syndrome (BCS). Diuretic agents were prescribed for the ascites but failed to provide relief. The patient was referred to our department for further evaluation and treatment. Angiography showed ostial obstruction of the main hepatic veins, with most of the portal hepatic flow draining from an inferior right hepatic vein (IRHV) into the inferior vena cava (IVC) thorough an intrahepatic portal venous and venovenous shunt. Access between the main hepatic veins and IVC was impossible, but cannulation between the IRHV and IVC was achieved. Because of the venovenous connection between the main hepatic vein and the IRHV, metallic stents were placed into two IRHVs to decrease congestion in the hepatic venous outflow. After stent placement followed by balloon expansion, the gradient pressure between the hepatic vein and IVC improved remarkably. The ascites and lower leg edema improved postoperatively, and long-term stent patency (6 years) was achieved.

Causes and Management of Endoscopic Retrograde Cholangiopancreatography-Related Perforation: A Retrospective Study.

BACKGROUND: Endoscopic retrograde cholangiopancreatography (ERCP) is essential for diagnosing and treating biliopancreatic disease. Because ERCP-related perforation can result in death, therapeutic decisions are important. The aim of this study was to determine the cause of ERCP-related perforation and suggest appropriate management. METHODS: Between January 1999 and August 2022, 7,896 ERCPs were performed in our hospital. We experienced 15 cases (0.18%) of ERCP-related perforation and conducted a retrospective review. RESULTS: Of the 15 patients, 6 were female and 9 were male, and the mean age was 77.1 years. According to Stapfer's classification, the 15 cases of ERCP-related perforation comprised 3 type I (duodenum), 3 type II (periampullary), 9 type III (distal bile duct or pancreatic duct), and no type IV cases. Fourteen of 15 (92.6%) were diagnosed during ERCP. The main cause of perforation was scope-induced damage, endoscopic sphincterotomy, and instrumentation penetration in type I, II, and III cases, respectively. Four patients with severe abdominal pain and extraluminal fluid collection underwent emergency surgery for repair and drainage. One type III patient with distal bile duct cancer underwent pancreaticoduodenectomy on day 6. Three type III patients with only retroperitoneal gas on computed tomography (CT) performed immediately after ERCP had no symptoms and needed no additional treatment. Seven of the 15 patents were treated by endoscopic nasobiliary drainage (n=5) or CT-guided drainage (n=2). There were no deaths, and all patients were discharged after treatment. CONCLUSIONS: Early diagnosis and appropriate treatment are important in managing ERCP-related perforation.

FGFR4 Inhibitor BLU9931 Attenuates Pancreatic Cancer Cell Proliferation and Invasion While Inducing Senescence: Evidence for Senolytic Therapy Potential in Pancreatic Cancer.

Fibroblast growth factor receptor 4 (FGFR4), one of four tyrosine kinase receptors for FGFs, is involved in diverse cellular processes. Activation of FGF19/FGFR4 signaling is closely associated with cancer development and progression. In this study, we examined the expression and roles of FGF19/FGFR4 signaling in human pancreatic ductal adenocarcinoma (PDAC). In human PDAC cases, FGFR4 expression positively correlated with larger primary tumors and more advanced stages. Among eight PDAC cell lines, FGFR4 was expressed at the highest levels in PK-1 cells, in which single-nucleotide polymorphism G388R in FGFR4 was detected. For inhibition of autocrine/paracrine FGF19/FGFR4 signaling, we used BLU9931, a highly selective FGFR4 inhibitor. Inhibition of signal transduction through ERK, AKT, and STAT3 pathways by BLU9931 reduced proliferation in FGF19/FGFR4 signaling-activated PDAC cells. By contrast, BLU9931 did not alter stemness features, including stemness marker expression, anticancer drug resistance, and sphere-forming ability. However, BLU9931 inhibited cell invasion, in part, by downregulating membrane-type matrix metalloproteinase-1 in FGF19/FGFR4 signaling-activated PDAC cells. Furthermore, downregulation of SIRT1 and SIRT6 by BLU9931 contributed to senescence induction, priming these cells for quercetin-induced death, a process termed senolysis. Thus, we propose that BLU9931 is a promising therapeutic agent in FGFR4-positive PDAC, especially when combined with senolysis (195/200).

Outcomes of Liver Transplantation in Small Infants.

Liver transplantation (LT) for small infants remains challenging because of the demands related to graft selection, surgical technique, and perioperative management. The aim of this study was to evaluate the short-term and longterm outcomes of LT regarding vascular/biliary complications, renal function, growth, and patient/graft survival in infants ≤3 months compared with those of an age between >3 and 6 months at a single transplant center. A total of 64 infants ≤6 months underwent LT and were divided into 2 groups according to age at LT: those of age ≤3 months (range, 6-118 days; XS group, n = 37) and those of age >3 to ≤6 months (range, 124-179 days; S group, n = 27) between 1989 and 2014. Acute liver failure was the main indication for LT in the XS group (n = 31, 84%) versus S (n = 7, 26%). The overall incidence of hepatic artery thrombosis and portal vein thrombosis/stricture were 5.4% and 10.8% in the XS group and 7.4% and 11.1% in the S group, respectively (not significant). The overall incidence of biliary stricture and leakage were 5.4% and 2.7% in the XS group and 3.7% and 3.7% in the S group, respectively (not significant). There was no significant difference between the 2 groups in terms of renal function. No significant difference was found between the 2 groups for each year after LT in terms of height and weight z score. The 1-, 5-, and 10-year patient survival rates were 70.3%, 70.3%, and 70.3% in the XS group compared with 92.6%, 88.9%, and 88.9% in the S group, respectively (not significant). In conclusion, LT for smaller infants has acceptable outcomes despite the challenges of surgical technique, including vascular reconstruction and graft preparation, and perioperative management.

Metastasis of Hepatocellular Carcinoma to the Esophagus: Case Report and Review.

A follow-up endoscopy in a 71-year-old Japanese man who had undergone a left lateral segmentectomy for HCC two years ago revealed an approximately 2 cm in diameter pedunculated polypoid mass in the middle part of the thoracic esophagus. Immunohistochemical staining of the endoscopic biopsy revealed a metastatic HCC esophageal tumor. As the patient's disease could be radically removed by preoperative examinations, we resected the metastatic esophageal tumor via right thoracotomy and esophagogastrostomy reconstruction. Histological examination of the resected specimen revealed that the esophageal tumor was compatible with a HCC metastasis. This is an extremely rare case of a solitary metastasis to the esophagus from HCC in the literature.

Successful treatment of limy bile syndrome extending to the common bile duct by laparoscopic cholecystectomy and common bile duct exploration: A case report and literature review.

Limy bile syndrome extending to the common bile duct (CBD) is a rare condition that lacks a standardized treatment. Laparoscopic cholecystectomy with laparoscopic choledocholithotomy by CBD exploration is preferred because it preserves the function of the sphincter of the Vater's papilla and allows treatment of both lesions. A 37-year-old man who was receiving entecavir for chronic hepatitis B developed right upper quadrant pain. Abdominal ultrasonography revealed a calcified shadow in the gallbladder and CBD. Abdominal imaging revealed a liquid-like material identified by a calcified shadow in two phases separated by a fluid-fluid level. Abdominal and 3-D drip infusion cholangiography CT showed stones in the gallbladder and CBD with limy bile. The patient underwent laparoscopic cholecystectomy and choledocholithotomy. Intraoperatively, white-yellow-colored bile and stones were drained from the CBD. A C-tube was placed. Postoperatively, remnant stones and radiopaque materials were absent. The stones comprised of >95% calcium carbonate.

Liver resection for early hepatocellular cancer: Comparison of centers in 3 different countries.

AIM: To compare patients who underwent resection of early stage hepatocellular cancer (HCC) in three different countries. METHODS: This retrospective study characterizes 573 stage I/II HCC patients treated with liver resection in 3 tertiary-referral centers: Tokyo (n = 250), Honolulu (n = 146) and Shanghai (n = 177). RESULTS: Shanghai patients were younger, predominantly male, hepatitis-B seropositive (94%) and cirrhotic (93%). Tokyo patients were older and more likely to have hepatitis-C (67%), smaller tumors, low albumin, and normal alpha-fetoprotein. The Honolulu cohort had the largest tumors and 30% had no viral hepatitis. Age-adjusted mortality at 1 and 5-years were lower in the Tokyo cohort compared to Honolulu and there was no difference in mortality between Shanghai and Honolulu cohorts. Elevated alpha-fetoprotein, low albumin and tumor > 5 cm were associated with increased 1-year mortality. These factors and cirrhosis were independently associated with increased 5-year mortality. Independent risk factors of survival varied when examined separately by center. CONCLUSION: The profile of early-stage HCC patients is strikingly different across countries and likely contributes to survival differences. Underlying differences in patient populations including risk factors/comorbidities influencing disease progression may also account for variation in outcomes.

Gene Expression Analysis of the Irrigation Solution Samples Collected during Vitrectomy for Idiopathic Epiretinal Membrane.

PURPOSE: The analysis of gene expression in idiopathic epiretinal membranes (iERMs) may help elucidate ERM formation and its pathology. Here, we conducted a case-control study, in order to determine the expression levels of cytokines and other genes in eyes with macular hole (MH) or iERM. METHODS: Twenty eyes, obtained from seven male and 13 female patients, were included in the study. The average age of the study subjects was 69.1 ± 7.67 years, and 15 eyes had iERM, while five eyes had MH. Irrigation solution samples were collected during vitrectomy, centrifuged, and the levels of cytokine and other mRNAs in the sediment were assessed using real-time PCR. The expression level of 11 cytokine genes, four transcription factor genes, two cytoskeletal genes, and genes encoding two extracellular matrix proteins in eyes with MH or iERM were determined and compared. RESULTS: The expression levels of interleukin 6 (IL6), tumor growth factor B2 (TGFB2), vascular endothelial growth factor A (VEGFA), chemokine C-X-C motif ligand 1 (CXCL1), v-rel avian reticuloendotheliosis viral oncogene homolog A (RELA), glial fibrillary acidic protein (GFAP), and tenascin C (TNC) were significantly higher in eyes with iERM than in eyes with MH. The expression of these genes was not associated with the preoperative visual acuity of the investigated patients. CONCLUSIONS: The obtained results indicate that real-time PCR analysis of irrigation solution samples collected during vitrectomy can help assess the expression levels of several genes, and that iERM is associated with the expression of pro-inflammatory genes and the genes expressed during angiogenesis and wound healing process (IL6, TGFB2, VEGFA, CXCL1, RELA, GFAP, and TNC).

Cecal Volvulus Following Elective Laparoscopic Cholecystectomy: A Case Report.

Cecal volvulus is characterized by torsion of the cecum around its own mesentery. However, cecal volvulus rarely develops soon after elective laparoscopic cholecystectomy. We report on a case of cecal volvulus that developed in a 54-year-old women 1 day after elective laparoscopic cholecystectomy and was successfully treated via colonoscopic decompression. The symptoms gradually improved in conjunction with recovery from postoperative ileus. Whether the incidence of volvulus has increased with the use of laparoscopic procedures, including laparoscopic cholecystectomy, has yet to be determined. Considering the current trend toward minimally invasive surgery, cecal volvulus should be considered in patients who have postoperative abdominal pain and distention.

Laparoscopic mesh repair for lumbar hernia after iliac crest bone harvest.

Lumbar hernia after iliac crest bone harvest is relatively rare. When it does occur, it presents as a flank abdominal protrusion through a lateroposterior abdominal wall defect. A laparoscopic approach for this type of hernia is reported to have advantages over the classic open method. Here, we present a case of a 49-year-old Caucasian man who presented with an enlarged left flank mass after iliac bone harvest for pseudarthrosis. He had undergone open onlay mesh repair for inferior lumbar hernia, but the hernia recurred 3 months postoperatively. Laparoscopic intraperitoneal onlay mesh repair using a composite mesh was performed 7 months after recurrence. The patient was discharged 6 days postoperatively without complications. No signs of recurrence were detected during 1-year follow-up period. The laparoscopic approach for lumbar hernia conferred excellent visualization of the hernia defect and enabled a safe mesh repair using intra-abdominal pressure to hold it in position. This approach provided all the benefits of minimally invasive surgery.

Impact of Neoadjuvant Chemoradiation on Short-Term Outcomes for Esophageal Squamous Cell Carcinoma Patients: A Meta-analysis.

BACKGROUND: Neoadjuvant chemoradiation (NCRT) has emerged as a component of the standard treatment for esophageal squamous cell carcinoma (SCC). The primary benefit of NCRT is an improvement in long-term survival; however, the impact of NCRT on short-term outcomes is unclear. METHODS: A comprehensive electronic literature search was performed via the MEDLINE (PubMed), Cochrane Library, and Google Scholar databases through November 2015 for the inclusion of randomized controlled trials (RCTs) that evaluated short-term outcomes of patients administered NCRT followed by surgery compared with surgery alone for resectable esophageal SCC. The main outcome measures were postoperative mortality and morbidity. A meta-analysis was performed using random-effects models to calculate odds ratios (ORs) with 95 % confidence intervals (CIs). RESULTS: Eight RCTs were included, for a total of 1058 patients. Meta-analysis of the overall postoperative mortality and cardiopulmonary complication rates showed that there was a significant increase for patients administered NCRT followed by surgery compared with surgery alone (OR 1.87, 95 % CI 1.07-3.28, p = 0.03, number of patients needed to harm = 33.3; and OR 2.12, 95 % CI 1.03-4.35, p = 0.04, respectively). Dropout before surgery was higher for patients in the NCRT followed by surgery group compared with patients in the surgery-alone group. NCRT has no statistically impact on anastomosis and other complications compared with surgery alone. CONCLUSIONS: NCRT for esophageal SCC significantly increases postoperative mortality and cardiopulmonary complications.

Distinct Profiles of Soluble Cytokine Receptors Between B-Cell Vitreoretinal Lymphoma and Uveitis.

PURPOSE: To determine the profiles of soluble cytokine receptors and cytokines, including mostly their ligands, in the vitreous humor of patients with B-cell vitreoretinal lymphoma (VRL) and uveitis. METHODS: Vitreous samples were collected from immunocompetent patients with VRL (n = 21), uveitis (n = 20), and idiopathic epiretinal membrane (n = 21) as controls. Cytometric beads assay were used to determine the vitreous concentrations of soluble receptors and cytokines. RESULTS: Vitreous levels of soluble IL-2 receptor α (sIL-2Rα), sIL-6R, soluble tumor necrosis factor receptor (TNFR) 1, sTNFR2, soluble vascular endothelial growth factor receptor (sVEGFR) 1, sVEGFR2, and IL-10 were higher in patients with VRL than in those with uveitis and controls, whereas those of sIL-1R1, sIL-1R2, and sIL-4R were higher in patients with uveitis than those with VRL and controls. In analyses in patients with VRL, elevation of sVEGFR1 and sVEGFR2 levels was more prominent in patients with systemic metastatic retinal lymphoma (SMRL) than in those with primary VRL/primary central nervous system lymphoma (PVRL/PCNSL). Furthermore, sIL-2Rα levels were increased in patients with VRL who developed subretinal lesions compared with in those who mainly had vitreous cavity opacity, positively correlated with the density of CD3+ cells in the vitrectomy cell blocks. CONCLUSIONS: The profiles of soluble cytokine receptors and cytokines in patients with VRL were different from those with uveitis. In addition, sVEGFR1 and sVEGFR2 levels may be differential diagnostic markers between PVRL/PCNSL and SMRL, and sIL-2Rα levels can anticipate infiltration of VRL cells into the subretina and/or retina.

Isolation, sequencing, and heterologous expression of the Paecilomyces variotii gene encoding S-hydroxymethylglutathione dehydrogenase (fldA).

The filamentous fungus Paecilomyces variotii NBRC 109023 (teleomorph: Byssochlamys spectabilis NBRC 109023) degrades formaldehyde at concentrations as high as 2.4 % (w/v). In many prokaryotes and in all known eukaryotes, formaldehyde degradation is catalyzed by S-hydroxymethylglutathione (S-HMGSH) dehydrogenase. We report here the isolation and characterization of the gene encoding S-HMGSH dehydrogenase activity in P. variotii. The 1.6-kb fldA gene contained 5 introns and 6 exons, and the corresponding cDNA was 1143 bp, encoding a 40-kDa protein composed of 380 amino acids. FldA was predicted to have 74.3, 73.7, 68.5, and 67.4 % amino acid identity to the S-HMGSH dehydrogenases of Hansenula polymorpha, Candida boidinii, Saccharomyces cerevisiae, and Kluyveromyces lactis, respectively. The predicted protein also showed high amino acid similarity (84∼86 %) to the products of putative fldA genes from other filamentous fungi, including Aspergillus sp. and Penicillium sp. Notably, the P. variotii fldA gene was able to functionally complement a Saccharomyces cerevisiae strain (BY4741 ∆sfa1) lacking the gene for S-HMGSH dehydrogenase. The heterologous expression construct rendered BY4741 ∆sfa1 tolerant to exogenous formaldehyde. Although BY4741 (parental wild-type strain) was unable to degrade even low concentrations of formaldehyde, BY4741 ∆sfa1 harboring Paecilomyces fldA was able to degrade 4 mM formaldehyde within 30 h. The findings from this study confirm the essential role of S-HMGSH dehydrogenase in detoxifying formaldehyde.

Radiotherapy for early-stage primary ocular adnexal mucosa-associated lymphoid tissue lymphoma.

BACKGROUND: Primary ocular adnexal mucosa-associated lymphoid tissue lymphoma (POAML) is a rare disease. The purpose of this study was to evaluate the treatment outcome and patterns of failure of patients with early-stage POAML treated with radiotherapy. PATIENTS AND METHODS: From 1995 to 2008, 53 patients with early-stage POAML were reviewed. Tumors were categorized as either superficial or mass-forming type. In principle, superficial lesions (n=11) were treated with 24 Gy, while the mass-forming lesions (n=42) were irradiated with 30 Gy. The median follow-up period was 3.9 years. RESULTS: All four cases of relapse had mass-forming lesions. The 5-year overall and progression-free survival rates were 100% and 91.5%, respectively. Although 30 patients experienced grade 2 or 3 late adverse events, no patients had radiation-related retinopathy. CONCLUSION: Early-stage POAML can be well-controlled with radiotherapy. However, the risk of distant relapse should be noted, in particular, for mass-forming tumors.

Long-term outcomes after Frey's procedure for chronic pancreatitis with an inflammatory mass of the pancreatic head, with special reference to locoregional complications.

BACKGROUND: Frey's procedure might be a good alternative to pylorus-preserving pancreaticoduodenectomy (PPPD) for patients with an inflammatory mass of the head of the pancreas, because it is technically easy and associated with low morbidity and good pain relief. PURPOSE: To analyze the short-term and long-term outcomes of Frey's procedure in comparison with PPPD and to evaluate the efficacy of Frey's procedure against preoperative locoregional complications. PATIENTS AND METHODS: From August 1997 through December 2007, 6 patients underwent Frey's procedure (as described by Frey and Smith), and 10 patients underwent PPPD. The mean follow-up times were 70.8 months (Frey's procedure) and 119.8 months (PPPD). Preoperative biliary stricture and duodenal stenosis were observed in 4 and 3 patients, respectively, of patients undergoing Frey's procedure. Pain intensity was assessed with a pain scoring system. Quality of life (QOL) was assessed with the European Organization for Research and Treatment of Cancer Quality of-Life Questionnaire-Core 30. Exocrine and endocrine pancreatic function was measured during follow-up. RESULTS: Significant reductions in total pain scores and all QOL scale scores were observed immediately after surgery in all patients (P<0.05). Frey's procedure was superior to PPPD with regard to physical status 7 years after surgery (P<0.05). One patient in the Frey group had a grade B pancreatic fistula, and 2 patients in the PPPD group had intra-abdominal bleeding and delayed gastric emptying. There were no re-operations or surgery-related deaths in either group. Diabetes developed postoperatively in 2 patients in the PPPD group. No patients with preoperative duodenal or biliary stricture or both had a relapse. Three patients in the PPPD group died during follow-up of diseases unrelated to chronic pancreatitis. CONCLUSION: Frey's procedure is safe and effective with regard to pain relief, preservation of pancreatic function, and improvement of QOL over the long term. Moreover, this procedure can also be used to treat preoperative biliary stricture and duodenal stenosis associated with an inflammatory mass of the pancreatic head.