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The aims of this pilot study were to establish a principle of molecular imaging of the pancreas and determine in vivo expression of epidermal growth factor receptor (EGF-R) and survivin using a novel endoscopic ultrasound-guided fine needle imaging (EUS-FNI) technique, which incorporates needle based confocal laser-induced endomicroscopy (nCLE) after intrapancreatic injection of FTIC-labeled antibodies. Studies were performed in anesthetized pigs. FITC-labeled specific antibodies against EGF-R and survivin were injected into the tail and neck of the pancreas using a 19 gauge needle introduced under EUS guidance. Thirty minutes later, nCLE was performed using a prototype needle-based confocal laser-induced endomicroscopy probe (Cellvizio AQ-Flex-19, Mauna Kea Technologies, Paris, France) to determine cellular and tissue localization of EGF-R and survivin in the pancreas. Then pigs were euthanized and specimens of pancreas from areas injected with antibodies were obtained for histologic examination under epifluorescence microscope.EUS-guided nCLE enabled visualization of EGF-R and survivin in pancreatic tissue. Expression of EGF-R and survivin in pancreas was confirmed by histology. EGF-R immunoreactivity was localized to majority of duct-lining cells and to the surface and cytoplasm of many acinar cells. Survivin was localized mainly to the acinar cells. This study demonstrated the feasibility of in vivo, real time visualization of EGF-R and survivin in the pancreas by local injection of FITC-labeled antibodies via EUS-guided fine needle injection, followed by EUS-guided needle based confocal laser-induced endomicroscopy.

Confocal laser-induced endomicroscopy (CLE) enables in vivo, real time visualization of the subsurface cells and tissue structures in gastrointestinal mucosa at a subcellular resolution of ≈1000x magnification. The aims of this pilot study were to establish a principle of molecular imaging and determine in vivo expression of epidermal growth factor receptor (EGF-R) and survivin in porcine esophageal and gastric mucosa using probe-based CLE (pCLE) and topically applied FITC-labeled antibodies. Studies were performed in anesthetized pigs. During endoscopy FITC-labeled antibodies against EGF-R and survivin were either sprayed onto esophageal and gastric mucosa in preselected areas or administered via submucosal injection. Thirty minutes later pCLE was performed using a through-the-scope probe (GastroFlex UHD, Cellvizio, Mauna Kea Technologies, Paris, France) to determine cellular and tissue localization of EGF-R and survivin. Then the pigs were euthanized and esophageal and gastric walls from the areas sprayed or injected with antibodies were collected for histologic examination under epifluorescence microscopy.CLE enabled visualization of EGF-R and survivin in esophageal and gastric mucosa and this was confirmed by histology. In the esophagus both EGF-R and survivin were localized predominantly to the keratinocyte progenitor cells. In the stomach, EGF-R was localized to progenitor zone cells and some epithelial cells. Localization of survivin was similar, but involved more surface epithelial cells. This study demonstrated feasibility of using CLE and topical administration of FITC labeled antibodies for in vivo localization of EGF-R and survivin in esophageal and gastric mucosa.

Introduction: Selective cannulation fails in approximately 3 % of endoscopic retrograde cholangiography (ERC) procedures. An endoscopic ultrasound-guided rendezvous technique (EUS - RV) may salvage failed cannulation. The aims of the current study were to determine the safety and efficacy of EUS - RV. Methods: A total of 40 patients underwent salvage EUS - RV. EUS - RV was attempted immediately after failed biliary cannulation. A dilated intra- or extra-hepatic biliary duct (IHBD or EHBD) was punctured from the stomach or the small intestine under EUS guidance followed by cholangiography and antegrade manipulation of the guide wire into the small intestine. Finally, the echoendoscope was exchanged for an appropriate endoscope and biliary cannulation was achieved over or adjacent to the guide wire. Result: EUS-RV appears safe and effective and may be considered as a primary salvage technique after failed cannulation. Antegrade manipulation of the guide wire into the small intestine was achieved in 29 of 40 patients (73 %; EHBD 25 /31 and IHBD 4/9). The reasons for failure were inability to advance the guide wire through an obstruction or a native ampulla. Re-attempt at ERC immediately after failed EUS - RV was made in seven of the 11 patients, and was successful in four. The remaining seven patients underwent percutaneous drainage within 3 days. Complications occurred in five patients (13 %), including pancreatitis, abdominal pain, pneumoperitoneum, and sepsis/death, which was unlikely to be related to the procedure. Conclusion: EUS - RV is safe and effective and should be considered as a primary salvage technique after failed cannulation. Immediate re-attempt at ERC after failed EUS - RV is warranted, as EUS-guided cholangiogram can facilitate biliary cannulation in some cases. Finally, prompt alternative biliary drainage should be available. [ABSTRACT FROM AUTHOR]

Background: Revascularization surgery has been reported to have a higher success rate than replantation due to sufficient venous return. However, in complex cases, success depends on a wide range of indications. This study aimed to investigate success rates in cohorts that included severe cases., Methods: This single-center, noninterventional, retrospective cohort study included 292 patients (349 digits) who underwent revascularization or replantation at our institution between January 2000 and December 2022. Sex, age, smoking history, comorbidities, affected digit, amputation level, complete or incomplete amputation, type of fracture and mechanism, artery diameter, needle, vein anastomosis in the revascularization subgroup, vein grafting, warm ischemic time, and outcomes were investigated and compared between the revascularization and replantation subgroups of the distal and proximal amputation groups., Results: In the distal amputation group, the arterial diameter in the revascularization subgroup was larger than that in the replantation subgroup ( P  < 0.05). In the proximal amputation group, the revascularization subgroup had a lower frequency of multiple amputations than the replantation subgroup ( P  < 0.05). Vein grafts were more frequently used in both revascularization subgroups than in the replantation subgroups ( P  < 0.05). However, the other injury severity indices were similar, and the success rates were not significantly different between the subgroups., Conclusions: The revascularization success rate was similar to that of replantation. Vein anastomosis or vein grafting to the veins should be advocated for revascularization in severe cases where skin bridges may not have sufficient venous return., Competing Interests: The authors have no financial interest to declare in relation to the content of this article. Disclosure statements are at the end of this article, following the correspondence information., (Copyright © 2024 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of The American Society of Plastic Surgeons.)

No difference in the success rate has been reported between the vein graft and non-vein graft groups in replantation/revascularization. However, this depends on a wide range of indications in difficult cases. This study aimed to investigate the selection bias in avoiding vein grafts., Methods: This is a single-center, noninterventional, retrospective cohort study comprising 229 patients (277 digits) who underwent replantation/revascularization between January 2000 and December 2020 at our institution. Sex, age, smoking history, comorbidities, affected side, level of amputation, complete or incomplete amputation, type of fracture and mechanism, diameter of the artery, needle, warm ischemic time, and results were investigated and compared between the subgroups with and without vein graft. Results were investigated between the subgroups with and without a vein graft in the distal and proximal groups., Results: In the distal group, the mean arterial diameter of the vein graft subgroup was larger than that of the non-vein graft subgroup [0.7 (0.1) mm and 0.6 (0.2) mm, respectively, P < 0.05]. In the proximal group, the vein graft subgroup had higher severity than the non-vein graft subgroup (comminuted fracture, 31.1% versus 13.4%; and avulsion or crush amputation, 57.8% versus 37.1%, respectively, P < 0.05). However, the success rate was not significantly different between the aforementioned subgroups., Conclusion: There was no significant difference between the vein graft and non-vein graft subgroups owing to the selection bias avoiding small arteries in the distal amputation and the absence of said bias in the proximal amputation., Competing Interests: The authors have no financial interest to declare in relation to the content of this article., (Copyright © 2023 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of The American Society of Plastic Surgeons.)

A 72-year-old woman was referred for the examination of wall thickening of the bile duct and a polyp-like lesion on the gallbladder. The bile duct and gallbladder lesions were observed to be continuous on abdominal ultrasonography. We performed a bile duct biopsy, and pathological findings showed hyperplasia of the lymphoid follicles without malignancy. We considered these two lesions to be the same lesion, and laparoscopic cholecystectomy was performed to make a definite diagnosis. The pathological examination of the resected gallbladder also showed hyperplasia of the lymphoid follicles. We diagnosed the patient with lymphoid hyperplasia of the gallbladder extending to the bile duct.

Background & Aims: The efficacy of endoscopic sphincterotomy (ES) before endoscopic transpapillary biliary drainage in preventing post-endoscopic retrograde cholangiopancreatography pancreatitis (PEP) has not been established. The aim of this study was to evaluate the effect of performing ES before biliary stent/tube placement on the occurrence of PEP., Methods: Three hundred seventy patients with biliary stricture requiring endoscopic biliary stenting were enrolled and randomly allocated to the ES group (n = 185) or non-ES group (n = 185). All participants were followed up for 30 days after the procedure. The data and occurrence of adverse events were prospectively collected. The primary outcome measure of this study was the incidence of PEP within 2 days of initial transpapillary biliary drainage. Secondary outcome measures were the incidence of other adverse events related to biliary stent/tube placement., Results: PEP occurred in 36 patients (20.6%) in the non-ES group and in 7 patients (3.9%) in the ES group (P < .001). The difference in the incidence of PEP between the 2 groups in the per-protocol population was 16.7% (95% confidence interval, 10.1%-23.3%), which was not within the noninferiority margin of 6%. Except for bleeding, the incidences of other adverse events were not significantly different between the groups., Conclusion: ES before endoscopic biliary stenting could have the preventive effect on the occurrence of PEP in patients with biliary stricture. University Hospital Medical Information Network Number, UMIN000025727.University Hospital Medical Information Network Clinical Trial Registry URL: https://www.umin.ac.jp/ctr/index.htm., (Copyright © 2022 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Oral uracil and tegafur plus Leucovorin(UFT/LV)therapy is one of the standard adjuvant chemotherapies for colorectal cancer, and is widely used without any serious adverse events. Herein, we describe a case of UFT/LV-induced acute liver failure in a 75-year-old woman who underwent laparoscopic sigmoidectomy for sigmoid colon cancer. She was diagnosed with advanced colon cancer and lymph node metastasis by postoperative histopathological analysis, and adjuvant chemotherapy was initiated. After 30 days of commencing the therapy, the patient visited our hospital with complaints of severe diarrhea and difficulty in food intake. The apparent cause of these symptoms was unclear on computed tomography(CT), and mild liver damage was revealed in blood test results. The hepatic disorder gradually progressed after the hospitalization, and the condition was diagnosed as acute hepatic insufficiency. Additionally, obvious atrophy of the liver parenchyma and significant ascites were confirmed on CT. Two months later, the platelet count decreased markedly, but fortunately, no bleeding occurred. There has been no recurrence since 2 years after the surgery without any additional adjuvant therapy.

Purpose: To determine if endoscopic retrograde cholangiopancreatography (ERCP) performed within 72 h after contrast enhanced computed tomography (CECT) increases contrast-induced nephrotoxicity (CIN) risk in patients with abdominal complaints., Method: This single-center retrospective cohort study included consecutive adult patients with abdominal complaints who underwent CECT between October 1, 2016, and June 30, 2019 at an emergency department (ED). CIN was diagnosed based on serum creatinine (SCr) level >0.5 mg/dL within 72 h after CECT or that increased >25 % compared to pre-CECT level. Logistic regression analysis was performed to determine independent risk factors for CIN, including age, sex, body mass index, comorbidities, medication, pre-CECT SCr level >1.5 mg/dL, and ERCP performed within 72 h after CECT. For persistent CIN, SCr level was obtained after 3 months at the earliest and compared to data obtained within 72 h after ERCP and CECT., Results: Of 1457 patients with CECT, 90 (6.2 %) underwent ERCP within 72 h after CECT and 93 (6.4 %) developed CIN. Multivariate analysis revealed that ERCP performed within 72 h after CECT (odds ratio, 3.31; 95 % confidence interval, 1.74, 6.29; p < 0.001) and pre-CECT SCr level >1.5 mg/dL (odds ratio, 9.86; 95 % confidence interval, 5.08, 19.2; p < 0.001) were independent risk factors for CIN. Of 93 patients with CIN, 10 (11 %) had persistent CIN. No specific factors were correlated with persistent CIN in the 3-month time frame., Conclusion: ERCP performed within 72 h after CECT and pre-CECT SCr level >1.5 mg/dL are associated with CIN development., Competing Interests: Declaration of Competing Interest None., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Thus far, no curved linear array endoscopic ultrasound (CLAEUS) findings were established as predictors of difficult selective bile duct cannulation (SBDC). This study aimed to identify CLAEUS findings to predict endoscopic retrograde cholangiopancreatography (ERCP) cases with difficult SBDC. This single-center, retrospective cohort study was conducted between July 2014 and June 2017. This study included all consecutive patients who underwent CLAEUS prior to naïve ERCP. A CLAEUS finding of the simultaneous depiction of bile and pancreatic ducts at the second portion of the duodenum (D2) (simultaneous depiction) was selected as a possible predictor of difficult SBDC, and the κ values in the evaluation of inter- and intra-observer variabilities for "simultaneous depiction" were 0.65 and 0.77, respectively, with substantial correlation. Among the 986 patients who underwent ERCP, 80 patients were relevant for evaluation. Logistic regression analysis revealed strong association between "simultaneous depiction" and difficult SBDC (odds ratio 15.4, 95% confidence interval 4.2-56.0; p<0.001). Among patients who underwent CLAEUS prior to naïve ERCP, a strong correlation was observed between "simultaneous depiction" and the risk of difficult SBDC. An endoscopist can prepare for difficult SBDC by "simultaneous depiction." The finding enables pertinent planning when performing ERCP, such as setting time limits and selecting alternative devices, techniques, and skilled endoscopists, for difficult SBDC with minimal complications including post-ERCP pancreatitis. However, a future prospective study is necessary to establish the procedure algorithm for suspected difficult SBDC cases based on CLAEUS., Competing Interests: The authors have declared that no competing interests exist.

Laparoscopy and endoscopy cooperative surgery(LECS)is the surgical procedure used to avoid excessive resection of the gastrointestinal wall and preserve its function. We report the case of a patient who was successfully treated with inverted LECS for gastrointestinal stromal tumor(GIST)in the remnant stomach and underwent distal gastrectomy. The patient was a 75- year-old man who received distal gastrectomy for gastric ulcer 28 years before. Three years before he was diagnosed as having gastric submucosal tumor(SMT)as a gastrointestinal tumor(GIST)by using EUS. As the tumor increased, he was admitted to our hospital. Upper gastrointestinal endoscopy revealed a 30mm SMT just below the cardiac part of the remnant stomach. Biopsy by EUS-FNA revealed CD34(-), c-kit(+), S-100(-), and a-SMA(-), which indicated gastric GIST. Inverted LECS was performed. His postoperative course was good, and he was discharged from the hospital 9 days after the surgery.

Background: Invasive fungal infection (IFI) is associated with high mortality after living donor liver transplant (LDLT). The aim of this study was to identify the risk factors for post-LDLT IFI for early diagnosis and improvement of antifungal treatment outcome., Methods: Risk analysis data were available for all 153 patients who underwent LDLT between January 2005 and April 2012., Results: During the follow-up period (1,553 ± 73 days, range 20-2,946 days), 15 patients (9.8%) developed IFI classified as "proven" (n = 8) and "probable" (n = 7) with fungal pathogens including Candida spp. (n = 10), Aspergillus spp. (n = 4), and Trichosporon (n = 2). Of these patients, 7 patients with IFI died despite treatment. The 1-, 3-, and 5-year survival rates were lower in patients with IFI than those without IFI (66.7/59.3/44.4 vs. 90.4/85.7/81.8%, respectively; p = 0.0026). Multivariate analysis identified model for end-stage liver disease score of ≥26 (OR 16.0, p = 0.0012) and post-transplant acute kidney injury (RIFLE criteria I- or F-class; OR 4.87, p = 0.047) as independent risk factors for IFI., Conclusion: Preoperative recipients' status and postoperative kidney dysfunction can affect an occurrence of post-transplant IFI. These risk factors would be taken into consideration for designation of proper antifungal therapy., (© 2018 S. Karger AG, Basel.)

The patient was a 59-year-old man with type 2 advanced gastric cancer in the antrum. Abdominal computed tomography revealed the primary tumor with regional lymph node metastasis. Distal gastrectomy and D2 lymph node dissection were performed. Histopathological findings indicated gastric small cell carcinoma. Lymph node metastasis was observed microscopically in the #6 lymph nodes. Peritoneal lavage cytology was positive. The pathologic stage of the disease was pT2(MP), med, INF b, ly2, v2, pPM0, pDM0, pN2(6/33: #5, #6), M1, P0, CY1, H0, stage Ⅳ, R1(cy+). After surgery, he received chemotherapy with capecitabine plus oxaliplatin. However, after 1 course of therapy the disease had progressed, and the patient was diagnosed with peritoneal metastasis. Chemotherapy of CDDP plus CPT-11 was initiated, and after 5 courses the patient died.

A 71-year-old man visited our hospital because ofepigastralgia and anorexia. Upper gastrointestinal endoscopy revealed type 1 gastric cancer. Contrast-enhanced abdominal CT revealed gastric wall thickening in the midgastric region and direct invasion ofthe transverse colon. CT findings also revealed a suspicion ofdissemination on the omentum and para-aortic lymph node swelling. We diagnosed gastric cancer with transverse colon invasion. Therefore, we performed distal gastrectomy with transverse colectomy and D2+No.16b1 lymph node dissection after obtaining patient consent. We observed direct tumor invasion into the transverse colon and seeding nodules on the omentum. Liver metastasis was not seen, and ascitic cytology was negative. He was discharged 16 days postoperatively, without any complications. Histopathological analysis revealed poorly differentiated adenocarcinoma and gastrocolic fistula. Postoperatively, S-1 was administered for 4 years as adjuvant chemotherapy. There has been no recurrence for 9 years after surgery.

A 25-year-old woman presented to our hospital with left flank pain and diarrhea. Contrast-enhanced abdominal computed tomography(CT)showed a target sign in the descending colon. She was diagnosed with intussusception of the colon. Colonoscopy revealed a tumor at the splenic flexure. We performed surgery and found an invaginated transverse colon at the splenic flexure. Reduction was unsuccessful with Hutchinson's maneuver, and we performed partial resection of the invaginated colon. Histopathological diagnosis was adenocarcinoma, tub1, SM2. Adult intussusception is uncommon, especially in young adults. It is usually caused by a polyp or tumor. We report a case of intussusception caused by colon cancer in a young female patient, and review the literature.

Combined modality therapy is sufficient to treat advanced rectal cancer with multiple metastases. Her, we report a case of long-term survival in a patient with multiple metastases from rectal cancer. A5 8-year-old man had previously undergone low anterior resection for advanced rectal cancer. Multiple liver and lung metastases were identified prior to operation; therefore, we initiated chemotherapy(FOLFOX). Partial resection of metastatic lesions and radiofrequency ablation(RFA)were also administered, but newly developed liver, lung, and adrenal gland metastases were identified. We changed the chemotherapy regimen and administered topical therapies(partial resection, RFA, hepatic arterial infusion chemotherapy, radiotherapy)for each chemotherapy-refractory metastatic lesion. Although the patient is in a tumor-bearing state, he is still alive 10 years after his first operation. This combined modality therapy is an option for patients with chemotherapy-refractory metastases from rectal cancer.

A79 -year-old woman underwent colonoscopic examination for positive occult blood. Aneoplastic lesion was seen in the orifice of the vermiform appendix. She was referred to our hospital and underwent colonoscopic examination again. The biopsy revealed poorly differentiated adenocarcinoma or mixed adenoneuroendocrine carcinoma(MANEC), and she was diagnosed with carcinoma of the appendix. She was treated by laparoscopic ileocecal resection with lymph node dissection (D3). Histopathological examination revealed goblet cell carcinoid(GCC)of the appendix with serosal invasion. No metastasis was detected in the dissected lymph nodes. This patient has been followed-up for 6 months after surgery and no recurrences have been detected.

Background: Immune-nutritional status has been recently reported as a prognostic factor in hepatocellular carcinoma (HCC). The controlling nutritional status (CONUT) score has been established as a useful tool to evaluate immune-nutritional status. This study aimed to investigate the efficacy of the CONUT score as a prognostic factor in patients undergoing hepatectomy for HCC., Methods: A total of 295 patients who underwent curative hepatectomy for HCC between January 2007 and December 2014 were retrospectively analyzed. Patients were divided into two groups according to the CONUT score. The impact of the CONUT score on clinicopathological, surgical, and long-term outcomes was evaluated. Subsequently, the impact of prognostic factors, including the CONUT score, associated with outcomes was assessed using multivariate analyses., Results: Of 295 patients, 118 (40%) belonged to the high CONUT group (CONUT score ≥ 3). The high CONUT group had a significantly lower 5-year recurrence-free survival rate than the low CONUT group (27.9 vs. 41.4%, p = 0.011) and a significantly lower 5-year overall survival rate (61.9 vs. 74.9%, p = 0.006). In multivariate analyses of prognostic factors, the CONUT score was an independent predictor of recurrence-free survival (hazard ratio = 1.64, p = 0.006) and overall survival (hazard ratio = 2.50, p = 0.001)., Conclusions: The CONUT score is a valuable preoperative predictor of survival in patients undergoing hepatectomy for HCC.

Background: Predictors for bile duct stone recurrence after endoscopic stone extraction have not yet been clearly defined and a study investigating naïve major duodenal papilla is warranted because studies focusing only on naïve major duodenal papilla are rare. The aim of this study was to observe the long-term outcomes of endoscopic bile duct stone extraction for naïve major duodenal papilla and to assess the predictors for recurrence., Methods: This was a retrospective cohort study that consisted of 384 patients with naïve papilla who underwent initial endoscopic bile duct stone extraction. Patients were followed up in outpatient department subsequent to complete stone clearance. Recurrence was defined as symptomatic repeated stone formation observed at least three months after the procedure. Stone recurrence, predictors of recurrence, and the recurrence rate, depending on each endoscopic treatment for major duodenal papilla, were examined., Results: In this study, 34 patients (8.9%) developed stone recurrence. The median time to recurrence was 439 days. Periampullary diverticulum and multiple stones were strong predictors of bile duct stone recurrence (RR, 5.065; 95% CI, 2.435-10.539 and RR: 2.4401; 95% CI: 1.0946-5.4396, respectively). The above two factors were independent predictors of stone recurrence as per logistic regression analysis adjusted for confounders (Periampullary diverticulum: OR, 7.768; 95% CI, 3.27-18.471; multiple stones: OR, 4.144; 95% CI, 1.33-12.915). No recurrence was observed after endoscopic papillary large balloon dilatation (0/20), whereas recurrence was observed in 7 patients after endoscopic papillary balloon dilatation (7/45) and in 27 patients after endoscopic sphincterotomy (27/319). However, these differences were not statistically significant (p = 0.105)., Conclusions: We determined that the presence of periampullary diverticulum and multiple stones are strong predictors for recurrence after endoscopic stone extraction. Moreover, endoscopic papillary large balloon dilatation tended to be correlated with non-recurrence of bile duct stone.

BACKGROUND Human leukocyte antigen (HLA) mismatch is a characteristic feature of post-orthotopic liver transplantation (OLT) hepatitis C. To investigate the importance of donor HLA-restricted immune cells in post-OLT hepatitis C recurrence, we analyzed the frequency of donor chimerism and the clinical course of post-OLT hepatitis C. MATERIAL AND METHODS We analyzed peripheral blood chimerism in 11 HCV-reinfected patients with post-HLA mismatched OLT. Patients were divided into 2 groups: the OLT chronic hepatitis C (CHC) group (n=8), exhibiting active hepatitis C recurrence; and the OLT-persistently normal ALT (PNALT) group (n=3), without active hepatitis. Chimerism was analyzed by flow cytometry using donor-specific anti-HLA antibodies in peripheral blood mononuclear cells from 1-100 days after OLT. Kidney (n=7) and lung (n=7) transplant recipients were also analyzed for comparison. As immune cells from the donor liver might contribute to post-OLT chimerism, the characteristics of perfusates from donor livers (n=10) were analyzed and defined. RESULTS Donor-derived cells were frequently observed in liver and lung transplant recipients. The frequency of donor-derived cells from the B cell subset was significantly higher in peripheral blood from OLT-CHC group than in that of the OLT-PNALT group. B cells, however, were not the predominant subset in the perfusates, indicating that inflow of donor-derived cells alone did not cause the chimerism. CONCLUSIONS Chimerism of B cells is frequent in liver transplant patients with early recurrence of hepatitis C. We propose that monitoring of early chimerism could facilitate early detection of chronic hepatitis C recurrence, although we need more cases to investigate.

Background and Aims: Pancreatic cystic neoplasms (PCNs) often need interval surveillance, including repeat EUS, but the role of repeat FNA with fluid analysis is poorly defined. The aim of this analysis is to evaluate the potential clinical significance of serial carcinoembryonic antigen (CEA) measurements by EUS-guided FNA (EUS-FNA) in the surveillance for PCNs., Patients: Patients who underwent EUS-FNA for PCNs were studied retrospectively. EUS-FNA findings were compared between index and prior procedures among patients who underwent repeat EUS-FNA., Results: A total of 400 patients with PCNs underwent EUS-FNA. Eighty-seven of those patients had prior EUS-FNA with cyst fluid analysis. Patients with repeat FNA were significantly more likely to have multiple cysts (57% vs 41%; P = .008), multilocular cysts (75% vs 62%; P = .042), connection to pancreatic duct (33% vs 18%; P = .005), and higher initial CEA levels (94.8 vs 25.6 ng/mL; P = .003) compared with patients who had only a single FNA. A comparison of prior and index FNAs did not show significant differences in EUS or cyst fluid analysis findings. After log transformation, the association between CEA level at prior and index FNA was moderate (R 2  = 0.626; P < .001), but cystic fluid CEA classification with a cutoff value of 192 ng/mL changed in 17 patients (20%), without significant changes in EUS findings., Conclusions: Repeat surveillance EUS-FNA resulted in stable CEA levels in the majority of patients, with spurious fluctuations of CEA in approximately 20% of patients. These data call into question any clinical significance attributed to an isolated interval rise in CEA level, especially in light of a stable EUS examination., (Copyright © 2016. Published by Elsevier Inc.)

Sarcopenia following liver surgery has been reported as a predictor of poor prognosis. Here we investigated predictors of outcomes in patients with hepatocellular carcinoma (HCC) and attempted to establish a new comprehensive preoperative assessment protocol. We retrospectively analyzed the cases of 254 patients who underwent curative hepatectomy for HCC with Child-Pugh classification A at our hospital between January 2007 and December 2013. Sarcopenia was evaluated by computed tomography measurement. The influence of sarcopenia on outcomes was evaluated. We used multivariate analyses to assess the impact of prognostic factors associated with outcomes, including sarcopenia. Of the 254 patients, 118 (46.5% ) met the criteria for sarcopenia, and 32 had an American Society of Anesthesiologists (ASA) physical status 3. The sarcopenic group had a significantly lower 5-year overall survival rate than the non-sarcopenic group (58.2% vs. 82.4% , p＝0.0002). In multivariate analyses of prognostic factors, sarcopenia was an independent predictor of poor survival (hazard ratio [HR]＝2.28, p＝0.002) and poor ASA status (HR＝3.17, p＝0.001). Sarcopenia and poor ASA status are independent preoperative predictors for poor outcomes after hepatectomy. The preoperative identification of sarcopenia and ASA status might enable the development of comprehensive approaches to assess surgical eligibility.

Background: Pancreatico-biliary malignancies exhibit similar characteristics, including obesity-related features and poor prognosis, and require new treatment strategies. Oxidative stress is known to induce DNA damage and carcinogenesis, and its reduction is viewed as being favorable. However, it also has anti-infection and anti-cancer functions that need to be maintained. To reveal the effect of oxidative stress on cancer progression, we evaluated oxidative stress and anti-oxidative balance in pancreatic cancer (PC) and cholangiocarcinoma (CC) patients, as well as the effect of add-on antioxidant treatment to chemotherapy in a mouse cholangiocarcinoma model., Methods: We recruited 84 CC and 80 PC patients who were admitted to our hospital. Serum levels of reactive oxygen metabolites (ROM) and the anti-oxidative OXY-adsorbent test were determined and the balance of these tests was defined as an oxidative index. A diabetic mouse-based cholangiocarcinoma model was utilized to evaluate the effects of add-on antioxidant therapy on cholangiocarcinoma chemotherapy., Results: Serum ROM was higher and anti-oxidant OXY was lower in CC patients with poor outcomes. These parameters were not significantly different in PC patients. In mice, vitamin E administration induced antioxidant hemeoxygenase (HO)-1 protein expression in cancer tissue, while the number of stem-like cells increased. l-carnitine administration improved intestinal microbiome and biliary acid balance, upregulated the hepatic mitochondrial membrane uptake related gene Cpt1 in non-cancerous tissue, and did not alter stem-like cell numbers., Conclusion: Oxidative stress balance was dysregulated in cholangiocarcinoma with poor outcome. The mitochondrial function-supporting agent l-carnitine is a good candidate to control oxidative stress conditions.

The operative mortality and morbidity of pancreaticoduodenectomy (PD) remain high. We analyzed PD patients' clinical characteristics and surgical outcomes and discuss how PD clinical outcomes could be improved. We retrospectively reviewed the cases of 400 patients who underwent a PD between January 1998 and April 2014 at Okayama University Hospital, a very-high-volume center. We identified and compared the clinical outcomes between two time periods (period 1: 1998-2006 vs. period 2: 2007-2014). The total postoperative mortality and major complication rates were 0.75% and 15.8% , respectively, and the median postoperative length of stay (LOS) was 32 days. Subsequently, patients who underwent a PD during period 2 had a significantly shorter LOS than those who underwent a PD during period 1 (29 days vs. 38.5 days, p＜0.001). The incidence of mortality and major complications did not differ between the two periods. In our multivariate analysis, period 1 was an independent factor associated with a long LOS (p＜0.001). The improvement of the surgical procedure and perioperative care might be related to the shorter LOS in period 2 and ot the consistently maintained low mortality rate after PD. The development of multimodal strategies to accelerate postoperative recovery may further improve PD's clinical outcomes.

Background and Aim: The gastric enteric nervous system (GENS) is organized into the submucosal plexus and the myenteric plexus that regulate muscle activity and mucosal functions, respectively. A non-invasive, in vivo visualization of GENS was not possible until recent introduction of needle-based confocal laser endomicroscopy (nCLE). Our aim was to determine the feasibility of in vivo visualization of GENS in the porcine stomach using endoscopic ultrasound (EUS) guided nCLE and local injection of molecular neuronal probe NeuroTrace., Methods: In anesthetized pigs during endoscopy, NeuroTrace was injected into the submucosa and muscularis propria of distal, and proximal stomach under EUS guidance and nCLE imaging was performed using the Cellvizio AQ Flex probe. After euthanasia, transmural gastric specimens from the areas of NeuroTrace injection were obtained for histology. We performed quantitative analysis of nCLE images recorded during in vivo studies: histologic evaluation of unstained specimens under fluorescence microscope for NeuroTrace localization. We also performed immunostaining of these specimens for nerve growth factor (NGF). In in vitro studies, we examined the uptake of NeuroTrace by glial cells., Results: The nCLE imaging successfully visualized neuronal cells and nerve fibers in distinctive image patterns. Fluorescence microscopy of mucosal sections showed that in vivo-injected NeuroTrace was retained in GENS components. NGF was strongly expressed in neural and glial cells, and the pattern of NGF staining was similar to that of NeuroTrace staining., Conclusions: This study demonstrates for the first time that combined use of EUS-guided nCLE and NeuroTrace is capable to visualize GENS., (© 2015 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Background: The purpose of this study is to determine the effects of anti-high mobility group box 1 (HMGB1) monoclonal antibody (mAb) on ischemia/reperfusion injury (IRI) and the mode of liver regeneration., Methods: Rats underwent 70% hepatectomy with IRI caused by clamping the hepatoduodenal ligament for 20 minutes, followed by the administration of anti-HMGB1 mAb immediately before declamping the hepatoduodenal ligament. Five animals were used for each time point. We then evaluated IRI, regeneration parameters and the status of HMGB1 in remnant livers., Results: The anti-HMGB1 mAb significantly ameliorated the degree of IRI in the remnant livers in association with the downregulation of HMGB1 protein. The ratio of Ki67-positive hepatocytes at 48 hours after 70% hepatectomy was significantly improved. Mean hepatocyte size was significantly reduced and cyclin-dependent kinase inhibitor 1 expression was significantly attenuated., Conclusions: Anti-HMGB1 mAb ameliorated IRI and improved the mode of liver regeneration after IRI followed by 70% hepatectomy in rats., (Copyright © 2016 Elsevier Inc. All rights reserved.)

An epidermoid cyst arising within an intrapancreatic accessory spleen (ECIAS) is rare, and also difficult to correctly diagnose before surgery. It is mostly misdiagnosed as a cystic tumor, such as a mucinous cystic neoplasm or as a solid tumor with cystic degeneration, such as a neuro endocrine tumor. We herein report a case of ECIAS and also perform a literature review of 35 reports of ECIAS. Although the preoperative diagnosis of ECIAS using conventional imaging is relatively difficult to make, careful preoperative examinations of the features on computed tomography and magnetic resonance imaging could lead to a correct preoperative diagnosis of ECIAS which might thereby reduce the number of unnecessary resections.

An 87-year-old woman on oral prednisolone was diagnosed with a cholecystoduodenal fistula (CDF) caused by a cytomegalovirus-associated duodenal ulcer (DU) and was managed conservatively. A CDF caused by a DU is extremely rare. Although surgical repair is recommended for the treatment of a CDF caused by cholecystolithiasis, appropriate treatment for CDF caused by a DU remains controversial. This case report of a CDF caused by a DU suggests that conservative treatment is feasible in the absence of DU-associated complications, such as an untreatable hemorrhage or obstruction; this finding is compatible with previously reported cases that were conservatively treated.

Background and Aims: The GI tract is innervated by the autonomic enteric nervous system, mainly composed of submucosal Meissner's plexus and myenteric Auerbach's plexus, which is essential for motility, blood flow regulation, and secretory functions. In vivo visualization of the esophageal enteric nervous system (EENS) during endoscopy has not been possible without invasive mucosal resection. This study aimed to visualize the EENS without mucosal resection, in vivo by using the novel probe, needle-based confocal laser-induced endomicroscopy (nCLE) with a fluorescence neuronal probe, NeuroTrace, under EUS guidance and to evaluate the feasibility of ex vivo imaging of the neuronal network in submucosal biopsy samples acquired at endoscopy., Methods: Four Yorkshire pigs were anesthetized and examined. In vivo experiment: During endoscopy, NeuroTrace was injected into the submucosa and muscularis propria of the middle and distal esophagus under EUS guidance, and nCLE imaging was performed. Ex vivo experiment: Submucosal tissue biopsy specimens from the porcine esophagus were obtained for ex vivo evaluation by using a "through-the-needle" forceps technique. After incubation of the samples in NeuroTrace solution, pCLE was used to visualize the EENS elements in the tissue., Results: Imaging of the EENS network by using EUS-guided nCLE was successful, both within the submucosa and the muscularis propria, and clearly visualized neuronal cells, glial cells, nerve bundles, and nerve fibers provided distinctive image patterns with excellent imaging quality. The use of the "through-the-needle" forceps technique achieved ex vivo images similar to those acquired in vivo., Conclusions: EUS-guided in vivo imaging of the enteric nervous system is feasible without mucosal resection and provides a novel ex vivo imaging alternative for human application. These novel, minimally invasive imaging approaches could be of tremendous diagnostic value to better characterize and explore the EENS of the GI tract., (Copyright © 2015 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.)