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Lymph node metastasis (LNM) is one of the most adverse prognostic factors in extrahepatic cholangiocarcinoma (EHCC) cases. As next-generation sequencing technology has become more widely available, the genomic profile of biliary tract carcinoma has been clarified. However, whether LNMs have additional genomic alterations in patients with EHCC has not been investigated. Here, we aimed to compare the genomic alterations between primary tumors and matched LNMs in patients with EHCC.Sixteen patients with node-positive EHCCs were included. Genomic DNA was extracted from tissue samples of primary tumors and matched LNMs. Targeted amplicon sequencing of 160 cancer-related genes was performed.Among the 32 tumor samples from 16 patients, 91 genomic mutations were identified. Genomic mutations were noted in 31 genes, including TP53, MAP3K1, SMAD4, APC, and ARID1A. TP53 mutations were most frequently observed (12/32; 37.5%). Genomic mutation profiles were highly concordant between primary tumors and matched LNMs (13/16; 81.3%), and an additional genomic mutation of CDK12 was observed in only one patient.Genomic mutations were highly concordant between primary tumors and matched LNMs, suggesting that genotyping of archived primary tumor samples may help predict genomic mutations of metastatic tumors in patients with EHCC.

Pancreatic ductal adenocarcinoma (PDA) is a fatal cancer for which even unfavorable clinicopathological factors occasionally fail to preclude long-term survival. We sought to establish a scoring system that utilizes measurable pre-intervention factors for predicting survival following surgical resection.We retrospectively analyzed 34 patients who died from short-term recurrences and 32 long-term survivors among 310 consecutively resected patients with PDA. A logistic regression model was used to define factors related to clinical parameters, molecular profiles of 18 pancreatic cancer-associated genes, and aberrant expression of major tumor suppressors.Carbohydrate antigen 19-9 (CA19-9) had the best ability to classify patients with short-term recurrence and long-term survivors [odds ratio 21.04, 95% confidence interval (CI) 4.612-96.019], followed by SMAD4 and TP53 mutation scoring (odds ratio 41.322, 95% CI 3.156-541.035). Missense TP53 mutations were strongly associated with the nuclear expression of p53, whereas truncating mutations were associated with the absence of nuclear p53. The former subset was associated with a worse prognosis. The combination of aberrant SMAD4 and mutation types of TP53 exhibited a better resolution for distinguishing patients with short-term recurrences from long-term survivors (compared with the assessment of the number of mutated KRAS, CDKN2A, TP53, and SMAD4 genes). Calibration of mutation scores combined with CA19-9 in a logistic regression model setting demonstrated a practical effect in classifying long survivors and patients with early recurrence (c-statistic = 0.876).Genetic information, i.e., TP53 mutation types and SMAD4 abnormalities, combined with CA19-9, will be a valuable tool for improving surgical strategies for pancreatic cancer.

Purpose This study evaluated the short-term outcomes and prognosis after laparoscopic total gastrectomy (LTG) in elderly patients aged >= 80 years in a multicenter retrospective cohort study using propensity score matching. Methods We retrospectively enrolled 440 patients who underwent curative LTG for gastric cancer at six institutions between January 2004 and December 2018. Patients were categorized into an elderly patient group (EG; age >= 80 years) and non-elderly patient group (non-EG; age < 80 years). Patients were matched using the following propensity score covariates: sex, body mass index, American Society of Anesthesiologists physical status, extent of lymph node dissection, and Japanese Classification of Gastric Carcinoma stage. Short-term outcomes and prognoses were compared. Results We identified 37 propensity score-matched pairs. The median operative time was significantly shorter, and postoperative stay was longer in the EG. In terms of postoperative outcomes, the rates of all complications were comparable. The median follow-up period of the EG and non-EG was 11.5 (1-106.4) months and 35.7 (1-110.0) months, respectively; there were significant differences in 5-year overall survival between the two groups (EG, 58.5% vs. non-EG, 91.5%; P = 0.031). However, there were no significant differences in 5-year disease-specific survival (EG, 62.1% vs. non-EG, 91.5%; P = 0.068) or 5-year disease-free survival (EG, 52.9% vs. non-EG, 60.8%; P = 0.132). Conclusions LTG seems to be safe and feasible in elderly patients. LTG had a limited effect on morbidity, disease recurrence, and survival in elderly patients. Therefore, age should not prevent elderly patients from benefitting from LTG.

Purpose Delirium is associated with longer hospital stays and increased medical costs and mortality. This study explored the risk factors for postoperative delirium in gastroenterological surgery and investigated the association between qualitative changes in risk factors and the incidence of postoperative delirium. Methods A total of 418 patients > 18 years old who underwent gastroenterological surgery at our department between April 2018 and September 2019 were included. Risk factors were identified by comparing patients with and without postoperative delirium. Continuous variables were evaluated graphically using cubic spline curves. A logistic regression analysis was performed to assess independent risk factors. Results The incidence of postoperative delirium was 6.9%. The cubic spline curve showed that the incidence of postoperative delirium began to increase at 50 years old and increased sharply at 70 years old. A multiple logistic regression analysis of patients > 50 years old identified 5 risk factors: age >= 70 years, preoperative serum albumin 50 years old undergoing gastroenterological surgery.

Background The aim of this study was to evaluate the long-term nutritional state of patients with gastric cancer who underwent laparoscopic proximal gastrectomy with double-tract reconstruction (LPG-DTR) using oblique jejunogastrostomy method (OJG). Methods Medical records of 38 patients who underwent LPG-DTR using OJG (21 patients) or laparoscopic total gastrectomy with Roux-en-Y reconstruction (LTG-RY) (17 patients) between October 2011 and March 2018 were retrospectively reviewed. In these patients, clinicopathologic variables were analyzed using propensity score matching for age, sex, body mass index, American Society of Anesthesiologists physical state, clinical stage, and lymph node dissection. Operative outcomes and postoperative nutritional status were compared between the 2 groups. Results A total of 16 patients were matched to analyze the LPG-DTR and LTG-RY groups. The serum hemoglobin, total protein, and albumin levels at 12 months postoperatively (P=0.008, 0.034, and 0.049) and serum hemoglobin level at 24 months (P=0.025) in the LPG-DTR group was significantly superior to those in the LTG-RY group. Conclusions The postoperative nutritional status as long-term outcomes of patients who underwent LPG-DTR using OJG was significantly superior to those who underwent LTG-RY. The results hereby presented suggest that LPG-DTR using OJG for gastric cancer produces better postoperative nutritional status.

Pancreatic neuroendocrine microadenoma (NEMA) is a nonfunctioning neuroendocrine tumor of less than 5 mm. Most studies of NEMA were based on autopsies, and few reports have revealed the clinical frequency of NEMA. We investigated the clinicopathological features of NEMA.The pathological results of the pancreatic resection specimens of patients, older than 18 years, who underwent pancreatic resection at Hokkaido University Hospital between April 2008 and December 2020 were retrospectively reviewed. The NEMAs were re-examined in detail and examined by immunohistochemical staining.Among 850 patients enrolled in this study, 24 NEMAs were identified in 12 patients (1.4%). Of the 12 patients, 2 patients had multiple endocrine neoplasia type 1, and the others had no hereditary disease, including 2 patients with multiple NEMAs. A difference in the number of NEMA was observed between patients with multiple endocrine neoplasia type 1 and sporadic NEMA. Intratumoral Ki-67 heterogeneity was correlated with the Ki-67 index. One grade 2 NEMA (Ki-67 index, 4.6%) was detected, but ATRX and DAXX labeling showed intact nuclear protein expression.Multiple sporadic NEMAs and grade 2 NEMAs were observed, suggesting that NEMA may have malignant potential. Thus, NEMAs should be carefully monitored for lymph node metastasis and postoperative recurrence.

The pathological tumor classification of distal cholangiocarcinoma in the American Joint Committee on Cancer (AJCC) Cancer Staging Manual 8th edition is based on invasive depth, whereas that of perihilar cholangiocarcinoma (PHCC) continues to be layer-based. We aimed to clarify whether invasive depth measurement based on invasive tumor thickness (ITT) could help determine postoperative prognosis in patients with PHCC. We enrolled 184 patients with PHCC who underwent hepatectomy plus extrahepatic bile duct resection or hepatopancreatoduodenectomy with curative intent. ITT was measured using simple definitions according to the sectioning direction or gross tumor pattern. The median ITT was 5.8 mm (range 0.7–15.5). Using the recursive partitioning technique, ITT was classified into grades A (ITT

Background Lymph node (LN) metastasis in pancreatic body-tail cancer is a poor prognostic factor and the optimal LN dissection area for distal pancreatectomy (DP) remains unclear. Lymphatic flow from the tumors is thought to depend on the tumor sites. We examined LN metastasis frequency based on tumor site and recurrent patterns post-DP. Methods With a retrospective, single institutional study, we examined 100 patients who underwent DP as an upfront surgery for pancreatic cancer over 17 years. Tumor sites were classified as tumor confined to pancreatic body (and neck) (Pb(n) ); and pancreatic tail (Pt). We compared metastatic LN and recurrence patterns based on tumor site. The median overall survival (OS) and disease-free survival (DFS) were analyzed. Results LN metastasis occurred in 59/100 (59.0%), with 23 and 25 tumors located in the Pb(n) , and Pt, respectively. Those with the tumor in Pt had metastases to #10, #11d/p, and #18 LN mainly. However , the patients with the Pb(n) tumor had metastases to #8a/p, #11p, and #14p/d LN. There was no metastasis to #10 and #11d LN . The OS and DFS were 34 and 15 months, respectively. No significant difference was found in the OS, DFS, and recurrence patterns based on tumor sites. Conclusion Differences in metastatic LN sites were observed in pancreatic body-tail cancer when tumors were confined to the left or right of the left aortic edge. Although it is necessary to validate this finding with a large-scale study, organ-preserving DP might be a treatment option for selected patients depending on the tumor sites.

Objectives Neoadjuvant chemotherapy (NAC) has improved overall survival in patients with pancreatic ductal adenocarcinoma (PDAC), but its effects on immune gene signatures are unknown. Here, we examined the immune transcriptome after NAC for PDAC. Methods Resected tumor specimens were obtained from 140 patients with PDAC who received surgery first (n = 93) or NAC (n = 47). Six patients were randomly selected from each group, and RNA was extracted from tumor tissues. We compared 770 immune-related genes among the 2 groups using nCounterPanCancer Immune Profiling (NanoString Technologies, Seattle, Wash). Gene clusters were classified into 14 immune function groups based on gene ontology argolism by nSolver 4.0 software (NanoString Technologies), and corresponding immune cell function scores were compared. Results Eleven genes (LY86, SH2D1A, CD247, TIGIT, CR2, CD83, LAMP3, CXCR4, DUSP4, SELL, and IL2RA) were significantly downregulated in the NAC group. Gene expression analysis showed that the functions of regulatory T cells, B cells, and natural killer CD56 dim cells were significantly decreased in the NAC group. Conclusions Neoadjuvant chemotherapy may suppress regulatory T cells and B-cell function in the PDAC microenvironment. The 11 identified genes could be useful for predicting the efficacy of NAC and could be therapeutic targets for PDAC.

Over the past 30 years, the therapeutic outcome for pancreatic ductal adenocarcinoma (PDAC) has remained stagnant due to the lack of effective treatments. We performed a genome-wide analysis to identify novel therapeutic targets for PDAC. Our analysis showed that Homo sapiens chromosome 16 open reading frame 74 (C16orf74) was upregulated in most patients with PDAC and associated with poor prognosis. Previously, we demonstrated that C16orf74 interacts with the catalytic subunit alpha of protein phosphatase 3 and plays an important role in PDAC invasion. However, the pathophysiologic function of C16orf74 is still unclear. In this study, through the analysis of C16orf74 interaction, we demonstrate a new strategy to inhibit the growth and invasion of PDAC. C16orf74 exists in the homodimer form under the cell membrane and binds integrin αVβ3 and is also involved in invasion by activating Rho family (Rac1) and MMP2. Considering that this dimeric form was found to be involved in the function of C16orf74, we designed an 11R-DB (dimer block) cell-permeable dominant-negative peptide that inhibits the dimer form of C16orf74. 11R-DB suppressed invasion and proliferation of PDAC cell lines by inhibiting phosphorylation of Akt and mTOR and also by inactivation of MMP2. 11R-DB also showed antitumor effects in an orthotopic xenograft model and peritoneal metastasis model. Thus, this study demonstrates that dimerized C16orf74, present in the cell membrane, is involved in pancreatic cancer invasion and proliferation. In addition, the C16orf74 dimer block cell-permeable peptide (11R-DB) has a potent therapeutic effect on PDAC in vitro and in vivo.

Bacteremia occurring after extensive hepatic resection and biliary reconstruction (Hx + Bx) for biliary cancer is a critical infectious complication. This study evaluated postoperative bacteremia and examined the potential usefulness of surveillance cultures.We retrospectively reviewed 179 patients who underwent Hx + Bx for biliary cancer from January 2008 to December 2018 in our department.Bacteremia occurred in 41 (23.0%) patients. Patients with bacteremia had a longer operation time and more frequent intraoperative transfusion and more frequently developed organ/space surgical site infection (SSI) than those without bacteremia. The most frequently isolated bacterial species from blood cultures were Enterococcus faecium (29.3%), Enterobacter cloacae (24.4%), and Enterococcus faecalis (22.0%). The SIRS duration of bacteremia associated with organ/space SSI was significantly longer than that of other infectious complications (median 96 h vs. 48 h; p = 0.043). Bacteremia associated with organ/space SSI occurred most often by postoperative day (POD) 30. The concordance rate of bacterial species between blood and surveillance cultures within POD 30 was 67-82%.Bacteremia associated with organ/space SSI required treatment for a long time and typically occurred by POD 30. Postoperative surveillance cultures obtained during this period may be useful for selecting initial antibiotic therapy because of their high concordance rate with blood cultures.

This retrospective study aimed to clarify whether the postoperative prognosis differs between right and left hepatectomy for Bismuth type I/II perihilar cholangiocarcinoma. Preoperative images of 195 patients with perihilar cholangiocarcinoma were reexamined. Patients with Bismuth type I/II perihilar cholangiocarcinoma without a difference in extraductal tumor invasion between the right and left sides of the hepatic portal region were classified into those undergoing left (L group) or right (R group) hepatectomy. Twenty-three patients (11.8%) were classified into the L group and 33 (16.9%) into the R group. All eight patients with pTis/1 belonged to the L group. The L group had significantly less liver failure than the R group (p = 0.001). One patient (4.3%) in the L group and four patients (12.1%) in the R group died from postoperative complications. Among 48 patients with pT2, the L group tended to have better overall survival (median, 12.2 vs. 5.6 years; p = 0.072), but not recurrence-free survival (median, 9.1 vs. 3.6 years; p = 0.477), in comparison to the R group. Postoperative survival after left hepatectomy for Bismuth type I/II perihilar cholangiocarcinoma is expected to be as long as that after right hepatectomy.

Background There is no international consensus concerning the role of surgical treatment of metastatic pancreatic ductal adenocarcinoma (mPDAC), but favorable prognoses can be expected for highly selected patients. Methods A comprehensive literature search of the PubMed and Cochrane databases was conducted using combinations of keywords to 4 July 2018. Eligible studies were those reporting on patients with histologically confirmed mPDAC undergoing surgery with curative intent. We excluded case reports with fewer than five patients, insufficient descriptions of survival data, and palliative or cytoreductive surgery as well as studies that assessed para-aortic lymph node metastasis or peritoneal washing cytology. Results Thirteen studies were deemed eligible, and six studies were identified from their references. The studies involved 428 patients who underwent surgical resection for liver metastases (n = 343), lung metastases (n = 57), and peritoneal dissemination (n = 28). Median overall survival (OS) in patients with synchronous liver metastases who underwent conversion surgery following favorable response to initial chemotherapy was 27 or 34 months, and peritoneum metastases was 28 months. Median OS after the initial treatment was varied from 51 to 121 months in metachronous lung metastasis and from 24 to 40 months in metachronous liver metastasis, respectively. Conclusion Encouraging OS was indicated in patients with synchronous mPDAC of liver and peritoneum who underwent conversion surgery. Metastasectomy for metachronous lung and liver oligometastases could be considered a practical treatment option.

The pT classification of the 8th American Joint Committee on Cancer (AJCC) for distal cholangiocarcinoma (DCC) is classified according to depth of invasion (DOI), which is the distance from the basal lamina to the most deeply advanced tumor cells. The Nagoya group proposed a new T classification for DCC based on invasive tumor thickness (ITT), which is the maximal vertical distance of the invasive cancer component (the ITT grade). In this study, we aimed to validate the ITT grade for the next pT classification of DCC in 110 patients. ITT could be measured in all patients, but DOI could only be measured in 62 (56%) patients. According to ITT grade, patients were classified into grades A to D, as follows: grade A, ITT1 mm (n=9); grade B, ITT 1 mm or more but5 mm (n=35); grade C, ITT 5 mm or more but10 mm (n=40); and grade D, ITT 10 mm or greater (n=26). The median overall survival times in patients with ITT grades A, B, C, and D were 12.8, 5.7, 3.7, and 2.0 years, respectively. ITT grade could discriminate postoperative survivals between grades. On multivariate analysis, ITT grade, regional lymph node metastasis, and distant metastasis were selected as independent prognostic factors. In summary, our results showed that ITT grade was a suitable alternative to DOI for pT classification in the next edition of the AJCC for DCC.

Background: Upfront surgery is recommended in patients with potentially resectable pancreatic ductal adenocarcinoma (R-PDAC) by National Comprehensive Center Network (NCCN) guidelines. However, even among R-PDACs, there is a subset that demonstrates extremely poor prognosis. The purpose of this study was to identify preoperative prognostic factors for upfront surgical resection of R-PDACs. Methods: The records of 278 consecutive patients with PDAC who underwent curative resection between 2001 and 2015 in a single institution were retrospectively reviewed. Preoperative factors to predict prognosis in patients with R-PDAC according to the NCCN guidelines were analyzed. Results: Of the 278 patients who underwent resection, 153 R-PDACs received upfront surgery with a median survival time (MST) of 26.4months. Tumor location (pancreatic head) (odds ratio [OR] 1.97, 95% confidence interval [CI] 1.14-3.40; P=0.015), preoperative cancer antigen 19-9 (CA19-9) >100U/mL (OR 1.92, 1.31-2.80; P=0.0009), and tumor size >20mm (OR 1.50, 1.02-2.19; P=0.038) were identified as preoperative independent predictive risk factors for poor prognosis in patients with R-PDACs. In the patients with R-PDAC, 5-year survival was 60.7%, 21.5%, and 0% in patients with 0, 1 or 2, and 3 risk factors, respectively. There were significant differences in overall survival between the three groups (P

Background: This study aimed to compare the postoperative outcomes after laparoscopic total gastrectomy (LTG) with esophagojejunostomy (EJS) performed using the overlap method or the functional method in a multicenter retrospective study with propensity score matching. Methods: We retrospectively enrolled all patients who underwent curative LTG for gastric cancer at 6 institutions between January 2004 and December 2018. Patients were categorized into the overlap group (OG) or functional group (FG) based on the type of anastomosis used in EJS. Patients in the groups were matched using the following propensity score covariates: age, sex, body mass index, American Society of Anesthesiologists physical status, extent of lymph node dissection, and Japanese Classification of Gastric Carcinoma stage. The surgical results and postoperative outcomes were compared. Results: We identified 69 propensity score-matched pairs among 440 patients who underwent LTG. There was no significant between-group difference in the median operative time, intraoperative blood, or number of lymph nodes resected. In terms of postoperative outcomes, the rates of all complications [Clavien-Dindo (CD) classification >= II; OG 13.0 vs. FG 24.6%, respectively; P=0.082], complications more severe than CD grade III (OG 8.7 vs. FG 18.8%, respectively; P=0.084), and the occurrence of EJS leakage and stenosis more severe than CD grade III (OG 7.3% vs. FG 2.9%, P=0.245; OG 1.5 vs. FG 8.7%, P=0.115, respectively) were comparable. The median follow-up period was 830 days (range, 18 to 3376 d), and there were no differences in overall survival between the 2 groups. Conclusions: There was no difference in surgical outcomes and overall survival based on the type of anastomosis used for EJS after LTG. Therefore, selection of anastomosis in EJS should be based on each surgeon's preference and experience.

Organ-preserving surgery (OPS) has been accepted for pancreatic neuroendocrine neoplasms, particularly for the management of small tumors. This study aimed to analyze the surgical outcome following this treatment at our institute, focusing on the perioperative factors and postoperative locoregional recurrence.We analyzed 71 consecutive patients with no synchronous liver metastasis. These patients were classified into 1 of 2 groups: the standard operation group (SOG, 41 patients) with prophylactic regional lymph node dissection and the organ-preserving surgery group (OPG, 30 patients). We performed OPS based on size criteria (tumor size1.5 cm in nonfunctional pancreatic neuroendocrine neoplasms and2 cm in insulinoma with no evident bulky lymph node swelling on preoperative imaging).The median follow-up periods were 37 months. The OPG included enucleation, partial resection, proximal parenchymal pancreatectomy, central pancreatectomy, spleen-preserving distal pancreatectomy, and Warshaw operation. The SOG included pancreatoduodenectomy and distal pancreatectomy, showing no statistically significant differences between the 2 groups in terms of operation time, hospitalization duration, and postoperative complications. Ten patients showed lymph node metastasis (25%) only in the SOG. There were no locoregional recurrent cases in the OPG.In selected patients, OPS may be effective based on the appropriate tumor size criteria.

Previous studies have shown that curative resection (R0 resection) was among the most crucial factors for the long-term survival of patients with PHCC. To achieve R0 resection, we performed the transhepatic direct approach and resection on the limits of division of the hepatic ducts. Although a recent report showed that the resection margin (RM) status impacted PHCC patients’ survival, it is still unclear whether RM is an important clinical factor. To describe a technique of transhepatic direct approach and resection on the limit of division of hepatic ducts, investigate its short-term surgical outcome, and validate whether the radial margin (RM) would have a clinical impact on long-term survival of perihilar cholangiocarcinoma (PHCC) patients. Consecutive PHCC patients (n = 211) who had undergone major hepatectomy with extrahepatic bile duct resection, without pancreaticoduodenectomy, in our department were retrospectively evaluated. R0 resection rate was 92% and 86% for invasive cancer-free and both invasive cancer-free and high-grade dysplasia-free resection, respectively. Overall 5-year survival rate was 46.9%. Univariate analysis showed that preoperative serum carcinoembryonic antigen level (> 7.0 mg/dl), pathological lymph node metastasis, and portal vein invasion were independent risk factors, but R status on both resection margin and bile duct margin was not an independent risk factor for survival. The transhepatic direct approach to the limits of division of the bile ducts leads to the highest R0 resection rate in the horizontal margin of PHCC. Further examination will be needed to determine the adjuvant therapy for PHCC to improve patient survival.

Diagnosing peritoneal dissemination is essential for selecting the appropriate therapeutic strategy for patients with pancreatic cancer. Intraoperative laparoscopic diagnosis enables the selection of less invasive surgical strategies. Photodynamic diagnosis using 5-aminolevulinic acid may improve gastrointestinal cancer diagnostic accuracy, although weak fluorescence is not easily detected. Here we aimed to improve this sensitivity using laparoscopic spectrophotometry.Photodynamic diagnosis was performed using serial dilutions of protoporphyrin IX, and its detectability using laparoscopic spectrophotometry was compared with that using naked-eye observation. Five-aminolevulinic acid-photodynamic diagnosis was performed for pancreatic cancer cell lines, and a murine peritoneal disseminated nodule model was established. We compared laparoscopic spectrophotometry and naked-eye observation results using white and fluorescent lights and compared them to routine histopathological examination results. Photodynamic diagnoses were made in 2017 and 2018 in eight patients with pancreatic cancer.Weaker fluorescence of the diluted protoporphyrin IX samples was better detected with spectrophotometry than with naked-eye observation. Moreover, a spectrograph of protoporphyrin IX in multiple cell lines was detected by spectrophotometry. In the murine model, the detection rates were 62 %, 78 %, and 90 % for naked-eye observation with white light, fluorescent light, and spectrophotometry, respectively. Comparisons of fluorescent light-negative peritonea with and without pathological metastases showed significantly higher spectrophotometric intensities in the former (P0.010). In clinical studies, three fluorescent light-negative spectrophotometry-positive pathologically metastatic lesions were observed.Laparoscopic spectrophotometry in the murine model and extraperitoneally photodynamic diagnoses using spectrophotometry in clinical practice are sensitive photodynamic diagnostic techniques.

/ObjectivesThe aim of this study was to clarify the oncological outcomes of patients with intraductal papillary mucinous neoplasm (IPMN) who underwent limited resection (LR).This retrospective study analyzed the data of 110 patients with IPMN. Patients with IPMN without a history of pancreatitis who had neither tumor infiltration nor regional lymph node swelling on imaging findings underwent LR. We assessed the oncological outcomes of LR for patients with IPMN by comparing the surgical outcomes of LR and standard resection.LR was performed in 50 patients (45.5%), including duodenum-preserving pancreatic head resection (n = 31), middle-pancreatectomy (n = 12), spleen-preserving distal pancreatectomy (n = 3), total parenchymal pancreatectomy (n = 3), and partial resection (n = 1). In the LR group, 18 patients had postoperative complications of Clavien-Dindo classification ≥ IIIa. After histopathological examination, the presence of high-grade dysplasia (HGD) and invasive carcinoma (IC) were observed in nine and three patients, respectively, in the LR group, and eight and 22 patients, respectively, in the standard resection group. There was a significant difference in the histopathological diagnosis of IC between the two groups (p0.001). Finally, in the LR group, postoperative recurrences occurred in three patients, and the 5-, 10-, and 15-year disease-specific survival rates were all 97.0%.For patients with IPMN judged to have no infiltrating lesions based on the detailed imaging examination, LR is acceptable and may be considered as an alternative to standard resection.

Postoperative pancreatic fistula is a main cause of fatal complications post-pancreatoduodenectomy. However, no universally accepted drainage management exists for clinically relevant postoperative pancreatic fistulas. We retrospectively evaluated cases in which drain contrast imaging was used to determine its utility in identifying clinically relevant postoperative pancreatic fistulas post-pancreatoduodenectomy. Between January 2014 and December 2018, 209 consecutive patients who underwent pancreatoduodenectomy in our institute were retrospectively analyzed. Drain monitoring with contrast imaging was performed in 47 of the cases. We classified drain contrast type into three categories and evaluated postoperative outcome in each group: (1) fistulous tract group—only the fistula was contrasted; (2) fluid collection group – fluid collection connected to the drain fistula; and (3) pancreatico-anastomotic fistula group—fistula connected to the digestive tract. The durations of postoperative hospital stay and drainage were significantly shorter in the fistulous tract group than in the fluid collection group (31 vs. 46 days, p = 0.0026; and 12 vs. 38 days, p

Background: Conversion surgery (CS) is expected as a new therapeutic strategy for patients with unresectable pancreatic cancer (UR-PC). We analyzed outcomes of CS for patients with UR-PC and evaluated the survival benefit of CS. Methods: Thirty-four patients diagnosed with UR-PC according to the National Comprehensive Cancer Network guideline underwent CS in our hospital. Resectability was considered by multimodal images in patients who underwent nonsurgical treatment (NST) for more than 6 months. CS was performed only in patients who were judged to be able to undergo R0 resection. Results: Twenty-six patients had locally advanced PC, and eight had distant metastases. The median duration of NST was 9 (range 5-44) months. R0 resection was achieved in 30 patients (88.2%). Six patients (17.6%) showed Evans grade ≥III. Three- and 5-year overall survival (OS) rates from initial treatment were 74% and 56.9%, respectively, with median survival time (MST) of 5.3 years. The actual 5-year OS rate in 19 patients was 47.4% with an MST of 4.0 years. Patients with Evans grade ≥III had a better prognosis than those with Evans grade

Background We have reported the effectiveness of laparoscopy-assisted stomach-partitioning gastrojejunostomy Roux-en-Y reconstruction (LASPGJ-RY) for gastric outlet obstruction (GOO). The aim of this study was to evaluate the surgical outcomes of totally laparoscopic stomach-partitioning gastrojejunostomy Roux-en-Y reconstruction (TLSPGJ-RY) for GOO. Materials and methods This retrospective study enrolled 19 consecutive patients with GOO. Surgical outcomes of LASPGJ-RY (LA group; n=8) and TLSPGJ-RY (TL group; n=11) between January 2004 and 2015 were compared. The patients' background characteristics, operative findings, postoperative complications, and period to starting postoperative chemotherapy were examined. Results Eligible cases included 6 patients with gastric cancer, 4 with pancreatic cancer, 4 with duodenal cancer, 4 with urologic malignancies, and 1 with benign duodenal stenosis. The patients' background characteristics were not significantly different. In surgical outcomes, there were no significant differences in operating time, bleeding, complications (≥Clavien-Dindo grade IIIA), and postoperative hospital stay between the groups. The time to resume diet was significantly shorter in the TL group (median, 3 d; range, 3 to 6 d) than in the LA group (median, 5 d; range, 3 to 7 d; P=0.0093), and the number of patients who could receive chemotherapy after surgery was significantly higher in the TL group (P=0.039). Conclusions TLSPGJ-RY was a safe and feasible gastrojejunostomy procedure for GOO. TLSPGJ-RY might be useful for early resumption of oral intake after surgery.

Background: Post-hepatectomy liver failure (PHLF) is a serious complication after major hepatectomy with extrahepatic bile duct resection (Hx with EBDR) that may cause severe morbidity and even death. The purpose of this study was to compare several criteria systems as predictors of PHLF-related mortality following Hx with EBDR for perihilar cholangiocarcinoma (PHCC). Methods: The study cohort consisted of 222 patients who underwent Hx with EBDR for PHCC. We compared several criteria systems, including previously established criteria (the International Study Group of Liver Surgery (ISGLS) criterion; and the “50-50” criterion), and our institution’s novel systems “Max T-Bili” defined as total bilirubin (T-Bili) >7.3 mg/dL during post-operative days (POD) 1–7, and the “3-4-50” criterion, defined as total bilirubin >4 mg/dL and prothrombin time Results: Thirteen patients (5.8%) died from PHLF-related causes. The 3-4-50 criterion showed high positive predictive values (39.1%), the 3-4-50, Max T-Bili, and 50-50 criterion showed high accuracies (91.7, 86.9, and 90.5%, respectively) and varying sensitivities (69.2, 69.2, and 38.5% respectively). Conclusions: The 3-4-50, Max T-Bili, and 50-50 criterion were all useful for predicting PHLF-related mortality after Hx with EBDR for PHCC.

Background Whether to classify “advanced (subserosal layer or greater invasion)” biliary carcinoma centered in the cystic duct (BCCD) as gallbladder carcinoma (GBC) or perihilar cholangiocarcinoma (PHCC) remains unclear. Methods The clinicopathological features and overall survival (OS) of patients with advanced BCCD were examined through a comparison with those of patients with advanced PHCC and with GBC. Results 290 patients were classified as 199 PHCC, 44 GBC, and 47 BCCD. Patients with BCCD (median, 23 months) had significantly worse OS than those with PHCC (44 months, p = 0.030). OS of patients with BCCD, all of whom were classified as pT3 or pT4 by the American Joint Committee on Cancer (AJCC) classification of GBC, was similar to 27 patients with pT3 or pT4 GBC (23 months, p = 0.840). When the patients with BCCD were classified by the AJCC classification of PHCC, 36 were classified as pT2. OS among the patients with BCCD classified as pT2 by the PHCC classification (29 months) was significantly worse than that among patients classified as pT2 PHCC (48 months, p = 0.040). Conclusion These findings suggest that advanced BCCD is appropriately classified as a subtype of GBC because it can grow through the serosa.

Background: Proximal early gastric cancer is a good indication for totally laparoscopic proximal gastrectomy (TLPG) with double-tract reconstruction (DTR). However, when most of the dietary intake passes through the escape route of the jejunum, the functional benefits of proximal gastrectomy might be similar to those after total gastrectomy. Our DTR procedure was improved for easy passage through the remnant stomach. The purposes of this study were to present a novel technique for intracorporeal DTR using linear staplers after TLPG and to investigate surgical outcomes. Methods: DTR was performed using linear staplers only. A side-to-side jejunogastrostomy with twisting of both the remnant stomach and the anal jejunum was performed for the purpose of passing meals through the remnant stomach (an oblique jejunogastrostomy technique). The ten patients who underwent TLPG with DTR from January 2011 to August 2016 in Hokkaido University Hospital were retrospectively reviewed. Their clinicopathological characteristics and surgical and postoperative outcomes were collected and analyzed. Results: The median duration of operation was 285 (range 146-440) min. No patients required blood transfusions. The number of dissected lymph nodes was 32 (range 22-56). There were no intraoperative complications, and no cases were converted to open surgery. All the patients were pT1N0M0 stage IA. No anastomotic leakage or complications were detected. Postoperative gastrography after reconstruction showed that contrast medium flowed mainly to the remnant stomach. The average percentage body weight loss was 14.0 +/- 7.1% at 10 months. The average percentage decrease in serum hemoglobin was 5.4 +/- 10.4% at 12 months. Conclusions: This novel technique for intracorporeal DTR provided a considerable advantage by the passage of dietary intake to the remnant stomach after LPG.

The differences between perihilar cholangiocarcinoma (PHCC) and distal cholangiocarcinoma (DCC) regarding recurrence and the factors that affect recurrence after surgery are unclear. This study aims to investigate the differences in recurrence patterns between patients with PHCC and those with DCC after surgical resection with curative intent. It also investigates the risk factors associated with recurrence and survival thereafter. The postoperative courses of 366 patients with extrahepatic cholangiocarcinomas (EHCCs), including 236 with PHCC and 130 with DCC, who underwent surgical resections were investigated retrospectively. During follow-up, tumors recurred in 143 (60.6%) patients with PHCC and in 72 (55.4%) patients with DCC. Overall survival (OS) after surgery, recurrence-free survival (RFS), and OS after recurrence were similar for the patients with PHCC and those with DCC. The cumulative probability of recurrence declined 3 years after surgery in the patients with PHCC and those with DCC. A multivariable analysis determined that, among the patients with PHCC and those with DCC, regional lymph node metastasis was a significant risk factor associated with RFS. Ten patients with PHCC and eight patients with DCC with two or fewer sites of recurrence in a single organ underwent resections. A multivariable analysis determined that recurrent tumor resection was an independent prognostic factor associated with OS after recurrence in the patients with PHCC and those with DCC. Postoperative survival did not differ between the patients with PHCC and those with DCC. Frequent surveillances for recurrence are needed for 3 years after surgical resection of EHCCs. In selected patients, surgery for recurrent EHCCs might be associated with improved outcomes.

It has been clear that the clinical responses by applying immune checkpoint inhibitor alone are limited. To better improve this limited clinical response, combinational therapy has been focused. We recently reported the association between EMT related factors and PD-L1 expression in the extrahepatic hilar cholangiocarcinoma, and its role as a surrogate biomarker for patient prognosis. We here report clinical relevance of combinational therapy of HDAC inhibitors and anti-PD-L1 antibody as an immune checkpoint inhibitors.

A few studies have analysed the experiences of junior residents during the initial stages of their clinical training at community-based medical institutions for gaining initial experience as doctors using an associated learning theory framework. In this study, we investigated this learning process using an experiential learning model. The survey was administered through interviews and a written questionnaire to 10 junior residents involved in the initial postgraduate clinical training at two clinics in Tokyo operated by family physicians. The interview data were analysed qualitatively, whereas the results of the questionnaire, which included an experiential learning scale, were analysed quantitatively. In the qualitative analysis, 59 themes were identified and classified into reflective observation, abstract conceptualisation, and active experimentation, as featured in the experiential learning cycle. The average scores for experiential learning before and after training at a community-based medical institution, as measured based on the experiential learning scale, exhibited a significant increase after the training. Experiential learning of junior residents was observed in various situations during their training period at a community-based medical institution, where active experimentation was the most commonly observed form of experiential learning.

Background: It is often difficult to perform percutaneous radiofrequency ablation (RFA) for hepatic tumors beneath the diaphragm. Diaphragmatic thermal damage is one of the fatal late complications of percutaneous transdiaphragmatic RFA. Our experience with laparoscopic transthoracic transdiaphragmatic intraoperative RFA (LTTI-RFA) for hepatic tumors beneath the diaphragm is reported. Methods: Ten patients who underwent LTTI-RFA from 2009 to 2012 were evaluated. Two cases had concomitant partial hepatectomy, and one underwent RFA for two tumors at the same time. The diagnosis was hepatocellular carcinoma in eight cases and metastatic hepatic tumors in two cases. Nine of eleven tumors were located at segments 7 and 8. Nine tumors were less than 20 mm in diameter. The patients were placed in the half left lateral decubitus position with single-lumen tube intubation. After placement of four abdominal ports, a 12-mm port was inserted in the fourth or fifth intercostal space into the diaphragm. The tumor was ablated by an RFA needle through the port. The routine follow-up consisted of laboratory tests and abdominal imaging every 3-6 months. Results: The median operation time for only one tumor was 137 minutes (range, 105-187 minutes). The median number of times for ablation was three. Severe postoperative complications (>Clavien-Dindo IIIa) were observed in one case (right upper limb paralysis). The median follow-up period was 35 months (range, 11-43 months). There was no local tumor progression. Recurrent hepatic tumor appearance occurred in other parts of the liver in 6 of the 11 patients. Conclusions: Laparoscopic transthoracic transdiaphragmatic RFA is an acceptable procedure with a low rate of local recurrence.

Background Outcomes of proximal parenchymal pancreatectomy (PPP) as compared to pancreatoduodenectomy (PD) have not been reported. The aim of this study was to describe the short- and long-term outcomes of patients with low-grade pancreatic head lesions who underwent PPP or PD. Methods Patients who underwent PPP or PD for low-grade lesions between 2009 and 2017 were included. Operative factors including postoperative complications and nutritional indicators during the first-year postoperatively were compared. Results A total of 13 and 14 patients underwent PPP and PD respectively. The PPP group demonstrated significantly less intraoperative blood loss and shorter postoperative hospital stay than the PD group. No significant differences were noted in the incidence of postoperative complications between the two groups. Nutritional indices were significantly better in the PPP group at 3 months post-surgery, but these nutritional indices were not significantly different at 6 months and 1-year. None of 12 patients who underwent PPP and did not require biliary resection developed postoperative cholangitis. None of the 12 PPP patients without preoperative diabetes developed impaired glucose tolerance after surgery. Discussion The complication rate of PPP is equivalent to that of PD. PPP demonstrated better short-term nutritional status than PD. Moreover, preservation of the total duodenum and bile duct may reduce the risk of developing postoperative diabetes and cholangitis.

Background: Laparoscopic inguinal hernia repair is considered technically difficult. Although a simulation-based curriculum has been developed to help trainees, access to simulation training outside North America is limited. This study aimed to develop an educational system for the transabdominal preperitoneal (TAPP) approach based on the TAPP checklist, an assessment tool we had developed and validated earlier. Material and methods: Consensus within the TAPP education working group consisting of local TAPP experts, hernia experts and a surgical educator to develop educational tools and the educational system based on the TAPP checklist. The system was piloted in several institutes, and participants were surveyed on its efficacy. Results: We systematically developed an educational video and training manual explaining each item of the TAPP checklist and conveying basic knowledge of the procedure. We integrated the training tool with evaluation and feedback to develop an educational system. In a pilot study, seven trainees at five hospitals were trained using this system and found it very useful for mastering the TAPP procedure. Conclusions: We have developed a training system for TAPP procedure and successfully implemented it in several hospitals. Further research will focus on the educational value of this tool.

OBJECTIVE Item response theory (IRT) was originally developed to make performance assessments more accurate. However, IRT analysis of the intraoperative performance of surgical trainees could help identify the elements that the trainees find difficult during the skill acquisition process. The aim of this study was to identify the essential portions of the skill acquisition process of a surgical procedure using the IRT. DESIGN The 24-item assessment checklist was used to evaluate a recorded intra-operative performance of a laparoscopic inguinal hernia repair. The scores were analyzed using IRT to calculate the difficulty and discrimination level of each item. SETTING Fifteen institutes. PARTICIPANTS Thirty surgical trainees. RESULTS A total of 123 assessments were analyzed. The item analysis showed the procedure specific item “traction of peritoneum (difficulty: −0.45; discrimination: 19.37)” and generic items “instrument handling (difficulty: −0.59; discrimination: 3.82)” and “flow of procedure (difficulty: 0.09; discrimination: 3.27)” to be key elements in the skill acquisition process of the procedure. CONCLUSIONS Key elements in the skill acquisition process of the procedure were quantitatively identified by applying the IRT analysis. This could lead to the use of IRT in designing and developing a more effective training curriculum.

Background Metastasis to para-aortic lymph nodes (PAN) in hilar malignancies is considered distant metastasis. Fluorescence imaging using near infrared fluorescence light and indocyanine green (ICG-NIR imaging) are widely employed for identifying the sentinel lymph node, which might be an ideal alternative procedure for whole excisional biopsy of PAN. However, there has been no report about ICG-NIR imaging in hilar malignancies. The purpose of this study was to determine the optimal dose for indocyanine green to detect PAN and to reveal the detection rate of ICG-NIR imaging for lymphatic flow toward regional lymph nodes (RLN) or PAN from the Calot’s triangle. Patients and methods We enrolled 62 patients with hepato-pancreatic-biliary malignancies in this study. The dose of ICG was optimized in the first 15 patients and the detection rate for RLN and PAN was evaluated in the remaining 47. We observed that the optimal administered dose of ICG for detecting fluorescent signals in PAN was 5 mg/mL. Results Using this dose, RLN and PAN fluorescence were detected in 29 of 42 patients. Fluorescent signals were recorded in the lymph nodes (LN) along the bile duct and the posterior surface of the head of the pancreas. We also detected PAN fluorescent signals on the right side of the aorta around the left renal vein. We recommend 5 mg/ml of ICG to visualize lymphatic flow from the hepatoduodenal ligament to PAN using ICG-NIR imaging. However, because detection rate of RLN and PAN were 69%, respectively, further improvement for this procedure will be necessary for clinical application.

Esophagectomy is the standard treatment for esophageal cancer, but has a high rate of postoperative complications. Some studies reported the various scoring system to estimate the postoperative complications. However, there were according to various surgical methods and included intra- and post-operative factors. Recently, minimally invasive esophagectomy (MIE) is becoming the first-line treatment for esophageal cancer. The aim of this study was to investigate the risk factors of postoperative complications and to establish a useful system for predicting postoperative complications after transthoracic MIE. From 2007 to 2015, 90 patients who underwent transthoracic MIE at our department were enrolled. Patients were divided into two groups according to postoperative complication: patients with major complications (n = 32) and without major complications (n = 58). Major complication was defined as ≥ IIIa in the Clavien–Dindo classification. Multivariate analysis identified four independent risk factors for predicting postoperative complications: age [≥ 70 years; odd ratio (OR) 6.88; p = 0.001]; sex (male; OR 5.24; p = 0.031); total protein level (

Hilar malignancy can occasionally be associated with high grade dysplasia (HGD) adjacent to invasive malignancy. For patients with HGD extending into the intrapancreatic bile duct, the authors adopted intrapancreatic bile duct resection (IP-BDR). The aims of this study were to compare the incidence of clinically relevant postoperative pancreatic fistula (CR-POPF), distal R0 resection and local recurrence within the distal bile duct remnant for patients undergoing extrahepatic bile duct resection without pancreaticoduodenectomy (with or without IP-BDR).Patients who presented with hilar malignancy and underwent extrahepatic bile duct resection without pancreaticoduodenectomy between January 2005 and December 2016 were identified and the outcomes retrospectively evaluated.Of 217 patients who met the inclusion criteria 62 (29%) patients underwent IP-BDR. There was a significant difference between patients undergoing standard resection vs. IP-BDR in terms of CR-POPF (5% (8/155) patients: vs 18% (11/62), p 0.001). There were no significant differences between two groups of R0 status on distal margin (5% (8/155) patients: vs 10% (6/62), p = 0.359). No patient developed recurrence within the residual intrapancreatic bile duct.The incidence of CR-POPF after IP-BDR for hilar malignancies was 18%. IP-BDR was associated with CR-POF, but does not appear to alter survival or local recurrence rate.

The development of surgical site infection (SSI) after biliary reconstruction is highly influenced by the presence of preoperative bacteria in the bile juice. We selected vancomycin and piperacillin/tazobactam (VCM + PIPC/TAZ) as perioperative prophylactic antibiotics for patients undergoing pancreaticoduodenectomy. This study aimed to retrospectively analyze the effectiveness of VCM + PIPC/TAZ compared to cefmetazole. Seventy-two patients who underwent pancreaticoduodenectomy between April 2015 and March 2017 at our department were evaluated. Forty patients were administered cefmetazole as the perioperative prophylactic antibiotic, and 32 were administered VCM + PIPC/TAZ. The intraoperative VCM blood concentration (incision, biliary reconstruction, and wound closure) was measured during surgery to confirm the hemodynamics. The frequency of SSIs was significantly lower in the VCM + PIPC/TAZ group (8/32 patients) than in the cefmetazole group (20/40 patients, P = 0.031). Postoperatively, significantly fewer patients in the VCM + PIPC/TAZ group (4/32 patients) required ≥ 15 days of additional antibiotic administration compared to those in the cefmetazole group (14/40 patients, P = 0.033). Six of 32 patients in the VCM + PIPC/TAZ group showed redneck syndrome symptoms. There was no significant difference in the VCM blood concentration between patients with and without SSIs. The use of VCM + PIPC/TAZ can reduce the incidence of SSI after pancreaticoduodenectomy and also reduce the need for the additional administration of antibiotics for ≥ 15 days after surgery.

Melanoma antigen family A4 (MAGEA4), a cancer/testis antigen, is overexpressed and is thus an immunotherapy target in various malignant tumors, including non-small cell lung cancer. However, whether MAGEA4 induces or inhibits the apoptosis of lung cancer cells remains controversial, as is its prognostic significance, particularly since there is no reliable method with which to detect MAGEA4 specifically. In this study, we optimized assay conditions to detect MAGEA4 based on cells transiently transfected with MAGEA genes, and found that MAGEA4 was expressed in four of eight non-small cell lung cancer cell lines, and in 25.4% of clinical lung cancer specimens. We also found that MAGEA4 overexpression decreased apoptosis, as measured by the levels of cleaved caspase-3 in stably transfected 293F cells. Notably, patients with nuclear MAGEA4, but not p53 expression exhibited a significantly poorer survival than those expressing both nuclear MAGEA4 and p53. Indeed, multivariate analysis identified nuclear MAGEA4 as an independent prognostic factor (P=0.0042), albeit only in the absence of p53. In this study, to the best of our knowledge, we are the first to demonstrate that the function and prognostic value of MAGEA4 depends on its subcellular localization and on the p53 status.

It has been reported that preoperative embolization or intraoperative reconstruction of the replaced right hepatic artery (rRHA) in order to secure the arterial blood flow to the liver and biliary tract are useful for patients who have undergone pancreaticoduodenectomy (PD) with concomitant rRHA resection. In this study, the feasibility of concomitant resection of rRHA in PD without preoperative embolization or intraoperative reconstruction were retrospectively evaluated with a particular focus on postoperative complications. We retrospectively analyzed 323 consecutive patients who underwent PD. In 51 patients (15.8%), an rRHA was detected. Nine of 51 patients underwent combined rRHA resection during PD. Eight patients showed tumor abutment, and one patient had accidental intraoperative damage of the rRHA. Although there were no cases of bilioenteric anastomotic failure, a hepatic abscess occurred in one patient. This patient was treated with percutaneous transhepatic abscess drainage and was cured immediately without suffering sepsis. Postoperative complications of Clavien-Dindo classification ≥ IIIa were found in three patients, and R0 resection was achieved in six. Surgical outcomes showed no significant differences between the rRHA-resected and non-resected groups. Moreover, there were no significant differences in laboratory data related to liver functions between the rRHA-resected and non-resected groups before surgery and on postoperative days 1, 3, 5, and 7. Simple resection of the rRHA following an unintended or accidental injury during PD is not associated with severe morbidity and should be considered as an alternative to a technically difficult reconstruction.

Delayed gastric emptying (DGE) is one of the most common morbidities of pancreaticoduodenectomy (PD). The aim of this study was to clarify whether the incidence of DGE can be reduced by side-to-side gastric greater curvature-to-jejunal anastomosis in subtotal stomach-preserving pancreaticoduodenectomy (SSPPD). The clinical data of 253 patients who had undergone PD were examined. Of a total of 188 patients who had undergone SSPPD, a gastrojejunostomy (GJ) was performed with end-to-side anastomosis in 87 patients (SSPPD-ETS group), and a GJ was performed with a greater curvature side-to-jejunal side anastomosis in 101 patients (SSPPD-STS group). After propensity score matching, the matched cohort consisted of 74 patients in each group. The postoperative data were evaluated according to the International Study Group of Pancreatic Surgery grade of DGE. The total incidence of DGE was 9.4% in the SSPPD-ETS group and 4% in the SSPPD-STS group, with no significant difference (p = 0.1902). A significant difference was observed between the two groups in the incidence of DGE grade C (p = 0.0426). The incidence of total DGE was not reduced statistically in the STS group compared with the ETS group, but reduced DGE grade C. Side-to-side anastomosis might be associated with a reduced incidence of DGE grade C.

Background The high frequency of surgical site infections (SSIs) after hepato-pancreato-biliary (HPB) surgery is a problem that needs to be addressed. This prospective, randomized, controlled study examined whether perioperative prophylactic use of antibiotics based on preoperative bile culture results in HPB surgery could decrease SSI. Methods Participants comprised 126 patients who underwent HPB (bile duct, gallbladder, ampullary, or pancreatic) cancer surgery with biliary reconstruction at Hokkaido University Hospital between August 2008 and March 2013 (UMIN Clinical Trial Registry #00001278). Before surgery, subjects were randomly allocated to a targeted group administered antibiotics based on bile culture results or a standard group administered cefmetazole. The primary endpoint was SSI rates within 30 days after surgery. Secondary endpoint was SSI rates for each operative procedure. Results Of the 126 patients, 124 were randomly allocated (targeted group, n = 62; standard group, n = 62). Frequency of SSI after surgery was significantly lower in the targeted group (27 patients, 43.5%) than in the standard group (44 patients, 71.0%; P = 0.002). Among patients who underwent pancreaticoduodenectomy and hepatectomy, SSI occurred significantly less frequently in the targeted group (P = 0.001 and P = 0.025, respectively). Conclusions This study demonstrated that preoperative bile culture-targeted administration of prophylactic antibiotics decreased SSIs following HBP surgery with biliary reconstruction.

Recently, distal pancreatectomy with en bloc celiac axis resection (DP-CAR) or modified Appleby procedure for locally advanced pancreatic body cancer is increasingly reported. However, actual long-term survival data are still unknown. This study retrospectively reviewed 80 consecutive patients with pancreatic body cancer who underwent DP-CAR at a single institution. The study included 40 men and 40 women with a median age of 65 years (range, 44–85 years). A pancreatic fistula was the most common complication, occurring in 47 patients (57.5 %). Other complications with a high incidence were ischemic gastropathy (23 patients, 28.8 %) and delayed gastric emptying (20 patients, 25 %). According to the Clavien-Dindo classification, the major complications, defined as complications of grade 3 or higher, were observed in 33 patients (41.3 %), and the in-hospital mortality involved four patients (5 %). For all 80 patients, the 1-, 2-, and 5-year overall survivals (OSs) were respectively 81.1, 56.9, and 32.7 %, and the median survival time was 30.9 months. The actual 5-year survival for the 61 patients whose surgery was performed five or more years earlier was 27.9 % (17 of 61). The 1-, 2-, and 5-year OSs for the patients who underwent preoperative therapy (100, 90, and 78.8 %) were significantly better than for those who underwent upfront surgery (77.9, 51.5, and 26.7 %; P

The surgical indications for patients with pancreatic head cancer (PHC) with clinical portal vein (PV) invasion (cPV) remain controversial. The present study aimed to determine the ability of computed tomography (CT) to diagnose pathological PV involvement (pPV) in PHC.We evaluated the morphological features (length and circumference) and two sets of diagnostic criteria for cPV determined from preoperative CT findings of 112 consecutive patients who underwent pancreatoduodenectomy for PHC. This study is listed in the UMIN Clinical Trials Registry (UMIN-CTR; No: UMIN000016827).Five patients were excluded because enhanced CT data were missing. Morphological features have low diagnostic ability for pPV. We diagnosed 67 patients with cPV based on our diagnostic criteria and those of Klauss, and 42 of them had pPV. The negative predictive values of these diagnostic criteria for pPV were satisfactory (95%) and the positive predictive value was relatively low (61.2%). Postoperative survival could be predicted based on the cPV type.An accurate diagnosis of pPV based on morphological features determined by preoperative CT is difficult. However, preoperative CT appears useful for selecting patients with PHC who could be candidates for pancreaticoduodenectomy with or without PV resection.

Whether concomitant hepatic artery resection (HAR) improves the prognosis for advanced perihilar cholangiocarcinoma remains controversial. The aim of the present study was to compare short- and long-term surgical results of HAR versus standard resection (SR) for perihilar cholangiocarcinoma using propensity score matching.Among 209 patients with perihilar cholangiocarcinoma patients who underwent resection in our department, 28 patients underwent HAR, and the remaining 181 patients underwent SR. To adjust for differences in clinicopathological factors, including difficulty in surgery, between groups, propensity score matching was used at a 1:1 ratio, resulting in a comparison of 24 patients per group. The study protocols were approved by our institutional review board (015-0365), enrolled in UMIN-CTR (No: UMIN000019927), and conducted according to the Declaration of Helsinki.No significant differences were seen in overall incidence of postoperative complications (Clavien-Dindo classification ≥IIIa: 37.5% in SR group vs. 62.5% in HAR group; P = 0.080), except for postoperative liver abscess formation (P = 0.020). Five-year overall survival rates were 30.3% and 20.4%, respectively. No significant difference in overall survival rate was apparent between the SR and HAR groups (P = 0.150).Despite being a demanding procedure, concomitant HAR appears feasible for selected patients with perihilar cholangiocarcinoma.

The HLA class I antigen processing machinery (APM) plays a crucial role in the anticancer immune response. The aim of this study was to assess the clinical significance of APM components in esophageal cancer. A total of 11 esophageal cancer cell lines were evaluated by Western blot analysis for 13 HLA class I APM components. There was a different expression pattern among cancer cell lines for HLA class I heavy chain (HLA-HC), β2 microglobulin, Tapasin, TAP-1, TAP-2, LMP-7 and LMP-10. Immunohistochemical staining utilizing a tissue microarray method for HLA class I APM expression showing different expression patterns among cell lines was performed for 95 surgical specimens from patients with esophageal cancer. Prognostic factors were the down-regulation of HLA-HC, and the up-regulation of β2 microglobulin and TAP-1 in the cancer tissues. Multivariate analysis using a Cox regression model indicated that the down-regulation of HLA-HC, and up-regulation of TAP-1 in cancer tissues are independent, unfavorable prognostic factors (hazard ratio, 2.361 and 2.297; P=0.0141 and 0.0145, respectively). Although there was no significant difference in survival for selected p-stage I and II patients (n=54) in all APM components, only down-regulation of HLA-HC was an unfavorable prognostic factor by a Cox regression model for selected p-stage III and IV patients (n=41). In conclusion, the current results suggest that the down-regulation of HLA-HC in tumors is especially associated with a poor prognosis among advanced esophageal cancer patients.

Smad2 is a critical mediator of TGF-β signals that are known to play an important role in a wide range of biological processes in various cell types. Its role in the development of the CNS, however, is largely unknown. Mice lacking Smad2 in the CNS (Smad2-CNS-KO) were generated by a Cre-loxP approach. These mice exhibited behavioral abnormalities in motor coordination from an early postnatal stage and mortality at approximately 3 weeks of age, suggestive of severe cerebellar dysfunction. Gross observation of Smad2-CNS-KO cerebella demonstrated aberrant foliations in lobule IX and X. Further analyses revealed increased apoptotic cell death, delayed migration and maturation of granule cells, and retardation of dendritic arborization of Purkinje cells. These findings indicate that Smad2 plays a key role in cerebellar development and motor function control.

Sonic hedgehog (SHH) signaling, acting in a combinatorial manner with androgen signaling, is essential for prostate patterning and development. Recently, elevated activation of SHH signaling has been shown to play important roles in proliferation, progression and metastasis of prostate cancer. In this report, we demonstrate for the first time, that GLI1, which has been shown to play a central role in SHH signaling in prostate cancer, can act as a co-repressor to substantially block androgen receptor (AR)-mediated transactivation, at least in part, by directly interacting with AR. Our observations suggest that the SHH-GLI pathway might be one of determinants governing the transition of prostate cancer from anandrogen-dependent to an androgen-independent state by compensating, or even superseding androgen signaling.

Activin, a member of the transforming growth factor-β family, has been known to be a growth and differentiating factor. Despite its pluripotent effects, the roles of activin signaling in prostate cancer pathogenesis are still unclear. In this study, we established several cell lines that express a constitutive active form of activin type IB receptor (ActRIBCA) in human prostate cancer cells, ALVA41 (ALVA-ActRIBCA). There was no apparent change in the proliferation of ALVA-ActRIBCA cells in vitro; however, their migratory ability was significantly enhanced. In a xenograft model, histological analysis revealed that the expression of Snail, a cell-adhesion-suppressing transcription factor, was dramatically increased in ALVA-ActRIBCA tumors, indicating epithelial mesenchymal transition (EMT). Finally, mice bearing ALVA-ActRIBCA cells developed multiple lymph node metastases. In this study, we demonstrated that ActRIBCA signaling can promote cell migration in prostate cancer cells via a network of signaling molecules that work together to trigger the process of EMT, and thereby aid in the aggressiveness and progression of prostate cancers.