A case report of carcinoma of the papilla of Vater associated with a hyperplasia-dysplasia-carcinoma sequence by pancreaticobiliary maljunction.

BACKGROUND: Pancreaticobiliary maljunction (PBM) is a known risk factor for biliary tract cancer. However, its association with carcinoma of the papilla of Vater (PVca) remains unknown. We report a case with PVca that was thought to be caused by the hyperplasia-dysplasia-carcinoma sequence, which is considered a mechanism underlying PBM-induced biliary tract cancer. CASE PRESENTATION: A 70-year-old woman presented with white stool and had a history of cholecystectomy for the diagnosis of a non-dilated biliary tract with PBM. Esophagogastroduodenoscopy revealed a tumor in the papilla of Vater, and PVca was histologically proven by biopsy. We finally diagnosed her with PVca concurrent with non-biliary dilated PBM (cT1aN0M0, cStage IA, according to the Union for International Cancer Control, 8th edition), and subsequently performed subtotal stomach-preserving pancreaticoduodenectomy. Pathological findings of the resected specimen revealed no adenomas and dysplastic and hyperplastic mucosae in the common channel slightly upstream of the main tumor, suggesting a PBM related carcinogenic pathway with hyperplasia-dysplasia-carcinoma sequence. Immunostaining revealed positivity for CEA. CK7 positivity, CK20 negativity, and MUC2 negativity indicated that this PVca was of the pancreatobiliary type. Genetic mutations were exclusively detected in tumors and not in normal tissues, and bile ducts from formalin-fixed paraffin-embedded samples included mutated-ERBB2 (Mutant allele frequency, 81.95%). Moreover, of the cell-free deoxyribonucleic acid (cfDNA) extracted from liquid biopsy mutated-ERBB2 was considered the circulating-tumor deoxyribonucleic acid (ctDNA) of this tumor. CONCLUSIONS: Herein, we report the first case of PVca with PBM potentially caused by a "hyperplasia-dysplasia-carcinoma sequence" detected using immunostaining and next-generation sequencing. Careful follow-up is required if pancreaticobiliary reflux persists, considering the possible development of PVca.

Reconsidering resectable oncological conditions in pancreatic tail cancer: A multicenter retrospective study on prognostic factors in pancreatic tail cancer after resection (HOPS Pt-01).

BACKGROUND: Pancreatic tail cancer (Pt-PC) is generally considered resectable when metastasis is absent, but doubts persist in clinical practice due to the variability in local tumor extent. We conducted a multicenter retrospective study to comprehensively identify prognostic factors associated with Pt-PC after resection. METHODS: We enrolled 100 patients that underwent distal pancreatectomy. The optimal combination of factors influencing relapse-free survival (RFS) was determined using the maximum likelihood method (MLM) and corrected Akaike and Bayesian information criteria (AICc and BIC). Prognostic elements were then validated to predict oncological outcomes. RESULTS: Therapeutic interventions included neoadjuvant treatment in 16 patients and concomitant visceral resection (CVR) in 37 patients; 89 patients achieved R0. Median RFS and OS after surgery were 23.1 and 37.1 months, respectively. AICc/BIC were minimized in the model with ASA-PS (≥2), CA19-9 (≥112 U/mL at baseline, non-normalized postoperatively), need for CVR, 6 pathological items (tumor diameter ≥19.5 mm, histology G1, invasion of the anterior pancreatic border, splenic vein invasion, splenic artery invasion, lymph node metastasis), and completed adjuvant treatment (cAT) for RFS. Regarding the predictive value of these 11 factors, area under the curve was 0.842 for 5-year RFS. Multivariate analysis of these 11 factors showed that predictors of RFS include CVR (hazard ratio, 2.13; 95 % confidence interval, 1.08-4.19; p = 0.028) and cAT (0.38, 0.19-0.76; p = 0.006). CONCLUSIONS: The MLM identified certain Pt-PC cases warranting consideration beyond resectable during clinical management. Particular attention should be paid to conditions requiring CVR, even though immortal time bias remains unresolved with adjuvant treatment.

Laparoscopic low anterior resection for rectal cancer wherein the inferior mesenteric artery arose from the superior mesenteric artery: a case report.

BACKGROUND: Few cases have been reported of colorectal cancer with inferior mesenteric artery (IMA) branching abnormalities; therefore, the lymphatic flow in such cases remains unknown. We report the first case of locally advanced rectal cancer in which the IMA arose from the superior mesenteric artery (SMA) in which we achieved to visualize the lymphatic flow. CASE PRESENTATION: A 65-year-old woman complaining of bloody stools was investigated in our hospital and suspected with rectal cancer. Colonoscopy and abdominal enhanced computed tomography (CT) revealed a circumscribed, localized ulcerative tumor in the rectum. 3-Dimensional contrast-enhanced computed tomography (3D-CT) showed that the IMA arose from the SMA. The patient was diagnosed with rectal cancer (cT3N0M0, cStage IIa) and laparoscopic low anterior resection was performed. The sigmoid colon was resected using the medial approach. Only the plexus of the colic branch of the lumbar splanchnic nerve was observed at the site where the root of the IMA usually exists and showed interruption of the indocyanine green (ICG) fluorescence-illuminated lymphatics. The root of the IMA was ligated, and Japanese D3 lymphadenectomy was performed, preserving the accessory middle colic artery. All fluorescent lymph nodes were resected. The pathological diagnosis was pT4aN1aM0 stage IIIb. The patient's postoperative course was uneventful. Adjuvant chemotherapy was administered, and the patient was recurrence-free at 1.5 years after surgery. CONCLUSIONS: We were able to perform safe and appropriate surgery oncologically, despite abnormal vascular anatomy, due to preoperative identification using 3D-CT and intraoperative navigation using ICG administration.

Indocyanine green fluorescence imaging ensures perfusion of the remnant stomach during laparoscopic splenectomy in a patient after distal gastrectomy: A case report.

BACKGROUND: After distal gastrectomy, ischemic necrosis of the remnant stomach is a rare but serious complication. For distal pancreatectomy or splenectomy, ensuring adequate blood supply to the remnant stomach is important for patients with a history of distal gastrectomy. We report a case of successful splenectomy with indocyanine green (ICG) used to evaluate the blood supply to the remnant stomach in a patient after distal gastrectomy. CASE PRESENTATION: A 65-year-old woman who underwent distal gastrectomy for gastric cancer a year earlier had a splenic tumor that was increasing in size. We planned laparoscopic splenectomy because there was a possibility of a malignant splenic tumor. Intraoperative ICG fluorescence imaging confirmed perfusion of the remnant stomach. The patient was discharged on postoperative day 8 after an uncomplicated postoperative course. CONCLUSION: ICG fluorescence imaging is useful for evaluating blood flow to the remnant stomach during laparoscopic splenectomy in patients after distal gastrectomy.

Perioperative Predictors of Early Recurrence for Resectable and Borderline-Resectable Pancreatic Cancer.

We aimed to identify the perioperative predictors of the early recurrence (ER) of resectable and borderline-resectable pancreatic ductal adenocarcinomas (PDACs). After surgery for a PDAC, most patients develop a recurrence. Predictive factors may therefore guide therapeutic decision-making. Patients (n = 234) who underwent a pancreatectomy for a PDAC between 2006 and 2019 were included. The postrecurrence survival (PRS) was estimated using Kaplan-Meier curves. Predictive factors for an ER were assessed using logistic regression analyses; 93 patients (39.7%) were recurrence-free at the last follow-up. Patients with an ER (n = 85, 36.3%), defined as a recurrence within the first 12 months after surgery, had 1- and 2-year PRS rates of 38.7% and 9.5%, respectively, compared with 66.9% and 37.2% for those with a late recurrence (n = 56, 23.9%; both p < 0.001). The most common site of an ER was the liver (55.3%) with a significantly shorter median overall survival time than that with either a local or a lung recurrence (14.5 months; p < 0.001). Preoperative and postoperative risk factors for an ER included a tumor size >3.0 cm (odds ratio (OR): 3.11, 95% confidence interval (CI): 1.35-7.14) and preoperative carbohydrate antigen 19-9 (CA19-9) levels >52 U/mL (OR: 3.25, 95% CI: 1.67-6.30) and a pathological tumor size >3.0 cm (OR: 2.00, 95% CI: 1.03-3.90) and postoperative carbohydrate antigen 19-9 levels >37 U/mL (OR: 2.11, 95% CI: 1.02-4.36), respectively. Preoperatively (>52 U/mL) and postoperatively (>37 U/mL) elevated CA19-9 and a tumor size >3.0 cm were independent predictors for an ER after a pancreatectomy for a PDAC.

Conversion pancreaticoduodenectomy with dual arterial reconstructions for locally advanced pancreatic cancer: Case report and literature review.

INTRODUCTION: Extended pancreatectomy for initially unresectable locally advanced (URLA) pancreatic carcinoma (PC) often requires combined arterial resection/reconstruction. By limiting candidate arterial inflow after combined resection of the celiac arterial system over a long distance, great saphenous vein graft (GSVG) is an alternative conduit for obtaining non-anatomical arbitrary arterial inflow. PRESENTATION OF CASE: A 66-year-old woman was diagnosed with URLA pancreatic head carcinoma involving the region from the celiac axis (CA) to the common hepatic and proximal splenic artery (SA). She received 10 courses of modified FOLFIRINOX followed by concurrent chemoradiotherapy including S1 with favorable response. The duration of disease control and normalization of serum carbohydrate antigen 19-9 (CA19-9) exceeded 10 months, and conversion surgery was planned. Extended pancreaticoduodenectomy (PD) required concomitant resection of the CA to the proper hepatic and SA. The dual arterial reconstructions involved a GSVG interposition from the abdominal aorta to the distal SA to preserve the entire stomach, and from the mesenteric second jejunal artery to the right hepatic artery. The patient achieved pathological R0 resection with a histological response of Evans grade IIB. DISCUSSION: Reconstruction of the distal SA with GSVG in extended PD enabled preservation of the subtotal stomach and distal pancreas, even when the root of the CA was transected. CONCLUSION: Multiple arterial reconstructions using GSVG might be useful in extended pancreatectomy to preserve visceral organs, offer better quality of life in terms of oral intake and nutritional status, and control blood glucose than after total pancreatectomy concomitant with subtotal gastrectomy.

A drainage strategy for postoperative pancreatic fistula after left-sided pancreatectomy based on the wall status of collected fluid.

PURPOSE: Postoperative pancreatic fistula (POPF) after pancreatectomy is one of the severe postoperative adverse events. We aimed to clarify the outcomes of a strategy for POPF after left-sided pancreatectomy with one-step endoscopic ultrasonography-guided drainage (EUSD) and percutaneous drainage (PCD) based on the wall status of collected fluid. METHODS: From January 2012 to September 2017, 90 of 336 patients developed grade B/C POPF and were retrospectively analyzed. Primary outcome measures were the technical and clinical success and resolution rates. Secondary outcome measures were time from surgery to intervention, and time from intervention to discharge/resolution or stent/tube removal and adverse events. RESULTS: Seventeen patients underwent EUSD and 73 patients underwent PCD for POPF. The technical success rates were 100% in both the EUSD and PCD groups. The clinical success and resolution rates in the EUSD group were 100%, while those in the PCD group were 98.6%. The time from surgery to intervention was significantly longer in the EUSD group than in the PCD group (20 vs. 11 days, p < 0.001). The time from intervention to discharge/resolution was significantly shorter in the EUSD group than in the PCD group (11 vs. 22 days, p < 0.001/10 vs. 20 days, p < 0.001). The time from intervention to stent/tube removal was significantly shorter in the PCD group than in the EUSD group (20.5 vs. 873 days, p < 0.001). Adverse event rates were similar in the two groups (11.8% vs. 5.5%). CONCLUSION: A drainage strategy for POPF based on the wall status of collected fluid is appropriate.

Effect of Rikkunshito, a Traditional Japanese Herbal Medicine, on Delayed Gastric Emptying and Oral Dietary Intake After Pancreaticoduodenectomy: A Prospective, Randomized, Single-Center, Open-Labeled Study.

INTRODUCTION: Delayed gastric emptying (DGE) remains an important problem after pancreaticoduodenectomy (PD). There is a lack of effective treatments for early recovery of oral dietary intake. Rikkunshito (RKT), a Japanese herbal medicine, has been gaining attention as a facilitator of gastric emptying. We evaluated the effects of RKT on DGE after PD. METHODS: In this prospective, randomized, open-labeled study, patients were randomly allocated before PD in a 1:1 ratio to the RKT group or the control group that received no additional treatment. The RKT group received 2.5 g of RKT three times daily (7.5 g/day) from postoperative day (POD) 1 to POD 21. The primary endpoint was the incidence of DGE. Secondary endpoints were short-term postoperative outcomes including oral dietary intake volume and perioperative changes in levels of the hormones ghrelin and leptin. Patients were observed until hospital discharge. RESULTS: Twenty-six patients in each group (n = 52) completed the protocol treatment and were included in the analysis set. There were no statistically significant differences in basic characteristics and operative factors. The overall incidence of DGE was not statistically different between the RKT and control groups (30.8% vs 30.8%, p>0.9999). There were no statistically significant differences in the amount of postoperative oral dietary intake represented by total dietary intake (TDI) up to POD 14 and POD 21, complications, and length of hospital stay. No adverse events related to this study were observed. In the RKT group, total ghrelin and acyl-ghrelin were significantly upregulated and leptin was significantly downregulated earlier than in the control group. CONCLUSION: RKT treatment from POD 1 to 21 did not reduce the incidence of DGE and had no clinically beneficial effect on short-term postoperative outcomes irrespective of changes in hormone levels.

Arteriovenous malformation in the pancreatic head initially mimicking a hypervascular mass treated with duodenum-preserving pancreatic head resection: a case report.

BACKGROUND: The mainstay treatment for arteriovenous malformation in the pancreatic head (Ph-AVM) is standard pancreatectomy, especially pancreaticoduodenectomy (PD), or interventional endovascular treatment. We report the first case of Ph-AVM treated with duodenum-preserving pancreatic head resection (DPPHR) performed to preserve the periampullary organs. CASE PRESENTATION: A 59-year-old man presenting with back pain underwent contrast-enhanced computed tomography followed by angiography of the anterior superior pancreaticoduodenal artery. He was diagnosed with Ph-AVM and indicated for DPPHR with preservation of the periampullary organs; Ph-AVM's benign nature seldom requires lymph node dissection. During the operation, the right colon was mobilized and the omental bursa was released to expose the periampullary structures. The pancreas was transected just above the superior mesenteric vein. The inferior pancreaticoduodenal artery and papillary arteries branching from the posterior superior pancreaticoduodenal artery were carefully preserved to maintain the blood flow to the lower bile duct and papilla of Vater. The remnant pancreas was reconstructed with pancreaticogastrostomy using the modified Blumgart method. Pathological examination of the resected specimen revealed an irregular course of the arteries and veins concomitant with marked dilation throughout the pancreatic head. The patient was pathologically diagnosed with Ph-AVM. He developed hematemesis caused by a rupture of the pseudoaneurysm on postoperative day 20 and underwent coil embolization. A bilio-enteric fistula and stenosis of the common bile duct were found and treated by placement of an endoscopic biliary stent. At the 8-month follow-up, the Ph-AVM had not recurred. CONCLUSIONS: Compared to PD, DPPHR confers the clinical benefit of preserving the periampullary organs, although further studies are needed to confirm this. Therefore, the choice of this procedure should be based on the surgical morbidities and long-term outcome of the patient.

Clinical usefulness of saphenous vein graft in major arterial reconstruction during extended pancreatectomy.

PURPOSE: Extended pancreatectomy for locally advanced pancreatobiliary malignancy often involves combined major arterial resection (AR) and reconstruction (ARc). By limiting candidate inflow for ARc after combined resection of the celiac arterial system over a long distance, we evaluated whether great saphenous vein graft (GSVG) is an alternative conduit for obtaining non-anatomical arterial inflow. METHODS: ARc with GSVG conduit was undertaken prior to resection. GSVG was harvested and anastomosed end-to-side with the reconstructing artery and then mostly passed via the retroperitoneal para-inferior vena cava route. Side-to-end anastomosis of GSVG inflow was established with the right common iliac artery or abdominal aorta. RESULTS: Among 468 consecutive pancreatobiliary surgeries, ARc with GSVG was undertaken in seven cases. Primary cancers were in the pancreas in six patients and distal bile duct in one. Radical surgery was performed with pancreaticoduodenectomy in six patients and total pancreatectomy in one. Hepatic artery (HA) was concomitantly resected and reconstructed by GSVG in six patients or by the jejunal artery in one patient. Median operative time and intraoperative blood loss were 763 min and 350 ml, respectively. Serum level of AST, ALT, and LDH in patients with HA reconstruction by GSVG peaked by the second postoperative day and promptly normalized. Postoperative morbidity (CD ≥ III) was encountered in one patient. No surgical mortality was observed. Postoperative serum liver enzymes promptly decreased in ARc patients with GSVG to HA. CONCLUSION: Arterial reconstruction with GSVG prior to resection was performed securely and might help to reduce postoperative liver dysfunction.

Conversion surgery for initially unresectable biliary malignancies: a multicenter retrospective cohort study.

PURPOSE: Few studies have focused on conversion surgery for biliary malignancy; thus, it is not clear if this treatment modality can extend the survival of patients with unresectable biliary malignancy. We conducted a multicenter retrospective cohort study to evaluate the surgical outcomes of conversion surgery in this setting and analyze long-term survival. METHODS: We collected clinical data retrospectively on patients who underwent conversion surgery for biliary malignancy. RESULTS: Twenty-four patients met our inclusion criteria. Preoperative chemotherapy regimens or chemoradiation therapy regimens were administered based on the institutional criteria, and surgical procedures were chosen based on tumor location. Morbidity occurred in 16 patients (66.7%), and 1 patient died of liver failure after surgery. The overall 5-year survival rate following initial therapy was 43.2%, and the median survival time was 57.4 months. The corresponding values following surgery were 38.2% and 34.3 months, respectively. The 5-year survival rate of the 24 patients who received both chemotherapy and surgery was significantly better than that of 110 patients treated with chemotherapy only (p < 0.001). CONCLUSION: Conversion surgery for initially unresectable biliary malignancies may be feasible and achieve long-term survival for selected patients.

Glucose-Dependent FOXM1 Promotes Epithelial-to-Mesenchymal Transition Via Cellular Metabolism and Targeting Snail in Human Pancreatic Cancer.

OBJECTIVES: Transcription factor Forkhead box protein M1 (FOXM1) plays critical roles in the progression of cancer including epithelial-to-mesenchymal transition (EMT). The aim of this study is to characterize the regulatory mechanisms of FOXM1 in EMT via pancreatic cancer metabolism. METHODS: We investigated the regulation of EMT via mitochondrial respiration by FOXM1 using pancreatic cancer cell lines HPAC and PANC-1 and normal human pancreatic duct epithelial cells. RESULTS: Forkhead box protein M1 and Snail were strongly expressed in HPAC and PANC-1. Epithelial-to-mesenchymal transition-modulated claudin-1 level was lower in PANC-1 than in HPAC. In both cell lines in low-glucose medium, FOXM1 and Snail were decreased and claudin-1 was increased. Knockdown of FOXM1 increased claudin-1 and decreased Snail in both cell lines. Low-glucose medium and downregulation of FOXM1 inhibited the cell migration in both cell lines. In both cell lines, mitochondrial respiration was at higher levels in low-glucose medium than in high-glucose medium. Downregulation of FOXM1 induced mitochondrial respiration in high-glucose medium. In normal human pancreatic duct epithelial cells, FOXM1 and Snail were low and claudin-1 was highly expressed, whereas overexpression of FOXM1 decreased claudin-1. CONCLUSIONS: Glucose-dependent FOXM1 promoted EMT via Snail and pancreatic cancer metabolism.

Tricellular tight junction protein LSR/angulin-1 contributes to the epithelial barrier and malignancy in human pancreatic cancer cell line.

Lipolysis-stimulated lipoprotein receptor (LSR)/angulin-1 is a crucial molecule of tricellular contacts in the epithelial barrier of normal cells and the malignancy of cancer cells. To investigate whether LSR/angulin-1 affects the epithelial barrier and malignancy in human pancreatic cancer, human pancreatic cancer cell line HPAC was used. Treatment with EGF or TGF-ß increased the expression of LSR, but not tricellulin (TRIC), and induced the localization of LSR and TRIC to bicellular tight junctions from tricellular tight junctions. TGF-ß receptor type-1 inhibitor EW-7197 prevented changes of the distribution and the barrier function of LSR by TGF-ß. Knockdown of LSR increased cell migration, invasion, proliferation and EGF ligand amphiregulin expression and decreased the epithelial barrier. Treatment with amphiregulin induced cell migration and invasion and knockdown of amphiregulin prevented the increases of cell migration, invasion and proliferation caused by knockdown of LSR. Treatment with LSR ligand peptide angubindin-1 decreased the epithelial barrier and the expression of LSR, but not TRIC, and increased cell invasion. Knockdown of TRIC decreased cell migration and the epithelial barrier. In immunohistochemical analysis of human pancreatic cancer tissues, LSR and TRIC were found to be localized at the cell membranes of normal pancreatic ducts and well-differentiated pancreatic ductal adenocarcinomas (PDAC), whereas in poorly differentiated PDAC, LSR was weakly detected in the cytoplasm. Amphiregulin was highly expressed in the cytoplasm of well- and poorly differentiated PDAC. In pancreatic cancer, LSR contributes to the epithelial barrier and malignancy via growth factors and may be a potential targeting molecule in the therapy.

Clinical usefulness of conversion surgery for unresectable pancreatic cancer diagnosed on multidetector computed tomography imaging: Results from a multicenter observational cohort study by the Hokkaido Pancreatic Cancer Study Group (HOPS UR-01).

BACKGROUND AND AIM: Effective multidisciplinary approaches for unresectable pancreatic cancer (UR-PC) that include modern chemotherapeutic regimens and subsequent conversion surgery (CS) are being developed. The aim of this study was to evaluate outcomes of patients clinically diagnosed with UR-PC, focusing on the efficacy of CS. METHODS: Patients ineligible for two multicenter phase II studies conducted by the Hokkaido Pancreatic Cancer Study Group (HOPS) were recruited. Sequential treatment regimens, conversion to radical surgery, and overall survival (OS) were analyzed by multidetector computed tomography (MDCT)-based UR factors. Univariate and multivariate analyses were performed to identify predictors of OS. RESULTS: Sixty-six of 247 intended recruits for HOPS studies from October 2013 to April 2016 were included. Unresectability was due to locally advanced (LA) disease and metastasis (M) in 42 and 24 patients, respectively. Induction therapy began with chemotherapy (CT) and chemoradiotherapy (CRT) in 44 and 17 patients, respectively, of whom 23 received modern CT regimens. Radical surgery was completed in 12 (LA, 10; M, two) with a median treatment interval of 10.3 months (range, 2-32). Eleven patients (91.6%) achieved pathological R0 resection. Median OS was significantly longer in patients who underwent CS than those who did not (44.1 vs 14.5 months, P < 0.0001). CS was an independent predictor of OS (hazard ratio, 0.078; 95% confident interval, 0.017-0.348; P = 0.001). CONCLUSION: Conversion surgery after a favorable response to sequential treatment might prolong survival in patients with UR-PC. Precise diagnosis on MDCT followed by sequential multimodal anticancer treatment is essential.

Central pancreatectomy in portal annular pancreas for metastatic renal cell carcinoma: a case report.

BACKGROUND: Portal annular pancreas (PAP) is a rare congenital anatomical abnormality of the pancreas in which the portal vein is encircled by aberrant parenchyma, and special attention is needed for pancreatic resections. This is the first report of central pancreatectomy (CP) in a PAP for metastatic renal cell carcinoma (RCC). CASE PRESENTATION: A 76-year-old man who had a history of left nephrectomy for renal cancer not otherwise specified 36 years earlier and radical cystectomy for bladder cancer 4 years earlier was incidentally found to have a pancreatic tumor and a liver tumor. The pancreatic tumor was diagnosed as metastasis of clear cell RCC, and the liver tumor was diagnosed as moderately differentiated hepatocellular carcinoma (HCC) on preoperative histological evaluation. Preoperative computed tomography imaging showed a type 3A PAP, in which the main pancreatic duct (MPD) ran ventral to the portal vein (anteportal type), and the aberrant parenchyma was located cranial to the confluence of the portal vein and splenic vein (suprasplenic type). After adhesiotomy and partial liver resection, CP was performed. With intraoperative ultrasound guidance, the aberrant parenchyma of the PAP could be preserved, avoiding additional resection. Thus, two pancreatic transections were performed, creating a single-cut margin that contained the MPD in the distal pancreas. Oncologically safe margins were confirmed by intraoperative pathological diagnosis. The distal pancreas was reconstructed by pancreatojejunostomy in the routine procedures. The pathological diagnosis of the surgical specimens was identical to the preoperative diagnosis. A postoperative pancreatic fistula (POPF) developed from the proximal stump of the head of the pancreas, necessitating no specific treatment other than drainage. The patient showed no signs or symptoms of recurrent RCC or abnormal pancreatic function for 2 years after the operation, although a histologically proven new HCC lesion developed distant from the initial site 8 months after the operation. CONCLUSIONS: Precise preoperative evaluation of the tumor features and PAP allowed adequate surgical strategies to be planned. Intraoperative ultrasound was useful to minimize parenchymal resections of the PAP. CP is still a challenging procedure in terms of the development of POPF.

Current status of site-specific cancer registry system for the clinical researches: aiming for future contribution by the assessment of present medical care.

BACKGROUND: The current status of site-specific cancer registry has not been elucidated, but sufficient system is found in some societies. The purpose of this study was to clear the present condition of site-specific cancer registries in Japan and to suggest for the improvement. METHODS: The questionnaire was conducted by the study group of the Ministry of Health, Labor, and Welfare. It consisted of 38 questions, conflicts of interest, clinical research method, informed consent and funding for registry. We distributed this questionnaire to 28 academic societies, which had published the clinical practice guideline(s) assessed under Medical Information Network Distribution Service (MINDS). RESULTS: The concept of the importance in assessment for medical quality by the data of the site-specific cancer registry was in good consensus. But the number of the society with the mature registry was limited. The whole-year registry with the scientific researches in the National Clinical Database (NCD) and in the Translational Research Informatics Center (TRI) might seem to be in success, because assured enhancement may be estimated. Now, academic societies have the structural factors, i.e., the financial limitation in the registry maintenance and the data analysis, and in the difficulty of employment of the researchers with skill and talent. CONCLUSIONS: To manage the site-specific cancer registry effectively, the scientific registry system will be essentially important. Each academic society had much experienced highly qualified clinical researches in past. Accordingly, the scientific suggestion and co-operation should be of great importance for the improvement.

Current status of projects for developing cancer-related clinical practice guidelines in Japan and recommendations for the future.

BACKGROUND: The current status and adoption of cancer-related clinical practice guidelines in Japan has not been elucidated yet. The purpose of this study was to propose roles and suggestions to develop future cancer-related clinical guidelines. METHODS: A questionnaire consisting of four domains with a total of 17 questions was developed. We distributed the questionnaire to 28 specific academic organizations in Japan which have developed any cancer-related clinical practice guidelines and which were funded by the Ministry of Health, Labor, and Welfare. RESULTS: Most organizations have investigated nationwide dissemination and adoption of clinical practice guidelines. The rate of adoption in clinical practice was estimated at approximately ≥ 70%. However, organizations with smaller budgets reported surveying approximately 60% of the time, whereas the ones with larger budgets reported approximately 100% success in surveying about their guidelines. The presidents of the organizations agreed that a new organization operated directly by the national government was necessary. CONCLUSION: In Japan, to develop cancer-related clinical practice guidelines, a study of clinical validation is necessary. Sufficient funds must be available to support the project to maintain and revise the guidelines. Furthermore, legal and ethical issues should be solved before establishing any registry system.

Case report: Long-term survival of a pancreatic cancer patient immunized with an SVN-2B peptide vaccine.

A 62-year-old woman who underwent surgery to treat pancreatic cancer provided written, informed consent to undergo adjuvant therapy with gemcitabine, tegafur, and uracil. However, this was stopped after only 14 days due to Grade 4 neutropenia. She was then started on vaccine therapy with Survivin 2B peptide (SVN-2B) including IFA and INF-α. Although metastatic lung tumors were identified and resected at 82 months after surgery, the patient has remained free of new or relapsed disease for 12 years thereafter. Tetramer and ELISPOT assays revealed the continuous circulation of SVN-2B-restricted cytotoxic T-lymphocytes (CTLs) in her peripheral blood, and CTL clones had specific activity for SVN-2B at 12 years after surgery. The adverse effects of the peptide vaccination were tolerable and comprised low-grade headache, nausea, and fatigue. A prognosis beyond 10 years in the face of pancreatic cancer with distant metastasis is extremely rare. This experience might indicate the value of cancer vaccination therapy.

Involvement of Pancreatic Stellate Cells in Regeneration of Remnant Pancreas after Partial Pancreatectomy.

BACKGROUND AND OBJECTIVES: Mechanism of regeneration of remnant pancreas after partial pancreatectomy (PX) is still unknown. In this study, effect of siRNA against the collagen specific chaperone, HSP47, which inhibits collagen secretion from activated pancreas stellate cells (aPSCs), and induces their apoptosis, on regeneration of remnant pancreas was determined. METHODS: Pancreatectomy was performed according to established methods. Proliferation of cells was assessed by BrdU incorporation. Immunostaining of HSP47 was employed to identify PSCs. Progenitor cells were identified by SOX9 staining. Acinar cells were immunostained for amylase. Co-culture of acinar cells with aPSCs were carried out in a double chamber with a cell culture insert. siRNA HSP47 encapsulated in vitamin A-coupled liposome (VA-lip siRNA HSP47) was delivered to aPSCs by iv injection. RESULTS: In remnant pancreas of 90% PX rat, new areas of foci were located separately from duodenal areas with normal pancreatic features. After PX, BrdU uptake of acinar cells and islet cells significantly increased, but was suppressed by treatment with VA-lip siRNA HSP47. BrdU uptake by acinar cells was augmented by co-culturing with aPSCs and the augmentation was nullified by siRNA HSP47. BrdU uptake by progenitor cells in foci area was slightly enhanced by the same treatment. New area which exhibited intermediate features between those of duodenal and area of foci, emerged after the treatment. CONCLUSION: aPSCs play a crucial role in regeneration of remnant pancreas, proliferation of acinar and islet cells after PX through the activity of secreted collagen. Characterization of new area emerged by siRNA HSP47 treatment as to its origin is a future task.

Effects of antecolic versus retrocolic reconstruction for gastro/duodenojejunostomy on delayed gastric emptying after pancreatoduodenectomy: a systematic review and meta-analysis.

BACKGROUND: Delayed gastric emptying (DGE) is a relatively common complication after pancreatoduodenectomy (PD). The aim of this study was to determine whether DGE is affected by antecolic or retrocolic reconstruction for gastro/duodenojejunostomy after PD. METHODS: A literature search was performed of the MEDLINE (PubMed), Ovid SP, ISI Web of Knowledge, EMBASE, and Cochrane databases to identify randomized controlled trials (RCTs) and clinical observational studies related to this topic from January 1995 to November 2014. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated for categorical outcomes, and mean differences (MD) using fixed-effect and random-effects models were calculated for the meta-analysis. RESULTS: Fourteen studies including 1969 patients met the inclusion criteria. Six studies were RCTs, and eight studies were clinical observational studies. DGE was less common in the antecolic reconstruction group than in the retrocolic reconstruction group (OR = 0.24 [0.12-0.48], P < 0.0001). Postoperative days to start solid foods (MD = -3.67 d [-5.10 to -2.33], P < 0.00001) and length of hospital stay (MD = -2.90 d [-5.36 to -2.33], P < 0.00001) were also significantly in favor of the antecolic reconstruction group. There was no difference in the incidence of pancreatic fistula, intra-abdominal fluid collection or abscess, biliary fistula, or mortality. However, in the subgroup analyses, using the data of six RCTs or seven studies according to the International Study Group of Pancreatic Surgery definition, there was no significant difference in the incidence of DGE. CONCLUSIONS: Antecolic reconstruction for gastro/duodenojejunostomy does not seem to offer an advantage over retrocolic reconstruction with respect to DGE after PD.