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Primary pancreatic lymphomas are extremely rare, accounting for 0.1-0.5% of malignant lymphomas and about 0.2% of primary pancreatic tumors. They occur most commonly in the pancreatic head of elderly males, with diffuse large B-cell lymphoma being the most common subtype. Primary pancreatic follicular lymphoma is the most commonly reported primary pancreatic indolent lymphoma, accounting for 9-14% of primary pancreatic lymphomas. We report two cases of primary pancreatic follicular lymphoma treated with obinutuzumab, a second-generation humanized anti-CD20 monoclonal antibody, and bendamustine. One was diagnosed by endoscopic ultrasound-guided fine-needle aspiration, while the other required laparoscopic lymph node sampling to reach a diagnosis. Both achieved complete response with induction therapy and opted for maintenance therapy with obinutuzumab. We also conducted a literature review of primary pancreatic follicular lymphoma cases reported over the last 30 years.

Background Peritoneal metastasis is one of the most important poor prognostic factors in advanced pancreatic cancer (PC). Whether the prognosis of PC with peritoneal metastasis has improved with the advent of gemcitabine plus nab-paclitaxel (GnP) and modified FOLFIRINOX (mFFX) is uncertain. The aim of this study was to evaluate the improvements in treatment outcomes of PC with peritoneal metastasis. Methods We retrospectively investigated consecutive PC patients with peritoneal metastasis treated with chemotherapy at our institution between 2010 and 2019. We compared the clinical characteristics and survival outcomes according to the period of diagnosis (group A, 2010–2014; group B, 2015–2019) and chemotherapy regimen. We also examined the prognostic factors for overall survival (OS). Results Among 180 patients included (GnP 88; mFFX 14; other regimens 78), distant metastasis was confined to the peritoneum in 89 patients. Although group B had a worse performance status compared to group A, median OS was significantly longer in group B. GnP and mFFX showed a significantly higher objective response rate and disease control rate in addition to longer progression free survival and OS compared to other regimens. The administration of GnP or mFFX, performance status, and neutrophil to lymphocyte ratio ≥5 were identified as independent prognostic factors for OS. Furthermore, the amount of ascites and extent of peritoneal metastasis were significantly associated with OS in patients with distant metastasis confined to the peritoneum. Conclusions The prognosis of PC with peritoneal metastasis has significantly improved over time with the advent of GnP and mFFX.

Objective With the introduction of modified FOLFIRINOX and gemcitabine plus nab-paclitaxel therapy for unresectable pancreatic cancer, erlotinib plus gemcitabine therapy is now occasionally used as late-line therapy. This study investigates outcomes of treatment with erlotinib plus gemcitabine for unresectable pancreatic cancer. Methods We retrospectively analysed consecutive patients with unresectable pancreatic cancer treated with erlotinib plus gemcitabine as the third or later-line chemotherapy between March 2014 and December 2020 in our hospital. Results A total of 56 patients were included (third line/fourth or later line = 42/14). All patients were previously treated with gemcitabine plus nab-paclitaxel and 45 patients were previously treated with modified FOLFIRINOX. The median progression-free survival (PFS) and overall survival (OS) were 1.6 and 4.6 months, respectively. The disease control rate was 21.4%. Performance status, modified Glasgow prognostic score and carcinoembryonic antigen level were independently associated with survival. Our prognostic model using these parameters could classify patients into good (n = 32) and poor (n = 24) prognostic groups. The median PFS and OS were longer in good than in poor prognostic group, but the difference in PFS was very small (PFS: 2.1 vs. 1.4 months, P = 0.01. OS: 6.8 vs. 2.4 months, P < 0.01). Interstitial pneumonia occurred in one patient (1.8%). Conclusions Benefits of erlotinib plus gemcitabine as late-line chemotherapy were limited, particularly with respect to PFS. Development of more effective third-line treatment options is desirable in the future.

Objective and method: To examine the effect of altitude swimming training on BNP (Brain natriuretic peptide) and ANP (Atrial Natriuretic Peptide) levels, and evaluate if BNP and ANP can be hemodynamic markers of hypoxia- and traininginduced stress, Ten collegiate swimmers (Tr) who participated in the altitude training camp at 1900m and 5 healthy subjects (Con) were participated in this study. Blood samples were obtained before the training (day0: Pre), during the training (day5: T1, 10: T2, 16: T3), and after the training (5th after descent: Post). Results: Chronologically, BNP of Tr decreased immediately after ascent and increased thereafter, however the changes were not significant. ANP levels were almost unchanged in Tr, whereas there was an increase at T1 in Con compared with Tr (P

Objectives To compare the treatment outcomes of gemcitabine with nab-paclitaxel (GnP) and modified FOLFIRINOX (mFFX; a combination of fluorouracil, leucovorin, irinotecan, and oxaliplatin) for metastatic pancreatic cancer. Methods We retrospectively analyzed consecutive patients with metastatic or recurrent pancreatic cancer treated with GnP or mFFX as the first-line chemotherapy between March 2014 and December 2019 in our hospital. Treatment outcomes were compared using propensity score matching to adjust for age, sex, performance status, carcinoembryonic antigen levels, carbohydrate antigen 19-9 levels, and disease status (metastatic or recurrent). Results Five hundred sixty-eight patients were included (GnP/mFFX, 456/112). After propensity score matching, 218 patients were extracted. The median age was around 61 years, and the proportion of performance status 0 was approximately 90%. The median overall survival values were 14.6 and 15.5 months (P = 0.45), and the median progression-free survival was 7.4 months (P = 0.53) for GnP and mFFX, respectively. The disease control rates were higher in the GnP group (82.6% vs 67.9%, P = 0.02). In nonhematologic adverse events, grade 3/4 anorexia and diarrhea occurred significantly more frequently in the mFFX group. Conclusions Gemcitabine with nab-paclitaxel had a higher disease control rate and lower rates of severe anorexia and diarrhea in our propensity-matched population.

Elderly pancreatic cancer (PC) patients are often considered vulnerable to treatment and standard treatment strategy for this subpopulation is uncertain. Cachexia and sarcopenia are reported to be associated with reduced physical performance, reduced anti-tumor response, increased chemotherapy toxicity, and poor prognosis in several malignancies. The aim of this study was to evaluate the impact of cachexia and sarcopenia on the clinical course of elderly PC patients receiving chemotherapy. We retrospectively investigated consecutive elderly metastatic PC patients (≥ 75 years) treated with chemotherapy at our institution between January 2015 and April 2020. Skeletal muscle index was calculated at the third lumbar vertebra using pretreatment computed tomography. We evaluated time to treatment failure (TTF), progression-free survival (PFS), overall survival (OS), early treatment discontinuation, relative dose intensity (RDI), and severe adverse events (AEs). Among 80 patients included (gemcitabine plus nab-paclitaxel [GnP] 52; gemcitabine 21; S1 6; modified FOLFIRINOX 1), cachexia and sarcopenia were present in 48 (60%) and 61 (76%) patients, respectively. Cachexia was associated with older age, worse performance status, higher level of neutrophil to lymphocyte ratio, worse nutritional status, and shorter TTF and PFS. Furthermore, it was also associated with early treatment discontinuation, reduced RDI of nab-paclitaxel, and increased incidence of grade 4 neutropenia in patients receiving GnP. On the other hand, sarcopenia had less impact on the clinical course of elderly PC patients. In our experience, cachexia was considered an effective tool in the management of elderly PC patients receiving palliative chemotherapy.

Single-balloon enteroscopy-assisted endoscopic retrograde cholangiopancreatography (SBE-ERCP) has been increasingly performed for the treatment of malignant biliary obstruction (MBO) in patients with surgically altered anatomy (SAA), however evidence is scarce. Therefore, we conducted this study to evaluate the efficacy and safety of self-expandable metallic stent (SEMS) placement using a short type SBE.We retrospectively examined consecutive patients with SAA who received initial SEMS for MBO at our institution between February 2016 and February 2019. We evaluated patient characteristics, technical and functional success rates, time to recurrent biliary obstruction (TRBO) and complications according to the location of the biliary stricture.A total of 26 patients were included in this study. The primary tumor was gastric cancer in 12, pancreatic cancer in 6, cholangiocarcinoma in 6 and gallbladder cancer in 2. The biliary stricture site was distal bile duct in 14, hilar bile duct in 3 and hepaticojejunostomy (HJ) anastomosis in 9. Technical and functional success rates were 92 and 88%, respectively. TRBO, median survival time, overall rate of RBO and early complications were not different according to the stricture site (SEMS placement

Drug-induced interstitial lung disease (ILD) is one of the most serious adverse events with a high mortality rate and represents a serious clinical problem. However, gemcitabine plus nab-paclitaxel (GnP)-induced ILD in pancreatic cancer (PC) patients has not been thoroughly investigated. Therefore, we conducted this study to examine the clinical characteristics of GnP-induced ILD and identify risk factors for developing ILD. We retrospectively investigated consecutive patients with PC who received GnP between January 2015 and April 2020. We compared the clinical characteristics and overall survival (OS) according to ILD occurrence and explored risk factors including ABO blood type for developing ILD. Of the 910 patients included in this study, ILD occurred in 20 patients (2.2%). PC patients who developed ILD had a significantly higher frequency of blood type B compared to those without ILD (42% vs. 22%, p ˂ 0.05). Other baseline characteristics including smoking history and current/previous lung disease were not different between the two groups. Median time from initiation of GnP to onset of ILD was 80 days. All patients recovered from ILD and OS was not significantly different according to ILD occurrence. Multivariate analysis revealed that blood type B was an independent risk factor for developing ILD. We demonstrated that GnP-induced ILD occurred in 2.2% of PC patients with no mortality and OS did not differ according to ILD occurrence. Furthermore, we clarified that ABO blood type B was an independent risk factor for developing ILD in PC patients receiving GnP.

Background and study aims Self-expandable metallic stents (SEMS) are now widely used even for patients with borderline resectable (BR) pancreatic cancer (PC), as neoadjuvant therapy has become common. Therefore, we conducted this study to evaluate safety of SEMS placement in the population including BR PC and to explore risk factors for recurrent biliary obstruction (RBO), pancreatitis, and cholecystitis. Patients and methods We retrospectively investigated consecutive patients with PC who received initial SEMS between January 2015 and March 2019. We compared time to RBO (TRBO), causes of RBO, and stent-related adverse events (AEs) according to resectability status. Univariate and multivariate analyses were performed to explore risk factors for TRBO, pancreatitis, and cholecystitis. Results A total of 135 patients were included (BR 31 and unresectable [UR] 104). Stent-related AEs occurred in 39 patients: pancreatitis 14 (mild/moderate/severe 1/6/7), cholecystitis 12, and non-occluding cholangitis 13. TRBO, causes of RBO, and stent-related AEs were not significantly different according to resectability status. Overall rate of RBO was higher in UR PC due to the longer follow-up period. Sharp common bile duct (CBD) angulation was an independent risk factor for short duration of TRBO. High pancreatic volume index and SEMS of high axial force were independent risk factors for pancreatitis, whereas tumor involvement to orifice of cystic duct was the only risk factor for cholecystitis. Conclusions We demonstrated that SEMS can be safely deployed even in patients with BR PC. Sharp CBD angulation and high pancreatic volume index were identified as novel risk factors for RBO and pancreatitis, respectively, after SEMS placement.

Background The prognosis of borderline resectable (BR) pancreatic cancer (PC) has improved by multidisciplinary therapy. However, the differences in clinical course between pancreatic head (Ph) and pancreatic body and tail (Pbt) cancer has not been fully elucidated. Therefore, we conducted this study to compare the clinical course of BR PC patients according to tumor location. Methods We retrospectively investigated consecutive patients with BR PC who initiated neoadjuvant chemotherapy (NAC) between March 2015 and April 2019. We compared clinicopathological characteristics, treatment, recurrence pattern and post recurrence treatment between Ph and Pbt cancer patients. We also compared recurrence free survival (RFS) and overall survival (OS) according to tumor location. Results A total of 108 patients with BR PC were included. Tumor location was Ph 74 and Pbt 34, respectively. Initial regimen of NAC was nab-paclitaxel/gemcitabine in 106 and gemcitabine in 2, respectively. Although Pbt location was associated with more advanced T stage, it showed similar N stage, pathological stage, RFS, OS, and details of adjuvant chemotherapy compared to Ph location. The most common site of postoperative recurrence was liver-only recurrence in Ph tumor (32% vs. 6%, p = 0.04) and peritoneal dissemination-only recurrence in Pbt tumor (35% vs. 11%, p = 0.06). Furthermore, Ph cancer patients received a higher rate of monotherapy compared to Pbt cancer patients (19% vs. 0%, p = 0.08). Conclusions In our experience tumor location was not a prognostic factor for OS in BR PC. Postoperative recurrence pattern and treatment after recurrence were different according to tumor location.

Background and study aims Endoscopic ultrasound (EUS)-guided tissue acquisition is sometimes required to diagnose small solid pancreatic lesions. The aim of this study was to evaluate the diagnostic yield of EUS-guided tissue acquisition for small solid pancreatic lesions and the differences in diagnostic yield among different needles. Patients and method We retrospectively analyzed consecutive patients who had undergone EUS-guided tissue acquisition for solid pancreatic lesions less than 2 cm between November 2012 and June 2019. Three types of needles were evaluated in this study: a 22-gauge fine-needle aspiration (FNA) Lancet needle, a 20-gauge fine-needle biopsy (FNB) Menghini needle with a lateral forward bevel, and a 22-gauge FNB Franseen needle. We evaluated the diagnostic yield and safety of the procedure using these needles. Results We analyzed 160 patients with 163 lesions. The overall sensitivity, specificity, and accuracy were 92.0 %, 100 %, and 92.6 %, respectively. In the histological plus cytological diagnosis, accuracies of the Lancet, Menghini, and Franseen needles were 92.7 %, 97.0 %, and 85.7 %, respectively (P = 0.10). In the histological diagnosis alone, the negative predictive values (NPVs) of the Lancet, Menghini, and Franseen needles were 13.3 %, 53.3 %, and 27.3 %, respectively (P = 0.08). Adverse events occurred in four cases (2.5 %): one postprocedural bleeding, two cases of pancreatitis, and one pancreatic abscess. Conclusions EUS-guided tissue acquisition for small solid pancreatic lesions has a high diagnostic yield and safety. This study suggested a difference in the diagnostic yield of each needle for small solid pancreatic lesions.

Infected acute necrotic collections (ANC) and walled-off necrosis (WON) of the pancreas are associated with high mortality. The difference in mortality between open necrosectomy and minimally invasive therapies in these patients remains unclear. This retrospective multicenter cohort study was conducted among 44 institutions in Japan from 2009 to 2013. Patients who had undergone invasive treatment for suspected infected ANC/WON were enrolled and classified into open necrosectomy and minimally invasive treatment (laparoscopic, percutaneous, and endoscopic) groups. The association of each treatment with mortality was evaluated and compared. Of 1159 patients with severe acute pancreatitis, 122 with suspected infected ANC or WON underwent the following treatments: open necrosectomy (33) and minimally invasive treatment (89), (laparoscopic three, percutaneous 49, endoscopic 37). Although the open necrosectomy group had a significantly higher mortality on univariate analysis (p = 0.047), multivariate analysis showed no significant associations between open necrosectomy or Charlson index and mortality (p = 0.29, p = 0.19, respectively). However, age (for each additional 10 years, p = 0.012, odds ratio [OR] 1.50, 95% confidence interval [CI] 1.09–2.06) and revised Atlanta criteria-severe (p = 0.001, OR 7.84, 95% CI 2.40–25.6) were significantly associated with mortality. In patients with acute pancreatitis and infected ANC/WON, age and revised Atlanta criteria-severe classification are significantly associated with mortality whereas open necrosectomy is not. The mortality risk for patients undergoing open necrosectomy and minimally invasive treatment does not differ significantly. Although minimally invasive surgery is generally preferred for patients with infected ANC/WON, open necrosectomy may be considered if clinically indicated.

Objectives A multivariate index calculated using plasma free amino acids (PFAA index) was reported as a diagnostic biomarker for pancreatic cancer (PaC). Although diabetes mellitus (DM) is expected to be an early diagnostic indicator of PaC, identifying the high-risk individuals among patients with DM is warranted. We evaluated the diagnostic yield of the PFAA index for PaC in patients with DM. Methods We compared the diagnostic yield of the PFAA index between individuals with and those without DM. Cases and controls were recruited prospectively, and controls were matched to cases at a 1:1 ratio for age, sex, and DM status. Results A total of 180 case–control pairs were included in the analysis. The prevalence of DM was 53.3%. The sensitivity of the PFAA index was 66.7% in cases with DM and 56.0% in those without DM (P = 0.14), and the specificity was 92.7% in controls with DM and 94.0% in those without DM (P = 0.95). Conclusions This matched case-control study revealed a comparable diagnostic yield of the PFAA index for PaC in individuals with and those without DM. The PFAA index can be used as a biomarker for further diagnostic imaging in selected patients with DM.

Antimicrobial prophylaxis is not generally recommended for patients with severe acute pancreatitis (SAP) owing to the limited clinical benefits. Nonetheless, it is frequently administered in actual practice given the patients' critical condition and the lack of solid evidence showing adverse effects of antimicrobial prophylaxis. We evaluated herein an association between antimicrobial prophylaxis and invasive pancreatic candidiasis as an adverse effect in patients with SAP.This is a retrospective cohort study of all consecutive patients with SAP who were admitted to the study institutions (n = 44) between January 1, 2009, and December 31, 2013. We performed multivariable logistic regression analysis adjusting for the extent of pancreatic necrosis and surgical interventions for invasive pancreatic candidiasis.Of the 1097 patients with SAP, 850 (77.5%) received antimicrobial prophylaxis, and 21 (1.9%) had invasive pancreatic candidiasis. In multivariable logistic regression analysis, antimicrobial prophylaxis was significantly associated with the development of invasive pancreatic candidiasis (adjusted odds ratio, 4.23; 95% confidence interval, 1.14-27.6) (P = 0.029).The results suggest that antimicrobial prophylaxis may contribute to the development of invasive pancreatic candidiasis, and therefore, the routine use of antimicrobial prophylaxis for SAP may be discouraged.

Biliary tract cancer refers to a group of malignancies including cholangiocarcinoma, gallbladder cancer, and ampullary cancer. While surgical resection is considered the only curative treatment, postoperative recurrence can sometimes occur. Adjuvant chemotherapy is used to prolong prognosis in some cases. Many unresectable cases are also treated with chemotherapy. Therefore, systemic chemotherapy is widely introduced for the treatment of biliary tract cancer. Evidence on chemotherapy for biliary tract cancer is recently on the increase. Combination chemotherapy with gemcitabine and cisplatin is currently the standard of care for first-line chemotherapy in advanced cases. Recently, FOLFOX also demonstrated efficacy as a second-line treatment. In addition, efficacies of isocitrate dehydrogenase inhibitors and fibroblast growth factor receptor inhibitors have been shown. In the adjuvant setting, capecitabine monotherapy has become the standard of care in Western countries. In addition to conventional cytotoxic agents, molecular-targeted agents and immunotherapy have been evaluated in multiple clinical trials. Genetic testing is used to check for genetic alterations and molecular-targeted agents and immunotherapy are introduced based on tumor characteristics. In this article, we review the latest evidence of chemotherapy for biliary tract cancer.

Periampullary cancers are often diagnosed at advanced stages and can cause both biliary and duodenal obstruction. As these two obstructions reduce patients’ performance status and quality of life, appropriate management of the disease is important. Combined malignant biliary and duodenal obstruction is classified according to the location and timing of the duodenal obstruction, which also affect treatment options. Traditionally, surgical bypass (gastrojejunostomy and hepaticojejunostomy) has been performed for the treatment of unresectable periampullary cancer. However, it has recently been substituted by less invasive endoscopic procedures due to its high morbidity and mortality. Thus, endoscopic double stenting (transpapillary stenting and enteral stenting) has become the current standard of care. Limitations of transpapillary stenting include its technical difficulty and the risk of duodenal-biliary reflux. Recently, endoscopic ultrasound-guided procedures have emerged as a novel platform and have been increasingly utilized in the management of biliary and duodenal obstruction. As the prognosis of periampullary cancer has improved due to recent advances in chemotherapy, treatment strategies for biliary and duodenal obstruction are becoming more important. In this article, we review the treatment strategies for combined malignant biliary and duodenal obstruction based on the latest evidence.

Pancreatic cancer is the fourth leading cause of cancer-related death in Japan. Pancreatic cancer is categorized as resectable, borderline resectable, or unresectable based on the degree of adjacent vascular invasion and the presence of distant metastases. Neoadjuvant chemotherapy with gemcitabine and S-1 (NAC-GS) has recently become a standard option for resectable pancreatic cancer in Japanese patients. According to previous reports, GS is considered to be relatively safe and feasible treatment for Japanese patients, including the elderly. However, NAC-GS is occasionally associated with severe adverse events which may ultimately render the patient unfit for surgery. A 60-year-old man with resectable pancreatic cancer suffered from severe necrotic enteritis during NAC-GS, which required surgical resection. Considering the time course and histological findings of the resected bowel, S-1 was believed to be the causative agent. The low urinary dihydrouracil to uracil ratio also suggested possible dihydropyrimidine dehydrogenase deficiency, which may have hindered the metabolism of S-1 and contributed to the development of necrotic enteritis. Life-threatening enteritis occurs in approximately 0.3% of all patients who receive S-1. As initial symptoms are non-specific, patients should be instructed to lower the hurdle for contacting the hospital during NAC-GS.

OBJECTIVES In patients with severe acute pancreatitis (SAP), early enteral nutrition (EN) is recommended by major clinical practice guidelines, but the exact timing for the initiation of EN is unknown. METHODS We conducted a post hoc analysis of the database for a multicenter (44 institutions) retrospective study of patients with SAP in Japan. The patients were classified into 3 groups according to the timing of EN initiation after the diagnosis of SAP: within 24 hours, between 24 and 48 hours, and more than 48 hours. The primary outcome was in-hospital mortality. RESULTS Of the 1094 study patients, 176, 120, and 798 patients started EN within 24 hours, between 24 and 48 hours, and more than 48 hours after SAP diagnosis, respectively. On multivariable analysis, hospital mortality was significantly better with EN within 48 hours than with more than 48 hours (adjusted odds ratio, 0.49; 95% confidence interval, 0.29-0.83; P < 0.001) but did not significantly differ between the groups with EN starting within 24 hours and between 24 and 48 hours (P = 0.29). CONCLUSIONS Enteral nutrition within 24 hours may not confer any additional benefit on clinical outcomes compared with EN between 24 and 48 hours.

BACKGROUND Stenting against recurrent biliary obstruction (RBO) after placement of covered metal stent (CMS) for distal malignant biliary obstruction (MBO) is still challenging. This study investigated the feasibility of a novel laser-cut fully CMS with anti-reflux valve in patients with distal MBO refractory to conventional CMS. METHODS Patients who underwent Duckbill-type metal stent (DMS) placement between June 2019 and May 2020 were included. Early complications, causes of RBO including non-occlusion cholangitis, and time to RBO (TRBO) were evaluated. TRBO of DMS was also compared with that of previous CMS. RESULTS Thirty patients were included: pancreatic cancer/metastatic lymph nodes in 29 patients/one patient; duodenal stenosis in 13 patients. Technical and functional success were achieved in all patients. Mild cholangitis and mild pancreatitis developed in each one. Median follow-up period was 167 days (range, 23-527 days). RBO occurred in nine patients (30%): sludge formation in four patients, hemobilia in one patient, symptomatic distal stent migration in three patients, and non-occlusion cholangitis in one patient. TRBO of DMS was significantly longer than that of previous CMS (median 224 days vs median 120 days, P = .0025). DMS was successfully removed in all of six patients when re-intervention was needed. CONCLUSIONS Duckbill-type metal stent might be safe and effective in patients with distal MBO refractory to conventional CMS.

Background. A higher Ki-67 labeling index is associated with a poorer prognosis in gastroenteropancreatic neuroendocrine neoplasms. It has also been proposed that the Ki-67 labeling index may increase during disease progression from the primary site to metastatic sites. Although biopsy specimens are used to measure the Ki-67 labeling index, heterogeneity in lesions is thought to affect the assessment of the Ki-67 labeling index. To overcome tumor heterogeneity, we evaluated the variability in the Ki-67 labeling index between primary lesions and hepatic metastases by analyzing only surgically resected specimens. Methods. We conducted a single-center retrospective study to analyze the variability in the Ki-67 labeling index and the change in tumor grade between the primary site and metastatic hepatic sites in 19 patients diagnosed with gastroenteropancreatic neuroendocrine neoplasms at the Cancer Institute Hospital of the Japanese Foundation for Cancer Research from 1998 to 2018. Both the primary site and metastatic hepatic sites were surgically resected. Results. Among the 19 patients with gastroenteropancreatic neuroendocrine neoplasms, 12 patients (63%) showed higher levels of the Ki-67 labeling index at metastatic hepatic sites than at the primary site. The median Ki-67 labeling index levels for the primary lesion and metastatic hepatic lesions were 5% and 10%, respectively. The Ki-67 labeling index levels were significantly elevated in the metastatic hepatic lesions compared to the primary lesion ( P = .002). Conclusions. This study addressed the heterogeneity of the Ki-67 labeling index by analyzing only surgically resected specimens. We observed a statistically significant increase in the Ki-67 labeling index in hepatic metastases compared to the primary lesion.

Intraductal papillary mucinous neoplasm (IPMN) sometimes forms fistulas with other organs due to high pressure of pancreatic duct filled with huge amount of mucus. Pancreatobiliary fistula may cause obstructive jaundice due to the mucus and it is hard to manage the jaundice by endoscopic biliary stenting because of high viscosity of the bile. We report a case of IPMN with pancreatobiliary fistula managed by endoscopic ultrasound (EUS)-guided hepaticogastrostomy (HGS). The patient was 87 years old and presented with obstructive jaundice. As a transpapillary biliary stent was considered to have a risk of migration due to the absence of bile duct stenosis, a nasobiliary catheter was placed as an initial drainage. However, the catheter was frequently obstructed by mucus. The patient was intolerable for surgery because of his age. Considering the intrahepatic bile was serous, EUS-HGS was performed and jaundice improved successfully. This case study revealed that EUS-HGS might be a therapeutic option for obstructive jaundice caused by an IPMN-associated pancreatobiliary fistula.

Background The prognostic impact of tumour location (pancreatic head vs. pancreatic body/tail) and first-line chemotherapy regimen (gemcitabine plus nab-paclitaxel vs. modified FOLFIRINOX) has not been fully elucidated in locally advanced pancreatic cancer. Therefore, we conducted this study to examine the prognostic impact of tumour location and first-line chemotherapy regimen. Methods We retrospectively investigated locally advanced pancreatic cancer patients who initiated first-line chemotherapy (gemcitabine plus nab-paclitaxel or modified FOLFIRINOX) between March 2014 and December 2019. We compared clinical characteristics and survival outcomes according to chemotherapy regimen and tumour location. Furthermore, we examined the prognostic factors associated with overall survival using cox proportional hazards model. Distant metastasis pattern was also compared according to tumour location. Results A total of 128 patients were included (GnP 95, mFFX 33; Ph 66, Pbt 62). Distribution of chemotherapy regimen was balanced between pancreatic head and pancreatic body/tail cancers. Eight patients underwent conversion surgery and 81 patients (63%) developed distant metastasis. Although patients receiving modified FOLFIRINOX were significantly younger and tended to have better performance status compared to patients receiving gemcitabine plus nab-paclitaxel, radiological tumour response, progression-free survival, overall survival and chemotherapy-related adverse events were similar between the two groups except for grades 3–4 anorexia (9% vs. 1%, P = 0.05). Furthermore, overall survival was similar between pancreatic head and pancreatic body/tail cancers. Conversion surgery and radiation therapy were identified as independent prognostic factors for overall survival. The most common site of distant metastasis was liver metastasis in both groups and pattern of distant metastasis was not different between the two groups. Conclusions In our experience, tumour location and first-line chemotherapy regimen were not a prognostic factor for overall survival in locally advanced pancreatic cancer.

Background Although the efficacy of neoadjuvant chemotherapy with gemcitabine plus S-1 (NAC GS) has recently been reported in resectable pancreatic cancer, severe adverse events were frequently observed. Sarcopenia has been reported to be associated with reduced antitumor response and chemotherapy toxicity in several malignancies. The aim of this study is to evaluate the impact of body composition on short-term outcomes of NAC GS in resectable pancreatic cancer patients. Methods Clinicopathological data of consecutive patients treated with NAC GS at our institution from February 2019 to April 2020 were retrospectively reviewed. Anthropometric variables were calculated at the third lumbar vertebra using pretreatment computed tomography images. We investigated the association between body composition variables, and antitumor response and chemotherapy toxicity. Results Among 62 patients included in this study, 25 patients (40%) were sarcopenic at diagnosis. Sixty-one patients received surgery at our institution and 57 patients received pancreatic resection (R0/R1 resection 56/1). Fifty-six patients completed two cycles of NAC GS and severe adverse events (≥grade 3) occurred in 42 patients (hematologic toxicity 41 patients [66%]; non-hematologic toxicity 3 patients). Body mass index and total adipose tissue index were significantly lower in sarcopenic patients compared to non-sarcopenic patients. Completion rate of NAC, rate of treatment delay/interruption, relative dose intensity of gemcitabine and S-1, radiological and pathological tumor response after NAC were not different between sarcopenic and non-sarcopenic patients. Furthermore, there was no significant association between body composition, and severe adverse events and intolerance. Conclusions In our experience, NAC GS was similarly tolerable and effective in resectable pancreatic cancer patients regardless of the presence of sarcopenia.

No evidence has shown the efficacy of Sodium Risedronate (Risedronate) for glucocorticoid-induced osteoporosis (GIO) in patients with Rheumatoid arthritis (RA). The aim of this study was to explore the effectiveness and safety of Risedronate for GIO complicated with RA.This was a six-month randomized, double-blind, placebo-controlled trial of 95 patients with GIO complicated with RA from 19 centers. The primary endpoint was the change from baseline in lumbar spine bone mineral density (L-BMD). Secondary endpoints included changes in femoral neck and total hip BMD and bone turnover markers, as well as rheumatoid arthritis Disease Activity Score with 28-joint counts. Incident of non-traumatic spine fractures and adverse events were tracked as safety endpoints.Increase in L-BMD was significantly greater in the Risedronate group compared to the Placebo group (Risedronate: 3.49% [95% CI: 1.92-5.05] vs Placebo: 0.12% [95% CI: -2.07 to 2.30],Risedronate was effective in increasing L-BMD and was well tolerated in patients with GIO complicated with RA.

Brain metastases are extremely rare in patients with pancreatobiliary neuroendocrine caricnoma (PB-NEC). In this case report, we report two rare cases of brain metastases in patients with PB-NEC. Each patient was diagnosed with brain metastases five and ten months after the initial diagnosis of PB-NEC. It is noteworthy that the serum tumor marker neuron-specific enolase (NSE) or pro-gastrin-releasing peptide (Pro-GRP) was elevated, although the primary and metastatic lesions other than in the brain were under control with systemic chemotherapy. Moreover, the patients complained of no neurological symptoms until they were diagnosed with brain metastases. Although the incidence of brain metastases of PB-NEC is exceedingly low, it is important to keep in mind the possibility of brain metastases during the course of treatment for PB-NEC. In addition, we discuss a strategy of treatment and screening for brain metastases of PB-NEC in this case report.

Duodenal varices are ectopic varices that are rare but can involve any site along the digestive tract outside the gastroesophageal region. Ectopic variceal bleeding is generally massive and life threatening; the mortality rate is approximately 40%. Up to 17% of ectopic varices occur in the duodenum. However, duodenal varices pose a significant therapeutic challenge due to the lack of standard treatment guidelines. We report a case of duodenal variceal bleeding secondary to portal vein stenosis in a 77-year-old woman receiving chemotherapy for unresectable perihilar cholangiocarcinoma. The patient presented with melena, nausea, vomiting and unstable vital signs suggestive of hemorrhagic shock. Emergency esophagogastroduodenoscopy revealed large nodular varices with a ruptured erosion on top in the superior duodenal angle, and variceal bleeding had stopped by the time of the procedure. Subsequent computed tomography showed the development of portosystemic collaterals; therefore, we performed percutaneous portal vein stent placement to reduce portal vein pressure. Since persistent bleeding was suspected, we also performed endoscopic injection sclerotherapy and achieved successful hemostasis with an improvement in liver function. This case revealed that a combination of portal vein stent placement and endoscopic injection sclerotherapy might be an effective therapy for duodenal variceal bleeding caused by portal vein stenosis.

Highlight Sasaki and colleagues report their experience with double stenting combined with endoscopic ultrasound-guided choledochoduodenostomy using a new anti-reflux metal stent to prevent duodenobiliary reflux in combined biliary and duodenal obstruction. This double stenting method is a new strategy for the management of combined biliary and duodenal obstruction.

Background There is no established second-line treatment after failure of gemcitabine plus nab-paclitaxel (GnP) therapy for metastatic pancreatic cancer (MPC). The purpose of this study was to evaluate the efficacy and tolerability of the modified FOLFIRINOX (mFFX) as a second-line therapy for MPC and to investigate prognostic factors for survival. Methods From 2015 to 2019, we retrospectively reviewed the medical records of consecutive patients receiving mFFX for MPC after failure of GnP therapy. Patients were treated every 2 weeks with mFFX (intravenous oxaliplatin 85 mg/m2, intravenous irinotecan 150 mg/m2, and continuous infusion of 5-fluorouracil 2400 mg/m2 for 46 h without bolus infusion). Results In total, 104 patients received mFFX. The median overall survival (OS) was 7.0 months (95% confidence interval [CI]: 6.2–9.8) and the progression-free survival (PFS) 3.9 months (95% CI 2.8–5.0). The objective response rate was 10.6% and the disease control rate 56.7%. The median relative dose intensities of oxaliplatin, irinotecan, and infusional 5-FU were 80.0% (range 21.5–100%), 77.2% (range 38.1–100%), and 85.9% (range 36.9–100%), respectively. Grade 3–4 toxicities were reported in 57 patients (54.8%), including neutropenia, leukopenia, anemia, febrile neutropenia, and peripheral sensory neuropathy. Glasgow prognostic score and carcinoembryonic antigen level were independently associated with survival. Our prognostic model using these parameters could classify the patients into good (n = 38), intermediate (n = 47), and poor (n = 19) prognostic groups. The median OS and PFS time was 14.7 (95% CI 7.6–16.3) and 7.6 months (95% CI 4.1–10.5) for the good prognostic factors, 6.5 (95% CI 5.5–10.0) and 3.6 months (95% CI 2.7–4.8) for the intermediate prognostic factors and 5.0 (95% CI 2.9–6.6) and 1.7 months (95% CI 0.9–4.3) for the poor prognostic factors, respectively. Conclusions The mFFX showed to be a tolerable second-line treatment for MPC after GnP failure. Our prognostic model might be useful for deciding whether mFFX is indicated in this setting.

Early identification of severe disease of acute pancreatitis (AP) is of critical importance to improve the prognosis. Fluid sequestration (FS), calculated from administrated fluid and fluid output, is a simple prognostic parameter. We examined its utility in the early phase of AP. We retrospectively investigated AP patients between January 2009 and April 2017. We compared FS in the first 24 h (FS24) with FS in the first 48 h (FS48) and administrated fluid volume within the first 24 h (FV24). Diagnostic yield for predicting intensive care unit (ICU) admission and persistent organ failure (POF) was assessed using receiver operating characteristic curves. We also evaluated risk factors for developing severe disease of AP. A total of 400 AP patients were included in the analysis (median age 64 years; male 60%). According to the Japanese severity criteria, 158 patients (40%) were diagnosed as severe disease. The rates of mortality, ICU admission and POF were 0.8%, 4.5% and 7.3%, respectively. FS24 showed a similar predictive accuracy in comparison with FS48 and was superior to FV24 in predicting ICU admission and POF. FS24 ≥ 1.6 L, male sex, presence of systemic inflammatory response syndrome and computed tomography severity index ≥ 3 on admission were independent risk factors for disease progression in AP in the multivariate analysis. FS24 was a simple and easily calculated parameter with high predictive accuracy for discriminating patients who needed intensive care. Patients with FS24 ≥ 1.6 L had an increased risk of developing severe disease.

Purpose Our previous phase I trial suggested feasibility of addition of leucovorin (LV) to S-1 and gemcitabine therapy in advanced pancreatic cancer. The aim of this phase II trial was to assess the efficacy and toxicity of gemcitabine, S-1 and LV (GSL) combination therapy for advanced pancreatic cancer. Methods Chemotherapy-naïve patients with histologically or cytologically proven advanced pancreatic cancer were enrolled. Gemcitabine was administered at a dose of 1000 mg/m2 by 30 min infusion on days 1, S-1 40 mg/m2 orally twice daily and LV 25 mg orally twice daily on days 1 to 7 every 2 weeks. Primary end point was progression free survival (PFS). Results A total of 49 patients with advanced pancreatic cancer (19 locally advanced and 30 metastatic) were enrolled. Overall response rate and disease control rate were 32.7% and 87.8%. The median PFS and overall survival (OS) were 10.8 (95% confidence interval [CI], 7.4-13.5) and 20.7 (95% CI 13.0-NA) months with 1-year survival rate of 73.4%. Major Grade 3-4 toxicities were neutropenia (22.4%) and stomatitis (14.3%). No toxicity related death was observed. Conclusions In this single center, phase II trial, gemcitabine, S-1 and LV combination therapy was tolerable and can potentially be a treatment option for advanced pancreatic cancer.

Background and study aims While endoscopic ultrasound (EUS)-guided drainage of pancreatic fluid collection (PFC) is recommended to be performed ≥ 4 weeks after onset of acute pancreatitis (AP), early ( Patients and methods Consecutive patients who received EUS-guided drainage (EUS-PCD) of infected or symptomatic PFC at the University of Tokyo were retrospectively studied. Contraindications for EUS-PCD are lack of encapsulation or adhesion to the gastrointestinal tract. Safety and effectiveness of early vs delayed (≥ 4 weeks) EUS-PCD were compared. Results A total of 35 patients underwent EUS-PCD (12 early and 23 delayed) using 19 large-bore fully-covered metallic stent and 16 plastic stents. The median diameter of PFC was 110 mm (40 – 180) and 122 mm (17 – 250) in the early and delayed drainage groups, respectively. Median time from onset of AP to drainage was 23 and 85 days for early and delayed drainage, respectively. The technical success rate of EUS-guided drainage was 100 %. Endoscopic necrosectomy was performed in six early and 16 cases of delayed drainage. The adverse event rate was 25 % (3 bleeding) and 13 % (2 perforations and 1 CO2 retention) in the early and delayed drainage groups, respectively. Two patients died (1 early and 1 delayed) due to multiorgan failure. Conclusion Endoscopic drainage and subsequent necrosectomy of symptomatic PFC within 4 weeks after onset of acute pancreatitis was feasible, given that the collection was encapsulated and attached to the gastrointestinal tract.

Purpose The survival benefit of first-line chemotherapy (CT1) for biliary tract cancer (BTC) is now established but the role of second-line chemotherapy (CT2) has not been fully elucidated yet. Methods Consecutive advanced BTC patients receiving CT1 between 2000 and 2016 were retrospectively studied. We investigated the safety and efficacy of CT2, prognostic factors for residual survival after CT1, and explored subgroups who would benefit from CT2. Results Among 294 patients receiving CT1 for advanced BTC, CT2 was given in 139 patients (47%). CT2 provided a response rate of 4%, a disease control rate of 52%, a median progression-free survival of 2.8 and overall survival of 7.7 months, respectively. CT2 was associated with longer residual survival after CT1 (hazard ratio [HR] 0.61, p

Exocrine pancreatic insufficiency may impair the nutritional status in pancreatic cancer (PC), but the role of pancreatic enzyme replacement therapy (PERT) is not fully evaluated. Therefore, we conducted this multicenter open-label randomized controlled trial to evaluate the role of PERT in PC patients.Patients with unresectable PC receiving chemotherapy were randomly assigned to pancrelipase and nonpancrelipase groups. Patients in the pancrelipase group took oral pancrelipase of 48,000 lipase units per meal. N-benzoyl-tryrosyl para-aminobenzoic acid (NBT-PABA) test was performed at baseline. Our primary endpoint was change in body mass index (BMI) at 8 weeks. Secondary endpoints were change in other nutritional status at 8 weeks and overall survival.A total of 88 patients were enrolled between May 2014 and May 2016. The NBT-PABA test was lower than the normal range in 90%. There were no significant differences in change in BMI at 8 weeks: 0.975 and 0.980 in the pancrelipase and the nonpancrelipase groups, respectively (P = 0.780). The other nutritional markers were also comparable. The median overall survival was 19.0 and 12.0 months (P = 0.070).In this randomized controlled trial, pancrelipase failed to improve the change in BMI at 8 weeks in PC patients receiving chemotherapy.

An 87-year-old man was admitted to our hospital due to fever and elevated liver enzymes. Computed tomography (CT) scan revealed bile duct stones with a dilated biliary system, which confirmed the diagnosis of cholangitis. A 12-cm simple hepatic cyst was also seen in the right liver, which had been detected on CT scan 5 years before, and did not change in size. Fever did not subside even after endoscopic biliary drainage and a repeated CT scan showed an enlarged cyst up to 14 cm, suggesting cyst infection. An enlarged hepatic cyst collapsed after percutaneous transhepatic drainage, along with resolution of fever. Simple hepatic cysts are common and most of them are asymptomatic. Infection of simple hepatic cysts is a rare condition and the major entry route is considered as the biliary tract as communication between the biliary tract and cysts is reportedly observed in those cases. However, in our case, no communication was seen on cholangiogram or cystogram on fluoroscopy and bilirubin level of the cyst aspirate was low. Given the fact that patients with cholangitis are rarely complicated by hepatic cyst infection, other routes of bacterial entry to simple hepatic cysts should also be considered.

The role of carbohydrate antigen 19-9 (CA19-9) kinetics in patients with biliary tract cancer (BTC) receiving chemotherapy remains to be elucidated. A total of 185 advanced or recurrent BTC patients receiving a first line chemotherapy between January 2006 and March 2016, were retrospectively studied. Serum CA19-9 was measured at baseline and after two cycles of chemotherapy, and patients were categorized based on CA19-9 response: CA19-9 decrease group (≥ 30% decrease), stable group (

Highlight Sasaki and colleagues inserted a balloon enteroscope to the collapsed blind end of the jejunum, and percutaneously punctured the retrieval balloon under ultrasound guidance to insert a jejunal tube. This balloon puncturing method is safe for inserting a jejunal tube percutaneously via the collapsed blind end of the elevated jejunum.

Background /Objectives: Severe acute pancreatitis (SAP) has a high mortality rate despite ongoing attempts to improve prognosis through a various therapeutic modalities. This study aimed to delineate etiology-based routes that may guide clinical decisions for the treatment of SAP. Methods Using data from a recent retrospective multicenter study in Japan, we analyzed the association between clinical outcomes, mainly in-hospital mortality and pancreatic infection, and various etiologies while considering confounding factors. We performed additional multivariate analyses and built decision tree models. Results The 1,097 participating patients were classified into the following groups by etiology: alcohol (n = 436, 39.7%); cholelithiasis (n = 230, 21.0%); idiopathic (n = 227, 20.7%); and others (n = 204, 18.6%). Mortality at hospital discharge was 8.4%, 12.2%, 16.7%, and 16.2% in the alcohol, cholelithiasis, idiopathic, and others groups, respectively. According to multivariable analysis, early enteral nutrition (EN) was significantly associated with reduced in-hospital mortality only in the cholelithiasis group. However, there was a consistent association between age and the need for mechanical ventilation and increased mortality, regardless of etiology. Our decision tree models presented different contributing factors depending on the etiology and patient background. Interaction analysis showed that EN and the use of prophylactic antibiotics may influence these results differently according to etiology. Conclusions No study has yet used comprehensive models to investigate etiology-related prognostic factors for SAP; our results can, therefore, be used as a reference for improving clinical decisions.

Background: Altitude training has often been conducted just before main competition games in many sports. An increase in the frequency of upper respiratory tract infections and gastrointestinal infections due to an altitude-induced suppression of the immune system has been reported after altitude training. Salivary secretory immunoglobulin A (SIgA) is the major immunoglobulin of the mucosal immune system. A suppressive effect of heavy training on SIgA has been reported. However, little is known regarding the effects of repetitive altitude training and hypoxic exposure on SIgA. The objective of this study was to evaluate the changes in SIgA in swimmers undergoing repetitive altitude training at 1,900 m. Methods: Nine collegiate swimmers who experienced their first altitude training experience (FT group) were compared to nine swimmers who experienced repetitive training (RT group) and non-training subjects (Con group). Saliva was collected before ascent and eight times every 2 days during altitude training. SIgA levels were measured by enzyme-linked immunosorbent assays. Results: Compared to the Con group, SIgA levels and the secretion velocity were decreased after ascent and were slowly restored in both the FT and RT groups. The chronological trends in SIgA levels were similar, even though the decline in SIgA levels in the FT group was larger than that in the RT group. Conclusion: Altitude training and experience with altitude training may be one of the factors influencing SIgA. J Clin Med Res. 2019;11(8):550-555 doi: https://doi.org/10.14740/jocmr3884

The purpose of the present study was to compare the effect of alendronate treatment on lumbar bone mineral density (BMD) and bone turnover in men and postmenopausal women with osteoporosis. Sixty men with primary or secondary osteoporosis and 318 women with postmenopausal osteoporosis were treated with alendronate. The primary end points were lumbar BMD and urinary cross-linked N-terminal telopeptides of type I collagen (NTX) and serum alkaline phosphatase (ALP) levels. The secondary end point was the incidence of vertebral and nonvertebral fractures. Forty-seven (78.3%) men and 254 (79.9%) women who could complete the 12-month trial were analyzed. The mean ages of men and postmenopausal women were 69.1 and 70.4 years, respectively. Both men and postmenopausal women showed higher levels of urinary NTX as compared with normal range of premenopausal women. Alendronate treatment decreased urinary NTX level by 39.2% in men and 45.4% in postmenopausal women at 3 months and serum ALP level by 17.8 and 21.0%, respectively, at 12 months. Following reduction in bone turnover markers, lumbar BMD increased 5.8 and 7.6% in men and postmenopausal women, respectively, at 12 months. Reduction in urinary NTX level and increase in lumbar BMD were smaller in men than in postmenopausal women. The incidence of vertebral and nonvertebral fractures was 10.6 and 8.5%, respectively, in men and 8.3 and 7.5%, respectively, in postmenopausal women, with no significant difference in these incidences between them. These results suggested that alendronate treatment effectively increased lumbar BMD from baseline in men with primary or secondary osteoporosis following reduction in bone turnover, although its efficacy did not appear to be greater than in postmenopausal women with osteoporosis.

The purpose of this study was to investigate the effect of alendronate on metacarpal and lumbar bone mineral density (BMD), bone resorption, and chronic back pain in postmenopausal women with osteoporosis. Eighty postmenopausal women with osteoporosis, 59–88 years of age, were divided into two groups of 40 each according to the site of BMD measurement: the metacarpus (M) and the lumbar spine (L). All of them were treated with alendronate (5 mg/day) for 12 months. Metacarpal or lumbar BMD was measured by computed X-ray densitometry or dual-energy X-ray absorptiometry in the M or the L group, respectively, at baseline and every 6 months. Urinary cross-linked N-terminal telopeptides of type I collagen (NTX) were measured by enzyme-linked immunosorbent assay, and chronic back pain was evaluated by face scale score at baseline and every 6 months in both groups. There were no significant differences in baseline characteristics, including age, body mass index, years since menopause, urinary NTX level, face scale score, or number of prevalent vertebral fractures per patient between the two groups. Urinary NTX level was reduced and chronic back pain was improved similarly in both groups. Whereas metacarpal BMD did not significantly change in the M group (0.20% increase), lumbar BMD increased by 8.15% in the L group. These results suggest that although alendronate increases BMD of the lumbar spine, which is rich in cancellous bone, and improves chronic back pain, with suppression of bone resorption in postmenopausal women with osteoporosis, it may fail to increase cortical BMD of the metacarpus, a distal site of the upper extremity.

Alendronate decreases the urinary levels of cross-linked N-terminal telopeptides of type I collagen (NTX; about 45% at 3 months) and serum levels of alkaline phosphatase (ALP; about 27% at 24 months), leading to an increase in lumbar spine bone mineral density (BMD; about 9% at 24 months) in postmenopausal Japanese women with osteoporosis. However, the effectiveness of oral bisphosphonates on osteoporosis remains to be established in patients who have undergone a gastrectomy. The objective of the present case series study was to examine the effect of alendronate on BMD and bone turnover markers in post-gastrectomy osteoporotic patients. Sixteen patients (3 men and 13 postmenopausal women) with osteoporosis, who had undergone a gastrectomy (mean age: 69.1 years), were recruited in our outpatient clinic. All the patients were treated with alendronate (5 mg daily or 35 mg weekly) for 24 months. The effects of alendronate on lumbar spine (women) or total hip (men) BMD and urinary NTX and serum ALP levels were examined. A total or partial gastrectomy had been performed for eight patients each. The mean duration after surgery was 16.0 years. With alendronate therapy, urinary NTX levels significantly decreased at 3 months (−27.0%). Serum ALP levels decreased (−12.1%) and lumbar spine BMD increased (+5.2%), but total hip BMD did not significantly change (+0.6%) at 24 months. No severe adverse events were observed, and alendronate therapy was well tolerated. These results suggest that alendronate mildly increases lumbar spine BMD by mildly reducing bone turnover in osteoporotic patients after a gastrectomy.

Aim The renin-angiotensin system (RAS) was investigated as a target for cancer treatment. Patients and methods A total of 287 patients with biliary tract cancer (BTC) receiving chemotherapy were retrospectively studied to evaluate the role of inhibition of RAS by angiotensin system inhibitors (ASIs). Progression-free survival (PFS) and overall survival (OS) were compared between 74 patients with hypertension, on ASIs (ASI group), 50 patients with hypertension not on ASIs (non-ASI with HT group) and 163 patients without hypertension (non-HT group). Interactions between the use of ASIs and various subgroups were explored. Results The median PFS was 3.6, 3.9 and 4.6 months (p=0.495) and the median OS was 11.6, 10.9 and 13.1 months (p=0.668), respectively. The use of ASIs was not associated with OS (hazard ratio 1.00, p=0.975) and no subgroups with better survival were identified. Conclusion No survival benefit from ASIs was observed in BTC.

662 Background: Little is known about the clinicopathological and prognostic differences between borderline resectable (BR) pancreatic head (Ph) and pancreatic body/tail (Pbt) cancer. Therefore, we conducted this study to compare the clinicopathological features and prognosis of BR pancreatic cancer (PC) according to the location of the primary tumor. Methods: We retrospectively investigated consecutive patients with BR PC who initiated neoadjuvant chemotherapy (NAC) between March 2015 and April 2019. We compared clinicopathological characteristics and prognosis between Ph and Pbt cancer. Furthermore, multivariate survival analysis was performed using cox proportional hazard model. Results: A total of 104 patients with BR PC (median age 68, male 49%) were included in this study. The location of the tumor was Ph 72 and Pbt 32, respectively. The initial regimen of NAC was nab-paclitaxel/gemcitabine in 102 and gemcitabine in 2, respectively. The median cycle of NAC was 4. Median age, sex, primary tumor size, performance status, neutrophil to lymphocyte ratio, and serum level of carbohydrate antigen 19-9 at the time of the initiation of NAC were not significantly different between Ph and Pbt cancer, while the modified glasgow prognostic score (mGPS) was lower in Pbt cancer (mGPS = 0; 78% vs. 94%, p = 0.05). R0/R1 resection rate (81% vs. 69%, p = 0.21) and median survival time (928 days vs. NA, p = 0.13) were also not different between Ph and Pbt cancer. Multivariate survival analysis revealed that R0/R1 resection (HR, 0.11; p < 0.01) and Ph (HR, 2.29; p = 0.03) were independent prognostic factors for survival in patients with BR PC. Conclusions: Although R0/R1 resection rate was similar between BR Ph and Pbt cancer, Pbt cancer had a higher rate of mGPS score of 0 compared to Ph cancer. Furthermore, R0/R1 resection (HR, 0.11) and Ph (HR, 2.29) were independent prognostic factors for survival in patients with BR PC.

Iwamoto J, Sato Y, Uzawa M, Takeda T, Matsumoto H. Therapeutics and Clinical Risk Management. 2010;6:593–600.The Editor-in-Chief and Publisher of Therapeutics and Clinical Risk Management wish to issue an Expression of concern for the above published article.The Journal Editors received notification from an investigator raising concerns about the published paper. These concerns relate to the high similarity in content to the article ‘Experience with alendronate treatment for 7 years among Japanese men with osteoporosis or osteopenia and clinical risk factors for fractures’. Iwamoto J, Uzawa M. Clinical Rheumatology. 2016;35:205–212. There were also concerns raised relating to the timeline for study conduct and manuscript preparation. The article reports the study took place between July 1st and September 30th, 2010 and was submitted for publication on Oct 24, 2010.Dove Medical Press attempted to contact the authors of the article and their affiliated institution regarding these concerns but received no response. As we were unable to make a definitive conclusion, we would like to alert readers to these issues and allow them to draw their own conclusions. This decision follows the recommendations of the Committee on Publication Ethics (COPE).The Editor and Dove Medical Press make every effort to ensure publication ethics are upheld and are committed to supporting the high standards of the Therapeutics and Clinical Risk Management journal.Read the original article&nbsp

The Editor-in-Chief has retracted this article because two of the three studies [1, 2] included in the meta-analysis (cited as references 11 and 12) have been retracted due to fabrication of the data, which has rendered the results of this meta-analysis invalid.

Biliary drainage via endoscopic retrograde cholangiopancreatography (ERCP) is the first-line treatment for acute cholangitis. Despite the established effectiveness of urgent biliary drainage in patients with severe acute cholangitis, the indication of this procedure for non-severe acute cholangitis is controversial. To assess the safety of elective drainage (≥ 12 h of admission) for non-severe acute cholangitis. We retrospectively identified 461 patients with non-severe acute cholangitis who underwent endoscopic biliary drainage. Using linear regression models with adjustment for a variety of potential confounders, we compared elective versus urgent biliary drainage (