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Oxaliplatin, widely used as a chemotherapy drug for colorectal cancer, is known to cause various adverse reactions. In particular, special attention for the development of portal hypertension associated with porto-sinusoidal vascular disease is necessary, as it is a serious adverse life-threating reaction, although rare. We herein report a case of oxaliplatin-related portal hypertension that developed several years after oxaliplatin administration and led to esophageal varices and refractory massive ascites. Clinical physicians should be aware of the possibility of oxaliplatin-induced portal hypertension and its possible development over a long period after discontinuation of the drug.

Immune checkpoint inhibitors (ICIs), which have anti-tumor effects, are currently approved for treatment of several kinds of advanced malignancies. However, with their increasing use, a variety of immune-related adverse events (irAEs) in administered patients have been reported. We herein report a rare case of the simultaneous onset of acute pancreatitis and colitis as irAEs during nivolumab treatment given to a patient with renal cell carcinoma, who then shown marked improvement with corticosteroid therapy.

Gastrointestinal stromal tumors (GISTs) develop in the digestive tract, mainly in the stomach, small intestine, colon, or esophagus. However, primary tumors with the same pathologic features as GISTs have been reported to occur outside of the digestive tract and are called extragastrointestinal stromal tumor (EGIST). We herein report a rare case of EGIST arising from the greater omentum in a patient with abdominal pain caused by intraperitoneal bleeding from the tumor.

We investigated the effects of jammer-type racing swimsuits (RS) on swimming performance during arm-stroke-only (pull) and whole-body stroke (swim) in 25-m front-crawl with maximal effort. Twelve well-trained male collegiate swimmers wore RS and a conventional swimsuit (CS) and performed three tests: pull, swim, and pull using the system to measure active drag (MAD pull). Swimming velocity and intra-abdominal pressure (IAP) were determined in all tests. Stroke indices during pull and swim and drag-swimming velocity relationship and maximum propulsive power during MAD pull were also determined. Swimming velocities during pull and swim while wearing an RS (1.59 ± 0.13 and 1.77 ± 0.09 m·s

ObjectiveStenting is an established endoscopic therapy for malignant gastric outlet obstruction (mGOO). The choice of stent (covered vs uncovered) has been examined in prior randomised studies without clear results.DesignIn a multicentre randomised prospective study, we compared covered (CSEMS) with uncovered self-expandable metal stents (UCSEMS) in patients with mGOO; main outcomes were stent dysfunction and patient survival, with subgroup analyses of patients with extrinsic and intrinsic tumours.ResultsOverall survival was poor with no difference between groups (probability at 3 months 49.7% for covered vs 48.4% for uncovered stents; log-rank for overall survival p=0.26). Within that setting of short survival, the proportion of stent dysfunction was significantly higher for uncovered stents (35.2% vs 23.4%, p=0.01) with significantly shorter time to stent dysfunction. This was mainly relevant for patients with extrinsic tumours (stent dysfunction rates for uncovered stents 35.6% vs 17.5%, pConclusionsDue to poor patient survival, minor differences between covered and uncovered stents may be less relevant even if statistically significant; however, subgroup analysis would suggest to use covered stents for intrinsic and uncovered stents for extrinsic malignancies.

Purpose FOLFOXIRI plus bevacizumab is regarded as a first-line therapeutic option for selected patients with metastatic colorectal cancer (mCRC). Our aim was to assess the efficacy and safety of induction treatment with FOLFOXIRI plus bevacizumab in patients with untreated mCRC harboring UGT1A1 wild (*1/*1), or single-hetero (*1/*6 or *1/*28) genotypes. Methods Twelve cycles of FOLFOXIRI plus bevacizumab were administered to patients with untreated mCRC. The primary endpoint was the overall response rate (ORR) assessed by central independent reviewers. Secondary endpoints included time to treatment failure (TTF), progression-free survival (PFS), overall survival (OS), relative dose intensity (RDI), R0 resection rate, and safety. The exploratory objectives were early tumor shrinkage (ETS) and depth of response (DoR). Results Of the 47 patients enrolled, 46 and 44 patients were eligible for the safety and efficacy analysis, respectively. The primary endpoint was met. The ORR was 63.6% (95% CI 47.8–77.6). At a median follow-up of 25.4 months, median TTF, PFS, and OS was 8.1, 15.5, and 34.4 months, respectively. The median RDI of 5-fluorouracil, irinotecan, oxaliplatin, and bevacizumab was 72, 69, 62, and 71%, respectively. R0 resection rate was 22.7%. Grade 3 or higher adverse events (≥ 10%) included neutropenia (65.2%), febrile neutropenia (26.1%), leukopenia (23.9%), anorexia (10.9%), nausea (10.9%), and diarrhoea (10.9%). No treatment-related deaths were observed. ETS and DoR were 70.5 and 45.4%, respectively. Conclusions FOLFOXIRI plus bevacizumab induction treatment of Japanese patients was shown to be beneficial and manageable, although caution is required since the treatment causes febrile neutropenia.

Endoscopic ultrasound-guided tissue acquisition (EUS-TA) plays a crucial role in the diagnosis of pancreatic tumors. The present study aimed to investigate the current status of needle tract seeding (NTS) after EUS-TA of pancreatic tumors based on a nationwide survey in Japan.Patients who underwent surgical resection of primary pancreatic tumors after EUS-TA performed between April 2010 and March 2018 were surveyed. The incidence rates of NTS were determined, and compared in patients with pancreatic ductal adenocarcinomas (PDACs) and other tumors, and in patients who underwent transgastric and transduodenal EUS-TA of PDACs. The detailed features and prognosis of patients with NTS were also assessed.A total of 12,109 patients underwent surgical resection of primary pancreatic tumors after EUS-TA. The overall incidence rate of NTS was 0.330%, and the NTS rate was significantly higher in patients with PDAC than in those with other tumors (0.409% vs. 0.071%, P=0.004). NTS was observed in 0.857% of patients who underwent transgastric EUS-TA, but in none of those who underwent transduodenal EUS-TA. Of the patients with NTS of PDACs, the median time from EUS-TA to occurrence of NTS and median patient survival were 19.3 and 44.7 months, respectively, with 97.4% of NTS located in the gastric wall and 65.8% of NTS resected. The patient survival was significantly longer in patients who underwent NTS resection than in those without NTS resection (P=0.037).NTS appeared only after transgastric not after transduodenal EUS-TA. Careful follow-up provides an opportunity to remove localized NTS lesions by gastrectomy.

In the present study, we aimed to clarify the impact of the Assisted swim (A-swim; towing from propulsion direction) on front crawl performance at maximum and sub-maximum effort levels. Methods: Fourteen male collegiate swimmers (age, 21.0 ± 2.0 years; height, 1.73 ± 0.05 m; weight, 67.1 ± 7.1 kg) participated. Participants swam 25-m front crawl at maximal (Max) and submaximal intensity (Submax (80% of the max stroke rate (SR))) with and without an assist (assisted swimming with a towing device and normal swim (N-swim) without the device) for a total of four lengths. In addition to swim velocity (V), SR, and stroke length (SL), one stroke cycle was broken down into four phases—glide, pull, push, and recovery—and analyzed the duration of each phase. Results: A significant interaction of level of efforts and presence/absence of towing was confirmed in V, SR, and SL. V and SL showed a significant increase in A-swim compared to N-swim at both Max and Submax. SR was significantly higher in A-swim than in N-swim only at Max. Each phase of stroke showed a significant difference in recovery at Submax and push at Max. Conclusions: Despite considering the impact of propulsion from towing, A-swim increased SR, in addition to the V and SL, of swimmers compared with N-swim. This work was supported by the JSPS KAKENHI Grant Number JP21K11360 and through the Portuguese Foundation for Science and Technology (FCT), I.P., under project UIDB/04045/2020. info:eu-repo/semantics/publishedVersion

Previous studies have suggested that interleukin-33 (IL-33) is involved in the pathogenesis of ulcerative colitis (UC), though the detailed mechanisms are not fully known. We investigated IL-33-mediated colonic homeostasis using a mechanistic method. Il33−/− mice were more tolerant to dextran sulfate sodium-induced acute colitis than the wild type and also showed delayed recovery from colitis with recombinant IL-33 (rIL-33) administration. Unexpectedly, microarray analysis identified significant downregulation of the Abcg5/8 genes in mouse colons following rIL-33 treatment. ABCG5/8 are known cholesterol transporters in the small intestine and liver, though their colon activities have not been elucidated, thus their role in IL-33-mediated inflammation was investigated. In vitro, toll-like receptor (TLR) stimulation upregulated ABCG5/8 mRNA expression in Caco2 and HCT-15 cells, with subsequent downregulation by rIL-33, while inhibition of ABCG5/8 along with their siRNA increased TLR-stimulated IL-8 production. Together, these results indicated that colonic ABCG5/8 play a regulatory role in TLR-induced inflammation, while histological inflammation in human UC was correlated positively with the level of mucosal IL-33 and inversely with that of colonic ABCG5/8. This is the first report of IL-33-mediated downregulation of colonic ABCG5/8 in a colitis recovery phase, indicating their involvement in UC pathogenesis and potential as a therapeutic target. The authors investigated the potential mechanisms of interleukin-33 (IL-33) in the pathogenesis of ulcerative colitis. IL-33 was found to sustain mucosal inflammation by down-regulation of protective ABCG5/8 during recovery from colitis. These results may help to increase understanding regarding the IL-33-mediated pathogenesis of ulcerative colitis and potentially contribute to creation of a novel therapeutic strategy.

Simple Summary Developing therapeutic resistance to monoclonal antibodies (mAbs) causes increasing failure in oral squamous cell carcinoma (OSCC) treatment. A clear understanding of the molecular basis for drug resistance will pave the way for OSCC management and a new effective therapeutic modality. This review elucidates the role played by EMT during the emergence of mAbs resistance and the configuration of the tumor microenvironment. The cancer cells that undergo the EMT process also cause significant energy substrate consumption which leads to a limited number and function of effective T-cells, eventually leading to immune evasion. This review firstly reveals the implicit crosstalk between the EMT, energy metabolism, and therapeutic resistance of mAbs. A focus on the rebalanced energy homeostasis in cancer cells and T-cells may provide a new perspective on the treatment of OSCC. Abstract Oral squamous cell carcinoma (OSCC) is a major type of cancer that accounts for over 90% of all oral cancer cases. Recently developed evidence-based therapeutic regimens for OSCC based on monoclonal antibodies (mAbs), such as cetuximab, pembrolizumab, and nivolumab, have attracted considerable attention worldwide due to their high specificity, low toxicity, and low rates of intolerance. However, the efficacy of those three mAbs remains poor because of the low rate of responders and acquired resistance within a short period of time. The epithelial–mesenchymal transition (EMT) process is fundamental for OSCC growth and metastasis and is also responsible for the poor response to mAbs. During EMT, cancer cells consume abundant energy substrates and create an immunosuppressive tumor microenvironment to support their growth and evade T cells. In this review, we provide an overview of the complex roles of major substrates and signaling pathways involved in the development of therapeutic resistance in OSCC. In addition, we summarize potential therapeutic strategies that may help overcome this resistance. This review aims to help oral oncologists and researchers aiming to manage OSCC and establish new treatment modalities.

The study aimed to experimentally verify the efficacy of wearing flotation aids to add buoyancy from the pelvis to the side of the thigh on the swimming performance of beginning swimmers who were capable of swimming around 25 meters at a time. The study recruited seven male university students who were members of the Physical Education Department and who lacked experience in specialized swimming instruction. The study found statistical difference in prone flotation between the use of flotation aids (7.27±1.92 sec) and without flotation aids (3.50±0.72 sec). During swimming for distance in a 5 min. swim test, we found statistical difference between the use of flotation aids (185.0±29.6 m) and without flotation aids (172.6±24.4 m). Moreover, no overall differences in stroke length and stroke rate were observed flotation and no flotation use.

Linear immunoglobulin A dermatosis (LAD) is rarely complicated in patients with ulcerative colitis (UC), though the long-term prognosis in those with concurrent LAD and UC is not fully understood. Here, we report findings obtained in follow-up examinations performed over a 10-year period of a UC patient initially complicated with LAD. We treated an 18-year-old male for relapse of UC with deteriorating blisters diagnosed as LAD. Following successful induction therapy for both UC and LAD with oral prednisolone, the patient was followed for 10 years. Skin condition remained good at each examination, even with second and third relapses of UC. Our findings in this case indicate that LAD is rarely complicated with UC, while it has no association with colitis disease activity. Furthermore, adequate treatment following an initial diagnosis of LAD is important for management of affected UC patients.

We report a case of sigmoid endometriosis diagnosed preoperatively based on endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) findings. A 42-year-old female came to us with left lower abdominal pain and bloating that had started 3 months prior. CT and MRI results showed wall thickening of the sigmoid colon. A colonoscopy procedure could not be completed because passage through the sigmoid colon was blocked due to severe stenosis, while mucosal biopsy samples obtained during that procedure could not confirm a diagnosis. EUS-FNA was then performed and specimens were obtained from the muscular layer with stenosis, which revealed a thickened hypoechoic lesion. Histological findings obtained by use of EUS-FNA demonstrated a large amount of fibrosis in endometrial glands and a diagnosis of sigmoid endometriosis was confirmed by additional immunostaining. Thus, a laparoscopic sigmoidectomy was performed, with sigmoid endometriosis finally diagnosed. Confirmation of a diagnosis of intestinal endometriosis based on histological findings of mucosal biopsy specimens obtained by colonoscopy is difficult, because endometrial implants are primarily located in the serosal and/or muscular layer. When safe aspiration is possible, we consider that EUS-FNA can be an effective method for preoperative diagnosis of intestinal endometriosis, which may contribute to avoidance of unnecessary or excessive surgery.

Summary Background IgG4-related disease is a newly recognised immunopathological entity that includes autoimmune pancreatitis, IgG4-related sialadenitis, and IgG4-related kidney disease. To understand the genetic landscape of IgG4-related disease, we did a genome-wide association study. Methods We did a genome-wide association study of Japanese individuals, initially screening 857 patients with IgG4-related disease at 50 Japanese research institutions and DNA samples from 2082 healthy control participants from the Nagahama Prospective Genome Cohort for the Comprehensive Human Bioscience. From Oct 27, 2008, to July 22, 2014, we enrolled 835 patients and used data from 1789 healthy participants. Only patients with confirmed diagnosis of IgG4-related disease according to the international diagnostic criteria were included. Genotyping was done with the Infinium HumanOmni5Exome, HumanOmni2.5Exome, or HumanOmni2.5 Illumina arrays, and genomic distributions were compared between case and control samples for 958 440 single nucleotide polymorphisms. The HLA region was extensively analysed using imputation of HLA alleles and aminoacid residues. Fine mapping of the FCGR2B region was also done. Associations between clinical manifestations of disease and the genetic variations identified in these two genes were examined. Findings We identified the HLA-DRB1 (p=1·1×10−11) and FCGR2B (p=2·0×10−8) regions as susceptibility loci for IgG4-related disease. We also identified crucial aminoacid residues in the β domain of the peptide-binding groove of HLA-DRB1, in which the seventh aminoacid residue showed the strongest association signal with IgG4-related disease (p=1·7×10−14), as has been reported with other autoimmune diseases. rs1340976 in FCGR2B showed an association with increased FCGR2B expression (p=2·7×10−10) and was in weak linkage disequilibrium with rs1050501, a missense variant of FCGR2B previously associated with systemic lupus erythematosus. Furthermore, rs1340976 was associated with the number of swollen organs at diagnosis (p=0·011) and IgG4 concentration at diagnosis (p=0·035). Interpretation Two susceptibility loci for IgG4-related disease were identified. Both FCGR2B and HLA loci might have important roles in IgG4-related disease development. Common molecular mechanisms might underlie IgG4-related disease and other immune-related disorders Funding The Japanese Ministry of Health, Labour, and Welfare, the Japanese Agency of Medical Research and Development, and Kyoto University Grant for Top Global University Japan Project.

Objective Acute cholangitis is occasionally life-threatening and requires immediate treatment. For the management of acute cases, globally accepted diagnostic criteria and the use of severity grading, as defined in the Tokyo Guidelines 2018 (TG18), are recommended. This study was performed to explore the association between acute cholangitis and the level of adenosine 5'-triphosphate (ATP) in blood as determined with a simple measurement method. Methods Twenty-three consecutive patients admitted for acute cholangitis and 14 healthy individuals were enrolled. Based on the TG18, the patients were categorized according to the degree of severity as Grade I, II, or III. We measured the amount of ATP in blood samples using a bioluminescence meter and evaluated the correlation with the degree of severity. Results The ATP/total hemoglobin (tHgb) level showed a significant decline in association with an increase in severity, as that in the healthy controls was 236.60 ± 8.10 and in the Grade I, II, and III groups was 238.56 ± 6.98, 186.88 ± 7.62, and 154.60 ± 11.01, respectively (p

The aim of this study was to: (1) verify differences between swimmers of the same competitive level in variables related to the start and finish (50 m and 100 m freestyle); (2) verify if starting and finish variables are responsible for faster race time, and which starting variables are responsible for the start performance in such events. For the 50 m and 100 m freestyle race at the junior European Championships 2019, 86 and 88 male swimmers were analysed, respectively. A set of starting and finishing variables were used for analysis. Both races (50 m: p < 0.001; 100 m: p < 0.001) presented a significant level effect for the final race time. The same trend was observed for the start and finish performances. For both races, hierarchical linear modelling retained the 15 m mark time and finish speed as predictors. The 50 m start retained the reaction time and underwater speed, and the 100 m start retained the reaction time and the water break distance. This indicates the underwater phase of the start is of substantial importance to improve the 15 m mark time. Coaches and swimmers are advised to enhance the start underwater phase, and finish segments to improve the swimmers’ performance This work is supported by national funds (FCT - Portuguese Foundation for Science and Technology) under the project UIDB/DTP/04045/2020 info:eu-repo/semantics/publishedVersion

Background: When in water, the Centers of Buoyancy (CoB) and Mass (CoM) of the human body are positioned cranially and caudally, respectively. With increasing distance between these centers, the sinking torque of the lower limbs increases, with a subsequent decrease in swimming performance due to increased drag. Objective: To clarify the effect of additional buoyancy swimsuits on swimming performance. Methods: The subjects were eight competitive male swimmers of mean ±SD age 21±2 years. Swimming performance was compared between Conventional (CS) and Additional Buoyancy Swimsuits (ABS). CoM and CoB were identified on land and in water, respectively, with the swimmers maintaining a horizontal posture. CoM was measured by the reaction board method. CoB was calculated as the force exerted in the vertical direction accompanied by changes in inspiratory volume. Swimming velocity and Blood Lactate (BL) concentration value during 200 m front crawl in trials at four different speeds (curve test) were recorded as swimming performance. Results: No significant difference in inspiratory volume was observed between CS and ABS (small effect size, d=0.28). The distance between CoM and CoB was significantly shorter for CS than ABS (p < 0.001; large effect size, d=1.08). Both swimming velocity at BL of 4 mmol·L-1 and maximal effort were significantly faster for ABS (p < 0.042; 0.008), with large effect size (d=0.91; 0.98). However, there was no significant difference in maximal BL between CS and ABS (small effect size, d=0.37). Conclusion: ABS improves swimming performance by streamlining the horizontal posture.

Objective: Quiescent ulcerative colitis (UC) patients often have irritable bowel syndrome (IBS)-like symptoms and we recently showed that the prevalence of IBS-like symptoms in UC patients in clini...

The aim of this study was to analyse the detraining process that occurs during a season break, and its influence on the performance, anthropometrics, and biomechanics of young swimmers. The sample included 54 young swimmers (22 boys: 12.79 +/- 0.71 years; 32 girls: 11.78 +/- 0.85 years). Performance for the 100 m freestyle and anthropometric and biomechanical variables were evaluated as main determinants. Performance impaired significantly for boys (2.17%) and girls (1.91%). All anthropometric variables increased between moments of assessment for boys and girls. Overall, the boys enhanced all biomechanical variables during the detraining period, and girls showed mixed results. For both sexes, the stroke index was the variable with the highest increase (boys: Delta = 16.16%; d = 0.89; p = 0.001; girls: Delta = 19.51%; d = 1.06; p = 0.002). Hierarchical linear modelling showed that the height retained the amount of impairment in the performance. One unit of increase in the height (cm) led to less 0.41 s impairment in the performance. Present data indicated that during an 11-weeks detraining period, young swimmers impaired their performance, but the determinant factors showed an impaired relationship. This increase in the determinant factors is mainly related to the increase in the swimmers' anthropometrics. Moreover, the increase in height was responsible for retaining the performance impairment. This project was supported by National Funds through FCT -Portuguese Foundation for Science and Technology (UID/DTP/04045/2019), and the European Fund for regional development (FEDER) allocated by the European Union through the COMPETE 2020 Programme (POCI01-0145-FEDER-006969). info:eu-repo/semantics/publishedVersion

Aim: Few reports of the prophylactic use of soft coagulation with hemostatic forceps for postendoscopic papillectomy hemorrhage (PEPH) have been presented. The aim of this study was to clarify the utility of that procedure for prophylaxis. Materials and Methods: From April 2009 to March 2012, PEPH was treated in four patients after the development of the condition with a conventional procedure at our institution. Thereafter, from April 2012 to March 2016, soft coagulation using hemostatic forceps was performed as prophylactic hemostasis following an EP in five patients. For the latter procedure, the hemostatic forceps device (FD411‑QR, Olympus, Tokyo, Japan) was used in a closed position, with the coagulation wave set at 60 W (VIO 300D; ERBE, Tubingen, Germany). The primary outcome was the onset of PEPH, which was defined as a decrease in hemoglobin ≥2 g/dL after EP. Secondary endpoints were the success rate and the incidence of adverse events of soft coagulation using hemostatic forceps for emergency bleeding cases after EP. Results: The incidence of PEPH was 20% (1 of 5 cases) in the prophylactic procedure group, which was lower than that in the conventional procedures group (75%, 3 of 4 cases), though the difference was not statistically significant (P = 0.206, Fisher’s exact test). All cases of PEPH were successfully treated by soft coagulation using hemostatic forceps. Conclusion: Soft coagulation with hemostatic forceps may be suitable for use as a routine technique following EP to prevent PEPH.

A 70-year-old woman with loss of appetite was referred to our hospital for further examinations. Computed tomography revealed a low density tumor in the body of the pancreas measuring 4 cm in diameter. The main pancreatic duct was dilated on both the head and caudal side of the tumor. Magnetic resonance imaging showed the mass as a low intensity area in T1-weighted and high intensity area in T2-weighted images. Endoscopic retrograde cholangiopancreatography findings indicated that the main pancreatic duct was continuous with the lumen of the tumor. A cytological examination of pancreatic juice showed a class IV tumor. A distal pancreatectomy was performed as a curative resection procedure. The findings of hematoxylin eosin staining and mucus trait led to a diagnosis of invasive cancer derived from an intraductal papillary mucinous neoplasm (IPMN). We also performed sequencing analysis to investigate GNAS and K-RAS mutations in the tumor, though neither the GNAS mutation c602G>A nor K-RAS mutation c35G>A were observed. Cases negative for a GNAS mutation can be considered to have an increased risk of invasive cancer derived from an IPMN.

Purpose: To compare treatment outcomes and adverse events between concurrent chemoradiotherapy with docetaxel, cisplatin, and 5-fluorouracil (DCF-RT) and conventional concurrent chemoradiotherapy with cisplatin and 5-fluorouracil (CF-RT). Methods and Materials: We retrospectively investigated treatment outcomes and adverse events in 121 patients with advanced esophageal cancer who underwent concurrent chemoradiotherapy with CF-RT (n = 83) or DCF-RT (n = 38). In the CF-RT group, patients were administered cisplatin (70 mg/m2) and 5-fluorouracil (700 mg/m2) for 5 days; in the DCF-RT group, patients were administered docetaxel (50 mg/m2), cisplatin (50 mg/m2), and 5-fluorouracil (500 mg/m2) for 5 days. The radiotherapy dose was 1.8-2 Gy per session, up to a total of 50-60 Gy. Results: The complete response (CR) rate was 37.8% in the CF-RT group and 52.6% in the DCF-RT group. Overall survival (OS) rates at 2 and 3 years were 45.0% and 37.5%, respectively, in the CF-RT group and 62.9% and 56.7%, respectively, in the DCF-RT group, with a significant intergroup difference (p = 0.032). Progression-free survival rates at 2 and 3 years were 44.1% and 36.9%, respectively, in the CF-RT group and 45.0% and 45.0%, respectively, in the DCF-RT group (p = 0.10). Local control rates at 2 and 3 years were 59.1% and 54.6%, respectively, in the CF-RT group and 71.8% and 71.8%, respectively, in the DCF-RT group (p = 0.12). The incidence of Grade 3/4 leukopenia was 55.4% (n = 46) in the CF-RT group and 78.9% (n = 30) in the DCF-RT group, with a significant intergroup difference (p = 0.022). The incidence of Grade 3/4 neutropenia was 47.0% (n = 39) in the CF-RT group and 65.8% (n = 25) in the DCF-RT group, with a notable albeit not statistically significant difference between the groups (p = 0.054). There were no significant intergroup differences in anemia, thrombocytopenia, radiation-induced dermatitis, radiation esophagitis, or late adverse events. Conclusions: Rates of OS and CR were improved after treatment with DCF-RT compared with CF-RT. Although DCF-RT-treated patients had higher rates of leukopenia, treatment safety was ensured through proper management of myelotoxicity. DCF-RT is a promising treatment regimen for advanced esophageal cancer.

Prophylactic granulocyte-colony stimulating factor(G-CSF)is necessary for some cancer patients receiving anti-cancer drugs. However, it is difficult for cancer patients in rural areas to receive G-CSF as outpatients because of inconvenient official transport, lack of public support, and low activity levels due to age. To resolve this problem, we began conducting a critical path(G-path)with regional medical institutions from 2011.We retrospectively surveyed the clinical records of cancer patients receiving prophylactic G-CSF using G-path at our hospital.Eighty-two patients who were administered a total of 254 cycles of chemotherapy were examined between January 2011 and December 2016. Diseases included malignant lymphoma(n=64), pancreatic cancer(n=7), soft tissue sarcoma(n=5), and others(n=6). The median age of the patients was 70(range: 24-94)years. Fifty-three patients visited medical offices, and 31 patients visited regional hospitals. In 245 of 254(96%)cycles, planned G-CSF administration was performed. In 37 of 254(15%)cycles, infectious episodes developed, but patients needed hospitalization for only 5 cycles(2%).Cooperation between clinics and hospitals using G-path reduced ambulatory burden and prevented severe infection. Cooperation in supportive care may allow for equal accessibility to cancer treatment.

Fecal calprotectin level in ulcerative colitis patients is correlated with endoscopic findings. However, its association with various ulcerative colitis disease types has not been elucidated. In the present study, we investigated the correlation of fecal calprotectin level with endoscopic findings as compared to blood biomarkers according to ulcerative colitis disease type. Fecal calprotectin as well as the blood biomarkers: C-reactive protein (CRP), white blood count (WBC), erythrocyte sedimentation rate (ESR), hemoglobin, platelet count (PLT), and serum albumin (Alb) were measured in patients who underwent a complete colonoscopy. Disease type was divided into proctitis, left-sided colitis, and extensive colitis. Correlations of fecal calprotectin and blood biomarker levels with Mayo endoscopic subscore were analyzed. A total of 186 colonoscopy examinations were performed in 124 patients with ulcerative colitis. Fecal calprotectin level showed a significant correlation with Mayo endoscopic subscore regardless of disease type (proctitis, r = 0.54, p

Background and Aim The serotonin reuptake transporter (SERT) terminates serotonin activity by removing it from interstitial space. Downregulated colonic SERT expression has been reported in irritable bowel disease (IBS), and symptoms resembling IBS occur in cases of inflammatory bowel disease (IBD) in remission; thus, a common pathogenesis for IBS and IBD is possible. However, little is known regarding SERT expression in colonic mucosa of IBD patients during healing. Methods Twenty-two ulcerative colitis (UC) patients underwent colonoscopy examinations, during which inflamed mucosa was distinguished from that undergoing healing. Healing mucosa was classified into regular and irregular vessel patterns by narrowband imaging magnifying colonoscopy. Expressions of SERT and various inflammation-related genes in biopsy samples were assessed using a polymerase chain reaction array system and real-time polymerase chain reaction. Colitis model mice were established by administration of dextran sodium sulfate or transfer of CD4+ T cells isolated from SAMP1 mice, then time-course changes of SERT and inflammatory gene expressions were observed in colonic mucosa. Results In UC patients, SERT expression in inflamed mucosa was significantly lower than in healing mucosa. SERT expression was decreased in healing mucosa with an irregular vessel pattern with mildly increased levels of inflammatory gene expression. In mice, SERT expression was suppressed in inflamed mucosa and continuously observed with low-grade mucosal inflammation during colitis healing. Conclusions Sserotonin reuptake transporter expression is downregulated in healing colonic mucosa of UC patients and that suppression may be dependent on the presence of remaining low-grade colonic inflammation.

Objectives Several studies report on the outcomes of self-expandable metallic stents (SEMSs) deployment for malignant gastric outlet obstruction (GOO). However, data was mostly based on the analysis of single-center studies including only a small number of patients. This study aimed to evaluate clinical outcomes after the deployment of SEMS in patients with malignant GOO and to compare the clinical outcomes of two metallic stents with different designs. Methods Altogether 125 consecutive patients from five institutions were included. Clinical outcomes were evaluated according to technical success, clinical success, stent patency period, survival period and complications. A comparison of clinical outcomes between Niti-S pyloric/duodenal and WallFlex duodenal stents was also undertaken. Results Rates for clinical and technical success were 100% and 92.0%, respectively. The median stent patency and survival periods were 72.0 days (range 3–775 days) and 75.0 days (range 3–775 days), respectively. The rate of overall adverse events was 28.8%. The rate of stent dysfunction was 16.8%, and that of adverse events, except stent dysfunction was 12.0%. Massive bleeding occurred in two patients as a late complication. The clinical success rate for Niti-S stent was significantly higher than that for WallFlex stent (96.2% vs 84.8%, P = 0.023). Conclusions We successfully deployed a SEMS in malignant GOO. The selection of a SEMS with a lower axial force may be important for patients to resume the oral food intake. Additionally, consideration must be given to the appropriate management of fatal bleeding as a late complication.

A 60-year-old woman was admitted to our hospital with upper abdominal pain and jaundice. Computed tomography showed a 9-cm mass that was penetrated by the common hepatic artery in the pancreatic head area. Endoscopic retrograde pancreatography revealed no stenosis or obstruction of the main pancreatic duct, and a cytologic examination of the patient's pancreatic juice was negative. Next, endoscopic ultrasound-guided fine needle aspiration was performed. The immunohistological findings of the specimen revealed a diffuse large B-cell lymphoma. The size of the tumor was significantly reduced after 8 cycles of R-CHOP chemotherapy (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone).

134 Background: FOLFOXIRI-Bmab has been recognized as one of the standard first-line treatments for mCRC. We conducted a single arm, multicenter, phase II study to assess the efficacy and safety of FOLFOXIRI-Bmab in pts with untreated mCRC harboring UGT1A1(*6 and *28) wild or single hetero genotype. Methods: Pts received FOLFOXIRI-Bmab (irinotecan 165 mg/m2, oxaliplatin 85 mg/m2, l-leucovorin 200mg/m2, fluorouracil 3200 mg/m2 and Bmab 5mg/kg repeated biweekly) up to a maximum of 12 cycles, followed by the sequential therapy which consisted of the remaining drugs if any of the individual drugs were discontinued at the investigator’s discretion. Protocol therapy was continued until progressive disease, an unacceptable adverse event, tumor resection or consent withdrawal. The primary endpoint was ORR evaluated by central reviewers. Secondary endpoints include TTF, PFS, OS, R0 resection rate, relative dose intensity (RDI) and safety. The exploratory objectives were early tumor shrinkage (ETS), depth of response (DoR). Results: 47 pts were enrolled from 16 centers between April 2015 and May 2017, of whom 1 was excluded for not meeting the inclusion criteria. The full analysis set consisted of 44 pts because 2 had no target lesions that were considered measurable lesion by central reviewers. 46 pts had the following characteristics: median age 58 (29-68), 57% male, 76% PS0, 22% right-sided tumors and 52% UGT1A1 wild. RAS status was 37% wild, 52% mutant, 11% unknown. Primary endpoint was met. The ORR was 63.6% (95% CI, 47.8-77.6). ETS and DoR was 70.5%, 43.9%, respectively. R0 resection rate was 23%. Median PFS was 15.5mo (95% CI, 11.5-23.4). Median TTF was 8.1mo (95% CI, 5.3-10.1). Median OS was 34.4mo (95% CI, 26.4-not reached). The mean RDI of fluorouracil, irinotecan and oxaliplatin were 71%, 67%, and 64%, respectively. Grade 3 or higher adverse events (≥10%) were neutropenia (65.2%), febrile neutropenia (FN) (26.1%), anorexia (10.9%), nausea (10.9%), and diarrhea (10.9%). No treatment-related deaths were observed. Conclusions: Our results of FOLFOXIRI-Bmab in Japanese pts showed to be beneficial and manageable although caution to FN is required. Clinical trial information: NCT02497157.

Background and Aims Histologic diagnosis of autoimmune pancreatitis (AIP) using EUS-guided FNA (EUS-FNA) is difficult. To address this issue, new fine-needle biopsy (FNB) needles were recently developed. Here, we prospectively evaluated 2 newly designed EUS-FNB needles for histologic evaluation in patients with type 1 AIP. Methods This was a prospective, randomized, multicenter trial comparing biopsy specimens obtained with a 22-gauge Franseen needle or a 20-gauge forward-bevel needle in patients with suspected type 1 AIP. AIP was diagnosed according to international consensus diagnostic criteria. The primary endpoint was the sensitivity of EUS-FNB needles, and secondary endpoints were the amount of specimen obtained, histology of the pancreas based on evaluation of lymphoplasmacytic sclerosing pancreatitis (LPSP), and contribution of histologic findings to the diagnosis of AIP. Results One hundred ten patients were randomly assigned to the Franseen group (22-gauge Franseen needle) or the forward-bevel group (20-gauge forward-bevel needle). EUS-FNB sampling was successful in all patients. Nine patients were excluded because of diagnoses other than AIP. Compared with the forward-bevel needle, the Franseen needle obtained a significantly greater number of high-power fields. Of 101 patients, 39 patients (78%) in the Franseen group and 23 patients (45%) in the Forward-bevel group were diagnosed with level 1 or 2 LPSP (P = .001). Thirty-six patients could not be diagnosed with type 1 AIP without EUS-FNB specimen results. Conclusions The 22-gauge Franseen needle should be routinely used for histologic diagnosis of type 1 AIP. (Clinical trial registration number: UMIN 000027668.)

OBJECTIVES Pancreatic metastases (PMs) account for 1% to 2% of pancreatic tumors, and their prognostic significance is poorly defined. We evaluated the incidence and clinical characteristics of primary tumors and defined prognostic factors. METHODS This retrospective study of 39 Japanese tertiary referral hospitals (January 2005 to August 2015) analyzed patient and tumor characteristics and survival time. Kaplan-Meier analysis and Cox proportional hazards models were applied to evaluate overall survival and prognostic factors, respectively. RESULTS We enrolled 159 patients with a pathologic diagnosis of PM. The most common primary tumor was renal cell carcinoma (38.4%), followed by lung cancer (24.5%), colorectal cancer (11.3%), and sarcoma (6.3%). Eight patients were lost during follow-up, and 151 patients were included for statistical analysis. Median overall survival was 43.0 months, and the 5-year survival rate was 42.6%. Multivariate analysis identified 3 independent prognostic factors: extrapancreatic metastasis (hazard ratio, 2.13; 95% confidence interval, 1.11-4.07; P = 0.02), tumor-related symptoms at diagnosis (hazard ratio, 5.39; 95% confidence interval, 2.92-9.91; P < 0.001), and pathologic diagnosis of primary tumors (P < 0.001). CONCLUSIONS Treatment strategies and prognoses for PMs completely differ according to the primary tumor type. A definitive pathologic diagnosis of PMs is essential for selecting the appropriate treatment.

Backgrounds In ATTRACTION-2 trial, nivolumab (NIVO) showed better outcome compared with best supportive care in advanced gastric cancer (AGC) patients (pts) at least two previous regimens. (NIVO has changed the treatment of AGC in Japan.) Methods: From Nov 2017 to Feb 2019, we retrospectively investigated 25 pts with AGC who received NIVO. Results: The patient demographics were as follows: median age, 67 (range, 39-82); male/female ratio, 18:7; performance status (PS) 0/1/2, 9/14/2; unresectable /recurrent, 20 /5; HER2 positive, 3; deep vein thrombosis, 3; intestinal type /diffuse type, 13 /12; primary site EGJ/UML/UM/ML/U/M/L, 2/2/1/3/5/4/8; site of metastases lymph node /liver /peritoneum /ovary, 13 /8 /9 /1; and previous treatment regimens 2 regimens /3 regimens /≥4 regimens, 9 /10 /6. Response rate (RR) was 12% and disease control rate (DCR) was 28%. The median progression free survival (PFS) was 4.1 months (95% confidence interval [CI], 2.8-NA) and the median overall survival (OS) was 11.8 months (95% CI, 8.2-12.8). In histologic subtypes and PS, there were no difference in PFS and OS between pts with intestinal type and diffuse type as well as between those with PS of 0 and 1-2. As for the number of previous treatment regimens, there was no difference in PFS between pts who received ≥3 regimens and pts who received 2 regimens. However, the former had significantly longer OS compared with the latter. Ten patients (40%) developed immune-related adverse event (ir-AE) and four (16%) did severe ir-AE (≥grade 3). Conclusions: The current study showed better results and longer OS for AGC pts who received NIVO with acceptable toxicities. The limitation is a small number of patients accompanied by a potential of selection with retrospective manner, thus warrants a further studies.

Introduction Recent evidence demonstrates that gram-positive bacteria are commonly found in patients with febrile neutropenia, and that this is caused by translocation of the bacteria from the intestinal tract. At the Innovative Cancer Center of our institution, we found that Escherichia coli and Streptococcus mitis/Streptococcus oralis are commonly found in blood cultures, in addition to Staphylococcus epidermidis. Objective Our aim was to determine the types of bacteria found in blood cultures of patients receiving anti-cancer treatments in order to better define strategies for infection prevention and for selecting appropriate antibiotics. Methods Blood cultures collected from inpatients at our hospital between April 2015 and March 2018 were analyzed to determine the presence of bacterial species. Results E. coli was the most common bacteria found in patients with solid cancers. On the other hand, S. epidermidis was the most common bacteria in patients with hematologic cancer, followed by E. coli and S. mitis/S. oralis. S. mitis and S. oralis were detected on and after the day of oral care in these patients. Discussion There was a difference in the prevalence of the types of bacterial species found in patients with solid cancers compared with those with hematologic cancers. Specifically, S. epidermidis was more prevalent in patients with hematologic cancers than those admitted within other departments of our institution. These findings suggest that infection in these patients may have occurred due to contamination of a sample and/or via the infusion site. We also demonstrated that the prevalence of oral bacteria was high in patients with hematologic cancers. Thus, it is necessary to re-examine the practice of antibiotic prophylaxis during oral care, especially the type of antibiotics and the duration of the treatment.

Objectives The aim of this study was to assess prevailing treatment of pancreatolithiasis in Japan. Methods We surveyed clinical data from 1834 patients (1479 men and 355 women) at 125 hospitals. Results Extracorporeal shock-wave lithotripsy (ESWL) was performed alone in 103 patients (5.6%), ESWL plus an endoscopic procedure in 446 (24.3%), endoscopic treatment alone in 261 (14.2%), and surgery in 167 (9.1%). Other treatments were given to 358 (19.5%), whereas 499 (27.2%) received no treatment. Symptoms were relieved in 85.7% after ESWL, 80.8% after endoscopic treatment alone, and 92.8% after surgery. Early complication rates within 3 months after ESWL, endoscopic treatment alone, and surgery were 8%, 4.5%, and 27.1%, respectively. Late complications after ESWL, endoscopic procedures alone, and surgery were 1.7%, 2.5%, and 8.2%, respectively. Symptom relief but also early and late complications were greater after surgery than after ESWL and endoscopic treatment. Among 417 patients undergoing ESWL, 61 (14.6%) required surgery, as did 32 (16%) of 200 patients treated endoscopically. Surgery was required less frequently following initial operative treatment (11/164 patients [6.7%]). Nonsurgical initial treatments were chosen more frequently. Conclusions First-line treatment of pancreatolithiasis should be ESWL with or without endoscopy because of minimal invasiveness and fewer complications.

The correct name of the corresponding author should be ''Nobuhiko Fukuba'', and not ''Nobuhiko Fukuban'' as given in the original publication of the article.