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Background: The efficacy of adjuvant chemotherapy for high-risk stage II colon cancer (CC) has not been well established. Using propensity score matching, we previously reported that the 3-year disease-free survival (DFS) rate was significantly higher in patients treated with uracil and tegafur plus leucovorin (UFT/LV) against surgery alone. We report the final results, including updated 5-year overall survival (OS) rates and risk factor analysis outcomes. Methods: In total, 1902 high-risk stage II CC patients with T4, perforation/penetration, poorly differentiated adenocarcinoma/mucinous carcinoma, and/or < 12 dissected lymph nodes were enrolled in this prospective, non-randomized controlled study based on their self-selected treatment. Oral UFT/LV therapy was administered for six months after surgery. Results: Of the 1880 eligible patients, 402 in Group A (surgery alone) and 804 in Group B (UFT/LV) were propensity score-matched. The 5-year DFS rate was significantly higher in Group B than in Group A (P = 0.0008). The 5-year OS rates were not significantly different between groups. The inverse probability of treatment weighting revealed significantly higher 5-year DFS (P = 0.0006) and 5-year OS (P = 0.0122) rates in group B than in group A. Multivariate analyses revealed that male sex, age ≥ 70 years, T4, < 12 dissected lymph nodes, and no adjuvant chemotherapy were significant risk factors for DFS and/or OS. Conclusion: The follow-up data from our prospective non-randomized controlled study revealed a considerable survival advantage in DFS offered by adjuvant chemotherapy with UFT/LV administered for six months over surgery alone in individuals with high-risk stage II CC. Trial registration: Japan Registry of Clinical Trials: jRCTs031180155 (date of registration: 25/02/2019), UMIN Clinical Trials Registry: UMIN000007783 (date of registration: 18/04/2012). [ABSTRACT FROM AUTHOR]

Purpose: The goal of the current study was to identify prognostic factors for disease-free survival (DFS) and overall survival (OS) in high-risk stage II colon cancer. Methods: The subjects were patients with histologically confirmed stage II colon cancer undergoing R0 resection who met at least one of the following criteria: T4, perforation/penetration, poorly differentiated adenocarcinoma, mucinous carcinoma, and < 12 examined lymph nodes. Patients self-selected surgery alone or a 6-month oral uracil and tegafur plus leucovorin (UFT/LV) regimen. Serum CEA mRNA at ≥ 24 h after surgery and < 2 weeks after registration was also examined as a potential prognostic factor for stage II colon cancer. This study is registered with UMIN-CTR (protocol ID: UMIN000007783). Results: 1880 were included in the analysis to identify prognostic factors for DFS and OS in patients with high-risk stage II colon cancer. In multivariate analyses, gender, depth of tumor invasion, extent of lymph node dissection, number of examined lymph nodes, and postoperative adjuvant chemotherapy (POAC) emerged as significant independent prognostic factors for DFS. Similarly, multivariate analysis showed that age, gender, depth of tumor invasion, perforation/penetration, extent of lymph node dissection, number of examined lymph nodes, and POAC were significant independent prognostic factors for OS. Univariate analyses showed no significant difference in DFS or OS for CEA mRNA-positive and mRNA-negative cases. Conclusion: This study showed that gender, depth of tumor invasion, extent of lymph node dissection, number of examined lymph nodes, and lack of use of POAC were significant independent prognostic factors in stage II colon cancer. [ABSTRACT FROM AUTHOR]

Purpose: Chemotherapy-induced taste alteration is a side effect that can result in malnutrition and reduced quality of life in cancer patients. However, the underlying causes of this phenomenon remain unclear, and evidence-based treatments have not been established. This study focused on patients’ subjective symptoms of taste alterations aimed to explore how the sensitivity to basic tastes changes due to anticancer agents and how alterations in one taste perception are associated with changes in other tastes during chemotherapy. Methods: A cross-sectional questionnaire-based interview survey was conducted on 215 patients undergoing chemotherapy. The subjective sensitivity to each basic taste was assessed using a visual analog scale, and the incidence of taste alterations due to different chemotherapy regimens was calculated. Multivariate logistic regression analysis was performed to determine whether there were associations between changes in one taste sensitivity and changes in other taste sensitivities. Results: Approximately half (49.5%) of the patients experienced chemotherapy-induced taste alterations. An analysis of subjective changes in basic tastes revealed that the salt and umami taste systems were more sensitive to chemotherapy than other taste systems. Patients with altered sensitivity to sweet taste were significantly more likely to report altered sensitivity to salt, bitter, and sour tastes. Moreover, umami–salt and bitter–sour taste sensitivities were significantly related to each other. Conclusion: This study suggests that changes in subjective sensitivities to one basic taste during chemotherapy may be accompanied by changes in other tastes in specific combinations. Considering taste associations in dietary guidance may help improve the nutritional status of cancer patients experiencing taste alterations due to chemotherapy. [ABSTRACT FROM AUTHOR]

Purpose: This randomized crossover trial investigated the effects of Daikenchuto (DKT: TJ-100) on gastrointestinal symptoms of patients after colon and rectosigmoid cancer surgery. Methods: Among patients who had completed surgery for colon cancer, including rectosigmoid cancer, over 6 months ago, 20 who complained of gastrointestinal symptoms were enrolled. Subjects were randomly assigned to two sequences: sequences: A and B. In period 1, sequence A subjects were orally administered DKT, whereas sequence B subjects were untreated for 28 days. After a 5-day interval, in period 2, sequences A and B were reversed. Quality-of-life markers (GSRS and VAS), the Sitzmark transit study, the orocecal transit time (lactulose hydrogen breath test) and Gas volume score were evaluated before and after each period with findings compared between the presence of absence of DKT administration. Results: Between sequences, there were no significant differences in clinicopathological characters or any evaluations before randomization. There was no carryover effect in this crossover trial. The administration of DKT significantly ameliorated the GSRS in total, indigestion, and diarrhea, although the planned number of subjects for inclusion in this trial was not reached. Conclusions: DKT may ameliorate subjective symptoms for postoperative patients who complain of gastrointestinal symptoms. [ABSTRACT FROM AUTHOR]

Purpose: The short- and long-term efficacy, safety, and pharmacokinetics of teduglutide were analyzed in adult Japanese patients with short bowel syndrome and intestinal failure (SBS-IF). Methods: Patients received teduglutide 0.05 mg/kg/day in clinical trials (TED-C14-004, SHP633-306, and extension SHP633-307). Data were analyzed at 24 weeks and an interim data cut-off of 4.5 years. Results: The parenteral support (PS) volume decreased by ≥ 20% for 9/18 patients at 24 weeks and in all 11 patients by data cut-off in SHP633-307. The mean (standard deviation) PS volume decreased from baseline at 24 weeks in TED-C14-004 (−30.1 ± 25.9%) and SHP633-306 (−25.6 ± 25.5%), and at data cut-off in SHP633-307 (−57.08 ± 28.49%). Teduglutide was absorbed quickly. The adverse events were consistent with the underlying disease and known adverse drug reactions. Anti-teduglutide antibody titers declined with long-term treatment. Conclusions: In Japanese adults with SBS-IF, teduglutide treatment was associated with clinically meaningful reductions in PS requirements, similar to findings in prior international studies. No new safety concerns specific to the Japanese SBS-IF patient population were identified with short- or long-term teduglutide treatment. Anti-teduglutide antibody titers disappeared in most Japanese adults with long-term treatment. These results constitute the longest evaluation of teduglutide treatment within clinical trials reported to date. [ABSTRACT FROM AUTHOR]

Introduction: Recently, complicated intra-abdominal infections (cIAI) have been caused not only by Escherichia coli, Klebsiella pneumoniae, Enterobacter cloacae, and Pseudomonas aeruginosa, but also by extended-spectrum β-lactamase-producing Enterobacterales members. Ceftolozane–tazobactam (CTLZ–TAZ) is considered to exhibit therapeutic effects against cIAI. Studies on the concentrations of antibiotics in abdominal tissues directly affected by cIAI are limited. Therefore, in this study, we investigated the pharmacokinetics of CTLZ–TAZ in abdominal tissue and simulated the administration regimen required to achieve the pharmacodynamic target for cIAI-causing bacteria. Methods: Patients scheduled for elective lower gastrointestinal surgery were intravenously administered preoperative CTLZ–TAZ (1 g CTLZ and 0.5 g TAZ). Plasma, peritoneal fluid, peritoneum, and subcutaneous adipose tissue samples were collected during the surgery, and CTLZ as well as TAZ concentrations were measured. The noncompartmental and compartmental pharmacokinetic parameters were then estimated. Site-specific pharmacodynamic target attainment analysis using 1.5 g of CTLZ–TAZ was performed. Results: CTLZ–TAZ was administered to nine patients (once to five patients and twice to four patients). The mean peritoneal fluid-to-plasma ratio (one dose/two doses) for CTLZ was 0.74/1.15, which was slightly higher than the mean peritoneal fluid-to-plasma ratio for TAZ (0.95/1.13). The ratio for subcutaneous adipose was lower than those for peritoneal fluid and peritoneum tissues. We also discovered that the average ratio of CTLZ and TAZ concentrations in all tissues was maintained at or above 2:1. In our investigation of pharmacodynamic target attainment in each tissue, the desired bactericidal effect was attained with all CTLZ–TAZ (1.5 g) administration regimens [q12h (3 g/day), q8h (4.5 g/day), and q6h (6 g/day)]. Conclusion: To the best of our knowledge, this is the first study investigating the optimal pharmacodynamic level of CTLZ–TAZ in the abdominal tissue against cIAI-causing bacteria. This study also serves as a guideline for designing an optimal administration regimen based on pharmacodynamic target attainment for cIAI-causing bacteria. Details of the trial registration: The institutional review board of Hiroshima University Hospital, CRB6180006. The Japan Registry of Clinical Trials, jRCTs061190025. [ABSTRACT FROM AUTHOR]

Background: Patients with longstanding inflammatory bowel disease are at high risk of developing intestinal cancers. In this study, we aimed to elucidate the differences between intestinal cancers associated with ulcerative colitis and Crohn's disease. Methods: Intestinal cancers in ulcerative colitis and Crohn's disease patients treated between 1983 and 2020 at 43 Japanese institutions were retrospectively analyzed.. Results: A total of 1505 intestinal cancers in 1189 ulcerative colitis and 316 Crohn's disease patients were studied. Almost all of ulcerative colitis-associated cancers (99%) were in the colon and rectum, whereas half of Crohn's disease-associated cancers (44%) were in the anus, with 11% in the small intestine. Ulcerative colitis-associated cancers were diagnosed more frequently by surveillance (67% vs. 25%, P < 0.0001) and at earlier stages (stages 0–1, 71% vs. 27%, P < 0.0001) compared with Crohn's disease-associated cancers. Colorectal cancers associated with Crohn's disease showed a significantly worse 5-year overall survival rate than those associated with ulcerative colitis (stage 2, 76% vs. 89%, P = 0.01, stage 3, 18% vs. 68%, P = 0.0009, and stage 4, 0% vs. 13%, P = 0.04). Surveillance correlated with earlier diagnoses for ulcerative colitis- and Crohn's disease-associated intestinal cancers, whereas shorter intervals between endoscopic examinations correlated with an earlier cancer diagnosis in ulcerative colitis patients but not in Crohn's disease patients. Conclusions: The clinical and oncological features of ulcerative colitis- and Crohn's disease-associated cancers were very different. Crohn's disease-associated cancers were diagnosed at more advanced stages and were detected less frequently by surveillance. Additionally, they showed a significantly poorer prognosis. [ABSTRACT FROM AUTHOR]

Febrile neutropenia (FN) is an infectious complication that develops during chemotherapy. Although the oral cavity can be an important infection route, it is unknown whether the oral environment is associated with FN. The present study examined the relationship between the oral environment using periodontal inflamed surface area (PISA), a new periodontal disease parameter, and FN in hematologic cancer patients undergoing chemotherapy. In this retrospective cohort study, 157 patients were divided into FN onset during chemotherapy (n = 75) and the FN negative groups (n = 82). The associations of risk factors related to the intraoral environment were assessed. Logistic regression analysis showed that types of blood cancer (odds ratio 1.98; P < 0.01), use of a high-risk regimen (odds ratio 4.44; P < 0.05), prophylaxis treatment with human granulocyte colony-stimulating factor (G-CSF) (odds ratio 4.15; P < 0.01) and PISA (odds ratio 1.02; P < 0.01) were independent factors associated with FN onset. Finally, propensity score matching was performed between two groups; 37 matched pairs were generated. PISA was significantly higher in the FN group than the FN negative group. There was a significant relationship between PISA and FN onset (P = 0.035). The present findings indicate that periodontitis treatment before starting cancer treatment is recommended as supportive care for preventing FN onset during chemotherapy. [ABSTRACT FROM AUTHOR]

This study aimed to develop the feasible and effective universal screening strategy of the notable SARS-CoV-2 variants by Sanger Sequencing Strategy and then practically applied it for mass screening in Hiroshima, Japan. A total of 734 samples from COVID-19 confirmed cases in Hiroshima were screened for the notable SARS-CoV-2 variants (B.1.1.7, B.1.351, P.1, B.1.617.2, B.1.617.1, C.37, B.1.1.529, etc.). The targeted spike region is amplified by nested RT-PCR using in-house designed primer set hCoV-Spike-A and standard amplification protocol. Additionally, randomly selected 96 samples were also amplified using primer sets hCoV-Spike-B and hCoV-Spike-C. The negative amplified samples were repeated for second attempt of amplification by volume-up protocol. Thereafter, the amplified products were assigned for Sanger sequencing using corresponding primers. The positive amplification rate of primer set hCoV-Spike-A, hCoV-Spike-B and hCoV-Spike-C were 87.3%, 83.3% and 93.8% respectively for standard protocol and increased to 99.6%, 95.8% and 96.9% after second attempt by volume-up protocol. The readiness of genome sequences was 96.9%, 100% and 100% respectively. Among 48 mutant isolates, 26 were B.1.1.7 (Alpha), 7 were E484K single mutation and the rest were other types of mutation. Moreover, 5 cluster cases with single mutation at N501S were firstly reported in Hiroshima. This study indicates the reliability and effectiveness of Sanger sequencing to screen large number of samples for the notable SARS-CoV-2 variants. Compared to the Next Generation Sequencing (NGS), our method introduces the feasible, universally applicable, and practically useful tool for identification of the emerging variants with less expensive and time consuming especially in those countries where the NGS is not practically available. Our method allows not only to identify the pre-existing variants but also to examine other rare type of mutation or newly emerged variants and is crucial for prevention and control of pandemic. [ABSTRACT FROM AUTHOR]

Background: Rectourethral fistula is a rare disease with a wide variety of etiologies and clinical presentations. A definitive surgical procedure for rectourethral fistula repair has not been established. Case presentation: A 13-year-old boy sustained a penetrating injury to the perineum, and developed a symptomatic rectourethral fistula thereafter. Conservative management through urinary diversion and transanal repair was unsuccessful. Fecal diversion with loop colostomy was performed, and three months later, a fistula repair was performed via a transperineal approach with interposition of a local gluteal tissue flap. There were no postoperative complications, and magnetic resonance imaging studies confirmed the successful closure of the fistula. The urinary and fecal diversions were reverted 1 and 6 months after the fistula repair, respectively, and postoperative excretory system complications did not occur. Conclusions: The transperineal approach with interposition of a local gluteal tissue flap provides a viable surgical option for adolescent patients with rectourethral fistulas who are unresponsive to conservative management. [ABSTRACT FROM AUTHOR]

Background: Mycoplasma hominis is a human commensal bacterium of the urogenital tract, and extragenital infection caused by M. hominis has rarely been reported. The identification of M. hominis is challenging, and surgeons are generally not aware that this bacteria can cause postoperative infection. Here, we report a rare case of postoperative mediastinitis caused by M. hominis after cardiac surgery in an immunocompetent patient. Case presentation: A 54-year-old man presented with pain and purulent discharge from the wound after aortic valve replacement and patent foramen ovale closure. However, Gram staining and culture of bacteria from the purulent discharge was negative, and empiric sulbactam/ampicillin therapy was not effective. This patient developed mediastinitis and rupture of a pseudoaneurysm of the ascending aorta caused by mediastinitis, and re-operation was performed. Then, postoperative mediastinitis caused by M. hominis or Ureaplasma species was suspected and bacterial cultures targeting these pathogens were performed. M. hominis was identified from abscess and tissue obtained from the surgical site and urine. A final diagnosis of postoperative mediastinitis caused by M. hominis was determined. The patient was initially treated with levofloxacin and then with minocycline for 3 weeks. The patient's clinical condition improved; the patient was transferred to another hospital. Conclusion: The role of M. hominis as a cause of postoperative infection might be underestimated in cardiac surgery. M. hominis should be considered when culture-negative purulent discharge is observed or there is no response to standard empiric treatment of postoperative infections. [ABSTRACT FROM AUTHOR]

Ulcerative colitis (UC), which mainly consists of mucosal lesions, rarely form colovesical or rectovesical fistulas, although few cases of fistula formation associated with comorbidities have been reported. We report a case of UC-associated rectal cancer diagnosed following symptoms associated with rectovesical fistula. A 40-year-old man with a 31-year history of extensive UC presented with difficulty in defecation. Two years before the current presentation, he had experienced pneumaturia, and the examination then had revealed a rectal neoplastic lesion and rectovesical fistula; however, tissue biopsy showed no malignancy. Therefore, he requested for observation with no further treatment. Current examination suggested the rectal tumor had grown to invade the bladder. Tissue biopsy showed no malignancy. However, the clinical symptoms and examination findings strongly indicated UC-associated rectal cancer with bladder invasion; thus, open total proctocolectomy with partial cystectomy was performed. Histopathological evaluation of the rectal neoplastic lesion revealed UC-associated rectal cancer originating from the inflammatory mucosa, and the rectovesical fistula was found to be caused by the rectal cancer invading the bladder. Therefore, other colorectal cancers should be considered even though tissue biopsy does not reveal malignant lesions in UC patients with fistula. [ABSTRACT FROM AUTHOR]

The urinary antigen test (UAT) is a rapid diagnostic method for pneumococcal pneumonia, but the high false-negative rate of 30% may affect its reliability. To maximize the utility of UAT, it is necessary to investigate the patient factors affecting UAT results. However, there is no report elucidating the association between its utility and pre-existing lung abnormalities. We retrospectively reviewed 388 patients with pneumococcal pneumonia confirmed by blood and/or sputum culture tests. Finally, 94 of 388 patients who had the results of UAT and computed tomography scans were enrolled to evaluate the association between the utility of UAT and patient factors including pulmonary emphysema and fibrosis. The overall positive rate of UAT was 69.1%. The positive rates of UAT in the patients with emphysema were significantly lower than those in individuals without emphysema (33.3% and 77.6%, p < 0.001). Univariate logistic regression analysis showed that the presence of emphysema was associated with a low positive rate (odds ratio 6.944, 95% confidence interval 2.268–21.231). Multivariate logistic analysis showed that the presence of emphysema and lower levels of serum blood urea nitrogen (BUN) were significantly and independently associated with a low positive rate. The combination of emphysema and BUN can potentially stratify the positive rate of UAT in patients with pneumococcal pneumonia. Patients with pneumococcal pneumonia and emphysema have a lower positive rate of UAT. Additionally, the combination of emphysema and serum BUN value may be useful to evaluate the reliability of the negative results of pneumococcal UAT. [ABSTRACT FROM AUTHOR]

Purpose: Staphylococcus aureus is a relatively uncommon causative agent of urinary tract infection (UTI). However, the clinical features of S. aureus-related UTI are unclear. Thus, we aimed to clarify how patients with S. aureus bacteriuria develop UTI and determine the features and clinical risk factors of symptomatic S. aureus-related UTI. Methods: We performed a retrospective study of patients at the Hiroshima University Hospital for whom S. aureus had been isolated from urine culture from January 2010 to December 2017. The characteristics (age, sex, body mass index, indwelling catheterization, renal stones, hydronephrosis, anticancer drug use, diabetes mellitus, steroid use, serum albumin, antibiotic use in the past 1 month, estimated glomerular filtration rate, benign prostate hyperplasia, and neurogenic bladder) of patients with UTI and those without UTI were compared, and the risk factors for S. aureus-related UTI were identified by multiple logistic regression model. Results: A total of 286 patients with S. aureus bacteriuria were analyzed; 33 patients developed UTI. The causative pathogens were methicillin-sensitive S. aureus and methicillin-resistant S. aureus (MRSA) in 14 and 19 patients, respectively, who developed UTI. This study demonstrated that indwelling catheterization, hydronephrosis, and renal stones are significantly associated with S. aureus-related UTI (p = 0.01, odds ratio = 3.1; and p < 0.01, odds ratio = 7.0; and p = 0.02, odds ratio = 1.2; respectively) and hypoalbuminemia in MRSA-related UTI (p < 0.01). Conclusion: Paying attention to risk factors, specifically indwelling catheterization, renal stones, and hydronephrosis, will be an effective strategy for prevention of S. aureus-related UTI with persistent staphylococcal bacteriuria. [ABSTRACT FROM AUTHOR]

Background: The guidelines for the prevention, detection, and management of gastroenterological surgical site infections (SSIs) were published in Japanese by the Japan Society for Surgical Infection in 2018. This is a summary of these guidelines for medical professionals worldwide. Methods: We conducted a systematic review and comprehensive evaluation of the evidence for diagnosis and treatment of gastroenterological SSIs, based on the concepts of the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system. The strength of recommendations was graded and voted using the Delphi method and the nominal group technique. Modifications were made to the guidelines in response to feedback from the general public and relevant medical societies. Results: There were 44 questions prepared in seven subject areas, for which 51 recommendations were made. The seven subject areas were: definition and etiology, diagnosis, preoperative management, prophylactic antibiotics, intraoperative management, perioperative management, and wound management. According to the GRADE system, we evaluated the body of evidence for each clinical question. Based on the results of the meta-analysis, recommendations were graded using the Delphi method to generate useful information. The final version of the recommendations was published in 2018, in Japanese. Conclusions: The Japanese Guidelines for the prevention, detection, and management of gastroenterological SSI were published in 2018 to provide useful information for clinicians and improve the clinical outcome of patients. [ABSTRACT FROM AUTHOR]

Tumor necrosis factor-alpha inhibitor (TNFi) treatment is effective for ulcerative colitis (UC) and Crohn's disease (CD). Although several meta-analyses have been performed to evaluate the association between TNFi treatment and surgical morbidity, the results are controversial. We conducted a systematic review and meta-analysis of the prevention of surgical site infection (SSI) after surgery for UC and CD in patients on TNFis, based on literature published between January 2000 and May 2019 (registered on PROSPERO, No. CRD42019134156). Overall, 2175 UC patients in 13 observational studies (OBSs) and 7084 CD patients in 16 OBSs were included. The incidences of incisional (INC) SSI and organ/space (O/S) SSI after surgery for UC were 179/1985 (9.0%) and 176/2175 (8.1%), respectively. TNFi use was not associated with the incidences of INC SSI (odds ratio (OR) 1.04, 95% confidence interval (CI) (0.47–2.32) or O/S SSI (OR 1.85, 95% CI (0.82–4.20)) after surgery for UC. The INC SSI and O/S SSI incidences after surgery for CD were 289/3089 (9.4%) and 526/7,084 (7.4%), respectively. Preoperative TNFi use was not associated with INC SSI (OR 0.98, 95% CI (0.52–1.83)) or O/S SSI incidence (OR 1.09, 95% CI (0.78–1.52)) after surgery for CD. We did not find a significant association between preoperative TNFi use and SSI in surgery for UC or CD. [ABSTRACT FROM AUTHOR]

Background: Invasive micropapillary carcinoma (IMPC) is a relatively rare subtype of gastric adenocarcinoma and has aggressive histopathologic characteristics, including lymphatic and vascular invasion. However, the associated long-term survival outcomes remain unclear. This study aimed to compare the clinicopathological characteristics and prognosis of gastric adenocarcinoma with and without IMPC using propensity score-matched (PSM) analysis. Methods: Patients with gastric adenocarcinoma who underwent gastrectomy between 2006 and 2015 were included in the analysis. PSM analysis was performed to compensate for the background heterogeneity between the groups. The primary endpoint was disease-free survival (DFS) after gastrectomy, and the secondary endpoints were disease-specific survival (DSS) and recurrence pattern. Results: Of 882 patients who underwent gastrectomy for gastric adenocarcinoma, with a follow-up duration greater than 36 months, 35 were diagnosed as having gastric adenocarcinoma with IMPC. After PSM, 70 patients, including 35 with IMPC and 35 without IMPC, were selected. Gastric adenocarcinoma with IMPC is characterized by lymphatic invasion (94% versus 69%, p = 0.012). Patients with IMPC had significantly poorer DFS than those without IMPC, with 3-year DFS rates of 62.2% and 93.4% (p = 0.003), respectively. Furthermore, a significant difference was also observed in DSS (p = 0.016); patients with IMPC more frequently developed liver metastasis (20%) than those without IMPC (3%, p = 0.006). Conclusions: Resected gastric carcinoma with IMPC was associated with poorer DFS and DSS; furthermore, an increased rate of lymphatic invasion and liver metastasis was noted than in cases without IMPC. [ABSTRACT FROM AUTHOR]

Purpose: To determine a recommended dose for a biweekly combination neoadjuvant chemotherapy including gemcitabine, nab-paclitaxel, and S-1 (GAS) for patients with locally advanced pancreatic ductal adenocarcinoma (LAPC).Methods: Patients with borderline resectable or unresectable LAPC without distant metastasis were eligible for this study. The planned dosages of gemcitabine (mg/m2, day 1), nab-paclitaxel (mg/m2, day 1), and S-1 (mg/day, days 1-7) were 800/100/60-100 at level 1, and 1000/125/60-100 at level 2. The treatment cycle was repeated every 2 weeks, and patients were assessed for resectability and response to the treatment after 6 cycles. This study was registered with UMIN Clinical Trial Registry (UMIN000016630).Results: We enrolled 16 patients with LAPC in this study. At dose level 1, one of 8 patients experienced dose-limiting toxicity (DLT). One of the next 8 patients also experienced DLT at dose level 2. Based on these results, level 2 was considered the recommended dose for this regimen. Pancreatectomy with curative intent could be performed in 13 of the 16 patients. R0 resection was performed in 12 of 13 patients.Conclusion: In conclusion, recommended doses for a biweekly GAS chemotherapy regimen were determined as nab-paclitaxel: 125 mg/m2, gemcitabine: 1000 mg/m2 on day 1, S-1: <1.25 m2, 60 mg; 1.25-1.5 m2, 80 mg; >1.5 m2, 100 mg twice a day on days 1-7. GAS chemotherapy showed good preliminary efficacy with mild toxicity in this study, and warrants a further phase 2 trial to investigate the efficacy of the GAS regimen for LAPC. [ABSTRACT FROM AUTHOR]

Background: This exploratory trial was conducted to investigate whether daikenchuto accelerates the recovery of gastrointestinal function in patients undergoing open surgery for sigmoid or rectosigmoid cancer.Methods: Eighty-eight patients who underwent colectomy at one of the 11 clinical trial sites in Japan from January 2009 to June 2011 were registered in the study. Patients received either placebo or daikenchuto (15.0 g/day, 5 g three times a day) from postoperative day 2 to postoperative day 8. The study end points included the gastrointestinal tract transit time evaluated with radiopaque markers and the time to first flatus. The safety profile of daikenchuto was also evaluated until postoperative day 8.Results: Seventy-one patients (daikenchuto, n = 38; placebo, n = 33) were statistically analyzed. Although the number of radiopaque markers in the anal side of the small intestine at 6 h was significantly greater in the daikenchuto group than in the placebo group (15.19 vs 10.06, p = 0.008), the total transit analysis results and the mean time to first flatus did not differ significantly between the two groups.Conclusions: Daikenchuto has a positive effect on the resolution of delayed gastric emptying, but has a limited effect on the resolution of postoperative paralytic ileus after open surgery in patients with sigmoid or rectosigmoid cancer. Daikenchuto may contribute to early oral intake in the postoperative course. [ABSTRACT FROM AUTHOR]

Background: Telomerase activity and human telomerase reverse transcriptase (TERT) have been reported as markers of tumor aggressiveness and poor prognosis in several digestive cancers. In the present study, we examined telomerase activity and TERT expression in ampullary carcinoma to determine whether these parameters could be used as indicators of aggressiveness and prognosis. Methods: Telomerase activity was analyzed by using the telomeric repeat amplification protocol assay, and TERT was examined by immunohistochemistry in ampullary carcinoma tissue samples resected from 46 patients. Results: Telomerase activity was detected in 42 (91.3%) ampullary carcinomas and 27 (58.7%) showed high activity, whereas TERT expression was detected in 35 (76.1%), including 21 with weak expression and 14 with strong expression. Univariate analysis revealed that histological grade ( P = 0.029), tumor depth ( P < 0.001), nodal status ( P = 0.013), UICC stage ( P = 0.009), perineural invasion ( P < 0.001), and telomerase activity ( P = 0.031) were significantly associated with disease-specific survival. In multivariate analysis, only telomerase activity remained an independent predictor of prognosis ( P = 0.043). There was no statistical significance for survival among the three grades of TERT expression ( P = 0.054); however, in subgroup analysis, patients with strong TERT expression showed significantly poorer prognosis than those without TERT expression ( P = 0.013). Conclusions: Our results suggest that high telomerase activity and strong TERT expression may serve as new prognostic markers for evaluating the prognosis of patients with resected ampullary carcinoma. [ABSTRACT FROM AUTHOR]

Background: The prognosis of patients with cholangiocarcinoma is unsatisfactory. Therefore, evaluation of prognostic factors and establishment of new therapeutic strategies are needed to improve their long-term survival. The aim of this study was to identify useful prognostic factors for patients with intrahepatic, hilar, and distal cholangiocarcinoma. Materials and Methods: Records of 127 patients with cholangiocarcinoma (21 with intrahepatic cholangiocarcinoma, 50 with hilar cholangiocarcinoma, and 56 with distal cholangiocarcinoma) who underwent surgical resection were reviewed retrospectively. Relationships between survival and clinicopathological factors including patient demographics and tumor characteristics were evaluated using univariate and multivariate analysis. Results: For all 127 patients, overall 1-, 3-, 5-year survival rates were 80, 51, and 40%, respectively. Univariate analysis revealed that adjuvant chemotherapy ( P = .049), tumor differentiation ( P = .014), lymph node metastasis ( P < .001), surgical margin status ( P < .001), UICC pT factor ( P < .001), and UICC stage ( P < .001) were associated significantly with survival. UICC pT factor ( P = .007), adjuvant chemotherapy ( P = .009), surgical margin status ( P = .012), and lymph node metastasis ( P = .014) remained independently associated with long-term survival by multivariate analysis. The 5-year survival rates of patients with or without positive surgical margins were 13 and 49%, respectively. The 5-year survival rates of patients treated with or without adjuvant chemotherapy were 47 and 36%, respectively. Conclusions: R0 resection and adjuvant chemotherapy may be mandatory to achieve long-term survival for patients with cholangiocarcinoma. [ABSTRACT FROM AUTHOR]

Background: Pancreatic cancer is one of the most deadly cancers, and serum carbohydrate antigen 19-9 (CA19-9) level has been reported to be a useful prognostic marker in pancreatic cancer. The purpose of this study was to determine which prognostic factor (preoperative or postoperative serum CA19-9 level) is more useful. Methods: Pre- and postoperative serum CA19-9 levels were measured in 109 patients who underwent surgical resection for pancreatic cancer between 1998 and 2009, and their relationships to clinicopathological factors and overall survival were analyzed with univariate and multivariate methods. Results: In univariate analysis, tumor location ( P = 0.019), postoperative adjuvant chemotherapy ( P < 0.001), residual tumor factor status ( P < 0.001), UICC pT stage ( P = 0.004), lymph node metastasis ( P = 0.015), and UICC final stage ( P = 0.015) were significantly associated with overall survival. Differences in overall survival were significant between groups divided on the basis of four postoperative CA19-9 cutoff values (37, 100, 200, and 500 U/ml) but not significant between groups divided on the basis of the same four preoperative CA19-9 cutoff values. Pre- to postoperative increase in CA19-9 level also was significantly associated with poor prognosis. In multivariate analysis, postoperative adjuvant chemotherapy (hazard ratio, 1.59; P = 0.004) and postoperative CA19-9 cutoff value of 37 U/ml (HR, 1.64; P = 0.004) remained independent predictors of prognosis. Conclusions: Postoperative CA19-9 level is a better prognostic factor than preoperative CA19-9 level, and curative surgery for resectable pancreatic cancer should be tried regardless of the preoperative CA19-9 level. [ABSTRACT FROM AUTHOR]

This study was a pharmacokinetic (PK)-pharmacodynamic (PD) target attainment analysis of meropenem in Japanese adult patients. Plasma drug concentration data (265 samples from 42 patients) were used for population PK modeling and Monte Carlo simulation to assess the probability of attaining the PK-PD target (40% of the time above the MIC for the bacterium). The final population PK model identified creatinine clearance (Clcr, ml/min) and body weight (BW, kg) as the most significant covariates: Cl (l/h) = 0.0905 9 Clcr + 2.03, Vc (l) = 0.199 9 BW, Q (l/h) = 4.02, and Vp (l) = 4.55, where Cl is the clearance, Vc and Vp are the volumes of distribution of the central and peripheral compartments, respectively, and Q is the intercompartmental clearance. The Monte Carlo simulation developed the PK-PD breakpoints (the highest MIC values at which the probabilities of target attainment in plasma are 80% or more) for meropenem regimens, the values of which varied with the Clcr and BW of the patient. The simulation also demonstrated that 0.25 g every 12 h (0.5-h infusion) achieved a target attainment probability of 82.4-100% against Escherichia coli, methicillin-susceptible Staphylococcus aureus, Haemophilus influenzae, and Streptococcus pneumoniae isolates. However, against Pseudomonas aeruginosa isolates, 0.5 g every 8 h or 1 g every 8 h was required to achieve 80% or more probability in most typical patients. These results provide a PK-PD-based strategy for tailoring a meropenem regimen according to Clcr and BW of a Japanese adult patient and susceptibility of the causative bacteria. [ABSTRACT FROM AUTHOR]

Postoperative adjuvant therapy is mandatory for biliary carcinoma because of its unfavorable prognosis. The aim of this study was to evaluate the indication for postoperative adjuvant therapy in biliary carcinoma. The charts of 139 consecutive patients with biliary carcinoma (37 ampullary carcinomas, 36 distal carcinomas, 38 carcinomas of the gallbladder, and 28 hilar cholangiocarcinomas) who underwent surgical resection were retrospectively reviewed. Recurrence rates and survival rates after surgery were analyzed. Of the 139 carcinomas, the recurrence rates of International Union Against Cancer (UICC) stages IA, IB, IIA, IIB, and III cancers were 9%, 20%, 60%, 83%, and 100%, respectively. The recurrence rates of UICC stages II and III cancers were significantly higher than that of UICC stage I cancer (82% vs 13%, P < 0.001). The 5-year survival rates for patients with UICC stages IA, IB, IIA, IIB, and III cancers were 85%, 75%, 36%, 20%, and 0%, respectively. The 5-year survival rates for UICC stages II and III cancers were significantly lower than that for UICC stage I cancer (21% vs 82%, P < 0.001). Postoperative adjuvant therapy should be given to patients with UICC stages II and III biliary carcinomas because of their high rate of recurrence and the poor prognosis. [ABSTRACT FROM AUTHOR]

The aim of this study was to identify prognostic factors in patients undergoing pancreatoduodenectomy with lymphadenectomy for ampullary carcinoma. The records of 46 consecutive patients with ampullary carcinoma who underwent pancreatoduodenectomy from 1988 through 2006 were retrospectively reviewed. A 98% rate of potentially curative (R0) resection was achieved. There was no 30-day mortality. Overall 5-year survival rate was 64%. Univariate analysis revealed that T3 and T4 tumor (i.e., pancreatic parenchymal invasion) (P < 0.001), lymph node metastasis (P = 0.01), and perineural invasion (P < 0.001) were significant predictors of poor prognosis. Furthermore, perineural invasion was found to be a significant independent predictor of poor prognosis by multivariate analysis (P = 0.024). Pancreatoduodenectomy with lymphadenectomy for ampullary carcinoma is a safe surgical procedure with an acceptable cure rate. The presence of perineural invasion may be useful for predicting poor prognosis in patients with ampullary carcinoma who undergo potentially curative resection. [ABSTRACT FROM AUTHOR]

OBJECTIVE: A variety of charcoal-containing devices are purported to minimize problems with odoriferous rectal gas; however, the evidence supporting the efficacy of these products is virtually all anecdotal. We objectively evaluated the ability of these devices to adsorb two malodorous, sulfide gases (hydrogen sulfide and methylmercaptan) instilled at the anus.MATHODS: Via a tube, 100 ml of nitrogen containing 40 ppm of sulfide gases and 0.5% H2 was instilled at the anus of six healthy volunteers who wore gas impermeable Mylar® pantaloons over their garments. Since H2 is not adsorbed by charcoal, the fraction of the sulfide gases removed could be determined from the concentration ratio of sulfide gas: H2 in the pantaloon space relative to the ratio in instilled gas.RESULTS: Measurements with no device in place showed that subjects' garments removed 22.0± 5.3% of the sulfide gases, and results obtained with each device were corrected for this removal. The only product that adsorbed virtually all of the sulfide gases was briefs constructed from an activated carbon fiber fabric. Pads worn inside the underwear removed 55–77% of the sulfide gases. Most cushions were relatively ineffective, adsorbing about 20% of the gases.CONCLUSIONS: The ability of charcoal-containing devices to adsorb odoriferous rectal gases is limited by incomplete exposure of the activated carbon to the gases. Briefs made from carbon fiber are highly effective; pads are less effective, removing 55–77% of the odor; cushions are relatively ineffective.(Am J Gastroenterol 2005;100:1–4) [ABSTRACT FROM AUTHOR]

Background The aim of this study was to assess the long-term (greater than 2 years) results of seton drainage on anal fistulae in patients with Crohn's disease. Methods. Between September 1990 and September 1999, 32 patients with Crohn's disease underwent seton drainage for complex anal fistulae. The median followup time in these patients was 62 months (range, 25-133 months). In 10 patients (31.3%), recurrent perineal abscesses occurred with inlying seton drainage, and these were drained by re-insertion of the seton. A Malecot catheter was also inserted in 8 patients with recurrence. Results. The overall success rate of long-term seton usage was 87.5%. The subsequent associated procedure was simple seton removal (n = 9), secondary core-out fistulectomy (n = 7), or lay-open fistulotomy (n = 4). Eleven patients still had the seton in place. Recurrence developed in 3 patients (33%) who underwent simple seton removal and in 2 patients (18.2%) who underwent the secondary core-out procedure or fistulotomy. At the last follow-up examination, continence had not changed in 28 (87.5%) of the 32 patients. No change in continence was experienced by 10 of the 11 patients who underwent secondary fistulotomy or the secondary core-out procedure. Conclusions. Long-term seton drainage for complex anal fistula in Crohn's disease is efficacious in both treating sepsis and preserving anal sphincter function. A relatively good result was achieved by the secondary core-out procedure or fistulotomy at the time of seton removal. [ABSTRACT FROM AUTHOR]

Changes in the intestinal flora were investigated in patients administered antibiotics for 4 days after a gastrectomy. Twenty-four patients were divided into each of the following groups: cefazolin, 1 g every 8 h; cefozopran, 0.5 g every 8 h; flomoxef, 1 g every 8 h. All drugs were administered intravenously for a 4-day period. Antibiotic prophylaxis caused no major change in the total number of anaerobes because of the preservation of the Bacteroides fragilis group. However, the number of Bifidobacterium, Lactobacillus, Eubacterium, and Veillonella spp. decreased by an average of 100-fold. These changes were accompanied by an overgrowth of Enterococcus spp. and Pseudomonas aeruginosa. Four days of antibiotic prophylaxis after surgery caused a suppression of colonization resistance in the intestinal flora. Certain genera of anaerobes may thus play an important role in preventing overgrowth of antibiotic-resistant organisms after surgery. Surgeons should decide the duration of antibiotic use after carefully considering its influence on the intestinal flora. [ABSTRACT FROM AUTHOR]

Involvement of the gastroduodenum is extremely rare in Crohn's disease. For obstructing duodenal Crohn's disease, bypass procedures have traditionally been selected. However, more recently, strictureplasty has become an acceptable surgical option. We treated two Crohn's disease patients with short proximal duodenal stenosis, using Finney-type strictureplasty. Their postoperative courses were uneventful and they have remained asymptomatic during follow-up periods of more than 5 years, and 4 months, respectively. Owing to the good clinical results of our two patients, we consider strictureplasty to be indicated for short proximal duodenal stenosis in Crohn's disease. [ABSTRACT FROM AUTHOR]

< 0.05). The surgical site infection rate was 18% in group 1 and 13% in group 2. Organisms isolated from the sites of postoperative infections were not identical with those from the peritoneal fluid. This relatively brief course preparation minimized the emergence of resistant strains. However, in spite of the colonic bacterial burden and the intraoperative inoculation in the patients with mechanical cleansing alone, their incidence of subsequent infections was comparable to that of patients who were administered oral antibiotics provided that the prophylactic antibiotic was administered for 3 days after surgery. [ABSTRACT FROM AUTHOR]

To determine the effect of antibiotics used for the treatment of postoperative infections on the normal intestinal flora in patients who have undergone gastroenterological surgery, we performed a prospective randomized study in patients who had undergone distal gastrectomy. Cefazoline was administered up to postoperative day 3 for prophylaxis. For the treatment of postoperative infections, either panipenem/betamipron (PAPM/BP; n = 5) or sulbactam/cefoperazone (SBT/CPZ; n = 5) was adminstered to ten patients with signs of postoperative infections. Feces were examined for bacteria before and 4 and 7 days after the commencement of administration of these therapeutic antibiotics. The anaerobic bacterial count decreased significantly in four of five patients treated with SBT/CPZ, from 1010.2±0.36/g before treatment to 105.22±3.51/g. In the PAPM/BP-treated group, the anaerobic bacterial count did not change after antibiotic therapy. We also investigated the major genera of colonic anaerobes, and found that the numbers of bifidobacteria were maintained during PAPM/BP administration. However, in the SBT/CPZ group, the number of bifidobacteria decreased to below the detection limit in four of five patients. Little change was observed in the aerobic bacterial count in either group. However, Enterobacteriaceae were replaced by enterococcus or candida in all patients from the SBT/CPZ group and in one of five patients from the PAPM/BP group. Physicians should be alert for the possible clinical consequences of changes in intestinal microflora after antibiotic treatment of postoperative infections. [ABSTRACT FROM AUTHOR]

Pancreatic ascites can occur in association with the rupture of a pseudocyst or the disruption of a pancreatic duct during the natural course of chronic pancreatitis. We report herein the successful treatment of three patients with pancreatic ascites by performing a surgical procedure after 4–6 weeks of total parenteral nutrition (TPN) proved ineffective. The principles of our surgical procedure for pancreatic ascites are as follows: (1) minimum pancreatic tissue is resected; (2) surgical intervention to repair leaking sites is not necessary; (3) pancreatic duct drainage is facilitated by an intestinal Rouxen-Y loop; (4) An external drainage tube is inserted through the Roux-en-Y loop into the main pancreatic duct. All three patients who underwent our surgical procedure had a good outcome. Although the mean follow-up time is still only 18.3 months, their condition has improved, with no evidence of recurrent ascites. Thus, our surgical procedure should be considered as an appropriate treatment for pancreatic ascites because it can be applied for all types of leakage, including leakage from the posterior wall of pancreas; it preserves pancreatif function, especially endocrine function; and it enables preservation of the spleen. [ABSTRACT FROM AUTHOR]

We report herein on the follow-up of ten consecutive patients who underwent perineal rectosigmoidectomy, and discuss the indications, surgical technique, and outcomes of this procedure. The median age of the patients was 79 years, with a range of 26 to 85 years, and eight patients had complicating medical conditions. Of five patients who underwent this procedure for a recurrent prolapse after another type of perineal procedure, four had previously undergone the Thiersch operation combined with the Gant-Miwa technique. The mean length of the excised rectum and sigmoid colon was 22.1 cm. Pain was minimal or absent in all patients and oral intake was commenced after 2 days. There were no mortalities, but anastomotic leakage occurred in one patient. The mean follow-up period was 3.5 years. Only one patient developed recurrent rectal prolapse 24 months after the operation. Of seven patients who underwent concomitant levatoroplasty for incontinence, five became fully continent within 3 weeks after the operation, while the remaining two improved after 2 months. We propose that perineal rectosigmoidectomy is indicated for patients who have suffered an early recurrence of prolapse after another transperineal repair; elderly or highrisk patients with incontinence; male patients; and patients with an incarcerated or gangrenous prolapsed rectal segment. [ABSTRACT FROM AUTHOR]

Background: Chronic idiopathic colonic pseudo-obstruction (CICP) is a rare disease, defined as a condition of the chronically damaged colon, without obstruction or stenosis, and a pathological abnormality in the myenteric plexus. To date, there is no effective medication for CICP, and existing medication is not useful, making surgery the only effective treatment. Laparoscopic surgery is useful for reducing surgical trauma and postoperative adhesion. Herein, we report a patient with recurrent laxative-uncontrolled bowel obstruction, who underwent successful treatment with laparoscopic total colectomy based on preoperative detailed evaluation of bowel function. Case presentation: A 77-year-old female patient without any past abdominal or psychological medical history was referred to our hospital because of chronic constipation and abdominal pain. Contrast-enhanced computed tomography, barium enema, cine magnetic resonance imaging, and defecography indicated an enlarged colon from the cecum to the transverse colon (proximal to the splenic flexure) without apparent mechanical obstruction, and a collapsed colon from the descending colon to the rectum, with reduced peristalsis. Bowel movements of the rectum and anorectal function were normal. Based on these findings, we diagnosed CICP and performed laparoscopic total colectomy and ileo-rectal anastomosis in this case. Postoperative recovery was good, without the need for postoperative laxatives. Pathologically, no degeneration of the muscle layers or Auerbach's plexus was found in the resected specimen. Conclusion: Surgery is the only effective treatment for patients with CICP. Careful imaging before surgery is important for detecting the extent of excision required. This will reduce the need for additional surgery due to symptom relapse in the remnant colon. However, continued observation of the patient is required. [ABSTRACT FROM AUTHOR]

We report a case of progression of primary biliary cirrhosis (PBC) after proctocolectomy for ulcerative colitis. A 43-year-old woman underwent a total proctocolectomy after being diagnosed with ulcerative colitis. In the course of the preoperative investigation, liver function test results were within the normal range. Four months after the proctocolectomy, the patient showed a high level of alkaline phosphatase (2398 IU/l) and a positive anti-mitochondrial antibody titer (>1:160). There were no associated symptoms. A liver biopsy demonstrated expansion of all portal areas by infiltrates of lymphocytes and histiocytes. These appearances indicated chronic biliary disease and were compatible with PBC. The association of PBC and ulcerative colitis is rare. However, a review of the recent literature suggests that PBC and ulcerative colitis may be associated; this combination should be kept in mind. [ABSTRACT FROM AUTHOR]