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The Japan Gastroenterological Association (JGA) published the first version of clinical guidelines for chronic diarrhea 2023. These guidelines describe the definition, classification, diagnostic criteria, diagnostic testing methods, epidemiology, pathophysiology, and treatment of chronic diarrhea, and provide flowcharts for the diagnosis and treatment of chronic diarrhea based on the latest evidence. Treatment for chronic diarrhea begins by distinguishing secondary chronic constipation with a clear etiology, such as drug-induced diarrhea, food-induced diarrhea, systemic disease-associated diarrhea, infection-associated diarrhea, organic disease-associated diarrhea, and bile acid diarrhea. The first line of treatment for chronic diarrhea in the narrow sense, defined in these guidelines as functional diarrhea in routine medical care, is lifestyle modification and dietary therapy. The first medicines to be considered for oral treatment are probiotics for regulating the gut microbiome and anti-diarrheals. Other medications, such as 5HT3 receptor antagonists, anticholinergics, Kampo medicine, psychotherapy, antibiotics, bulking agents, adrenergic agonists, and somatostatin analogs, lack sufficient evidence for their use, highlighting a challenge for future research. This Clinical Guidelines for Chronic Diarrhea 2023, which provides the best clinical strategies for treating chronic diarrhea in Japan, will also be useful for medical treatment worldwide., (© 2024 The Author(s). Published by S. Karger AG, Basel.)

The Japan Gastroenterological Association published the first version of its clinical guidelines for chronic constipation 2023. Based on the latest evidence, these guidelines describe the definition, classification, diagnostic criteria, diagnostic testing methods, epidemiology, pathophysiology, and treatment of chronic constipation. They include flowcharts for both diagnosis and treatment of chronic constipation. In the treatment of chronic constipation, the first step involves differentiating between secondary forms, such as organic disease-associated constipation, systemic disease-associated constipation, and drug-induced constipation. The next step is to determine whether the chronic constipation stems from a motility disorder, a form of primary chronic constipation. For functional constipation and constipation-predominant irritable bowel syndrome, treatment should be initiated after evaluating symptoms like reduced bowel movement frequency type or defecation difficulty type. The first line of treatment includes the improvement of lifestyle habits and diet therapy. The first drugs to consider for oral treatment are osmotic laxatives. If these are ineffective, secretagogues and ileal bile acid transporter inhibitors are candidates. However, stimulant laxatives are exclusively designated for as-needed use. Probiotics, bulk-forming laxatives, prokinetics, and Kampo medicines, for which there is insufficient evidence, are considered alternative or complementary therapy. Providing the best clinical strategies for chronic constipation therapy in Japan, these clinical guidelines for chronic constipation 2023 should prove useful for its treatment worldwide., (© 2024 The Author(s). Published by S. Karger AG, Basel.)

Introduction: Colorectal cancer (CRC) is one of the major life-threatening complications in patients with Crohn's disease (CD). Previous studies of CD-associated CRC (CD-CRC) have involved only small numbers of patients, and no large series have been reported from Asia. The aim of this study was to clarify the prognosis and clinicopathological features of CD-CRC compared with sporadic CRC., Methods: A large nationwide database was used to identify patients with CD-CRC (n = 233) and sporadic CRC (n = 129,783) over a 40-year period, from 1980 to 2020. Five-year overall survival (OS), recurrence-free survival (RFS), and clinicopathological characteristics were investigated. The prognosis of CD-CRC was further evaluated in groups divided by colon cancer and anorectal cancer (RC). Multivariable Cox regression analysis was used to adjust for confounding by unbalanced covariables., Results: Compared with sporadic cases, patients with CD-CRC were younger; more often had RC, multiple lesions, and mucinous adenocarcinoma; and had lower R0 resection rates. Five-year OS was worse for CD-CRC than for sporadic CRC (53.99% vs 71.17%, P < 0.001). Multivariable Cox regression analysis revealed that CD was associated with significantly poorer survival (hazard ratio 2.36, 95% confidence interval: 1.54-3.62, P < 0.0001). Evaluation by tumor location showed significantly worse 5-year OS and RFS of CD-RC compared with sporadic RC. Recurrence was identified in 39.57% of CD-RC cases and was mostly local., Discussion: Poor prognosis of CD-CRC is attributable primarily to RC and high local recurrence. Local control is indispensable to improving prognosis., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of The American College of Gastroenterology.)

Introduction: The aim of this study was to evaluate the effect of biologics on the risk of advanced-stage inflammatory bowel disease (IBD)-associated intestinal cancer from a nationwide multicenter data set., Methods: The medical records of patients with Crohn's disease (CD) and ulcerative colitis (UC) diagnosed with IBD-associated intestinal neoplasia (dysplasia or cancer) from 1983 to 2020 were included in this study. Therapeutic agents were classified into 3 types: biologics, 5-aminosalicylic acid, and immunomodulators. The pathological cancer stage was compared based on the drug used in both patients with CD and UC., Results: In total, 1,042 patients (214 CD and 828 UC patients) were included. None of the drugs were significantly associated with cancer stage in the patients with CD. In the patients with UC, an advanced cancer stage was significantly associated with less use of biologics (early stage: 7.7% vs advanced stage: 2.0%, P < 0.001), 5-aminosalicylic acid, and immunomodulators. Biologic use was associated with a lower incidence of advanced-stage cancer in patients diagnosed by regular surveillance (biologics [-] 24.5% vs [+] 9.1%, P = 0.043), but this was not the case for the other drugs. Multivariate analysis showed that biologic use was significantly associated with a lower risk of advanced-stage disease (odds ratio = 0.111 [95% confidence interval, 0.034-0.356], P < 0.001)., Discussion: Biologic use was associated with a lower risk of advanced IBD-associated cancer in patients with UC but not with CD. The mechanism of cancer progression between UC and CD may be different and needs to be further investigated., (Copyright © 2023 by The American College of Gastroenterology.)

Background: The increasing incidence of older-onset ulcerative colitis (UC), which has a higher risk of surgery, is a global health issue. However, data regarding intravenous steroid treatment, one of the important treatment options to avoid surgery, for older-onset UC is lacking., Aims: To evaluate the association between onset age and effectiveness of intravenous steroids in UC., Methods: This retrospective multicentre (27 facilities) cohort study included moderate-to-severe hospitalised UC patients who underwent their first intravenous steroids between April 2014 and July 2019. The primary outcome was clinical remission at day 30, using two-item patient-reported outcome scoring. The key secondary outcomes were risks of surgery and adverse events (death, infection and venous thrombosis) within 90 days. A modified Poisson regression model was used for analysis., Results: Overall, 467 UC patients (384 younger-onset and 83 older-onset) were enrolled. Clinical remission at day 30 was observed in 252 (65.6%) among younger-onset patients and 43 (51.8%) among older-onset patients (adjusted risk difference, -21.7% [95% CI, -36.1% to -7.2%]; adjusted risk ratio [ARR], 0.74 [95% CI, 0.59 to 0.93]). The risks of surgery and adverse events were higher in older-onset UC (20.5% vs. 3.1%; ARR, 8.92 [95% CI, 4.13 to 19.27], 25.3% vs. 9.1%; ARR, 2.19 [95% CI, 1.22 to 3.92], respectively). Four deaths occurred, all involving older-onset UC. The risks of infection and venous thrombosis were also higher in older-onset UC (18.1% vs. 8.6%, 7.2% vs. 0.5%, respectively)., Conclusions: Older-onset was associated with a lower effectiveness of intravenous steroids with higher risks of surgery and adverse events in UC., (© 2022 John Wiley & Sons Ltd.)

Purpose: We evaluated the recent incidence of surgery and the changing surgery trends for ulcerative colitis (UC) in Japan due to the increasing use of anti-tumor necrosis factor (TNF) agents., Methods: A questionnaire survey was performed to assess the number of surgeries, surgical indications, surgical timing, and immunosuppressive treatments before surgery between 2007 and 2017., Results: A total of 3801 surgical cases were reported over 11 years. The prevalence of UC surgery decreased over the period studied. The rate of prednisolone (PSL) use did not change. The prevalence of both calcineurin inhibitors (CNIs) and anti-TNF agents increased during the period studied (p < 0.01). The prevalence of urgent/emergent surgery did not change. The most distinctive change in surgical indications was the increase in cancer/dysplasia (CAC), the prevalence of which increased from 20.2% in 2007 to 34.8%., Conclusion: The prevalence of UC surgery seems to be decreasing according to the increasing rate of anti-TNF agent and CNI administration. However, the indication of CAC significantly increased. Further research should evaluate whether or not long-term remission maintained with several agents can lead to increasing CAC.

Background: Pouchitis is a major long-term complication of ileal pouch-anal anastomosis for ulcerative colitis. The aim of this study is to investigate the efficacy of leukocytapheresis for the treatment of active pouchitis., Methods: Eight patients with active pouchitis received leukocytapheresis weekly for 5 weeks in an open-label treatment protocol together with baseline therapy., Results: Patients showed significant improvement in their pouchitis disease activity index scores, from 9.5 (range, 8-10) to 4.0 (range, 2-8) (P < 0.05). Six (75%) of the 8 treated patients achieved remission. No adverse events were observed., Conclusions: Leukocytapheresis therapy could be a new therapeutic strategy for patients with pouchitis after ileal pouch-anal anastomosis for ulcerative colitis. These encouraging results lead us to propose a randomized controlled trial.

There are conflicting reports on the agreement between the Clinical and Laboratory Standards Institute disk diffusion (M44-A) and reference broth microdilution (M27-A) methods for determination of antifungal susceptibility of yeasts. The antifungal susceptibility of 541 yeasts, the majority of which were from the oral cavity, was determined using these two methods and the accuracy of the disk diffusion method assessed for clinical testing of various Candida species. Of the strains tested, Candida albicans predominated (390 out of 541). The classification of susceptibility determined by the disk diffusion method was largely in concordance with that obtained using the broth dilution method, regardless of species within Candida genus. The overall observed agreement between these two methods was 94.7% for fluconazole and 96.7% for voriconazole was with a 'very major' discrepancy level of 1.5% and 1.7% respectively. This study demonstrates a strong agreement of the simple disk diffusion method with the more labour intensive 'gold standard' broth microdilution method. These findings would support the use of the disk diffusion method in a routine mycology service.

The aim of this study is to assess the usefulness of fluoroscopic cystocolpoproctography in the treatment of female pelvic organ prolapse. The presence or absence of rectocele, enterocele, sigmoidocele, and the cystocele on cystocolpoproctography was retrospectively analyzed in 46 consecutive patients. A rectocele was detected in 4.5% of the patients, postvaginal hernia in 19.7%, cystocele in 3.0%, complete rectal prolapse in 53.0%, massive rectal prolapse in 10.6%, and incomplete rectal prolapse in 4.5% of the patients on cystocolpoproctography. Perineal hernia can include a combination of cystocele, rectocele, uterine prolapse, enterocele and rectal prolapse. Accurate diagnosis of the coexisting abnormalities is essential in planning reconstructive procedures so that the risks of recurrence and reoperation can be minimized. Fluoroscopic cystocolpoproctography provides direct visualization and quantification of female pelvic organ prolapse, information that usually can only be inferred by physical examination.

Hand-assisted laparoscopic total colectomy for ulcerative colitis has allowed less invasive operations in acute severe colitis and poor risk, and has not yet been widely applied for the reason of prolong the operating time in comparison with open surgery. We present the advantages of the use of the LigaSure Atlas vessel sealing for vascular control during laparoscopic surgery. A retrospective study was conducted to compare 15 patients who underwent hand-assisted laparoscopic total colectomy using an ultrasonic coagulator from January 1988 to September 2002 (US group) with 18 patients who were operated using LigaSure Atlas (LS group) from October 2002 to December 2003. There was no significant difference in the background factors of patients between both groups. The operating time was 225 +/- 58 min in the LS group and less than 280 +/- 105 min in the US group. Intraoperative blood loss was 91 +/- 22 ml in the LS group and less than 212 +/- 178 ml in the US group. Postoperative bleeding did not occur in the LS group, but occurred in 1 patient in the US group (6.6%) and this patient required re-operation. Postoperative seroma formation in the abdomen was found in 3 patients of the US group (20%). The procedure using LigaSure Atlas reduced the operating time, intraoperative bleeding and operator's stress in comparison with standard ultrasonic coagulation.

Anal sphincteric resection for rectal cancer is most commonly followed by colostomy in the lower abdominal wall, which enforces quite a poor quality of life due to a permanent stoma. For surgeons treating lower rectal cancer, the goal is to achieve defecation via the anus without placing a stoma. Internal sphincteric resection, partial external sphincteric resection and coloanal anastomosis have been reported for the treatment of lower rectal cancer with avoiding a colostoma. Extended resection of the external sphincter, however, limits patient's daily activities because of poor functional results and necessitates reconstruction of damaged anal function. This paper describes a case of graciloplasty for postoperative anal dysfunction that yielded a good clinical outcome in a 65-year-old female who had undergone very low anterior resection with complete internal and partial external sphincteric resection for lower rectal cancer.

Intussusception accounts for almost all cases of intestinal obstruction in children. In contrast, intussusception in adults is relatively rare. An 86-year-old Japanese female with rectal bleeding came to our hospital via ambulance. At first, colonoscopy findings revealed the sigmoid colon cancer. Ultrasonography showed a hypoechoic mass with a multiple concentric ring sign. Computed tomography showed a round fluid-filled cystic structure. Colon contrast studies demonstrated stenosis in the rectosigmoid colon. A laparotomy was performed. The sigmoid colon was intussuscepted to the rectosigmoid colon. We employed both rectosigmoid and sigmoid colon resection. The resected specimen showed that the disease was advanced sigmoid colon cancer with ulcer formation due to an ischemic change. Tumor was 4.5 cm x 2.0 cm in size. The disease was histopathologically diagnosed as advanced sigmoid colon cancer, well-differentiated adenocarcinoma. We report here a case of adult intussusception due to the sigmoid colon cancer.

We report a case of intussusception during enteral nutrition after esophagectomy. The case was a 60-year-old patient who underwent subtotal esophagectomy via the right thoraco-abdominal approach, reconstructed with esophagogastrostomy. He underwent tube feeding through gastrostomy after surgery. The tip of the feeding tube was emplaced in the jejunum. He complained of intermittent abdominal pain and the drainage volume through the gastric decompression tube was increased on the 2nd week from surgery. There was no abnormal finding on abdominal CT or or radiography of the digestive tract, and so a diagnosis of intussusception was made and laparotomy was performed. There was descending intussusception with the jejunum where the feeding tube was emplaced. Enterectomy was not necessary in this case. Adult intussusception is rare. The surgery is sometimes the cause for intussusception. Another cause is use of a long intestinal tube. Since enteral nutrition has priority for nutritional support after esophagectomy, it is important to make an early decision whether surgical intervention is required or not, using abdominal examination by CT, ultrasound and contrast radiography, when bowel obstruction occurs during enteral nutrition through a feeding tube.

Arginine supplementation increases glutamine levels in muscle and plasma. Since glutamine production is increased in catabolic states, these observations prompted us to investigate whether the flux of arginine to glutamine was increased in tumor-bearing (TB) rats, and we measured the synthesis rate of glutamine from arginine in control versus TB rats receiving standard total parenteral nutrition (TPN) solution. Male Donryu rats (N = 36; body weight, 200 to 225 g) were divided into two groups, control and TB rats. Yoshida sarcoma cells (1 x 10(6)) were inoculated into the back of the rats (n = 18) subcutaneously on day 0. The rats were given free access to water and rat chow. On day 5, all animals, including non-TB rats (n = 18), were catheterized at the jugular vein and TPN was begun. On day 10, TPN solution containing either U-14C-glutamine (2.0 microCi/h) or U-14C-arginine (2.0 microCi/h) was infused as a 6-hour constant infusion. At the end of the isotope infusion, plasma was collected to determine the glutamine production rate in rats receiving U-14C-glutamine, and the ratio of specific activity of glutamine to specific activity of arginine was measured in rats receiving U-14C-arginine. Only 2 g tumor caused a decrease in glutamine levels and an increase in glutamine and arginine production. The low flux rate of arginine to glutamine was observed in control rats (Arg to Gln, 41.0 +/- 11.9 mumol/kg/h). On the other hand, TB caused a significant increase in Arg to Gln compared with the control (213.3 +/- 66.1 mumol/kg/h, P < .01 v control). An increase in the flux rate of Arg to Gln was associated with an enhancement in the ratio of specific activity of ornithine to specific activity of arginine in TB rats (control 51.5% +/- 10.9% v 77.4% +/- 8.9%, P < .05). We conclude that (1) glutamine and arginine metabolism is altered with very small tumors, (2) although the flux of Arg to Gln was increased in TB and rats, the small increase in Arg to Gln cannot explain the observed large increase in Gln production.

The objectives of this study were to determine whether high doses of fentanyl anesthesia reduced the surgical stress level and to elucidate the effect of fentanyl anesthesia on protein turnover after esophagectomy. Seventeen male patients with esophageal cancer were divided into two groups, conventional anesthesia (CA) and fentanyl anesthesia (FA). The FA patients received 134.0 +/- 15.3 microg/kg fentanyl citrate and the CA patients 15.7 +/- 7.4 microg/kg fentanyl during the surgery. Protein turnover was measured by the method of bolus infusion of [15N]glycine (1 g). High dose of fentanyl anesthesia reduced cortisol levels during the surgery (CA 38.0 +/- 13.8 pg/ml vs FA 13.5 +/- 2.4, P < 0.05) and interleukin-6 levels in the plasma after the surgery (P < 0.02). The postoperative nitrogen retention was greater with fentanyl anesthesia than with conventional anesthesia. Both protein synthesis and breakdown rates were increased with fentanyl anesthesia, while they were unaltered in CA patients. Postoperative fibrinogen synthesis rate was greater with FA than with CA (CA 51.1 +/- 9.2%/day vs FA 100.9 +/- 14.0, P < 0.01). The protein turnover and fibrinogen synthesis data suggested a shorter duration of shock phase in FA patients than in CA patients. We concluded that a high dose of fentanyl anesthesia reduced surgical stress levels and shortened the postoperative shock phase, resulting in a nitrogen-sparing effect.

Purpose: The authors evaluated the efficacy of extended radical (three-field) lymphadenectomy for esophageal cancer compared with less radical (two-field) lymphadenectomy. STUDY SUBJECTS AND ANALYTIC METHODS: The mortality and morbidity rates, postoperative courses, and survival rates were compared between 63 patients who underwent three-field lymph node dissection and 65 who underwent two-field lymph node dissection at Kurume University Hospital from 1986 to 1991. Long-term quality of life after surgery was compared between 37 patients who underwent three-field dissection and 35 who underwent two-field dissection from 1980 to 1991., Results: Three-field dissection resulted in better survival for patients with positive lymph node metastasis from a carcinoma in the upper thoracic or midthoracic esophagus compared with two-field dissection. The mortality rates, postoperative courses and quality of life were the same for both procedures., Conclusions: Three-field dissection is preferred for upper thoracic or midthoracic esophageal cancer because of improved survival, acceptable mortality and morbidity rates, and good postoperative course and quality of life.

Background: Since tumor-bearing rats are deficient in glutamine, we investigated whether (1) glutamine and glutathione deficiency occur in tumor-bearing rats, (2) glutamine supplementation caused an increase of glutathione levels in host tissues and tumor, (3) glutamine enhances protein synthesis in host tissues, and (4) glutamine stimulated the tumor to synthesize protein and DNA., Methods: Male Donryu rats were randomized into four groups: (1) non-tumor-bearing rat (NTB) + standard total parenteral nutrition (STPN); (2) NTB + glutamine-supplemented TPN (GTPN); (3) tumor-bearing rat (TB) + STPN; (4) TB + GTPN. On day 0 AH109A rat hepatoma cells were subcutaneously injected into the backs of rats to induce tumor. The animals were maintained on TPN for 6 days from day 10 through day 15. On day 15, 1-14C-leucine was given by a 5-hour continuous infusion (2.0 microCi/h per rat) to determine the fractional synthesis rate and endogenous leucine production. The levels of glutamine and glutathione were measured by HPLC. the tumor DNA synthesis was estimated by bromodeoxyuridine labeling index., Results: Tumor development led to a significant weight loss, but this weight loss was significantly lessened by glutamine supplementation because of an increase in muscle protein synthesis. Glutamine did not enhance tumor weight, protein, and DNA synthesis in the tumor. Tumor development caused a significant reduction of glutathione in the muscle, jejunum, and liver, but supplemented glutamine increased the levels of glutathione in the jejunum., Conclusion: Glutamine supplementation is beneficial in preventing deficiencies of glutamine and glutathione and in improving protein metabolism in tumor-bearing rats.

One of the physiological roles of glutamine is as a precursor for DNA synthesis. The aims of this study were to determine (1) whether glutamine-supplemented total parenteral nutrition (TPN) enhanced DNA and protein synthesis in the liver and (2) whether glutamine uptake was increased following partial hepatectomy in rats. Male Donryu rats (n = 59; body weight, 250-275 g) were randomized into four groups: (1) sham operation + standard TPN solution (C-STPN); (2) C + glutamine-supplemented TPN (C-GTPN); (3) 70% partial hepatectomy + STPN (H-STPN); (4) partial hepatectomy + GTPN (H-GTPN). On Day 0, rats underwent either a sham operation or 70% partial hepatectomy and concomitantly were catheterized in the jugular vein. TPN was begun immediately after the surgery. GTPN was isocaloric and isonitrogenous with STPN and 25% of total nitrogen was given as glutamine. On Day 2, the animals were sacrificed after either a continuous infusion of 1-14C-leucine or a bolus i.v. injection of bromodeoxyuridine. The rate of hepatic regeneration was enhanced with glutamine supplementation (H-STPN, 60.8 +/- 1.6% vs H-GTPN, 66.3 +/- 2.0, P < 0.05) due to an increase in protein synthesis in the liver (H-STPN, 134.0 +/- 10.3%/day vs H-GTPN, 160.9 +/- 6.9, P < 0.05) and DNA synthesis in hepatocytes (H-STPN, 23.1 +/- 2.5% vs H-GTPN, 31.4 +/- 2.9, P < 0.05). The uptake of glutamine by the liver was increased following hepatectomy with GTPN supplementation.(ABSTRACT TRUNCATED AT 250 WORDS)