Evidence-based clinical guidelines for chronic constipation 2023.

In July 2023 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 frequency of bowel movement frequency type or defecation difficulty type. The first line of treatment includes 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 medicine, 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.

Evacuatory Dysfunction after Stapled Hemorrhoidopexy: A Case Report of Rectal Pocket Syndrome.

A 60 year-old male was referred to the authors' hospital with a persistent urge to defecate. The patient had undergone stapled hemorrhoidopexy (SH) for the treatment of prolapsed hemorrhoids approximately 10 years earlier. He started to have difficulty with defecation and a false sense of urgency shortly after the surgery. Computed tomography showed a diverticulum-like fistula along the circumference of the rectum. Colonoscopy revealed communication between the diverticular cavity and the rectal lumen. The cavity contained a thumbnail-sized fecalith. When the fecalith was removed, the patient's urge to defecate dissipated. The patient was diagnosed with rectal pocket syndrome secondary to SH. The lower rectum was transected, and the remaining rectum and the anal canal were anastomosed by manual suture. Temporary ileostomy with double orifices was performed. The ileostomy was closed 3 months later. The patient experienced no subsequent difficulty with defecation or urgency.

Physiological study of anal sphincteric resection in an experimental porcine model.

This study was conducted to compare and evaluate the extent of anal sphincteric resection and the degree of anal dysfunction in sphincter saving operations for lower rectal cancer using experimental porcine models. Each 10 Clawn miniature pigs underwent transanal intersphincteric resection (ISR), ISR with partial (one-quarter) external sphincteric resection (ESR-25%), and ISR with partial (one-half) external sphincteric resection (ESR-50%). An anorectal physiological study was performed before, one month, and three months after surgery in these three groups. The anal maximum resting pressure (AMRP) decreased from 45.1 cmH(2)O in the control group to 14.8, 14.3 and 11.1 cmH(2)O one month after surgery, and to 15.2, 8.8 and 5.2 cmH(2)O three months after surgery, in the ISR, ESR-25% and ESR-50% groups, respectively. The anal maximum squeezing pressure (AMSP) decreased from 81.7 cmH(2)O in the control group to 42.1, 40.1 and 41.1 cmH(2)O one month after surgery in the ISR, ESR-25% and ESR-50% groups, respectively. Three months after surgery, the MSP increased to 78.1 and 68.1 cmH(2)O in the ISR and ESR-25% groups, respectively, but the ESR-50% group showed a significantly lower MSP of 39.2 cmH(2)O compared with other two groups. The ratio of the potential difference on electromyographic (EMG) was 0.19 in the ESR-50% group, and this value was significantly lower than 0.8 in the ISR and ESR-25% groups, one month after surgery. Three months after surgery, the potential ratio of EMG was increased almost to the preoperative level both in the ISR and ESR-25% groups, but the ratio of the potential difference in the ESR-50% group with redness, sore and soiling around anus was 0.19 and significantly lower compared with other groups. The results of this study indicate that porcine models with additional resection of less than one quarter of the external anal sphincter have little anal dysfunction. A human clinical trial is needed to determine the ESR for very low rectal cancer.

Leukocytapheresis for the treatment of active pouchitis: a pilot study.

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.

Experimental study of Composix mesh for ventral hernia.

We aimed to compare conventional single-layer mesh and composite mesh in terms of the degree of tissue repair on the abdominal wall side of the mesh and the degree of mechanical adhesion to the intestine and to confirm the stability of composite mesh. We used a single-layer polypropylene (PP) mesh and a two-layer Composix mesh (E/X type) consisting of a PP mesh and an expanded polytetrafluoroethylene mesh. Twenty rats were divided into two groups. Three months after mesh placement, histopathologically, ingrowth of granulation tissue into the mesh on the abdominal wall side was prominent without mesh shrinkage or shift in either group. In the PP mesh group, 50% of the rats had firm adhesions between the mesh and the intestine, whereas the Composix mesh group had no adhesions to the intestine. Unlike conventional PP mesh, Composix mesh prevented adhesions to the intestine on the peritoneal side without impairing tissue union with the visceral peritoneum, suggesting its usefulness in clinical onlay mesh repair for ventral defects.

Perineal hernia in women : assessment with evacuation fluoroscopic cystocolpoproctography.

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.

Effects of antineoplaston AS2-1 against post-operative lung metastasis in orthotopically implanted colon cancer in nude rat.

We have investigated the efficacy and mechanisms of antineoplaston AS2-1 against post-operative lung metastasis following removal of implanted human colon cancer in nude rat. The influence of AS2-1 on in vitro KM12SM human colon carcinoma cell activities (growth, cell cycle, and apoptosis) was evaluated. AS2-1 was administered perorally after removal of the implanted KM12SM cecal cancer in nude rat. AS2-1 inhibited KM12SM cell proliferation through G1 cell arrest and, at a higher concentration, induction of apoptosis. AS2-1 showed significant reduction in lung metastasis at 5 weeks after cecal removal. The survival rate in the AS2-1 group was significantly higher than that in the control. TUNEL staining on the lung metastatic tumors revealed that the apoptosis index (AI) in the AS2-1 group was significantly higher. Antineoplaston AS2-1 showed an antimetastatic effect against post-operative lung metastases from colon cancer through G1 cell arrest and the subsequent induction of apoptosis.

Oncologic and functional results of total mesorectal excision and autonomic nerve-preserving operation for advanced lower rectal cancer.

PURPOSE: Total mesorectal excision contains two different procedures: autonomic nerve preservation, and autonomic nerve sacrifice. It is unclear whether autonomic nerve preservation is suitable curative procedure. We clarify the significance of autonomic nerve preservation for an advanced lower rectal cancer. METHODS: All 403 patients curatively resected between 1975 and 1999 were clinicopathologically studied. Between 1975 and 1984, all patients routinely received total mesorectal excision without autonomic nerve preservation (TME-P(-) group). Since 1985, total mesorectal excision with autonomic nerve preservation has been performed in 81 percent of patients (TME-P(+) group). The remaining patients received TME-P(-) because of suspicious invasion to autonomic nerve plexus. All clinical and pathologic data were entered into a computer database. Long-term follow-up was used to analyze the oncologic and functional results of TME-P(+) group compared with TME-P(-) group. RESULTS: The follow-up rate was 98.1 percent. In either Dukes A+B or Dukes C disease, the TME-P(+) group did not increase local recurrence or decrease ten-year disease-free survival compared with the TME-P(-) group of Period 1975 to 1984. The TME-P(-) group of Period 1985 to 1999 had the highest distant metastasis and the lowest survival rates than any other groups. Urinary or sexual function was well preserved in the TME-P(+) group. CONCLUSIONS: Autonomic nerve preservation is oncologically and functionally excellent and suitable for almost all patients with advanced lower rectal cancer. Intensive chemotherapy is needed for patients whose autonomic nerves were killed in suspicion of nerve invasion.

Clipless hand-assisted laparoscopic total colectomy using Ligasure Atlas.

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.

A case of argon plasma coagulation therapy for hemorrhagic rectal tumor in a highly aged patient.

A 95-year-old woman admitted to our hospital for senile dementia showed hemorrhage from rectum, and colonoscopy was performed. Circumferential hemorrhagic concomitant nodular aggregated tumor was found spreading from just above denticulate line to the lower rectum. She has a past history of rectal tumor, for which endoscopic mucosal resection was performed in 1998. Based on the biopsy finding, the tumor was diagnosed as a highly differentiated adenocarcinoma, and the hemorrhage was speculated to be induced by local recurrence. Considering patient's very high age and poor risks, argon plasma coagulation (APC) therapy succeeded in controlling the hemorrhage. After the therapy, the tumor itself showed no tendency to grow, and clinical course remained favorable for 10 months up to now. APC therapy is considered useful for the hemorrhagic tumors in the gastrointestinal tract in the highly aged patients with high risk.

Graciloplasty for internal and external sphincteric resection of lower rectal cancer.

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.

Long-term survival following treatment with antineoplastons for colon cancer with unresectable multiple liver metastases: report of a case.

We report a case of survival for nearly 8 years after treatment of unresectable multiple liver metastases from colon cancer, using microwave ablation and the nontoxic antitumor agent, the antineoplastons. A 72-year-old man diagnosed with adenocarcinoma of the ascending colon and 14 bilateral liver metastases underwent a right hemicolectomy combined with microwave ablation of six metastatic liver tumors. We also decided to give antineoplastons to inhibit metastatic tumor growth and recurrence. Antineoplaston A10 was given intravenously, followed by oral antineoplaston AS2-1. Computed tomography scans done 1 and 4 years after the initial diagnosis showed recurrent tumors in S(4) and S(7), respectively. The patient underwent a second and a third microwave ablation of the recurrent tumors, and has survived for nearly 8 years without suffering any serious adverse effects. He is currently free from cancer. This case report demonstrates the potential effectiveness of the nontoxic antitumor agent, the antineoplastons, for controlling liver metastases from colon cancer.

Up-regulation in dihydropyrimidine dehydrogenase activity by raltitrexed causes antagonism in combination with 5-fluorouracil.

BACKGROUND AND METHODS: We have studied the influence of raltitrexed, a specific thymidylate synthase (TS) inhibitor, on dihydropyrimidine dehydrogenase (DPD) activity in cultured cancer cells and in transplanted tumors in nude mice. Further, we investigated the combined effect of raltirexed and 5-fluorouracil (5-FU) on the in vitro anti-tumor effect and its correlation to the DPD activity and mRNA level. RESULTS: By raltitrexed treatment, the DPD activity and mRNA level were increased in HuTu-80 small intestine carcinoma cells, and in its transplanted tumors. On the other hand, raltitrexed showed no influence on DPD activity in MIAPaCa2 pancreatic carcinoma cells. In the study of cell growth activity, the results showed that in MIAPaCa2, the Combination Index (CI) was 0.57 +/- 0.03, representing a synergistic effect, while in HuTu-80, the CI was 1.26 +/- 0.09, representing an antagonistic effect. CONCLUSION: Raltitrexed may up-regulate DPD activity in tumor cells, resulting in antagonism when combined with 5-FU.

Endoluminal ultraflex stent for palliative treatment of malignant rectosigmoidal obstruction.

Rectosigmoidal obstruction due to a malignant tumor usually requires emergency surgical treatment, and colostomy is usually inevitable. This report describes our experience with the use of endoluminal self-expanding metallic stents in the treatment for rectosigmoidal obstruction in patients with unresectable recurrent colorectal cancer or intra-abdominal dissemination. A total of 5 cases were included (4 male and 1 female) with a mean age of 70.8 (range, 63-80) years. A self-expanding noncovered Ultraflex, 10 cm in length and 22 mm in diameter, was emplaced at the site of the obstruction under both endoscopic and fluoroscopic guidance. Each patient had a recurrent malignancy (colorectal cancer, 3; ovarian cancer, 1; gastric cancer, 1). No subsequent surgery was planned due to ascites or extensive intra-abdominal dissemination. There was no mortality related to the procedure. Immediate decompression with symptomatic relief was achieved. One stent later became obstructed due to tumor ingrowth, and in two cases there was intermittent bleeding from the tumor and these were treated by argon plasma coagulation (APC) endoscopically. The use of self-expanding Ultraflex stent provides good palliation for unresectable advanced tumors that cause left colonic obstruction.

Transanal dilation using circular stapling for benign rectal stenosis: report of a case.

When a simple procedure such as bougie, balloon dilation and transanal incision are not effective for severe stenosis after colorectal anastomotic leakage, a surgical operation is required. We report a case of transanal dilation using circular stapling for severe stricture in the colorectal anastomosis following low anterior resection.

Expression of tumor rejection antigens in colorectal carcinomas.

BACKGROUND: The authors recently reported that the SART2 and SART3 antigens encode tumor epitopes recognized by HLA-A24-restricted and tumor-specific cytotoxic T lymphocytes (CTLs) established from esophageal carcinoma patients. The current study investigated these antigens to explore a potential molecule for specific immunotherapy for colorectal carcinoma patients. METHODS: The SART2 and SART3 antigens were investigated by Western blotting in colorectal carcinoma cell lines and in cancer tissues. For induction of CTLs, peripheral blood mononuclear cells (PBMCs) of HLA A-24-positive cancer patients were stimulated in vitro with peptides. RESULTS: The 140 kD SART3 antigen was expressed in both the cytosol and nuclear fractions of all six colon carcinoma cell lines, 27 of 41 (65.9%) cytosol fractions, 30 of 41 (73.2%) nuclear fractions of colorectal carcinoma tissue samples, and in 0 of 7 non-tumorous tissues. The 100 kD SART2 antigen was expressed in the cytosol fractions of 2 of 6 colon carcinoma cell lines, 5 of 20 (25%) cytosol fractions of colorectal carcinoma tissue samples, and in 0 of 7 non tumorous tissues. HLA-A24-restricted CTLs cytotoxic to colon carcinoma cells were induced from PBMCs of colon carcinoma patients by stimulation with the two immunogenic peptides of SART3. CONCLUSIONS: The SART3 antigen could be an appropriate target molecule for specific immunotherapy for colorectal carcinoma patients.

[Efficacy of postoperative adjuvant chemotherapy for colorectal cancer].

We attempted postoperative adjuvant chemotherapy for stage II or III colorectal cancer. To investigate the efficacy of the adjuvant chemotherapy, we retrospectively reviewed all 293 colorectal cancer patients who underwent curative resection between 1990 and 1996 in Kurume University Hospital. The patients were divided into two groups according to whether or not they received postoperative adjuvant chemotherapy. Patients in Group 1 (n = 156) underwent resection followed by administration of oral fluorouracil. Some also received intravenous 5-FU or MMC after surgery. Patients in Group 2 (n = 95) underwent surgery alone. The disease-free survival rate in Group 1 was significantly higher than that in Group 2, but only for those with rectal cancer, with no significant difference for those with colon cancer. The results were also analyzed according to tumor stage, degree of lymphatic and venous invasion, and histological grading. Findings were similar between the two groups for those with stage II, stage IIIa, a low grade of lymphatic and venous invasion, and well-differentiated adenocarcinoma. Postoperative adjuvant chemotherapy in colorectal cancer might reduce the risk of recurrence, particularly in cases of rectal cancer. However, postoperative adjuvant chemotherapy was insufficient for those with highly advanced cancer or a biologically aggressive tumor.

Laparoscopic intraperitoneal repair of postoperative ventral incisional hernia using Composix mesh.

This report describes the technique and early results obtained with a simple laparoscopic intraperitoneal onlay Composix mesh repair for postoperative ventral hernia. Composix mesh is constructed from one layer of polypropylene mesh and another layer of expanded polytetrafluoroethylene (ePTFE). From March 2000 to October 2001, we performed laparoscopic repair of postoperative ventral hernia in 9 patients. Four (44%) of these patients had a history of at least one failed hernia repair. The size of the abdominal wall defect varied from 4 x 5 cm to 10 x 12 cm (median, 8 x 9 cm). In all cases, the Composix mesh (Bard Inc. USA) was stapled to the peritoneal surface of the abdominal wall, leaving the sac in situ. No death occurred as a result of surgery. Intraoperative small bowel injury occurred in one patient (11.1%) for whom surgery was converted to laparotomy and small bowel resection. No infection was observed. The length of hospital stay varied from 5 to 10 days (median, 5.6 days). During the follow-up period of 8 to 15 months (median, 2 months), there was no recurrence of hernia. Laparoscopic Composix mesh onlay repair is a safe, easy, and effective procedure with minimal discomfort and a low early recurrence rate.