Impact of bowel movement condition on immune checkpoint inhibitor efficacy in patients with advanced non-small cell lung cancer.

BACKGROUND: Cancer immunotherapy is under development as a promising alternative strategy for treating advanced non-small cell lung cancer (NSCLC). However, the development of novel biomarkers to optimize the use of immune checkpoint inhibitors (ICIs) is still ongoing. Gut microbiota are known to regulate a host's immunity and are associated with the response to ICIs in melanoma. Therefore, we analyzed the association between ICI treatment efficacy and bowel movement condition in patients with NSCLC. METHODS: This retrospective study analyzed patients with advanced NSCLC who were treated with ICIs between December 2015 and March 2018 at University Hospital Kyoto Prefectural University of Medicine in Kyoto, Japan. The association between stool abnormalities and ICI efficacy was investigated. We defined patients with constipation or those who used a laxative as the stool abnormality group. RESULTS: We retrospectively enrolled 40 patients with advanced NSCLC who were treated with ICIs. The median age was 69.5 years; 20 patients had a stool abnormality and 20 patients did not. The disease control rates were lower in NSCLC patients with stool abnormalities than in those without stool abnormalities (20% vs. 77.8%, respectively; P = 0.0016). The time to treatment failure with ICI treatment was shorter in NSCLC patients with stool abnormalities compared with those without stool abnormalities (P = 0.003; odds ratio, 3.09; 95% confidence interval 1.41-6.78). CONCLUSION: Stool abnormality might be a predictive biomarker for the clinical benefit of ICI treatment in patients with NSCLC. Further investigations are warranted to validate our findings.

REGOSARC: Regorafenib versus placebo in doxorubicin-refractory soft-tissue sarcoma-A quality-adjusted time without symptoms of progression or toxicity analysis.

BACKGROUND: In a placebo-controlled, randomized phase 2 trial (ClinicalTrials.gov identifier NCT01900743), regorafenib improved progression-free survival (PFS) for patients with doxorubicin-pretreated advanced nonadipocytic sarcoma. A quality-adjusted time without symptoms of progression or toxicity (Q-TWiST) post hoc exploratory analysis was applied to provide an integrated measure of its clinical benefit. METHODS: In the base-case analysis, each patient's overall survival (OS) was partitioned into 3 mutually exclusive health states: the time with a grade 3 or 4 adverse event (TOX), the time without symptoms of disease or grade 3 or 4 toxicity from treatment, and the time after tumor progression or relapse. The time spent in each state was weighted with a health-state utility associated with that state and was summed to calculate the Q-TWiST. The stability of the base-case analysis was explored with several sensitivity analyses. RESULTS: In nonadipocytic sarcoma, the PFS was (4.0 months [2.6-5.5 months] with regorafenib vs 1.0 month [0.9-1.8 months] with a placebo; hazard ratio, 0.36 [0.25-0.53]; P < .0001); the OS was 13.4 months (8.6-17.3 months) with regorafenib and 9.0 months (6.8-12.5 months) with a placebo (hazard ratio, 0.67 [0.44-1.02]). With the classic definition of TOX (including all grade 3 and 4 clinical adverse events), the Q-TWiSTs were 8.0 months (7.0-9.0 months) with regorafenib and 5.7 months (4.9-6.4 months) with a placebo (P < .001). CONCLUSIONS: For patients with doxorubicin-pretreated soft-tissue sarcoma, regorafenib significantly improved quality-adjusted survival in comparison with a placebo. Cancer 2017;123:2294-2302. © 2017 The Authors. Cancer published by Wiley Periodicals, Inc. on behalf of American Cancer Society. This is an open access article under the terms of the Creative Commons Attribution NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.

Botulinum Toxin Injection for Treatment of Chronic Anal Fissure: Is There Any Dose-Dependent Efficiency? A Meta-Analysis.

BACKGROUND: Chronic anal fissure (CAF) is a linear split of the anoderm. The minimally invasive management of CAF such as botulinum toxin (BT) injection is recommended. However, the exact efficient dose of BT, number of injections per session and the injection sites are still debatable. The aim of this analysis was to assess the dose-dependent efficiency of botulinum toxin injection for CAF. METHODS: PubMed and Web of Science databases were searched for terms: "anal fissure" AND "botulinum toxin." Studies published between October 1993 and May 2015 were included and had to meet the following criteria: (1) chronic anal fissure, (2) prospective character of the study, (3) used simple BT injection without any other interventions and (4) no previous treatment with BT. RESULTS: A total of 1577 patients from 34 prospective studies used either Botox or Dysport formulations were qualified for this meta-analysis. A total number of BT units per session ranged from 5 to 150 IU, whereas the efficiency across analyzed studies ranged from 33 to 96 %. Surprisingly, we did not observe a dose-dependent efficiency (Spearman's rank correlation coefficient, ρ = 0.060; p = 0.0708). Moreover, there were no BT dose-dependent postoperative complications or fecal incontinence and significant difference in healing rates compared BT injection into the anal sphincter muscles. CONCLUSIONS: BT injection has been an accepted method for the management of CAF. Surprisingly, there is no dose-dependent efficiency, and the postoperative incontinence rate is not related to the BT dosage regardless the type of formulation of botulinum neurotoxin used. Moreover, no difference in healing rate has been observed in regard to the site and number of injections per session.

Polyethylene Glycol 3350 and Docusate Sodium Compared With Docusate Sodium Alone After Urogynecologic Surgery: A Randomized Controlled Trial.

OBJECTIVE: To compare time to first bowel movement and additional gastrointestinal outcomes between women receiving polyethylene glycol 3350 (PEG3350) and docusate sodium and docusate sodium alone after urogynecologic surgery. METHODS: Participants received twice-daily 100 mg docusate sodium and were randomized to daily 1) PEG3350 or 2) inert placebo for 5 days after urogynecologic surgery. They completed bowel diaries, Bristol stool scale, validated Patient Assessment of Constipation Symptom Questionnaire, and Patient Assessment of Constipation Quality-of-Life Questionnaire preoperatively and 1 week after surgery. Our primary outcome was time to first bowel movement after surgery. To detect a 1-day difference in time to first bowel movement (4 compared with 3 days), 63 participants were needed in each group. RESULTS: From September 2012 through March 2015, 145 women were randomized and 131 (90%) analyzed: 66 received PEG3350, and 65 received placebo. Polyethylene glycol 3350 did not significantly reduce time to first bowel movement after surgery compared with placebo (2.77 days [interquartile range 1.86-3.40] compared with 2.92 days [interquartile range 1.85-4.02] P=.25). Women in the PEG3350 group were less likely to take additional laxatives postoperatively, and the PEG3350 group was more adherent to the study drug regimen. Questionnaire scores, fecal incontinence, and urgency were similar between groups. CONCLUSION: In women taking routine docusate sodium after urogynecologic surgery, adding PEG3350 postoperatively did not reduce time to first bowel movement. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, https://clinicaltrials.gov, NCT01691742.

Botulinum toxin type A (BOTOX) for refractory myofascial pelvic pain.

OBJECTIVE: To assess intralevator botulinum toxin type A (Botox) injections for refractory myofascial pelvic pain with short tight pelvic floor. METHODS: Retrospective cohort study of all women with intralevator Botox injection (100-300 Units) from 2005 through 2010 for refractory myofascial pelvic pain. Primary outcomes were self-reported pain on palpation and symptom improvement. Secondary outcomes included postinjection complications and a second injection. Pain was assessed during digital palpation of the pelvic floor muscles using a scale of 0 to 10, with 10 being the worst possible pain. Follow-up occurred at less than 6 weeks after injection and again at 6 weeks or more. Data are presented as median (interquartile range) or proportion. RESULTS: Thirty-one patients met eligibility criteria; 2 patients were lostto follow-up and excluded. The median age was 55.0 years (38.0-62.0 years). Before Botox injection, the median pain score was 9.5 (8.0-10.0). Twenty-nine patients (93.5%) returned for the first follow-up visit; 79.3% reported improvement in pain, whereas 20.7% reported no improvement. The median pain with levator palpation was significantly lower than before injection (P<0.0001). Eighteen women (58.0%) had a second follow-up visit with a median pain score that remained lower than before injection (P<0.0001). Fifteen (51.7%) women elected to have a second Botox injection; the median time to the second injection was 4.0 months (3.0-7.0 months). Three (10.3%) women developed de novo urinary retention, 2 patients (6.9%) reported fecal incontinence, and 3 patients (10.3%) reported constipation and/or rectal pain; all adverse effects resolved spontaneously. CONCLUSIONS: Intralevator injection of Botox demonstrates effectiveness in women with refractory myofascial pelvic pain with few self-limiting adverse effects.

Complications following formalin installation in the treatment of radiation induced proctitis.

Formalin installation has been safely and effectively used to treat refractory bleeding caused by radiation proctitis. This study evaluated the results of such treatment in terms of outcome and complications. All four patients who underwent formalin irrigation for transfusion-dependent radiation proctitis over a 15-month period were evaluated retrospectively. The procedure was performed under sedation in the operating room, with patients in the prone jack-knife position. A solution of 4% formalin was introduced in aliquots of 50 ml kept in contact with the mucosa for 30 s and then cleared away using saline irrigation; five to six aliquots were used in each session. In a fifth patient formalin-soaked gauze pads were applied directly to the injured mucosa. At a mean follow-up of 18 months (range 6-26) two patients had repeat episodes of bleeding, one underwent successful repeat irrigation, and the other refused further treatment. One patient suffered from severe anococcygeal pain and worsening of incontinence after the procedure. The pain was treated with lidocaine ointment and sitz baths with partial success. Another patient developed severe formalin-induced colitis 5 days after the procedure, which required intravenous antibiotics and hydration. Formalin installation may be effective in controlling refractory bleeding due to radiation induced proctitis. The procedure, however, is not risk free and may induce major complications such as acute colitis.

Bowel preparation for colonoscopy: a randomized prospective trail comparing sodium phosphate and polyethylene glycol in a predominantly elderly population.

Many patients find polyethylene glycol-based preparations (PEG) difficult to take because of the large volume of fluid they are required to consume. One hundred and sixteen predominantly elderly patients were randomized to receive either sodium phosphate (n = 61) or PEG (n = 55) bowel preparations before colonoscopy. Patients with a history of symptomatic ischaemic heart disease or cerebrovascular disease in the preceding 6 months, severe liver disease or heart failure, or serum creatinine above 200 micrograms/L were excluded from the study. Each patient filled in a questionnaire about the bowel preparation prior to the procedure. The colonoscopists, who were not aware which preparation had been used, were asked to complete a questionnaire about the quality of the bowel preparation after the procedure. The patients found the sodium phosphate preparation slightly more tolerable than PEG. Side effects were slightly more common with sodium phosphate. Neither difference was statistically significant. However, 91% of patients who had previously had PEG found sodium phosphate easier to take. Approximately 25% of patients in each group experienced at least one episode of incontinence. The colonoscopists found no difference in the overall quality of the bowel preparation. The amount of fluid in the colon was greater in patients prepared with PEG. As expected, patients taking sodium phosphate developed hyperphosphataemia (mean phosphate level before colonoscopy 1.56 mmol/L, normal 0.8 -1.3). They also had a lower mean serum potassium level (3.8 mmol/L) than the PEG group (4.2 mmol/L). However, there were no clinically significant consequences. Sodium phosphate was a safe and effective bowel preparation for colonoscopy in this carefully selected group of patients. It was preferred by patients who had previously had PEG. Many elderly patients were found to develop faecal incontinence, irrespective of the type of bowel preparation used.