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Current controversies about rectal cancer treatment are examined and discussed in this book. In particular, oncologic outcomes, which claim an aggressive approach over the primary tumour, lymph nodes and distant metastasis. Also, the functional outcome, whose important objective is to preserve the anal sphincter and the preservation of the pelvic nervous plexus. Radical resection with total mesorectal excision is the mainstay of rectal cancer treatment. However, it is associated with significant surgical morbidity/mortality, possible stoma surgery/complications and long-term gastrointestinal dysfunction with deterioration in quality of life. This book also explores the risk factors of local recurrence after curative resection in patients with middle and lower rectal carcinoma. The relationships between mesorectal metastasis and local recurrence and the possible correlations between circumferential resection margin status and local recurrence were identified. The relationships between local recurrence and clinicopathologic characteristics of middle and lower rectal carcinoma were also evaluated.

Background Preoperative radiochemotherapy (RCT) is recommended in France prior to total mesorectal excision in patients with mid or low locally advanced rectal cancer (LARC) (cT3/T4 and/or N+) because it has been shown to improve local control. Preoperative RCT has also disadvantages including the absence of proven impact on metastatic recurrence and the risk of late side effects on bowel and genitourinary function. In patients with primarily resectable LARC, preoperative systemic chemotherapy without pelvic irradiation could be used as an alternative to RCT. Methods This study is a multicenter, open-label randomized, 2-arm phase III non-inferiority trial. Patients with mid or low resectable LARC (cT3N0 or cT1-T3N+ with circumferential resection margin [CRM] > 2 mm on pretreatment MRI) will be randomized to either modified FOLFIRINOX for 3 months or RCT (Cap50 intensified-modulated radiotherapy). All patients have restaging MRI after preoperative treatment. The primary endpoint is 3-year progression-free survival (PFS) from the time to randomization including progression during preoperative treatment. Secondary endpoints are treatment related toxicity, treatment compliance, R0 resection rate, sphincter saving surgery rate, postoperative morbidity and mortality rates, loco-regional recurrence free survival, overall survival, bowel and sexual functions at diagnosis, quality of life, radiologic and pathologic response after preoperative treatment. The number of patients required is 574. Discussion The choice of modified FOLFIRINOX for preoperative chemotherapy is supported by recent and consistent data on safety and efficacy of this regimen on rectal cancer. The use of preoperative chemotherapy instead of RCT could be associated with pronounced advantages in terms of functional results and quality of life in cancer survivors. However and first of all, the non-inferiority of preoperative chemotherapy compared to RCT on oncologic outcome has to be validated. If this study demonstrates the non-inferiority of chemotherapy compared to RCT, this can lead to a crucial change in clinical practice in a large subset of rectal cancer patients. Trial registration ClinicalTrials.gov NCT03875781 (March 15, 2019). Version 1.1.

Background Transabdominal ultrasonography and transperineal ultrasonography (TPUS) appear correspond to colonoscopy (CS) for evaluating ulcerative colitis (UC) activity, but their utility in UC diagnosis remains unclear. This research compared the accuracy of TPUS and CS for assessing rectal activity and differentiating noninflammatory bowel disease proctitis from UC in pediatric cases. Methods The study is a blinded, prospective, and controlled trial. Prospectively, values of fecal calprotectin (FCP) and findings of the TPUS and CS were compared between child cases of UC and non-IBD proctitis. Findings of rectal wall thickening (RWT), rectal wall flow (RWF) on power Doppler, and microvascular signal at wall circumference (MSWC) on monochrome superb microvascular imaging assessed using TPUS were compared with the CS. Results Thirty patients with Mayo endoscopic subscore (MES) 0 to 1 UC, 57 with MES 2 to 3 UC, and 44 with proctitis were registered. Fecal calprotectin, RWF, and MSWC indicated significant differences among the groups (P < .05). Rectal wall thickening showed no significant difference between MES 0–1 and proctitis (P = .76). Rectal wall thickening and MSWC were independent predictors of endoscopic activity of UC, resulting in a sensitivity and specificity of 100% for RWT ≥4.5 mm and positive MSWC. Fecal calprotectin and RWF were independent predictors for differentiating MES 0 to 1 and proctitis, and FCP and RWT were independent predictors for differentiating MES 2 to 3 and proctitis. Sensitivity and specificity were 77.2% and 80.9%, respectively, for FCP >242.5 μg/g and RWF negative; and they were both 100% for RWT >4.1 mm and MSWC positive. Conclusions Transperineal ultrasonography with mSMI may enable the evaluation of rectal activity and differentiation of UC from non-IBD proctitis with accuracy comparable to endoscopy. Lay Summary Transperineal ultrasonography with superb microvascular imaging can differentiate ulcerative colitis from noninflammatory bowel disease proctitis and is therefore useful in distinguishing whether diarrhea and bloody stool during the treatments of ulcerative colitis are due to recurrence or infection.

ᅟ Obstruction and perforation due to colorectal cancer represent challenging matters in terms of diagnosis, life-saving strategies, obstruction resolution and oncologic challenge. The aims of the current paper are to update the previous WSES guidelines for the management of large bowel perforation and obstructive left colon carcinoma (OLCC) and to develop new guidelines on obstructive right colon carcinoma (ORCC). Methods The literature was extensively queried for focused publication until December 2017. Precise analysis and grading of the literature has been performed by a working group formed by a pool of experts: the statements and literature review were presented, discussed and voted at the Consensus Conference of the 4th Congress of the World Society of Emergency Surgery (WSES) held in Campinas in May 2017. Results CT scan is the best imaging technique to evaluate large bowel obstruction and perforation. For OLCC, self-expandable metallic stent (SEMS), when available, offers interesting advantages as compared to emergency surgery; however, the positioning of SEMS for surgically treatable causes carries some long-term oncologic disadvantages, which are still under analysis. In the context of emergency surgery, resection and primary anastomosis (RPA) is preferable to Hartmann’s procedure, whenever the characteristics of the patient and the surgeon are permissive. Right-sided loop colostomy is preferable in rectal cancer, when preoperative therapies are predicted. With regards to the treatment of ORCC, right colectomy represents the procedure of choice; alternatives, such as internal bypass and loop ileostomy, are of limited value. Clinical scenarios in the case of perforation might be dramatic, especially in case of free faecal peritonitis. The importance of an appropriate balance between life-saving surgical procedures and respect of oncologic caveats must be stressed. In selected cases, a damage control approach may be required. Medical treatments including appropriate fluid resuscitation, early antibiotic treatment and management of co-existing medical conditions according to international guidelines must be delivered to all patients at presentation. Conclusions The current guidelines offer an extensive overview of available evidence and a qualitative consensus regarding management of large bowel obstruction and perforation due to colorectal cancer.

BackgroundWith the aging of the population and rising incidence of thromboembolic events, the clinical use of antithrombotic agents is also increasing. There are few reports yet on the management of antithrombotic agent use in patients undergoing cold snare polypectomy (CSP).AimsThe aim of this study was to evaluate whether continued administration of antithrombotic agents in patients undergoing CSP would be associated with an increased rate of delayed post-polypectomy bleeding (DPPB).MethodsA total of 1177 colorectal polyps in 501 patients were resected at Omori Red Cross Hospital between October 2017 and March 2018. The polyps were divided into two groups depending on whether the patients received antithrombotic agent treatment or not: the antithrombotic group (911 polyps) and the no-antithrombotic group (266 polyps).ResultsAmong the 1177 polyp resections, there was no case of DPPB, including in the antithrombotic group. Immediate bleeding occurred in a total of 63 (5.4%) cases. Polyp location in the rectum (OR (95% CI) 2.64 (1.223–5.679); p = 0.013), polyp size ≥ 6 mm (OR (95% CI) 4.64 (2.719–7.933); p < 0.001), polypoid growth pattern (OR (95% CI) 2.78 (1.607–4.793); p < 0.001), and antithrombotic agent use (OR (95% CI) 2.98 (1.715–5.183); p < 0.001) were identified as significant risk factors of immediate bleeding.ConclusionsContinued use of antithrombotic agents does not increase the risk of DPPB, even in those receiving multiple antithrombotic agents. Thus, it is safe to perform CSP even in multiple agent users. Prospective, randomized studies are necessary to confirm our results.

BackgroundMast cell activation is thought to be involved in visceral hypersensitivity, one of the main characteristics of the irritable bowel syndrome (IBS). A study was therefore undertaken to investigate the effect of the mast cell stabiliser ketotifen on rectal sensitivity and symptoms in patients with IBS.Methods60 patients with IBS underwent a barostat study to assess rectal sensitivity before and after 8 weeks of treatment. After the initial barostat, patients were randomised to receive ketotifen or placebo. IBS symptoms and health-related quality of life were scored. In addition, mast cells were quantified and spontaneous release of tryptase and histamine was determined in rectal biopsies and compared with biopsies from 22 age- and gender-matched healthy volunteers.ResultsKetotifen but not placebo increased the threshold for discomfort in patients with IBS with visceral hypersensitivity. This effect was not observed in normosensitive patients with IBS. Ketotifen significantly decreased abdominal pain and other IBS symptoms and improved quality of life. The number of mast cells in rectal biopsies and spontaneous release of tryptase were lower in patients with IBS than in healthy volunteers. Spontaneous release of histamine was mostly undetectable but was slightly increased in patients with IBS compared with healthy volunteers. Histamine and tryptase release were not altered by ketotifen.ConclusionsThis study shows that ketotifen increases the threshold for discomfort in patients with IBS with visceral hypersensitivity, reduces IBS symptoms and improves health-related quality of life. Whether this effect is secondary to the mast cell stabilising properties of ketotifen or H1 receptor antagonism remains to be further investigated.Trial Registration NumberNTR39, ISRCTN22504486.

Colorectal cancer (CRC) is the second most common cause of cancer death in the United States. Every 3 years, the American Cancer Society provides an update of CRC occurrence based on incidence data (available through 2016) from population-based cancer registries and mortality data (through 2017) from the National Center for Health Statistics. In 2020, approximately 147,950 individuals will be diagnosed with CRC and 53,200 will die from the disease, including 17,930 cases and 3,640 deaths in individuals aged younger than 50 years. The incidence rate during 2012 through 2016 ranged from 30 (per 100,000 persons) in Asian/Pacific Islanders to 45.7 in blacks and 89 in Alaska Natives. Rapid declines in incidence among screening-aged individuals during the 2000s continued during 2011 through 2016 in those aged 65 years and older (by 3.3% annually) but reversed in those aged 50 to 64 years, among whom rates increased by 1% annually. Among individuals aged younger than 50 years, the incidence rate increased by approximately 2% annually for tumors in the proximal and distal colon, as well as the rectum, driven by trends in non-Hispanic whites. CRC death rates during 2008 through 2017 declined by 3% annually in individuals aged 65 years and older and by 0.6% annually in individuals aged 50 to 64 years while increasing by 1.3% annually in those aged younger than 50 years. Mortality declines among individuals aged 50 years and older were steep-est among blacks, who also had the only decreasing trend among those aged younger than 50 years, and excluded American Indians/Alaska Natives, among whom rates remained stable. Progress against CRC can be accelerated by increasing access to guideline-recommended screening and high-quality treatment, particularly among Alaska Natives, and elucidating causes for rising incidence in young and middle-aged adults.

Distant metastasis (DM) is the main cause of treatment failure in locally advanced rectal cancer. Adjuvant chemotherapy is usually used for distant control. However, not all patients can benefit from adjuvant chemotherapy, and particularly, some patients may even get worse outcomes after the treatment. We develop and validate an MRI-based radiomic signature (RS) for prediction of DM within a multicenter dataset. The RS is proved to be an independent prognostic factor as it not only demonstrates good accuracy for discriminating patients into high and low risk of DM in all the four cohorts, but also outperforms clinical models. Within the stratified analysis, good chemotherapy efficacy is observed for patients with pN2 disease and low RS, whereas poor chemotherapy efficacy is detected in patients with pT1–2 or pN0 disease and high RS. The RS may help individualized treatment planning to select patients who may benefit from adjuvant chemotherapy for distant control. Distant metastasis (DM) is the main cause of treatment failure in locally advanced rectal cancer. Here, the authors developed and validated a radiomic signature (RS) for prediction of DM within a multicenter dataset, and suggest that it may help with stratification of patients who might benefit from adjuvant chemotherapy for DM.

Molecular mechanisms driving disease course and response to therapy in ulcerative colitis (UC) are not well understood. Here, we use RNAseq to define pre-treatment rectal gene expression, and fecal microbiota profiles, in 206 pediatric UC patients receiving standardised therapy. We validate our key findings in adult and paediatric UC cohorts of 408 participants. We observe a marked suppression of mitochondrial genes and function across cohorts in active UC, and that increasing disease severity is notable for enrichment of adenoma/adenocarcinoma and innate immune genes. A subset of severity genes improves prediction of corticosteroid-induced remission in the discovery cohort; this gene signature is also associated with response to anti-TNFα and anti-α 4 β 7 integrin in adults. The severity and therapeutic response gene signatures were in turn associated with shifts in microbes previously implicated in mucosal homeostasis. Our data provide insights into UC pathogenesis, and may prioritise future therapies for nonresponders to current approaches. The severity of ulcerative colitis, and response to treatment, is highly variable. Here, the authors examine rectal gene expression signatures and faecal microbiomes of children and adults with the disease and provide new insights in to pathogenesis.