Putrescine supplementation limits the expansion of pks+ Escherichia coli and tumor development in the colon.

Escherichia coli that harbor the polyketide synthase (pks) genomic island produce colibactin and are associated with sporadic colorectal cancer development (CRC). Given the considerable prevalence of pks+ bacteria in healthy individuals, we sought to identify strategies to limit the growth and expansion of pks+ E. coli. We found that culture supernatants of the probiotic strain E. coli Nissle 1917 were able to inhibit the growth of the murine pathogenic strain pks+ E. coli NC101 (EcNC101). We performed a non-targeted analysis of the metabolome in supernatants from several E. coli strains and identified putrescine as a potential postbiotic capable of suppressing EcNC101 growth in vitro. The effect of putrescine supplementation was then evaluated in the azoxymethane (AOM)/dextran sulfate sodium (DSS) mouse model of CRC in mice colonized with EcNC101. Putrescine supplementation inhibited the growth of pks+ E. coli; reduced the number and size of colonic tumors; and downmodulated the release of inflammatory cytokines in the colonic lumen. Additionally, putrescine supplementation led to shifts in the composition and function of gut microbiota, characterized by an increase of the Firmicutes/Bacteroidetes ratio and enhanced acetate production. The effect of putrescine was further confirmed in vitro using a pks+ E. coli strain isolated from a CRC patient. These results suggest that probiotic-derived metabolites can be used as an alternative to live bacteria in individuals at risk of developing CRC due to the presence of pks+ bacteria in their colon.

Modulating Gut Microbiota Prevents Anastomotic Leak to Reduce Local Implantation and Dissemination of Colorectal Cancer Cells after Surgery.

PURPOSE: Anastomotic leak (AL) is a major complication in colorectal cancer surgery and consists of the leakage of intestinal content through a poorly healed colonic wound. Colorectal cancer recurrence after surgery is a major determinant of survival. We hypothesize that AL may allow cancer cells to escape the gut and lead to cancer recurrence and that improving anastomotic healing may prevent local implantation and metastatic dissemination of cancer cells. EXPERIMENTAL DESIGN: We investigated the association between AL and postoperative outcomes in patients with colorectal cancer. Using mouse models of poor anastomotic healing, we assessed the processes of local implantation and dissemination of cancer cells. The effect of dietary supplementation with inulin and 5-aminosalicylate (5-ASA), which activate PPAR-γ in the gut, on local anastomotic tumors was assessed in mice undergoing colonic surgery. Inulin and 5-ASA were also assessed in a mouse model of liver metastasis. RESULTS: Patients experiencing AL displayed lower overall and oncologic survival than non-AL patients. Poor anastomotic healing in mice led to larger anastomotic and peritoneal tumors. The microbiota of patients with AL displays a lower capacity to activate the antineoplastic PPAR-γ in the gut. Modulation of gut microbiota using dietary inulin and 5-ASA reinforced the gut barrier and prevented anastomotic tumors and metastatic spread in mice. CONCLUSIONS: Our findings reinforce the hypothesis that preventing AL is paramount to improving oncologic outcomes after colorectal cancer surgery. Furthermore, they pave the way toward dietary targeting of PPAR-γ as a novel way to enhance healing and diminish cancer recurrence.

Primary malignant melanoma of the vagina: A case report.

Malignant primary melanoma of the vagina (PMV) is a rare type of non-cutaneous melanoma often discovered in postmenopausal women. PMV has a very aggressive disease course and a poor prognosis. The best course of treatment is not presently agreed upon. In this report, we describe the case of a 68-year-old woman presenting with a malignant PMV and its subsequent management. The patient presented with right vaginal pain, abnormal vaginal bleeding and a new vaginal mass. A PET scan identified a 28 × 38 mm hypermetabolic vaginal lesion, without nodal involvement or distant metastasis. A posterior exenteration type 2B was performed, including the anal mucosa. Sentinel lymph node dissection, vaginal and rectal resection as well as a terminal colostomy were also carried out. Final staging was FIGO stage III and T4bN1. Four months later, the patient presented with a recurrent vaginal bleed and intra-vaginal induration. Imaging revealed loco-reginal recurrence at the site of the primary malignancy with countless metastases. The patient opted for palliative care given the early disseminated recurrence and her multiple comorbidities. We review the treatment options for PMV, mainly the importance of surgery as the mainstay of treatment as well as the interest of adding checkpoint inhibitor immunotherapy or targeted therapy to the treatment plan. We also summarize the characteristics of PMV and its main prognostic factors.

Accuracy in Polyp Size Measurement Among Surgeons, Gastroenterologists, Trainees, and Experts: A Prospective Video-Based Study.

INTRODUCTION: Polyp size determination plays an important role in endoscopic decision making and follow-up determination. However, there is a lack of knowledge of endoscopist accuracy for polyp sizing and efficacy of available tools for size measurement. Our aim was to compare the accuracy of visual assessment, snare, forceps, and virtual scale endoscope (VSE) in estimating polyp size among a diverse group of endoscopists. METHODS: We conducted a prospective video-based study. One hundred twenty polyps measured and recorded along with all available measurement tools were randomized to visual assessment, snare, forceps, or VSE group. Eleven endoscopists conducted video-based measurement using the randomized measurement tool. Primary outcome was relative accuracy in polyp size measurement compared with caliper measurement immediately postresection. RESULTS: One thousand three hundred twenty measurements were performed. VSE had statistically significantly higher relative accuracy when compared to forceps (79.3 vs 71.3%; P < 0.0001). Forceps had statistically significantly higher relative accuracy when compared to visual assessment (71.3 vs 63.6%; P = 0.0036). There was no statistically significant difference when comparing visual assessment and snare-based measurements (63.6 vs 62.8%; P = 0.797). Overall, 21.5% of polyps >5 mm were misclassified as ≤5 mm and 17.3% of polyps ≥10 mm were misclassified as <10 mm. VSE had the lowest percentage of polyps >5 mm misclassified as ≤5 mm (2.6%), polyps ≤5 mm misclassified as >5 mm (5.1%), and polyps <10 mm misclassified as ≥10 mm (1.7%). DISCUSSION: Visual size estimation of polyps is inaccurate independently of training level, sex, and specialty. Size measurement accuracy can be improved using forceps and yields the highest relative accuracy when an adaptive scale technology is used.

Gut microbiota influence anastomotic healing in colorectal cancer surgery through modulation of mucosal proinflammatory cytokines.

OBJECTIVE: Colorectal cancer (CRC) is the third most diagnosed cancer, and requires surgical resection and reconnection, or anastomosis, of the remaining bowel to re-establish intestinal continuity. Anastomotic leak (AL) is a major complication that increases mortality and cancer recurrence. Our objective is to assess the causal role of gut microbiota in anastomotic healing. DESIGN: The causal role of gut microbiota was assessed in a murine AL model receiving faecal microbiota transplantation (FMT) from patients with CRC collected before surgery and who later developed or not, AL. Anastomotic healing and gut barrier integrity were assessed after surgery. Bacterial candidates implicated in anastomotic healing were identified using 16S rRNA gene sequencing and were isolated from faecal samples to be tested both in vitro and in vivo. RESULTS: Mice receiving FMT from patients that developed AL displayed poor anastomotic healing. Profiling of gut microbiota of patients and mice after FMT revealed correlations between healing parameters and the relative abundance of Alistipes onderdonkii and Parabacteroides goldsteinii. Oral supplementation with A. onderdonkii resulted in a higher rate of leaks in mice, while gavage with P. goldsteinii improved healing by exerting an anti-inflammatory effect. Patients with AL and mice receiving FMT from AL patients presented upregulation of mucosal MIP-1α, MIP-2, MCP-1 and IL-17A/F before surgery. Retrospective analysis revealed that patients with AL present higher circulating neutrophil and monocyte counts before surgery. CONCLUSION: Gut microbiota plays an important role in surgical colonic healing in patients with CRC. The impact of these findings may extend to a vast array of invasive gastrointestinal procedures.

Prevalence of pks + bacteria and enterotoxigenic Bacteroides fragilis in patients with colorectal cancer.

BACKGROUND: Colorectal cancer (CRC) is the third most diagnosed cancer and the second most common cause of cancer deaths worldwide. CRC patients present with an increase in pathogens in their gut microbiota, such as polyketide synthase-positive bacteria (pks +) and enterotoxigenic Bacteroides fragilis (ETBF). The pks + Escherichia coli promotes carcinogenesis and facilitates CRC progression through the production of colibactin, a genotoxin that induces double-strand DNA breaks (DSBs). ETBF is a procarcinogenic bacterium producing the B. fragilis toxin (bft) that promotes colorectal carcinogenesis by modulating the mucosal immune response and inducing epithelial cell changes. METHODS: Fecal samples were collected from healthy controls (N = 62) and CRC patients (N = 94) from the province of Québec (Canada), and a bacterial DNA extraction was performed. Fecal DNA samples were then examined for the presence of the pks island gene and bft using conventional qualitative PCR. RESULTS: We found that a high proportion of healthy controls are colonized by pks + bacteria (42%) and that these levels were similar in CRC patients (46%). bft was detected in 21% of healthy controls and 32% of CRC patients, while double colonization by both pks + bacteria and ETBF occurred in 8% of the healthy controls and 13% of the CRC patients. Most importantly, we found that early-onset CRC (< 50 years) patients were significantly less colonized with pks + bacteria (20%) compared to late-onset CRC patients (52%). CONCLUSIONS: Healthy controls had similar levels of pks + bacteria and ETBF colonization as CRC patients, and their elevated levels may place both groups at greater risk of developing CRC. Colonization with pks + bacteria was less prevalent in early-compared to late-onset CRC.

The concurrence of an enterocutaneous fistula and granulomatosis with polyangiitis: The role of immunosuppression as a bridge to definitive surgical treatment.

BACKGROUND AND AIM: Granulomatosis with polyangiitis (GPA) is a systemic disease that consists of vasculitis and granulomatous inflammation, and that usually affects the respiratory tract, the ear, nose, and throat sphere, and the kidneys. GPA may also cause skin manifestations that include ulcerations, nodules, or papules. An enterocutaneous fistula (ECF) is an abnormal tract that connects the skin surface to the gastrointestinal system. METHODS: We report the first case of an ECF as a concurrent clinical manifestation during a new-onset GPA in a 68-year-old male patient. RESULTS: The patient presented with an abdominal cutaneous wound with subcutaneous abscess that evolved into an ECF with spontaneous enteric drainage. He also complained of nasal crusting, epistaxis, and cough, with further investigation revealing bilateral pulmonary nodules. Transthoracic biopsy was performed and was suggestive of necrotizing vasculitis. A diagnosis of autoimmune vasculitis was highly suspected, and an immunosuppressive regimen of corticosteroid and intravenous cyclophosphamide was initiated. Significant improvement was noted in nasal manifestations, cough, and the output of the ECF. Definitive surgical management of the ECF was performed successfully. CONCLUSION: To the best of our knowledge, the presentation of a GPA with an ECF has not been previously reported and poses major challenges to medical and surgical treatment, as it constitutes a dilemma as to how to address an autoimmune process requiring immunosuppression in the context of an infectious condition. This presentation suggests that immunosuppression in these patients may still be considered. RELEVANCE FOR PATIENTS: The concomitant presence of an ECF with abscess, an infectious process, and of an autoimmune disorder requiring immunosuppression is a major medical challenge. This case suggests that immunosuppression may still be considered in these patients to promote a better control of the concomitant ECF before definitive surgical therapy.

Mesenteric Lymph Node Recurrence of a Primary Colorectal Leiomyosarcoma.

Primary colorectal leiomyosarcoma is an excessively rare entity. It is associated with an aggressive behavior and typically favor hematogenous spread. The current standard of care is surgical resection. A 49-year-old patient presented with a 2-month history of fever. A PET-scan revealed a hypermetabolic mass in the transverse colon, and colonoscopy confirmed a tumor. A right hemicolectomy was performed. Histopathological diagnosis was of a leiomyosarcoma. Fourteen months after the surgery, a follow-up abdominal scan revealed a 2 cm mesenteric lymph node that was hypermetabolic on PET-scan. The mesenteric lymph node was resected and histopathology confirmed a leiomyosarcoma metastasis. This case opens the controversy on the management of rare lymph node recurrences in colorectal leiomyosarcoma.

Anisakiasis in a Canadian patient with incarcerated epigastric hernia.

Anisakiasis is human zoonotic parasitic infection caused by a nematode parasite called Anisakis. This infection is usually reported in Asian countries where consumption of raw seafood is common. Very few cases have been reported in North America. We present the case of a female Canadian patient with an Anisakis larvae in an incarcerated ventral hernia. Cases of Anisakis infections are exceedingly rare in western countries, with very few previous reports describing extra-gastrointestinal cases. Diagnosis is often difficult since the symptoms of anisakiasis are not pathognomonic. As the larvae cannot survive in the body, conservative treatment might be effective in intestinal anisakiasis and surgery is usually performed when complications are encountered. Preventive measures are crucial and include educating the public about the risks of raw fish consumption and the importance of visually inspecting consumed fish and freezing it before ingestion to kill the larvae and prevent the infection.

Image Guided Adaptive Endorectal Brachytherapy in the Nonoperative Management of Patients With Rectal Cancer.

PURPOSE: Organ preservation or nonoperative management of rectal cancer is of growing interest. Image guided adaptive endorectal brachytherapy is a radiation dose escalation modality: we explored its role in elderly patients unfit for surgery and patients refusing surgery. METHODS AND MATERIALS: In this registry study, patients with rectal cancer who were ineligible for surgery received 40 Gy in 16 fractions of pelvic external beam radiation therapy. They subsequently received 3 weekly image guided adaptive brachytherapy boosts of 10 Gy to the residual tumor, for a total of 30 Gy in 3 fractions. Complete clinical response (cCR) and local control were the primary endpoints. RESULTS: 94 patients were included; the median age was 81.1 years. With a median follow-up of 1.9 years, the proportion of cCR was 86.2%, the tumor regrowth proportion was 13.6%, and the cumulative incidence of local relapse was 2.7% at 1 year and 16.8% at 2 years. When considering responders and nonresponders, the 2-year local control was 71.5%. The overall survival at 2 years was 63.6%. Acute rectal grade 1 to 2 toxicity included all patients: 12.8% of patients had late bleeding requiring iron replacement, blood transfusions, or argon plasma therapy. CONCLUSIONS: Results of this registry study, evaluating radiation dose escalation for elderly medically unfit patients with unselected tumors, reveal that a high proportion of patients achieved cCR with a manageable toxicity profile. This technology will likely contribute to the challenging nonoperative management paradigm of rectal cancer.

YouTube Videos as a Source of Information on Colorectal Cancer: What Do Our Patients Learn?

YouTube is the second most visited website in the world. No studies to date have characterized and evaluated YouTube videos on colorectal cancer (CRC) although these videos could influence patient decision-making, notably regarding screening and prevention. This study aims to report the characteristics and quality of these videos as patient education resources for CRC. YouTube's search engine was queried with different search phrases relating to CRC. The first two pages of each search result were analyzed. Two specialists devised a critical appraisal tool with a list of criteria to assess the videos. Quantitative YouTube parameter analyses and criteria assessment were performed. Inter-rater agreement was assessed between three raters. A total of 46 videos were eligible to be included in the study. The videos were on average 4:51 ± 3:27 min long. The videos had 10 times as many likes as dislikes. Less than half the videos discussed risk factors and protective factors. Only 41% of videos mentioned screening tests and only about a quarter discussed them. Palliative care was only mentioned in 2% of videos. A single video could obtain a perfect score on the critical appraisal tool. Length was the unique parameter associated with a high score on the criteria list. There is thus a need for more authoritative and comprehensive videos easily identifiable by the patients. Video popularity is not associated with comprehensiveness. Currently, YouTube might not be an education resource for CRC suited to every patient.

Ectopic jejunal pancreas with pancreatitis mistaken for a post-transplant lymphoproliferative disease in an immunosuppressed kidney transplant patient.

An ectopic pancreas, also known as pancreatic rest or heterotopic pancreas, consists of pancreatic tissue found in a location with no continuity with the anatomic pancreas. This lesion can occasionally cause gastrointestinal obstruction, ulceration or become inflamed and cause ectopic pancreatitis. We present the case of a 29-year-old immunocompromised female patient due to a previous kidney transplant. She presented with nausea and vague abdominal discomfort and was admitted for investigation and treatment of an acute kidney injury. A small bowel mass of unknown etiology was incidentally found on abdominal computed tomography imaging. Due to the high suspicion of a post-transplant lymphoproliferative disease, a surgical exploration took place and revealed the presence of a pancreatic rest with chronic pancreatitis. Ectopic pancreas diagnosis is challenging and surgical exploration is warranted when a neoplastic process is suspected.

Conservative management of pelvic sepsis with severe shock and multiple organ dysfunction syndrome after rubber-band ligation of internal haemorrhoids: surgery is not the only option.

Rubber-band ligation (RBL) is a safe and cost-effective approach to internal haemorrhoids. Potential side effects include pain, bleeding, urinary retention and occasionally pelvic sepsis and systemic inflammatory response syndrome (SIRS). At-risk patients are mainly those with immunocompromising conditions. Although aggressive surgical debridement or diverting colostomy appear to be obvious options when patients' life is threatened, their superiority to conservative measures has not been proven. We present the case of a 58-year-old female patient who presented 48 h after a RBL with pelvic pain, dysuria and leukocytosis. Her condition deteriorated rapidly that ventilator and inotropic support were required for a severe SIRS for almost 10 days. Laparoscopic exploration and imaging showed a rectosigmoiditis, ascites and superficial rectal necrosis with no transmural damage requiring an emergent surgery. Conservative management could possibly be a valid option in post-RBL pelvic sepsis even when severe associated multiple organ failure is present.

Gastrointestinal mucormycosis after abdominal aortic aneurysm repair and prolonged hospitalization: A case report and review of the literature.

INTRODUCTION: Mucormycosis is a rare fungal infection typically affecting immunocompromised hosts. One form of the disease affects the gastrointestinal tract. PRESENTATION OF CASE: We present the case of a 70-year old patient with no recognized risk factors that developed gastrointestinal mucormycosis after urgent abdominal aortic aneurysm repair. DISCUSSION: There are several risk factors for this infection, such as hematological malignancies, solid organ or stem cell transplants and diabetes. The infectious agent causes thrombosis and necrosis of involved tissues and organs and carries a high mortality rate. CONCLUSION: Mucormycosis is an opportunistic infection which can sometimes affect the gastrointestinal tract. A high index of suspicion is necessary in order to make an early diagnosis and promptly start an appropriate treatment regimen.

Metastatic rectal neuroendocrine tumor presenting as an inguinal mass: A case report and review of literature.

INTRODUCTION: Neuroendocrine tumors (NET) are a heterogeneous group of rare carcinomas that most often manifest along the gastrointestinal tract. Some of these tumors have the ability to secrete vasoactive peptides and hormones. PRESENTATION OF CASE: The present report describes the case of a previously healthy 52-year old man who presented with a painful right inguinal mass. Upon surgical exploration, a lymph node metastasis of a high-grade NET was found. Further investigations revealed a rectal NET with pulmonary, pelvic and penile metastases. The patient was treated with 6 cycles of carboplatin and etoposide. Although initial follow-up imaging after 3 cycles of chemotherapy revealed stable disease, there was progression of the metastases after completion of systemic treatment. Second and third-line chemotherapy regimens were instituted along with pelvic and whole-brain radiation therapy extending the patient's survival to 18 months after the initial diagnosis. DISCUSSION: This case highlights the aggressive nature high-grade NETs as described in the current literature. Treatment modalities of colorectal NETs include local excision for non-metastatic disease and systemic palliative chemotherapy for advanced disease. However, there are no controlled trials in favor of palliative chemotherapy. CONCLUSION: Rectal NETs are rare tumors which often have an atypical presentation or present in advanced stages. Currently, surgical options exist for local disease while treatment modalities for more advanced disease is still under investigation.

Can community surgeons perform laparoscopic colorectal surgery with outcomes similar to tertiary care centres?

INTRODUCTION: The use of the laparoscopic approach in colorectal surgery (LCS) is the subject of active debate. Studies demonstrating its safety and feasibility in tertiary care centres are now available. The aim of this study was to examine the results of LCS performed in a community hospital setting. METHODS: We prospectively studied 100 patients who underwent an LCS at the North Bay District Hospital (a 200-bed community hospital located 350 km away from the nearest tertiary care centre). All operations were performed by 2 community surgeons who transitioned themselves from an open to a laparoscopic approach. RESULTS: Between October 2000 and December 2003, 100 patients (56 women and 44 men, mean age 64 yr) underwent an LCS for benign (n = 54) and malignant (n = 46) disease. Median operating time was 165 minutes (range 70350 min), and the conversion rate was 10%. The intraoperative complication rate was 3%. There were 10 major postoperative complications and 14 minor postoperative complications. There was no intraoperative mortality and one 30-day mortality secondary to cardiogenic shock. The median length of stay was 4.5 days (range 245 d). At a mean follow-up of 18 months, no trocar site or wound recurrences were noted. The mean number of resected lymphnodes was 10.6. CONCLUSION: Our study suggests that it is possible for community surgeons to transition themselves from an open to a laparoscopic approach and to perform LCS with outcomes similar to those of tertiary care centres.

Telementoring: an important enabling tool for the community surgeon.

This study evaluated the efficacy of telementoring as an enabling tool for community general surgeons to perform advanced laparoscopic surgical procedures. We present a series of 19 patients who underwent advanced laparoscopic surgical procedures in two community hospitals, between November 2002 and July 2003, by four community surgeons with no formal advanced laparoscopic training. Each surgeon was telementored by an expert surgeon from a tertiary care hospital. Telementoring was achieved with real-time two-way audio-video communications over Internet Protocol or Integrated Services Digital Network lines with bandwidths from 385 kbps to 1.2 mbps. The procedures included 10 bowel resections, 5 Nissen fundoplications, 2 splenectomies, 1 reversal of a Hartmann procedure, and 1 ventral hernia repair. Two of the 19 procedures (11%) were converted to open. There were no intraoperative complications and two postoperative complications (11%). The primary surgeon considered telementoring useful in all cases (median score, 4 of 5). The mentor was also comfortable with the quality of the laparoscopic surgery performed (median score, 4 of 5). Telecommunication bandwidth for audio and video transmission was found to be a critical factor in the quality of telementoring process. Telementoring is safe and feasible. It allows community surgeons with no formal advanced laparoscopic training to benefit from expert intraoperative advice during the performance of advanced laparoscopic procedures. It may also reduce health-care costs by avoiding the need to refer and transfer patients to tertiary care centers.