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.

A mycotic aneurysm of a jejunal branch treated by aneurysmectomy without bowel resection.

Jejunal artery pseudoaneurysms are extremely rare, accounting for <1% of all visceral artery pseudoaneurysms. Fewer than 50 cases were reported in literature during the previous century. This case report describes the case of a 72-year-old man who underwent aneurysmectomy to treat a 21-mm mycotic jejunal artery pseudoaneurysm found in the setting of endocarditis. This pseudoaneurysm was treated with laparotomy, and gentle dissection of the tissues surrounding the pseudoaneurysm was performed before ligation and resection. This allowed for vascular collateral branch preservation, which, thus, avoided concomitant bowel resection. This report highlights the feasibility of this technique.

Safety and clinical efficacy of EUS-guided pelvic abscess drainage.

Background and Objectives: EUS is a potential alternative for the drainage of abscesses. The aim of this study was to determine if EUS-guided pelvic abscess drainage is technically feasible, safe, and a valid option for abscess resolution. Methods: We conducted a retrospective review from 2002 to 2020 at a single quaternary institution. EUS-guided pelvic abscess drainage via the transrectal route was performed in all patients with or without drain/stent placement. Technical and clinical success of EUS-guided pelvic abscess drainage was analyzed. Descriptive analyses and Fisher exact test were performed. Results: Sixty consecutive patients were included in the study (53.5% male; mean age, 53.8 ± 17.9 years). Pelvic abscesses occurred mainly postoperatively (33 cases; 60.0%) and from complicated diverticulitis (14 cases; 23.3%). Mean diameter was 6.5 ± 2.4 cm (80% unilocular). Drainage was performed with EUS-guided stent placement (double-pigtail plastic or lumen-apposing metal) in 74.5% of cases and with aspiration alone for the remainder. Technical success occurred in 58 cases (97%). Of those with long-term follow-up after EUS-guided pelvic abscess drainage (n = 55; 91.7%), complete abscess resolution occurred in 72.7% of all cases. Recurrence occurred in 8 cases (14.5%) and persisted in 7 patients (12.5%), 7 of which were successfully retreated with EUS-guided pelvic abscess drainage. Accounting for these successful reinterventions, the overall rate of abscess resolution was 85.5%. Abscess resolution rate improved with drain placement (83%). Accounting for 7 repeat EUS-guided pelvic abscess drainages, overall abscess resolution improved. Two deaths occurred (3.4%) because of sepsis from failed source control in patients who had previously failed medical, radiological, and surgical treatment. Conclusions: EUS-guided pelvic abscess drainage is technically feasible, safe, and an effective alternative to radiological or open surgical drainage. It also offers favorable clinical outcomes in different clinical situations.

A new clinical severity score for the management of acute small bowel obstruction in predicting bowel ischemia: a cohort study.

BACKGROUND: Small bowel obstruction (SBO) is a common hospital admission diagnosis. Identification of patients who will require a surgical resection because of a nonviable small bowel remains a challenge. Through a prospective cohort study, the authors aimed to validate risk factors and scores for intestinal resection, and to develop a practical clinical score designed to guide surgical versus conservative management. PATIENTS AND METHODS: All patients admitted for an acute SBO between 2004 and 2016 in the center were included. Patients were divided in three categories depending on the management: conservative, surgical with bowel resection, and surgical without bowel resection. The outcome variable was small bowel necrosis. Logistic regression models were used to identify the best predictors. RESULTS: Seven hundred and thirteen patients were included in this study, 492 in the development cohort and 221 in the validation cohort. Sixty-seven percent had surgery, of which 21% had small bowel resection. Thirty-three percent were treated conservatively. Eight variables were identified with a strong association with small bowel resection: age 70 years of age and above, first episode of SBO, no bowel movement for greater than or equal to 3 days, abdominal guarding, C-reactive protein greater than or equal to 50, and three abdominal computer tomography scanner signs: small bowel transition point, lack of small bowel contrast enhancement, and the presence of greater than 500 ml of intra-abdominal fluid. Sensitivity and specificity of this score were 65 and 88%, respectively, and the area under the curve was 0.84 (95% CI: 0.80-0.89). CONCLUSION: The authors developed and validated a practical clinical severity score designed to tailor management of patients presenting with an SBO.

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.

Minimally invasive management of a paraduodenal hernia with intestinal malrotation.

Paraduodenal hernias (PDHs) are rare entities that may present with acute or subacute symptoms, and which pose challenges to prompt diagnosis and treatment. The minimally invasive management of these hernias is emerging as a new compelling approach to optimize surgical recovery. We present the case of a 42-year-old female patient who presented with acute abdominal pain and symptoms of bowel obstruction. Abdominal imaging suggested the presence of a left PDH. Laparoscopic exploration was performed. Intestinal malrotation was noted with incarceration of a small bowel loop in the Landzert fossa. The incarcerated bowel loop was freed and primary repair of the hernial defect was performed. PDHs are usually congenital and involve a herniation of abdominal content into the left mesocolon, between the mesocolon and the posterior abdominal wall. Minimally invasive treatment, consisting of adhesiolysis and repair of the hernial defect, seems to be a valid and safe option.

Raoultella ornithinolytica: Emergence and Resistance.

Raoultella ornithinolytica is an encapsulated Gram-negative, oxidase-negative, catalase-positive, aerobic, non-motile rod that belongs to the Enterobacteriaceae family. This bacterium was initially classified in the genus Klebsiella as Klebsiella ornithinolytica, until the creation of the genus Raoultella in 2001. R. ornithinolytica is usually found in water environments and soil, and due to its ability to convert histidine to histamine, it has been associated with histamine poisoning in humans. R. ornithinolytica is an emerging entity in human infections, with several reports of virulent infections in comorbid at-risk patients. Increasing reports are potentially due to better and more precise identification tools. The objective of this article is to provide a comprehensive review of reported cases of R. ornithinolytica infections, the emergent virulence of described multiresistant strains, and an overview of currently used identification methods.

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.

Transcriptomic Analysis and High-dimensional Phenotypic Mapping of Mononuclear Phagocytes in Mesenteric Lymph Nodes Reveal Differences Between Ulcerative Colitis and Crohn's Disease.

BACKGROUND AND AIMS: Crohn's disease [CD] and ulcerative colitis [UC] are distinct forms of inflammatory bowel disease. Heterogeneity of HLA-DR+SIRPα + mononuclear phagocytes [MNPs], including macrophages [MΦ], monocyte-derived [Mono] cells, and dendritic cells [DCs], was reported in gut tissue but not yet investigated in mesenteric lymph nodes [MLNs] of IBD patients. We here compared the phenotype, function, and molecular profile of HLA-DR+SIRPα + MNPs in CD and UC MLNs. METHODS: Cell distribution, morphology, immune function, and transcriptomic [bulk RNAseq] and high-dimensional protein expression profiles [CyTOF] of HLA-DR+SIRPα + MNPs were examined in MLNs of UC [n = 14], CD [n = 35], and non-IBD [n = 12] patients. RESULTS: Elevated frequencies of CD14+CD64+CD163+ [Mono/MΦ-like] MNPs displaying monocyte/MΦ morphology and phagocytic function were a distinct feature of UC MLNs. In CD, the proportion of CD14-CD64-CD163- [DC-like] cells was augmented relative to Mono/MΦ-like cells; DC-like cells drove naïve T cell proliferation, Th1 polarisation, and Th17 TCM plasticity. Gene expression profile corroborated the nature of DC-like cells, best represented by BTLA, SERPINF, IGJ and, of Mono/MΦ-like cells, defined by CD163, MARCO, MAFB, CD300E, S100A9 expression. CyTOF analysis showed that CD123+ plasmacytoid cells predominated over conventional DCs in DC-like cells. Four CD163+ clusters were revealed in Mono/MΦ-like cells, two of which were enriched in MARCO-CD68dimHLA-DRdim monocyte-like cells and MARCOhiCD68hiHLA-DRhi Mɸ, whose proportion increased in UC relative to CD. CONCLUSIONS: Defining the landscape of MNPs in MLNs provided evidence for expansion of CD163+ Mono/MΦ-like cells in UC only, highlighting a distinction between UC and CD, and thus the potential contribution of monocyte-like cells in driving colitis.

Gastric necrosis late after a Collis-Nissen procedure.

A Nissen procedure is an efficient surgical approach to treat gastroesophageal reflux disease. It is sometimes combined with a Collis gastroplasty to lengthen the functional distal esophagus to allow a 360° Nissen fundoplication without tension. We present the case of a 76-year-old female patient, with a history of a Collis-Nissen procedure, who developed extensive gastric necrosis after ingesting a significant quantity of maize. She underwent an urgent total gastrectomy with Roux-en-Y esophagojejunostomy. The cause of ischemia and necrosis in this case is believed to be an insufficient blood supply due to excessive intraluminal pressure. Necrosis of the gastric cavity is usually more likely to be due to venous insufficiency as veins' walls are less resistant to compression than arterial vessels. Gastric necrosis after a Collis-Nissen procedure is exceedingly rare, and symptoms of such a complication are usually vague and not pathognomonic, which might delay surgical care and increase morbidity.

Differential Pathogenic Th17 Profile in Mesenteric Lymph Nodes of Crohn's Disease and Ulcerative Colitis Patients.

The drug targets IL23 and IL12 regulate pathogenicity and plasticity of intestinal Th17 cells in Crohn's disease (CD) and ulcerative colitis (UC), the two most common inflammatory bowel diseases (IBD). However, studies examining Th17 dysregulation in mesenteric lymph nodes (mLNs) of these patients are rare. We showed that in mLNs, CD could be distinguished from UC by increased frequencies of CCR6+CXCR3-RORγ+Tbet-CD4+ (Th17) memory T cells enriched in CD62Llow effector memory T cells (TEM), and their differentially expressed molecular profile. Th17 TEM cells (expressing IL17A, IL17F, RORC, and STAT3) displayed a higher pathogenic/cytotoxic (IL23R, IL18RAP, and GZMB, CD160, PRF1) gene signature in CD relative to UC, while non-pathogenic/regulatory genes (IL9, FOXP3, CTLA4) were more elevated in UC. In both CD and UC, IL12 but not IL23, augmented IFNγ expression in Th17 TEM and switched their molecular profile toward an ex-Th17 (Th1*)-biased transcriptomic signature (increased IFNG, and decreased TCF7, IL17A), suggesting that Th17 plasticity occurs in mLNs before their recruitment to inflamed colon. We propose that differences observed between Th17 cell frequencies and their molecular profile in CD and UC might have implications in understanding disease pathogenesis, and thus, therapeutic management of patients with IBD.

Extended thromboprophylaxis with low-molecular weight heparin (LMWH) following abdominopelvic cancer surgery.

BACKGROUND: Venous thromboembolism (VTE) includes deep vein thrombosis (DVT) and pulmonary embolism (PE). Certain abdominopelvic cancer surgeries are associated with a six to 14-fold increased risk of DVT versus surgeries for benign disease, and extended thromboprophylaxis using perioperative LMWHs may further reduce VTE rates over standard duration administration. This review assesses the value of extended low molecular weight heparin (LMWH) thromboprophylaxis as a recommended strategy after abdominopelvic cancer surgery. DATA SOURCES: Six eligible randomized controlled trials (RCTs), seven meta-analyses (MAs), and five non-randomized cohort studies were identified evaluating extended versus standard thromboprophylaxis following abdominopelvic cancer surgery. FINDINGS AND CONCLUSIONS: Available evidence showed significantly reduced rates of VTE for extended versus standard LMWH thromboprophylaxis following abdominopelvic cancer surgery, with some studies showing trends toward reduced rates of symptomatic VTE events. Many of these studies showed significantly reduced rates of proximal DVT and some showed trends toward reduced PE, suggesting potentially important clinical benefits.

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.

Clinical presentation and management of atraumatic splenic rupture.

Atraumatic splenic rupture is a rare, but well-documented and life-threatening clinical entity that is often misdiagnosed. Clinicians should include this entity in their differential diagnosis using clinical judgement even in the absence of a history of trauma.

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.