Low-fat/high-fibre diet prehabilitation improves anastomotic healing via the microbiome: an experimental model.

BACKGROUND: Both obesity and the presence of collagenolytic bacterial strains (Enterococcus faecalis) can increase the risk of anastomotic leak. The aim of this study was to determine whether mice chronically fed a high-fat Western-type diet (WD) develop anastomotic leak in association with altered microbiota, and whether this can be mitigated by a short course of standard chow diet (SD; low fat/high fibre) before surgery. METHODS: Male C57BL/6 mice were assigned to either SD or an obesogenic WD for 6 weeks followed by preoperative antibiotics and colonic anastomosis. Microbiota were analysed longitudinally after operation and correlated with healing using an established anastomotic healing score. In reiterative experiments, mice fed a WD for 6 weeks were exposed to a SD for 2, 4 and 6 days before colonic surgery, and anastomotic healing and colonic microbiota analysed. RESULTS: Compared with SD-fed mice, WD-fed mice demonstrated an increased risk of anastomotic leak, with a bloom in the abundance of Enterococcus in lumen and expelled stool (65-90 per cent for WD versus 4-15 per cent for SD; P = 0·010 for lumen, P = 0·013 for stool). Microbiota of SD-fed mice, but not those fed WD, were restored to their preoperative composition after surgery. Anastomotic healing was significantly improved when WD-fed mice were exposed to a SD diet for 2 days before antibiotics and surgery (P < 0·001). CONCLUSION: The adverse effects of chronic feeding of a WD on the microbiota and anastomotic healing can be prevented by a short course of SD in mice. Surgical relevance Worldwide, enhanced recovery programmes have developed into standards of care that reduce major complications after surgery, such as surgical-site infections and anastomotic leak. A complementary effort termed prehabilitation includes preoperative approaches such as smoking cessation, exercise and dietary modification. This study investigated whether a short course of dietary prehabilitation in the form of a low-fat/high-fibre composition can reverse the adverse effect of a high-fat Western-type diet on anastomotic healing in mice. Intake of a Western-type diet had a major adverse effect on both the intestinal microbiome and anastomotic healing following colonic anastomosis in mice. This could be reversed when mice received a low-fat/high-fibre diet before operation. Taken together, these data suggest that dietary modifications before major surgery can improve surgical outcomes via their effects on the intestinal microbiome.

ANTECEDENTES: Tanto la obesidad como la presencia de cepas bacterianas colagenolíticas (Enterococcus faecalis) pueden aumentar el riesgo de fuga anastomótica. El objetivo de este estudio fue determinar si los ratones alimentados durante un tiempo prolongado con una dieta de tipo occidental con alto contenido en grasas (western type diet, WD) desarrollaban una fuga anastomótica en asociación con una microbiota alterada, así como determinar si una dieta estándar preoperatoria de corta duración baja en grasa/alta en fibra (standard diet, SD) podía mitigar la aparición de fuga. MÉTODOS: Ratones machos C57BL/6 obtenidos de Charles River fueron asignados aleatoriamente a una dieta chow estándar (SD) o a una dieta de tipo occidental obesogénica (WD) durante 6 semanas, seguida de la administración preoperatoria de antibióticos y la realización de una anastomosis en el colon. La microbiota se analizó longitudinalmente después de la operación y se correlacionó con la curación utilizando una puntuación de cicatrización anastomótica ya establecida. En experimentos repetidos, los ratones con una WD durante 6 semanas fueron expuestos a una SD durante 2, 4 y 6 días antes de la cirugía de colon, analizándose la cicatrización de la anastomosis y la microbiota del colon. RESULTADOS: Los ratones alimentados con WD en comparación con los alimentados con SD presentaron un mayor riesgo de fuga anastomótica con un rápido incremento en la abundancia de Enterococcus (65-90% para WD versus 4-15% para SD, P < 0,01). La microbiota de ratones alimentados con SD, pero no con WD, se restableció a su composición preoperatoria después de la operación. La cicatrización anastomótica mejoró significativamente cuando los ratones alimentados con WD fueron expuestos a una dieta SD durante 2 días antes del tratamiento antibiótico y de la cirugía (P < 0,01). CONCLUSIÓN: En ratones, los efectos adversos de una alimentación crónica con una WD sobre la microbiota y la cicatrización anastomótica se pueden prevenir mediante una SD de corta duración.

Bowel preparation under siege.

An analysis of the results and conclusions from the most recent RCTs of the role of mechanical bowel preparation before colonic surgery is presented. The results indicate a wide disparity in the methods, results and conclusion of these studies, and the lack of microbial culture confirmation to advance understanding of how to move the field forward. Controversy on bowel preparation in colorectal surgery.

Novel de novo synthesized phosphate carrier compound ABA-PEG20k-Pi20 suppresses collagenase production in Enterococcus faecalis and prevents colonic anastomotic leak in an experimental model.

BACKGROUND: Previous work has demonstrated that anastomotic leak can be caused by collagenolytic bacteria such as Enterococcus faecalis via an effect on wound collagen. In humans, E. faecalis is the organism cultured most commonly from a leaking anastomosis, and is not routinely eliminated by standard oral or intravenous antibiotics. Novel strategies are needed to contain the virulence of this pathogen when present on anastomotic tissues. METHODS: Polyphosphorylated polymer ABA-PEG20k-Pi20 was tested in mice for its ability to prevent anastomotic leak caused by collagenolytic E. faecalis. The study design included a distal colonic resection and anastomosis followed by introduction of E. faecalis to anastomotic tissues via enema. Mice were assigned randomly to receive either ABA-PEG20-Pi20 or its unphosphorylated precursor ABA-PEG20k in their drinking water. The development of anastomotic leak was determined after the animals had been killed. RESULTS: Overnight incubation of two different E. faecalis collagenolytic strains with 2 mmol/l of ABA-PEG20k-Pi20 led to near complete inhibition of collagenase production (from 21 000 to 1000 and from 68 000 to 5000 units; P < 0·001; 6 samples per group) without suppressing bacterial growth. In mice drinking 1 per cent ABA-PEG20k-Pi20, the phosphate concentration in the distal colonic mucosa increased twofold and leak rates decreased from eight of 15 to three of 15 animals (P < 0·001). In mice drinking ABA-PEG20k-Pi20, the percentage of collagenolytic colonies among E. faecalis populations present at anastomotic tissue sites was decreased by 6-4800-fold (P = 0·008; 5 animals). CONCLUSION: These data indicate that oral intake of ABA-PEG20k-Pi20 may be an effective agent to contain the virulence of E. faecalis and may prevent anastomotic leak caused by this organism. Clinical relevance Progress in understanding the pathogenesis of anastomotic leak continues to point to intestinal bacteria as key causative agents. The presence of pathogens such as Enterococcus faecalis that predominate on anastomotic tissues despite antibiotic use, coupled with their ability to produce collagenase, appears to alter the process of healing that leads to leakage. Further antibiotic administration may seem logical, but carries the unwanted risk of eliminating the normal microbiome, which functions competitively to exclude and suppress the virulence of pathogens such as E. faecalis. Therefore, non-antibiotic strategies that can suppress the production of collagenase by E. faecalis without affecting its growth, or potentially normal beneficial microbiota, may have unique advantages. The findings of this study demonstrate that drinking a phosphate-based polymer can achieve the goal of preventing anastomotic leak by suppressing collagenase production in E. faecalis without affecting its growth.

Gut microbiome influences on anastomotic leak and recurrence rates following colorectal cancer surgery.

BACKGROUND: The pathogenesis of colorectal cancer recurrence after a curative resection remains poorly understood. A yet-to-be accounted for variable is the composition and function of the microbiome adjacent to the tumour and its influence on the margins of resection following surgery. METHODS: PubMed was searched for historical as well as current manuscripts dated between 1970 and 2017 using the following keywords: 'colorectal cancer recurrence', 'microbiome', 'anastomotic leak', 'anastomotic failure' and 'mechanical bowel preparation'. RESULTS: There is a substantial and growing body of literature to demonstrate the various mechanisms by which environmental factors act on the microbiome to alter its composition and function with the net result of adversely affecting oncological outcomes following surgery. Some of these environmental factors include diet, antibiotic use, the methods used to prepare the colon for surgery and the physiological stress of the operation itself. CONCLUSION: Interrogating the intestinal microbiome using next-generation sequencing technology has the potential to influence cancer outcomes following colonic resection.

The natural history of anal transition zone inflammation and possible relationship to pouchitis: a long-term longitudinal study.

AIM: Reservoir ileitis (pouchitis) is the most common complication after pelvic pouch surgery for ulcerative colitis and the aetiology remains largely unknown. The anal transition zone (ATZ) contains the only remaining colonic epithelium after ileal pouch anal anastomosis (IPAA) and may provide important clues as to whether ulcerative colitis and pouchitis share a common pathogenesis. The aim of this study was to evaluate longitudinally the long-term histological changes in the ATZ and their relationship to the incidence of pouchitis. METHOD: Patients with a double-stapled IPAA for ulcerative colitis at an academic medical centre with at least 10 years of clinical and histological follow-up were identified from a prospective database. Annual ATZ and pouch biopsies were taken and interpreted by two expert gastrointestinal pathologists. ATZ histological variability score, the incidence of pouchitis, and function were correlated over time. ATZ biopsies were scored from one to three based on the extent of inflammation. RESULTS: Sixteen of the 114 patients having IPAA fulfilled the criteria for admission to the study. There were 179 biopsies of the ATZ. All exhibited variability in ATZ histology over time and 81% had a 2-unit change in their inflammatory score. There was no correlation between pouchitis and histological severity score of the ATZ. Similarly, function over time did not vary with the intensity of ATZ inflammation. CONCLUSION: ATZ inflammation varies substantially over time in most patients. But these changes from year to year did not correlate with function or the occurrence of pouchitis.

Minimally invasive colon resection for malignant colonic conditions is associated with a transient early increase in plasma sVEGFR1 and a decrease in sVEGFR2 levels after surgery.

INTRODUCTION: Plasma VEGF levels increase after minimally invasive colorectal resection (MICR) and remain elevated for 2-4 weeks. VEGF induces physiologic and pathologic angiogenesis by binding to endothelial cell (EC) bound VEGF-Receptor-1 (VEGFR1) and VEGFR2. Soluble forms of these receptors sequester plasma VEGF, decreasing the amount available to bind to EC-bound receptors. Ramifications of surgery-related plasma VEGF changes partially depend on plasma levels of sVEGFR1 and sVEGFR2. This study assessed perioperative sVEGFR1 and sVEGFR2 levels after MICR in patients with colorectal cancer. METHODS: Forty-five patients were studied; blood samples were taken from all patients preoperatively (preop) and on postoperative days (POD) 1 and 3; in most a fourth sample was drawn between POD 7-30. Late samples were bundled into two time points: POD 7-13 and POD 14-30. sVEGFR1 and sVEGFR2 levels were measured via ELISA. sVEGFR2 data are reported as mean +/- SD and were assessed with the paired samples t test. sVEGFR1 data were not normally distributed. They are reported as median and 95% confidence interval (CI) and were assessed with the Wilcoxon signed-Rank test (p < 0.05). RESULTS: Preoperatively, the mean plasma sVEGFR2 level (7583.9 pg/ml) was greater than the sVEGFR1 result (98.3 pg/ml). Compared with preop levels, sVEGFR2 levels were significantly lower on POD 1 (6068.2 pg/ml, +/-2034.5) and POD 3 (6227.6 pg/ml, +/-2007.0), whereas sVEGFR1 levels were significantly greater on POD 1 (237.5 pg/ml; 95% CI, 89.6-103.5), POD 3 (200.2 pg/ml; 95% CI, 159-253), and POD 7-13 (102.9 pg/ml; 95% CI, 189.7-253). No differences were found on POD 7-13 for sVEGFR2 or POD 14-30 for either protein. CONCLUSIONS: sVEGFR2 values decreased and sVEGFR1 levels increased early after MICR; sVEGFR2 changes dominate due to their much larger magnitude. The net result is less plasma VEGF bound by soluble receptors and more plasma VEGF available to bind to ECs early after surgery.

The number of lymph nodes in colon cancer specimens: what do the numbers really mean?

AIM: Stage-specific survival for colon cancer is improved when more lymph nodes are identified in the surgical specimen. This association is typically attributed to staging effect, but may instead be a surrogate for tumour biology. METHOD: We retrospectively studied a cohort of 48 consecutively treated patients with Stage II colon cancer who underwent complete resection between January 2000 and December 2002. Archived H&E slides were reviewed for lymphocytic infiltration at the leading edge, presence and degree of sinus histiocytosis in the largest node and the presence of lymph node hyperplasia. RESULTS: The mean number of lymph nodes identified was 14.1 +/- 9.4. T stage was strongly associated with the number of nodes identified (P = 0.01) and the presence of a significant degree of sinus histiocytosis approached statistical significance (P = 0.077). No statistically significant relationship existed between number of lymph nodes in a specimen and tumour location (P = 0.44), grade (P = 0.56) or lymphovascular invasion (P = 0.64). CONCLUSIONS: T stage is highly associated with the number of nodes found in a colon cancer specimen; a significant degree of sinus histiocytosis may also be predictive. Finding more nodes may be a surrogate for tumour or host-related factors that impact prognosis.

Minimally invasive colon resection is associated with a transient increase in plasma sVEGFR1 levels and a decrease in sVEGFR2 levels during the early postoperative period.

INTRODUCTION: Plasma vascular endothelial growth factor (VEGF) levels are elevated for 2-4 weeks after minimally invasive colorectal resection (MICR). VEGF induces wound and tumor angiogenesis by binding to endothelial cell (EC)-bound VEGF-receptor 1 (VEGFR1) and VEGFR2. Soluble receptors (sVEGFR1, sVEGFR2) sequester VEGF in the blood and decrease VEGF's proangiogenic effect. The importance of the MICR-related VEGF changes depends on the effect of surgical procedures on sVEGFR1 and sVEGFR2; this study assessed levels of these proteins after MICR for benign indications. METHODS: Blood samples were taken (n=39) preoperatively (preop) and on postoperative days (POD) 1 and 3; in most cases a fourth sample was drawn between POD 7 and 30. sVEGFR1 and sVEGFR2 levels were measured via enzyme-linked immunosorbent assay (ELISA), which detects free and VEGF bound soluble receptor. Late samples were bundled into POD 7-13 and POD 14-30 time points. Results are reported as mean and standard deviation. The data was assessed with paired-samples t-test. RESULTS: Preop, mean plasma sVEGFR2 level (9,203.7+/-1,934.3 pg/ml) was significantly higher than the sVEGFR1 value (132.5+/-126.2 pg/ml). sVEGFR2 levels were significantly lower on POD 1 (6,957.8+/-1,947.7 pg/ml,) and POD 3 (7,085.6+/-2,000.2 pg/ml), whereas sVEGFR1 levels were significantly higher on POD 1 (220.0+/-132.8 pg/ml) and POD 3 (182.7+/-102.1 pg/ml) versus preop results. No differences were found on POD 7-13 or 14-30. CONCLUSIONS: sVEGFR2 values decreased and sVEGFR1 levels increased early after MICR; due to its much higher baseline, the sVEGFR2 changes dominate. The net result is less VEGF bound to soluble receptor and more free plasma VEGF.

Managing anastomotic leaks from intestinal anastomoses.

A leaking intestinal anastomosis is typically regarded as a devastating post-operative complication. The reported incidence ofanastomotic leakage is highly variable and depends on the definitions used and the anatomical location involved. Early leaks are usually readily diagnosed and aggressive management is warranted. Late leaks may be unrecognised and are likely to be underreported in the literature; diagnosis and treatment in this setting requires a thoughtful, individualised approach.

Posterior spinal ligament rupture associated with laryngeal mask insertion in a patient with undisclosed unstable cervical spine.

A case of posterior spinal ligament rupture associated with a general anaesthetic for a laparoscopic cholecystectomy is reported. The role of the general anaesthetic in this case is discussed and a review of the literature is presented.

Ganglioneuromatous polyposis: a premalignant condition. Report of a case and review of the literature.

A 40-year-old man with ganglioneuromatous polyposis and an aggressive coexisting colorectal cancer is described. Contrary to previous reports, we believe that ganglioneuromatous polyposis should be considered a premalignant condition.