Dirk Van de Putte

How to assess intestinal viability during surgery: A review of techniques

Objective and quantitative intraoperative methods of bowel viability assessment are essential in gastrointestinal surgery. Exact determination of the borderline of the viable bowel with the help of an objective test could result in a decrease of postoperative ischemic complications. An accurate, reproducible and cost effective method is desirable in every operating theater dealing with abdominal operations. Numerous techniques assessing various parameters of intestinal viability are described by the studies. However, there is no consensus about their clinical use. To evaluate the available methods, a systematic search of the English literature was performed. Virtues and drawbacks of the techniques and possibilities of clinical application are reviewed. Valuable parameters related to postoperative intestinal anastomotic or stoma complications are analyzed. Important issues in the measurement and interpretation of bowel viability are discussed. To date, only a few methods are applicable in surgical practice. Further studies are needed to determine the limiting values of intestinal tissue oxygenation and flow indicative of ischemic complications and to standardize the methods.

Anastomotic complications after Ivor Lewis esophagectomy in patients treated with neoadjuvant chemoradiation are related to radiation dose to the gastric fundus.

PURPOSE Neoadjuvant chemoradiation (CRT) is increasingly used in locally advanced esophageal cancer. Some studies have suggested that CRT results in increased surgical morbidity. We assessed the influence of CRT on anastomotic complications in a cohort of patients who underwent CRT followed by Ivor Lewis esophagectomy. PATIENTS AND METHODS Clinical and pathologic data were collected from all patients treated with neoadjuvant CRT (36 Gy combined with 5-fluorouracil and cisplatin) followed by Ivor Lewis esophagectomy. On the radiotherapy (RT) planning computed tomography scans, normal tissue volumes were drawn encompassing the proximal esophageal region and the gastric fundus. Within these volumes, dose-volume histograms were analyzed to generate the total dose to 50% of the volume (D(50)). We studied the ability of the D(50) to predict anastomotic complications (leakage, ischemia, or stenosis). Dose limits were derived using receiver operating characteristics analysis. RESULTS Fifty-four patients were available for analysis. RT resulted in either T or N downstaging in 51% of patients; complete pathologic response was achieved in 11%. In-hospital mortality was 5.4%, and major morbidity occurred in 36% of patients. Anastomotic complications (AC) developed in 7 patients (13%). No significant influence of the D(50) on the proximal esophagus was noted on the anastomotic complication rate. The median D(50) on the gastric fundus, however, was 33 Gy in patients with AC and 18 Gy in patients without AC (p = 0.024). Using receiver operating characteristics analysis, the D(50) limit on the gastric fundus was defined as 29 Gy. CONCLUSIONS In patients undergoing neoadjuvant CRT followed by Ivor Lewis esophagectomy, the incidence of AC is related to the RT dose on the gastric fundus but not to the dose received by the proximal esophagus. When planning preoperative RT, efforts should be made to limit the median dose on the gastric fundus to 29 Gy with a V(30) below 40%.

Lymphatic spread, nodal count and the extent of lymphadenectomy in cancer of the colon

In colon cancer, the biological significance of lymphatic tumour spread remains a matter of debate, which impacts on related questions such as the ideal extent of lymphadenectomy and the prognostic significance of lymph node counts. Several lines of evidence suggest that metastasis to locoregional nodes occurs early and is a stochastic, rather than a stepwise phenomenon, and in essence reflects the tumour-host-metastasis relationship. Not surprisingly, therefore, several clinical trials failed to identify a survival benefit from extensive lymphadenectomy compared to standard resection. The recently described complete mesocolic excision technique, which aims to improve survival by maximizing nodal clearance, should be subjected to a prospective randomized trial. There has been a fairly consistent and intriguing relation between nodal counts and survival in colon cancer. Therapeutic effects of more extensive removal of invaded nodes seem an unlikely explanation for the observed association. Similarly, several findings argue against stage migration as the only or even the most important explanation. The available literature shows an extensive array of factors confounding the nodal count-survival relationship, which are correlated to the patients clinical characteristics, pathology variables, and factors relating to the individual (treating surgeon and pathologist) and institutional healthcare levels. More research into the biology of nodal spread and the nodal count-survival relationship is indicated and may have important implications for therapy such as the further introduction of minimally invasive surgery and the identification of novel and potentially modifiable factors impacting on both nodal counts and survival.

Risk factors and consequences of anastomotic leakage after Ivor Lewis oesophagectomy

OBJECTIVES Oesophageal carcinoma (EC) remains an aggressive disease. Despite extensive changes in therapeutic modalities, surgical resection remains the first choice therapy for curable oesophageal cancer patients. Anastomotic sites are prone to serious complications such as leakage, fistula, bleeding and stricture. Leakage of the anastomosis (AL) remains one of the main causes of postoperative morbidity and mortality. The purpose of this study was to identify predictors associated with postoperative leakage after Ivor Lewis oesophagectomy and its consequences in a single centre. METHODS We performed a retrospective analysis of 412 Ivor Lewis oesophageal resections in a single institute between 2005 and 2014. Univariable and multivariable logistic regression have been used to identify predictors of AL and its impact on postoperative outcome and overall survival. Kaplan-Meier curve was used to analyse overall survival and log-rank analysis to determine odds ratio. RESULTS A total of 412 patients were evaluated. Mean age was 62 ± 11 years (77% male). Overall leak rate was 2.9%. In-hospital or 30-day mortality was 4.4%. Mean intensive care unit (ICU) stay was 1 day and mean hospital stay was 19 days. A history of renal failure, diabetes, higher American Society of Anaesthesiologists score and current cigarette and corticosteroid use were identified as predictors of AL on univariable analysis. Multivariable analysis identified active smoking [P = 0.05, odds ratio (OR) 4.34, 95% confidence interval (CI): 0.98-19.28] and active corticosteroid use (P < 0.001, OR 15.8, 95% CI: 3.25-76.7) as independent significant predictors. A history of diabetes tended to be associated with a higher leakage rate but failed to reach statistical significance. AL was associated with a longer ICU and hospital stay and a significantly higher mortality (42% in the AL group vs 3% in the control group, P < 0.0001). CONCLUSIONS Anastomotic leakage after oesophagectomy is a major cause of postoperative morbidity and mortality. Identifying risk factors preoperatively can contribute to the prevention of postoperative complications.

N-glycan based biomarker distinguishing non-alcoholic steatohepatitis from steatosis independently of fibrosis

BACKGROUND Non-alcoholic fatty liver disease is a spectrum of disorders ranging from steatosis to non-alcoholic steatohepatitis (NASH). Steatosis of the liver is benign, whereas NASH can progress to cirrhosis or even hepatocellular carcinoma. Currently, a liver biopsy is the only validated method to distinct NASH from steatosis. AIM The objective of this study was to identify a biomarker specific for NASH based on the N-glycosylation of serum proteins. METHODS N-glycosylation patterns were assessed using DNA sequencer-assisted fluorophore-assisted capillary electrophoresis and compared with histology. RESULTS Initially, a glycomarker (log[NGA2F]/[NA2]) was developed based on the results obtained in 51 obese non-alcoholic patients scheduled for bariatric surgery. Multivariate analysis showed that our glycomarker had the lowest P-value of all biomarkers in distinguishing NASH from steatosis (P=0.069). The glycomarker was validated in a cohort of 224 non-alcoholic fatty liver disease patients. In both pilot and validation study, glycomarker score increased in ascending amount of lobular inflammation (single-factor ANOVA, P ≤ 0.001 and P=0.012, respectively). The N-glycan profile of immunoglobulin G in the NASH population confirmed the significantly increased undergalactosylation present in these patients. CONCLUSION Our glycomarker specifically recognises liver inflammation in obese individuals which is the main trigger for the development of steatohepatitis and can differentiate between steatosis and NASH.

Life-threatening side effects of malabsorptive procedures in obese patients necessitating conversion surgery: a review of 17 cases.

Abstract Background : malabsorptive surgery (MAS) can cause huge weight loss but is also known for its serious side effects. We investigated whether conversion surgery is an effective treatment for MAS-induced complications. Methods : we searched our hospital database for patients who underwent conversion surgery after MAS. Any complication was recorded till time of conversion. The conversion techniques and their effect on the course of the patients were analyzed and compared to the situation after MAS. Results : we identified 17 patients who suffered a wide range of complications after biliopancreatic diversion (BPD) (n = 11), biliopancreatic diversion with duodenal switch (BPD-DS) (n = 4), or distal gastric bypass (D-GBP) (n = 2). After a (mean ± SD) period of 6.0 ± 3.6 years the MAS was either converted to a gastric bypass (GBP) in 6 patients or an elongation of the common limb (ECL) in 9 patients. Two conversions were atypical. After a (mean ± SD) follow-up of 2.4 ± 2.5 years the majority of blood test results improved. The incidence of most complaints diminished except abdominal discomfort, critical illness polyneuropathy, need for total parenteral nutrition (TPN), wheelchair dependency, and asthenia. One patient died of irreversible liver failure after 3 liver transplantations. Two patients died of cachexia. The preferred conversion technique is still unclear. Conclusions : MAS can cause invalidating and life-threatening side effects. If there are signs of incipient deterioration in organ function and/or nutritional status, conversion surgery should not be delayed. Although we have the impression that early conversion causes better outcome, many patients experience lifelong postoperative complications.

A Joint Mechanism of Action for Sacral Neuromodulation for Bladder and Bowel Dysfunction

Sacral neuromodulation (SNM) is a clinically effective intervention for treatment of urinary and bowel disorders. The aim is to establish the hypothesis that there is a common mechanism of action for SNM in both systems. Current knowledge includes the following: (1) Therapeutic parameters may be different for the 2 efficacy measures. (2) SNM invokes neural circuits that can be observed as neurochemical changes in specific neuroanatomic structures downstream from the therapy delivery site. (3) There are important central nervous system effects for both therapies. (4) Clinical observations regarding normal continence sensations as well as physiological measures of continence are different for the 2 therapy areas.

Peritumoral endothelial indoleamine 2, 3-dioxygenase expression is an early independent marker of disease relapse in colorectal cancer and is influenced by DNA mismatch repair profile

Targeting immune checkpoint molecules has become a major new strategy in the treatment of several cancers. Indoleamine 2,3-dioxygenase (IDO)-inhibitors are a potential next-generation immunotherapy, currently investigated in multiple phase I-III trials. IDO is an intracellular immunosuppressive enzyme and its expression/activity has been associated with worse prognosis in several cancers. The aim of this study was to investigate the expression pattern of IDO in colorectal cancer (CRC). In a cohort of 94 CRC patients, primary tumors (PTs) with corresponding tumor-draining lymph nodes (TDLNs, n = 93) and extranodal/distant metastases (n = 27) were retrospectively analyzed by immunohistochemical staining for IDO, CD8 and Foxp3. 45 MSS and 37 MSI-H tumors were selected to compare IDO expression, as these tumors are considered to have different immunogenicity. A highly consistent expression pattern of IDO was observed in the PT, TDLNs and metastases, indicating that immune resistance may be determined very early in the disease course. IDO was expressed both by tumoral cells and host endothelial cells and these expressions were highly correlated (p < 0.001). IDO expression was observed more frequently in the MSI-H subset compared with the MSS subset (43% vs 22% for tumoral expression (p = 0.042) and 38% vs 16% for endothelial expression (p = 0.021)). Endothelial IDO expression was demonstrated to be a negative prognostic marker for recurrence free survival independent of disease stage and DNA mismatch repair (MMR) status (HR 20.67, 95% CI: 3.05–139.94; p = 0.002). These findings indicate that endothelial IDO expression in primary CRC, in addition to the MMR profile, may be helpful in disease stratification.

Effect of abdominopelvic sepsis on cancer outcome in patients undergoing sphincter saving surgery for rectal cancer

In rectal cancer, the significance of abdominopelvic sepsis (APS) on metastatic tumor growth remains uncertain. We aimed to analyze the effect of abdominopelvic sepsis on long‐term survival in patients undergoing restorative rectal cancer surgery.

Primary intestinal aspergillosis resulting in acute intestinal volvulus after autologous stem cell transplantation in a patient with relapsed non-Hodgkin lymphoma: report on a rare infectious complication and a review of the literature

ABSTRACT Objectives: Since primary intestinal aspergillosis is a severe infectious complication with a high morbidity and mortality in immunocompromised patients, we want to draw attention to this rare entity and the importance of early recognition. Methods: We report a case of documented primary intestinal aspergillosis in a patient receiving an autologous stem cell transplantation (SCT). Furthermore, this article gives a short reflection on the occurrence of invasive aspergillosis in autologous SCT and the value of serum galactomannan levels based on literature search and linked with the case. Results: In this case the patient presented on day +8 after autologous SCT for a relapsed diffuse large B-cell lymphoma with an acute abdomen with urgent need for surgical intervention. Biopsy revealed the presence of fungal colonies due to aspergillosis and voriconazole was started. Until that day the systematically taken serum galactomannan tests were all negative or pending. Initially there was some resistance to perform surgery in the presence of neutropenia and thrombocytopenia but in the end it provided the definitive diagnosis and should not be delayed. Until now this patient is in good health and retains a complete remission. Conclusion: With this case, we would like to emphasize that early recognition of primary intestinal aspergillosis is of the utmost importance as it is a rare but serious infectious complication. It should be included in the differential diagnosis of neutropenic patients with sudden onset abdominal pain and ongoing fever, even in the absence of a positive serum galactomannan.