Spatial proteogenomics reveals distinct and evolutionarily conserved hepatic macrophage niches.

The liver is the largest solid organ in the body, yet it remains incompletely characterized. Here we present a spatial proteogenomic atlas of the healthy and obese human and murine liver combining single-cell CITE-seq, single-nuclei sequencing, spatial transcriptomics, and spatial proteomics. By integrating these multi-omic datasets, we provide validated strategies to reliably discriminate and localize all hepatic cells, including a population of lipid-associated macrophages (LAMs) at the bile ducts. We then align this atlas across seven species, revealing the conserved program of bona fide Kupffer cells and LAMs. We also uncover the respective spatially resolved cellular niches of these macrophages and the microenvironmental circuits driving their unique transcriptomic identities. We demonstrate that LAMs are induced by local lipid exposure, leading to their induction in steatotic regions of the murine and human liver, while Kupffer cell development crucially depends on their cross-talk with hepatic stellate cells via the evolutionarily conserved ALK1-BMP9/10 axis.

Bariatric surgery post-liver transplantation: A Belgian nationwide study.

Weight gain poses a rising concern post-liver transplantation (LT), and metabolic dysfunction-associated steatotic liver disease might impair graft health. The timing is crucial when considering bariatric surgery (BS) in a population with liver disease or transplantation. BS can be considered for post-LT weight gain, although the evidence is limited and the long-term outcome still uncertain. We conducted a national retrospective analysis in 5 Belgian transplant centers and included 25 patients with an LT followed by a bariatric procedure. A total of 187 LT patients without BS were included for comparison. Clinical, biochemical, and outcome data were retrospectively retrieved. In our nationwide cohort, 25 patients had undergone BS post-LT, at a median 3.5 years after LT. Twenty-one (84.0%) patients received a sleeve gastrectomy (SG). Patients were predominantly male (72.0%), with a lower age at time of transplantation compared with the non-BS population (54.5 vs. 60.6, p <0.001). Weight loss was significant and sustained, with a decrease in body mass index from 41.0±4.5 pre-BS to 32.6±5.8 1-3 years post-BS ( p <0.001) and 31.1±5.8 3-5 years post-BS ( p <0.001). Three pre-BS (12.0%) patients presented with recurrent and one (4.0%) de novo metabolic dysfunction-associated steatotic liver disease after LT, with 100% resolution post-BS ( p =0.016). Notable reductions were observed in alanine transaminase levels (40.5±28.5 U/L to 27.1±25.1 U/L post-BS, p =0.05) and HbA1c levels (6.9±1.6 to 6.0±1.4 post-BS, p <0.001). Three patients were re-transplanted, and eight patients died, of which five (20.0%) due to a nonhepatic malignancy and one (4.0%) due to liver failure. SG is the favored BS post-LT and has proven to be safe and feasible in a post-LT setting with favorable metabolic consequences. SG post-LT is a valid treatment for de novo and recurrent metabolic dysfunction-associated steatotic liver disease post-LT. Although we report on the largest cohort to date, there is still a need for larger cohorts to examine the effect of BS on patient and graft survival.

Patients hospitalized with alcohol-related liver disease and prior bariatric surgery are more prone to develop acute-on-chronic liver failure.

BACKGROUND & AIMS: Patients with a history of bariatric surgery (BS) are susceptible to developing alcohol use disorder. We and others have previously shown that these patients can develop severe alcohol-related liver disease (ARLD). Our aim was to describe the demographics, co-morbidities and mortality of a hospitalized population diagnosed with alcohol-related liver disease, in relation to BS. METHODS: We included 299 patients hospitalized with ARLD at the Ghent University Hospital between 1 January 2018 and 31 December 2022. Clinical, biochemical and outcome data were retrospectively retrieved from the most recent hospitalization. Statistical analysis was performed using the t test, Mann-Whitney U and χ2 tests. RESULTS: Thirteen per cent (39/299) of patients admitted with ARLD had a history of bariatric surgery, of whom 25 (64.1%) had undergone Roux-en-Y gastric bypass. Patients with a history of BS were predominantly female (76.9%), in contrast to the non-BS population (29.2%) (p < .0001), and despite being significantly younger (p < .0001) and had a similar survival (61.5% vs. 58.1%). Bariatric surgery and older age at diagnosis were both significantly associated with poorer transplant-free survival. The cause of death was acute-on-chronic liver failure in 73.3% of BS patients, compared to only 19.2% of those without a history of BS (p < .0001). The weekly amount of alcohol consumed (p = .012) and duration of use (p < .0001) were significantly lower/shorter in the BS population. CONCLUSIONS: BS patients hospitalized with ARLD are predominantly younger women with a lower cumulative alcohol consumption compared to those without prior BS. BS impacted transplant-free survival, with ACLF as the predominant cause of death in these patients.

Intervention pathways for low anterior resection syndrome after sphincter-saving rectal cancer surgery: A systematic scoping review.

AIM: Low anterior resection syndrome (LARS) has a large impact on patients' quality of life. Several heterogeneous intervention pathways are suggested in the literature. The steps and timing of the different steps in the pathways are unclear. This systematic scoping review aims to map the range of intervention pathways for LARS after sphincter-saving rectal cancer surgery. METHODS: A search was undertaken on four databases (CINAHL, EMBASE, PubMed, and Web of Science). Any type of paper describing intervention pathways for patients with LARS following sphincter-saving surgery was included. Excluded were patients with a stoma, no full paper, no intervention pathway and not being written in English or Dutch. The review was registered with Open Science Framework (10.17605/OSF.IO/JB5H8). Narrative synthesis of the results was performed by charting and summarising key results. RESULTS: A total of 373 records were screened and 12 papers were included. There was a high variability among the intervention pathways, including which patients should be included. The number of pathway steps ranged from 2-6. Most intervention pathways were treatment-led. Intervention options ranged from conservative measures to a permanent stoma. Pathway flow was highly variable and sometimes not well described, with different or no timings provided for the start, progression, or end of the pathways. Three studies discussed the use of a nurse to coordinate the pathway. CONCLUSION: This systematic scoping review shows that despite similarities in treatment options there are variations in which treatments are included, when treatments should be instigated, and even which patients should be treated.

Information and counselling needs of patients with major low anterior resection syndrome: A qualitative study.

AIMS AND OBJECTIVES: The aim was to explore the information and counselling needs of rectal cancer survivors confronted with major low anterior resection syndrome. BACKGROUND: Rectal cancer survivors are often confronted with bowel problems after surgery. This is called low anterior resection syndrome. Patients are unsure what to expect after treatment and healthcare professionals often underestimate the impact of low anterior resection syndrome on patients' lives. DESIGN: A qualitative study with a grounded theory approach was conducted. METHODS: Patients were recruited between 2017 and 2019 in three hospitals, and a call was distributed in two patients' organisations. Semi-structured interviews with patients confronted with major low anterior resection syndrome were performed. An iterative process between data collection and data analysis was used. Data analysis was done using the constant comparative method, and investigators' triangulation was applied. Qualitative data were reported following COREQ guidelines. The study was registered at Clinicaltrials.gov NCT04896879. RESULTS: A total of 28 patients were interviewed until theoretical data saturation. Before surgery patients' need for information varied according to their individual coping mechanisms. Some patients required information before surgery, while others considered this too overwhelming. When confronted with LARS, patients desired that healthcare professionals recognised its impact and clarified its expected evolution. A proactive counselling with an easy accessible and approachable healthcare professional was beneficial. CONCLUSION: Patients expressed several needs regarding the information before rectal cancer surgery and counselling of low anterior resection syndrome after surgery. RELEVANCE TO CLINICAL PRACTICE: Better knowledge and understanding of major low anterior resection syndrome and its challenges by healthcare professionals are crucial. Especially the impact on quality of life is significant for patients and underestimated by healthcare professionals. Information before surgery and counselling when confronted with major low anterior resection syndrome should be optimised and tailored to patients' needs.

A rare complication of laparoscopic Roux-en-Y gastric bypass: case report of gastric remnant necrosis.

Gastric remnant necrosis is a very rare, but potential life-threatening complication after laparoscopic Roux-en-Y gastric bypass (LRYGB). We report a case of gastric remnant necrosis that was complicated by peritonitis and resulted in septic shock in a 49-year-old woman who had undergone a LRYGB three months prior to admission. An emergent laparoscopy with subtotal gastrectomy was performed. The patient was treated for septic shock and could leave the hospital in a good condition. Potential etiological factors for gastric remnant necrosis were elaborated.

Interprofessional perspectives on care for patients with low anterior resection syndrome: A qualitative study.

AIM: Many patients are confronted with low anterior resection syndrome after rectal surgery. The perspectives of both healthcare professionals and patients on the impact of bowel problems may differ. This study aimed to explore experiences of healthcare professionals on how to provide, organise and optimise care for patients with low anterior resection syndrome from an interprofessional perspective. METHODS: An explorative qualitative design was used. Healthcare professionals were recruited in October 2018 in one general teaching hospital and one university hospital. Twenty one healthcare professionals from different professions caring for patients with low anterior resection syndrome were included in three focus group interviews. RESULTS: Healthcare professionals confirmed a lack of focus on patients who are confronted with low anterior resection syndrome and stated a need for a standardised approach of care. Additionally, three levels for care optimization emerged from the data: information before surgery with strong emphasis on the timing of informing, counselling of patients when confronted with low anterior resection syndrome and organisation of care. CONCLUSIONS: Healthcare professionals find it important to adopt the moment and amount of information to the coping mechanism and timing of the trajectory. Counselling and follow-up of patients with LARS should be organised proactively and should not remain restricted to pharmacological and nutritional advice. A possible strategy is to develop and implement late effects nurse-led clinics coordinated by the clinical nurse specialist.

Patient-reported outcomes after pelvic exenteration for colorectal cancer: A systematic review.

AIM: Pelvic exenteration (PE) carries high morbidity. Our aim was to analyse the use of patient-reported outcome measures (PROMs) in PE patients. METHOD: Search strategies were protocolized and registered in PROSPERO. PubMed, Embase, Cochrane Library, Google Scholar, Web of Science and ClinicalTrials.gov were searched with the terms 'patient reported outcomes', 'pelvic exenteration' and 'colorectal cancer'. Studies published after 1980 reporting on PROMs for at least 10 PE patients were considered. Study selection, data extraction, rating of certainty of evidence (GRADE) and risk of bias (ROBINS-I) were performed independently by two reviewers. RESULTS: Nineteen of 173 studies were included (13 retrospective, six prospective). All studies were low to very low quality, with an overall moderate/serious risk of bias. Studies included data on 878 patients with locally advanced rectal cancer (n = 344), recurrent rectal cancer (n = 411) or cancer of unknown type (n = 123). Thirteen studies used validated questionnaires, four used non-validated measures and two used both. Questionnaires included the Functional Assessment of Cancer Therapy-Colorectal questionnaire (n = 6), Short Form Health Survey (n = 6), European Organization for Research and Treatment for Cancer (EORTC) Quality of Life Questionnaire C30 (n = 6), EORTC-CR38 (n = 4), EORTC-BLM30 (n = 1), Brief Pain Inventory (n = 2), Short Form 12 (n = 1), Assessment of Quality of Life (n = 1), Short Form Six-Dimension (n = 1), the Memorial Sloan Kettering Cancer Center Sphincter Function Scale (n = 1), the Cleveland Global Quality of Life (n = 1) or other (n = 4). Timing varied between studies. CONCLUSIONS: Whilst the use of validated questionnaires increased over time, this study shows that there is a need for uniform use and timing of PROMs to enable multicentre studies.

Clinical utility of near-infrared perfusion assessment of the gastric tube during Ivor Lewis esophagectomy.

BACKGROUND: Anastomotic leakage (AL) after Ivor Lewis esophagectomy with intrathoracic anastomosis carries a significant morbidity. Adequate perfusion of the gastric tube (GT) is an important predictor of anastomotic integrity. Recently, near infrared fluorescent (NIRF) imaging using indocyanine green (ICG) was introduced in clinical practice to evaluate tissue perfusion. We evaluated the feasibility and efficacy of GT indocyanine green angiography (ICGA) after Ivor Lewis esophagectomy. METHODS: This retrospective analysis used data from a prospectively kept database of consecutive patients who underwent Ivor Lewis (IL) esophagectomy with GT construction for cancer between January 2016 and December 2020. Relevant outcomes were feasibility, ICGA complications and the impact of ICGA on AL. RESULTS: 266 consecutive IL patients were identified who matched the inclusion criteria. The 115 patients operated with perioperative ICGA were compared to a control group in whom surgery was performed according to the standard of care. ICGA perfusion assessment was feasible and safe in all 115 procedures and suggested a poorly perfused tip in 56/115 (48.7%) cases, for which additional resection was performed. The overall AL rate was 16% (43/266), with 12% (33/266) needing an endoscopic our surgical intervention and 6% (17/266) needing ICU support. In univariable and multivariable analyses, ICGA was not correlated with the risk of AL (ICGA:14.8% vs non-ICGA:17.2%, p = 0.62). However, poor ICGA perfusion of the GT predicted a higher AL rate, despite additional resection of the tip (ICGA poorly perfused: 19.6% vs ICG well perfused: 10.2%, p = 0.19). CONCLUSIONS: ICGA is safe and feasible, but did not result in a reduction of AL. The interpretation and necessary action in case of perioperative presence of ischemia on ICGA have yet to be determined. Prospective randomized trials are warranted to analyze its benefit on AL in esophageal surgery. Trial registration Ethical approval for a prospective esophageal surgery database was granted by the Ethical committee of the Ghent University Hospital. Belgian registration number: B670201111232. Ethical approval for this retrospective data analysis was granted by our institutional EC. REGISTRATION NUMBER: BC-09216.

Divergent dynamics in systemic and tissue-specific metabolic and inflammatory responses during weight loss in subjects with obesity.

AIM: Dysfunction of adipose and muscle tissue associates with obesity-related co-morbidities such as insulin resistance (IR) and inflammation. This study investigates changes in systemic and tissue-specific markers of IR and inflammation after gastric bypass surgery (GBS) in subjects with obesity. METHODS: Prospective study, twenty subjects with obesity (50 ± 10 years, 14 men). Prior to, and six months and one year after GBS, subcutaneous abdominal adipose tissue (SAT), skeletal muscle and fasting serum samples were collected. Serum levels of C-reactive protein (CRP), glucose and insulin were determined using standard laboratory assays and serum IL-6, IL-10 and TNF-α levels were determined using ELISA. Tissue mRNA expression of inflammation and insulin/glucose metabolism markers were analyzed using qPCR. RESULTS: After GBS, HOMA-IR, CRP and IL-6 serum levels decreased. In SAT, expression of bone morphogenetic protein 4 (BMP4), IL-6, IL-10 and MCP1 decreased and GLUT4 increased (all p < 0.05). In muscle, expression of BMP4, GLUT4 and IL-6 decreased and of MCP1 and IRS-1 increased (all p < 0.05). CONCLUSION: Systemic improvements in inflammation and IR after GBS are only partially mirrored by corresponding changes in adipokine and myokine expression patterns. As changes in expression of other markers of inflammation and insulin/glucose metabolism appear less consistent and even divergent between tissues, the inflammatory and IR status at systemic level cannot be extrapolated to the situation in metabolically active tissues.

Physiological Disturbance in Fatty Liver Energy Metabolism Converges on IGFBP2 Abundance and Regulation in Mice and Men.

Fatty liver occurs from simple steatosis with accumulated hepatic lipids and hepatic insulin resistance to severe steatohepatitis, with aggravated lipid accumulation and systemic insulin resistance, but this progression is still poorly understood. Analyses of hepatic gene expression patterns from alb-SREBP-1c mice with moderate, or aP2-SREBP-1c mice with aggravated, hepatic lipid accumulation revealed IGFBP2 as key nodal molecule differing between moderate and aggravated fatty liver. Reduced IGFBP2 expression in aggravated fatty liver was paralleled with promoter hypermethylation, reduced hepatic IGFBP2 secretion and IGFBP2 circulating in plasma. Physiologically, the decrease of IGFBP2 was accompanied with reduced fatty acid oxidation and increased de novo lipogenesis potentially mediated by IGF1 in primary hepatocytes. Furthermore, methyltransferase and sirtuin activities were enhanced. In humans, IGFBP2 serum concentration was lower in obese men with non-alcoholic fatty liver disease (NAFLD) and steatohepatitis (NASH) compared to non-obese controls, and liver fat reduction by weight-loss intervention correlated with an increase of IGFBP2 serum levels. In conclusion, hepatic IGFBP2 abundance correlates to its circulating level and is related to hepatic energy metabolism and de novo lipogenesis. This designates IGFBP2 as non-invasive biomarker for fatty liver disease progression and might further provide an additional variable for risk prediction for pathogenesis of fatty liver in diabetes subtype clusters.

Is the Human Brain Capable of Controlling Seven Degrees of Freedom?

BACKGROUND: Conventional rigid laparoscopic instruments offer five degrees of freedom (DOF). Robotic instruments add two independent DOFs allowing unconstrained directional steering. Several nonrobotic instruments have been developed with the additional DOFs, but with these devices, surgeon's wrist movements are not intuitively transmitted into tip movements. In this study, a new articulated instrument has been evaluated. The aim of the study was to compare learning curves and performances of conventional laparoscopic instruments, the da Vinci system and Steerable devices in a crossover study. MATERIALS AND METHODS: A total of 16 medical students without any laparoscopic experience were trained for 27 h to operate all of a rigid, a robotic, and a new Steerable instrument in a random order. Learning curves and ultimate experience scores were determined for each instrument. Strain in wrist and shoulders was assessed with a visual analog score. RESULTS: Performing the suturing task with rigid and robot instruments required 4 h of training, compared with 6 h to master the Steerable instrument. After 9 h of training with each instrument, completing the complex suturing pattern required 662 ± 308 s with rigid instruments, 279 ± 90 s with the da Vinci system, and 279 ± 53 s with the Steerable instrument. Pain scores were significantly higher after using the rigid instruments compared with the Steerable instruments. CONCLUSIONS: Transmission of torque and the presence of additional two DOFs in combination with reduced crosstalk significantly improved the instrument dexterity where the Steerable platform is concerned. Although the learning curve is longer, once mastered, it provides enhanced surgical freedom.

Articulated Instruments and 3D Visualization: A Synergy? Evaluation of Execution Time, Errors, and Visual Fatigue.

Objective. The introduction of advanced endoscopic systems, such as the Storz Image1S and the Olympus Endoeye, heralds a new era of 3-dimensional (3D) visualization. The aim of this report is to provide a comprehensive overview of the neurophysiology of 3D view, its relevance in videoscopy, and to quantify the benefit of the new 3D technologies for both rigid and articulated instruments. Method. Sixteen medical students without any laparoscopic experience were trained each for a total of 27 hours. Proficiency scores were determined for rigid and articulated instruments under 2D and 3D visualization conditions. Results. A reduction in execution time of 14%, 28%, and 36% was seen for the rigid instruments, the da Vinci, and Steerable instruments, respectively. A reduction in errors of 84%, 92%, and 87% was seen for the rigid instruments, the da Vinci, and Steerable instruments, respectively. Conclusion. 3D visualization greatly augments endoscopic procedures. The advanced endoscopic systems employed in the recent study caused no visual fatigue or discomfort. The benefit of 3D was most distinct with articulated instruments.

Intraoperative radiation therapy for rectal cancer and recurrent intra-abdominal sarcomas.

PURPOSE: The aim of this study was to evaluate the effect of high-dose-rate intraoperative radiation therapy (HDR-IORT) in a multimodality treatment on the local control (LC) and the overall survival (OS) rate in locally advanced rectal cancer (LARC), locally recurrent rectal cancer (LRRC) and recurrent intra-abdominal sarcomas (RS). MATERIALS AND METHODS: A retrospective analysis was performed on 27 patients who were treated with radical resection and HDR-IORT between April 2007 and January 2017. Patient, tumor and surgical characteristics were analyzed and the perioperative (<30 days) and long-term complications (>30 days) were assessed and graded. RESULTS: None of the patients with LARC (n = 4) developed a local recurrence and all patients were still alive at the end of the follow-up. The LC rates of LRRC (n = 17) after one and three years were respectively 48% and 40% and the one, three and five years OS were respectively 93%, 62% and 44%. For RS (n = 6), the LC rates after one and three years were both 33% and the one and three years OS rate were respectively 83% and 46%. CONCLUSIONS: The results of our study show that HDR-IORT could be a valuable asset in the multimodality management of LARC, LRRC and RS.

The novel adipokine WISP1 associates with insulin resistance and impairs insulin action in human myotubes and mouse hepatocytes.

AIMS/HYPOTHESIS: Wingless-type (Wnt) inducible signalling pathway protein-1 (WISP1) has been recently identified as a proinflammatory adipokine. We examined whether WISP1 expression and circulating levels are altered in type 2 diabetes and whether WISP1 affects insulin signalling in muscle cells and hepatocytes. METHODS: Serum and visceral adipose tissue (VAT) biopsies, for analysis of circulating WISP1 levels by ELISA and WISP1 mRNA expression by real-time quantitative RT-PCR, were collected from normal-weight men (control group, n = 33) and obese men with (n = 46) and without type 2 diabetes (n = 56) undergoing surgery. Following incubation of primary human skeletal muscle cells (hSkMCs) and murine AML12 hepatocytes with WISP1 and insulin, insulin signalling was analysed by western blotting. The effect of WISP1 on insulin-stimulated glycogen synthesis and gluconeogenesis was investigated in hSkMCs and murine hepatocytes, respectively. RESULTS: Circulating WISP1 levels were higher in obese men (independent of diabetes status) than in normal-weight men (mean [95% CI]: 70.8 [55.2, 86.4] ng/l vs 42.6 [28.5, 56.6] ng/l, respectively; p < 0.05). VAT WISP1 expression was 1.9-fold higher in obese men vs normal-weight men (p < 0.05). Circulating WISP1 levels were positively associated with blood glucose in the OGTT and circulating haem oxygenase-1 and negatively associated with adiponectin levels. In hSkMCs and AML12 hepatocytes, recombinant WISP1 impaired insulin action by inhibiting phosphorylation of insulin receptor, Akt and its substrates glycogen synthase kinase 3ß, FOXO1 and p70S6 kinase, and inhibiting insulin-stimulated glycogen synthesis and suppression of gluconeogenic genes. CONCLUSIONS/INTERPRETATION: Circulating WISP1 levels and WISP1 expression in VAT are increased in obesity independent of glycaemic status. Furthermore, WISP1 impaired insulin signalling in muscle and liver cells.

CDH13 abundance interferes with adipocyte differentiation and is a novel biomarker for adipose tissue health.

BACKGROUND: CDH13, an atypical member of the cadherin superfamily, has been identified in adipocyte secretomes of lean mouse models. CDH13 abundance differs in mouse models according to their susceptibility to develop metabolic disorders, but the role of CDH13 in adipose tissue is unknown. METHODS: Secreted CDH13 protein levels and mRNA levels in visceral adipose tissue were determined in lean and obese mouse models. In vitro studies were performed in 3T3-L1 adipocytes to determine the role of CDH13 in adipocyte differentiation. The pathophysiological impact of visceral adipose tissue CDH13 mRNA and circulating CDH13 levels were determined in humans (normal-weight men n = 37, obese men n = 109 including n = 51 type 2 diabetes patients) and in obese patients (n = 14) pre- and post-metabolic surgery. RESULTS: This study shows that in visceral adipose tissue CDH13 protein secretion and mRNA levels were decreased in obese mouse models. Mechanistically, CDH13 affects lipid metabolism during adipogenesis but not in mature adipocytes. CDH13 knockdown during adipogenesis reduced fatty acid uptake and lipid content in developing adipocytes. Furthermore, CDH13 depletion during adipogenesis lowered the induction of PPARγ and C/EBPα expression. These observations are of pathophysiological impact since visceral adipose tissue CDH13 mRNA and circulating CDH13 levels were decreased in obese men compared to normal-weight controls. Weight loss induced by bariatric surgery restored circulating CDH13 to levels found in normal-weight controls. CONCLUSIONS: CDH13 levels in adipose tissue and the circulation are affected by obesity in mouse models and humans and are restored by weight loss in humans. CDH13 interferes with the differentiation potential of adipocytes and therefore is a marker for plasticity of fat tissue that might reflect the health status of adipose tissue.

Long-term survival after multimodality therapy including surgery for metastatic esophageal cancer.

BACKGROUND AND OBJECTIVES: Esophageal cancer (EC) remains an aggressive disease with a poor survival. Management of metastatic EC is limited to palliative chemotherapy (CT). Scientific contributions regarding the role of surgery are scarce and controversial. We analysed outcome of surgically treated metastatic EC patients. METHODS: We retrospectively identified surgically treated metastatic EC patients from our esophagectomy database. The aim of this study was to evaluate surgical complications, pathological response, oncological outcome and mean survival of these aggressively treated stage IV cancer patients. RESULTS: Twelve stage IV patients with disease presentation limited to outfield lymph node (LN) and/or liver metastasis were treated with an aggressive multimodality treatment including surgery. Mean age was 58 years (75% male, 75% Adenocarcinomas). Median postoperative hospital stay was 15 d. Radiological anastomotic leakage occurred in one patient. In hospital, mortality was nil. Complete resection was achieved in all but one. Metastatic recurrence occurred in 64% of R0 resected patients. At date of censoring, after a median follow-up of 22 months, 50% of the surgical resected patients are still alive and 33% are free of disease recurrence. Kaplan-Meier curves show a possibility to long-term survival after aggressive multimodality therapy including surgery. CONCLUSIONS: In selected metastatic EC patients, multimodality treatment including surgery has an acceptable surgical outcome with a potentially long-term survival.

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

BACKGROUND: 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. METHODS: Data were used from the Belgian PROCARE rectal cancer registry. The effect of abdominopelvic infection on survival was assessed in uni- and multivariable Cox regression models. The effect of clinical and pathological covariates was controlled by propensity score-based matching of cases with controls. The effect of abdominopelvic sepsis on the rate of local and metastatic recurrence was evaluated using crosstabulation and the Pearson χ2 test. RESULTS: In univariable analysis, the presence of APS was associated with significantly worse overall survival (HR 1.3, P = 0.025). After propensity score matching including age, BMI, tumor level, pTstage, pN stage, CRM, tumor grade, number of lymph nodes, and presence of lymphovascular invasion, the association of APS with OS was no longer significant (HR 1.26, 95%CI 0.92-1.74, P = 0.15). No differences were observed in the risk of local or metastatic recurrence (3.6% vs 2.9% and 13% vs 16.5%). CONCLUSIONS: In this analysis APS after rectal cancer resection was not significantly associated with OS, metastatic, or local recurrence.

Functional outcome after Ivor Lewis esophagectomy for cancer.

BACKGROUND: Little is known on functional outcome after Ivor Lewis esophagectomy (ILE) with intrathoracic anastomosis. METHODS: Patients who underwent ILE were identified from a prospective database. Clinicopathological data were retrieved and compared with functional outcome data based on patient self-assessment by a standard questionnaire. Predictive factors for selected functional complaints were identified with logistic regression analyses. RESULTS: Three hundred and twenty-two patients (80.4% male, mean age 62 years) were studied. Indications for surgery were adenocarcinoma (62.4%), squamous cell carcinoma (28%), and HG Barrett dysplasia (7%). Preoperative chemoradiation (CRT) was administered to 42.5% of patients. Anastomotic leakage occurred in 5.6% and was associated with higher age and diabetes mellitus. Functional symptoms identified were reflux (39%), delayed gastric emptying (37%), dumping (21.4%), and anastomotic stenosis (16%). In the multivariate models, anastomotic stenosis was associated with smaller stapler diameter and presence of esophagitis. Postoperative reflux was associated with higher BMI, whereas dumping was predicted by female gender and age. The quality of life questionnaires revealed a good general health status in 82% of the patients. CONCLUSIONS: Functional complaints after ILE consist of reflux, delayed gastric emptying, dumping, and dysphagia, and are affected by age, gender, BMI, diabetes mellitus, and stapler diameter.

AURORA: bariatric surgery registration in women of reproductive age - a multicenter prospective cohort study.

BACKGROUND: The expansion of the obesity epidemic is accompanied with an increase in bariatric procedures, in particular in women of reproductive age. The weight loss induced by the surgery is believed to reverse the negative impact of overweight and obesity on female reproduction, however, research is limited to in particular retrospective cohort studies and a growing number of small case-series and case-(control) studies. METHODS/DESIGN: AURORA is a multicenter prospective cohort study. The main objective is to collect long-term data on reproductive outcomes before and after bariatric surgery and in a subsequent pregnancy. Women aged 18-45 years are invited to participate at 4 possible inclusion moments: 1) before surgery, 2) after surgery, 3) before 15 weeks of pregnancy and 4) in the immediate postpartum period (day 3-4). Depending on the time of inclusion, data are collected before surgery (T1), 3 weeks and 3, 6, 12 or x months after surgery (T2-T5) and during the first, second and third trimester of pregnancy (T6-T8), at delivery (T9) and 6 weeks and 6 months after delivery (T10-T11). Online questionnaires are send on the different measuring moments. Data are collected on contraception, menstrual cycle, sexuality, intention of becoming pregnant, diet, physical activity, lifestyle, psycho-social characteristics and dietary supplement intake. Fasting blood samples determine levels of vitamin A, D, E, K, B-1, B-12 and folate, albumin, total protein, coagulation parameters, magnesium, calcium, zinc and glucose. Participants are weighted every measuring moment. Fetal ultrasounds and pregnancy course and complications are reported every trimester of pregnancy. Breastfeeding is recorded and breast milk composition in the postpartum period is studied. DISCUSSION: AURORA is a multicenter prospective cohort study extensively monitoring women before undergoing bariatric surgery until a subsequent pregnancy and postpartum period. TRIAL REGISTRATION: Retrospectively registered (July 2015 - NCT02515214 ).