Citations

AbstractBackgroundHepatectomy is standard treatment for colorectal liver metastases; however, it is unclear whether liver metastases from other primary cancers should be resected or not. The Japanese Society of Hepato‐Biliary‐Pancreatic Surgery therefore created clinical practice guidelines for the management of metastatic liver tumors.MethodsEight primary diseases were selected based on the number of hepatectomies performed for each malignancy per year. Clinical questions were structured in the population, intervention, comparison, and outcomes (PICO) format. Systematic reviews were performed, and the strength of recommendations and the level of quality of evidence for each clinical question were discussed and determined. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was used to assess evidence and make recommendations.ResultsThe eight primary sites were grouped into five categories based on suggested indications for hepatectomy and consensus of the guidelines committee. Fourteen clinical questions were devised, covering five topics: (1) diagnosis, (2) operative treatment, (3) ablation therapy, (4) the eight primary diseases, and (5) systemic therapies. The grade of recommendation was strong for one clinical question and weak for the other 13 clinical questions. The quality of the evidence was moderate for two questions, low for 10, and very low for two.A flowchart was made to summarize the outcomes of the guidelines for the indications of hepatectomy and systemic therapy.ConclusionsThese guidelines were developed to provide useful information based on evidence in the published literature for the clinical management of liver metastases, and they could be helpful for conducting future clinical trials to provide higher‐quality evidence.

BACKGROUND: Colorectal cancer seldom presents at the splenic flexure. Small series on left flexure tumors reported a high occurrence of negative prognostic factors called into question as causes of poor prognosis. However, because of the small number of cases, no definite conclusions can be drawn. OBJECTIVE: The aim of this study was to compare clinical-pathologic characteristics and short- and long-term outcomes of left flexure tumors with other colonic locations. DESIGN: This was a retrospective analysis of consecutive patients who underwent surgery for tumors at the splenic flexure. Each tumor was paired in a 1 to 1 fashion with a right-sided and sigmoid tumor. SETTINGS: The study was conducted in 10 international centers. PATIENTS: A total of 641 patients with left flexure tumors were included in the study. MAIN OUTCOME MEASURES: Overall survival and cancer-specific survival were measured. RESULTS: Left flexure tumors presented more frequently with stenosis (30.5%; p < 0.001), with lesions infiltrating beyond the serosa (21.9%; p = 0.001) and with a high rate of mucinous histology (8.8%; p = 0.001). Looking at long-term prognosis, no differences were observed among the 3 groups, both considering overall and cancer-specific survival. However, left flexure tumors recurred more frequently as peritoneal carcinomatosis (20.6%; p < 0.001). LIMITATIONS: This study was limited because of its retrospective nature. CONCLUSIONS: Although left flexure tumors display several negative prognostic factors, they are not characterized by a worse prognosis compared with other colon cancer locations. See Video Abstract at http://links.lww.com/DCR/B395. CARACTERÍSTICAS CLÍNICO-PATOLÓGICAS Y RESULTADOS A LARGO PLAZO DEL CÁNCER DE COLON DE ÁNGULO IZQUIERDO: UN ANÁLISIS RETROSPECTIVO DE UNA COHORTE MULTICÉNTRICA INTERNACIONAL ANTECEDENTES: El cáncer colorrectal rara vez se presenta en el ángulo esplénico. Pequeñas series sobre tumores de ángulo izquierdo informaron una alta incidencia de factores pronósticos negativos cuestionados como causas de mal pronóstico. Sin embargo, debido al pequeño número de casos, no se pueden sacar conclusiones definitivas. OBJETIVO: El objetivo de este estudio fue comparar las características clínico-patológicas, los resultados a corto y largo plazo de los tumores de ángulo izquierdo con otras ubicaciones de colon. DISEÑO: Análisis retrospectivo de pacientes consecutivos que se sometieron a cirugía por tumores en el ángulo esplénico. Cada tumor se emparejó de forma individual con un tumor del lado derecho y sigmoide. AJUSTES: El estudio se realizó en 10 centros internacionales. PACIENTES: Se incluyeron en el estudio un total de 641 pacientes con tumores del ángulo izquierdo. PRINCIPALES MEDIDAS DE RESULTADO: Supervivencia general y específica del cáncer RESULTADOS: Los tumores de ángulo izquierda se presentaron con mayor frecuencia con estenosis (30.5%, p <0.001), con lesiones infiltradas más allá de la serosa (21.9%, p = 0.001), y con una alta tasa de histología mucinosa (8.8%, p = 0.001). En cuanto al pronóstico a largo plazo, no se observaron diferencias entre los tres grupos, considerando la supervivencia general y específica del cáncer. Sin embargo, los tumores de ángulo izquierdo recurrieron con mayor frecuencia como carcinomatosis peritoneal (20,6%; p <0,001). LIMITACIONES: Este estudio fue limitado debido a su naturaleza retrospectiva. CONCLUSIONES: Aunque los tumores de ángulo izquierdo muestran varios factores pronósticos negativos, no se caracterizan por un peor pronóstico en comparación con otras ubicaciones de cáncer de colon. Consulte Video Resumen en http://links.lww.com/DCR/B395.

AbstractBackgroundPersistent loss of skeletal muscle mass and function as well as altered fat metabolism are frequently observed in severe sepsis survivors. Studies examining sepsis‐associated tissue dysfunction from the perspective of the tissue microenvironment are scarce. In this study, we comprehensively assessed transcriptional changes in muscle and fat at single‐cell resolution following experimental sepsis induction.MethodsSkeletal muscle and visceral white adipose tissue from control mice or mice 1 day or 1 month following faecal slurry‐induced sepsis were used. Single cells were mechanically and enzymatically prepared from whole tissue, and viable cells were further isolated by fluorescence activated cell sorting. Droplet‐based single‐cell RNA‐sequencing (scRNA‐seq; 10× Genomics) was used to generate single‐cell gene expression profiles of thousands of muscle and fat‐resident cells. Bioinformatics analyses were performed to identify and compare individual cell populations in both tissues.ResultsIn skeletal muscle, scRNA‐seq analysis classified 1438 single cells into myocytes, endothelial cells, fibroblasts, mesenchymal stem cells, macrophages, neutrophils, T‐cells, B‐cells, and dendritic cells. In adipose tissue, scRNA‐seq analysis classified 2281 single cells into adipose stem cells, preadipocytes, endothelial cells, fibroblasts, macrophages, dendritic cells, B‐cells, T‐cells, NK cells, and gamma delta T‐cells. One day post‐sepsis, the proportion of most non‐immune cell populations was decreased, while immune cell populations, particularly neutrophils and macrophages, were highly enriched. Proportional changes of endothelial cells, neutrophils, and macrophages were validated using faecal slurry and cecal ligation and puncture models. At 1 month post‐sepsis, we observed persistent enrichment/depletion of cell populations and further uncovered a cell‐type and tissue‐specific ability to return to a baseline transcriptomic state. Differential gene expression analyses revealed key genes and pathways altered in post‐sepsis muscle and fat and highlighted the engagement of infection/inflammation and tissue damage signalling. Finally, regulator analysis identified gonadotropin‐releasing hormone and Bay 11‐7082 as targets/compounds that we show can reduce sepsis‐associated loss of lean or fat mass.ConclusionsThese data demonstrate persistent post‐sepsis muscle and adipose tissue disruption at the single‐cell level and highlight opportunities to combat long‐term post‐sepsis tissue wasting using bioinformatics‐guided therapeutic interventions.

BACKGROUND: Restorative total proctocolectomy with IPAA may not be feasible in some patients because of technical intraoperative limitations. OBJECTIVE: This study aimed to assess preoperative predictors for intraoperative IPAA and review management. DESIGN: This is a retrospective review. SETTING: This study was conducted at Cleveland Clinic between January 2010 and May 2018. PATIENTS: Patients ≥18 years of age who underwent ileoanal pouch surgery were included. Patients with successful pouch creation as planned were grouped as “successful IPAA creation.” Operative reports of patients who underwent alternative procedures were reviewed to identify cases when the pouch was preoperatively planned but intraoperatively abandoned (IPAA-abandoned group). Multivariate logistic regression models were developed to determine predictors of intraoperative pouch abandonment. We also reviewed the management of patients in whom the initial pouch creation failed. MAIN OUTCOME MEASURES: The primary outcomes measured were preoperative predictors for intraoperative ileoanal pouch abandonment. RESULTS: A total of 1438 patients were offered an ileoanal pouch; 21 (1.5%) experienced pouch abandonment due to inadequate reach (n = 17) and other technical reasons (n = 4). These patients underwent alternative procedures such as end or loop ileostomy with/without proctectomy. Multivariate logistic regression analysis indicated male sex (OR, 6.021; 95% CI, 1.540–23.534), BMI (OR, 1.217; 95% CI, 1.114–1.329), and a 2-stage procedure (OR, 14.510; 95% CI, 4.123–51.064) as independent factors associated with intraoperative abandonment of pouch creation. Alternative procedures were total proctocolectomy with end ileostomy (n = 14) and total abdominal colectomy with end ileostomy without proctectomy (n = 7). Ultimately, pouch creation was achieved in 6 of 21 patients after a median interval of 8.8 (range, 4.1–34.8) months. All patients had intentional weight loss before a reattempt and total abdominal colectomy with end ileostomy without proctectomy as their initial procedure. LIMITATIONS: This study was limited by its retrospective nature. CONCLUSIONS: Ileoanal pouch abandonment is rare and can be mitigated by initial total abdominal colectomy and weight loss. Male, obese patients are at a higher risk of failure. Intraoperative assessment of ileoanal pouch feasibility should occur before rectal dissection. See Video Abstract at http://links.lww.com/DCR/B156. PREDICCIÓN MULTIVARIANTE DEL ABANDONO INTRAOPERATORIO DE LA ANASTOMOSIS ANAL CON BOLSA ILEAL ANTECEDENTES: La proctocolectomía total restaurativa con anastomosis de bolsa ileoanal puede no ser posible en algunos pacientes debido a limitaciones técnicas intraoperatorias. OBJETIVO: Evaluar los predictores preoperatorios para el abandono intraoperatorio de la bolsa ileoanal y revisar el manejo. DISEÑO: Revisión retrospectiva. MARCO: Cleveland Clinic entre Enero de 2010 y mayo de 2018. PACIENTES: Pacientes > 18 años que se sometieron a cirugía de bolsa ileoanal. Los pacientes con una creación exitosa de la bolsa según lo planeado se agruparon como “creación exitosa de anastomosis de bolsa ileoanal”. Se revisaron los informes operativos de los pacientes que se sometieron a procedimientos alternativos para identificar los casos en que la bolsa se planificó preoperatoriamente pero se abandonó intraoperatoriamente (grupo de “anastomosis anal de bolsa ileoanal abandonada”). Se desarrollaron modelos de regresión logística multivariante para determinar los predictores del abandono intraoperatorio de la bolsa. También revisamos el manejo de pacientes que fallaron en la creación inicial de la bolsa. MEDIDAS DE RESULTADOS PRINCIPALES: Predictores preoperatorios para el abandono intraoperatorio de la bolsa ileoanal. RESULTADOS: A un total de 1438 pacientes se les ofreció una bolsa ileoanal; 21 (1.5%) experimentaron abandono de la bolsa debido a un alcance inadecuado (n = 17) y otras razones técnicas (n = 4). Estos pacientes se sometieron a procedimientos alternativos como ileostomía final o de asa con / sin proctectomía. El análisis de regresión logística multivariante indicó género masculino (OR, 6.021; IC 95%, 1.540–23.534), índice de masa corporal (OR, 1.217; IC 95%, 1.114–1.329) y procedimiento en 2 etapas (OR, 14.510; IC 95%, 4.123–51.064) como factores independientes asociados con el abandono intraoperatorio de la creación de la bolsa. Los procedimientos alternativos fueron la proctocolectomía total con ileostomía final (n = 14) y la colectomía abdominal total con ileostomía final sin proctectomía (n = 7). Finalmente, la creación de la bolsa se logró en 6/21 pacientes después de un intervalo medio de 8.8 (rango, 4.1–34.8) meses. Todos los pacientes tuvieron pérdida de peso intencional antes de la reintenta y colectomía abdominal total con ileostomía final sin proctectomía como procedimiento inicial. LIMITACIONES: Naturaleza retrospectiva. CONCLUSIONES: El abandono de la bolsa ileoanal es raro y puede mitigarse mediante la colectomía abdominal total inicial y la pérdida de peso. Los pacientes masculinos y obesos tienen un mayor riesgo de fracaso. La evaluación intraoperatoria de la viabilidad de la bolsa ileoanal debe ocurrir antes de la disección rectal. Consulte Video Resumen en http://links.lww.com/DCR/B156. (Traducción—Dr. Yesenia Rojas-Kahlil)

Obesity is a serious health concern and is associated with a reduced quality of life and a number of chronic diseases, including diabetes, heart disease, stroke, and cancer. With obesity rates on the rise worldwide, adipose tissue biology has become a top biomedical research priority. Despite steady growth in obesity-related research, more investigation into the basic biology of adipose tissue is needed to drive innovative solutions aiming to curtail the obesity epidemic. Adipose progenitor cells (APCs) play a central role in adipose tissue homeostasis and coordinate adipose tissue expansion and remodeling. Although APCs are well studied, defining and characterizing APC subsets remains ambiguous because of ill-defined cellular heterogeneity within this cellular compartment. In this study, we used single-cell RNA sequencing to create a cellular atlas of APC heterogeneity in mouse visceral adipose tissue. Our analysis identified two distinct populations of adipose tissue–derived stem cells (ASCs) and three distinct populations of preadipocytes (PAs). We identified novel cell surface markers that, when used in combination with traditional ASC and preadipocyte markers, could discriminate between these APC subpopulations by flow cytometry. Prospective isolation and molecular characterization of these APC subpopulations confirmed single-cell RNA sequencing gene expression signatures, and ex vivo culture revealed differential expansion/differentiation capabilities. Obese visceral adipose tissue featured relative expansion of less mature ASC and PA subpopulations, and expression analyses revealed major obesity-associated signaling alterations within each APC subpopulation. Taken together, our study highlights cellular and transcriptional heterogeneity within the APC pool, provides new tools to prospectively isolate and study these novel subpopulations, and underscores the importance of considering APC diversity when studying the etiology of obesity.

Goals: The study aimed to compare the level and characteristics of disease-related knowledge of patients with inflammatory bowel disease (IBD) between the West and the East using an international version of a questionnaire regarding knowledge of inflammatory bowel disease (IBD-KNOW). Background: The authors recently developed a new questionnaire regarding IBD-KNOW, which showed excellent test characteristics in Korea. Study: The IBD-KNOW questionnaire was administered to 100 patients with IBD from tertiary referral hospitals in the United States and Korea. Scores were calculated and compared between US and Korean patients, and factors associated with high scores were analyzed. Results: A total of 196 (100 US and 96 Korean) patients with IBD completed the questionnaires. Analysis of the baseline characteristics revealed that male sex, smoking status, disease duration, history of IBD-related operations, family history of IBD, and use of corticosteroids or biologics were significantly different between US and Korean patients. The mean IBD-KNOW score was higher in US patients than in Korean patients (14.8 vs. 11.3; P<0.001). Multivariate analyses showed that a high IBD-KNOW score (top 25%) was associated with a positive family history of IBD (odds ratio, 2.90; P=0.025) in US patients with IBD and with the use of biologics (odds ratio, 3.65; P=0.008) in Korean patients with IBD. Conclusions: The IBD-KNOW questionnaire, an updated assessment tool of IBD-related knowledge, is simple, reliable, and available in various patient populations. IBD-KNOW can be used to identify the factors affecting the level of IBD-related knowledge to improve the quality of care in patients with IBD through a personalized approach.

Objective: The aim of this study was to develop and externally validate the first evidence-based guidelines on minimally invasive pancreas resection (MIPR) before and during the International Evidence-based Guidelines on Minimally Invasive Pancreas Resection (IG-MIPR) meeting in Miami (March 2019). Summary Background Data: MIPR has seen rapid development in the past decade. Promising outcomes have been reported by early adopters from high-volume centers. Subsequently, multicenter series as well as randomized controlled trials were reported; however, guidelines for clinical practice were lacking. Methods: The Scottisch Intercollegiate Guidelines Network (SIGN) methodology was used, incorporating these 4 items: systematic reviews using PubMed, Embase, and Cochrane databases to answer clinical questions, whenever possible in PICO style, the GRADE approach for assessment of the quality of evidence, the Delphi method for establishing consensus on the developed recommendations, and the AGREE-II instrument for the assessment of guideline quality and external validation. The current guidelines are cosponsored by the International Hepato-Pancreato-Biliary Association, the Americas Hepato-Pancreato-Biliary Association, the Asian-Pacific Hepato-Pancreato-Biliary Association, the European-African Hepato-Pancreato-Biliary Association, the European Association for Endoscopic Surgery, Pancreas Club, the Society of American Gastrointestinal and Endoscopic Surgery, the Society for Surgery of the Alimentary Tract, and the Society of Surgical Oncology. Results: After screening 16,069 titles, 694 studies were reviewed, and 291 were included. The final 28 recommendations covered 6 topics; laparoscopic and robotic distal pancreatectomy, central pancreatectomy, pancreatoduodenectomy, as well as patient selection, training, learning curve, and minimal annual center volume required to obtain optimal outcomes and patient safety. Conclusion: The IG-MIPR using SIGN methodology give guidance to surgeons, hospital administrators, patients, and medical societies on the use and outcome of MIPR as well as the approach to be taken regarding this challenging type of surgery.

ABSTRACT The last decade has seen a sharp increase in the number of scientific publications describing physiological and pathological functions of extracellular vesicles (EVs), a collective term covering various subtypes of cell‐released, membranous structures, called exosomes, microvesicles, microparticles, ectosomes, oncosomes, apoptotic bodies, and many other names. However, specific issues arise when working with these entities, whose size and amount often make them difficult to obtain as relatively pure preparations, and to characterize properly. The International Society for Extracellular Vesicles (ISEV) proposed Minimal Information for Studies of Extracellular Vesicles (“MISEV”) guidelines for the field in 2014. We now update these “MISEV2014” guidelines based on evolution of the collective knowledge in the last four years. An important point to consider is that ascribing a specific function to EVs in general, or to subtypes of EVs, requires reporting of specific information beyond mere description of function in a crude, potentially contaminated, and heterogeneous preparation. For example, claims that exosomes are endowed with exquisite and specific activities remain difficult to support experimentally, given our still limited knowledge of their specific molecular machineries of biogenesis and release, as compared with other biophysically similar EVs. The MISEV2018 guidelines include tables and outlines of suggested protocols and steps to follow to document specific EV‐associated functional activities. Finally, a checklist is provided with summaries of key points.

AbstractBackgroundLaparoscopic pancreaticoduodenectomy (LPD) requires sufficient laparoscopic training for optimal outcomes. Our aim is to determine the learning curve and investigate the factors influencing surgical outcomes during the learning curve.MethodsWe analyzed surgical results of 150 consecutive cases of LPD performed by three hepatopancreatobiliary surgeons during their 50 first cases. Learning curves were constructed by cumulative sum (CUSUM) analysis. Preoperative factors influencing resection time and blood loss were investigated in the introductory and stable periods.Results The learning curve could be divided into three phases: initial (1–20 cases), plateau (21–30), and stable (31–50). Resection time with lymph node dissection was significantly longer during the introductory period (initial and plateau periods) (P < 0.01) but not the stable phase (P = 0.51). Multivariate analysis revealed that patients with pancreatitis had longer resection times and massive blood loss in both the introductory and stable periods (stable phase). High visceral fat area was also significantly related to massive blood loss in the introductory period (P = 0.04).ConclusionsHepatopancreatobiliary surgeons need more than 30 cases until LPD becomes stable. Lymph node dissection and patients with high visceral fat area and concomitant pancreatitis should be avoided during the introductory period of the learning curve.