SAGES/AHPBA guidelines for the use of microwave and radiofrequency liver ablation for the surgical treatment of hepatocellular carcinoma or colorectal liver metastases less than 5 cm.

BACKGROUND: Primary hepatocellular carcinoma (HCC) and colorectal liver metastases (CRLM) represent the liver's two most common malignant neoplasms. Liver-directed therapies such as ablation have become part of multidisciplinary therapies despite a paucity of data. Therefore, an expert panel was convened to develop evidence-based recommendations regarding the use of microwave ablation (MWA) and radiofrequency ablation (RFA) for HCC or CRLM less than 5 cm in diameter in patients ineligible for other therapies. METHODS: A systematic review was conducted for six key questions (KQ) regarding MWA or RFA for solitary liver tumors in patients deemed poor candidates for first-line therapy. Subject experts used the GRADE methodology to formulate evidence-based recommendations and future research recommendations. RESULTS: The panel addressed six KQs pertaining to MWA vs. RFA outcomes and laparoscopic vs. percutaneous MWA. The available evidence was poor quality and individual studies included both HCC and CRLM. Therefore, the six KQs were condensed into two, recognizing that these were two disparate tumor groups and this grouping was somewhat arbitrary. With this significant limitation, the panel suggested that in appropriately selected patients, either MWA or RFA can be safe and feasible. However, this recommendation must be implemented cautiously when simultaneously considering patients with two disparate tumor biologies. The limited data suggested that laparoscopic MWA of anatomically more difficult tumors has a compensatory higher morbidity profile compared to percutaneous MWA, while achieving similar overall 1-year survival. Thus, either approach can be appropriate depending on patient-specific factors (very low certainty of evidence). CONCLUSION: Given the weak evidence, these guidelines provide modest guidance regarding liver ablative therapies for HCC and CRLM. Liver ablation is just one component of a multimodal approach and its use is currently limited to a highly selected population. The quality of the existing data is very low and therefore limits the strength of the guidelines.

TONSL Is an Immortalizing Oncogene and a Therapeutic Target in Breast Cancer.

Study of genomic aberrations leading to immortalization of epithelial cells has been technically challenging due to the lack of isogenic models. To address this, we used healthy primary breast luminal epithelial cells of different genetic ancestry and their hTERT-immortalized counterparts to identify transcriptomic changes associated with immortalization. Elevated expression of TONSL (Tonsoku-like, DNA repair protein) was identified as one of the earliest events during immortalization. TONSL, which is located on chromosome 8q24.3, was found to be amplified in approximately 20% of breast cancers. TONSL alone immortalized primary breast epithelial cells and increased telomerase activity, but overexpression was insufficient for neoplastic transformation. However, TONSL-immortalized primary cells overexpressing defined oncogenes generated estrogen receptor-positive adenocarcinomas in mice. Analysis of a breast tumor microarray with approximately 600 tumors revealed poor overall and progression-free survival of patients with TONSL-overexpressing tumors. TONSL increased chromatin accessibility to pro-oncogenic transcription factors, including NF-κB and limited access to the tumor-suppressor p53. TONSL overexpression resulted in significant changes in the expression of genes associated with DNA repair hubs, including upregulation of several genes in the homologous recombination (HR) and Fanconi anemia pathways. Consistent with these results, TONSL-overexpressing primary cells exhibited upregulated DNA repair via HR. Moreover, TONSL was essential for growth of TONSL-amplified breast cancer cell lines in vivo, and these cells were sensitive to TONSL-FACT complex inhibitor CBL0137. Together, these findings identify TONSL as a regulator of epithelial cell immortalization to facilitate cancer initiation and as a target for breast cancer therapy. SIGNIFICANCE: The chr.8q24.3 amplicon-resident gene TONSL is upregulated during the initial steps of tumorigenesis to support neoplastic transformation by increasing DNA repair and represents a potential therapeutic target for treating breast cancer.

SAGES/AHPBA guidelines for the use of minimally invasive surgery for the surgical treatment of colorectal liver metastases (CRLM).

BACKGROUND: Colorectal liver metastases (CRLM) occur in roughly half of patients with colorectal cancer. Minimally invasive surgery (MIS) has become an increasingly acceptable and utilized technique for resection in these patients, but there is a lack of specific guidelines on the use of MIS hepatectomy in this setting. A multidisciplinary expert panel was convened to develop evidence-based recommendations regarding the decision between MIS and open techniques for the resection of CRLM. METHODS: Systematic review was conducted for two key questions (KQ) regarding the use of MIS versus open surgery for the resection of isolated liver metastases from colon and rectal cancer. Evidence-based recommendations were formulated using the GRADE methodology by subject experts. Additionally, the panel developed recommendations for future research. RESULTS: The panel addressed two KQs, which pertained to staged or simultaneous resection of resectable colon or rectal metastases. The panel made conditional recommendations for the use of MIS hepatectomy for both staged and simultaneous resection when deemed safe, feasible, and oncologically effective by the surgeon based on the individual patient characteristics. These recommendations were based on low and very low certainty of evidence. CONCLUSIONS: These evidence-based recommendations should provide guidance regarding surgical decision-making in the treatment of CRLM and highlight the importance of individual considerations of each case. Pursuing the identified research needs may help further refine the evidence and improve future versions of guidelines for the use of MIS techniques in the treatment of CRLM.

Multi-society consensus conference and guideline on the treatment of gastroesophageal reflux disease (GERD).

BACKGROUND: Gastroesophageal reflux disease (GERD) is one of the most common diseases in North America and globally. The aim of this guideline is to provide evidence-based recommendations regarding the most utilized and available endoscopic and surgical treatments for GERD. METHODS: Systematic literature reviews were conducted for 4 key questions regarding the surgical and endoscopic treatments for GERD in adults: preoperative evaluation, endoscopic vs surgical or medical treatment, complete vs partial fundoplication, and treatment for obesity (body mass index [BMI] ≥ 35 kg/m2) and concomitant GERD. Evidence-based recommendations were formulated using the GRADE methodology by subject experts. Recommendations for future research were also proposed. RESULTS: The consensus provided 13 recommendations. Through the development of these evidence-based recommendations, an algorithm was proposed for aid in the treatment of GERD. Patients with typical symptoms should undergo upper endoscopy, manometry, and pH-testing; additional testing may be required for patients with atypical or extra-esophageal symptoms. Patients with normal or abnormal findings on manometry should consider undergoing partial fundoplication. Magnetic sphincter augmentation or fundoplication are appropriate surgical procedures for adults with GERD. For patients who wish to avoid surgery, the Stretta procedure and transoral incisionless fundoplication (TIF 2.0) were found to have better outcomes than proton pump inhibitors alone. Patients with concomitant obesity were recommended to undergo either gastric bypass or fundoplication, although patients with severe comorbid disease or BMI > 50 should undergo Roux-en-Y gastric bypass for the additional benefits that follow weight loss. CONCLUSION: Using the recommendations an algorithm was developed by this panel, so that physicians may better counsel their patients with GERD. There are certain patient factors that have been excluded from included studies/trials, and so these recommendations should not replace surgeon-patient decision making. Engaging in the identified research areas may improve future care for GERD patients.

Surgical approach to microwave and radiofrequency liver ablation for hepatocellular carcinoma and colorectal liver metastases less than 5 cm: a systematic review and meta-analysis.

BACKGROUND: Primary hepatocellular carcinoma (HCC) and colorectal liver metastases (CRLM) represent the two most common malignant neoplasms of the liver. The objective of this study was to assess outcomes of surgical approaches to liver ablation comparing laparoscopic versus percutaneous microwave ablation (MWA), and MWA versus radiofrequency ablation (RFA) in patients with HCC or CRLM lesions smaller than 5 cm. METHODS: A systematic review was conducted across seven databases, including PubMed, Embase, and Cochrane, to identify all comparative studies between 1937 and 2021. Two independent reviewers screened for eligibility, extracted data for selected studies, and assessed study bias using the modified Newcastle Ottawa Scale. Random effects meta-analyses were subsequently performed on all available comparative data. RESULTS: From 1066 records screened, 11 studies were deemed relevant to the study and warranted inclusion. Eight of the 11 studies were at high or uncertain risk for bias. Our meta-analyses of two studies revealed that laparoscopic MW ablation had significantly higher complication rates compared to a percutaneous approach (risk ratio = 4.66; 95% confidence interval = [1.23, 17.22]), but otherwise similar incomplete ablation rates, local recurrence, and oncologic outcomes. The remaining nine studies demonstrated similar efficacy of MWA and RFA, as measured by incomplete ablation, complication rates, local/regional recurrence, and oncologic outcomes, for both HCC and CRLM lesions less than 5 cm (p > 0.05 for all outcomes). There was no statistical subgroup interaction in the analysis of tumors < 3 cm. CONCLUSION: The available comparative evidence regarding both laparoscopic versus percutaneous MWA and MWA versus RFA is limited, evident by the few studies that suffer from high/uncertain risk of bias. Additional high-quality randomized trials or statistically matched cohort studies with sufficient granularity of patient variables, institutional experience, and physician specialty/training will be useful in informing clinical decision making for the ablative treatment of HCC or CRLM.

Minimally invasive versus open hepatectomy for the resection of colorectal liver metastases: a systematic review and meta-analysis.

BACKGROUND: While surgical resection has a demonstrated utility for patients with colorectal liver metastases (CRLM), it is unclear whether minimally invasive surgery (MIS) or an open approach should be used. This review sought to assess the efficacy and safety of MIS versus open hepatectomy for isolated, resectable CRLM when performed separately from (Key Question (KQ) 1) or simultaneously with (KQ2) the resection of the primary tumor. METHODS: PubMed, Embase, Google Scholar, Cochrane CENTRAL, International Clinical Trials Registry Platform (ICTRP), and ClinicalTrials.gov databases were searched to identify both randomized controlled trials (RCTs) and non-randomized comparative studies published during January 2000-September 2020. Two independent reviewers screened literature for eligibility, extracted data from included studies, and assessed internal validity using the Cochrane Risk of Bias 2.0 Tool and the Newcastle-Ottawa Scale. A random-effects meta-analysis was performed using risk ratios (RR) and mean differences (MD). RESULTS: From 2304 publications, 35 studies were included for meta-analysis. For staged resections, three RCTs and 20 observational studies were included. Data from RCTs indicated MIS having similar disease-free survival (DFS) at 1-year (RR 1.03, 95%CI 0.70-1.50), overall survival (OS) at 5-years (RR 1.04, 95%CI 0.84-1.28), fewer complications of Clavien-Dindo Grade III (RR 0.62, 95%CI 0.38-1.00), and shorter hospital length of stay (LOS) (MD -6.6 days, 95%CI -10.2, -3.0). For simultaneous resections, 12 observational studies were included. There was no evidence of a difference between MIS and the open group for DFS-1-year, OS-5-year, complications, R0 resections, blood transfusions, along with lower blood loss (MD -177.35 mL, 95%CI -273.17, -81.53) and shorter LOS (MD -3.0 days, 95%CI -3.82, -2.17). CONCLUSIONS: Current evidence regarding the optimal approach for CRLM resection demonstrates similar oncologic outcomes between MIS and open techniques, however MIS hepatectomy had a shorter LOS, lower blood loss and complication rate, for both staged and simultaneous resections.

Social support provided to bariatric surgery patients through a facebook group may improve weight loss outcomes.

BACKGROUND: Patients' social support has been shown to impact outcomes after bariatric surgery. We have previously shown that a Facebook group administered by bariatric providers offers an effective alternative social support mechanism to in-person support groups, with higher patient participation. Our aim was to determine whether participation in this Facebook group could improve patient outcomes after bariatric surgery. METHODS: After institutional board approval, our center's Facebook group members were electronically surveyed about their perceived value of group participation and their Facebook group usage frequency. We also collected patient age, sex, insurance, preoperative weight, type of procedure, hospital stay, postoperative complications, and weight loss from the electronic medical record. To assess the impact of Facebook group participation we compared patient outcomes between "frequent users" (those checking the Facebook group's activity at least once a week), "infrequent users", and a control group of all patients operated on during the year prior to the establishment of the Facebook group. The groups were compared after adjusting for potential confounding factors. RESULTS: 250 out of 1400 Facebook group patients responded to the survey (18%). 195 patients were frequent and 55 were infrequent users. Outcomes were compared with 211 control patients. The groups did not differ in their baseline characteristics apart from their sex. Frequent users had a higher weight loss compared to the other groups up to 2 years postoperatively but no difference in the overall complications. On multivariable analysis, frequency of Facebook use was the main factor associated with 0.5-, 1-, and 2-year weight loss. CONCLUSION: Frequent participation in a Facebook support group after bariatric surgery was associated with improved early weight loss outcomes. If additional longer-term studies confirm our findings, offering similar social support groups may become essential after bariatric surgery, especially during times of social isolation when in-person social support meetings may not be feasible.

High-risk bariatric candidates: does red-flagging predict the post-operative course?

BACKGROUND: Standards for preoperative bariatric patient selection include a thorough psychological evaluation. Using patients "red-flagged" during preoperative evaluations, this study aims to identify trends in long-term follow-up and complications to further optimize bariatric patient selection. METHODS: A multidisciplinary team held a case review conference (CRC) to discuss red-flagged patients. A retrospective chart review compared CRC patients to control patients who underwent bariatric surgery in the same interval. Patients under 18 years old, undergoing revisional bariatric surgery, or getting band placement were excluded. High-risk characteristics causing CRC inclusion, preoperative demographics, percent follow-up and other postoperative outcomes were collected up to 5 years postoperatively. If univariate analysis revealed a significant difference between cohorts, multivariable analysis was performed. RESULTS: Two hundred and fifty three patients were red-flagged from 2012 to 2013, of which 79 underwent surgery. After excluding 21 revisions, 3 non-adult patients, and 6 band patients, 55 red-flagged patients were analyzed in addition to 273 control patients. Patient age, sex, initial BMI, ASA, and co-morbidities were similar between groups, though flagged patients underwent RYGB more frequently than control patients. Notably, percent excess BMI loss and percent follow-up (6 months-5 years) were similar. In multivariable analysis, minor complications were more common in flagged patients; and marginal ulcers, endoscopy, and dilation for stenosis were more common in flagged versus control patients who underwent RYGB. Perforation, reoperation, revision, incisional hernia, and internal hernia were statistically similar in both groups, though reoperation was significantly more common in patients with multiple reasons to be flagged compared to controls. CONCLUSION: Bariatric patients deemed high risk for various psychosocial issues have similar follow-up, BMI loss, and major complications compared to controls. High-risk RYGB patients have greater minor complications, warranting additional counseling of high-risk patients.

Postoperative 4-Year Outcomes in Septuagenarians Following Bariatric Surgery.

BACKGROUND: Bariatric surgery is the most effective treatment for obesity; however, its utilization in older patients remains low. There is a dearth of literature on long-term effectiveness and safety of bariatric surgery in septuagenarian patients. The aim of this study was to compare the short- and long-term outcomes of bariatric surgery in this population. METHODS: Patients who underwent primary laparoscopic Roux-en-Y gastric bypass (LRYGB) or laparoscopic sleeve gastrectomy (LSG) at our institution between 2011 and 2015 were included. Patients were divided into two age groups: < 70 and ≥ 70 years. Outcomes included postoperative hospital length of stay (LOS), 30-day complications, up to 4-year complications, 90-day mortality, comorbidity resolution, and 4-year weight loss (BMI change-ΔΒΜΙ). The groups were also compared using multivariable analyses adjusting for potential confounders (gender, preoperative BMI, and type of procedure). RESULTS: Twenty-nine septuagenarians who underwent 21 LRYGB (72.4%) and 8 LSG (27.6%) were compared to 1016 patients aged < 70 years operated on during the same time period. Additionally, following the multivariable analyses, the septuagenarians had higher LOS (3 vs 2.3 days, p = 0.01), 4-year complications (38% vs 23%, p = 0.012), and less comorbidities' resolution but similar 4-year ΔBMI (- 8.6 vs - 10, p = 0.421), and 30-day complications (10% vs 6%, p = 0.316). CONCLUSION: Bariatric surgery in carefully selected septuagenarians can be accomplished with acceptable safety and comparable postoperative weight loss at 4 years. Surgeons may consider broadening their selection criteria to include this patient subgroup but may allow the patients to reap its benefits if offered earlier in life.

Guidelines for the performance of minimally invasive splenectomy.

BACKGROUND: Minimally invasive splenectomy (MIS) is increasingly favored for the treatment of benign and malignant diseases of the spleen over open access approaches. While many studies cite the superiority of MIS in terms of decreased morbidity and length of stay over a traditional open approach, the comparative effectiveness of specific technical and peri-operative approaches to MIS is unclear. OBJECTIVE: To develop evidence-based guidelines that support clinicians, patients, and others in decisions on the peri-operative performance of MIS. METHODS: A guidelines committee panel of the Society of American Gastrointestinal and Endoscopic Surgeons (SAGES) including methodologists used the Grading of Recommendations Assessment, Development and Evaluation approach to grade the certainty of evidence and formulate recommendations. RESULTS: Informed by a systematic review of the evidence, the panel agreed on eight recommendations for the peri-operative performance of MIS for adults and children in elective situations addressing six key questions. CONCLUSIONS: Conditional recommendations were made in favor of lateral positioning for non-hematologic disease, intra-operative platelet administration for patients with idiopathic thrombocytopenic purpura instead of preoperative administration, and the use of mechanical devices to control the splenic hilum. Further, a conditional recommendation was made against routine intra-operative drain placement.

SAGES guidelines for the surgical treatment of gastroesophageal reflux (GERD).

BACKGROUND: Gastroesophageal Reflux Disease (GERD) is an extremely common condition with several medical and surgical treatment options. A multidisciplinary expert panel was convened to develop evidence-based recommendations to support clinicians, patients, and others in decisions regarding the treatment of GERD with an emphasis on evaluating different surgical techniques. METHODS: Literature reviews were conducted for 4 key questions regarding the surgical treatment of GERD in both adults and children: surgical vs. medical treatment, robotic vs. laparoscopic fundoplication, partial vs. complete fundoplication, and division vs. preservation of short gastric vessels in adults or maximal versus minimal dissection in pediatric patients. Evidence-based recommendations were formulated using the GRADE methodology by subject experts. Recommendations for future research were also proposed. RESULTS: The panel provided seven recommendations for adults and children with GERD. All recommendations were conditional due to very low, low, or moderate certainty of evidence. The panel conditionally recommended surgical treatment over medical management for adults with chronic or chronic refractory GERD. There was insufficient evidence for the panel to make a recommendation regarding surgical versus medical treatment in children. The panel suggested that once the decision to pursue surgical therapy is made, adults and children with GERD may be treated with either a robotic or a laparoscopic approach, and either partial or complete fundoplication based on surgeon-patient shared decision-making and patient values. In adults, the panel suggested either division or non-division of the short gastric vessels is appropriate, and that children should undergo minimal dissection during fundoplication. CONCLUSIONS: These recommendations should provide guidance with regard to surgical decision-making in the treatment of GERD and highlight the importance of shared decision-making and patient values to optimize patient outcomes. Pursuing the identified research needs may improve future versions of guidelines for the treatment of GERD.

Is peroral endoscopic myotomy (POEM) more effective than pneumatic dilation and Heller myotomy? A systematic review and meta-analysis.

BACKGROUND: Achalasia is a rare, chronic, and morbid condition with evolving treatment. Peroral endoscopic myotomy (POEM) has gained considerable popularity, but its comparative effectiveness is uncertain. We aim to evaluate the literature comparing POEM to Heller myotomy (HM) and pneumatic dilation (PD) for the treatment of achalasia. METHODS: We conducted a systematic review of comparative studies between POEM and HM or PD. A priori outcomes pertained to efficacy, perioperative metrics, and safety. Internal validity of observational studies and randomized trials (RCTs) was judged using the Newcastle Ottawa Scale and the Cochrane Risk of Bias 2.0 tool, respectively. RESULTS: From 1379 unique literature citations, we included 28 studies comparing POEM and HM (n = 21) or PD (n = 8), with only 1 RCT addressing each. Aside from two 4-year observational studies, POEM follow-up averaged ≤ 2 years. While POEM had similar efficacy to HM, POEM treated dysphagia better than PD both in an RCT (treatment "success" RR 1.71, 95% CI 1.34-2.17; 126 patients) and in observational studies (Eckardt score MD - 0.43, 95% CI - 0.71 to - 0.16; 5 studies; I2 21%; 405 patients). POEM needed reintervention less than PD in an RCT (RR 0.19, 95% CI 0.08-0.47; 126 patients) and HM in an observational study (RR 0.33, 95% CI 0.16, 0.68; 98 patients). Though 6-12 months patient-reported reflux was worse than PD in 3 observational studies (RR 2.67, 95% CI 1.02-7.00; I2 0%; 164 patients), post-intervention reflux was inconsistently measured and not statistically different in measures ≥ 1 year. POEM had similar safety outcomes to both HM and PD, including treatment-related serious adverse events. CONCLUSIONS: POEM has similar outcomes to HM and greater efficacy than PD. Reflux remains a critical outcome with unknown long-term clinical significance due to insufficient data and inconsistent reporting.

Surgical treatment of GERD: systematic review and meta-analysis.

BACKGROUND: Gastroesophageal reflux disease (GERD) has a high worldwide prevalence in adults and children. There is uncertainty regarding medical versus surgical therapy and different surgical techniques. This review assessed outcomes of antireflux surgery versus medical management of GERD in adults and children, robotic versus laparoscopic fundoplication, complete versus partial fundoplication, and minimal versus maximal dissection in pediatric patients. METHODS: PubMed, Embase, and Cochrane databases were searched (2004-2019) to identify randomized control and non-randomized comparative studies. Two independent reviewers screened for eligibility. Random effects meta-analysis was performed on comparative data. Study quality was assessed using the Cochrane Risk of Bias and Newcastle Ottawa Scale. RESULTS: From 1473 records, 105 studies were included. Most had high or uncertain risk of bias. Analysis demonstrated that anti-reflux surgery was associated with superior short-term quality of life compared to PPI (Std mean difference = - 0.51, 95%CI - 0.63, - 0.40, I2 = 0%) however short-term symptom control was not significantly superior (RR = 0.75, 95%CI 0.47, 1.21, I2 = 82%). A proportion of patients undergoing operative treatment continue PPI treatment (28%). Robotic and laparoscopic fundoplication outcomes were similar. Compared to total fundoplication, partial fundoplication was associated with higher rates of prolonged PPI usage (RR = 2.06, 95%CI 1.08, 3.94, I2 = 45%). There was no statistically significant difference for long-term symptom control (RR = 0.94, 95%CI 0.85, 1.04, I2 = 53%) or long-term dysphagia (RR = 0.73, 95%CI 0.52, 1.02, I2 = 0%). Ien, minimal dissection during fundoplication was associated with lower reoperation rates than maximal dissection (RR = 0.21, 95%CI 0.06, 0.67). CONCLUSIONS: The available evidence regarding the optimal treatment of GERD often suffers from high risk of bias. Additional high-quality randomized control trials may further inform surgical decision making in the treatment of GERD.

SAGES guidelines for the use of peroral endoscopic myotomy (POEM) for the treatment of achalasia.

BACKGROUND: Peroral endoscopic myotomy (POEM) is increasingly used as primary treatment for esophageal achalasia, in place of the options such as Heller myotomy (HM) and pneumatic dilatation (PD) OBJECTIVE: These evidence-based guidelines from the Society of American Gastrointestinal and Endoscopic Surgeons (SAGES) intend to support clinicians, patients and others in decisions about the use of POEM for treatment of achalasia. RESULTS: The panel agreed on 4 recommendations for adults and children with achalasia. CONCLUSIONS: Strong recommendation for the use of POEM over PD was issued unless the concern of continued postoperative PPI use remains a key decision-making concern to the patient. Conditional recommendations included the option of using either POEM or HM with fundoplication to treat achalasia, and favored POEM over HM for achalasia subtype III.

SAGES guidelines: an appraisal of their quality and value by SAGES members.

BACKGROUND: The Society of American Gastrointestinal and Endoscopic Surgeons (SAGES) Guidelines Committee develops evidence-based guidelines for practicing surgeons using standard methodology. Our objective was to survey the SAGES membership regarding guidelines' quality, use, and value and identify topics of interest for new guideline development. METHODS: An anonymous online survey was emailed in October 2019 to SAGES members. Respondents were asked 18 questions on their use and evaluation of SAGES guidelines and SAGES reviews and to provide suggestions for new guideline topics and areas of improvement. The survey was open for 6 weeks with a 3-week reminder. RESULTS: Of 548 responders, most were minimally invasive (41%) or general surgeons (33%). There was an even distribution between academic (46%) and non-academic practice (24% private practice, 23% hospital employed). Most used SAGES guidelines frequently (22%) or occasionally (68%) and found them to be of value (83%), above average quality (86%), and easy to use (74%). While most stated it was important (35%) or very important (58%) that SAGES continues to follow "rigorous guidelines development processes," common suggestions were for more timely updates and improved web access. Of 442 overlapping topic suggestions, 60% fell into overarching categories of hernia, bariatric, robotic, HPB, and colorectal surgery. CONCLUSIONS: The SAGES guidelines are used frequently and valued by its users for their quality and content. Topics proposed by SAGES members and valuable insight from this survey can guide creation of new guidelines and refinement of established guidelines and processes.

Safe Cholecystectomy Multi-society Practice Guideline and State of the Art Consensus Conference on Prevention of Bile Duct Injury During Cholecystectomy.

BACKGROUND: BDI is the most common serious complication of laparoscopic cholecystectomy. To address this problem, a multi-society consensus conference was held to develop evidenced-based recommendations for safe cholecystectomy and prevention of BDI. METHODS: Literature reviews were conducted for 18 key questions across 6 broad topics around cholecystectomy directed by a steering group and subject experts from 5 surgical societies (Society of Gastrointestinal and Endoscopic Surgeons, Americas Hepato-Pancreato-Biliary Association, International Hepato-Pancreato-Biliary Association, Society for Surgery of the Alimentary Tract, and European Association for Endoscopic Surgery). Evidence-based recommendations were formulated using the grading of recommendations assessment, development, and evaluation methodology. When evidence-based recommendations could not be made, expert opinion was documented. A number of recommendations for future research were also documented. Recommendations were presented at a consensus meeting in October 2018 and were voted on by an international panel of 25 experts with greater than 80% agreement considered consensus. RESULTS: Consensus was reached on 17 of 18 questions by the guideline development group and expert panel with high concordance from audience participation. Most recommendations were conditional due to low certainty of evidence. Strong recommendations were made for (1) use of intraoperative biliary imaging for uncertainty of anatomy or suspicion of biliary injury; and (2) referral of patients with confirmed or suspected BDI to an experienced surgeon/multispecialty hepatobiliary team. CONCLUSIONS: These consensus recommendations should provide guidance to surgeons, training programs, hospitals, and professional societies for strategies that have the potential to reduce BDIs and positively impact patient outcomes. Development of clinical and educational research initiatives based on these recommendations may drive further improvement in the quality of surgical care for patients undergoing cholecystectomy.

Breast Heterogeneity: Obstacles to Developing Universal Biomarkers of Breast Cancer Initiation and Progression.

BACKGROUND: Predicting outcomes and response to therapy through biomarkers is a major challenge in cancer research. In previous studies, we suggested that inappropriate "normal" tissue samples used for comparison with tumors, inter-individual heterogeneity in gene expression, and genetic ancestry all influence biomarker expression in tumors. The aim of this study was to investigate these factors in breast cancer using breast tissues from healthy women and normal tissue adjacent to tumor (NAT) with matrix metalloproteinase 7 (MMP7) as a candidate biomarker. STUDY DESIGN: RNA sequencing was performed on primary luminal progenitor cells from healthy breast, NATs, and tumors to identify transcriptomes enriched in NATs and breast cancer. Expression of select genes was validated via quantitative reverse transcription polymerase chain reaction of RNA and via immunohistochemistry of a tissue microarray of normal, NAT, and tumor samples of different genetic ancestry. RESULTS: Twenty-six genes were significantly overexpressed in NATs and tumors compared with healthy controls at messenger RNA level and formed a para-inflammatory network. MMP7 had the greatest expression in tumor cells, with upregulation confirmed by quantitative reverse transcription polymerase chain reaction. Tumor-enriched but not NAT-enriched expression of MMP7 compared with healthy controls was reproduced at protein levels. When stratified by genetic ancestry, tumor-specific increase of MMP7 reached statistical significance in women of European ancestry. CONCLUSIONS: Transcriptome differences across healthy, NAT, and tumor tissue in breast cancer demonstrate an active para-inflammatory network in NATs and indicate unsuitability of NATs as "normal controls" in biomarker discovery. The discordance between transcriptomic and proteomic MMP7 expression in NATs and the influence of genetic ancestry on its protein expression highlight the complexity in developing universally acceptable biomarkers of breast cancer and the importance of genetic ancestry in biomarker development.

HIV Retesting of HIV-Negative Pregnant Women in the Context of Prevention of Mother-to-Child Transmission of HIV in Primary Health Centers in Rural Zambia: What Did We Learn?

BACKGROUND: This observational study describes implementation of HIV retesting of HIV-negative women in prevention of mother-to-child transmission (PMTCT) services in Zambia. METHODS: Uptake of retesting and PMTCT services were compared across age, parity, and weeks of gestation at the time of the first HIV test, antiretrovirals regime, and HIV early diagnosis results from infants born to HIV-positive mothers. RESULTS: A total of 19 090 pregnant women were tested for HIV at their first antenatal visit, 16 838 tested HIV-negative and were offered retesting 3 months later: 11 339 (67.3%) were retested; of those, 55 (0.5%) were HIV positive. Uptake of the PMTCT package by women HIV positive at retest was not different but HIV-exposed infants born to women who retested HIV positive were infected at a higher rate (11.1%) compared to those born to women who tested HIV positive at their initial test (3.2%). CONCLUSION: We suggest rigorously (1) measuring the proportion of MTCT attributable to women who seroconvert during pregnancy and possibly adjust PMTCT approaches and (2) addressing the substantial loss to follow-up of HIV-negative pregnant women before HIV retesting.

Sarcopenia in emergency abdominal surgery.

BACKGROUND: Sarcopenia, a loss of skeletal muscle mass associated with aging, is a practical measure of frailty and has been previously identified as a predictor of outcomes in surgical cohorts including cancer resection and elderly patients. We hypothesized that sarcopenia, as measured by preoperative computerized tomography (CT) scan, predicts mortality and morbidity in emergent laparotomy. METHODS: Institutional American College of Surgeons National Surgical Quality Improvement Program data were queried for adult patients who underwent open emergency abdominal surgery between 2008 and 2013. Patients with abdominal CT scans within 30 d before surgery were included, and cross-sectional areas of the psoas muscles at vertebral level L4 were summed, normalized by patient height, and stratified by sex. The influence of this total psoas area (TPA) on postoperative morbidity and mortality was evaluated using univariate and multivariate analysis. RESULTS: Of 781 surgeries, 593 (75.9%) had appropriate preoperative CT scans. Median patient age was 61 years old, median TPA was 1719 mm2, and median body mass index was 26.7. Univariate analysis demonstrated a significant association between TPA and total postoperative morbidity (P = 0.0133), increased length of stay (<0.0001), and 90-d mortality (P = 0.0008) but not 30-d mortality (P = 0.26). In multivariate analysis, TPA lost its significance compared to more influential predictors of mortality, including American Society of Anesthesiologists classification. CONCLUSIONS: Sarcopenia, as measured by TPA, significantly predicted mortality in univariate analysis but lost significance in multivariate analysis when factors such as American Society of Anesthesiologists score were included. Because TPA is readily available at no additional risk or cost, it is a convenient additional tool for preoperative risk assessment and counseling.