The impact of disclosure of conflicts of interest in studies comparing robot-assisted and laparoscopic cholecystectomies-a persistent problem.

INTRODUCTION: Accurate disclosure of conflicts of interest (COI) is critical to interpretation of study results, especially when industry interests are involved. We reviewed published manuscripts comparing robot-assisted cholecystectomy (RAC) and laparoscopic cholecystectomy (LC) to evaluate the relationship between COI disclosures and conclusions drawn on the procedure benefits and safety profile. METHODS: Searching Pubmed and Embase using key words "cholecystectomy", laparoscopic" and "robotic"/"robot-assisted" retrieved 345 publications. Manuscripts that compared benefits and safety of RAC over LC, had at least one US author and were published between 2014 and 2020 enabling verification of disclosures with reported industry payments in CMS's Open Payments database (OPD) (up to 1 calendar year prior to publication) were included in the analysis (n = 37). RESULTS: Overall, 26 (70%) manuscripts concluded that RAC was equivalent or better than LC (RAC +) and 11 (30%) concluded that RAC was inferior to LC (RAC-). Six manuscripts (5 RAC + and 1 RAC-) did not have clearly stated COI disclosures. Among those that had disclosure statements, authors' disclosures matched OPD records among 17 (81%) of RAC + and 9 (90%) RAC- papers. All 11 RAC- and 17 RAC + (65%) manuscripts were based on retrospective cohort studies. The remaining RAC + papers were based on case studies/series (n = 4), literature review (n = 4) and clinical trial (n = 1). A higher proportion of RAC + (85% vs 45% RAC-) manuscripts used data from a single institution. Authors on RAC + papers received higher amounts of industry payments on average compared to RAC- papers. CONCLUSIONS: It is imperative for authors to understand and accurately disclose their COI while disseminating scientific output. Journals have the responsibility to use a publicly available resource like the OPD to verify authors' disclosures prior to publication to protect the process of scientific authorship which is the foundation of modern surgical care.

Outcomes following robot-assisted versus laparoscopic sleeve gastrectomy: the New York State experience.

INTRODUCTION: Laparoscopic sleeve gastrectomy (LSG) represents more than half of all bariatric procedures in the USA, and robot-assisted sleeve gastrectomy (RSG) is becoming increasingly common. There is a paucity of evidence regarding postoperative surgical outcomes (> 30 days) in RSG patients, especially as these patients move between multiple hospital systems. METHODS: Using 2012-2018 New York State's inpatient and ambulatory data from the Statewide Planning and Research Cooperative System, bivariate and multivariate analyses were employed to examine patient long-term outcomes, postoperative complications, and charges following RSG versus LSG in unmatched and propensity score-matched (PSM) samples. RESULTS: Among the 72,157 minimally invasive sleeve gastrectomies identified, 2365 (2.6%) were RSGs. In the PSM sample (2365 RSG matched to 23,650 LSG), RSG cases were more likely to be converted to an open procedure (2.3% vs 0.2% LSG patients, p < 0.01) and had a longer mean length of stay (LOS; 2.1 vs. 1.8 days LSG, p < 0.01). Postoperative complications were not different between RSG and LSG patients, but the proportion of emergency room visits resulting in inpatient readmissions was higher among RSG patients (5.5% vs. 4.2% in LSG patients, p < .01). Among the super obese (body mass index ≥ 50) patients, conversions to open procedure and LOS were also significantly higher for RSG versus LSG cases. Average hospital charges for the index admission ($47,623 RSG vs $35,934 LSG) and cumulative changes for 1 year from the date of surgery ($57,484 RSG vs $43,769 LSG) were > 30% higher for RSG patients. CONCLUSIONS: RSG patients were more likely to have conversions to open procedures, longer postoperative stay, readmissions, and higher charges for both the index admission and beyond, compared to LSG patients. No clear advantages emerged for the utilization of the robotic platform for either average risk or extremely obese patients.

Multisite study of Titan SGS stapler in longitudinal gastric resection.

BACKGROUND: Standardization of the laparoscopic sleeve gastrectomy procedure is needed to improve patient outcomes. A single-fire 23 cm stapler was developed to streamline the operation. Comparative testing conducted on excised human tissue has demonstrated the superiority of the novel Titan SGS stapler to two commonly utilized commercial devices in both staple line integrity and burst pressure. We hypothesized that the stapler would be safe and effective in creating longitudinal gastric resections in human patients. METHODS: 61 patients were enrolled to undergo gastric resection with the Titan SGS stapler. Perioperative interventions and post-operative adverse events were recorded. Upper GI study was completed on post-operative day 1, and patients were followed for 6 weeks post-operatively to determine any subacute device-related adverse events. RESULTS: Surgeon feedback for intraoperative device utilization and post-operative gastric pouch shape were positive. Adverse events were found to be mild, limited, and generally well-known effects of bariatric surgery. One episode of post-operative hemorrhage required surgical takeback, with no criminal bleeding vessel identified. CONCLUSION: The Titan SGS stapler is both safe and effective in sleeve gastrectomy pouch creation.

Frailty predicts risk of life-threatening complications and mortality after pancreatic resections.

BACKGROUND: To assess the effect of frailty on morbidity and mortality after partial pancreatectomy. METHODS: A retrospective analysis of National Surgical Quality Improvement Project from 2005-2010 was conducted. A modified frailty index was created based on previously validated methodology. Patients were classified as nonfrail, low frailty, intermediate frailty, and frail. Outcomes of pancreatoduodenectomy and distal pancreatectomy were examined. RESULTS: In the study, 13,020 patients were analyzed (8,729 pancreatoduodenectomy and 4,291 distal pancreatectomy). Among the pancreatoduodenectomy and distal pancreatectomy patients, frail patients regardless of the degree of frailty were older, more likely male, had a greater body mass index, lower serum albumin, and greater weight loss compared with the nonfrail patients (all P ≤ .05). Postoperatively, a stepwise increased risk of grade 4 complications (Clavien/Dindo) and mortality was noted from nonfrail to frail patients. Every 1-point increase in modified frailty index was associated with a significantly increased risk of grade 4 complications (∼2-6 times) and mortality (∼2-10 times) from low-frail to frail (adjusted for age, sex, body mass index, albumin, weight loss, and type of pancreatectomy). An abbreviated frailty index incorporating 8 variables was as predictive as the modified frailty index (P = .68). CONCLUSION: An 11-point frailty index as measured in National Surgical Quality Improvement Project predicts serious complications and death after pancreatectomy. A modification of this index with 8 factors continues to have similar predictive ability. Consideration of frailty may be beneficial prior to the pancreatic surgeon and particularly in discussion of operative risk and selection of patients who might receive benefit from pre-operative optimization.

FolC2-mediated folate metabolism contributes to suppression of inflammation by probiotic Lactobacillus reuteri.

Bacterial-derived compounds from the intestinal microbiome modulate host mucosal immunity. Identification and mechanistic studies of these compounds provide insights into host-microbial mutualism. Specific Lactobacillus reuteri strains suppress production of the proinflammatory cytokine, tumor necrosis factor (TNF), and are protective in a mouse model of colitis. Human-derived L. reuteri strain ATCC PTA 6475 suppresses intestinal inflammation and produces 5,10-methenyltetrahydrofolic acid polyglutamates. Insertional mutagenesis identified the bifunctional dihydrofolate synthase/folylpolyglutamate synthase type 2 (folC2) gene as essential for 5,10-methenyltetrahydrofolic acid polyglutamate biosynthesis, as well as for suppression of TNF production by activated human monocytes, and for the anti-inflammatory effect of L. reuteri 6475 in a trinitrobenzene sulfonic acid-induced mouse model of acute colitis. In contrast, folC encodes the enzyme responsible for folate polyglutamylation but does not impact TNF suppression by L. reuteri. Comparative transcriptomics between wild-type and mutant L. reuteri strains revealed additional genes involved in immunomodulation, including previously identified hdc genes involved in histidine to histamine conversion. The folC2 mutant yielded diminished hdc gene cluster expression and diminished histamine production, suggesting a link between folate and histadine/histamine metabolism. The identification of genes and gene networks regulating production of bacterial-derived immunoregulatory molecules may lead to improved anti-inflammatory strategies for digestive diseases.

Comprehensive genomic analysis identifies novel subtypes and targets of triple-negative breast cancer.

PURPOSE: Genomic profiling studies suggest that triple-negative breast cancer (TNBC) is a heterogeneous disease. In this study, we sought to define TNBC subtypes and identify subtype-specific markers and targets. EXPERIMENTAL DESIGN: RNA and DNA profiling analyses were conducted on 198 TNBC tumors [estrogen receptor (ER) negativity defined as Allred scale value ≤ 2] with >50% cellularity (discovery set: n = 84; validation set: n = 114) collected at Baylor College of Medicine (Houston, TX). An external dataset of seven publically accessible TNBC studies was used to confirm results. DNA copy number, disease-free survival (DFS), and disease-specific survival (DSS) were analyzed independently using these datasets. RESULTS: We identified and confirmed four distinct TNBC subtypes: (i) luminal androgen receptor (AR; LAR), (ii) mesenchymal (MES), (iii) basal-like immunosuppressed (BLIS), and (iv) basal-like immune-activated (BLIA). Of these, prognosis is worst for BLIS tumors and best for BLIA tumors for both DFS (log-rank test: P = 0.042 and 0.041, respectively) and DSS (log-rank test: P = 0.039 and 0.029, respectively). DNA copy number analysis produced two major groups (LAR and MES/BLIS/BLIA) and suggested that gene amplification drives gene expression in some cases [FGFR2 (BLIS)]. Putative subtype-specific targets were identified: (i) LAR: androgen receptor and the cell surface mucin MUC1, (ii) MES: growth factor receptors [platelet-derived growth factor (PDGF) receptor A; c-Kit], (iii) BLIS: an immunosuppressing molecule (VTCN1), and (iv) BLIA: Stat signal transduction molecules and cytokines. CONCLUSION: There are four stable TNBC subtypes characterized by the expression of distinct molecular profiles that have distinct prognoses. These studies identify novel subtype-specific targets that can be targeted in the future for the effective treatment of TNBCs.

Novel somatic and germline mutations in intracranial germ cell tumours.

Intracranial germ cell tumours (IGCTs) are a group of rare heterogeneous brain tumours that are clinically and histologically similar to the more common gonadal GCTs. IGCTs show great variation in their geographical and gender distribution, histological composition and treatment outcomes. The incidence of IGCTs is historically five- to eightfold greater in Japan and other East Asian countries than in Western countries, with peak incidence near the time of puberty. About half of the tumours are located in the pineal region. The male-to-female incidence ratio is approximately 3-4:1 overall, but is even higher for tumours located in the pineal region. Owing to the scarcity of tumour specimens available for research, little is currently known about this rare disease. Here we report the analysis of 62 cases by next-generation sequencing, single nucleotide polymorphism array and expression array. We find the KIT/RAS signalling pathway frequently mutated in more than 50% of IGCTs, including novel recurrent somatic mutations in KIT, its downstream mediators KRAS and NRAS, and its negative regulator CBL. Novel somatic alterations in the AKT/mTOR pathway included copy number gains of the AKT1 locus at 14q32.33 in 19% of patients, with corresponding upregulation of AKT1 expression. We identified loss-of-function mutations in BCORL1, a transcriptional co-repressor and tumour suppressor. We report significant enrichment of novel and rare germline variants in JMJD1C, which codes for a histone demethylase and is a coactivator of the androgen receptor, among Japanese IGCT patients. This study establishes a molecular foundation for understanding the biology of IGCTs and suggests potentially promising therapeutic strategies focusing on the inhibition of KIT/RAS activation and the AKT1/mTOR pathway.

Pediatric data sharing in genomic research: attitudes and preferences of parents.

OBJECTIVE: In the United States, data from federally funded genomics studies are stored in national databases, which may be accessible to anyone online (public release) or only to qualified researchers (restricted release). The availability of such data exposes participants to privacy risk and limits the ability to withdraw from research. This exposure is especially challenging for pediatric participants, who are enrolled in studies with parental permission. The current study examines genomic research participants' attitudes to explore differences in data sharing (DS) preferences between parents of pediatric patients and adult patients. METHODS: A total of 113 parents of pediatric patients and 196 adult participants from 6 genomics studies were randomly assigned to 3 experimental consent forms. Participants were invited to a follow-up structured interview exploring DS preferences, study understanding, and attitudes. Descriptive analyses and regression models were built on responses. RESULTS: Most parents (73.5%) and adult participants (90.3%) ultimately consented to broad public release. However, parents were significantly more restrictive in their data release decisions, not because of understanding or perceived benefits of participation but rather autonomy and control. Parents want to be more involved in the decision about DS and are significantly more concerned than adult participants about unknown future risks. CONCLUSIONS: Parents have the same altruistic motivations and grasp of genomics studies as adult participants. However, they are more concerned about future risks to their child, which probably motivates them to choose more restrictive DS options, but only when such options are made available.