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BackgroundOccult metastatic tumors, below imaging thresholds, are a limitation of staging systems that rely on cross-sectional imaging alone and are a cause of the routine understaging of pancreatic ductal adenocarcinomas (PDACs). We investigated circulating tumor cells (CTCs) as a preoperative predictor of occult metastatic disease and as a prognostic biomarker for PDAC patients.Experimental DesignA total of 126 patients (100 with cancer, 26 with benign disease) were enrolled in our study and CTCs were identified and enumerated from 4 mL of venous blood using the microfluidic NanoVelcro assay. CTC enumeration was correlated with clinicopathologic variables and outcomes following both surgical and systemic therapies.ResultsCTCs were identified in 78% of PDAC patients and CTC counts correlated with increasing stage (ρ = 0.42, p < 0.001). Of the 53 patients taken for potentially curative surgery, 13 (24.5%) had occult metastatic disease intraoperatively. Patients with occult disease had significantly more CTCs than patients with local disease only (median 7 vs. 1 CTC, p < 0.0001). At a cut-off of three or more CTCs/4 mL, CTCs correctly identified patients with occult metastatic disease preoperatively (area under the receiver operating characteristic curve 0.82, 95% confidence interval (CI) 0.76–0.98, p < 0.0001). CTCs were a univariate predictor of recurrence-free survival following surgery [hazard ratio (HR) 2.36, 95% CI 1.17–4.78, p = 0.017], as well as an independent predictor of overall survival on multivariate analysis (HR 1.38, 95% CI 1.01–1.88, p = 0.040).ConclusionsCTCs show promise as a prognostic biomarker for PDAC patients at all stages of disease being treated both medically and surgically. Furthermore, CTCs demonstrate potential as a preoperative biomarker for identifying patients at high risk of occult metastatic disease.

Background Rapid adoption of robotic-assisted general surgery procedures, particularly for cholecystectomy, continues while questions remain about its benefits and utility. The objective of this study was to compare the clinical effectiveness of robot-assisted cholecystectomy for benign gallbladder disease as compared with the laparoscopic approach. Methods A literature search was performed from January 2010 to March 2020, and a narrative analysis was performed as studies were heterogeneous. Results Of 887 articles screened, 44 met the inclusion criteria (range 20–735,537 patients). Four were randomized controlled trials, and four used propensity-matching. There were variable comparisons between operative techniques with only 19 out of 44 studies comparing techniques using the same number of ports. Operating room time was longer for the robot-assisted technique in the majority of studies (range 11–55 min for 22 studies, p < 0.05; 15 studies showed no difference; two studies showed shorter laparoscopic times), while conversion rates and intraoperative complications were not different. No differences were detected for the length of stay, surgical site infection, or readmissions. Across studies comparing single-port robot-assisted to multi-port laparoscopic cholecystectomy, there was a higher rate of incisional hernia; however, no differences were noted when comparing single-port robot-assisted to single-port laparoscopic cholecystectomy. Conclusions Clinical outcomes were similar for benign, elective gallbladder disease for robot-assisted compared with laparoscopic cholecystectomy. Overall, the rates of complications were low. More high-quality studies are needed as the robot-assisted technique expands to more complex gallbladder disease, where its utility may prove increasingly beneficial. Systematic review registration PROSPERO CRD42020156945

Background Antiplatelet agents are central in the management of vascular disease. The use of dual antiplatelet therapy (DAPT) for the management of thromboembolic complications must be weighed against bleeding risk in the perioperative setting. This balance is critical in patients undergoing cardiac or non-cardiac surgery. The management of patients on DAPT for any indication (including stents) is not clear and there is limited evidence to guide decision-making. This review summarizes current evidence since 2015 regarding the occurrence of major adverse events associated with continuing, suspending, or varying DAPT in the perioperative period. Methods A research librarian searched PubMed and Cochrane from November 30, 2015 to May 17, 2022, for relevant terms regarding adult patients on DAPT for any reason undergoing surgery, with a perioperative variation in DAPT strategy. Outcomes of interest included the occurrence of major adverse cardiac events, major adverse limb events, all-cause death, major bleeding, and reoperation. We considered withdrawal or discontinuation of DAPT as stopping either aspirin or a P2Y12 inhibitor or both agents; continuation of DAPT indicates that both drugs were given in the specified timeframe. Results Eighteen observational studies met the inclusion criteria. No RCTs were identified, and no studies were judged to be at low risk of bias. Twelve studies reported on CABG. Withholding DAPT therapy for more than 2 days was associated with less blood loss and a slight trend favoring less transfusion and surgical re-exploration. Among five observational CABG studies, there were no statistically significant differences in patient death across DAPT management strategies. Few studies reported cardiac outcomes. The remaining studies, which were about procedures other than exclusively CABG, demonstrated mixed findings with respect to DAPT strategy, bleeding, and ischemic outcomes. Conclusion The evidence base on the benefits and risks of different perioperative DAPT strategies for patients with stents is extremely limited. The strongest signal, which was still judged as low certainty evidence, is that suspension of DAPT for greater than 2 days prior to CABG surgery is associated with less bleeding, transfusions, and re-explorations. Different DAPT strategies’ association with other outcomes of interest, such as MACE, remains uncertain. Systematic review registration A preregistered protocol for this review can be found on the PROSPERO International Prospective Register of systematic reviews ( http://www.crd.york.ac.uk/PROSPERO/ ; registration number: CRD42022371032).

Background The current (seventh edition) American Joint Commission on Cancer (AJCC) Staging System for pancreatic ductal adenocarcinoma (PDAC) dichotomizes pathologic lymph node (LN) involvement into absence (pN0) or presence (pN1) of disease. The recently announced eighth edition also includes stratification on the number of positive nodes. Furthermore, LNs detected on preoperative imaging (CT, MRI, or endoscopic ultrasound—EUS) are considered to be pathologically involved in other gastrointestinal cancers. However, this is less well defined for PDAC. Therefore, the three aims of this study were to determine (1) whether the new AJCC staging system led to more accurate staging, (2) the number of nodes needed to be examined to detect pathologic involvement, and (3) if pN disease could be reliably detected on preoperative imaging in PDAC. Methods A retrospective review of all patients undergoing pancreatectomy at a single US academic center from January 1990 to September 2015. Pathology reports of resected specimens were reviewed to determine the total number of LNs examined and those positive for metastasis. CT, MRI, and/or EUS reports were used to determine the presence or absence of preoperatively detectable LN enlargement. Results Of the 490 surgical resections for PDAC, pN1 disease was detected in 59.4% ( n  = 291) and was positively correlated with the number of LNs pathologically examined ( P  < 0.001). Patients with pN1 disease had a shorter overall survival (OS) than those without nodal involvement (25.1 vs. 44.0 months; P  < 0.001); however, OS was not different when stratifying by the number of nodes as on the eighth AJCC system. Pathologic examination of > 20 LNs in treatment naïve patients was optimal to detect pN1 disease and predict longer OS for those without nodal involvement (median survival > 41.1 months, P  = 0.03 when compared to < 15 or 15–19 LNs examined). LNs were detected by CT, MRI, or EUS in 30.7% (103/335) of patients. The positive predictive value (PPV) of preoperative LN detection for pathologic involvement was 77.3% for treatment naïve patients and 84.2% for those without biliary obstruction. Conclusions Although the LN scoring in the seventh PDAC AJCC Staging System was sufficient to predict OS of our patients, more LNs than previously considered (20 vs. 15) were optimal to detect pathologic involvement. Preoperative LN detection was an accurate predictor of pN1 disease for treatment naïve patients without biliary obstruction.

Ac-PSMA-617 targeted-therapy has demonstrated efficacy in 75-85% of patients; however, responses are not durable. We aimed to establish translatable mouse models of disseminated prostate cancer (PCa) to evaluate effectiveness of Ac-PSMA-617 at various disease stages. : C4-2, C4-2B, or 22Rv1 cells were injected into the left ventricle of male NSG mice. Disease progression was monitored using bioluminescence imaging (BLI). For treatment, mice were injected with 40 kBq Ac-PSMA-617 at one (early treatment cohort) or three weeks (late treatment cohort) post-inoculation. Treatment efficacy was monitored by BLI of whole-body tumor burden. Mice were sacrificed based on body conditioning score. : C4-2 cells yielded metastases in liver, lungs, spleen, stomach, bones, and brain - achieving a clinically relevant model of widespread metastatic disease. The disease burden in the early treatment cohort was stable over 27 weeks in 5/9 mice and progressive in 4/9 mice. These mice were sacrificed due to brain metastases. Median survival of the late treatment cohort was superior to controls (13 vs. 7 weeks; p<0.0001) but inferior to that in the early treatment cohort (13 vs. 27 weeks; p<0.001). Late cohort mice succumbed to extensive liver involvement. The 22Rv1 and C4-2B systemic models were not used for treatment due to high kidney metastatic burden or low take rate, respectively. : C4-2 cells reproduced metastatic cancer spread most relevantly. Early treatment with Ac-PSMA-617 prevented liver metastases and led to significant survival benefit. Late treatment improved survival without reducing tumor burden in the liver, the main site of metastasis. The current findings suggest that early Ac-PSMA-617 intervention is more efficacious in the setting of widespread metastatic PCa.

Background Duodenal neuroendocrine tumors (dNETs) are rare, and their management is not well-defined. National Comprehensive Cancer Network (NCCN) guidelines recommend surgical resection of large dNETs (> 2 cm) and endoscopic resection of small tumors (< 2 cm). We compared the survival outcomes between surgical and endoscopic resection in various dNET sizes. Methods A retrospective cohort study was conducted using patient data from Surveillance, Epidemiology, and End Results Program (SEER) database. Variables analyzed included age, tumor size, grade, stage, and lymph node status. Disease-specific survival (DSS) was compared for endoscopic and surgical groups in dNET size strata: 0–0.5, 0.5–1, 1–2, 2–3, and > 3 cm. Kaplan–Meier and multivariable Cox proportional hazards models were used for survival analysis. Results The study included 465 patients, with 124 (26.7%) undergoing surgical resection. The average age was 61.9 years, and tumor sizes ranged from 0.1 to 10.5 cm. Endoscopic resection had 40.5% of tumors between 0 and 0.5 cm, while surgery had only 21% ( p  < 0.001). In the surgical cohort, 79.8% had grade 1 tumors compared to 88.3% in the endoscopy group ( P  = 0.024). Among surgically resected cases, 48.4% (60 patients) had lymph node involvement. Age, tumor size, grade, and stage did not significantly predict survival after surgical resection. Stratified by tumor size, no difference in DSS was observed between surgery and endoscopy groups. Conclusions Endoscopic resection demonstrated similar survival outcomes to surgical resection across dNET sizes in this national analysis. Given the risks and the lack of survival benefits for surgery, endoscopic resection may be beneficial for both small and large tumors. Further studies are warranted to validate the current NCCN guidelines.

BackgroundObesity is a major threat to public health and traditional bariatric surgery continues to have low utilization. Endoscopic treatments for obesity have emerged that offer less risk, but questions remain regarding efficacy, durability, and safety. We compared the efficacy of endoscopic bariatric procedures as compared to other existing treatments.MethodsA literature search of Embase, Cochrane Central, and Pubmed was conducted from January 1, 2014 to December 7, 2021, including endoscopic bariatric therapies that were FDA or CE approved at the time of search to non-endoscopic treatments. Thirty-seven studies involving 15,639 patients were included. Primary outcomes included % total body weight loss (%TBWL), % excess body weight loss (%EBWL), and adverse events. Secondary outcomes included quality of life data and differences in hemoglobin A1C levels. Strength of clinical trial and observational data were graded according to the Cochrane methods.ResultsIntragastric balloons achieved greater %TBWL with a range of 7.6–14.1% compared to 3.3–6.7% with lifestyle modification at 6 months, and 7.5–14.0% compared to 3.1–7.9%, respectively, at 12 months. When endoscopic sleeve gastroplasty (ESG) was compared to laparoscopic sleeve gastrectomy (LSG), ESG had less %TBWL at 4.7–14.4% compared to 18.8–26.5% after LSG at 6 months, and 4.5–18.6% as compared to 28.4–29.3%, respectively, at 12 months. For the AspireAssist, there was greater %TBWL with aspiration therapy compared to lifestyle modification at 12 months, 12.1–18.3% TBWL versus 3.5–5.9% TBWL, respectively. All endoscopic interventions had higher adverse events rates compared to lifestyle modification.ConclusionThis review is the first to evaluate various endoscopic bariatric therapies using only RCTs and observational studies for evaluation of weight loss compared with conservative management, lifestyle modification, and bariatric surgery. Endoscopic therapies result in greater weight loss compared to lifestyle modification, but not as much as bariatric surgery. Endoscopic therapies may be beneficial as an alternative to bariatric surgery.

BackgroundPancreatic enucleation (PE) is a viable option for the removal of non-malignant pancreatic masses leading to complete preservation of organ function. Nevertheless, PE is associated with substantial rates of post-operative pancreatic fistula (POPF), particularly when the mass is close to the main pancreatic duct (MPD). Preoperative stenting of the MPD may prevent its injury when performing PE. This paper describes a novel technique of “deep” PE preceded by endoscopic stenting of the MPD.MethodsFrom January 2017 to May 2019, patients with small pancreatic neuroendocrine tumors proximal to the MPD were candidates for PE with previous stenting of the MPD at the University of Verona, Italy, and at the UCLA Medical Center, Los Angeles, California. The endoscopic stenting was scheduled either the day before or 3 weeks before surgery, depending on the participating institute.ResultsTen patients were included in this pilot study. The endoscopic procedure was successful and well tolerated in all cases. Open, laparoscopic and robotic PE were performed. Seven patients had surgical complications. Among these, six developed a post-operative pancreatic fistula (POPF), but neither grade C fistulas nor disruptions of the MPD were detected. At pathology, a low grade pancreatic neuroendocrine tumor was confirmed in all cases.ConclusionIn the setting of high-volume centers, this procedure is safe, and it is associated with acceptable short-term surgical morbidity. The preoperative stenting of the MPD might extend the surgical indications for PE.

There is unexplained deficit in size and function of the exocrine pancreas in type 1 diabetes (T1D). We obtained pancreas from an individual with pre-T1D obtained at surgery and addressed the question, what is the relative inflammation in the exocrine and endocrine pancreas in pre-T1D in the absence of the potential confounding changes at autopsy or in brain dead organ donors. Pancreas was removed surgically from a 36 year woman for benign neuroendocrine tumors (NET). The patient had gestational diabetes at age 29 and has a 23 year old sister with T1D. Pre-operative fasting glucose of 109 mg/dl and HbA1C 5.8% revealed prediabetes with an anti-GAD 1,144 (5–250 U/ml) together with family history implying pre-T1D. There was patchy low grade immune infiltration in some, but not all, islets that met criteria for autoimmune insulitis. The exocrine pancreas showed more abundant inflammation with areas of chronic pancreatitis and acinar to ductal metaplasia, and with other areas of atrophy and fatty infiltration. In pre-T1D inflammation may be more prominent in the exocrine than the endocrine pancreas, calling into question the sequence of events and assumed islet centric basis of autoimmunity leading to T1D.

The utilization of robot-assisted minimally invasive esophagectomy (RAMIE) for esophageal cancer is increasing, despite limited data comparing RAMIE with other surgical approaches. To evaluate the literature for clinical outcomes of RAMIE compared with video-assisted minimally invasive esophagectomy (VAMIE) and open esophagectomy (OE). A systematic search of PubMed, Cochrane, Ovid Medline, and Embase databases from January 1, 2013, to May 6, 2020, was performed. Studies that compared RAMIE with VAMIE and/or OE for cancer were included. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) reporting guideline, data were extracted by independent reviewers. A random-effects meta-analysis of 9 propensity-matched studies was performed for the RAMIE vs VAMIE comparison only. A narrative synthesis of RAMIE vs VAMIE and OE was performed. The outcomes of interest were intraoperative outcomes (ie, estimated blood loss [EBL], operative time, lymph node [LN] harvest), short-term outcomes (anastomotic leak, recurrent laryngeal nerve [RLN] palsy, pulmonary and total complications, and 90-day mortality), and long-term oncologic outcomes. Overall, 21 studies (2 randomized clinical trials, 11 propensity-matched studies, and 8 unmatched studies) with 9355 patients were included. A meta-analysis was performed with 9 propensity-matched studies comparing RAMIE with VAMIE. The random-effects pooled estimate found an adjusted risk difference (RD) of -0.06 (95% CI, -0.11 to -0.01) favoring fewer pulmonary complications with RAMIE. There was no evidence of differences between RAMIE and VAMIE in LN harvest (mean difference [MD], -1.1 LN; 95% CI, -2.45 to 0.25 LNs), anastomotic leak (RD, 0.0; 95% CI, -0.03 to 0.03), EBL (MD, -6.25 mL; 95% CI, -18.26 to 5.77 mL), RLN palsy (RD, 0.01; 95% CI, -0.08 to 0.10), total complications (RD, 0.05; 95% CI, -0.01 to 0.11), or 90-day mortality (RD, -0.01; 95% CI, -0.02 to 0.0). There was low certainty of evidence that RAMIE was associated with a longer disease-free survival compared with VAMIE. For OE comparisons (data not pooled), RAMIE was associated with a longer operative time, decreased EBL, and less pulmonary and total complications. In this study, RAMIE had similar outcomes as VAMIE but was associated with fewer pulmonary complications compared with VAMIE and OE. Studies on long-term functional and cancer outcomes are needed.