Stucky, Chee‐Chee

Background: Upfront resectable pancreatic ductal adenocarcinoma (PDAC) is defined by the NCCN as disease with ≤180° portomesenteric vein (PMV) abutment. However, the clinical significance of PMV abutment in this cohort remains unexplored, and we sought to investigate its impact. Methods: This multi-institutional study included patients who underwent pancreatoduodenectomy (PD) for upfront resectable PDAC from 2002 to 2023. Patients with PDAC with ≤180° PMV abutment were compared with those without. Overall survival (OS) was compared and stratified based on whether patients underwent upfront surgery or neoadjuvant therapy (NAT). Results: Among 1,446 patients included, 521 (36.0%) had PMV abutment. Median OS for patients with PMV abutment was 28.8 months compared with 31.2 months for those without ( P =.17). In a stratified analysis of patients who underwent upfront surgery, patients with PMV abutment had worse OS (19.2 vs 27.6 months; P <.05) and lower R0 resection rates (63.1% vs 87.2%; P <.05) compared with those without. However, in patients who underwent NAT, this difference in R0 resection rate was not observed (91.4% vs 94.0%, respectively; P =.27). Furthermore, there was no significant difference in median OS with NAT (42.5 vs 51.6 months, respectively; P =.48). Conclusions: In this largest cohort to date of patients with upfront resectable PDAC, PMV abutment was associated with worse OS compared with no PMV abutment when an upfront resection strategy was used. The use of NAT in patients with PMV abutment mitigated this survival difference with increased R0 resection rates. These findings suggest that patients with upfront resectable PDAC with PMV abutment benefit from a NAT approach for optimal survival outcomes, and that the current criteria guidelines need to be redefined.

Abstract Objective Intraoperative parathyroid hormone (ioPTH) monitoring is crucial during parathyroid surgery to ensure chemical cure. However, delays in processing can prolong operative times. This study evaluates the effectiveness of a checklist to expedite ioPTH assay processes. Methods A multidisciplinary checklist was developed to standardize ioPTH collection and workflow. Thirty patients treated with use of the checklist were prospectively studied, while 30 patients treated without use of the checklist were retrospectively reviewed. Time intervals for post–15‐minute ioPTH assay results were compared. Results Thirty age‐ and sex‐matched patients were included in each group (n = 60) involving 5 surgeons. The intervention and control group had a mean baseline PTH of 140.9 and 130.3 pg/mL and a post–15‐minute ioPTH of 69.6 and 52.0 pg/mL, respectively. The mean time from sample collection to the post–15‐minute ioPTH assay result was significantly reduced in the intervention as compared to the control group (22.2 vs 33.3 minutes; P < .01). The proportional operative time spent awaiting ioPTH assay results was also reduced (24.4 vs 34.1%; P < .01). In subgroup analysis, a significant difference in the total operative time was found in adenomatous disease (68.0 vs 92.2 minutes, P < .05) but not four‐gland hyperplasia (119.3 vs 142.3 minutes). Discussion The implementation of a simple intraoperative checklist effectively reduces the overall ioPTH assay processing time, creating a more efficient surgical workflow. It is low‐cost and requires minimal additional resources. Implications for Practice This quality improvement intervention holds promise for broader adoption in parathyroid surgery to reduce delays and optimize patient care.

Importance Pathologic complete response (pCR) is increasingly used as a surrogate end point for survival in randomized clinical trials (RCTs) in the field of gastrointestinal oncology. Although this approach has been endorsed by the US Food and Drug Administration, it is still novel and incompletely verified. Objective To evaluate the trial-level association between pCR and survival in rectal cancer RCTs examining the effectiveness of neoadjuvant therapy. Data Sources A meta-analysis was conducted to identify eligible RCTs in PubMed, EMBASE, and Cochrane databases published between database inception to January 3, 2024. Study Selection RCTs evaluating neoadjuvant therapies in patients with rectal cancer who underwent subsequent surgical resection and reported pCR, overall survival (OS), and disease-free survival (DFS) were included. Data Extraction and Synthesis Two investigators extracted the data, which were verified by a third author. The risk of bias and the certainty of the evidence were evaluated using the Cochrane Risk of Bias Tool, version 2, and the Grading of Recommendations Assessment, Development, and Evaluation tool, respectively. Adjusted odds and hazard ratios with their 95% CIs were extracted. Weighted linear regression was used to assess the correlation between pCR and both OS and DFS. Main Outcomes and Measures Trial-level correlation between pCR and both OS and DFS. Results Twenty-five RCTs, including 11 882 patients, met the inclusion criteria. On meta-regression analysis, pCR was not correlated with OS (β = 0.37; 95% CI, −0.98 to 1.71; P = .57). Similarly, pCR was not correlated with DFS (β = −0.84; 95% CI, −2.55 to 0.87; P = .32). Two studies (8%) used in the meta-analysis had high risk of bias. On sensitivity analysis excluding these studies, pCR was still not associated with OS or DFS. Subgroup analysis of RCTs using total neoadjuvant therapies was not possible due to limited sample size. Conclusions and Relevance In this systematic review and meta-analysis of RCTs comparing neoadjuvant therapies in rectal cancer, there was no trial-level association between pCR and survival. These results suggest that the use of pCR as a surrogate end point for survival should be reexamined and used more cautiously.

Objective: We comparatively analyzed the longitudinal outcomes of conversion to open procedure, laparoscopic subtotal cholecystectomy (CCY), and laparoscopic cholecystostomy tube placement. Background: Severe cholecystitis often causes dense inflammation that distorts the hepatocystic anatomy and can make safe dissection during CCY challenging. However, controversy exists regarding the optimal bailout procedure in such situations. Methods: The New York and Florida State all-claims databases were queried for patients who underwent laparoscopic CCY for acute cholecystitis from 2012 to 2021. Hierarchical logistic regression models were used to obtain adjusted estimates, with fixed effects assigned to patient-level variables and random effects assigned to hospital identifiers to adjust for intraclass correlation. Results: Of 384,948 laparoscopic CCYs performed, 5448 (1.4%) were not completed laparoscopically; 1370 underwent conversion to open procedure, 2646 underwent laparoscopic subtotal CCY, and 1432 underwent laparoscopic cholecystostomy tube placement. The conversion to open rate decreased from 0.6% in 2012 to 0.3% in 2021, while the laparoscopic subtotal CCY rate increased from 0.2% in 2012 to 1.4% in 2021. The 1-year bile duct injury (BDI) rate was highest for the conversion to open group (4.4%), followed by the laparoscopic subtotal CCY (0.8%) and laparoscopic cholecystostomy tube groups (0.3%, P<0.001). On adjusted analyses with the conversion to open group as the control, laparoscopic subtotal CCY (OR: 0.17, P<0.001) and laparoscopic cholecystostomy tube were associated with lower BDI rates (OR: 0.08, P<0.001, Figure). The 1-year postoperative endoscopic biliary intervention rate was lowest for the conversion to open group (4.2%), followed by the laparoscopic subtotal CCY (8.4%) and the laparoscopic cholecystostomy tube groups (8.8%, P<0.001). The completion CCY rates for the laparoscopic subtotal CCY and laparoscopic cholecystostomy tube groups were 2.1% and 23.4%, respectively. Among completion CCYs, the open rates were 56.4% in the laparoscopic subtotal CCY group versus 24.5% in the laparoscopic cholecystostomy tube group (P<0.001). Conclusions: In patients with severe cholecystitis requiring a bailout procedure, the BDI rate was highest after conversion to open procedure. Laparoscopic subtotal CCY and laparoscopic cholecystostomy tube were associated with lower BDI rates at the cost of higher postoperative endoscopic biliary intervention rates. Completion CCYs were required in 2.1% and 23.4% of patients who underwent laparoscopic subtotal CCY and laparoscopic cholecystostomy tube placement, respectively, of which the former group’s CCY was more likely to require an open operation.

The incidence of pancreatic neuroendocrine tumors (PNETs) is on the rise primarily due to the increasing use of cross-sectional imaging. Most of these incidentally detected lesions are non-functional PNETs with a small proportion of lesions being hormone-secreting, functional neoplasms. With recent advances in surgical approaches and systemic therapies, the management of PNETs have undergone a paradigm shift towards a more individualized approach. In this manuscript, we review the histologic classification and diagnostic approaches to both functional and non-functional PNETs. Additionally, we detail multidisciplinary approaches and surgical considerations tailored to the tumor’s biology, location, and functionality based on recent evidence. We also discuss the complexities of metastatic disease, exploring liver-directed therapies and the evolving landscape of minimally invasive surgical techniques.

The incidence of biliary tract cancer in Ontario, Canada, is rising, highlighting the urgency of clinical trial enrollment to move the needle in cancer‐specific outcomes. The integration of natural language processing and population registries demonstrate the immense potential of future generation registries in allowing us to more accurately discern population‐level data.

ImportanceCancer is one of the leading causes of death in the United States, with the obesity epidemic contributing to its steady increase every year. Recent cohort studies find an association between bariatric surgery and reduced longitudinal cancer risk, but with heterogeneous findings.ObservationsThis review summarizes how obesity leads to an increased risk of developing cancer and synthesizes current evidence behind the potential for bariatric surgery to reduce longitudinal cancer risk. Overall, bariatric surgery appears to have the strongest and most consistent association with decreased incidence of developing breast, ovarian, and endometrial cancers. The association of bariatric surgery and the development of esophageal, gastric, liver, and pancreas cancer is heterogenous with studies showing either no association or decreased longitudinal incidences. Conversely, there have been preclinical and cohort studies implying an increased risk of developing colon and rectal cancer after bariatric surgery. A review and synthesis of the existing literature reveals epidemiologic shortcomings of cohort studies that potentially explain incongruencies observed between studies.Conclusions and RelevanceStudies examining the association of bariatric surgery and longitudinal cancer risk remain heterogeneous and could be explained by certain epidemiologic considerations. This review provides a framework to better define subgroups of patients at higher risk of developing cancer who would potentially benefit more from bariatric surgery, as well as subgroups where more caution should be exercised.

Background Pancreatic ductal adenocarcinoma (PDAC) is a challenging target for immunotherapy because it has an immunosuppressive tumor microenvironment. Neoadjuvant chemoradiotherapy can increase tumor-infiltrating lymphocyte (TIL) density, which may predict overall survival (OS). We hypothesized that adding programmed cell death protein 1 (PD-1) blockade to chemoradiotherapy would be well tolerated and increase TILs among patients with localized PDAC. Methods Patients were randomized 2:1 to Arm A (receiving pembrolizumab plus chemoradiotherapy (capecitabine and external beam radiation)) or Arm B (receiving chemoradiotherapy alone) before anticipated pancreatectomy. Primary endpoints were (1) incidence and severity of adverse events during neoadjuvant therapy and (2) density of TILs in resected tumor specimens. TIL density was assessed using multiplexed immunofluorescence histologic examination. Results Thirty-seven patients were randomized to Arms A (n=24) and B (n=13). Grade ≥3 adverse events related to neoadjuvant treatment were experienced by 9 (38%) and 4 (31%) patients in Arms A and B, respectively, with one patient experiencing dose-limiting toxicity in Arm A. Seventeen (71%) and 7 (54%) patients in Arms A and B, respectively, underwent pancreatectomy. Median CD8+ T-cell densities in Arms A and B were 67.4 (IQR: 39.2–141.8) and 37.9 (IQR: 22.9–173.4) cells/mm2, respectively. Arms showed no noticeable differences in density of CD8+Ki67+, CD4+, or CD4+FOXP3+ regulatory T cells; M1-like and M2-like macrophages; or granulocytes. Median OS durations were 27.8 (95% CI: 17.1 to NR) and 24.3 (95% CI: 12.6 to NR) months for Arms A and B, respectively. Conclusions Adding pembrolizumab to neoadjuvant chemoradiotherapy was safe. However, no convincing effect on CD8+ TILs was observed.

Abstract Purpose: Pancreatic ductal adenocarcinoma (PDAC) trials have evaluated CTLA-4 and/or PD-(L)1 blockade in patients with advanced disease in which bulky tumor burden and limited time to develop antitumor T cells may have contributed to poor clinical efficacy. Here, we evaluated peripheral blood and tumor T cells from patients with PDAC receiving neoadjuvant chemoradiation plus anti–PD-1 (pembrolizumab) versus chemoradiation alone. We analyzed whether PD-1 blockade successfully reactivated T cells in the blood and/or tumor to determine whether lack of clinical benefit could be explained by lack of reactivated T cells versus other factors. Experimental Design: We used single-cell transcriptional profiling and TCR clonotype tracking to identify TCR clonotypes from blood that match clonotypes in the tumor. Results: PD-1 blockade increases the flux of TCR clonotypes entering cell cycle and induces an IFNγ signature like that seen in patients with other GI malignancies who respond to PD-1 blockade. However, these reactivated T cells have a robust signature of NF-κB signaling not seen in cases of PD-1 antibody response. Among paired samples between blood and tumor, several of the newly cycling clonotypes matched activated T-cell clonotypes observed in the tumor. Conclusions: Cytotoxic T cells in the blood of patients with PDAC remain sensitive to reinvigoration by PD-1 blockade, and some have tumor-recognizing potential. Although these T cells proliferate and have a signature of IFN exposure, they also upregulate NF-κB signaling, which potentially counteracts the beneficial effects of anti–PD-1 reinvigoration and marks these T cells as non-productive contributors to antitumor immunity. See related commentary by Lander and DeNardo, p. 474