Richard Zheng

Background: Effects of neoadjuvant immunotherapy (NIT) before liver resection are not well-described in hepatocellular carcinoma (HCC). Survival and R0 resection rates in HCC patients undergoing curative-intent resection with or without NIT were evaluated. Methods: A retrospective study of stage I-III HCC patients undergoing hepatectomy from the 2017–2022 National Cancer Database was performed. Patients receiving NIT were exactly matched 1:3 to non-NIT patients by clinical stage. Primary outcomes were margin positivity, 30- and 90-day mortality, and overall survival. Results: After matching 510 patients, 97 received NIT and 291 did not (non-NIT). Resections included segmental (178, 45.9%), lobar (149, 38.4%), and extended hepatectomy (61, 15.7%). The NIT group included ablation (6, 6.2%), radiation (25, 25.8%), and Y90 (18, 18.6%). The non-NIT group included 124 (42.6%) chemotherapy, 23 (7.9%) chemotherapy plus ablation, 31 (10.7%) chemotherapy plus radiation, four (1.4%) radiation, and 109 (37.5%) upfront surgery. NIT patients were treated more at high-volume (41.2% vs. 0%) and academic/research centers (85.4% vs. 50.5%). NIT R0 resection rates were higher (97.9% vs. 93.2%, p = 0.009). Median survival was higher in the NIT group (59.1 vs. 50.4 months, p = 0.002); 30- and 90-day mortality were similar. NIT was not independently associated with improved survival in multivariable Cox regression (HR 0.73, 95% CI [0.35, 1.55]), although the effect estimate indicates a protective effect may be present. Conclusions: NIT was associated with higher R0 resection rates and overall survival without increasing short-term mortality in selected patients at high-volume academic centers, but was not independently associated with survival when adjusting for confounders. As we continue to see increasing use of immunotherapy in the neoadjuvant setting, these findings should be considered hypothesis-generating and warrant prospective validation before widespread adoption for HCC.

Background: The P53 gene is the most common tumor‐suppressor gene mutated in pancreatic ductal adenocarcinoma (PDAC). The gene's normal function is critical for regulation of replication, DNA repair, and apoptosis. The purpose of our study is to determine the impact of the various P53 mutation subtypes on survival in resected PDAC.Methods: This is a retrospective cohort study assessing patients that underwent curative‐intent resection for PDAC between the years of 2016–2022. Next generation sequencing (NGS) was performed on patient tumors. P53 tumor genotypes were grouped into wild‐type (WT), gain‐of‐function (GOF) mutations (R175H, R248W, R248Q, R273H, R282W, G245S) and all other non‐GOF mutations.Results: The study included a total of 330 patients with resected PDAC. P53 mutations were found in tumors of 243 patients (74%), and 87 (26%) patients had WT P53. Among patients with mutant P53 tumors, 58 patients (24%) had a GOF mutation, and 185 patients (76%) had a non‐GOF mutation. Survival analysis showed that non‐GOF P53 mutations were associated with the shortest overall survival compared with WT and GOF (25.6 ± 2.4 months vs. 32.2 ± 3.6 months, vs. 36.2 ± 4.4 months, respectively. p = 0.038). Similarly, non‐GOF mutations were associated with the shortest disease‐free survival (14.6 ± 1.2 months, vs. 19.6 ± 3.5 months, vs. 18.3 ± 3.6 months, respectively. p = 0.039).Conclusions: Our data suggest that P53 mutations grouped by functional status may hold differential prognostic value regarding survival and recurrence of patients with PDAC. Further investigations are required to validate these findings.

The impact of pancreaticoduodenectomy on absorption of drugs in the duodenum remains largely unknown. We aim to characterize the pharmacokinetics of apixaban in patients who had previously undergone pancreaticoduodenectomy. A single 10-mg dose of apixaban was administered to 4 volunteers who underwent pancreaticoduodenectomy at least 6 months prior. The maximum plasma apixaban concentration (C_max) and area under the plasma concentration time-curve (AUC_0-24, AUC_0-inf) were compared against healthy historical control subjects (N = 12). Geometric mean ratios (GMR) with 90% confidence interval (CI) were calculated for determination of comparative bioequivalence. In pancreaticoduodenectomy patients, AUC_0-24 and AUC_0-inf were 1,861 and 2,080 ng×h/mL, respectively. The GMRs of AUC_0-24 and AUC_0-inf between study subjects and healthy controls were 1.27 (90% CI 0.88 - 1.83) and 1.18 (90% CI 0.82 - 1.72). The mean C_max of apixaban was 201 ng/mL (SD 15.6) occurring at a median t_max of 3.25 hours (range 2.5 - 4 hours). The GMR of C_max between study subjects and healthy controls was 1.12 (90% CI 0.77 - 1.63). The pharmacokinetic characteristics of apixaban in subjects who had undergone pancreaticoduodenectomy are not significantly different from those of healthy controls. Though the sample size of this study is small, results suggest that no change to apixaban dose regimen is needed in patients who have had a pancreaticoduodenectomy.

Background: Parenchymal-sparing approaches to pancreatectomy are technically challenging procedures but allow for preserving a normal pancreas and decreasing the rate of postoperative pancreatic insufficiency. The robotic platform is increasingly being used for these procedures. We sought to evaluate robotic parenchymal-sparing pancreatectomy and assess its complication profile and efficacy. Methods: This systematic review consisted of all studies on robotic parenchymal-sparing pancreatectomy (central pancreatectomy, duodenum-preserving partial pancreatic head resection, enucleation, and uncinate resection) published between January 2001 and December 2022 in PubMed and Embase. Results: A total of 23 studies were included in this review (n = 788). Robotic parenchymal-sparing pancreatectomy is being performed worldwide for benign or indolent pancreatic lesions. When compared to the open approach, robotic parenchymal-sparing pancreatectomies led to a longer average operative time, shorter length of stay, and higher estimated intraoperative blood loss. Postoperative pancreatic fistula is common, but severe complications requiring intervention are exceedingly rare. Long-term complications such as endocrine and exocrine insufficiency are nearly nonexistent. Conclusions: Robotic parenchymal-sparing pancreatectomy appears to have a higher risk of postoperative pancreatic fistula but is rarely associated with severe or long-term complications. Careful patient selection is required to maximize benefits and minimize morbidity.

Background: The impact of pancreaticoduodenectomy (PD) on absorption of drugs in the duodenum remains largely unknown. We aim to characterize the pharmacokinetics of apixaban in patients who have previously underwent PD. Methods: A single 10 mg dose of apixaban was administered to four volunteers who underwent PD at least 6 months prior. The maximum plasma apixaban concentration (C_max) and area under the plasma concentration time-curve (AUC_0-24, AUC_0-inf) were compared against healthy historical control subjects (N=12). Geometric mean ratios (GMR) with 90% confidence interval (CI) were calculated for determination of comparative bioequivalence. Results: In PD patients AUC_0-24 and AUC_0-inf were 1861 and 2080 ng•hr/mL, respectively. The GMRs of AUC_0-24 and AUC_0-inf between study subjects and healthy controls were 1.27 (90% CI 0.88-1.83) and 1.18 (90% CI 0.82-1.72). The mean C_max of apixaban was 201 ng/mL (SD 15.6) occurring at a median T_max of 3.25 hours (range 2.5-4 hours). The GMR of C_max between study subjects and healthy controls was 1.12 (90% CI 0.77-1.63). Conclusions: The pharmacokinetic characteristics of apixaban in subjects who have undergone PD are not significantly different from those of healthy controls. No changes in their dosing regimen are recommended. ClinicalTrials.gov Identifier: NCT04191928

We received the critique of our article ¹ Woodward S.G. Rios-Diaz A.J. Zheng R. et al. Finding the most favorable timing for cholecystectomy after percutaneous cholecystostomy tube placement: an analysis of institutional and national data. J Am Coll Surg. 2021; 232 : 55-64 Abstract Full Text Full Text PDF PubMed Scopus (4) Google Scholar from Sakamoto and Lefor and appreciate the feedback. In their letter to the editor, Sakamoto and Lefor identified 3 main points of clarification within our article, with the first questioning the exclusion of patients undergoing cholecystectomy within the same admission of percutaneous cholecystostomy tube (PCT) placement, the second point addressing patients with retained common bile duct stones postoperatively as it relates to PCT timing, and finally, using a linear assumption in analyzing the relationship between surgical complications and duration of PCT. We would like to address these points.