Paul Hansen

OBJECTIVE: To compare short-term surgical outcomes and quality of life (QOL) between single-port laparoscopic cholecystectomy (SPLC) and classic 4-port laparoscopic cholecystectomy (CLC). BACKGROUND: There is significant interest in further reducing the trauma associated with surgical procedures. Although a number of observational studies have suggested that SPLC is a feasible alternative to CLC, there is a lack of data from randomized studies validating any benefit over CLC. METHODS: Eligible patients were randomized to receive SPLC or CLC. Operative and perioperative outcomes, including cosmesis and QOL were analyzed. RESULTS: Forty-three patients were randomized to SPLC (n = 21) or CLC (n = 22). There were no significant differences between groups for most preoperative demographics, American Society of Anesthesiology score, gallstone characteristics, local inflammation, blood loss, or length of stay. Patients undergoing SPLC were older than those receiving CLC (57.3 years vs. 45.8 years, P < 0.05). Operative times for SPLC were greater than CLC (88.5 minutes vs. 44.8 minutes, P < 0.05). Overall and cosmetic satisfaction, QOL as determined by the SF-36 survey, postoperative complications, and post-operative pain scores between discharge and 2-week postoperative visit were not significantly different between groups. Wound infection rates were similar in both groups. The SPLC group contained 1 retained bile duct stone, 1-port site hernia, and 1 postoperative port site hemorrhage. CONCLUSIONS: SPLC procedure time was longer and incurred more complications than CLC without significant benefits in patient satisfaction, postoperative pain and QOL. SPLC may be offered in carefully selected patients. Larger randomized trials performed later in the learning curve with SPLC may identify more subtle advantages of one method over another.

PURPOSE: Minimally invasive therapies such as transarterial chemoembolization and radiofrequency ablation are used for hepatic metastatic neuroendocrine tumor (NET) therapy. Results from another minimally invasive therapy, radioembolization, remain unknown. The purpose of this multicenter open label phase II study was to assess the efficacy and safety of yttrium-90 (Y) radioembolization for treating hepatic metastatic NET using a primary outcome of tumor response and secondary outcomes of serologic toxicities and survival. MATERIAL/METHODS: In this multicenter study, all patients underwent lobar radioembolization using glass or resin Y radioembolic agents. Patients were assessed serologically and radiographically at 2 to 4 weeks and then at 1 to 3 month intervals after treatment. We 1) compared liver volumes, radiation doses, and serologic liver function tests (unpaired t test, P = 0.05) and 2) assessed tumor response, serologic toxicity, and median survival from first Y therapy. The clinicaltrials.gov identifier was NCT00532740. RESULTS: Forty-two patients underwent radioembolization using glass (mean age 58 +/- 12 years) or resin (mean age 61 +/- 11 years) microspheres. A statistically significant greater median radiation dose was delivered to each lobe using glass (right lobe 117 Gy; left lobe 108 Gy) than using resin (right 50.8 Gy; left 44.5 Gy) (P < 0.01). Using Response Criteria in Solid Tumors, 92% of glass and 94% of resin patients were classified as partial response or stable disease at 6 months after treatment. Six patients experienced grade 3/4 toxicities during the follow-up period. Median survival was 22 months (glass) and 28 months (resin) (P = 0.82). CONCLUSION: Y radioembolization of metastatic NET is a viable therapy with acceptable toxicity. Further investigation is warranted.

Pancreatic ductal adenocarcinoma (PDAC) has traditionally been thought of as an immunologically quiescent tumor type presumably because of a relatively low tumor mutational burden (TMB) and poor responses to checkpoint blockade therapy. However, many PDAC tumors exhibit T cell inflamed phenotypes. The presence of tertiary lymphoid structures (TLS) has recently been shown to be predictive of checkpoint blockade response in melanomas and sarcomas, and are prognostic for survival in PDAC. In order to more comprehensively understand tumor immunity in PDAC patients with TLS, we performed RNA-seq, single and multiplex IHC, flow cytometry and predictive genomic analysis on treatment naïve, PDAC surgical specimens. Forty-six percent of tumors contained distinct T and B cell aggregates reflective of “early-stage TLS” (ES-TLS), which correlated with longer overall and progression-free survival. These tumors had greater CD8+ T cell infiltration but were not defined by previously published TLS gene-expression signatures. ES-TLS+ tumors were enriched for IgG1 class-switched memory B cells and memory CD4+ T cells, suggesting durable immunological memory persisted in these patients. We also observed the presence of active germinal centers (mature-TLS) in 31% of tumors with lymphocyte clusters, whose patients had long-term survival (median 56 months). M-TLS-positive tumors had equivalent overall T cell infiltration to ES-TLS, but were enriched for activated CD4+ memory cells, naive B cells and NK cells. Finally, using a TCGA-PDAC dataset, ES-TLS+ tumors harbored a decreased TMB, but M-TLS with germinal centers expressed significantly more MHCI-restricted neoantigens as determined by an in silico neoantigen prediction method. Interestingly, M-TLS+ tumors also had evidence of increased rates of B cell somatic hypermutation, suggesting that germinal centers form in the presence of high-quality tumor neoantigens leading to increased humoral immunity that confers improved survival for PDAC patients.AbbreviationsTLS: tertiary lymphoid structures; GC: germinal center(s); PDAC: pancreatic ductal adenocarcinoma; RNA-seq: RNA sequencing; BCRseq: B cell receptor sequencing; HEV: high endothelial venule; PNAd: peripheral node addressin; TMB: tumor mutational burden; TCGA: the cancer genome atlas; PAAD: pancreatic adenocarcinoma; FFPE: formalin fixed paraffin embedded; TIME: tumor immune microenvironment.