The impact of surgical-oncologic textbook outcome in patients with stage I to III pancreatic ductal adenocarcinoma: A cross-validation study of two national registries.

BACKGROUND: Using national registries, we aimed to evaluate oncologic textbook outcomes in pancreatic ductal adenocarcinoma patients. METHODS: Patients with stage I to III pancreatic ductal adenocarcinoma and surgical resection from 2010 to 2020 in the US and Germany were identified using the National Cancer Database and National Cancer Registries data. The surgical-oncologic textbook outcome was defined as complete oncologic resection with no residual tumor and ≥12 harvested lymph nodes. The composite endpoint was defined as surgical-oncologic textbook outcome and receipt of perioperative systemic and/or radiation therapy. RESULTS: In total, 33,498 patients from the National Cancer Database and 14,589 patients from the National Cancer Registries were included. In the National Cancer Database, 28,931 (86%) patients had complete oncologic resection with no residual tumor, and 11,595 (79%) in the National Cancer Registries. 8,723 (26%) patients in the National Cancer Database and 556 (4%) in the National Cancer Registries had <12 lymph nodes harvested. The National Cancer Database shows 26,135 (78%) underwent perioperative therapy and 8,333 (57%) in the National Cancer Registries. Surgical-oncologic textbook outcome was achieved in 21,198 (63%) patients in the National Cancer Database and in 11,234 (77%) patients from the National Cancer Registries. 16,967 (50%) patients in the National Cancer Database and 7,878 (54%) patients in the National Cancer Registries had composite textbook outcome. Median overall survival in patients with composite textbook outcomes was 32 months in the National Cancer Database and 27 months in the National Cancer Registries (P < .001). In contrast, those with non-textbook outcomes had a median overall survival of 23 months in the National Cancer Database and 20 months in the National Cancer Registries (P < .001). CONCLUSION: Surgical-oncologic textbook outcomes were achieved in > 50% of stage I to III pancreatic ductal adenocarcinoma for both the National Cancer Database and the National Cancer Registries. Failure to achieve textbook outcomes was associated with impaired survival across both registries.

The Role of Adjuvant Therapy in Duodenal Adenocarcinoma and Intestinal Subtype Ampullary Carcinoma after Curative Resection.

OBJECTIVE: Defining the role of adjuvant therapy in duodenal adenocarcinoma (DAC) and intestinal subtype ampullary carcinoma (iAC). SUMMARY BACKGROUND DATA: DAC and iAC share a similar histological differentiation but the benefit of adjuvant therapy remains unclear. METHODS: Patients undergoing curative-intent surgical resection for DAC and iAC between 2010 and 2021 at five high-volume centers were included. Patient baseline, perioperative and long-term oncological outcomes were evaluated. Statistical testing was performed with SPSS 25 (IBM). RESULTS: A total of 136 patients with DAC and 171 with iAC were identified. Patients with DAC had more advanced tumors than those with iAC. Median overall survival (OS) in DAC patients was 101 months versus 155 months for iAC patients (P=0.098). DAC had a higher rate of local (14.1% vs. 1.2%, P<0.001) and systemic recurrence (30.4% vs. 3.5%, P<0.001). Adjuvant therapy failed to improve overall survival in all patients with DAC and iAC. For DAC, patients with perineural invasion, but not other negative prognostic factors had improved OS rates with adjuvant therapy (72 m vs. 44 m, P=0.044). IAC patients with N+ (190 m vs. 57 m, P=0.003), T3-4 (177 m vs. 59 m, P=0.050) and perineural invasion (150 m vs. 59 m, P=0.019) had improved OS rates with adjuvant therapy. CONCLUSION: While adjuvant therapy fails to improve OS in all patients with DAC and iAC in the current study, it improved overall survival in DAC patients with perineural invasion and in iAC patients with T3-4 tumors, positive lymph nodes, and perineural invasion.

Prediction of R Status in Resections for Pancreatic Cancer Using Simplified Radiological Criteria.

OBJECTIVE: Predicting R status before surgery for pancreatic cancer (PDAC) patients with upfront surgery and neoadjuvant therapy. SUMMARY BACKGROUND DATA: Negative surgical margins (R0) are a key predictor of long-term outcomes in PDAC. METHODS: Patients undergoing pancreatic resection with curative intent for PDAC were identified. Using the CT scans from the time of diagnosis, the 2019 NCCN borderline resectability criteria were compared to novel criteria: presence of any alteration of the superior mesenteric-portal vein (SMPV) and perivascular stranding of the superior mesenteric artery (SMA). Accuracy of predicting R status was evaluated for both criteria. Patient baseline characteristics, surgical, histopathological parameters, and long-term overall survival (OS) after resection were evaluated. RESULTS: A total of 593 patients undergoing pancreatic resections for PDAC between 2010 and 2018 were identified. Three hundred and twenty-five (54.8%) patients underwent upfront surgery, whereas 268 (45.2%) received neoadjuvant therapy. In upfront resected patients, positive SMA stranding was associated with 56% margin positive resection rates, whereas positive SMA stranding and SMPV alterations together showed a margin positive resection rate of 75%. In contrast to these criteria, the 2019 NCCN borderline criteria failed to predict margin status. In patients undergoing neoadjuvant therapy, only perivascular SMA stranding remained a predictor of margin positive resection, leading to a rate of 33% R+ resections. Perivascular SMA stranding was related to higher clinical T stage (P = 0.003) and clinical N stage (P = 0.043) as well as perineural invasion (P = 0.022). SMA stranding was associated with worse survival in both patients undergoing upfront surgery (36 vs 22 months, P = 0.002) and neoadjuvant therapy (47 vs 34 months, P = 0.050). CONCLUSIONS: The novel criteria were accurate predictors of R status in PDAC patients undergoing upfront resection. After neoadjuvant treatment, likelihood of positive resection margins is approximately halved, and only perivascular SMA stranding remained a predictive factor.

Long-term Outcomes of Parenchyma-sparing and Oncologic Resections in Patients With Nonfunctional Pancreatic Neuroendocrine Tumors <3 cm in a Large Multicenter Cohort.

INTRODUCTION: The role of parenchyma-sparing resections (PSR) and lymph node dissection in small (<3 cm) nonfunctional pancreatic neuroendocrine tumors (PNET) is unlikely to be studied in a prospective randomized clinical trial. By combining data from 4 high-volume pancreatic centers we compared postoperative and long-term outcomes of patients who underwent PSR with patients who underwent oncologic resections. METHODS: Retrospective review of prospectively collected clinicopathologic data of patients who underwent pancreatectomy between 2000 and 2021 was collected from 4 high-volume institutions. PSR and lymph node-sparing resections (enucleation and central pancreatectomy) were compared to those who underwent oncologic resections with lymphadenectomy (pancreaticoduodenectomy, distal pancreatectomy). Statistical testing was performed using χ 2 test and t test, survival estimates with Kaplan-Meier method and multivariate analysis using Cox proportional hazard model. RESULTS: Of 810 patients with small sporadic nonfunctional PNETs, 121 (14.9%) had enucleations, 100 (12.3%) had central pancreatectomies, and 589 (72.7%) patients underwent oncologic resections. The median age was 59 years and 48.2% were female with a median tumor size of 2.5 cm. After case-control matching for tumor size, 221 patients were selected in each group. Patients with PSR were more likely to undergo minimally invasive operations (32.6% vs 13.6%, P <0.001), had less intraoperative blood loss (358 vs 511 ml, P <0.001) and had shorter operative times (180 vs 330 minutes, P <0.001) than patients undergoing oncologic resections. While the mean number of lymph nodes harvested was lower for PSR (n=1.4 vs n=9.9, P <0.001), the mean number of positive lymph nodes was equivalent to oncologic resections (n=1.1 vs n=0.9, P =0.808). Although the rate of all postoperative complications was similar for PSR and oncologic resections (38.5% vs 48.2%, P =0.090), it was higher for central pancreatectomies (38.5% vs 56.6%, P =0.003). Long-term median disease-free survival (190.5 vs 195.2 months, P =0.506) and overall survival (197.9 vs 192.6 months, P =0.372) were comparable. Of the 810 patients 136 (16.7%) had no lymph nodes resected. These patients experienced less blood loss, shorter operations ( P <0.001), and lower postoperative complication rates as compared to patients who had lymphadenectomies (39.7% vs 56.9%, P =0.008). Median disease-free survival (197.1 vs 191.9 months, P =0.837) and overall survival (200 vs 195.1 months, P =0.827) were similar for patients with no lymph nodes resected and patients with negative lymph nodes (N0) after lymphadenectomy. CONCLUSION: In small <3 cm nonfunctional PNETs, PSRs and lymph node-sparing resections are associated with lower blood loss, shorter operative times, and lower complication rates when compared to oncologic resections, and have similar long-term oncologic outcomes.

Diversified Effects of Bile Contamination, Postoperative Infections, and Antimicrobial Resistance Level on the Oncologic Prognosis After Pancreatoduodenectomy for Ductal Adenocarcinoma.

BACKGROUND/AIM: Whether the presence of bacteria in the bile or postoperative infections sustained by microorganisms with different levels of drug-resistance are associated with changes in the oncologic prognosis of patients undergoing surgery for pancreatic cancer has not been thoroughly investigated. The aim was to study the association of bile contamination, postoperative infections, and multi-level resistance with long-term outcome. PATIENTS AND METHODS: Prospectively maintained databases were queried for patients who underwent pancreatoduodenectomy (PD). Patients who underwent preoperative biliary stenting prior to PD and an intraoperative bile culture were included. The levels of bacterial resistance of intraoperative bile cultures and of specimens of postoperative infections were stratified into multidrug sensitive (MDS), multidrug-resistant (MDR), and extensive drug-resistant (XDR). RESULTS: A total of 267 patients met the inclusion criteria. The Kaplan-Meier survival curves for overall survival (OS) of patients having no bacteriobilia or positive cultures with MDS versus MDR/XDR bacteria were not statistically different (log-rank=0.9). OS of patients stratified for no postoperative infection or infections by MDS was significantly better than those having MRD/XDR isolates (log-rank=0.04). A Cox multivariate model showed that having MRD/XDR postoperative infections was and independent variable for worse OS (HR=1.227; 95%CI=1.189-1.1918; p=0.036). CONCLUSION: Postoperative drug resistant infections are a significant risk factor for poor OS after pancreatoduodenectomy for ductal adenocarcinoma.

Concepts and Outcomes of Perioperative Therapy in Stage IA-III Pancreatic Cancer-A Cross-Validation of the National Cancer Database (NCDB) and the German Cancer Registry Group of the Society of German Tumor Centers (GCRG/ADT).

(1) Background: The aim of this study is to assess perioperative therapy in stage IA-III pancreatic cancer cross-validating the German Cancer Registry Group of the Society of German Tumor Centers-Network for Care, Quality, and Research in Oncology, Berlin (GCRG/ADT) and the National Cancer Database (NCDB). (2) Methods: Patients with clinical stage IA-III PDAC undergoing surgery alone (OP), neoadjuvant therapy (TX) + surgery (neo + OP), surgery+adjuvantTX (OP + adj) and neoadjuvantTX + surgery + adjuvantTX (neo + OP + adj) were identified. Baseline characteristics, histopathological parameters, and overall survival (OS) were evaluated. (3) Results: 1392 patients from the GCRG/ADT and 29,081 patients from the NCDB were included. Patient selection and strategies of perioperative therapy remained consistent across the registries for stage IA-III pancreatic cancer. Combined neo + OP + adj was associated with prolonged OS as compared to neo + OP alone (17.8 m vs. 21.3 m, p = 0.012) across all stages in the GCRG/ADT registry. Similarly, OS with neo + OP + adj was improved as compared to neo + OP in the NCDB registry (26.4 m vs. 35.4 m, p < 0.001). (4) Conclusion: The cross-validation study demonstrated similar concepts and patient selection criteria of perioperative therapy across clinical stages of PDAC. Neoadjuvant therapy combined with adjuvant therapy is associated with improved overall survival as compared to either therapy alone.

Gene of the month: T-cell immunoreceptor with immunoglobulin and ITIM domains (TIGIT).

Immune modulators play a crucial role in carcinogenesis and cancer progression by impairing cancer cell-targeted immune responses. T-cell immunoreceptor with immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domains (TIGIT) regulates T-cell function and cancer cell recognition and was therefore identified as a promising target for cancer immunotherapy. TIGIT is expressed in T cells and natural killer (NK) cells and has three ligands: CD155, CD112 and CD113. CD155 binds TIGIT with the highest affinity and promotes direct and indirect downregulation of T-cell response. TIGIT signalling further inhibits NK function and secretion of proinflammatory cytokines. An association between TIGIT expression and poor survival was identified in multiple cancer entities. Blocking TIGIT with monoclonal antibodies, and a combination of TIGIT and programmed cell death protein 1 blockade in particular, prevented tumour progression, distant metastasis and tumour recurrence in in vivo models. Inhibition of TIGIT is currently evaluated in first clinical trials.

Postoperative Outcomes of Tangential versus Segmental Resection and End-to-end Reconstruction of the Superior Mesenterico-Portal Vein During Pancreatoduodenectomy for Pancreatic Adenocarcinoma: A Single-Center Experience.

BACKGROUND/AIM: The impact of venous resections and reconstruction techniques on morbidity after surgery for pancreatic cancer (PDAC) remains controversial. PATIENTS AND METHODS: A total of 143 patients receiving pancreatoduodenectomy (PD) for PDAC between 2013 and 2018 were identified from a prospective database. Morbidity and mortality after PD with tangential resection versus end-to-end reconstruction were assessed. RESULTS: Fifty-two of 143 (36.4%) patients underwent PD with portal venous resection (PVR), which was associated with longer operation times [398 (standard error (SE) 12.01) vs. 306 (SE 13.09) min, p<0.001]. PVR was associated with longer intensive-care-unit stay (6.3 vs. 3.8 days, p=0.054); morbidity (Clavien-Dindo classification (CDC) grade IIIa-V 45.8% vs. 35.8%, p=0.279) and 30-day mortality (4.1% vs. 4.2%, p>0.99) were not different. Tangential venous resection was associated with similar CDC grade IIIa-IV (42.9% vs. 50.0%, p=0.781) and 30-day mortality rates (3.5% vs. 4.1%, p=0.538) as segmental resection and end-to-end venous reconstruction. CONCLUSION: Both tangential and segmental PVR appear feasible and can be safely performed to achieve negative resection margins.

A simple preoperative stratification tool predicting the risk of postoperative pancreatic fistula after pancreatoduodenectomy.

BACKGROUND: Postoperative pancreatic fistula (POPF) after pancreatoduodenectomy (PD) can be associated with severe postoperative morbidity. This study aims to develop a preoperative POPF risk calculator that can be easily implemented in clinical routine. METHODS: Patients undergoing PD were identified from a prospectively-maintained database. A total of 11 preoperative baseline and CT-based radiological parameters were used in a binominal logistic regression model. Parameters remaining predictive for grade B/C POPF were entered into the risk calculator and diagnostic accuracy measures and ROC curves were calculated for a training and a test patient cohort. The risk calculator was transformed into a simple nomogram. RESULTS: A total of 242 patients undergoing PD in the period from 2012 to 2018 were included. CT-imaging-based maximum main pancreatic duct (MPD) diameter (p = 0.047), CT-imaging-based pancreatic gland diameter at the anticipated resection margin (p = 0.002) and gender (p = 0.058) were the parameters most predictive for grade B/C POPF. Based on these parameters, a risk calculator was developed to identify patients at high risk of developing grade B/C POPF. In a training cohort of PD patients this risk calculator was associated with an AUC of 0.808 (95%CI 0.726-0.874) and an AUC of 0.756 (95%CI 0.669-0-830) in the independent test cohort. A nomogram applicable as a visual risk scale for quick assessment of POPF grade B/C risk was developed. CONCLUSION: The preoperative POPF risk calculator provides a simple tool to stratify patients planned for PD according to the risk of developing postoperative grade B/C POPF. The nomogram visual risk scale can be easily integrated into clinical routine and may be a valuable model to select patients for POPF-preventive therapy or as a stratification tool for clinical trials.