A systematic review and meta-analysis of germline BRCA mutations in pancreatic cancer patients identifies global and racial disparities in access to genetic testing.

BACKGROUND: Germline BRCA1 and BRCA2 mutations (gBRCAm) can inform pancreatic cancer (PC) risk and treatment but most of the available information is derived from white patients. The ethnic and geographic variability of gBRCAm prevalence and of germline BRCA (gBRCA) testing uptake in PC globally is largely unknown. MATERIALS AND METHODS: We carried out a systematic review and prevalence meta-analysis of gBRCA testing and gBRCAm prevalence in PC patients stratified by ethnicity. The main outcome was the distribution of gBRCA testing uptake across diverse populations worldwide. Secondary outcomes included: geographic distribution of gBRCA testing uptake, temporal analysis of gBRCA testing uptake in ethnic groups, and pooled proportion of gBRCAm stratified by ethnicity. The study is listed under PROSPERO registration number #CRD42022311769. RESULTS: A total of 51 studies with 16 621 patients were included. Twelve of the studies (23.5%) enrolled white patients only, 10 Asians only (19.6%), and 29 (56.9%) included mixed populations. The pooled prevalence of white, Asian, African American, and Hispanic patients tested per study was 88.7%, 34.8%, 3.6%, and 5.2%, respectively. The majority of included studies were from high-income countries (HICs) (64; 91.2%). Temporal analysis showed a significant increase only in white and Asians patients tested from 2000 to present (P < 0.001). The pooled prevalence of gBRCAm was: 3.3% in white, 1.7% in Asian, and negligible (<0.3%) in African American and Hispanic patients. CONCLUSIONS: Data on gBRCA testing and gBRCAm in PC derive mostly from white patients and from HICs. This limits the interpretation of gBRCAm for treating PC across diverse populations and implies substantial global and racial disparities in access to BRCA testing in PC.

Robotic Dual-Console Distal Pancreatectomy: Could it be Considered a Safe Approach and Surgical Teaching even in Pancreatic Surgery? A Retrospective Observational Study Cohort.

BACKGROUND: The study aims to assess the safety and feasibility of the robotic dual-console during a robotic distal pancreatectomy METHODS: The data of the consecutive patients submitted to RDP from 2012 to 2019 at the Verona University were retrieved from a prospectively maintained database. The patients submitted to RDP were divided into the dual-console platform group (DG) and compared to the standard robotic procedure group (SG). RESULTS: In the study period, 102 robotic distal pancreatectomies were performed, of whom 42 patients (41%) belonged to the DG and 60 patients (59%) to the SG. Higher operation time was recorded in the DG compared to the SG (410 vs. 265 min, p < 0.001). The overall conversion rate of the series was 7% (n 7 patients). All the conversions were observed in the SG (p = 0.021). No differences in morbidity or pancreatic fistula rate were recorded (p > 0.05). No mortality events in the 90th postoperative days were reported in this series. CONCLUSIONS: The robotic dual-console approach for distal pancreatectomy is safe, feasible, and reproducible. The postoperative surgical outcomes are comparable to the standard RDP with the single-console da Vinci Surgical System®. This surgical technique can widely and safely improve the robotic surgical training program.

Reshaping preoperative treatment of pancreatic cancer in the era of precision medicine.

This review summarises the recent evidence on preoperative therapeutic strategies in pancreatic cancer and discusses the rationale for an imminent need for a personalised therapeutic approach in non-metastatic disease. The molecular diversity of pancreatic cancer and its influence on prognosis and treatment response, combined with the failure of 'all-comer' treatments to significantly impact on patient outcomes, requires a paradigm shift towards a genomic-driven approach. This is particularly important in the preoperative, potentially curable setting, where a personalised treatment allocation has the substantial potential to reduce pancreatic cancer mortality.

Hypofractionated Stereotactic Body Radiation Therapy With Simultaneous Integrated Boost and Simultaneous Integrated Protection in Pancreatic Ductal Adenocarcinoma.

AIMS: To evaluate the safety and feasibility of stereotactic body radiation therapy (SBRT) with simultaneous integrated boost (SIB) and simultaneous integrated protection (SIP) in borderline resectable and locally advanced pancreatic ductal adenocarcinoma. MATERIALS AND METHODS: Patients receiving SBRT following induction chemotherapy from January 2017 to December 2018 were included in this observational analysis. SBRT was delivered in five consecutive daily fractions by administering 30 Gy to the planning target volume while simultaneously delivering a 50 Gy SIB to the tumour-vessel interface. SIP was created by lowering the dose to 25 Gy on the overlap area between the planning target volume and the planning organ at risk volume. The primary end point was acute and late gastrointestinal grade ≥3 toxicity. Secondary end points were freedom from local progression, overall survival and progression-free survival (PFS). RESULTS: Fifty-nine consecutive patients (27 borderline resectable and 32 locally advanced) were included. Fifty-eight patients (98.3%) completed the SBRT planned treatment and 35 patients (59.4%) received surgical resection following SBRT. No acute or late grade ≥3 SBRT-related adverse events were observed. The median follow-up time was 15.1 months in the overall cohort and 18.1 months in censored patients. One- and 2-year freedom from local progression rates were 85% and 80% versus 79.7% and 60.6% in resected and unresected patients, respectively (P = 0.33). The median overall survival and PFS were 30.2 months and 19 months from diagnosis and 19.1 months and 10.7 months from SBRT in the entire cohort. Resected patients had improved 2-year overall survival rates (72.5% versus 49%, P = 0.012) and median PFS (13 months versus 5 months; P < 0.001) relative to unresected patients. There was no survival difference between borderline resectable and locally advanced patients. CONCLUSIONS: SBRT with SIB/SIP had an excellent toxicity profile and could be administered safely on pancreatic ductal adenocarcinoma patients, even in a total neoadjuvant setting.

Modelling centralization of pancreatic surgery in a nationwide analysis.

BACKGROUND: The benefits of centralization of pancreatic surgery have been documented, but policy differs between countries. This study aimed to model various centralization criteria for their effect on a nationwide cohort. METHODS: Data on all pancreatic resections performed between 2014 and 2016 were obtained from the Italian Ministry of Health. Mortality was assessed for different hospital volume categories and for each individual facility. Observed mortality and risk-standardized mortality rate (RSMR) were calculated. Various models of centralization were tested by applying volume criteria alone or in combination with mortality thresholds. RESULTS: A total of 395 hospitals performed 12 662 resections; 305 hospitals were in the very low-volume category (mean 2·6 resections per year). The nationwide mortality rate was 6·2 per cent, increasing progressively from 3·1 per cent in very high-volume to 10·6 per cent in very low-volume hospitals. For the purposes of centralization, applying a minimum volume threshold of at least ten resections per year would lead to selection of 92 facilities, with an overall mortality rate of 5·3 per cent. However, the mortality rate would exceed 5 per cent in 48 hospitals and be greater than 10 per cent in 17. If the minimum volume were 25 resections per year, the overall mortality rate would be 4·7 per cent in 38 facilities, but still over 5 per cent in 17 centres and more than 10 per cent in five. The combination of a volume requirement (at least 10 resections per year) with a mortality threshold (maximum RSMR 5 or 10 per cent) would allow exclusion of facilities with unacceptable results, yielding a lower overall mortality rate (2·7 per cent in 45 hospitals or 4·2 per cent in 76 respectively). CONCLUSION: The best performance model for centralization involved a threshold for volume combined with a mortality threshold.

ANTECEDENTES: Los beneficios de la centralización de la cirugía pancreática están bien documentados, pero la política de actuación difiere entre los países. Este estudio tuvo como objetivo desarrollar modelos de centralización basados en varios criterios y analizar su aplicación en una cohorte nacional. MÉTODOS: Los datos de todas las resecciones pancreáticas realizadas entre 2014 y 2016 se obtuvieron del Ministerio de Salud italiano. La mortalidad se evaluó para diferentes categorías del volumen hospitalario y para cada centro individualmente. Se calculó la mortalidad observada y la tasa estandarizada de riesgo de mortalidad (risk standardized mortality rate, RSMR). Se analizaron varios modelos de centralización aplicando criterios de volumen solos o en combinación con umbrales de mortalidad. RESULTADOS: Un total de 395 hospitales realizaron 12.662 resecciones; 305 de ellos pertenecían a la categoría de muy bajo volumen (media de 2,6 resecciones/año). La mortalidad nacional fue del 6,2%, aumentando progresivamente del 3,1% en los hospitales de muy alto volumen al 10,6% en los hospitales de muy bajo volumen. Para fines de centralización, al aplicar un umbral de volumen mínimo ≥ 10 resecciones/año, se seleccionarían 92 centros, con una mortalidad global del 5,3%. Sin embargo, la mortalidad sería > 5% en 48 hospitales y > 10% en 17 hospitales. Si el volumen mínimo fuera de 25 resecciones/año, la mortalidad global sería del 4,7% en 38 hospitales, pero aún > 5% en 17 centros y > 10% en seis centros. La combinación de un volumen necesario (≥ 10 resecciones/año) con un umbral de mortalidad (RSMR ≤ 5% o ≤ 10%) permitiría excluir hospitales con resultados inaceptables, determinando una mortalidad global más baja (2,7% en 45 hospitales o 4,2% en 76 hospitales, respectivamente). CONCLUSIÓN: El mejor modelo para la centralización de resecciones pancreáticas incluyó un umbral para el volumen hospitalario combinado con un umbral de mortalidad.

Use of an intraoperative wound protector to prevent surgical-site infection after pancreatoduodenectomy: randomized clinical trial.

BACKGROUND: Surgical-site infection (SSI) increases treatment costs, duration of hospital stay and readmission rate after pancreatic surgery. This study aimed to assess whether a wound protector could reduce the risk of superficial incisional SSI after pancreatoduodenectomy. METHODS: This RCT included patients undergoing pancreatoduodenectomy at Verona University Hospital, between 2017 and 2018. The experimental group had a dual-ring wound protector, whereas the control group had standard surgical drapes. The groups were stratified by preoperative biliary stent placement. The primary outcome was the overall rate of superficial SSI. RESULTS: An interim analysis was conducted after 212 patients had been enrolled; 22 patients (10·4 per cent) were excluded owing to inability to complete the pancreatoduodenectomy, or the need for postoperative reintervention. Some 94 patients (49·5 per cent) had a wound protector and 96 (50·5 per cent) had standard drapes. There were no differences between groups in demographics, or in intraoperative findings, pathological data or surgical outcomes. The overall superficial SSI rate was 7·4 per cent, which did not differ between groups (7 per cent in each group; P = 0·585). Subanalysis of patients with a preoperative biliary stent showed a similar outcome (superficial SSI rate 9 versus 8 per cent with wound protector versus surgical drapes respectively; P = 0·536). The trial was stopped prematurely on the grounds of futility. CONCLUSION: Use of a wound protector did not reduce the rate of superficial SSI after pancreatoduodenectomy. Registration number: NCT03820648 (http://www.clinicaltrials.gov).

ANTECEDENTES: La infección de la herida quirúrgica (surgical-site infection, SSI), especialmente de la incisión, aumenta sobremanera los costes del tratamiento, la duración de la estancia y la tasa de reingresos en la cirugía de páncreas. En los últimos años se han introducido los protectores de las heridas (wound protectors, WP) con la intención de reducir la tasa de SSI. Este estudio tuvo como objetivo evaluar si un WP podría reducir la incidencia de la SSI superficial de la incisión (superficial incisional surgical-site infection, SI-SSI) en pacientes sometidos a duodenopancreatectomía cefálica (pancreaticoduodenectomy, PD). MÉTODOS: Ensayo aleatorizado controlado en el que se incluyeron los pacientes a los que se realizó una PD en la Universidad de Verona entre 2017 y 2018. En el grupo experimental se utilizó un WP de doble anillo, mientras que el grupo control se utilizaron tallas quirúrgicas convencionales (standard drape, SD). Los grupos se estratificaron también según la colocación preoperatoria de una prótesis biliar. RESULTADOS: Se incluyeron 212 pacientes, de los que 22 (10%) abandonaron el estudio debido a la imposibilidad de realizar la DP o a la necesidad de una reintervención durante el curso postoperatorio. Los pacientes se dividieron en 94 (49%) en el grupo WP y 96 (51%) en el grupo SD. No se detectaron diferencias entre grupos en cuanto a las variables demográficas y a los resultados intraoperatorios, patológicos o quirúrgicos. La tasa global de SI-SSI fue del 7,4%, que no difirió entre los grupos (WP 7,5% versus SD 7,3%, P = 0,585). Teniendo en cuenta los resultados descritos, se cumplieron los criterios de futilidad del análisis y el ensayo se interrumpió prematuramente. CONCLUSIÓN: En el entorno de un centro de alto volumen, la WP por si sola no redujo la tasa de SI-SSI. Cabría plantear su utilización dentro de un programa multimodal, que debería incluir un replanteamiento interno de la institución encaminado a la reducción de complicaciones infecciosas.

Surveillance for pancreatic cancer in high-risk individuals.

Background: Surveillance of individuals at high risk of pancreatic ductal adenocarcinoma (PDAC) and its precursors might lead to better outcomes. The aim of this study was to determine the prevalence and outcomes of PDAC and high-risk neoplastic precursor lesions among such patients participating in surveillance programmes. Methods: A multicentre study was conducted through the International CAncer of the Pancreas Screening (CAPS) Consortium Registry to identify high-risk individuals who had undergone pancreatic resection or progressed to advanced PDAC while under surveillance. High-risk neoplastic precursor lesions were defined as: pancreatic intraepithelial neoplasia (PanIN) 3, intraductal papillary mucinous neoplasia (IPMN) with high-grade dysplasia, and pancreatic neuroendocrine tumours at least 2 cm in diameter. Results: Of 76 high-risk individuals identified in 11 surveillance programmes, 71 had undergone surgery and five had been diagnosed with inoperable PDAC. Of the 71 patients who underwent resection, 32 (45 per cent) had PDAC or a high-risk precursor (19 PDAC, 4 main-duct IPMN, 4 branch-duct IPMN, 5 PanIN-3); the other 39 patients had lesions thought to be associated with a lower risk of neoplastic progression. Age at least 65 years, female sex, carriage of a gene mutation and location of a lesion in the head/uncinate region were associated with high-risk precursor lesions or PDAC. The survival of high-risk individuals with low-risk neoplastic lesions did not differ from that in those with high-risk precursor lesions. Survival was worse among patients with PDAC. There was no surgery-related mortality. Conclusion: A high proportion of high-risk individuals who had surgical resection for screening- or surveillance-detected pancreatic lesions had a high-risk neoplastic precursor lesion or PDAC at the time of surgery. Survival was better in high-risk individuals who had either low- or high-risk neoplastic precursor lesions compared with that in patients who developed PDAC.

Antecedentes: Se podrían obtener mejores resultados con el seguimiento de individuos de alto riesgo para adenocarcinoma ductal pancreático (pancreatic ductal adenocarcinoma, PDAC) y lesiones precursoras. El objetivo de este estudio fue determinar la prevalencia y los resultados del PDAC y de las lesiones precursoras de alto riesgo neoplásico en pacientes que participaron en programas de seguimiento. Métodos: Se llevó a cabo un estudio multicéntrico a través del registro internacional del consorcio CAPS (Common Automotive Platform Standard) para identificar a las personas de alto riesgo que se habían sometido a una resección pancreática o habían progresado a PDAC avanzado mientras estaban en seguimiento. Se definieron como lesiones neoplásicas precursoras de alto riesgo la neoplasia intraepitelial pancreática de tipo 3 (PanIN­3), la neoplasia papilar mucinosa intraductal (intraductal papillary mucinous neoplasia, IPMN) con displasia de alto grado y los tumores neuroendocrinos pancreáticos (pancreatic neuroendocrine tumours, PanNET) de ≥ 2 cm de diámetro. Resultados: De 76 individuos con lesiones de alto riesgo identificados en 11 programas de seguimiento, 71 fueron tratados quirúrgicamente y 5 fueron diagnosticados de un PDAC inoperable. De las 71 resecciones, 32 (45%) tenían PDAC o una lesión precursora de alto riesgo (19 PDAC, 4 IPMN de conducto principal, 4 IPMN de rama secundaria y 5 PanIN­3). Los otros 39 pacientes tenían lesiones que se consideraron asociadas con un menor riesgo de progresión neoplásica. La edad ≥ 65 años, el sexo femenino, el ser portador de una mutación genética y la localización de la lesión en la cabeza/proceso uncinado fueron factores asociados a las lesiones precursoras de alto riesgo o al PDAC. No hubo diferencias en la supervivencia de individuos de alto riesgo con lesiones neoplásicas de bajo riesgo frente a aquellos que presentaron lesiones precursoras de alto riesgo. La supervivencia fue peor en los pacientes con PDAC. No hubo mortalidad relacionada con la cirugía. Conclusión: Un elevado porcentaje de individuos de alto riesgo que se sometieron a resección quirúrgica tras la detección de lesiones pancreáticas en el seguimiento tenían una lesión precursora neoplásica de alto riesgo o un PDAC. La supervivencia fue mejor en individuos de alto riesgo que tenían lesiones precursoras neoplásicas de bajo o alto riesgo en comparación con aquellos pacientes que habían desarrollado un PDAC.

The prognostic impact of para-aortic lymph node metastasis in pancreatic cancer: A systematic review and meta-analysis.

PURPOSE: To evaluate by a meta-analytic approach the long-term prognostic impact of para-aortic lymph node (PALN) involvement in resected ductal adenocarcinoma of the pancreas. METHODS: MEDLINE, Embase, PubMed and the Cochrane Library were searched from January 1990 to June 2015. Trials reporting Kaplan-Meier curves and comparing overall long-term survival of negative and metastatic PALN in patients who underwent resection for pancreatic cancer were included. Lymph nodes were classified according to the Japan Pancreatic Society rules and identified using hematoxylin and eosin staining. Hazard ratios (HRs) and 95%CI were estimated for each trial and pooled in a meta-analysis. RESULTS: Thirteen eligible studies including 2141 patients (364 positive PALN; 1777 negative PALN) were identified. Most of the studies were retrospective. Heterogeneity among trials was high (I(2) = 98.7%; p < .001). PALN metastasis was associated with increased mortality when compared with patients with negative PALN regardless regional nodal status [HR 1.85, 95%CI 1.48-2.31; p < .001]. Median survival was significantly decreased in patients with positive PALN (WMD = -4.92 months 95%CI -6.40; -3.43; p < .001). Moreover, metastatic PALN affected mortality also when regional lymph nodes were positive [HR 1.67, 95%CI 1.34-2.08; p < .001]. No publication bias was detected. CONCLUSIONS: PALN metastasis appears to correlate with poor prognosis in patients with pancreatic adenocarcinoma. The assessment of PALN status may be considered for a more accurate staging of the disease and appropriated subgroup survival reporting. However, the definitive avoidance of the resection in case of intraoperative metastatic PALN needs further investigation.