Open radiofrequency ablation as upfront treatment for locally advanced pancreatic cancer: Requiem from a randomized controlled trial

BackgroundLocal ablation of pancreatic cancer has been suggested as an option to manage locally advanced pancreatic cancer (LAPC) although no robust evidence has been published to date to support its application. The aim of this study is to compare overall survival (OS) and progression-free survival (PFS) in patients receiving both radiofrequency ablation (RFA) and conventional chemoradiotherapy (CHRT) with patients receiving CHRT only.MethodsThis is a multicentre prospective randomized controlled trial (RCT). Patients with LAPC diagnosed by the Pancreas-Ablation-Team-Verona were randomly assigned to open RFA (Group A) or CHRT (Group B). Survival analyses were performed using the Kaplan-Meier method and compared using the log-rank test. Statistical significance was set at p < 0.05.ResultsOne hundred LAPC patients were enrolled from January 2014 to August 2016. 33% of patients in Group A did not receive the designated procedure because of intraoperative findings of liver (18.7%) or peritoneal metastases (43.8%), or technical contraindications (37.5%). We did not observe any statistically significant survival benefit from RFA compared to CHRT, neither in terms of OS (medians of 14.2 months and 18.1 months, respectively, p = 0.639) nor PFS (medians of 8 months and 6 months respectively, p = 0.570). Mortality was nil and RFA-related morbidity was 15.6%. In 13% of subjects, conversion to surgery occurred (2 after RFA and 11 after CHRT).ConclusionsThis is the first RCT evaluating the impact of upfront RFA in the multimodal treatment of LAPC. Compared to CHRT, RFA alone did not provide any advantage in terms of OS or PFS. It could be considered as a therapeutic option for LAPC within a multimodal context and after neoadjuvant therapies.     

Impact of neoadjuvant chemotherapy and stereotactic body radiation therapy (SBRT) on R0 resection rate for borderline resectable and locally advanced pancreatic cancer

BackgroundThe role of neoadjuvant stereotactic body radiation therapy (SBRT) in patients with borderline resectable pancreas cancer (BRPC) and locally advanced pancreas cancer (LAPC) remains controversial.MethodsWe retrospectively evaluated BRPC and LAPC patients treated at our institution who underwent 2–3 months of chemotherapy followed by SBRT to a dose of 30–33 Gy. Overall survival (OS) and recurrence-free survival (RFS) were estimated and compared by Kaplan–Meier and log-rank methods.ResultsWe identified 103 (85 BRPC and 18 LAPC) patients treated per our neoadjuvant paradigm between 2011 and 2018, with resectability based on NCCN definitions. Median follow up was 25 months. Of patients completing neoadjuvant therapy, 73 (71%) underwent definitive resection. Seventy-one (97%) patients with definitively resected tumors had R0 resection and 5 (7%) had a complete pathologic response CR to neoadjuvant therapy. The median overall survival (OS) of the cohort was 24 months. Those with a complete or marked pathologic response had significantly better OS than those with a moderate response (41 vs 24 months, p < 0.02) and patients unable to undergo definitive surgery (17 months, p < 0.0003). Six resected patients experienced grade ≥3 surgical complications.ConclusionsNeoadjuvant chemotherapy and SBRT are associated with promising pathologic response rates and R0 resection rates, with acceptable perioperative morbidity.     

Intraoperative radiotherapy vs concurrent chemoradiotherapy in the treatment of patients with locally advanced pancreatic cancer

PurposeThe purpose of the multi-institutional retrospective study was to evaluate whether intraoperative radiotherapy (IORT) has advantages in the treatment of patients with locally advanced pancreatic cancer (LAPC) compared with concurrent chemoradiotherapy (CCRT).Patients and methodsA total of 103 patients with LAPC whom was treated with IORT (Arm A; n = 50) or CCRT (Arm B; n = 53) from 2015.6 to 2016.7 were retrospectively identified. Data on feasibility, toxicity, and overall survival (OS) were evaluated.ResultsMost factors of the two cohorts were similar. The severe adverse events (grade 3 and 4) patients in Arm B were higher than patients in Arm A (34% vs 0%). Disease progression was noted in 38 patients (76%) in Arm A and 37 patients (69.8%) in Arm B. The median survival of patients in Arm A and B were 15.3 months (95% CI, 13.0–17.6 months) and 13.8 months (95% CI, 11.0–16.6 months), respectively. The 1-year survival rate were 66.3% in Arm A (95% CI, 52.3%–80.2%) and 60.9% in Arm B (95% CI, 46.4%–75.4%). There was no significant difference in OS between patients treated with IORT and with CCRT (p = 0.458).ConclusionOur results demonstrated that patients with LAPC treated with IORT showed fewer adverse events, less treatment time, and high feasibility compared to CCRT. Although, IORT has no advantages in survival and tumor control compared with CCRT.     

CA19.9 decrease >15% is a predictor of favourable outcome in patients treated for advanced pancreatic carcinoma: analysis of two independent cohorts

BackgroundAlthough carbohydrate antigen 19.9 (CA19.9) is widely used in pancreatic adenocarcinoma (PA), no consensual cut-off value of CA19.9 decrease has been established for treatment monitoring.MethodsThis was a retrospective study including patients with a baseline CA19.9 ≥ 37 UI/ml and with locally advanced or metastatic PA from two French centers. CA19.9 measurements were performed at baseline and first CT-scan evaluation. The aim was to use a training set to determine the best cut-off of CA19.9 decrease for predicting progressive disease (PD) and to analyze its performance in an independent validation cohort.ResultsA total of 95 and 93 patients were included in the training and validation sets, respectively. A ≤15% CA19.9 decrease was the best cut-off for predicting PD with a sensitivity (Se) = 68% and a specificity (Sp) = 90%. In the validation set, this threshold was associated with Se = 76% and Sp = 83%. A >15% CA19.9 decrease was significantly associated with improved PFS (median 8.3 versus 3.1 months, p < 0.0001) and OS (median 14 versus 7.2 months, p < 0.0001). A >15% CA19.9 decrease was also identified as a factor independently associated with OS (HRa = 0.25, 95% CI:0.14–0.44).ConclusionsA CA 19.9 decrease >15% is a favourable predictor of outcome in patients treated for advanced PA.     

Respect - A multicenter retrospective study on preoperative chemotherapy in locally advanced and borderline resectable pancreatic cancer

BackgroundNeoadjuvant chemotherapy has become a powerful tool to convert borderline resectable (BRPC) and locally advanced pancreatic cancers (LAPC) into a resectable scenario. However, data analyzing the optimal type of therapy are scarce. In the present multicenter retrospective study, we evaluated the influence of FOLFIRINOX (FFX) and gemcitabine (GEM)-based neoadjuvant therapy on patient prognosis.MethodsData on 239 patients from 7 centers across Europe was gathered using an online database. Patients having received their first cycle of chemotherapy for BRPC/LAPC before 06/2017, with a minimum follow-up of 12 months, were included in the intention-to-treat analysis.ResultsPatients treated with neoadjuvant FFX (n = 135) or gemcitabine + nab-paclitaxel (GNP) (n = 38) had significantly improved radiological response according to RECIST criteria as compared to single-agent GEM (n = 16), with a partial/complete response of 59.3%, 55.3% and 6.25% respectively (p = 0.001). Treatment with FFX (n = 135) and GNP (n = 38) resulted in higher resection rates compared to GEM (73.3%, 81.6% and 43.8%; p = 0.01 and p = 0.005). Regardless of regimen, patients who were resected had significantly prolonged overall survival compared to non-resected patients (p < 0.01). Complete pathological responses (ypT0 ypN0) were predominantly observed with FFX (p = 0.01). Adjuvant GNP in addition to successful neoadjuvant therapy and surgery resulted in a trend towards improved median survival as compared to postoperative observation (47.0 vs. 30.1 months, p = 0.06).ConclusionsRepresenting one of the largest studies published so far, our results reveal that patients with BRPC/LAPC should be offered either FFX or GNP to improve chances of resection and with this also survival.     

Multimodal therapy with or without irreversible electroporation for unresectable locally advanced pancreatic adenocarcinoma: a systematic review and meta-analysis

BackgroundIrreversible electroporation (IRE) is used as a locoregional treatment modality for patients with locally advanced pancreatic cancer (LAPC), but is non-curative and is associated with postoperative morbidity and mortality. We performed a systematic review and meta-analysis comparing survival outcomes of multimodal therapy with or without IRE.MethodsSeparate searches were performed for multimodal therapy + IRE and multimodal therapy alone given the lack of comparative literature using PubMed, SCOPUS, and Cochrane Library in 3/2021. We determined overall survival (OS) and progression-free survival (PFS) from diagnosis and time of IRE. Treatment-related morbidity and mortality was determined.ResultsOf 585 published articles, 48 met inclusion criteria for IRE (n = 27) and without IRE (n = 21) with data for 1420 (IRE) and 1348 (without IRE) patients. The 6/12/24 months OS with IRE was 99%/84%/28%. The 6/12/24 months OS without IRE was 99%/80%/12%. At 12 months from IRE, OS was 55% and PFS was 12%. The mean major complication and 90-day mortality rates for IRE were 17.95% and 2.65%.ConclusionMultimodal therapy alone is associated with similar OS to multimodal therapy + IRE in patients with LAPC. Most patients progress and nearly half die within 1 year of the IRE procedure. Given the lack of quality prospective data, IRE should remain experimental and be used with caution in LAPC.     

Impact of perioperative blood transfusion on survival in pancreatic neuroendocrine tumor patients: analysis from the US Neuroendocrine Study Group

BackgroundPacked red blood cell (PRBC) transfusion has been associated with worse survival in multiple malignancies but its impact on pancreatic neuroendocrine tumors (PNETs) is unknown. The aim of this study was to determine the impact of PRBC transfusion on survival following PNET resection.MethodsA retrospective cohort study of PNET patients was performed using the US Neuroendocrine Tumor Study Group database. Demographic and clinical factors were compared. Kaplan–Meier and log-rank analyses were performed. Factors associated with transfusion, overall (OS), recurrence-free (RFS) and progression-free survival (PFS) were assessed by logistic regression.ResultsOf 1129 patients with surgically resected PNETs, 156 (13.8%) received perioperative PRBC transfusion. Transfused patients had higher ASA Class, lower preoperative hemoglobin, larger tumors, more nodal involvement, and increased major complications (all p < 0.010). Transfused patients had worse median OS (116 vs 150 months, p < 0.001), worse RFS (83 vs 128 months, p < 0.01) in curatively resected (n = 1047), and worse PFS (11 vs 24 months, p = 0.110) in non-curatively resected (n = 82) patients. On multivariable analysis, transfusion was associated with worse OS (HR 1.80, p = 0.011) when controlling for TNM stage, tumor grade, final resection status, and pre-operative anemia.ConclusionPRBC transfusion is associated with worse survival for patients undergoing PNET resection.     

Regional lymph node sampling in hepatoma resection: insight into prognosis

BackgroundThe importance of regional lymph node sampling (LNS) during resection of hepatocellular carcinoma (HCC) is poorly understood. This study sought to ameliorate this knowledge gap through a nationwide population-based analysis.MethodsPatients who underwent liver resection (LR) for HCC were identified from Surveillance, Epidemiology and End Results (SEER-18) database (2003–2015). Cohort-based clinicopathologic comparisons were made based on completion of regional LNS. Propensity-score matching reduced bias. Overall and disease-specific survival (OS/DSS) were analyzed.ResultsAmong 5395 patients, 835 (15.4%) underwent regional LNS. Patients undergoing LNS had larger tumors (7.0vs4.8 cm) and higher T-stage (30.9 vs. 17.6% T3+, both p < 0.001). Node-positive rate was 12.0%. Median OS (50 months for both) and DSS (28 vs. 29 months) were similar between cohorts, but node-positive patients had decreased OS/DSS (20/16 months, p < 0.01). Matched patients undergoing LNS had equivalent OS (46 vs. 43 months, p = 0.869) and DSS (27 vs. 29 months, p = 0.306) to non-LNS patients. The prognostic impact of node positivity persisted after matching (OS/DSS 24/19 months, p < 0.01). Overall disease-specific mortality were both independently elevated (overall HR 1.71-unmatched, 1.56-matched, p < 0.01; disease-specific HR 1.40-unmatched, p < 0.01, 1.25-matched, p = 0.09).ConclusionRegional LNS is seldom performed during resection for HCC, but it provides useful prognostic information. As the era of adjuvant therapy for HCC begins, surgeons should increasingly consider performing regional LNS to facilitate optimal multidisciplinary management.     

Irreversible electroporation after induction chemotherapy versus chemotherapy alone for patients with locally advanced pancreatic cancer: A propensity score matching analysis

BackgroundLocally advanced pancreatic cancer (LAPC) is a devastating disease and irreversible electroporation (IRE) is a non-thermal ablation method that is especially suitable for the treatment of LAPC. This study aimed to compare the long-term survival of LAPC patients after induction chemotherapy followed by IRE and chemotherapy alone.MethodsFrom August 2015 to August 2017, a total of 132 patients with LAPC were identified. The oncological outcomes of these two treatments were analyzed by propensity score matching (PSM) analysis.ResultsBefore PSM analysis, patients with LAPC had better overall survival (OS) and progression-free survival (PFS) after induction chemotherapy followed by IRE than those who received chemotherapy alone (2-year OS rates, 57.9% vs 19.8%, P < 0.001; 2-year PFS rates, 31.4% vs 9.3%, P < 0.001). The baseline clinicopathological factors were balanced between the 2 groups through PSM analysis. Even after PSM, the OS and PFS rates of patients after induction chemotherapy followed by IRE treatment were superior to those of patients who received chemotherapy treatment alone (2-year OS rates, 57.9% vs 18.1%, P < 0.001; 2-year PFS rates, 31.4% vs 7.1%, P < 0.001). Multivariate Cox regression analysis indicated that chemotherapy plus IRE was a significant prognostic factor for both OS and PFS in patients of both the whole cohort and the matched cohort.ConclusionsInduction chemotherapy followed by IRE provided better OS and PFS than chemotherapy alone for patients with LAPC. This combination method may be a more suitable treatment for patients with LAPC.     

Hepatic arterial infusion chemotherapy for colorectal liver metastases revisited

BackgroundRecent reports indicate improved survival in patients undergoing surgical treatment for colorectal liver metastases (CRLM) with hepatic arterial infusion (HAI) pump chemotherapy compared to surgery alone.MethodsPatients who underwent resection and/or ablation of CRLM between 1996 and 2016 were included from a single-institution prospectively maintained database. Proportional hazards regression analysis was performed to determine predictors of overall survival (OS) and 3:1 propensity score analysis (PSA).ResultsOf 349 patients included, 36 had HAI pumps placed (HAI group) and 313 did not (no-HAI group). There was no difference in primary tumor grade (p = 0.24), ECOG status (p = 0.44), tumor number (p = 0.1), tumor size (p = 0.56), margin status (p = 0.76) between the two groups.Median overall survival was 44.7months vs 37.1months for the HAI versus no-HAI group (p = 0.01). Cox proportional hazards regression analysis demonstrated positive margin status (HR:2.47,p < 0.0001), HAI therapy (HR:0.56,p = 0.02), preoperative chemotherapy (HR:0.69,p = 0.02) and tumor diameter (HR:1.07,p = 0.005) as predictors of OS. In 3:1 PSA, 32 HAI subjects were matched with 87 non-HAI subjects balancing all covariates. Median OS was 42.4 months versus 35.6 months for the HAI versus no-HAI group (p = 0.03).ConclusionSurgical treatment of CRLM combined with HAI chemotherapy is associated with improved OS compared to surgery alone. Further study of this treatment approach is indicated.     

Open irreversible electroporation for isolated local recurrence of pancreatic ductal adenocarcinoma after primary surgery

Background/objectivesIrreversible electroporation (IRE) is an emerging treatment for locally advanced pancreatic cancer (LAPC) which in some cohorts has been associated with severe complications. Additionally, re-resection of isolated local recurrence (ILR) after pancreatic ductal adenocarcinoma (PDAC) can improve survival. We investigated safety, feasibility and oncologic outcomes in the first report on open IRE for unresectable ILR of PDAC in a staged surgical approach.MethodsRecords of the prospectively documented institutional database were screened for patients undergoing laparotomy in IRE-standby due to questionable resectability. Endpoints were morbidity, mortality and overall (OS) and progression free survival (PFS). Data of LAPC and ILR were compared statistically for safety and feasibility analysis.ResultsIntraoperative IRE was performed in 11 ILR and 14 LAPC. Six (54.5%) ILR and 10 (71.4%) LAPC patients had postoperative complications, type and frequency did not differ significantly. Major complications occurred in one ILR and two LAPC patients. Median OS was 20.0 months (95% CI: 2.7–37.3) after IRE for ILR and 28 (17.4–38.6) for LAPC. Median PFS after IRE was seven months for both ILR (4.1–9.9; n = 9) and LAPC (2.3–11.7; n = 13).ConclusionOpen IRE for unresectable ILR was associated with acceptable perioperative risk. In this small, highly selected subset of patients with limited therapeutic options ancillary treatment with IRE might improve survival. Randomized treatment studies are required to establish the definitive role of IRE as compared to palliative standards of care in unresectable recurrence of PDAC and inconvertible LAPC.     

Clinico-pathological correlates and survival outcomes in 214 resected ampullary adenocarcinomas – are outcomes different in intestinal and pancreatobiliary subtypes with adjuvant gemcitabine?

BackgroundEvidence suggests that intestinal type (IT) and pancreatobiliary (PB) subtypes of ampullary adenocarcinoma (AC) may have different outcomes. The current study evaluated differences in outcomes between these subtypes and the benefit of adjuvant chemotherapy (AT).MethodsA prospectively maintained database of patients who underwent upfront resection for AC from January 2012 to March 2016 was conducted. A dedicated pathologist reported differentiation between IT and PB subtypes.Results214 patients were included for analysis: 105 PB subtype and 109 IT subtype. With a median follow up of 46.3 months, estimated 4 year overall survival (OS) was 65.8%. In patients with stage II–III disease, lymph-node ratio (LNR) < 0.2 [Not reached (NR) vs. 30.72 months; p = 0.002], absence of perineural invasion (PNI) (NR vs. 31.61 months; p = 0.032) and AT (gemcitabine – 96.1%) (NR vs. 22.28 months) were prognostic for superior OS. There was no difference in OS between IT and PB subtypes, but both subtypes with stage II–III disease benefitted from AT statistically as compared to observation (IT: NR vs. 28.62 months; PB: 18.46 months vs. 58.09 months; p < 0.001).ConclusionsAC-IT and AC-PB did not have a different OS when treated with resection and adjuvant gemcitabine, though adjuvant therapy benefitted both subtypes individually.     

Locally advanced pancreatic cancer: a reliable contraindication to resection in the modern era?

BackgroundThe aim of this study is to present radiologically designated LAPC found to be resectable upon surgical exploration and evaluate the outcomes of such resections.MethodsSequential LAPC patients between 2013 and 2019 were staged and underwent resection were included in the analysis of both perioperative and long-term outcomes.ResultsTwenty-eight patients with radiologically-designated LAPC underwent surgical resection after chemotherapy with a median follow-up of 31.7 m,75% underwent pancreaticoduodenectomy. The margin positivity and local recurrence rates were 21.4% and 35.7%, respectively. When compared to the 30 BRPC controls, the LAPC group had a higher rates of an arterial resection (11vs.1; p = 0.002), but the groups were similar with regard to all other preoperative and intraoperative variables (p < 0.05). Perioperative morbidity rates were similar (25.9%vs21.4%; p = 0.53). The LAPC and BRPC groups were also equivalent with respect to median recurrence-free survival (9.0mo; 95%CI 6.3, 11.7vs.8.3mo; 95%CI 5.4, 11.2) and median overall survival (19.9mo; 95%CI 17.0, 22.7 vs. 19.9mo; 95%CI 14.8, 25.1), respectively.ConclusionDespite a radiologic designation of locally advanced pancreatic cancer, certain subtypes of LAPC warrant surgical exploration provided the operative surgeon is prepared for major arterial and/or venous resection. Pancreatectomy in these patients has acceptable morbidity and oncologic outcomes, similar to patients who are radiologically borderline resectable.     

The treatment and survival of elderly patients with locally advanced pancreatic cancer: A post-hoc analysis of a multicenter registry

BackgroundThe treatment options for patients with locally advanced pancreatic cancer (LAPC) have improved in recent years and consequently survival has increased. It is unknown, however, if elderly patients benefit from these improvements in therapy. With the ongoing aging of the patient population and an increasing incidence of pancreatic cancer, this patient group becomes more relevant. This study aims to clarify the association between increasing age, treatment and overall survival in patients with LAPC.MethodsPost-hoc analysis of a multicenter registry including consecutive patients with LAPC, who were registered in 14 centers of the Dutch Pancreatic Cancer Group (April 2015–December 2017). Patients were divided in three groups according to age (<65, 65–74 and ≥75 years). Primary outcome was overall survival stratified by primary treatment strategy. Multivariable regression analyses were performed to adjust for possible confounders.ResultsOverall, 422 patients with LAPC were included; 162 patients (38%) aged <65 years, 182 patients (43%) aged 65–74 and 78 patients (19%) aged ≥75 years. Chemotherapy was administered in 86%, 81% and 50% of the patients in the different age groups (p<0.01). Median overall survival was 12, 11 and 7 months for the different age groups (p<0.01).Patients treated with chemotherapy showed comparable median overall survival of 13, 14 and 10 months for the different age groups (p=0.11). When adjusted for confounders, age was not associated with overall survival.ConclusionElderly patients are less likely to be treated with chemotherapy, but when treated with chemotherapy, their survival is comparable to younger patients.     

Surgical resection is associated with improved long-term survival of patients with resectable pancreatic head cancer compared to multiagent chemotherapy

BackgroundStandard of care for resectable pancreatic cancer is a combination of surgical resection (SR) and multiagent chemotherapy (MCT). We aim to determine whether SR or MCT is associated with superior survival for patients receiving only single-modality therapy.MethodsPatients with stage I–IIb pancreatic head adenocarcinoma who received either MCT or SR were identified in the NCDB (2013–2015). Following a piecewise approach to estimating hazards over the course of follow-up, conditional overall survival (OS) at 30, 60, and 90 days after treatment initiation was estimated using landmark analyses.Results3103 patients received MCT alone (60.3%) and 2043 underwent SR alone (39.7%). SR had an OS disadvantage at 30 (HR 3.99, 95% CI 3.12–5.11) and 60 days (HR 1.85, 95% CI 1.4–2.45), but an OS advantage after 90 days (HR 0.59, 95% CI 0.55–0.64). In a landmark analysis conditioned on 90 days survival post treatment initiation, median OS was improved for SR (17.0 vs. 12.2 months, p < 0.0001); SR improved 3-year OS by 21.3% (p < 0.05), despite patients being older (median 72 vs. 67 years, p < 0.0001) with higher Charlson-Deyo comorbidity scores (≥2: 11.2 vs. 8.6%, p = 0.006).ConclusionFor patients with resectable pancreatic cancer, SR is associated with superior long-term survival compared to MCT.     

Feasibility and safety of liver transplantation or resection after transarterial radioembolization with Yttrium-90 for unresectable hepatocellular carcinoma

BackgroundThe benefit of transarterial radioembolization (TARE) in patients with unresectable hepatocellular carcinoma (HCC) is increasingly evidenced. However, data on outcome of liver transplantation or resection after TARE remain scarce. This study aimed to assess the safety and feasibility of surgery after TARE in patients with unresectable HCC.MethodsPatients exclusively undergoing TARE followed by either orthotopic liver transplantation (OLT) or liver resection (LR) for HCC between 2012 and 2016 were included. Primary outcomes were postoperative morbidity and mortality. Secondary outcomes were overall survival (OS) and response to TARE.ResultsAmong 349 patients with HCC treated with TARE, 32 (9%) underwent either OLT (n = 22) or LR (n = 10), which represent the study cohort. In this group, TARE induced decreased viable nodules (p < 0.001), an efficient downsizing (p < 0.001) as well as a significant downstaging based on BCLC classification (p < 0.001). Overall, major complications and mortality after surgery occurred in 5 (16%) and 1 (3%) patients, respectively. For the whole study cohort, OS was 47 months while survival rates at 1-, 3- and 5-years reached 97%, 86% and 86%, respectively.DiscussionLiver surgery after TARE is feasible and safe. This strategy allows to offer a curative treatment in a subset of patients with unresectable HCC.     

Impact of postoperative pancreatic fistula on long-term oncologic outcomes after pancreatic resection

BackgroundThe short-term morbidity associated with post-operative pancreatic fistula (POPF) is well established, however data regarding the long-term impact are lacking. We aim to characterize long-term oncologic outcomes of POPF after pancreatic resection through a single institution, retrospective study of pancreatic resections performed for adenocarcinoma from 2009 to 2016.MethodsKaplan–Meier survival analysis, logistic regression, and multivariate analysis (MVA) were used to evaluate impact of POPF on overall survival (OS), disease free survival (DFS), and receipt of adjuvant chemotherapy (AC).Results767 patients were included. 82 (10.6%) developed grade B (n = 67) or C (n = 15) POPF. Grade C POPF resulted in decreased OS when compared to no POPF (20.22 vs 26.33 months, p = 0.027) and to grade B POPF (20.22 vs. 26.87 months, p = 0.049). POPF patients were less likely to receive AC than those without POPF (59.5% vs 74.9%, p = 0.003) and grade C POPF were less likely to receive AC than all others (26.7% vs 74.2%, p = 0.0001).ConclusionPOPF patients are less likely to receive AC and more likely to have delay in time to AC. These factors are exacerbated in grade C POPF and likely contribute to decreased OS. These findings validate the clinical significance of the ISGPF definition of POPF.     

Outcome after resection for invasive intraductal papillary mucinous neoplasia is similar to conventional pancreatic ductal adenocarcinoma

Background/objectivesResections for intraductal papillary mucinous neoplasm (IPMN) have increased last decades. Overall survival (OS) for conventional pancreatic ductal adenocarcinoma (PDAC) is well known but OS for invasive IPMN (inv-IPMN) is not as conclusive. This study aims to elucidate potential differences in clinicopathology and OS between these tumor types and to investigate if the raised number of resections have affected outcome.MethodsConsecutive patients ≥18 years of age resected for inv-IPMN and PDAC at Karolinska University Hospital between 2009 and 2018 were included. Clinicopathological variables were analyzed in multivariable regression models. Outcome was assessed calculating two-year OS, estimating OS using the Kaplan-Meier model and comparing survival functions with log-rank test.Results513 patients were included, 122 with inv-IPMN and 391 with PDAC. During the study period both the proportion resected inv-IPMN and two-year OS, irrespective of tumor type, increased (2.5%–45%; p < 0.001 and 44%–57%; p = 0.005 respectively). In Kaplan-Meier survival analysis inv-IPMN had more favorable median OS (mOS) compared to PDAC (33.6 months vs 19.3 months, p = 0.001). However, in multivariable Cox Regression analysis, tumor type was not a predictor for death, but so were resection period, tumor subtype and N-stage (all p < 0.001).ConclusionIn this large single center observational cohort study, inv-IPMN seemed to have favorable survival outcome compared to PDAC, but after adjusting for predictors for death this benefit vanished. The combination of a pronounced increase in resected inv-IPMN and a concurrent hazard abatement for death within 2 years during the study period proved to be a principal factor.     

Adjuvant therapy is associated with improved overall survival in patients with pancreatobiliary or mixed subtype ampullary cancer after pancreatoduodenectomy - A multicenter cohort study

Background/ObjectiveThe benefit of adjuvant therapy in ampullary cancer (AMPAC) patients following pancreatoduodenectomy (PD) is debated. The aim of this study was to determine the role of adjuvant therapy after pancreatoduodenectomy (PD) in histological subtypes of AMPAC.MethodsPatients undergoing PD for AMPAC at 5 high-volume European surgical centers from 1996 to 2017 were identified. Patient baseline characteristics, surgical and histopathological parameters, and long-term overall survival (OS) after resection were evaluated.Results214 patients undergoing PD for AMPAC were included. ASA score (ASA1-2 149 vs. ASA 3–4 82 months median OS, p = 0.002), preoperative serum CEA (CEA <0.5 ng/ml 128 vs. CEA >0.5 ng/ml 62 months, p = 0.013), preoperative serum CA19-9 (CA19-9 < 40 IU/ml 147 vs. CA19-9 > 40IU/ml 111 months, p = 0.042), T stage (T1-2 163 vs. T3-4 98 months, p < 0.001), N stage (N0 159 vs. N+ 110 months, p < 0.001), grading (G1-2 145 vs. G3-4 113 months, p = 0.026), R status (R0 136 vs. R+ 38 months, p = 0.031), and histological subtype (intestinal subtype 156 vs. PB/M subtype 118 months, p = 0.003) qualified as prognostic parameters. In multivariable analysis, ASA score (HR 1.784, 95%CI 0.997–3.193, p = 0.050) and N stage (HR 1.831, 95%CI 0.904–3.707, p = 0.033) remained independent prognostic factors. In PB/M subtype AMPAC, patients undergoing adjuvant therapy showed an improved median overall survival (adjuvant therapy 85 months vs. no adjuvant therapy 65 months, p = 0.005), and adjuvant therapy remained an independent prognostic parameter in multivariate analysis (HR 0.351, 95%CI 0.151–0.851, p = 0.015). There was no significant benefit of adjuvant therapy in intestinal subtype AMPAC patients.ConclusionAdjuvant treatment seems indicated in pancreatobiliary or mixed type AMPAC.     

Oncologic impact of preoperative prognostic nutritional index change in resected pancreatic cancer following neoadjuvant chemotherapy

BackgroundAlthough several studies have focused on the oncologic impact of the preoperative prognostic nutritional index (PNI), there is no study correlating the preoperative PNI changes with the oncologic outcome of resected pancreatic cancer following neoadjuvant chemotherapy (NAC).MethodsWe retrospectively analyzed 107 pancreatic ductal adenocarcinoma patients who underwent NAC followed by surgical resection. ΔPNI was defined as post-NAC PNI subtracted from pre-NAC PNI. Patients were divided into high (≥-1.94, n = 54) and low ΔPNI groups (<-1.94, n = 53). Long-term oncologic outcomes, such as overall survival (OS) and disease-free survival (DFS), were compared. Univariate and multivariate analysis were used to identify independent prognostic factors.ResultsThe high ΔPNI group correlated with lower pre-NAC PNI (46.96 ± 4.68 vs. 51.77 ± 5.63, p < 0.001) and higher post-NAC PNI (50.05 ± 4.80 vs. 42.56 ± 7.44, p < 0.001) more than the low ΔPNI group. The high ΔPNI group was also associated with longer OS compared with the low ΔPNI group (mean OS: 63.97 months [95% CI: 49.95–77.99] vs. 41.16 months [95% CI: 27.66–54.66], p = 0.003); there was no significant difference in DFS (p > 0.05). Multivariate analysis revealed that low ΔPNI was an independent risk factor for OS (HR, 3.516; 95% CI, 1.885–6.558; p < 0.001), but not for DFS (p > 0.05).ConclusionsLow ΔPNI (<-1.94) was an independent risk factor for the overall survival of resected pancreatic cancer patients following NAC. In the preoperative setting, improving the PNI can better the long-term oncologic outcome of this condition.