Pathologic complete response following neoadjuvant therapy for pancreatic ductal adenocarcinoma: defining the incidence,predictors, and outcomes

BackgroundNeoadjuvant therapy (NT) is increasingly utilized for patients with pancreatic ductal adenocarcinoma (PDAC) but the nationwide incidence and long-term prognosis of a pathologic complete response (pCR) remains poorly understood.MethodsPatients with localized PDAC and known cT and pT stage who received NT prior to pancreatectomy from 2004 to 2016 were identified using the National Cancer Database. The clinicopathologic characteristics and long-term outcomes of patients who did and did not experience a pCR were compared.ResultsAmong 7,902 patients who underwent NT prior to pancreatectomy, 244 (3.1%) experienced a pCR while 7,658 (96.9%) did not. On multivariable regression, longer duration of NT (OR 1.20, 95% CI 1.14–1.27 per month) and use of preoperative radiation (OR 9.98, 95% CI 3.05–32.71) were independently associated with a pCR. Median overall survival (OS) was longer among patients who experienced a pCR (77 vs 26 months, p < 0.001). On multivariate analysis, pCR was the strongest predictor of improved OS (HR 0.43, 95%CI 0.32–0.58, p < 0.001).ConclusionA pCR following NT for PDAC occurs infrequently but is associated with significantly improved OS. Better predictors of response and more effective preoperative regimens should be aggressively sought.     

Contemporary outcomes of pancreaticoduodenectomy for benign and precancerous cystic lesions

BackgroundThe decision to undertake pancreaticoduodenectomy for benign and precancerous lesions has historically relied on outcomes data from operations for cancer. We aimed to describe risks for these specific patients and identify the highest risk groups.MethodsThe ACS-NSQIP pancreatic targeted data was queried for pancreaticoduodenectomies for benign and pre-cancerous neoplasms from 2014 to 2018. Baseline characteristics, operative techniques and outcomes were examined. Multivariate regression was performed to identify predictors of major complications.Results748 patients underwent pancreaticoduodenectomy for (n = 541,72.3%) IPMN, (n = 87,11.6%) MCN, (n = 78,10.4%) serous cystadenoma, and (n = 42,5.6%) solid pseudopapillary neoplasm. Median LOS was 8 days. Major complications (n = 135,18.0%), non-home discharges (n = 83,11.1%) and readmissions (n = 153,20.5%) occurred frequently. In patients ≥ 80 years of age (n = 37), major complications (n = 11,29.7%) and non-home discharge (n = 9,24.3%) were quite common. 5-item modified frailty index ≥ 0.4 (OR 1.84,95%CI 1.06–3.19,p = 0.030), Male sex (OR 1.729,95%CI 1.152–2.595,p = 0.008), Age ≥ 65 (OR 1.63,95%CI 1.05–2.54,p = 0.29) and African-American race (OR 2.50,95%CI 1.22–5.16,p = 0.013) were independent predictors of major morbidity.ConclusionsPancreaticoduodenectomies in this setting have high rates of major complications. Morbidity extends beyond the index hospitalization, with frequent readmission and non-home discharge. Patient specific factors, rather than technical or disease factors predicted outcomes. In certain patients, particularly those older than 80, the morbidity of this operation may exceed the cancer prevention benefits.     

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.     

The impact of intra- and postoperative fluid balance in pancreatic surgery - A retrospective cohort study

Background/objectivesThe aim of this study was to evaluate the impact of perioperative fluid administration in pancreatic surgery.MethodsPatients who underwent pancreatic resections were identified from our institution's prospectively maintained database. Fluid balances were recorded intraoperatively and at 24hr postoperatively. Patients were stratified into tertiles of fluid administration (low, medium, high). Adjusted multivariable analysis was performed and outcome measures were postoperative complications.ResultsA total of 211 patients were included from 2012 to 2017. Complication rates were POPF(B/C) 19.4%, DGE(B/C) 14.7%, PPH(C) 10.0% and CDC ≥ IIIb 26.1%. In multivariable analysis, high perioperative fluid balance was an independent risk factor associated with POPF (OR = 10.5, 95%CI 2.7–40.7, p = .001), CDC (OR = 2.5, 95%CI 1.2–5.3, p < .002), DGE (OR = 2.3, 95%CI 1.0–5.2, p = .017), PPH (OR = 6.7 95%CI 2.2–20.0, p = .038) and reoperation (OR = 3.1, 95%CI 1.6–6.2, p = .006). In multivariable analysis with intraoperative and postoperative fluid balances as separate predictors, intraoperative (OR = 2,5, 95%CI 1.2–5.5, p = .04) and postoperative fluid balance (OR = 2.5, 95%CI 1.2–5.5, p = .02) were predictors of POPF. Postoperative fluid balance was the only predictor for mortality (OR = 4.5, 95%CI 1.0–18.9, p = .041) and predictor for CDC (OR = 2.0, 95%CI 1.0–4.0, p = .043) and OHS days (OR = 6.9, 95%CI 0.03–13.7, p = .038).ConclusionsHigh postoperative fluid balance in particular is associated with postoperative morbidity. Maintaining a fluid-restrictive strategy postoperatively should be recommended for patients undergoing pancreatic surgery.     

The quality of pain management in pancreatic cancer: A prospective multi-center study

Background/objectivesPancreatic ductal adenocarcinoma (PDAC) is frequently associated with severe pain. Given the almost inevitably fatal nature of the disease, pain control is crucial. However, data on quality of pain management in PDAC is scarce.MethodsThis is a multi-center, prospective study to evaluate the quality of pain management in PDAC. Insufficient pain treatment (undertreatment) was prevalent if there was an incongruence between the patients level of pain and the potency of analgesic drug therapy. Determinants of pain and undertreatment were identified using multivariable logistic regression.Results139 patients with histologically confirmed PDAC were analyzed. The prevalence of pain was 63%, with approximately one third of the patients grading their pain as moderate to severe. Palliative stage (OR: 3.37, 95%CI: 1.23–9.21, p = 0.018) and localization of the primary tumor in the body or tail (OR: 2.57, 95%CI: 1.05–6.31, p = 0.039) were independent determinants of pain. Of those reporting pain, 60% were undertreated and in 89% pain interfered with activities and emotions. Age ≥ 70 years (OR: 3.20, 95%CI: 1.09–9.41, p = 0.035) was an independent predictor of undertreatment. Patients with longer-known PDAC ( ≥ 30 days) showed improved pain management compared to new cases (OR: 0.19, 95%CI: 0.05–0.81, p = 0.025). Treatment by gastroenterologists (OR: 0.22, 95%CI: 0.05–0.89, p = 0.034) was associated with less undertreatment.ConclusionsThe results show a high proportion of PDAC patients with pain, pain interference and undertreatment, whose characteristics could help to identify patients at risk in the future. Several changes in the management of cancer-related pain are necessary to overcome barriers to optimal treatment.     

Factors predicting ablation site recurrence following percutaneous microwave ablation of colorectal hepatic metastases

BackgroundMicrowave ablation (MWA) is a recognised treatment option for liver metastases. The size of the tumour is a well-established factor that influences the success of MWA. However, the effect of “heat sink” on the success of MWA for hepatic metastases is unclear. The aim of this study was to determine whether heat sink effect is a factor that contributes to ablation site recurrence (ASR).MethodsA prospectively maintained database of patients who underwent percutaneous MWA for treatment of colorectal liver metastases was analysed. Imaging and demographic characteristics were compared between metastases that recurred following ablation and those that did not. Proximity to a large hepatic vein was defined as <10 mm.Results126 ablations in 87 patients met the inclusion criteria and were studied over a median follow-up period of 28 (12–75) months. ASR was detected in 43 ablations (34%) and was associated with clinical risk score (CRS) ≥2 (OR 2.2 95% CI 1.3–3.3, p = 0.029), metastasis size (OR 0.953 95% CI (0.929–0.978), p < 0.001) and proximity to a large hepatic vein (OR 7.5 95%CI 2.4–22.8, p < 0.001). Proximity to a large hepatic vein was not associated with reduced overall survival (OS) but was associated with liver-specific recurrence (HR 4.7 95%CI 1.7–12.5, p = 0.004).ConclusionsIn addition to tumour size proximity to large hepatic venous structures is an independent predictor of ASR and liver-specific recurrence following MWA. However, this was not associated with overall survival.     

Systematic review and meta-analysis on targeted therapy in advanced pancreatic cancer

AimA systematic review and meta-analysis from literature has been performed to assess the impact of targeted therapy in advanced pancreatic cancer.MethodsBy searching different literature databases and major cancer meetings proceedings, data from all randomized clinical trials designed to investigate molecular targeted agents in the treatment of advanced pancreatic cancer were collected. The time-frame between January 2007 and March 2015 was selected. Data on predefined end-points, including overall survival, progression-free survival in terms of Hazard Ratio and response-rate were extracted and analyzed by a random effects model. Pooled data analysis was performed according to the DerSimonian and Laird test. The occurrence of publication bias was investigated through Begg's test by visual inspection of funnel plots.ResultsTwenty-seven randomized clinical trials for a total of 8205 patients were selected and included in the final analysis. A significant benefit was demonstrated for anti-EGFR agents on overall survival (HR = 0.880; 95% confidence interval (CI) 0.797–0.972; p = 0.011). In the pooled analysis no benefit on overall survival (OS: pooled HR = 0.957; 95%CI 0.900–1.017; p = 0.153), or progression-free survival (PFS: pooled HR = 0.908; 95%CI 0.817–1.010; p = 0.075) for targeted-based therapies as compared to conventional treatments could be demonstrated. No advantage was reported in response-rate (OR for RR = 1.210; 95%CI 0.990–1.478; p = 0.063). Begg's funnel plot showed no evidence of publication bias.ConclusionThe use of molecular targeted agents does not translate into clinical benefit. Therefore, our work highlights the need to identify predictive factors for patient selection and rationally designed clinical trials.     

Low serum albumin levels and in-hospital outcomes in patients with ST segment elevation myocardial infarction

Background and aimsLow serum albumin (SA) is associated with an increased risk of long-term adverse events (AEs) among patients with chronic coronary syndromes. Its prognostic role in patients with ST-elevation myocardial infarction (STEMI) is less clear. To investigate the association between low SA and in-hospital AEs in STEMI patients.Methods and resultsMulticenter retrospective cohort study of 220 STEMI patients undergoing primary percutaneous coronary intervention within 12 h from the onset of symptoms. Hypoalbuminemia was defined by serum SA <35 g/L. SA. In-hospital AEs were defined as cardiogenic shock, resuscitated cardiac arrest and death. Median SA was 38 (IQR 35.4–41.0) g/L and 37 (16.8%) patients showed hypoalbuminemia (<35 g/L) on admission. Patients with hypoalbuminemia were older, more frequently women and diabetics, prior CAD and HF. Furthermore, they showed lower hemoglobin levels and impaired renal function. At multivariable logistic regression analysis, diabetes (odds ratio [OR]:4.59, 95% confidence interval [CI] 1.71–12.28, p = 0.002) and haemoglobin (OR:0.52, 95%CI 0.37–0.72, p < 0.001) were associated with low SA. In a subgroup of 132 patients, SA inversely correlated with D-Dimer (rS −0.308, p < 0.001). Globally, twenty-eight (14.6%) AEs were recorded. Hypoalbuminemia (OR:3.43, 95%CI 1.30–9.07, p = 0.013), high-sensitive (HS)-Troponin peak above median (OR:5.41, 95%CI 1.99–14.7, p = 0.001), C-reactive protein (CRP) peak above median (OR:6.03, 95%CI 2.02–18.00, p = 0.001), and in-hospital infection (OR:3.61, 95%CI 1.21–10.80, p = 0.022) were associated with AEs.ConclusionLow SA levels are associated with worse in-hospital AEs in STEMI patients, irrespective of HS-troponin and CRP plasma levels. Our findings suggest that low SA may contribute to the pro-thrombotic phenotype of these patients.     

Systematic review and meta-analysis of fluid therapy protocols in acute pancreatitis: type,rate and route

BackgroundAdequate fluid resuscitation is paramount in the management of acute pancreatitis (AP). The aim of this study is to assess benefits and harms of fluid therapy protocols in patients with AP.MethodsMEDLINE, Embase, Science Citation Index and clinical trial registries were searched for randomised clinical trials published before May 2020, assessing types of fluids, routes and rates of administration.ResultsA total 15 trials (1073 participants) were included. Age ranged from 38 to 73 years; follow-up period ranged from 0.5 to 6 months. Ringer lactate (RL) showed a reduced number of severe adverse events (SAE) when compared to normal saline (NS) (OR 0.48; 95%CI 0.29–0.81, p = 0.006); additionally, NS showed reduced SAE (RR 0.38; 95%IC 0.27–0.54, p < 0.001) and organ failure (RR 0.30; 95%CI 0.21–0.44, p < 0.001) in comparison with hydroxyethyl starch (HES).High fluid rate fluid infusion showed increased mortality (OR 2.88; 95%CI 1.41–5.88, p = 0.004), increased number of SAE (RR 1.42; 95%CI 1.04–1.93, p = 0.030) and higher incidence of sepsis (RR 2.80; 95%CI 1.51–5.19, p = 0.001) compared to moderate fluid rate infusion.ConclusionsIn patients with AP, RL should be preferred over NS and HES should not be recommended. Based on low-certainty evidence, moderate-rate fluid infusion should be preferred over high-rate infusion.     

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.     

Treatment of hepatocellular carcinoma beyond the Milan criteria. A weighted comparative study of surgical resection versus chemoembolization

BackgroundOptimal treatment of hepatocellular carcinoma (HCC) beyond the Milan criteria (MC) is debated. The aim of the study was to assess overall-survival (OS) and disease-free-survival (DFS) for HCC beyond MC when treated by trans-arterial-chemoembolization (TACE) or surgical resection (SR).Methodbetween 2005 and 2015, all patients with a first diagnosis of HCC beyond MC(1 nodule>5 cm, or 3 nodules>3 cm without macrovascular invasion) were evaluated. Analyses were carried out through Kaplan–Meier, Cox models and the inverse probability weighting (IPW) method to reduce allocation bias. Sub-analyses have been performed for multinodular and single large tumors compared with a MC-IN cohort.Results226 consecutive patients were evaluated: 118 in SR group and 108 in TACE group. After IPW, the two pseudo-populations were comparable for tumor burden and liver function. In the SR group, 1–5 years OS rates were 72.3% and 35% respectively and 92.7% and 39.3% for TACE (p = 0.500). The median DFS was 8 months (95%CI:8–9) for TACE, and 11 months (95%CI:9–12) for SR (p < 0.001). TACE was an independent predictor for recurrence (HR 1.5; 95%CI: 1.1–2.1; p = 0.015). Solitary tumors > 5 cm and multinodular disease had comparable OS and DFS as Milan-IN group (p > 0.05).ConclusionSurgery allowed a better control than TACE in patient bearing HCC beyond MC. This translated into a significant benefit in terms of DFS but not OS.     

Endoscopic ultrasound acquired portal venous circulating tumor cells predict progression free survival and overall survival in patients with pancreaticobiliary cancers

Background and aimsDespite recent advances, patients with pancreaticobiliary cancers have a poor prognosis. We previously demonstrated the efficacy of endoscopic ultrasound (EUS) guided acquisition of portal vein (PV) blood for enumeration of circulating tumor cells (CTCs). The aim of this study was to assess PV-CTCs as potential biomarkers for the assessment of progression-free (PFS) and overall survival (OS) in patients with pancreaticobiliary cancers.Methods17 patients with biopsy-proven pancreaticobiliary malignancy were enrolled. CTCs were enumerated from both peripheral and PV blood. All patients were followed until death. PFS and OS were evaluated with the log-rank test and summarized with the use of Kaplan–Meier methods. Unadjusted and adjusted Cox-proportional hazards models were fitted to study the relationship between PV-CTCs and PFS and OS.ResultsAfter 3.5 years of follow-up, all patients had expired. PV-CTCs were detected in all patients (median PV-CTCs 62.0/7.5 mL (interquartile range [IQR] 17–132). The mean PFS in patients with PV-CTCs <185/7.5 mL was significantly longer than patients with PV-CTCs ≥185/7.5 mL (43.3 weeks vs. 12.8 weeks, log-rank p = 0.002). The mean OS in patients with PV-CTCs <185/7.5 mL was significantly longer than patients with PV-CTCs ≥185/7.5 mL (75.8 weeks vs. 29.5 weeks, log-rank p = 0.021). In an adjusted Cox-proportional hazards model, PV-CTCs were significant predictors of both PFS and OS (HR 1.004, p = 0.037; HR 1.004, p = 0.044 respectively).ConclusionIn this pilot and feasibility study, EUS-acquired PV-CTCs predicted PFS and OS. Our findings suggest that PV-CTCs can help provide important prognostic data for both providers and patients.     

Predictors of hospital transfer and associated risks of mortality in acute pancreatitis

BackgroundThere is limited research in prognosticators of hospital transfer in acute pancreatitis (AP). Hence, we sought to determine the predictors of hospital transfer from small/medium-sized hospitals and outcomes following transfer to large acute-care hospitals.MethodsUsing the 2010–2013 Nationwide Inpatient Sample (NIS), patients ≥18 years of age with a primary diagnosis of AP were identified. Hospital size was classified using standard NIS Definitions. Multivariable analyses were performed for predictors of “transfer-out” from small/medium-sized hospitals and mortality in large acute-care hospitals.ResultsAmong 381,818 patients admitted with AP to small/medium-sized hospitals, 13,947 (4%) were transferred out to another acute-care hospital. Multivariable analysis revealed that older patients (OR = 1.04; 95%CI 1.03–1.06), men (OR = 1.15; 95%CI 1.06–1.24), lower income quartiles (OR = 1.54; 95%CI 1.35–1.76), admission to a non-teaching hospital (OR = 3.38; 95%CI 3.00–3.80), gallstone pancreatitis (OR = 3.32; 95%CI 2.90–3.79), pancreatic surgery (OR = 3.14; 95%CI 1.76–5.58), and severe AP (OR = 3.07; 95%CI 2.78–3.38) were predictors of “transfer-out”. ERCP (OR = 0.53; 95%CI 0.43–0.66) and cholecystectomy (OR = 0.14; 95%CI 0.12–0.18) were associated with decreased odds of “transfer-out”.Among 507,619 patients admitted with AP to large hospitals, 31,058 (6.1%) were “transferred-in” from other hospitals. The mortality rate for patients “transferred-in” was higher than those directly admitted (2.54% vs. 0.91%, p < 0.001). Multivariable analysis revealed that being “transferred-in” from other hospitals was an independent predictor of mortality (OR = 1.47; 95% CI 1.22–1.77).ConclusionsPatients with AP transferred into large acute-care hospitals had a higher mortality than those directly admitted likely secondary to more severe disease. Early implementation of published clinical guidelines, triage, and prompt transfer of high-risk patients may potentially offset these negative outcomes.     

Correlating serum alpha-fetoprotein in hepatocellular carcinoma with response to Yttrium-90 transarterial radioembolization with glass microspheres (TheraSphere™)

BackgroundFew studies have assessed the relationship between serum alpha-fetoprotein (AFP) and yttrium-90 (Y-90) radioembolization response in hepatocellular carcinoma (HCC). The objective of the study was to evaluate whether peri-procedural serum AFP was correlated with Y-90 therapy response in HCC.MethodsPatients undergoing Y-90 radioembolization with glass microspheres (TheraSphere™) for HCC between 2006 and 2013 at a single center were evaluated. The relationship between AFP and 6-month radiographic improvement (complete or partial response by modified RECIST criteria), overall (OS), and disease-specific survival (DSS) were analyzed.ResultsSeventy-four patients underwent a total of 124 Y-90 infusions. Median age was 65 years, median AFP was 37 ng/mL (range: 2–112,593 ng/mL) and median model for end-stage liver disease score was 6.2 (range:1.8–11.2). Increased AFP was not associated with radiographic improvement (odds ratio (OR) = 0.99, 95% confidence interval (CI) = 0.75–1.30, p = 0.92). Median OS was 15.2 months and was increased in patients with low AFP compared to high AFP (30.8 months vs. 7.8 months, p < 0.001). On multivariable regression analysis, increased AFP was associated with worse OS (OR = 1.11, 95%CI = 1.01–1.22, p = 0.034) and DSS (OR = 1.13, 95%CI = 1.03–1.25, p = 0.018).ConclusionPre-infusion AFP independently predicted survival after Y-90 treatment for HCC, but not radiographic response, and can help guide treatment decisions.     

Prognostic significance of residual lymphovascular invasion after resection of locally advanced and borderline resectable pancreatic adenocarcinomas treated by neoadjuvant chemotherapy

BackgroundThe current study aimed to identify histological prognostic factors after resection of locally advanced (LA) and borderline (BL) pancreatic adenocarcinomas treated by neoadjuvant chemotherapy (NC).MethodsA retrospective review was performed of patients with LA and BL adenocarcinomas operated after NC between January 2010 and April 2018. Prognostic factors for survival were assessed by multivariate Cox analysis.ResultsOf the 84 patients, 29 had BL and 55 had LA pancreatic adenocarcinomas. Seventy-five patients underwent synchronous venous resection and 57 underwent arterial resection. The median overall survival from surgery was 21.10 months (BL 23-LA 21) (95% CI: 14.8–30.3) with 1-, 3-, and 5-year overall survival rates of 73%, 32%, and 20%, respectively. Multivariate analysis identified lymphovascular invasion (LVI) as an independent prognostic factor for overall survival (HR: 2.32, 95% CI: 1.28–4.22; p = 0.004). Patients without LVI (n = 37) had superior median overall and 5-year survival rates (31.0 months [40 from diagnosis]; 39%) compared to patients with LVI (n = 47; 14.4 months [22 from diagnosis]; 7%). The absence of residual LVI was associated with major pathologic response rates (p < 0.05).ConclusionThe persistence of LVI at pathology after resection of LA and BL treated by neoadjuvant chemotherapy predicts poor response and limited long-term survival.     

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.     

The impact of preoperative anemia on pancreatic resection outcomes

BackgroundPreoperative anemia is a risk factor for blood transfusions and delayed postoperative recovery, but few data are available for pancreatic surgery. Aim of the study was to analyze the impact of preoperative anemia on outcomes after pancreatic resection.MethodsRetrospective review of 1107 patients resected at San Raffaele Hospital (2015–2018). Preoperative anemia was defined as hemoglobin lower than 130 g/L for men and 120 g/L for women. Primary outcome was 90-day comprehensive complication index (CCI). Analysis was stratified according to type of surgery; proximal resections (pancreaticoduodenectomy and total pancreatectomy) versus distal pancreatectomy.ResultsIn 776 proximal resection patients, preoperative anemia was associated with increased CCI (24 ± 25 vs. 19 ± 23, p = 0.018) and perioperative allogenic blood transfusions (n = 124, 46% vs. n = 129, 26%; p < 0.001). Multivariate analysis showed that anemia was associated with a 7% (95%CI 0.02–0.57 p = 0.047) increase in CCI, and was an independent factor associated with perioperative blood transfusion (OR 2.762, 95%CI 1.72–4.49, p < 0.001). In 331 distal pancreatectomies, anemia was not associated to increased morbidity but only to an increased risk of perioperative blood transfusion.ConclusionPreoperative anemia is an independent risk factor for increased complication severity and blood transfusion in patients undergoing major pancreatic resection.     

Impact of care pathway adherence on recovery following distal pancreatectomy within an enhanced recovery program

BackgroundIn bowel surgery, adherence to enhanced recovery program (ERP) has been associated with improved recovery. The objective of this study was to evaluate the impact of adherence to ERP elements on outcomes, and identify factors associated with successful recovery following distal pancreatectomy (DP).MethodsData for 376 patients who underwent DP managed within an ERP including 16 perioperative elements were reviewed. Primary endpoint was successful recovery, a composite outcome defined as length of hospital stay≤7 days, no severe complications nor readmissions.ResultsPatients had a mean (SD) overall adherence of 76 (14)%. Overall, 166 (44%) patients had a successful recovery. There was a positive association between overall adherence and successful recovery (OR 1.19, 95%CI 1.08–1.31 for every additional element, p = 0.001), while an inverse relationship was found with comprehensive complication index (8% reduction, 95%CI -15 to −2%, p = 0.011). Adherence to postoperative phase interventions had the greatest impact on recovery (OR 1.29, 95%CI 1.13–1.47 for every additional postoperative element; p < 0.001). At multivariable regression, early termination of IV fluids was the only ERP element associated with successful recovery (OR 2.80, 95%CI 1.73–4.54; p < 0.001).ConclusionIncreased adherence to ERP elements was associated with successful early recovery and reduction of postoperative complication severity.     

Synchronous resection of colorectal cancer primary and liver metastases: an outcomes analysis

BackgroundConcurrent resection of the primary cancer and synchronous colorectal cancer liver metastases (CRCLM) was evaluated for differences in outcomes following stratification of both the liver and colorectal resection.MethodsConsecutive cases of synchronous resection of both the CRC primary and CRCLM were reviewed retrospectively at a single, high-volume institution over a 17-year period (2000–2017).Results273 patients underwent simultaneous resection of CRCLM. The distribution of the primary lesion was similar between the colon (52.4%) and rectum (47.6%), while 46.9% of patients had bilobar liver disease. Major liver/major colorectal resection (n = 24) were significantly more likely to experience colorectal specific morbidity (OR 3.98, 95% CI 1.56–10.15, p = 0.004), liver specific morbidity (OR 7.4, 95% CI 2.22–24.71, p = 0.001), total morbidity (OR 2.91, 95% CI 1.18–7.18, p = 0.020) and 90-day mortality (OR 5.50, 95% CI 1.27–23.81, p = 0.023). Failure to receive adjuvant chemotherapy secondary to postoperative morbidity was associated with significantly worsened survival (HR for death 5.91, 95% CI 1.59–22.01, p = 0.008).ConclusionsPostoperative morbidity precluding the administration of adjuvant chemotherapy is associated with an increase in mortality. Combining a major liver with major colorectal resection is associated with a significant increase in major morbidity and 90-day mortality, and should be avoided.     

Visceral adipose tissue is a better predictor than BMI in the alternative Fistula Risk Score in patients undergoing pancreatoduodenectomy

BackgroundMuscle attenuation (MA) and visceral adipose tissue (VAT) have not yet been included in the currently used alternative Fistula Risk Score (a-FRS). The aim of this study was to examine the added value of these parameters as predictors of clinically relevant postoperative pancreatic fistula (CR-POPF) in the a-FRS after pancreatoduodenectomy compared to Body Mass Index (BMI).MethodsA single center retrospective cohort study was performed in patients who underwent pancreatoduodenectomy between 2009 and 2018. The a-FRS model was reproduced, MA and VAT were both combined and separately added to the model instead of BMI using logistic regression analysis. Model discrimination was assessed by ROC-curves.ResultsIn total, 329 patients were included of which 55 (16.7%) developed CR-POPF. The a-FRS model showed an AUC of 0.74 (95%CI: 0.68–0.80). In this model, BMI was not significantly associated with CR-POPF (p = 0.16). The MA + VAT model showed an AUC of 0.81 (95%CI: 0.75–0.86). VAT was significantly associated with CR-POPF (per cm², OR: 1.01; 95%CI: 1.00–1.01; p < 0.001). The AUC of the MA + VAT model differed significantly from the AUC of the a-FRS model (p = 0.001).ConclusionVisceral adipose tissue is of added value in the a-FRS compared to BMI in predicting CR-POPF in patients undergoing pancreatoduodenectomy.