What is the impact of zinc deficiency for pancreatectomies in patients with pancreatic ductal adenocarcinoma?

Backgroundand purpose: Zinc is an essential element for human health and plays an important role in metabolic, immunological and other biological processes. The present study was conducted to investigate the association between zinc deficiency (ZD) and the perioperative clinical course in patients with pancreatic ductal adenocarcinoma (PDAC).MethodsOf 216 patients with PDAC who underwent elective pancreatectomy between 2013 and 2017 at our institution, 206 patients with sufficient clinical data were retrospectively reviewed. The perioperative variables were compared and the risk factors associated with infectious complications were identified.ResultsZD was preoperatively present in 36 (17.5%) of 206 patients with PDAC. In the patients of the ZD group, a higher proportion of males, higher preoperative modified Glasgow prognostic scores, a higher neutrophil-to-lymphocyte ratio, and a higher occurrence of postoperative infectious complications after pancreatectomy were observed, compared to the non-ZD group. By a univariate analysis, three risk factors were significantly associated with infectious complications after pancreatectomy: ZD (vs non-ZD: p = 0.002), serum albumin <3.5 g/dl (vs ≥ 3.5 g/dl: p = 0.005), and the procedure of pancreaticoduodenectomy (vs others: p = 0.013). By multivariate logistic regression analysis, the occurrence of infectious complications was significantly associated with ZD (OR 3.430, 95%CI 1.570 to 7.490, p = 0.002) and the procedure of pancreaticoduodenectomy (OR 2.030, 95%CI 1.090 to 3.770, p = 0.025).ConclusionsThe current study newly demonstrated that ZD could serve as a preoperative predictor of infectious complications after pancreatectomies in the patients with PDAC.     

A lack of postoperative complications after pancreatectomy contributes to the long-term survival of patients with pancreatic cancer

Background/Objectives: The objectives of this study were to identify the factors affecting patients’ survival and the characteristics of five-year survivors of pancreatic ductal adenocarcinoma (PDAC) after pancreatectomy as well as to clarify the correlation between the development of postoperative complications and a five-year survival.MethodsA total of 104 patients underwent pancreatectomy for PDAC between April 2005 and March 2013 with curative intent. Patients who survived for more than five years after pancreatectomy were classified as long-term survivors. Sixteen demographic and clinical variables and 10 pathological variables were comprehensively assessed for their associations with the patients’ survival time and long-term survival.ResultsThe presence of preoperative comorbidity (OR: 1.65, 95% CI 1.02–2.67, p = 0.042), postoperative overall complications (OR: 1.78, 95% CI 1.03–3.10, p = 0.041), a lymph node positivity ratio of ≥0.2 (OR: 3.04, 95% CI 1.51–6.11, p = 0.002), and portal invasion (OR: 2.58, 95% CI 1.48–4.49, p = 0.001) were identified as independent factors affecting the patients’ survival. The absence of postoperative overall complications was identified as an independent factor related to long-term survival in the multivariate analysis (OR: 0.08, 95% CI 0.01–0.82, p = 0.034).ConclusionsThe presence of preoperative comorbidity, postoperative overall complications, LNR ≥0.2, and portal invasion were prognostic factors affecting the patients’ survival, and avoiding postoperative complications after pancreatectomy might contribute to the long-term survival of PDAC patients after pancreatectomy. The further improvement of surgical procedures and perioperative care in order to reduce the rate of postoperative complications should be attempted.     

Prognostic significance of preoperative PNI and CA19-9 for pancreatic ductal adenocarcinoma: A multi-institutional retrospective study

BackgroundThe aim of this study was to investigate the clinical value of nutritional and immunological prognostic scores as predictors of outcomes and to identify the most promising scoring system for patients with pancreatic ductal adenocarcinoma (PDAC) in a multi-institutional study.MethodsData were retrospectively collected for 589 patients who underwent surgical resection for PDAC. Prognostic analyses were performed for overall (OS) and recurrence-free survival (RFS) using tumor and patient-related factors, namely neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, Prognostic Nutritional Index (PNI), Glasgow Prognostic Score (GPS), modified GPS, C-reactive protein-to-albumin ratio, Controlling Nutritional Status score, and the Geriatric Nutritional Risk Index.ResultsCompared with PDAC patients with high PNI values (≥46), low PNI (<46) patients showed significantly worse overall survival (OS) (multivariate hazard ratio (HR), 1.432; 95% CI, 1.069–1.918; p = 0.0161) and RFS (multivariate HR, 1.339; 95% CI, 1.032–1.736; p = 0.0277). High carbohydrate antigen 19–9 (CA19-9) values (≥450) were significantly correlated with shorter OS (multivariate HR, 1.520; 95% CI, 1.261–2.080; p = 0.0002) and RFS (multivariate HR, 1.533; 95% CI, 1.199–1.961; p = 0.0007). Stratification according to PNI and CA19-9 was also significantly associated with OS and RFS (log rank, P < 0.0001).ConclusionsOur large cohort study showed that PNI and CA19-9 were associated with poor clinical outcomes in PDAC patients following surgical resection. Additionally, combining PNI with CA19-9 enabled further classification of patients according to their clinical outcomes.     

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.     

Preoperative predictors for early and very early disease recurrence in patients undergoing resection of pancreatic ductal adenocarcinoma

BackgroundThis study aimed to identify predictors for early and very early disease recurrence in patients undergoing resection of pancreatic ductal adenocarcinoma (PDAC) resection with and without neoadjuvant therapy.MethodsIncluded were patients who underwent PDAC resection (2014–2016). Multivariable multinomial regression was performed to identify preoperative predictors for manifestation of recurrence within 3, 6 and 12 months after PDAC resection.Results836 patients with a median follow-up of 37 (interquartile range [IQR] 30–48) months and overall survival of 18 (IQR 10-32) months were analyzed. 670 patients (80%) developed recurrence: 82 patients (10%) <3 months, 96 patients (11%) within 3–6 months and 226 patients (27%) within 6–12 months. LogCA 19–9 (OR 1.25 [95% CI 1.10–1.41]; P < 0.001) and neoadjuvant treatment (OR 0.09 [95% CI 0.01–0.68]; P = 0.02) were associated with recurrence <3 months. LogCA 19–9 (OR 1.23 [95% CI 1.10–1.38]; P < 0.001) and 0–90° venous involvement on CT imaging (OR 2.93 [95% CI 1.60–5.37]; P < 0.001) were associated with recurrence within 3–6 months. A Charlson Age Comorbidity Index ≥4 (OR 1.53 [95% CI 1.09–2.16]; P = 0.02) and logCA 19–9 (OR 1.24 [95% CI 1.14–1.35]; P < 0.001) were related to recurrence within 6–12 months.ConclusionThis study demonstrates preoperative predictors that are associated with the manifestation of early and very early recurrence after PDAC resection. Knowledge of these predictors can be used to guide individualized surveillance and treatment strategies.     

Induction chemotherapy in pancreatic cancer: CA 19-9 may predict resectability and survival

BackgroundPreoperative/Neoadjuvant treatment (NT) is increasingly used in unresectable pancreatic cancer (PDAC). However, ∼40% of patients cannot be resected after NT and reliable preoperative response evaluation is currently lacking. We investigated CA 19-9 levels and their dynamics during NT for prediction of resectability and survival.MethodsWe screened our institution's database for patients who underwent exploration or resection after NT with gemcitabine-based therapy (GEM) or FOLFIRINOX (FOL). Pre- and post-NT CA 19-9, resection rate and survival were analyzed.ResultsOf 318 patients 165 (51.9%) were resected and 153 (48.1%) received exploration. In the FOL group (n = 103; 32.4%), a post-NT CA 19-9 cutoff at 91.8 U/ml had a sensitivity of 75.0% and a specificity of 76.9% for completing resection with an AUC of 0.783 in the ROC analysis (95% CI: 0.692–0.874; p < 0.001. PPV: 84.2%, NPV: 65.2%). Resected patients above the cutoff did not benefit from resection. Post-NT CA 19-9 <91.8 U/ml (OR 11.63, p < 0.001) and CA 19-9 ratio of <0.4 (OR 5.77, p = 0.001) were independent predictors for resectability in FOL patients.DiscussionCA 19-9 levels after neoadjuvant treatment with FOLFIRINOX predict resectability and survival of PDAC more accurately than dynamic values and should be incorporated into response evaluation and surgical decision-making.     

Radical antegrade modular pancreatosplenectomy (RAMPS): does adrenalectomy alter outcomes?

BackgroundRadical antegrade modular pancreatosplenectomy (RAMPS) has oncologic superiority compared to a standard distal pancreatectomy (DP). For tumors invading into the adrenal gland, a posterior RAMPS takes the left adrenal gland en bloc with the pancreas specimen. The aim of this analysis is to determine whether addition of adrenalectomy alters the outcomes of DP.MethodsThe American College of Surgeons (ACS) National Surgical Quality Improvement Program (NSQIP) Procedure-Targeted Pancreatectomy database was accessed from 2014 to 2019. Patients with pancreatic ductal adenocarcinoma (PDAC) undergoing posterior RAMPS were compared to patients having a standard DP. 30-day outcomes were analyzed using multivariable regression.Results3467 PDAC patients underwent DP; 159 (4.6%) also had an adrenalectomy. Posterior RAMPS patients had higher T stage (T3-4 77% vs. 58%, p < 0.01). On multivariable analysis, posterior RAMPS patients had worse perioperative outcomes including more transfusions (OR 2.78, p < 0.01), serious morbidity (OR 1.45, p = 0.04), prolonged hospital stay (OR 1.36, p < 0.05), and less optimal pancreatic surgery (OR 0.61, p < 0.01).ConclusionRadical antegrade modular pancreatosplenectomy with adrenalectomy (posterior RAMPS) is associated with worse perioperative outcomes compared to a standard distal pancreatectomy. Improved oncologic outcomes must be weighed against higher perioperative morbidity when selecting patients for this more extensive surgical resection.     

Increased clostridium difficile infection in the era of preoperative chemotherapy for pancreatic cancer

BackgroundIn recent trend of preoperative chemotherapy, postoperative clostridium difficile infection (CDI) might be increasing in pancreatic ductal adenocarcinoma (PDAC) patients. This study aimed to elucidate the inducement of postoperative CDI in the new era of preoperative chemotherapy.MethodsEligible patients were those who received pancreaticoduodenectomy for PDAC. Patients were classified into two groups according to the presence or absence of postoperative CDI, and the independently associated factors for postoperative CDI were investigated. Additionally, eligible patients were classified using the identified associated factors, and the duration of preoperative antimicrobial administration and incidence of CDI were compared between the groups.ResultsTwo hundred PDAC patients were eligible for this study, and postoperative CDI was detected in 15 (7.5%) patients. Multivariate analysis revealed that preoperative biliary tract infection (BTI) and chemotherapy (Chemo) were independently associated with postoperative CDI (OR, 4.05; 95% CI, 1.25–13.1; p = 0.0200 and OR, 3.64; 95% CI, 1.14–11.6; p = 0.0209, respectively). The patients were classified into four groups according to the presence or absence of preoperative BTI and Chemo (BTI-/Chemo-, BTI-/Chemo+, BTI+/Chemo- and BTI+/Chemo + group). The median durations of preoperative antimicrobial administration were 0, 2, 8 and 15 days in each group, respectively. Postoperative CDI was detected in 3.7%, 10.0%, 10.5% and 31.3% in each group, respectively, and patients in BTI+/Chemo + group suffered CDI more frequently compared to those in BTI-/Chemo-group (p = 0.00778).ConclusionsPreoperative BTI and chemotherapy might induce postoperative CDI for PDAC patients.     

Clinical significance and predictors of complete or near-complete histological response to preoperative chemoradiotherapy in patients with localized pancreatic ductal adenocarcinoma

BackgroundThe clinical value and predictors of a favorable histological response to preoperative chemoradiotherapy (CRT) in pancreatic ductal adenocarcinoma (PDAC) remains undefined.ObjectiveTo assess the significance and predictors of a favorable histological response to preoperative CRT in patients with localized PDAC.MethodsThe study included 203 patients with localized PDAC undergoing curative-intent resection after CRT. The rate of R0 resection and overall survival (OS) and recurrence-free survival (RFS) were correlated with the grading of histological response to determine optimal stratification. Clinical factors associated with a significant histological response were evaluated using multivariate regression analysis.ResultsAmong all patients, eight patients (3.9%) had a grade 4 (pCR); 40 (19.4%) had a grade 3 estimated rate of residual neoplastic cells <10% (near-pCR); and 155 (76.7%) had a grade 1/2 limited response. The 48 patients with pCR/near-pCR achieved significantly higher R0 resection rate (100%) than those with grade 1/2 (80.0%). The 5-year OS and RFS rates were significantly higher in the patients with pCR/near-pCR (45.3% and 36.5%) than in those with grade 1/2 (27.1% and 18.5%). Gemcitabine plus S-1 based CRT, serum CA19-9 level after CRT <83 U/mL, and interval from initial treatment to surgery ≥4.4 months were independent predictive factors for pCR/near-pCR.ConclusionspCR or near-pCR to preoperative CRT contributed to achieving a high rate of R0 resection and improving survival for localized PDAC. The use of gemcitabine plus S-1 as a radiosensitizer, lower serum CA19-9 level after CRT, and longer preoperative treatment duration were significantly associated with pCR or near-pCR.     

Association of preoperative biliary drainage technique with postoperative outcomes among patients with resectable hepatobiliary malignancy

BackgroundEndoscopic biliary stenting (EBS) and percutaneous transhepatic biliary drainage (PTBD) are two techniques used for preoperative biliary drainage prior to hepatobiliary resection. The objectives of this study were to determine predictors of the drainage technique selection and to evaluate the association between drainage technique and postoperative outcomes.MethodsUsing ACS NSQIP data (2014–2017), patients who underwent preoperative biliary drainage prior to hepatobiliary resection for malignancy were identified. Separate multivariable-adjusted, propensity score (PS) adjusted, and PS matched logistic regression models were constructed to evaluate the association between drainage technique and postoperative outcomes.ResultsOf 527 patients identified, 431 (81.8%) received EBS and 96 (18.2%) received PTBD. Patients who underwent PTBD had more preoperative co-morbidities, including higher ASA class, recent weight loss, and hypoalbuminemia (all p < 0.05). After multivariable adjustment, PTBD was significantly associated with 30-day DSM (OR 1.92, 95% CI 1.24–2.97, p = 0.004), overall SSI (OR 1.74, 95% CI 1.10–2.76, p = 0.019), and superficial SSI (OR 2.08, 95% CI 1.20–3.60, p = 0.010). These findings remained significant for both PS-adjusted and PS-matched models.ConclusionPatients undergoing hepatobiliary resection selected for PTBD had significantly more preoperative co-morbidities and nutritional deficits. Compared to EBS, PTBD was associated with significantly higher odds of postoperative morbidity and mortality.     

Gynecological and reproductive factors and the risk of pancreatic cancer: A case-control study

Background/Objectives: Pancreatic ductal adenocarcinoma (PDAC) has a higher incidence in men compared to women, although the difference in known risk factors cannot explain this disparity completely. Reproductive and hormonal factors have been demonstrated in pre-clinical studies to influence pancreatic carcinogenesis, but the few published data on the topic are inconsistent. The aim was to investigate the role of reproductive and hormonal factors on PDAC occurrence in women.MethodsWe conducted a unicenter case-control study; PDAC cases were matched to controls by age with a 1:2 ratio. Risk factors were screened through questionnaires about gynecologic and medical history. Comparisons were made using Chi-square and Fisher’s exact tests where appropriate for categorical variables and Student’s t-test for continuous variables. Logistic regression was used to calculate Odds Ratios (ORs) and their 95% confidence intervals (CI). Multivariable logistic regression models were adjusted for potential confounders.Results253 PDAC and 506 matched controls were enrolled. At logistic regression multivariable analysis adjusted for confounding factors, older age at menopause (OR:0.95 per year; 95% CI:0.91–0.98; p = 0.007), use of Oral Contraceptives (OR:0.52; 95% CI:0.30–0.89; p = 0.018), use of Hormonal Replacement Therapy (OR:0.31; 95% CI:0.15–0.64; p = 0.001), and having had two children (OR:0.57; 95% CI:0.38–0.84; p = 0.005) were significant, independent protective factors for the onset of PDAC.ConclusionsThese data confirm some previous findings on menopause age and number of births while, to our knowledge, this is the first study to show a protective effect of HRT and OC use. The results collectively support the hypothesis that exposure to estrogens plays a protective role towards PDAC.     

The role of coeliac axis resection in resected ductal adenocarcinoma of the distal pancreas: A result of tumour topography or a prognostic factor?

BackgroundWhether coeliac axis resection (CAR) results from tumour topography or a prognostic factor for distal pancreatic ductal adenocarcinoma (PDAC) remains unclear. We aimed to compare the clinicopathological data between distal pancreatectomy with en bloc CAR (DP-CAR) and distal pancreatectomy plus splenectomy (DP-S) and analyse the prognostic factors.MethodsWe retrospectively analysed clinicopathological data from 102 patients who underwent distal pancreatectomy for PDAC and the factors affecting disease-free survival (DFS) and overall survival (OS). Of these patients, 45 and 57 underwent DP-CAR and DP-S, respectively.ResultsDP-CAR was associated with more operative challenges than DP-S: more portomesenteric vein resections (48.9% vs. 14.0%), longer operations (320 vs. 242 min), and greater estimated blood loss (EBL) (600 vs. 200 ml). DP-CAR had larger tumours (5 vs. 4 cm), more perineural invasion (91.1% vs. 73.7%), and more microscopically positive surgical margins (20% vs. 3.5%), compared to DP-S. The major complication was clinically relevant postoperative pancreatic fistula (20.6%). The median DFS was 15.8 months and the median OS was 20.1 months. CAR was not associated with DFS or OS. EBL>700 ml, lymphovascular invasion (LVI), and adjuvant chemotherapy independently affected DFS and OS.ConclusionDP-CAR was associated with larger tumours and more surgical challenges but not with poorer DFS and OS than DP-S. CAR was more likely to result from tumour topography rather than from an adverse prognostic factor for resected distal PDAC. EBL>700 ml, LVI, and adjuvant chemotherapy were independent factors affecting the survival of patients with distal PDAC who underwent surgical resection.     

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.     

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.     

A preoperative score to predict early death after pancreatic cancer resection

BackgroundThis study aimed to develop and validate a preoperative prognostic model for death within one year post-surgery in patients with resectable pancreatic ductal adenocarcinoma (PDAC).MethodsA derivation cohort study of 296 patients who underwent surgical resection of PDAC was prospectively enrolled in an observational study. Preoperative predictors of one year mortality were used to develop a risk score which was then validated in an external cohort of 182 patients with resectable PDAC.ResultsSeventy-eight out of 296 patients (26%) died within the first year. Preoperative independent predictors of one year mortality were: nutritional status (Geriatric Nutritional Risk Index, OR 2.23, 1.14–4.38; p = 0.02), American Society of Anaesthesiologists’ score (OR 2.56, 1.1–5.98; p = 0.03), abdominal or back pain at presentation (OR 2.51, 1.05–5.9; p = 0.038) and non metastatic liver disease as comorbidity (OR 4.5, 1.05–19.3; p = 0.043). A score ranging from 0 to 7 points was developed. In the validation cohort, the model was able to predict early mortality (OR 7.1, 3.9–12.7; p < 0.0001), with a predictive ability of 53.5% (Nagelkerke R²), an area under the receiver operating characteristic curve of 88.7% and an acceptable calibration (goodness-of-fit test, p = 0.403).ConclusionsOur new simple risk score proved reliable in forecasting one year mortality in patients with resectable PDAC.     

Is early-stage pancreatic adenocarcinoma truly early: stage migration on final pathology with surgery-first versus neoadjuvant therapy sequencing

BackgroundNeoadjuvant therapy (NT) remains controversial in early-stage pancreatic ductal adenocarcinoma (PDAC), defined as clinical (c)Stage I-II. Our aim was to analyze rates of pathologic upstaging/downstaging for resectable PDAC treated with surgery-first (SF) vs. NT.MethodsUtilizing the National Cancer Data Base (NCDB), patients with cStage I-II PDAC who underwent pancreatoduodenectomy in 2006–2013 were pathologically staged using the AJCC 8th edition and compared by treatment sequencing.ResultsAmong 13,871 patients, 15.3% received NT. Despite higher pre-treatment T-stage (cT2: 71.9% vs. 56.3%, p < 0.001), NT patients had lower rates of pathologic nodal metastases (46.2% vs. 69.2% in SF, p < 0.001), suggesting higher rates of pathologic downstaging. In cStage II, 33.0% were upstaged to stage III after SF, vs. only 14.0% after NT. In cStage I, 65.5% were upstaged following SF, vs. 46.7% after NT (all p < 0.001). Patients with NT (HR-0.77, p < 0.001) or downstaging (HR-0.80, p < 0.001) had improved overall survival (OS).ConclusionNT is associated with reduction in unexpected upstaging, reduction in nodal positivity, and improved OS, compared to SF approach in putatively early-stage PDAC. Because clinical staging underestimates the underlying disease burden in resectable PDAC, patients with cStage I-II should be considered for NT.     

Preoperative serum ADAM12 levels as a stromal marker for overall survival and benefit of adjuvant therapy in patients with resected pancreatic and periampullary cancer

BackgroundWe evaluated the stroma marker A Disintegrin And Metalloprotease 12 (ADAM12) as a preoperative prognostic and treatment-predictive marker for overall survival (OS) in pancreatic ductal adenocarcinoma (PDAC) and periampullary cancers.MethodsMaterials were derived from the prospective nationwide Dutch Pancreas Biobank (2015–2017). We included patients who underwent resection because of PDAC/periampullary cancer or non-invasive IPMN (control group) and had a preoperative serum sample available. ADAM12 levels were dichotomized using a pre-defined cut-off (316 pg/mL). Univariable and multivariable Cox regression analyses (backward selection) were performed.ResultsMedian ADAM12 levels were 161 (IQR 79–352) pg/mL in 215 PDAC and periampullary adenocarcinomas. High ADAM12 levels (>316 pg/mL) predicted poor OS in the total group of pancreatic and periampullary adenocarcinomas (P = 0.04), but not after adjustment. In distal cholangiocarcinoma (n = 33), high ADAM12 levels predicted poor OS in univariable analysis (P = 0.02), but not in PDAC (P = 0.63). PDAC patients (n = 135) with high ADAM12 levels benefited from adjuvant treatment (median OS 27 vs 14 months, P = 0.02), whereas those with low levels did not (21 vs 21 months, P = 0.87).ConclusionHigh circulating ADAM12 levels, as a proxy for activated stroma, predict survival benefit from adjuvant chemotherapy in PDAC, requiring validation in future studies.     

Pathologic complete response to chemoembolization improves survival outcomes after curative surgery for hepatocellular carcinoma: predictive factors of response

BackgroundWe identified the predictive factors and prognostic significance of transarterial chemoembolization (TACE) for achieving pathologic complete response (pCR) before curative surgery for hepatocellular carcinoma (HCC) in hepatitis B–endemic areas.MethodsAmong 753 HCC patients treated with surgery, 124 patients underwent preoperative TACE before liver resection (LR), and 166 before liver transplantation (LT) between 2005 and 2016. Overall survival (OS) and recurrence-free survival (RFS) were analyzed. Pathologic response (PR) was defined as the mean percentage of necrotic area, and pCR was defined as the absence of viable tumor.ResultsA total of 34 (27%) and 38 (23%) patients had pCR before LR and LT, respectively. Alpha-fetoprotein (AFP) < 100 ng/mL and single tumor were significant preoperative predictors of pCR. OS and RFS were significantly improved in patients with pCR or a PR ≥ 90%, but not in patients with PR ≥ 50% after LR and LT. On multivariate analyses, PR ≥ 90% remained an independent predictor of better OS and RFS in LR and LT groups.ConclusionOverall, our data clearly demonstrate that pCR predicts favorable prognosis after curative surgery for HCC, and predictors of pCR are AFP <100 ng/mL and single tumor.     

Radical antegrade modular pancreatosplenectomy enhances local control of the disease in patients with left-sided pancreatic cancer

BackgroundRadical antegrade modular pancreatosplenectomy (RAMPS) was developed to enhance curability in patients with left-sided pancreatic cancer. However, no evidence is available regarding the prognostic superiority of RAMPS compared with conventional distal pancreatectomy (cDP). Here, we aimed to assess the oncological benefit of RAMPS by comparing surgical outcomes between patients who underwent cDP and RAMPS with propensity score (PS) adjustment.MethodsClinical data of 174 patients undergoing cDP and RAMPS between 2009 and 2016 at two high-volume centers were analyzed with PS matching. Recurrence-free survival (RFS), overall survival (OS), and local recurrence rates were compared between patients who underwent cDP and RAMPS.ResultsThe cDP and RAMPS groups were successfully matched with baseline characteristics. No differences were found in the 3-year RFS and OS rates between the two groups (3-year RFS: cDP 46% vs RAMPS 40%, p = 0.451, 3-year OS: cDP 57% vs RAMPS 53%, p = 0.692). However, the 3-year local recurrence rate was lower in the RAMPS (10%) than that in the cDP group (34%) (hazard ratio 0.275, 95% confidence interval 0.090–0.842, p = 0.02).ConclusionRAMPS is oncologically superior to conventional procedure in achieving local control of the disease in patients with left-sided pancreatic cancer.     

Treatment and overall survival of four types of non-metastatic periampullary cancer: nationwide population-based cohort study

BackgroundPeriampullary adenocarcinoma consists of pancreatic adenocarcinoma (PDAC), distal cholangiocarcinoma (DC), ampullary cancer (AC), and duodenal adenocarcinoma (DA). The aim of this study was to assess treatment modalities and overall survival by tumor origin.MethodsPatients diagnosed with non-metastatic periampullary cancer in 2012–2018 were identified from the Netherlands Cancer Registry. OS was studied with Kaplan–Meier analysis and multivariable Cox regression analyses, stratified by origin.ResultsAmong the 8758 patients included, 68% had PDAC, 13% DC, 12% AC, and 7% DA. Resection was performed in 35% of PDAC, 56% of DC, 70% of AC, and 59% of DA. Neoadjuvant and/or adjuvant therapy was administered in 22% of PDAC, 7% of DC, 7% of AC, and 12% of DA. Three-year OS was highest for AC (37%) and DA (34%), followed by DC (21%) and PDAC (11%). Adjuvant therapy was associated with improved OS among PDAC (HR = 0.62; 95% CI 0.55–0.69) and DC (HR = 0.69; 95% CI 0.48–0.98), but not AC (HR = 0.87; 95% CI 0.62–1.22) and DA (HR = 0.85; 95% CI 0.48–1.50).ConclusionThis retrospective study identified considerable differences in treatment modalities and OS between the four periampullary cancer origins in daily clinical practice. An improved OS after adjuvant chemotherapy could not be demonstrated in patients with AC and DA.