Ductal Adenocarcinoma Of Pancreatic Head Research Articles

Neural invasion severity is a strong predictor of local recurrence in pancreatic ductal adenocarcinoma.

In pancreatic ductal adenocarcinoma, neural invasion is being increasingly recognized as an unfavorable predictor of patient outcomes. Neural invasion severity seems to have a stronger clinical impact on patient prognosis than neural invasion status alone. Therefore, this study aims to assess the impact of severity of neural invasion on overall survival and disease-free survival in pancreatic ductal adenocarcinoma. To assess the impact of intrapancreatic neural invasion severity, tumor specimens resected from patients with pancreatic ductal adenocarcinoma between 2007 and 2014 were systematically re-evaluated, and neural invasion severity was determined using the standardized neural invasion severity score. In our cohort (n= 216), an increased neural invasion severity score was associated with markedly shorter overall survival in pancreatic head ductal adenocarcinoma (neural invasion severity score low: 22.8months vs neural invasion severity score high: 17.6months: P= .001). An external European validation cohort confirmed these results and showed significantly better survival of patients with lower neural invasion (20.5 vs 15.4months, P= .026). The disease-free survival time was also substantially decreased in patients with pancreatic head pancreatic ductal adenocarcinoma and increased neural invasion severity (neural invasion severity score low: 19.1months vs neural invasion severity score high: 10.4months; P= .004). Moreover, the neural invasion severity score was an important independent factor influencing overall survival (hazards ratio 1.024, P= .04) and disease-free survival (hazards ratio 1.03, P= .01) using an adjusted Cox proportional hazards model. Importantly, higher neural invasion severity score leads to significantly more and earlier local recurrence than to distant tumor recurrence. Neural invasion severity is a powerful independent factor influencing overall survival and local recurrence in patients with pancreatic ductal adenocarcinoma. Therefore, individuals with high neural invasion severity score values should be regarded as a specific subgroup of pancreatic ductal adenocarcinoma patients and may benefit from more tailored postoperative oncologic therapy.

Stepwise Analysis of Resection Margin Impact on Survival and Distant Metastasis in Pancreatic Head Ductal Adenocarcinoma.

The prognostic role of tumor cells in pancreatic ductal adenocarcinoma (PDAC) of the pancreatic head with direct microscopic infiltration (DMI) or in close proximity (≤1 mm) to the resection margin (RM) remains unclear. This single-center, retrospective study included specimens from 75 patients who underwent oncological resection of pancreatic head PDAC between February 2013 and July 2020. Two pathologists independently re-measured the distance between tumors and the multiple RMs. The impact of RM involvement for DMI, tumor cells within ≤1 mm, in general, and for individual RMs on overall survival (OS) and development of distant pulmonary (PM) and hepatic (HM) metastasis was analyzed. DMI of RMs was significantly associated with a shorter OS (median 5 vs 19 months, P = .02). The presence of tumor cells within ≤1 mm of RMs yielded a negative impact on OS with a trend toward significance (median 9 vs 21 months, P = .09). DMI and tumor cells within ≤1 mm of the pancreatic transection margin (PRM), individually, had a significant negative impact on OS (median 4 vs 19 months and 6 vs 19 months, P < .05), but not for any other individual RM. RM involvement of ≤1 mm of only the vascular circumferential resection margin (VCRM) resulted in a shorter time to HM development (P = 0.05). DMI of the posterior circumferential resection margin (PCRM) and VCRM, individually, showed shorter time to PM (P < .05). Potential clinical considerations include extended intraoperative evaluation of the PRM (1 mm) and intensified preoperative prediction of R1 resection as a basis for neoadjuvant therapy.

Radiological biomarker for the infiltration of the mesopancreas in patients undergoing upfront surgery for pancreatic head ductal adenocarcinoma: The MESO-PDAC project

Radiological biomarker for the infiltration of the mesopancreas in patients undergoing upfront surgery for pancreatic head ductal adenocarcinoma: The MESO-PDAC project

Prognostic value of para-aortic lymph node metastasis and dissection for pancreatic head ductal adenocarcinoma: a retrospective cohort study

Background: Para-aortic lymph node (PALN) metastasis affects approximately 20% of patients with pancreatic ductal adenocarcinoma (PDAC). However, the prognostic significance of PALN metastases and dissection remains unclear. Methods: This retrospective cohort study included patients with PDAC of the pancreatic head who had undergone pancreaticoduodenectomy (PD) at our center between January 2017 and December 2020. Results: A total of 234 patients were included in the study. PALN dissection improved the median overall survival (OS) without statistical significance (24.1 vs 18.1 months, P = .156). The median recurrence-free survival was significantly longer in the PALN-dissection group than the group without PALN dissection (18.2 vs 11.6 months, P = .040). Conversely, there were no significant differences in the long-term prognosis between the PALN-positive and PALN-negative subgroups in the PALN-dissection group. Multivariate analysis showed that PALN metastasis was not an independent risk factor for OS (hazard ratio: 0.831, 95% confidence interval: 0.538–1.285, P = .406). Conclusions: For patients with pancreatic head ductal adenocarcinoma, PD with PALN dissection may achieve survival prolongation and bridge the survival gap between patients with and without PALN metastasis without significantly increasing the perioperative risks.

Venous reconstruction thrombosis after pancreaticoduodenectomy with superior mesenteric/portal vein resection due to pancreatic cancer: an 8 years single institution experience

Background Superior mesenteric/portal vein reconstruction (SMPVR) thrombosis remains a challenging complication following pancreaticoduodenectomy concomitant with venous resection. In this context, we aimed to present our SMPVR experiences and identify potential clinicopathological factors that increased SMPVR thrombosis. Methods A total of 33 patients who underwent SMPVR during pancreaticoduodenectomy were analyzed. Of these, 26 patients who experienced pancreatic head ductal adenocarcinoma met our inclusion criteria. Patients’ data were compared as classified by SMPVR type and the development of SMPVR thrombosis. All interposition grafts were Dacron in this cohort. Results Types of SMPVR included: tangential resection with primary repair (n = 12); segmental resection with splenic vein preservation and either primary anastomosis (n = 8) or 14 mm tubular Dacron grafting (n = 1); segmental resection with splenic vein division either 14 mm tubular Dacron grafting (n = 2) or 14/7 mm ‘Y’–shaped Dacron grafting (n = 3). A total of four patients having 14/7 mm ‘Y’–shaped (n = 3) and 14 mm tubular Dacron (n = 1) developed SMPVR thrombosis (p = .001). Dacron grafting (p = .001) and splenic vein division (p = .010) were associated with SMPVR thrombosis. The median time to detection of SMPVR thrombosis was 4.3 months (2.5–21.0 months). The median follow-up time was 12.2 months (3.0–45 months). Conclusions During pancreaticoduodenectomy for pancreatic head ductal carcinoma, extended venous resection requiring SMPVR with ‘Y’–shaped and use of Dacron interposition grafts appeared to be associated with the development of SMPVR thrombosis. This result warrants further investigations.

Intraoperative electrochemotherapy of the posterior resection surface after pancreaticoduodenectomy: Preliminary results of a hybrid approach treatment of pancreatic cancer

BackgroundDespite extensive research in recent decades, pancreatic cancer continues to be among the most lethal forms of cancer, with no substantial increase in survival rates. Local recurrences account for approximately 30 per cent of all disease recurrences. With the intent to improve survival, we designed a novel, hybrid treatment strategy consisting of surgical resection and additional intraoperative electrochemotherapy of the posterior resection surface. We present the study protocols and preliminary findings of a prospective pilot study investigating this treatment approach. MethodsConsenting patients with resectable pancreatic head ductal adenocarcinoma who met the inclusion criteria were enrolled in the study. After surgical resection, electrochemotherapy with bleomycin was performed using plate electrodes to cover the area between anatomical landmarks. ResultsElectrochemotherapy of the posterior resection surface was feasible in all 7 patients. We observed pancreatic fistula grade B in only one patient; all other noted complications were Clavien-Dindo grade 2 or less. The hospital mortality was 0%. ConclusionsOur preliminary results suggest that a hybrid approach combining surgery with intraoperative electrochemotherapy is safe and feasible.

The prognostic significance of duodenal wall invasion in pancreatic adenocarcinoma

ObjectiveThe most recent edition of the American Joint Committee on Cancer Staging Manual (AJCC, 8th edition) relies only on tumor size for staging resectable pancreatic adenocarcinoma, and the presence of duodenal wall invasion (DWI) no longer has an impact on staging. However, very few studies have evaluated its significance. In this study, we aim to evaluate the prognostic significance of DWI in pancreatic adenocarcinoma.MethodsWe reviewed 97 consecutive internal cases of resected pancreatic head ductal adenocarcinoma, and clinicopathologic parameters were recorded. All cases were staged according to the 8th edition of AJCC, and the patients were divided into two groups based on the presence or absence of DWI.ResultsOut of our 97 cases, 53 patients had DWI (55%). In univariate analysis, DWI was significantly associated with lymphovascular invasion and lymph node metastasis (AJCC 8th edition pN stage). In univariate analysis of overall survival, age > 60, absence of DWI, and African American race were associated with worse overall survival. In multivariate analysis, age > 60, absence of DWI, and African American race were associated with worse progression-free survival and overall survival.ConclusionAlthough DWI is associated with lymph node metastasis, it is not associated with inferior disease-free/overall survival.

International assessment and validation of the prognostic role of lymph node ratio in patients with resected pancreatic head ductal adenocarcinoma.

Lymph node ratio (LNR; positive/harvested lymph nodes) was identified as overall survival predictor in several cancers, including pancreatic adenocarcinoma. It remains unclear if LNR is predictive of overall survival in pancreatic adenocarcinoma patients staged pN2. This study assessed the prognostic overall survival role of LNR in pancreatic adenocarcinoma patients in relation with lymph node involvement. A retrospective international study in six different centers (Europe and United States) was performed. Pancreatic adenocarcinoma patients who underwent pancreatoduodenectomy from 2000 to 2017 were included. Patients with neoadjuvant treatment, metastases, R2 resections, or missing data regarding nodal status were excluded. Survival curves were calculated using Kaplan-Meier method and compared using log-rank test. Multivariable Cox regressions were performed to find independent overall survival predictors adjusted for potential confounders. A total of 1,327 patients were included. Lymph node involvement (pN+) was found in 1,026 patients (77%), 561 pN1 (55%) and 465 pN2 (45%). Median LNR in pN+ patients was 0.214 [interquartile range (IQR): 0.105-0.364]. On multivariable analysis, LNR was the strongest overall survival predictor in the entire cohort [hazard ratio (HR) =5.5; 95% confidence interval (CI): 3.1-9.9; P<0.001] and pN+ patients (HR =3.8; 95% CI: 2.2-6.6; P<0.001). Median overall survival was better in patients with LNR <0.225 compared to patients with LNR ≥0.225 in the entire cohort and pN+ patients. Similar results were found in pN2 patients (worse overall survival when LNR ≥0.225). LNR appeared as an important prognostic factor in patients undergoing surgery for pancreatic adenocarcinoma and permitted to stratify overall survival in pN2 patients. LNR should be routinely used in complement to tumor-node-metastasis (TNM) stage to better predict patient prognosis.

S1731 Fibrosing Pancreatitis Initially Diagnosed as Ductal Adenocarcinoma by Endoscopic Ultrasound of a Pancreatic Mass in a Pediatric Patient

Introduction: Pancreatic cancer is very rare in the pediatric population. Incidence data is scarce, and few case reports have been published. Pancreatic ductal adenocarcinoma (PDA) is the most common subtype in adults, but is rare in children. We report a case of a benign pancreatic head mass in a pediatric patient initially diagnosed as PDA on endoscopic ultrasound (EUS) guided biopsy. Case Description/Methods: A 13-year-old male with past medical history of treated Helicobacter pylori infection 6 months prior was admitted for severe acute intermittent epigastric pain. Labs showed elevated transaminases and gamma-glutamyl transferase. Abdominal ultrasound demonstrated an indeterminate solid mass-like lesion of 3 cm at the pancreatic head, and the common bile duct (CBD) was dilated to 0.9 cm. Magnetic resonance cholangiopancreatography showed a 2.2 cm indeterminate lesion along the pancreatic head region with dilated CBD of 1.4 cm, tapering at the level of the lesion. On hospital day 3, the patient underwent esophagogastroduodenoscopy and EUS. A parenchymal mass of 2.2 cm was visualized in the head of pancreas, and fine needle biopsy was performed. Cytology diagnosis was well differentiated ductal adenocarcinoma. Serum carcinoembryonic antigen, carbohydrate antigen 19-9, and alpha-fetoprotein were all normal. The patient underwent elective Whipple procedure. Surprisingly, no malignancy was identified on the surgical specimen. Instead the findings supported a diagnosis of localized fibrosing pancreatitis with high background of immunoglobulin G4 with interlobular pattern. Patient was discharged home on post-operation day 13. EUS cytology was reviewed at a tertiary cancer center and later reported as acute on chronic inflammation without malignancy (Figure). Discussion: Despite increased use of EUS for diagnosis of pancreatic masses, 5-10% of patients who undergo Whipple procedure for presumed malignancy will have benign pathology: most commonly chronic fibrosing pancreatitis, chronic pancreatitis, or focal active pancreatitis. The false positive rate for diagnosing malignancy using EUS-fine needle aspiration (FNA) of solid pancreatic lesions is less than 1%. However, it may be higher in pediatrics as the prevalence of PDA is much lower in adults. For suspected cases of PDA in pediatric patients, additional review of EUS cytology at an experienced and dedicated cancer institution is advisable before further intervention to prevent the medical and psychosocial ramifications of a false positive cancer diagnosis.Figure 1.: (Left) A parenchymal mass (2.2 x 1.8 cm) in the head of the pancreas by endoscopic ultrasound (EUS) adjacent to the portal confluence, with the common bile duct dilated to 12.8 mm (marked by yellow cross signs). Initial cytopathology from EUS-FNA of pancreatic head mass A. Diff-Quik staining at low magnification, 4x. B. Smear is cellular and well preserved with sheets, clusters and single malignant cells, 10x. C. Cells have crowded nuclei, 20x. D. Malignant cells exhibit loss of polarity, irregular nuclear contours, finely granular chromatin and some with prominent nucleoli, 40x . Based on cytomorphological features, the mass is a well differentiated ductal adenocarcinoma of pancreatic head. Note: The review of this cytopathology by a tertiary cancer institution was inconsistent with malignancy. The glandular cells had mild cytologic atypia, and the acinar cells remained lobular in configuration. Although there was some higher nuclear to cytoplasmic ratio, no absolute nuclear enlargement was noticed.

TP53 gain-of-function mutations and impact on CDKN2A mutation on prognosis of pancreatic ductal adenocarcinoma.

e16294 Background: Developmentally pancreas head derives from ventral bud while pancreas neck, body and tail derive from dorsal bud. Pancreatic ductal adenocarcinoma (PDAC) frequently harbors multiple mutations including KRAS, TP53, CDKN2A, and others. It is unknown how TP53 gain-of-function (GOF) and non-gain-of-function (non-GOF) mutations affect the prognosis. Methods: We retrospectively examined a cohort of 741 Kaiser Permanente (KP) patients with locally advanced/metastatic PDAC who had NGS performed to determine the association of KRAS (mutKRAS), TP53 (mutp53) and CDKN2A (mutCDKN2A) mutations (individually and in combination) with overall survival (OS). We used Cox modeling to estimate hazard ratios (HR) adjusted for age, sex, ethnicity, performance status, Charlston Comorbidity Index, chemotherapy received, anatomic location and co-mutations. We also analyzed the TCGA PDAC dataset to examine the association of OS with these same mutations. Results: In the KP cohort, patient ages ranged from 36 to 94 years and approximately 50% were female. In 384 patients PDAC was on the head, and 357 patients had PDAC on a non-head location (neck, body, and tail). Those with head PDAC had modestly better OS compared to non-head PDAC (HR = 0.87), and this appeared to be driven by the subsets of patients with wtp53 (HR = 0.68), with wtKRAS (HR = .74) and with wtCDKN2A (HR = .78). Approximately 67.5% of patients had mutp53, 89.2% had mutKRAS and 44.8% had mutCDKN2A. Among all KP patients, OS was similar for patients with mutp53 vs. wtp53 (HR = 1.05); worse for patients with mutKRAS vs. wtKRAS (HR = 1.26), and worse for patients with mutCDKN2 vs. wtCDKN2A (HR = 1.51). Interestingly, among patients with a GOF mutp53, those with mutCDKN2A had substantially worse OS vs patients with wtCDKN2A (HR = 2.56, 95% CI 1.46-4.50). In contrast, among patients with a non-GOF mutp53, patients with mutCDKN2A had only moderately worse OS compared to patients with wtCDKN2A (HR = 1.37, 95% CI 1.06-1.79). Analysis of the TCGA PDAC dataset showed that the number of mutations (0, 1, 2, or 3, of p53, KRAS and CDKN2A) was associated with incrementally worse OS ( p &lt; .001). Conclusions: Better OS of head vs. non-head PDAC was primarily driven by patients with wtp53, wtKRAS, and wtCDKN2A. The adverse effect of mutCDKN2A on OS appears to be most pronounced in patients with GOF mutp53. Our TCGA analysis suggests interactions among TP53, KRAS and CDKN2A mutations in affecting PDAC survival.

External validation of three lymph node ratio-based nomograms predicting survival using an international cohort of patients with resected pancreatic head ductal adenocarcinoma

IntroductionLymph node ratio (LNR) is an important prognostic factor of survival in patients with pancreatic ductal adenocarcinoma (PDAC). This study aimed to validate three LNR-based nomograms using an international cohort. Materials and methodsConsecutive PDAC patients who underwent upfront pancreatoduodenectomy from six centers (Europe/USA) were collected (2000–2017). Patients with metastases, R2 resection, missing LNR data, and who died within 90 postoperative days were excluded. The updated Amsterdam nomogram, the nomogram by Pu et al., and the nomogram by Li et al. were selected. For the validation, calibration, discrimination capacity, and clinical utility were assessed. ResultsAfter exclusion of 176 patients, 1′113 patients were included. Median overall survival (OS) of the cohort was 23 months (95% CI: 21–25).For the three nomograms, Kaplan-Meier curves showed significant OS diminution with increasing scores (p < 0.01). All nomograms showed good calibration (non-significant Hosmer-Lemeshow tests). For the Amsterdam nomogram, area under the ROC curve (AUROC) for 3-year OS was 0.64 and 0.67 for 5-year OS. Sensitivity and specificity for 3-year OS prediction were 65% and 59%. Regarding the nomogram by Pu et al., AUROC for 3- and 5-year OS were 0.66 and 0.70. Sensitivity and specificity for 3-year OS prediction were 68% and 53%. For the Li nomogram, AUROC for 3- and 5-year OS were 0.67 and 0.71, while sensitivity and specificity for 3-year OS prediction were 63% and 60%. ConclusionThe three nomograms were validated using an international cohort. Those nomograms can be used in clinical practice to evaluate survival after pancreatoduodenectomy for PDAC.

The genetic landscape of pancreatic head ductal adenocarcinoma in China and prognosis stratification

BackgroundPancreatic ductal adenocarcinoma (PDAC) is the major subtype of pancreatic cancer and head PDACs show distinct characteristics from body/tail PDACs. With limited studies based on Asian population, the mutational landscape of Asian PDAC remains unclear.MethodsOne hundred fifty-one Chinese patients with head PDAC were selected and underwent targeted 425-gene sequencing. Genomic alterations, tumor mutational burden, and microsatellite instability were analyzed and compared with a TCGA cohort.ResultsThe genomic landscape of Chinese and Western head PDAC had identical frequently-mutated genes including KRAS, TP53, SMAD4, and CDKN2A. KRAS hotspot in both cohorts was codon 12 but Chinese PDACs containing more G12V but fewer G12R variants. Potentially pathogenic fusions, CHD2-BRAF and KANK1-MET were identified in two KRAS wild-type patients. Serum cancer antigens CA125 and CA19-9 were positively associated with SMAD4 alterations while high CEA was enriched in wild-type CDKN2A subgroup. The probability of vascular invasion was lower in patients with RNF43 alterations. The nomogram developed including histology grade, the mutation status of SMAD4, TGFBR2, and PREX2 could calculate the risk score of prognoses validated by Chinese and TCGA cohort.ConclusionsChinese head PDAC contained more KRAS G12V mutation than Western population. The well-performed nomogram may improve post-operation care in real-world practice.

Pancreatico-Duodenectomy for Pancreatic Ductal Adenocarcinoma: from Artery-First Approaches toTRIANGLE Operation.

Pancreatico-duodenectomy (PD) is the single hope for long-term survival in a patient with pancreatic head ductal adenocarcinoma (PDAC). Unfortunately, even after curative intent PD, the long-term survival of patients with PDAC remains under expectations, with high recurrence rates, including the loco-regional ones. Positive resection margins after resection of PDAC are frequent, and they have a detrimental effect on both recurrence and long-term survival rates, particularly the R1 (direct) ones, toward the mesopancreas. In the last years, there were made increased efforts by surgeons to introduce in clinical practice several technical refinements to the standard technique of PD better to resect the tumor, including an accurate lymph node dissection, hoping to increase the rate of negative resection margins, to decrease local recurrence rates and to improve prognosis. Furthermore, to extend the number of patients with resectable disease, a few surgical techniques were also intended to convert to resectability the patients with the regional disease (i.e., anatomical borderline resectable and locally advanced PDAC) in the context of multimodal therapies, particularly neoadjuvant therapies. With this, we briefly discuss a few technical refinements addressing the resection time of PD, like the artery-first approaches and the Triangle operation. Both surgical techniques aim for better clearance of the retroperitoneal space for nerves, lymphatic nodes, and vessels, including total mesopancreas excision.

Comparative Recurrence Analysis of Pancreatic Adenocarcinoma after Resection.

Purpose The relation between tumor sites of pancreatic ductal adenocarcinoma (PDAC) and recurrence was not fully investigated before. We aimed to describe the differences of recurrent patterns in PDAC of head and body/tail after curative surgery. Methods The recurrent patterns of PDAC were compared and the associations with clinical characteristics were analyzed in these patients. Prognostic factors of overall survival (OS) and progression-free survival (PFS) were analyzed and validated. Predictive systems were constructed and measured by the area under the AUC curve and concordance index (C-index). Results A total of 302 PDAC patients were included in this study, including 247 patients with PDAC of head and another 55 patients with PDAC of body/tail. Patients who developed tumor recurrence within 24 months after resection had significantly shorter OS in both groups. Liver metastasis occupied most of the tumor progressions and diminished while local recurrence increased gradually over time. The variation trends were similar for patients in both groups while these changes were more pronounced for patients in the head group. Local recurrence and liver-only metastasis seemed to indicate a better OS. Furthermore, predictive systems for OS and PFS prediction based on independent risk factors were established and showed significant higher values of AUC and C-indexes compared with the TNM stage system. Conclusions Different characteristics of progressions for PDAC of head and body/tail suggested biological heterogeneity. The exploration of these variations helps to provide personalized management of recurrence in PDAC.

Development and Validation of a Nomogram to Predict Survival in Pancreatic Head Ductal Adenocarcinoma After Pancreaticoduodenectomy.

BackgroundPancreatic head ductal adenocarcinoma (PHDAC) patients with the same tumor-node-metastasis (TNM) stage may share different outcomes after pancreaticoduodenectomy (PD). Therefore, a novel method to identify patients with poor prognosis after PD is urgently needed. We aimed to develop a nomogram to estimate survival in PHDAC after PD.MethodsTo estimate survival after PD, a nomogram was developed using the Tongji Pancreatic cancer cohort comprising 355 PHDAC patients who underwent PD. The nomogram was validated under the same conditions in another cohort (N = 161) from the National Taiwan University Hospital. Prognostic factors were assessed using LASSO and multivariate Cox regression models. The nomogram was internally validated using bootstrap resampling and then externally validated. Performance was assessed using concordance index (c-index) and calibration curve. Clinical utility was evaluated using decision curve analysis (DCA), X-tile program, and Kaplan–Meier curve in both training and validation cohorts.ResultsOverall, the median follow-up duration was 32.17 months, with 199 deaths (64.82%) in the training cohort. Variables included in the nomogram were age, preoperative CA 19-9 levels, adjuvant chemotherapy, Tongji classification, T stage, N stage, and differentiation degree. Harrell’s c-indices in the internal and external validation cohorts were 0.79 (95% confidence interval [CI], 0.76–0.82) and 0.83 (95% CI, 0.78–0.87), respectively, which were higher than those in other staging systems. DCA showed better clinical utility.ConclusionThe nomogram was better than TNM stage and Tongji classification in predicting PHDAC patients’ prognosis and may improve prognosis-based selection of patients who would benefit from PD.

External validation of three nomograms predicting survival using an international cohort of patients with resected pancreatic head ductal adenocarcinoma

Abstract Objective Lymph node ratio (LNR, positive lymph nodes/collected lymph nodes during surgery) was identified as an important prognostic factor of survival in resected pancreatic cancer. Several nomograms based on LNR were recently proposed to predict survival after pancreatoduodenectomy (PD). The present study aimed to externally validate 3 published nomograms using an international cohort. Methods Consecutive patients with ductal adenocarcinoma of the pancreatic head who underwent PD without neoadjuvant treatment from 6 tertiary centers in Europe and the USA were retrospectively collected from 2000 to 2017. Patients with metastases at diagnosis, R2 resection, missing data regarding LNR, and who died within 90 postoperative days were excluded. The 3 selected nomograms were the updated Amsterdam nomogram (including LNR, adjuvant therapy, margin status, and tumor grade), the nomogram by Pu et al. (including LNR, age, tumor grade, and T stage) and the nomogram by Li et al. (including LNR, age, tumor location, grade, size, and TNM stage). Overall survivals (OS) were calculated using Kaplan-Meier method. For the validation, calibration (Hosmer-Lemeshow test), discrimination capacity (ROC curves for 3-year OS), and clinical utility (sensitivity and specificity at the value of Youden index) were assessed. Results After exclusion of 95 patients with metastases, R2 resection, and who died within 90 postoperative days, 1167 patients were included. Median OS of the entire cohort was 23 months (95% confidence interval: 21-24). For the 3 nomograms, Kaplan-Meier curves showed significant diminution of OS with increasing scores (p &amp;lt; 0.01 for the 3 nomograms). All nomograms showed good calibration (non significant Hosmer-Lemeshow goodness-of-fit tests). For the updated Amsterdam nomogram, the area under the ROC curve (AUROC) for 3-year OS was 0.66. Sensitivity and specificity were 73% and 50%. Regarding the nomogram by Pu et al., the AUROC was 0.67. Sensitivity and specificity were 65% and 60%. For the nomogram by Li et al., the AUROC was 0.67, while sensitivity and specificity were 56% and 71%. Conclusion The 3 selected nomograms were validated using an external international cohort and displayed interesting and comparable predictive values. Those nomograms may be used in clinical practice to estimate survival after PD for ductal adenocarcinoma.

Impact of Neoadjuvant Chemotherapy and Pretreatment Biliary Drainage for Pancreatic Head Ductal Adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) is one of the leading causes of cancer-related deaths in the USA. Although management strategies have evolved, there are continued controversies about the use of neoadjuvant chemotherapy (NAC) and pretreatment biliary drainage (PBD) in patients with resectable and potentially resectable disease. We aimed to characterize the practice trends and outcomes for NAC and PBD. A single-center cohort study was performed. Electronic medical records were reviewed between 2011 and 2019, and 140 patients who had pancreaticoduodenectomy for PDAC were included. Diagnosis, treatment, and outcome data were captured. There were no statistically significant temporal trends relating to the use of chemotherapy and PBD. Overall, 41% of patients received NAC and had improved survival, independent of other factors. Of the 71% who received PBD, only 40% had appropriate indications; 30% experienced postprocedure complications, and 34% required reintervention. Factors associated with the application of PBD included preoperative jaundice (OR 70.5, 95% CI 21.4-306.6) and evaluation by non-tertiary therapeutic endoscopists (OR 3.9, 95% CI 1.3-13.6). PBD was associated with a 12-day delay in surgery among those who did not receive NAC (p = 0.005), but there were no differences in surgical complications or mortality. Our findings suggest that (1) NAC may confer a survival benefit and (2) PBD should be reserved for individuals with jaundice requiring NAC. Implementation of guidelines by North American gastroenterology societies, multidisciplinary treatment models, and delivery of care at high-volume tertiary centers may help optimize management.

Computed tomography in determining the differentiation of ductal adenocarcinoma of pancreatic head

To evaluate the features of «hypervascular rim», tumor dimensions and density as prognostic factors of differentiation of pancreatic head adenocarcinoma. Pancreatoduodenectomy was performed in 311 patients with pancreatic head adenocarcinoma for the period 2013-2019. A retrospective study included 81 patients who met the following criteria: available data of morphological and immunohistological examination indicating tumor grade from Grade 1 to Grade 3, as well as available preoperative CT images in four phases (native, arterial, portal and delayed). Tumor dimensions, density of the pancreas, adenocarcinoma and abdominal aorta by the phases of contrast enhancement were analyzed in all patients. Moreover, we estimated coefficient of relative enhancement change. Perifocal hypervascular enhancement was assessed in arterial and portal phases. Contrast-enhanced MRI was performed in 15 out of 81 patients. MR images were analyzed regarding a hypervascular rim, and the last one was compared with CT images. There was no significant difference in density values between different tumor grades. Coefficient of relative enhancement change >1 was observed in 63.64% of highly-differentiated tumors. REC ≤1 was found in 85.11% of tumors grade 2 and 82.6% of tumors grade 3 (p=0.005). According to Chi-square test, there was a correlation between tumor differentiation and hypervascular rim (p=0.03). Moderate and low differentiation was observed in 96.42% of tumors with perifocal enhancement. Hypervascular rim was absent in 81.82% of tumors grade 1. Adenocarcinoma grade 2 was found in 85.71% of cases with unclear perifocal enhancement. Preoperative contrast-enhanced CT is valuable to assume the tumor grade in patients with pancreatic head adenocarcinoma due to assessment of hypervascular rim and REC.

External Validation of Three Nomograms Predicting Survival Using an International Cohort of Patients with Resected Pancreatic Head Ductal Adenocarcinoma

Purpose: Lymph node ratio (LNR, positive lymph nodes/collected lymph nodes during surgery) was identified as an important prognostic factor of survival in resected pancreatic cancer. Several nomograms based on LNR were recently proposed to predict survival after pancreatoduodenectomy (PD). The present study aimed to externally validate 3 published nomograms using an international cohort. Methods: Consecutive patients with ductal adenocarcinoma of the pancreatic head who underwent PD without neoadjuvant treatment were retrospectively collected from 6 tertiary centers in Europe and the USA from 2000 to 2017. Patients with metastases at diagnosis, R2 resection, missing data regarding LNR, and who died within 90 postoperative days were excluded. The 3 selected nomograms were the updated Amsterdam nomogram (including LNR, adjuvant therapy, margin status, and tumor grade), the nomogram by Pu et al. (including LNR, age, tumor grade, and T stage) and the nomogram by Li et al. (including LNR, age, tumor location, grade, size, and TNM stage). Overall survivals (OS) were calculated using Kaplan-Meier method. For the validation, calibration (Hosmer-Lemeshow test), discrimination capacity (ROC curves for 3-year OS), and clinical utility (sensitivity and specificity at the value of Youden index) were assessed. Results: After exclusion of 95 patients with metastases, R2 resection, and who died within 90 postoperative days, 1167 patients were included. Median OS of the entire cohort was 23 months (95% CI: 21-24). For the 3 nomograms, Kaplan-Meier curves showed significant diminution of OS with increasing scores (p<0.01 for the 3 nomograms). All nomograms showed good calibration (non significant Hosmer-Lemeshow goodness-of-fit tests). For the updated Amsterdam nomogram, the area under the ROC curve (AUROC) for 3-year OS was 0.66. Sensitivity and specificity were 73% and 50%. Regarding the nomogram by Pu et al., the AUROC was 0.67. Sensitivity and specificity were 65% and 60%. For the nomogram by Li et al., the AUROC was 0.67, while sensitivity and specificity were 56% and 71%. Conclusion: The 3 selected nomograms were validated using an external international cohort and displayed interesting and comparable predictive values. Those nomograms may be used in clinical practice to estimate survival after PD for ductal adenocarcinoma.

Safety assessment of preoperative oil chemoembolization with nanoparticle albumin-bound paclitaxel in patients with pancreatic head adenocarcinoma

Results of combined treatment of 36 patients suffering from pancreatic head ductal adenocarcinoma are evaluated, including preoperative chemotherapy using nanodispersed albumin-stabilized paclitaxel (nab-paclitaxel) in intraarterial oil chemoembolization or intravenous administration and radical surgical treatment. Intraarterial oily chemoembolization of the pancreatic head consisted of the introduction of 17 patients (main group) into the gastroduodenal artery of an emulsion of super-liquid lipiodol (Lipiodol Ultra Fluid) in an aqueous solution of nab-pacliaxel 50 mg/m2 and gemcitabine 400 mg/m2. 19 patients (control group) were administered nab-paclitaxel 100 mg/m2 and gemcitabine 1000 mg/m2 intravenously according to standard guidelines. Safety and tolerability assessment of combined treatment with preoperative application of nab-paclitaxel was carried out in advance. Pil-preserving pancreatoduodenal resection is considered safe on day 710, after completion of preoperative chemotherapy with nab-paclitaxel. The use of nab-paclitaxel in preoperative intraarterial oily chemoembolization of the pancreatic head requires extension of the pancreatic crossing boundary to body level. Postoperative lethality and 4th degree complications according to the Clavien-Dindo classification were not observed. In the main group, grade 3a complication was observed in 2 (12%) patients and was represented by bleeding from acute gastric erosions resolved endoscopically. In the control group, complications of degree 3 were also noted in 2 (11%) patients and were represented by: one bleeding from acute stomach erosions that required endoscopic hemostasis and an intraabdominal abscess allowed by percutaneous drainage. In the main group, complications of the 2nd degree were recorded in 8 (47%) patients: in 3 (17%) patients the formation of pancreatic fistula was noted, in 4 (23%) postoperative pancreatitis was detected, and in 1 (6%) gastrostasis phenomena that required conservative therapy. In the control group, complications of the 2nd degree were observed in 11 (58%) patients and were presented: pancreatic fistulae in 2 (10%) patients, postoperative pancreatitis in 6 (31%) and gastrostasis in 3 (16%) patients. The most common complication observed in both groups was the suppression of a postoperative wound, corresponding to the 1st degree of severity: in the main group in 5 (29%) patients, in the control group in 7 (37%) patients. Thus, the use of intraarterial oil chemoembolization with nab-paclitaxel as a preoperative antitumor treatment can be considered safe.