Borderline Resectable Pancreatic Carcinoma Research Articles

Comparison of neoadjuvant treatment and surgery first for resectable or borderline resectable pancreatic carcinoma: A systematic review and network meta-analysis of randomized controlled trials.

Current treatment recommendations for resectable or borderline pancreatic carcinoma support upfront surgery and adjuvant therapy. However, neoadjuvant therapy (NT) seems to increase prognosis of pancreatic carcinoma and come to everyone's attention gradually. Randomized controlled trials offering comparison with the NT are lacking and optimal neoadjuvant treatment regimen still remains uncertain. This study aims to compare both treatment strategies for resectable or borderline resectable pancreatic cancer. The PRISMA checklist was used as a guide to systematically review relevant peer-reviewed literature reporting primary data analysis. We searched PubMed, Medline, EMBASE, Cochrane Datebase and related reviews for randomized controlled trials comparing neoadjuvant therapy with surgery first for resectable or borderline resectable pancreatic carcinoma. We estimated relative hazard ratios (HRs) for median overall survival and ratios risks (RRs) for microscopically complete (R0) resection among different neoadjuvant regimens and major complications. We assessed the effects of neoadjuvant therapy on R0 resection rate and median overall survival with Bayesian analysis. Thirteen eligible articles were included. Eight studies performed comparison neoadjuvant therapy with surgery first, and R0 resection rate was recorded in seven studies. Compared with surgery first, neoadjuvant therapy did increase the R0 resection rate (RR = 1.53, I2 = 0%, P< 0.00001), there was a certain possibility that gemcitabine + cisplatin (Gem+Cis) + Radiotherapy was the most favorable in terms of the fact that there was no significant difference concerning the results from the individual studies. In direct comparison, four studies were included and estimated that Neoadjuvant therapy improved mOS compared with upfront surgery (HR 0.68, 95% CI 0.58-0.92; P = 0.012; I2 = 15%), after Bayesian analysis it seemed that regimen with Cisplatin/ Epirubicin then Gemcitabine/ Capecitabine (PEXG) was most likely the best with a relatively small sample size. The rate of major surgical complications was available for six studies and ranged from 11% to 56% with neoadjuvant therapy and 11% to 45% with surgery first. There was no significant difference between neoadjuvant therapy and surgery first, also with a high heterogeneity (RR = 0.96, 95%CI = 0.65-1.43; P = 0.85; I2 = 46%). In conclusion neoadjuvant therapy might offer benefit over up-front surgery. Neoadjuvant therapy increased the R0 resection rate with gemcitabine + cisplatin + Radiotherapy that was the most favorable and improved mOS with Cisplatin/ Epirubicin then Gemcitabine/ Capecitabine (PEXG) that was most likely the best.

Impact of Different Surgical Approaches on Morbidity and Mortality in Patients with Borderline Resectable Pancreatic Head Carcinoma.

Radical surgical resection for pancreatic head carcinoma offers a chance for cure but unfortunately is only available to a limited number of patients. For a significant number of patients, palliative surgery remains the only option. The question of the most effective approach for patients with borderline resectable pancreatic head carcinoma (BRPHC) remains unresolved. Objective: The aim of the study was to compare the morbidity and mortality following R1 duodenocephalic pancreatectomy and double palliative bypass to explore the most optimal surgical treatment for patients with BRPHC. Our retrospective cohort study included 64 patients with BRPHC who underwent surgery from 2012 to 2019, with postoperative follow-up for three years. Morbidity and mortality parameters were examined based on the type of surgical treatment: R1 duodenocephalic pancreatectomy or palliative double bypass. Chi-square test, univariate regression, and Kaplan-Meier analysis were used as basic statistical methods in the analysis of the results. Patients undergoing R1 duodenocephalic pancreatectomy had a 3.69 times higher risk of developing biliary leak (p=0.039; 95%CI:1.066, 1.181) and shorter survival compared to those undergoing palliative double bypass (p=0.022). No statistically significant association was found between the type of surgical procedure and other postoperative complications. Our study suggests that the double palliative bypass procedure may be a better option than R1 resection for patients with BRPHC.

Failure of a Multi-Centric Clinical Trial Investigating Neoadjuvant Radio-Chemotherapy in Resectable Pancreatic Carcinoma (NEOPA-NCT01900327)-Which Lessons Are Learnt?

A significant number of clinical trials must be prematurely discontinued due to recruitment failure, and only a small fraction publish results and a failure analysis. Based on our experience on conducting the NEOPA trial on neoadjuvant radiochemotherapy for resectable and borderline resectable pancreatic carcinoma (NCT01900327-funded by the German Federal Ministry of Education and Research-BMBF), we performed an analysis of potential reasons for recruitment failure and general problems in conducting clinical trials in Germany. Systematic analysis of environmental factors, trial history, conducting and funding in the background of the published literature. The recruitment failure was based on various study-specific conceptional and local environmental aspects and in peculiarities of the German surgical study culture. General reservations against a neo-adjuvant study concept combined with game changing scientific progresses during the long-lasting planning and funding phase have led to a reduced interest in the trial design and recruitment. Trial planning and conducting should be focused, professionalized and financed on a national basis. Individual interests must be subordinated to reach the goal to perform more relevant and successful clinical trials in Germany. Bureaucratic processes must be further fastened between a trial idea and the start of a study.

Upfront surgery versus neoadjuvant chemotherapy for borderline resectable pancreatic carcinoma with venous encasement more than 180 degree, comparative study

Background Pancreatic cancer is considered the seventh cause of cancer-related death worldwide, and has low resection rate and a poor prognosis. Surgical resection to achieve R0 followed by adjuvant chemotherapy is the treatment of choice. Borderline resectable pancreatic cancer (BRPC) is technically difficult tumor with high risk of non-radical resection R1 and early postoperative recurrence. A neoadjuvant chemotherapy in BRPC instead of upfront surgical resection has advantages of increase R0 resection rate, treatment of undetected micro metastases and decrease postoperative pancreatic fistula. Objective Comparing the short-term outcome between upfront surgery and neoadjuvant chemotherapy for borderline resectable pancreatic carcinoma for venous encasement only as regards the ability to do R0 resection, early surgical complications and the progression rate of the disease Design Prospective cohort. Patients and methods Patients age between 20–70, with only venous encasement (no arterial encasement) with encasement&gt;180 degrees and a segment of venous encasement not more than 2 cm were included. Patients with an arterial encasement, distant metastasis, and not fit for chemotherapy were excluded. Results The upfront surgery group has higher resection rate (75%) with portal/SMV reconstruction needed in one-third of the cases (33.3%) while the neoadjuvant chemotherapy group has higher progression rate (55%) and low resection rate (only 20%). No significant difference between the groups as regards the complication rate (morbidity and mortality), R1 resection(margin invasion), blood loss or time of surgery. Conclusion Upfront surgery can be done in selected patients with BR-PDAC to avoid the progression of the disease with no statistically significant difference as regards the short-term complications in comparison to the neoadjuvant group.

Prognostic Value of Neoadjuvant Chemotherapy in Patients with Borderline Resectable Pancreatic Carcinoma Followed by Pancreatectomy with Portal Vein Resection and Reconstruction with Venous Allograft.

Neo-adjuvant chemotherapy (NAC) represents one of the current research hotspots in the field of pancreatic ductal adenocarcinoma (PDAC). The aim of this study is to evaluate the prognostic value of NAC in patients with borderline resectable pancreatic cancer (BRPC) followed by pancreatectomy with portal vein (PV) resection and reconstruction with venous allograft (VAG). Medical records of patients with BPRC who underwent pancreatectomy with concomitant PV resection and reconstruction with VAG between April 2013 and March 2021 were analyzed retrospectively. Outcomes of patients with and without NAC (NAC, Group 1 vs. non-NAC, Group 2) were compared with focus on R0 resection rates, morbidity, and survival. Of the 77 patients with pancreatectomy, PV resection and reconstruction with VAG were identified. Overall survival (OS) rates of 0.5-, 1-, and 2-year were 80.5%, 59.7%, and 31.2%, respectively (median survival time, MST, 14 months). Of these, 24 patients (Group 1) underwent operation following received NAC, and the remaining 53 patients did not (Group 2). The R0 resection rate of vascular margin was 100% vs. 84.9% (p = 0.04), respectively. Morbidity of post-operative pancreatic fistula (POPF) was 0% vs. 17.8% (p = 0.07), respectively. The OS of 0.5-, 1- and 2-year and MST of 2 groups were 83.3%, 66.7%, 41.7%, 16 months, and 79.2%, 55.6%, 26.4%, 13 months, respectively. Multivariate analysis revealed that carbohydrate antigen 19-9 (CA19-9) serum level and postoperative chemotherapy were independent prognostic factors in patients with BRPC after surgery. NAC might improve the R0 resection rate and POPF in patients with BRPC who underwent pancreatectomy with concomitant PV resection and reconstruction with VAG. Survival benefit exists in patients with BRPC who received NAC before pancreatectomy. Postoperative chemotherapy also had a favorable effect on OS of BRPC patients. Elevated CA 19-9 serum level is associated with poor prognosis, even after NAC-combining operation.

Current and emerging therapeutic strategies in pancreatic cancer: Challenges and opportunities.

Pancreatic carcinoma (PC) is one of the leading causes of cancer-related deaths worldwide. Despite early detection and advances in therapeutics, the prognosis remains dismal. The outcome and therapeutic approach are dependent on the stage of PC at the time of diagnosis. The standard of care is surgery, followed by adjuvant chemotherapy. The advent of newer drugs has changed the landscape of adjuvant therapy. Moreover, recent trials have highlighted the role of neoadjuvant therapy and chemoradiotherapy for resectable and borderline resectable PC. As we progress towards a better understanding of tumor biology, genetics, and microenvironment, novel therapeutic strategies and targeted agents are now on the horizon. We have described the current and emerging therapeutic strategies in PC.

Investigation of neoadjuvant therapy for borderline resectable pancreatic cancer

Aim: Although there are a few reports on the efficacy of neoadjuvant therapy (NAT) as a treatment for borderline resectable pancreatic carcinoma (BRPC), the topic remains controversial. Therefore, we conducted a retrospective study to analyze the long-term outcome. Method: Fifty-one patients who underwent neoadjuvant chemotherapy (NAC) or neoadjuvant chemoradiotherapy (NACRT) for BRPC at our hospital, between April 2003 and September 2019 were recruited in this study. Result: Altogether, 51 patients were diagnosed with BRPC based on the General Rules for the Study of Pancreatic Cancer (7th edition), of which, 15 had NAC, and 36 underwent NACRT. In total, 33 patients underwent resection of the pancreas (10 from NAC group (66.7%) and 23 from NACRT group (63.9%)), and 32 had radical surgery (9 from NAC group (60.0%) and 23 from NACRT group (63.9%)). R0 resection rate was 50% (16/32), and there was no significant difference between the NAC and NACRT groups (44.4% vs. 52.2%, P = 0.16). OS (21.0 months vs. 36.1 months, P = 0.974) and RFS (20.0 months vs. 24.0 months, P = 0.266) showed no significant differences between the NAC and NACRT groups. As revealed by the pathological findings, the percentage of patients with positive dissected peripancreatic tissue margin was significantly lower for the NACRT group than that of the NAC group (66.7% vs. 26.1%, P = 0.033). Conclusion: Although no significant difference was observed regarding long-term prognosis between the NAC and the NACRT groups, the results indicate the effectiveness of radiotherapy in local tumor control of BRPC.

Outcomes of Neoadjuvant Chemoradiation With and Without Systemic Chemotherapy in Resectable and Borderline Resectable Pancreatic Adenocarcinoma.

Introduction: Neoadjuvant therapy is increasingly being used for localized pancreatic adenocarcinoma. While there is evidence supporting neoadjuvant systemic chemotherapy as well as chemoradiation, more evidence is needed to determine whether systemic chemotherapy with chemoradiation offers benefits over chemoradiation alone. This study compares the outcomes of neoadjuvant chemoradiation therapy with and without systemic chemotherapy in resectable and borderline resectable pancreatic cancers.Methods: This retrospective study evaluated patients with resectable and borderline resectable pancreatic adenocarcinoma who completed neoadjuvant chemoradiation therapy with and without systemic chemotherapy prior to surgical resection. 149 patients met inclusion criteria, with 75 having resectable cancer and 74 having borderline resectable cancer. Outcomes included recurrence free and overall survival rates at 6, 12, and 36 months.Results: In resectable pancreatic carcinoma, 72% of patients treated with chemoradiation alone achieved 1 year recurrence free survival compared to 78% of patients treated with systemic chemotherapy and chemoradiation (p = 0.55). 28% of patients treated with chemoradiation alone had 3 years recurrence free survival compared to 31% of patients who received systemic and chemoradiation therapy (p = 0.75). In both treatment groups, 92% of patients lived past 1 year (p = 0.92), and 44% of patients survived at least 3 years (p = 0.95). In borderline resectable pancreatic carcinoma, 50% of patients treated with chemoradiation alone achieved 1 year recurrence free survival compared to 70% of patients treated with systemic chemotherapy and chemoradiation (p = 0.079). The 3 years recurrence free survival was 26 and 29% for the chemoradiation alone group and the systemic chemotherapy plus chemoradiation group, respectively (p = 0.85). There was no significant difference in 1 year overall survival: 85% of patients treated with chemoradiation alone survived compared to 92% of patients treated with systemic chemotherapy and chemoradiation (p = 0.32). Both groups had 41% 3 years overall survival (p = 0.96).Discussion: In resectable and borderline resectable pancreatic adenocarcinoma, there was no significant difference in overall or recurrence free survival between patients treated with chemoradiation with and without systemic chemotherapy. Our findings suggest that systemic neoadjuvant chemotherapy with chemoradiation and chemoradiation alone are efficacious treatments for localized pancreatic carcinoma. This brings into question whether more effective systemic chemotherapy is necessary to increase survival benefit.

Erratum to: Ablative treatment options for locally advanced unresectable and borderline resectable pancreatic carcinoma

Background Locally advanced unresectable (nonmetastatic) and borderline resectable pancreatic carcinomas represent a therapeutic challenge. Several minimally invasive local ablative techniques are available for local treatment in these situations. Objective Which interventional techniques and application options are currently available for pancreatic carcinoma and which oncological results could be achieved so far? Material and methods An analysis of reviews and studies was carried out. The selection of literature was based on searches in PubMed and the Cochrane library. The studies analyzed were reviews, meta-analyses and original articles mainly from the period between 2013 and 2018. Single case reports were not included in this review. Results Local ablative techniques are performed with various forms of energy and are associated with specific advantages and disadvantages. They have to be individually tailored to the specific patient and situation. Noninvasive thermal ablation with high-intensity focused ultrasound (HIFU) is primarily used for palliative pain relief. Solid tumors are the main indication for thermal necrosis with microwave ablation (MWA) and radiofrequency ablation (RFA). The use of irreversible electroporation (IRE) enables a selective destruction of tumor cells and can be performed in the vicinity of sensitive structures. This technique is applied for primary tumor control and also for accentuation of tumor margins during resection. Conclusion With local ablative techniques an improvement in the quality of life and possibly the prognosis can be achieved in patients with unresectable pancreatic cancer; however, the latter aspect has to be viewed with caution due to a current lack of well-founded data.

Current Clinical Strategies of Pancreatic Cancer Treatment and Open Molecular Questions.

Pancreatic cancer is one of the most lethal malignancies and is associated with a poor prognosis. Surgery is considered the only potential curative treatment for pancreatic cancer, followed by adjuvant chemotherapy, but surgery is reserved for the minority of patients with non-metastatic resectable tumors. In the future, neoadjuvant treatment strategies based on molecular testing of tumor biopsies may increase the amount of patients becoming eligible for surgery. In the context of non-metastatic disease, patients with resectable or borderline resectable pancreatic carcinoma might benefit from neoadjuvant chemo- or chemoradiotherapy followed by surgeryPatients with locally advanced or (oligo-/poly-)metastatic tumors presenting significant response to (neoadjuvant) chemotherapy should undergo surgery if R0 resection seems to be achievable. New immunotherapeutic strategies to induce potent immune response to the tumors and investigation in molecular mechanisms driving tumorigenesis of pancreatic cancer may provide novel therapeutic opportunities in patients with pancreatic carcinoma and help patient selection for optimal treatment.

Clinical efficacy of radical resection with individualized surgical approach for borderline resectable pancreatic head carcinoma

Objective To explore the clinical efficacy of radical resection with individualized surgical approach for borderline resectable pancreatic head carcinoma. Methods The retrospective descriptive study was conducted. The clinicopathological data of 54 patients with borderline resectable pancreatic head carcinoma who underwent radical resection with individualized surgical approach in the West China Hospital of Sichuan University from January 2015 to January 2018 were collected. There were 37 males and 17 females, aged from 37 to 73 years, with a median age of 59 years. For venous type borderline resectable pancreatic head carcinoma, surgery for pancreatic head carcinoma and (or) pancreatic head and neck carcinoma was performed via inferior mesenteric vein, and surgery for pancreatic uncinate process carcinoma was performed via inferior colon artery. For arterial type borderline resectable pancreatic head carcinoma, surgery for pancreatic head carcinoma and (or) pancreatic head and neck carcinoma was performed via medial uncinate artery, and surgery for pancreatic uncinate process carcinoma was performed via left posterior artery. Observation indicators: (1) surgical situations; (2) postoperative complications; (3) postoperative pathological examination; (4) follow-up. Patients were followed up by outpatient examination or telephone interview once every 3 months to detect survival up to March 2019. Measurement data with normal distribution were represented by Mean±SD. Measurement data with skewed distribution were represented by M (range), and count data were represented by absolute numbers or percentage. Kaplan-meier method was used to draw the survival curve and calculate the survival rate. Results (1) Surgical situations: all the 54 patients underwent expanded pancreatoduodenectomy combined with superior mesenteric vein/portal vein (SMV/PV) resection, including 15 via inferior mesenteric vein, 20 via inferior colon artery, 12 via medial uncinate artery, and 7 via left posterior artery. The operation time was (320±83)minutes, and the volume of intraoperative blood loss was (865±512)mL. (2) Postoperative complications: of 54 cases, 28 had postoperative complications, including 13 with grade 1 Clavien-Dindo complications, 12 with grade 2 Clavien-Dindo complications, 3 with grade 3 or above Clavien-Dindo complications. One of the 28 patients with postoperative complications died and 27 were improved after symptomatic and supportive treatment. (3) Postoperative pathological examination: of 54 patients, 31 had R0 resection and 23 had R1 resection. In the 23 patients with R1 resection, 5 underwent surgery via the inferior mesenteric vein (4 with involvement of pancreatic anterior surface, 1 with involvement of both pancreatic anterior and posterior surface), 9 underwent surgery via the inferior colon artery (2 with involvement of both pancreatic anterior and posterior surface, 2 with involvement of superior mesenteric artery margin, 2 with involvement of pancreatic posterior surface, 2 with involvement of pancreatic anterior surface, 1 with involvement of superior mesenteric artery margin and pancreatic posterior surface), 5 underwent surgery via the medial uncinate process artery (2 with involvement of superior mesenteric artery margin, 2 with involvement of both pancreatic anterior and posterior surface, 1 with involvement of pancreatic neck transected margin), and 4 underwent surgery via the left posterior artery (3 with involvement of superior mesenteric artery margin, 1 with involvement of both pancreatic anterior and posterior surface). Of 54 patients, 16 had no positive lymph nodes, 26 had 1-3 positive lymph nodes, and 12 had 4 or more positive lymph nodes. The tumor diameter was (3.20±0.14)cm. There were 48 of 54 patients with nerve infiltration, 41 with superior mesenteric vein and/or portal vein infiltration, and 11 with vascular thrombus. There were 17 of 54 patients with high differentiation and medium differentiation, and 37 with low differentiation and undifferentiation. (4) Follow-up: 54 patients were followed up for 1-42 months, with a median time of 19 months. The 1-, 3-year overall survival rate was 78.0%, 11.4%. Conclusion As for the borderline resectable pancreatic head cancer, individualized and customized surgical approach according to the location of tumor and the relationship with blood vessels is helpful to standardize the radical resection and avoid R2 resection. Key words: Pancreatic neoplasms; Pancreatic cancer; Borderline resectable; pancreaticoduodenectomy; Surgical approach; R2 resection; Efficacy

Thinking in the confusion, advancing in the challenges: hotspots in the comprehensive treatment of pancreatic carcinoma

Pancreatic carcinoma has the poorest prognosis in all the digestive cancers, and the management remains challenging. Nowadays the treatment strategy of pancreatic carcinoma has been changed from first into the mode of multi-disciplinary team (MDT) with surgery as a leading and crucial position. By historical review, some issues related to the strategy of borderline resectable pancreatic carcinoma, including value of neoadjuvant therapy, perioperative complications, laparoscopic pancreaticoduodenectomy were discussed and commentated. The breakthrough for managing pancreatic carcinoma will be based on early diagnosis and the development of biologic targeting therapy. The surgeons′ concept should constantly advance with the times, and the strategy pattern should be converted from local to system, from morphology to biology, and from surgery to oncology. Key words: Pancreatic neoplasms; Neoadjuvant the-rapy; Complication; Pancreaticoduodenectomy; Laparoscopy

Irreversible electroporation in borderline resectable pancreatic adenocarcinoma for margin accentuation

Achieving clear microscopic resection margins following pancreaticoduodenectomy (PD) is challenging particularly in borderline resectable pancreatic carcinoma (BRPC). Positive resection margins has been identified as a major independent prognostic factor. Irreversible electroporation (IRE) has emerged as a promising non-thermal ablative method that could be used in the treatment of pancreatic cancer as an adjunct to chemotherapy and surgery. This case report describes the successful simultaneous intraoperative IRE and PD in a patient with BRPC, achieving clear microscopic resection margins. Technical aspects and histology showing the effect of IRE are presented. The role of IRE in the treatment of pancreatic adenocarcinoma should be further evaluated in prospective studies.

Pancreaticoduodenectomy with irreversible electroporation margin enhancement for borderline resectable pancreatic carcinoma

Background: Borderline resectable pancreatic carcinoma (BRPC) as defined by NCCN guidelines, remains a challenging surgical problem, particularly in obtaining negative margins. In this study, surgical resection with irreversible electroporation for margin enhancement was evaluated to determine the long-term outcomes in BRPC. Methods: Patients with BRPC were included; those who underwent surgical resection with IRE (SIRE) were compared to those undergoing surgical resection alone (SR). The SR cohort was case-matched to demographic, operative, and oncologic parameters. Patients with concomitant vascular resection were excluded. Primary outcome measures included overall survival and disease recurrence. Results: Twenty patients were evaluated, ten in each group. Median overall survival was numerically higher in the SIRE group (13 months vs. 8 months, “p = 0.72”). At 2 years, SIRE patients had improved survival versus SR alone (70% vs. 20%, “p = 0.0145”). 1-year recurrence was numerically less in the SIRE group (20% vs. 30%, “p = 0.9770”). Conclusion: Surgical resection with IRE margin enhancement for BRPC may improve long term survival.

2．BR膵癌の臨床病理学的特徴とその治療戦略

2．BR膵癌の臨床病理学的特徴とその治療戦略

Effect of Neoadjuvant Nab-Paclitaxel plus Gemcitabine Therapy on Overall Survival in Patients with Borderline Resectable Pancreatic Cancer: A Prospective Multicenter Phase II Trial (NAC-GA Trial)

We conducted a prospective multicenter phase II trial of patients with borderline resectable pancreatic carcinoma to investigate the efficacy of neoadjuvant nab-paclitaxel plus gemcitabine therapy on overall survival (OS). The clinical trial primarily evaluated OS time from the first day of protocol therapy as a primary endpoint. The secondary endpoints were recurrence-free survival from the first day of protocol therapy, safety of the protocol therapy (adverse effect), morbidity based on the Clavien Dindo classification of more than III, response rate, preoperative/postoperative tumor marker (CA 19-9, CEA), rate of normalization, reduction rate of the maximum standardized uptake value on positron emission tomography-computed tomography (limited to institutions where positron emission tomography-computed tomography was available), chemotherapeutic effect grade based on Evans' classification, resection rate, R0 resection rate, surgical data (operative time, blood loss, transfusion, postoperative hospital day), overall morbidity rates (reoperation, rate of readmission, mortality), patient rate in postoperative adjuvant therapy (entry rate, completion rate), dose intensity, quality of life regarding fatigue and malaise assessed by the questionnaire of FACIT-F (Japanese version), and peripheral sensory neuropathy assessed by the questionnaire of the FACT/GOG-NTX subscale (version 4; Japanese version). Sixty patients were included in the study, and 18 leading Japanese institutions and hospitals (all high-volume centers in pancreatic surgery) participated in this trial.

An Interview with Carolyn M. Clancy

Current guidelines recommend computed tomographic (CT) scans for vascular staging of patients with pancreatic carcinoma; however, endoscopic ultrasonography (EUS) in these patients is not required and its utility in combination with CT scan is less well-defined. The purpose of this study is to explore the utility of EUS in addition to CT in identifying patients with borderline resectable pancreatic carcinoma (BRPC).We reviewed our database of patients with BRPC who went to surgery with curative intent. Inclusion criteria were preoperative staging with CT scan and EUS, completion of neoadjuvant chemotherapy and radiotherapy, and surgical resection.We identified 62 patients (average age of 65 ± 9 years, 60% male); 97% of patients underwent R0 resections. We found that 29% of patients were classified as BRPC by EUS alone, 23% by CT alone, and 48% by both modalities. Of 34 patients who required vein resection, EUS alone preoperatively identified 88% of these patients while CT alone identified 67%. EUS identified 11 patients who required vein resection that CT did not identify as BRPC, whereas CT identified 4 patients that EUS did not identify as BRPC. On multivariate analysis, EUS was associated with vein resection (P < 0.02), but CT scan findings, tumor size, and CA19-9 values were not associated (each P > 0.1).EUS complemented CT in identifying BRPC patients requiring vein resection, with nearly one-third of patients identified with EUS alone, supporting EUS use in addition to CT scan for vascular staging of patients with pancreatic carcinoma.

Prognostic impact of normalization of serum tumor markers following neoadjuvant chemotherapy in patients with borderline resectable pancreatic carcinoma with arterial contact.

The survival benefit of neoadjuvant therapy for patients with borderline resectable pancreatic carcinoma has been reported recently. However, prognostic factors for this strategy have not been clearly elucidated. The aim of this study was to clarify prognostic factors for patients with borderline resectable pancreatic carcinoma who received neoadjuvant chemotherapy. Medical records of 66 patients with pancreatic carcinoma with arterial contact who intended to undergo tumor resection following neoadjuvant chemotherapy were analyzed retrospectively. Prognostic factors were investigated by analyzing the clinicopathological factors with univariate and multivariate survival analyses. Gemcitabine plus S-1 was generally used as neoadjuvant chemotherapy. The objective response rate was 24%, and normalization of serum tumor markers following neoadjuvant chemotherapy was achieved in 29 patients (44%). Of the 66 patients, 60 patients underwent tumor resection and the remaining six patients did not due to distant metastases following neoadjuvant chemotherapy. For all 66 patients, overall 1-, 2-, and 5-year survival rates were 87.8, 54.5, and 20.5%, respectively (median survival time, 27.1 months) and multivariate analysis revealed that normalization of serum tumor markers was found to be an independent prognostic factor of better overall survival (P = 0.023). Moreover, for 60 patients who undergo tumor resection, normalization of serum tumor markers (P = 0.005) was independently associated with better overall survival by multivariate analysis. Patients with pancreatic carcinoma with arterial contact who undergo neoadjuvant chemotherapy and experience normalization of serum tumor markers thereafter may be good candidates for tumor resection.

Value of apparent diffusion coefficient prior to neoadjuvant therapy is a predictor of histologic response in patients with borderline resectable pancreatic carcinoma.

The parameters to predict histological response to neoadjuvant therapy remain controversial in borderline resectable pancreatic carcinoma (BRPC). Twenty-four patients who underwent diffusion-weighted magnetic resonance imaging (DW-MRI) prior to expected neoadjuvant chemo/chemoradiotherapy and surgery were reviewed retrospectively. Analyses for correlation between percent tumor cell destruction and the following was performed to investigate the parameter and cut off value: tumor size, whole tumor apparent diffusion coefficient (ADC) value of DW-MRI, maximum standardized uptake value of 18 F-fluorodeoxyglucose positron emission tomography, carbohydrate antigen 19-9, and their change ratios. The selected parameter was assessed for prediction ability of the histological response to neoadjuvant chemo/chemoradiotherapy and R0 curability. Pre-treatment ADC value was correlated with tumor cell destruction rate among all parameters (R=0.625, P=0.001). The ADC cut-off value for discriminating between nonresponders (grade I) and responders (grade IIa and more) after treatment was determined as 1.20×10-3 mm2 /s and the sensitivity, 100%; specificity, 75%; accuracy, 83% for responder, and the sensitivity, 100%; specificity, 63%; accuracy, 71% for R0 curability. Pre-treatment ADC value appeared to be a predictor of R0 curability in BRPC patients because of effective histological response to neoadjuvant therapy, and there was a significant correlation between the baseline ADC value and histological tumor cell destruction rate.

Irreversible electroporation as treatment of locally advanced and as margin accentuation in borderline resectable pancreatic adenocarcinoma.

In recent years, many local ablation technologies based on thermal damage have been used in the treatment of locally advanced pancreatic carcinoma (LAPC) and borderline resectable pancreatic carcinoma (BLRPC). However, they are associated with major complications because of possible vascular and ductal damage. Irreversible electroporation (IRE) is a nonthermal ablation technology that seems safe near vital vascular and ductal structures. IRE could be used as exclusive treatment of LAPC (en situ to IRE) after induction chemotherapy In BLRPC, surgery is not really radical in 6% of patients (microscopic residual) and local recurrences occur in 11-42% of apparent radical resections. IRE could be used as margin accentuation to increase posterior margin during radical surgery in BLRPC. Our outcomes are safety, time to progression. Secondary outcomes are overall survival, pain control and quality of life. We are performing a prospective evaluation of patients undergoing IRE for LAPC or BLRPC since July 2014. We have included patients with non-metastatic LAPC with maximum size ≤4cm (en situ to IRE) and patients with BLRPC (complementary IRE). We have performed induction chemotherapy in both groups. After treatment, patients were evaluated on days 1, 2, 4, 7, 14, 21, 30, 60 and 90 with amylase and lipase serum and abdominal drainage test. Based on Ethics Committee's request, follow-up imaging was performed at the 10thday for safety evaluation, at 30, 60 and 90days for response evaluation and then every 3months. Seven patients (two women and five men) underwent IRE. Two patients had LAPC and received en situ to IRE. In five patients affected by BLRPC we performed IRE and pancreatic head resection. In all patients, intraoperative imaging confirmed that the treatment of the whole tumor volume was complete. All seven patients demonstrated nonclinically relevant elevation of their amylase and lipase, which returned normal at 5days postprocedure. No patient showed evidence of clinical pancreatitis or fistula. No major complications were recorded. Patients with LAPC died of distant metastases 6month after treatment. At 3- and 6-month follow-up, all patients with BLPRC were alive and disease free. Only one patient has already reached 9-month follow-up and is alive and disease free. Our results are only preliminary. However, IRE ablation of LAPC and BLRPC seems a safe and feasible treatment.