Comprehensive multimodal management of borderline resectable pancreatic cancer:Current status and progress

Borderline resectable pancreatic cancer(BRPC)is a complex clinical entity with specific biological features.Criteria for resectability need to be assessed in combination with tumor anatomy and oncology.Neoadjuvant therapy(NAT)for BRPC patients is associated with additional survival benefits.Research is currently focused on exploring the optimal NAT regimen and more reliable ways of assessing response to NAT.More attention to management standards during NAT,including biliary drainage and nutritional support,is needed.Surgery remains the cornerstone of BRPC treatment and multidisciplinary teams can help to evaluate whether patients are suitable for surgery and provide individualized management during the perioperative period,including NAT responsiveness and the selection of surgical timing.

Borderline resectable pancreatic cancer: Definitions and management

Pancreatic cancer is the fourth leading cause of cancer death in the United States. While surgical resection remains the only curative option, more than 80% of patients present with unresectable disease. Unfortunately, even among those who undergo resection, the reported median survival is 15-23 mo, with a 5-year survival of approximately 20%. Disappointingly, over the past several decades, despite improvements in diagnostic imaging, surgical technique and chemotherapeutic options, only modest improvements in survival have been realized. Nevertheless, it remains clear that surgical resection is a prerequisite for achieving longterm survival and cure. There is now emerging consensus that a subgroup of patients, previously considered poor candidates for resection because of the relationship of their primary tumor to surrounding vasculature, may benefit from resection, particularly when preceded by neoadjuvant therapy. This stage of disease, termed borderline resectable pancreatic cancer, has become of increasing interest and is now the focus of a multiinstitutional clinical trial. Here we outline the history, progress, current treatment recommendations, and future directions for research in borderline resectable pancreatic cancer.

Selection criteria in resectable pancreatic cancer: A biological and morphological approach

Pancreatic ductal adenocarcinoma(PDA) remains one of the most aggressive tumors with a low rate of survival. Surgery is the only curative treatment for PDA, although only 20% of patients are resectable at diagnosis. During the last decade there was an improvement in survival in patients affected by PDA, possibly explained by the advances in cancer therapy and by improve patient selection by pancreatic surgeons. It is necessary to select patients not only on the basis of surgical resectability, but also on the basis of the biological nature of the tumor. Specific preoperative criteria can be identified in order to select patients who will benefit from surgical resection. Duration of symptoms and level of carbohydrate antigen 19.9 in resectable disease should be considered to avoid R1 resection and early relapse. Radiological assessment can help surgeons to distinguish resectable disease from borderline resectable disease and locally advanced pancreatic cancer. Better patient selection can increase survival rate and neoadjuvant treatment can help surgeons select patients who will benefit from surgery.

Borderline resectable pancreatic cancer:Certainties and controversies

Borderline resectable(BR)pancreatic ductal adenocarcinoma(PDAC)is currently a well-recognized entity,characterized by some specific anatomic,biological and conditional features:It includes patients with a stage of disease intermediate between the resectable and the locally advanced ones.The term BR identifies a tumour with an aggressive biological behaviour,on which a neoadjuvant approach instead of an upfront surgery one should be preferred,in order to obtain a radical resection(R0)and to avoid an early recurrence after surgery.Even if during the last decades several studies on this topic have been published,some aspects of BR-PDAC still represent a matter of debate.The aim of this review is to critically analyse the available literature on this topic,particularly focusing on:The problem of the heterogeneity of definition of BR-PDAC adopted,leading to a misinterpretation of published data;its current management(neoadjuvant vs upfront surgery);which neoadjuvant regimen should be preferably adopted;the problem of radiological restaging and the determination of resectability after neoadjuvant therapy;the post-operative outcomes after surgery;and the role and efficacy of adjuvant treatment for resected patients that already underwent neoadjuvant therapy.

Neoadjuvant therapy for resectable pancreatic cancer:a narrative review

The use of neoadjuvant therapy(NAT)for pancreatic ductal adenocarcinoma remains controversial and limited.Therefore,this literature review aimed to assess the feasibility,safety,and efficacy of this treatment.A database search of peer-reviewed articles published in English between January 1990 and June 2021 in PubMed,MEDLINE,and the Web of Science was performed.Original articles,review articles,and meta-analyses relevant to the topic were selected.We found 2 to 4 cycles with FOLFIRINOX,gemcitabine plus nab-paclitaxel,gemcitabine plus S-1,or gemcitabine alone were the most acceptable treatments.Considering the risk of adverse events and cancer progression,NAT is considered safe and tolerable,with a comparable resection rate.Although NAT can result in moderate tumor responses and some extent of local control(improvement of complete resection rate and negative lymph node metastases),no obvious survival benefit is observed.To date,the survival benefits of NAT for resectable pancreatic ductal adenocarcinoma have been very limited.It is too early to say that NAT is the best treatment option for resectable pancreatic cancer.

Pancreatoduodenectomy with Simultaneous Venous Resection for Advanced Ductal Pancreatic Head Cancer:A Case Control Study

Introduction: Surgical resection is the treatment of choice for pancreatic ductal adenocarcinoma (PDA). However, in case of venous tumor in-volvement, carcinomas are classified as borderline resectable and their preferential therapy remains controversial. The purpose of this study is to analyze the effectiveness of the surgical approach with simultaneous venous resection regarding perioperative outcome and long-term survival. Patients and methods: All patients that underwent pancreatoduodenectomy (PD) for PDA at our institution between 02/2002 and 12/2016 were analyzed retrospectively. A matched-pair analysis between patients that underwent PD with simultaneous venous resection (PDVR) and standard PD was performed to compare perioperative parameters, survival and factors relevant to long-term survival. Results: The study included 142 patients: 71 underwent PDVR and 71 underwent standard PD. Venous tumor infiltration could histopathologically be confirmed in 21 patients (29.58%). PDVR wasn’t associated with a higher rate of postoperative complications (56.34% for both groups), severe postoperative complications (28.17% vs. 23.94%) and mortality (5.63% vs. 9.86%) compared to standard PD. Median overall survival of both groups was 17 months (95% CI 10.89 - 23.11), without statistical significance between the two groups (PD 22 months, 95% CI 16.02 - 27.99 vs. PDVR 16 months, 95% CI 9.96 - 22.04, p = 0.087). Parameters associated with overall survival were his-topathologically proven venous tumor infiltration, the lymph node status and the necessity of postoperative blood transfusions. Conclusion: PDVR is justified, because peri- and post-operative morbidity and mortality, as well as long-term survival, are comparable to standard PD. Even in case of postoperatively histopathologically confirmed venous tumor infiltration, patients benefit over palliative treatment.

Clinical Analysis of Gemcitabine Combined with Tegafur Chemotherapy after Radical Surgery on Pancreatic Cancer

Objective:To study and analyze the clinical efficacy of gemcitabine combined with Tegafur chemotherapy after radical resection of pancreatic cancer.Methods:The subjects of the study were 200 patients who were admitted to the hospital from January 2018 to February 2021 requiring chemotherapy after radical resection of pancreatic cancer.According to the different treatment methods,they were divided into a experimental group(gemcitabine combined with Tegafur chemotherapy)and a control group(single gemcitabine chemotherapy),and the treatment efficacy of the two groups of patients was observed and compared.Results:Compared with the control group,patients in the experimental group had significantly better treatment efficacy,quality of life scores and post-treatment anxiety and depression scores.The difference between the groups was significant(p<0.05).Conclusion:Gemcitabine combined with Tegafur chemotherapy for patients requiring chemotherapy after radical resection of pancreatic cancer can significantly improve the treatment efficacy for the disease,improve the patient's quality of life,and ensure that the patient's emotional state during treatment is more positive.

Change in neoadjuvant chemotherapy could alter the prognosis of patients with pancreatic adenocarcinoma: A case report

BACKGROUND Neoadjuvant treatment has become a standard of care for borderline or locally advanced pancreatic cancer and is increasingly considered even for up-front resectable disease.The aim of this article is to present the case of a 62-year-old patient with locally advanced pancreatic adenocarcinoma who was successfully treated with gemcitabine plus nab-paclitaxel after the failure of the first line treatment.CASE SUMMARY Computerized tomography scan and magnetic resonance imaging demonstrated a nodular lesion of ill-defined limits in the body of the pancreas,measuring approximately 4.2 cm×2.7 cm,with an infiltrative aspect.The tumor had contact with the superior mesenteric vein,splenomesenteric junction and the proximal segment of the splenic artery,causing focal reduction of its lumens.Due to vascular involvement,neoadjuvant chemotherapy treatment with eight cycles of“folinic acid,5-fluorouracil,irinotecan and oxa-liplatine”(FOLFIRINOX)were performed.At the end of the cycles,surgery was performed,but the procedure was interrupted due to finding of lesions suspected of metastasis.Gemcitabine plus nab-paclitaxel was then successfully used for neoadjuvant treatment with subsequent R0 surgical resection.CONCLUSION Gemcitabine plus nab-paclitaxel may be effective as an alternative regimen when FOLFIRINOX fails as the first line of treatment,suggesting the need for further studies to identify which patients would benefit from each type of therapeutic approach.

A contemporary evidence basis for neoadjuvant chemotherapy in upfront resectable pancreatic adenocarcinoma:a systematic review of the literature

Pancreatic ductal adenocarcinoma(PDAC)is an aggressive cancer with poor survival.Local control through surgical resection paired with radiotherapy and chemotherapy comprise the primary tenets of treatment.Debate exists regarding the timing of treatment and ordering of systemic therapy and resection in the management of early stage disease.The goal of this study was to review the literature and describe the contemporary evidence basis for the role of neoadjuvant therapy(NAT)in the setting of upfront resectable(UP-R)PDAC.Five databases were searched in parallel to identify relevant original articles investigating neoadjuvant therapy where at least 1 study arm contained UP-R PDAC;studies with only borderline resectable or locally advanced disease were excluded.Due to the diversity in NAT regimens and study design between trials,qualitative analyses were performed to investigate patient selection,impact on perioperative and survival outcomes,safety,and cost effectiveness.Thirty-five studies met inclusion criteria,of which 24 unique trials are discussed here in detail.These studies included those trials using single agents as well as more recent trials comparing modern multiagent therapies,and several large database analyses.Overall the data suggest that NAT is safe,may confer survival benefit for appropriately selected patients,is cost effective,and is an appropriate approach for UP-R PDAC.Nevertheless,the risk for disease progression during upfront medical therapy,requires appropriate patient identification and close monitoring,and emphasizes the need for further discovery of more effective chemotherapeutics,useful biomarkers or molecular profiles,and additional prospective comparative studies.