Options and survival benefits of conversion therapy for unresectable hepatocellular carcinoma

In the study by Wu et al,patients with unresectable hepatocellular carcinoma were subjected to transarterial chemoembolization(TACE)as a conversion therapy in order to render their tumors suitable for resection.A nomogram was devised and shown to be effective in predicting the survival of these patients.Generalization of the results,however,is questionable since the study subjects consisted of patients who had resection after TACE while excluding patients with the same disease but not suitable for TACE.Immunotherapy can be considered to be an option for conversion therapy.However,markers for determining responses to a conversion therapy and for guiding the decision between TACE and sequential immunotherapy have been lacking.The question of whether effective conversion therapy can truly enhance overall survival remains unanswered.

Current landscape of preoperative neoadjuvant therapies for initial resectable colorectal cancer liver metastasis

Colorectal cancer liver metastasis(CRLM)presents a clinical challenge,and optimizing treatment strategies is crucial for improving patient outcomes.Surgical resection,a key element in achieving prolonged survival,is often linked to a heightened risk of recurrence.Acknowledging the potential benefits of preoperative neoadjuvant chemotherapy in managing resectable liver metastases,this approach has gained attention for its role in tumor downsizing,assessing biological behavior,and reducing the risk of postoperative recurrence.However,the use of neoadjuvant chemotherapy in initially resectable CRLM sparks ongoing debates.The balance between tumor reduction and the risk of hepatic injury,coupled with concerns about delaying surgery,necessitates a nuanced approach.This article explores recent research insights and draws upon the practical experiences at our center to address critical issues regarding considerations for initially resectable cases.Examining the criteria for patient selection and the judicious choice of neoadjuvant regimens are pivotal areas of discussion.Striking the right balance between maximizing treatment efficacy and minimizing adverse effects is imperative.The dynamic landscape of precision medicine is also reflected in the evolving role of gene testing,such as RAS/BRAF and PIK3CA,in tailoring neoadjuvant regimens.Furthermore,the review emphasizes the need for a multidisciplinary approach to navigate the comp-lexities of CRLM.Integrating technical expertise and biological insights is crucial in refining neoadjuvant strategies.The management of progression following neoadjuvant chemotherapy requires a tailored approach,acknowledging the diverse biological behaviors that may emerge.In conclusion,this review aims to provide a comprehensive perspective on the considerations,challenges,and advancements in the use of neoadjuvant chemotherapy for initially resectable CRLM.By combining evidencebased insights with practical experiences,we aspire to contribute to the ongoing discourse on refining treatment paradigms for improved outcomes in patients with CRLM.

Adjuvant chemotherapy for isolated resectable colorectal lung metastasis: A retrospective study using inverse probability treatment weighting propensity analysis

BACKGROUND The benefit of adjuvant chemotherapy(ACT)for patients with no evidence of disease after pulmonary metastasis resection(PM)from colorectal cancer(CRC)remains controversial.AIM To assess the efficacy of ACT in patients after PM resection for CRC.METHODS This study included 96 patients who underwent pulmonary metastasectomy for CRC at a single institution between April 2008 and July 2023.The primary end-point was overall survival(OS);secondary endpoints included cancer-specific survival(CSS)and disease-free survival(DFS).An inverse probability of treat-ment-weighting(IPTW)analysis was conducted to address indication bias.Sur-vival outcomes compared using Kaplan-Meier curves,log-rank test,Cox regre-ssion and confirmed by propensity score-matching(PSM).RESULTS With a median follow-up of 27.5 months(range,18.3-50.4 months),the 5-year OS,CSS and DFS were 72.0%,74.4%and 51.3%,respectively.ACT had no significant effect on OS after PM resection from CRC[original cohort:P=0.08;IPTW:P=0.15].No differences were observed for CSS(P=0.12)and DFS(P=0.68)between the ACT and non-ACT groups.Multivariate analysis showed no association of ACT with better survival,while sublobar resection(HR=0.45;95%CI:0.20-1.00,P=0.049)and longer disease-free interval(HR=0.45;95%CI:0.20-0.98,P=0.044)were associated with improved survival.CONCLUSION ACT does not improve survival after PM resection for CRC.Further well-designed randomized controlled trials are needed to determine the optimal ACT regimen and duration.

Evidence based radiation therapy for locally advanced resectable and unresectable gastric cancer

Despite the fact that gastric cancer is decreasing in incidence in the United States,it remains one of the most commonly diagnosed and most fatal cancers worldwide.In localised disease,surgery remains the cornerstone of treatment.Nevertheless,the low overall survival rates at 5 years due to locoregional and distant recurrences has led to a large debate regarding the role of radiation therapy and chemotherapy in addition to curative resection.Recent data have shown that,even with improved surgical techniques,locoregional failure rates in these patients ranged between 57% and 88%.Failures were noted in the gastric bed,regional nodes,gastric remnant,anastomosis and duodenal stump,all of which can be encompassed in a regional radiation f ield,indicating the need of further locoregional treatment.In this article,a comprehensive literature review of the reliable medical databases of PubMed and Cochrane is made and we present all available information on the role of radiation therapy in the preoperative and postoperative setting of gastric cancer.Data reported show that in locally advanced gastric cancer the addition of radiation therapy post surgery has signif icantly improved diseasefree survival as well as overall survival.Moreover,in unresectable gastric cancer,the combination of radiation therapy with chemotherapy has significantly improvedmean and overall survival rates.The role of radiation therapy in patients with resectable gastric cancer is being further evaluated in ongoing phase Ⅲ trials.

Conversion of Unresectable to Resectable Liver Metastases from Colorectal Carcinoma Using Hepatic Arterial Chronomodulated Chemotherapy: A Case Report and Short Literature Review

Background: The regional chronomodulated hepatic arterial infusion chemotherapy (HAIC) is an effective regimen for the treatment of patients with unresectable liver metastases from colorectal cancer, especially for the conversion into resectability. Aim: To demonstrate that chronomodulated HAI triplet chemotherapy according to OPTILIV protocol is well tolerated and displayed high antitumor activity in this heavily-pretreated patient. Case Presentation: A 54 years old patient from Russia was treated for a tumor in the ascending colon presented with 13 hepatic metastases ranging from 0.3 to 2.7 cm in diameter. He underwent a laparoscopic right hemicolectomy, 12 cycles of FOLFIRINOX combined to bevacizumab for the last 5 cycles, resulting in a partial response according to CT scan. It was decided to perform a two-stage hepatectomy at Paul Brousse hospital: left partial hepatectomy allowed the excision of 9 lesions. Radio frequency ablation was performed in 2 nodular lesions. Afterwards, the patient received 5 cycles of chronomodulated triplet chemotherapy into the hepatic artery, according to the OPTILIV protocol design, yet without cetuximab, because of the KRAS mutation in the liver metastases, with a partial re-sponse. The patient could then undergo the second stage of the planned right hepatectomy, which turned out to be an R0 resection followed by receiving three courses of chronomodulated HAIC. Disease progression was documented after 3 months. Chronomodulated FOLFIRI chemotherapy was re-started intravenously, in combination with Aflibercept and it was associated with further disease progression. The genetic analysis of our patient’s cancer revealed a high level of MSI. The patient was included in the Phase 2 CheckMate-142 trial and received nivolumab 3 mg/kg every 2 weeks within 3 months. Treatment was discontinued due to ineffectiveness. Then the patient underwent radiotherapy geared towards reduction of pain. Afterwards, the patient died from the disease progression 2 years after the beginning of treatment. Conclusion: In this article, the authors report a clinical case with chronomodulated HAIC as rescue therapy in a heavily pretreated patient with metastatic colorectal cancer, allowing to achieve an objective response despite prior progression on FOLFIRINOX (the same triplet chemo by IV route). This strategy permitted to overcome drug resistance and to perform further complete resection of the liver me-tastases with prolonged patient survival. Thus, chronomodulated HAI is useful in patients with liver metastases from colorectal cancer and de-serves to be further assessed prospectively in clinical trials chemotherapy.

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.

The effect of adjuvant chemotherapy in resectable cholangiocarcinoma: A meta-analysis and systematic review

Background: The benefit of adjuvant chemotherapy for resectable cholangiocarcinoma remains unclear due to the lack of randomized control studies. This study aimed to investigate the possible benefit of postoperative adjuvant chemotherapy for resectable cholangiocarcinoma. Data sources: Relevant research articles published before 1 st March 2018 in Pub Med, Embase and the Cochrane library databases were retrieved. Published data were extracted and analyzed by RevMan 5.3, and the results were presented as hazard ratios(HRs) [95% confidence intervals(CI)] and forest plots. Results: One prospective and eighteen retrospective studies were included, with a total number of 11,458 patients, 4696 of whom received postoperative chemotherapy. There was a significant improvement of the overall survival(OS) for patients who underwent operation + adjuvant chemotherapy compared to those who underwent operation alone(HR = 0.61; P < 0.001). Subgroup analyses show that the postoperative chemotherapy group compared with operation alone group are indicated as follows: hilar cholangiocarcinoma group(HR = 0.60; P < 0.001), intrahepatic cholangiocarcinoma group(HR = 0.60; P < 0.001), R1 resection group(HR = 0.71; P = 0.04), LN-positive diagnosis group(HR = 0.58; P < 0.001), gemcitabine-based chemotherapy group(HR = 0.42; P < 0.001), distal cholangiocarcinoma group(HR = 0.48; P = 0.17), R0 resection group(HR = 0.69; P = 0.43), and 5-flurouracil-based chemotherapy group(HR = 0.90; P = 0.66), respectively. Conclusions: Postoperative adjuvant chemotherapy can improve the OS in intrahepatic and hilar cholangiocarcinoma patients. However, distal cholangiocarcinoma patients gain no benefit from postoperative adjuvant chemotherapy. Prospective randomized trials are warranted in order to define the standard chemotherapy regimen.

Strategies for early detection of resectable pancreatic cancer

Pancreatic cancer is difficult to diagnose at an early stage and generally has a poor prognosis. Surgical resection is the only potentially curative treatment for pancreatic carcinoma. To improve the prognosis of this disease, it is essential to detect tumors at early stages, when they are resectable. The optimal approach to screening for early pancreatic neoplasia has not been established. The International Cancer of the Pancreas Screening Consortium has recently finalized several recommendations regarding the management of patients who are at an increased risk of familial pancreatic cancer. In addition, there have been notable advances in research on serum markers, tissue markers, gene signatures, and genomic targets of pancreatic cancer. To date, however, no biomarkers have been established in the clinical setting. Advancements in imaging modalities touch all aspects of the clinical management of pancreatic diseases, including the early detection of pancreatic masses, their characterization, and evaluations of tumor resectability. This article reviews strategies for screening high-risk groups, biomarkers, and current advances in imaging modalities for the early detection of resectable pancreatic cancer.

Pancreaticoduodenectomy for borderline resectable pancreatic head cancer with a modified artery-first approach technique

BACKGROUND： The treatment of borderline resectable pancreatic head cancer（BRPHC） is still controversial and challenging. The artery-first approaches are described to be the important options for the early determination. Whether these approaches can achieve an increase R0 rate, better bleeding control and increasing long-term survival for BRPHC are still controversial. We compared a previously reported technique, a modified artery-first approach（MAFA）, with conventional techniques for the surgical treatment of BRPHC.METHODS： A total of 117 patients with BRPHC undergone pancreaticoduodenectomy（PD） from January 2013 to June 2015 were included. They were divided into an MAFA group（n=78） and a conventional-technique group（n=39）. Background characteristics, operative data and complications were compared between the two groups.RESULTS： Mean operation time was significantly shorter in the MAFA group than that in the conventional-technique group（313 vs 384 min; P=0.014）; mean volume of intraoperative blood loss was significantly lower in the MAFA group than that in the conventional-technique group（534 vs 756 m L; P=0.043）; and mean rate of venous resection was significantly higher in the conventional-technique group than that in the MAFA group（61.5% vs 35.9%; P=0.014）. Pathologic data, early mortality and morbidity were not different significantly between the two groups.CONCLUSIONS： MAFA is safe, simple, less time-consuming, less intraoperative blood loss and less venous resection, and therefore, may become a standard surgical approach to PD for BRPHC with the superior mesenteric vein-portal vein involvement but without superior mesenteric artery invasion.

Radiofrequency Ablation vs. Hepatic Resection for Resectable Colorectal Liver Metastases

The treatments of resectable colorectal liver metastases（CRLM） are controversial. This study aimed to evaluate the relative efficacy and safety of hepatic resection（HR） and radiofrequency ablation（RFA） for treating resectable CRLM. Between January 2004 and May 2010, the enrolled patients were given hepatic resection（HR group; n=32） or percutaneous RFA（RFA group; n=21） as a first-line treatment for CRLM. All the tumors had a maximum diameter of 3.5 cm and all patients had five or less tumors. The patient background, tumor characteristics, cumulative survival rate and recurrence-free survival rate were assessed in both groups. There were significantly more patients with comorbidities in the RFA group than those in the HR group（17 in RFA group vs. 10 in HR group; P〈0.000）. The mean maximum tumor diameter in the HR group and RFA group was 2.25±0.68 and 1.89±0.62 cm（P=0.054）, and the mean number of tumors was 2.28±1.05 and 2.38±1.12（P=0.744）, respectively. The 1-, 3- and 5-year cumulative survival rates in the HR group were 87.5%, 53.1% and 31.3%, respectively, and those in the RFA group were 85.7%, 38.1% and 14.2%, respectively with the differences being not significant between the two groups（P=0.062）. The 1-, 3- and 5-year recurrence-free survival rates in the HR group were 90.6%, 56.3% and 28.1%, respectively, and those in the RFA group were 76.1%, 23.8% and 4.8%, respectively, with the differences being significant between the two groups（P=0.036）. In conclusion, as HR has greater efficacy than RFA in the treatment of resectable CRLM, we recommend it as the first option for this malignancy.

Neoadjuvant therapy for resectable pancreatic cancer

The use of neoadjuvant therapies has played a major role for borderline resectable and locally advanced pancreatic cancers(PCs). For this group of patients, preoperative chemotherapy or chemoradiation has increased the likelihood of surgery with negative resection margins and overall survival. On the other hand, for patients with resectable PC, the main rationale for neoadjuvant therapy is that the overall survival with current strategies is unsatisfactory. There is a consensus that we need new treatments to improve the overall survival and quality of life of patients with PC. However, without strong scientific evidence supporting the theoretical advantages of neoadjuvant therapies, these potential benefits might turn out not to be worth the risk of tumors progression while waiting for surgery. The focus of this paper is to provide the readers an overview of the most recent evidence on this subject.

Neoadjuvant treatment for resectable pancreatic adenocarcinoma

Pancreatic adenocarcinoma is the fourth leading cause of cancer mortality in the United States in both men and women, with a 5-year survival rate of less than 5%. Surgical resection remains the only curative treatment, but most patients develop systemic recurrence within 2 years of surgery. Adjuvant treatment with chemotherapy or chemoradiotherapy has been shown to improve overall survival, but the delivery of treatment remains problematic with up to 50% of patients not receiving postoperative treatment. Neoadjuvant therapy can provide benefits of eradication of micrometastasis and improved delivery of intended treatment. We have reviewed the findings from completed neoadjuvant clinical trials, and discussed the ongoing studies. Combinational cytotoxic chemotherapy such as fluorouracil, leucovorin, irinotecan, and oxaliplatin and gemcitabine plus nanoparticle albumin-bound(nab)-paclitaxel, active in the metastatic setting, are being studied in the neoadjuvant setting. In addition, novel targeted agents such as inhibitor of immune checkpoint are incorporated with cytotoxic chemotherapy in early-phase clinical trial. Furthermore we have explored the utility of biomarkers which can personalize treatment and select patients for target-driven therapy to improve treatment outcome. The treatment of resectable pancreatic adenocarcinoma requires multidisciplinary approach and novel strategies including innovative trials to make progress.

Pathologic tumor response to neoadjuvant therapy in borderline resectable pancreatic cancer

Background:Previous studies have demonstrated the prognostic significance of pathologic tumor response in pancreatic adenocarcinoma following neoadjuvant therapy(NAT).The aim of this study was to determine the incidence of significant pathologic response to NAT in borderline resectable pancreatic cancer(BRPC),and association of NAT regimen and other clinico-pathologic characteristics with pathologic response.Methods:Patients with BRPC who underwent NAT and pancreatic resection between January 2012 and June 2017 were included.Pathologic response was assessed on a qualitative scale based on the College of American Pathologists grading system.Demographics and baseline characteristics,oncologic treatment,pathology,and survival outcomes were compared.Results:Seventy-one patients were included for analysis.Four patients had complete pathologic responses(tumor regression score 0),12 patients had marked responses(score 1),42 had moderate responses(score 2),and 13 had minimal responses(score 3).Patients with complete or marked responses were more likely to have received neoadjuvant gemcitabine chemoradiation(62.5%,38.1%,and 23.1%of the complete/marked,moderate,and minimal response groups,respectively;P=0.04).Of the complete/marked,moderate,and minimal response groups,margins were negative in 75.0%,78.6%,and 46.2%(P=0.16);node negative disease was observed in 87.5%,54.8%,and 15.4%(P<0.01);and median overall survival was 50.0 months,31.7 months,and 23.2 months(P=0.563).Of the four patients with pathologic complete responses,three were disease-free at 66.1,41.7 and 31.4 months,and one was deceased with metastatic liver disease at 16.9 months.Conclusions:A more pronounced pathologic tumor response to NAT in BRPC is correlated with node negative disease,but was not associated with a statistically significant survival benefit in this study.

THE ROLE OF TARGETING THERAPY IN CYTOREDUCTION AND SEQUENTIAL RESECTION OF UNRESECTABLE HEPATOCELLULAR CARCINOMA

Despite unquestionable progress has been made inresection of small and large hepatocellular carcinoma'(HCC),the dismal outcome of unresectable HCC remains a great challenge.Fortunately,the progress of multidisciplinary approach,particularly with new treatment modalities,has provided a new hope for unresectable HCC.This paper reports 477 patients with surgically verified unresectable HCC treated by different modalities, sequential resection was done in 55 patients(11.5%)due to marked shrinkage of the tumor.Patients treated with hepatic artery ligation(HAL),cannulation with infusion (HAI)and plus intraarterial targeting therapy(131I-antiHCC Ferritin IgG,131I-antiHCC monoclonal antibody,or 131I-Lipiodol)has higher sequential resection rate(33. 0%,31/94)when compared with other combination treatment(HAL+HAI,HAL+HAI+radiotherapy,11.7% ,22/188),and single treatment group(Cryosurgery,HAL,or HAI,1.0%,2/195). The combination of targeting therapy played an important role to the increasing number of sequential resection during 1978 through 1992.The 5-year survival of the 55 patients with sequential resection was as nigh as 60.8%.By the end of June 1993,13 patients survived more than 5 years, the longest being 15 years.

CONVERSION OF SURGICALLY VERIFIED UNRESECTABLE TO RESECTABLE HEPATOCELLULAR CARCINOMA(A REPORT OF 26 PATIENTS WITH SUBSEQUENT RESECTION)

During the period 1978-1987, 255 patients with pathologically proven hepatocellular carcinoma (HCC) were determined by laparotomy to be un-resectable, 155 (60.8%) out of them had their tumor mainly confined in right or left lobe and considered to be potentially resectable if remarkable tumor shrinkage appears after treatment. Second look operation was performed in 26 (16.8%) out of the 155 patients after marked reduction of tumor size, resection was done in all of these 26 patients. Triple or quadruple combination treatment with hepatic artery ligation (HAL), hepatic artery infusion (HAI) with chemotherapy, radiotherapy using linear accelerator, and radioimmunotherapy using 131-I antihu-man HCC ferritin antibody yielded the highest conversion rate (29.8%, 14/47) as compared to double combination treatment with HAL+HAI, or cryosur-gery+HAL (16.9%, 12/71) and single treatment with HAL or HAI or HAE (embolization) (0%, 0/37). The median tumor size of these 26 patients was reduced from 9.5 cm to 5.0 cm after combination treatment. The median interval between the first laparotomy and the subsequent resection was 5.0 (2-16) months. The survival rates calculated by life table method were: 1-year 86.5%, 2-year 74.3% and 3-year 74.3%. Nine cases have survival more than 3 years. Thus, multimodality combination treatment with subsequent resection might prolong survival significantly for some patients with unresectable HCC particularly confined in right lobe of a cirrhotic liver.

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.

Systemic treatments for resectable carcinoma of the esophagus

One of the most prevalent malignancies in the world is esophageal cancer(EC).The 5-year survival rate of EC remains pitiful despite treatment advancements.Neoadjuvant chemoradiotherapy in conjunction with esophagectomy is the standard of care for patients with resectable disease.The pathological complete response rate,however,is not acceptable.A distant metastasis or a locoregional recurrence will occur in about half of the patients.To increase the clinical effectiveness of therapy,it is consequently vital to investigate cutting-edge and potent therapeutic modalities.The approach to the management of resectable EC using immunotherapy has been considerably altered by immune checkpoint inhibitors.Systemic immunotherapy has recently been shown to have the potential to increase the survival of patients with resectable EC,according to growing clinical data.A combination of chemotherapy,radiation,and immunotherapy may have a synergistic antitumor impact because,according to mounting evidence,these treatments can stimulate the immune system via a number of different pathways.In light of this,it makes sense to consider the value of neoadjuvant immunotherapy for patients with surgically treatable EC.In this review,we clarify the rationale for neoadjuvant immunotherapy in resectable EC patients,recap the clinical outcomes of these approaches,go through the upcoming and ongoing investigations,and emphasize the difficulties and unmet research requirements.

Borderline resectable pancreatic cancer and vascular resections in the era of neoadjuvant therapy

While pancreatic cancer is still characterized by early systemic spread and poor outcomes,the treatment of this disease has changed significantly in recent years due to major advancements in systemic therapy and advanced surgical techniques.Broader use of effective neoadjuvant approaches combined with aggressive surgical operations within a multidisciplinary setting has improved outcomes.Borderline resectable pancreatic cancer is characterized by tumor vascular invasion,and is a setting where the combination of potent neoadjuvant chemotherapy and aggressive surgical methods,including vascular resections and reconstructions,shows its full potential.Hopefully,this will lead to improved local control and curative treatment in a number of patients with this aggressive malignancy.

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.