Current standards and future perspectives in adjuvant treatment for biliary tract cancers

Biliary tract cancer, including cholangiocarcinoma (CCA) and gallbladder cancer (GBC) are rare tumours with a rising incidence. Prognosis is poor, since most patients are diagnosed with advanced disease. Only ~20% of patients are diagnosed with early-stage disease, suitable for curative surgery. Despite surgery performed with potentially-curative intent, relapse rates are high, with around 60–70% of patients expected to have disease recurrence. Most relapses occur in the form of distant metastases, with a predominance of liver spread. In view of high tumour recurrence, adjuvant strategies have been explored for many years, in the form of radiotherapy, chemo-radiotherapy and chemotherapy. Historically, few randomised trials were available, which included a variety of additional tumours (e.g. pancreatic and ampullary tumours); most evidence relied on phase II and retrospective studies, with no high-quality evidence available to define the real benefit derived from adjuvant strategies.Since 2017, three randomised phase III clinical trials have been reported; all recruited patients with resected biliary tract cancer (CCA and GBC) who were randomised to observation alone, or chemotherapy in the form of gemcitabine (BCAT study; included patients diagnosed with extrahepatic CCA only), gemcitabine and oxaliplatin (PRODIGE-12/ACCORD-18; included patients diagnosed with CCA and GBC) or capecitabine (BILCAP; included patients diagnosed with CCA and GBC). While gemcitabine-based chemotherapy failed to show an impact on patient outcome (relapse-free survival (RFS) or overall survival (OS)), the BILCAP study showed a benefit from adjuvant capecitabine in terms of OS (pre-planned sensitivity analysis in the intention-to-treat population and in the per-protocol analysis), with confirmed benefit in terms of RFS. Based on the BILCAP trial, international guidelines recommend adjuvant capecitabine for a period of six months following potentially curative resection of CCA as the current standard of care for resected CCA and GBC. However, BILCAP failed to show OS benefit in the intention-to-treat (non-sensitivity analysis) population (primary end-point), and this finding, as well as some inconsistencies between studies has been criticised and has led to confusion in the biliary tract cancer medical community.This review summarises the adjuvant field in biliary tract cancer, with evidence before and after 2017, and comparison between the latest randomised phase III studies. Potential explanations are presented for differential findings, and future steps are explored.     

The role of neoadjuvant chemotherapy or chemoradiotherapy for advanced gallbladder cancer – A systematic review

BackgroundNeoadjuvant chemotherapy for advanced gallbladder cancer (GBC) has recently been proposed as an alternative to adjuvant chemotherapy, with potential increase in resectability rate and overall survival.AimTo undertake a systematic review and critical appraisal of available literature on the use of neoadjuvant chemotherapy (NACT) or chemoradiotherapy (NACRT) in the treatment of advanced GBC.MethodsSystematic review carried out in line with the Meta-analysis Of Observational Studies in Epidemiology guidelines. Primary outcomes were clinical benefit rate (CBR) of neoadjuvant therapy, defined as percentage of complete response, partial response and stable disease, resectability rate and R0 resection. Secondary outcomes were overall and disease-free survival.Results8 studies met the inclusion criteria (n = 474), of which 398 (84.0%) received NACT and 76 (16.0%) received NACRT. 133 of 434 patients (30.6%) had progressive disease despite NACT or NACRT. The CBR was 66.6%. 17% of the patients who responded to chemotherapy did not proceed to surgery. 50.4% of the patients were considered suitable for surgical resection, of which 191 (40.3%) underwent curative resection. The R0 rate for the whole cohort was 35.4%. Overall survival ranged from 18.5 to 50.1 months for those who underwent curative resection versus 5.0–10.8 months for non-resected group.ConclusionsThere is insufficient data to support the routine use of NACT or NACRT in advanced GBC, as this has only benefited a third of whole cohort, who eventually achieved a R0 resection. Future studies should be in the form of randomized controlled trials to investigate the role of neoadjuvant therapy in advanced GBC.     

Lymphatic spread of T2 gallbladder carcinoma: Regional lymphadenectomy is required independent of tumor location

BackgroundThis study aimed to investigate the incidence and distribution of regional lymph node metastasis according to tumor location, and to clarify whether tumor location could determine the extent of regional lymphadenectomy in patients with pathological T2 (pT2) gallbladder carcinoma.MethodsIn total, 81 patients with pT2 gallbladder carcinoma (25 with pT2a tumors and 56 with pT2b tumors) who underwent radical resection were enrolled. Tumor location was determined histologically in each gallbladder specimen.ResultsSurvival after resection was significantly worse in patients with pT2b tumors than those with pT2a tumors (5-year survival, 72% vs. 96%; p = 0.027). Tumor location was an independent prognostic factor on multivariate analysis (hazard ratio, 14.162; p = 0.018). The incidence of regional lymph node metastasis was significantly higher in patients with pT2b tumors than in those with pT2a tumors (46% vs. 20%; p = 0.028). However, the number of positive nodes was similar between the two groups (median, 2 vs. 2; p = 0.910). For node-positive patients with pT2b tumors, metastasis was found in every regional node group (12%–63%), whereas even for node-positive patients with pT2a tumors, metastasis was observed in regional node groups outside the hepatoduodenal ligament.ConclusionsTumor location in patients with pT2 gallbladder carcinoma can predict the presence or absence of regional lymph node metastasis but not the number and anatomical distribution of positive regional lymph nodes. The extent of regional lymphadenectomy should not be changed even in patients with pT2a tumors, provided that they are fit enough for surgery.     

Prospective validation of the Parkland Grading Scale for Cholecystitis

Background

The Parkland Grading Scale for Cholecystitis (PGS) was developed as an intraoperative grading scale to stratify gallbladder (GB) disease severity during laparoscopic cholecystectomy (LC). We aimed to prospectively validate this scale as a measure of LC outcomes.

Tratamiento endourológico de la litiasis ureteral lumbar. ¿Qué aporta la ureterorrenoscopia flexible?

Introduction and objectivesCurrently, there are no established criteria regarding treatment for lumbar ureteral stones. The objective of this work is to present our results in the endourological treatment of this pathology, analyzing the variables associated with the use of the flexible ureterorenoscope.Material and methodsRetrospective review of 103 patients who underwent retrograde URS with semi-rigid or flexible ureterorenoscope. Proximal location: L2-L3. Medial location: L4-L5. Semirigid URS was the initial treatment, with conversion to flexible URS when it was required to complete the procedure. Success was defined as absence of residual fragments (6 weeks). Demographic, surgical, immediate postoperative variables, and those related to the stone, were analyzed. Their correlation with the use of the flexible ureterorenoscope was evaluated.ResultsMean age: 57.2 years (SD 15.6); there were 73 men (70.9%). Stone size: 8 mm (range 4-30; IQR 4.5). Proximal location: 58 (56.3%). Previous JJ: 44.7%. Previous nephrostomy: 10.7%. Semirigid URS with conversion to flexible URS: 51 (49.5%). Impacted stones: 28.2%. Intraoperative complications: 2 (1.9%). Postoperative JJ: 84.5%. Immediate postoperative complications: 23 (22.3%) (Clavien-Dindo I-II: 91.3%). Postoperative ureteral stricture: 5.8%. Success: 88.4%. Residual fragments: 12 (11.7%). Spontaneous passage: 6 (50%). Greater performance of flexible URS in proximal ureteral stones (P = 0.001) of more than 11 mm (P = 0.02) in univariate analysis, and in proximal stones [OR 3.5; 1.5-8.1; P = 0.004] in multivariate analysis.ConclusionsEndourological treatment obtained a high success rate in our sample. Size greater than 11 mm and proximal ureteral location in univariate and multivariate analysis, respectively, behaved as predictors of flexible URS.