Liver resection is justified for multinodular hepatocellular carcinoma in selected patients with cirrhosis: A multicenter analysis of 1,066 patients

BackgroundThe role of liver resection for multinodular (≥3 nodules) hepatocellular carcinoma (HCC) remains unclear, especially among patients with severe underlying liver disease. We sought to evaluate surgical outcomes among patients with cirrhosis and multinodular HCC undergoing liver resection.MethodsUsing a multicenter database, outcomes among cirrhotic patients who underwent curative-intent resection of HCC were examined stratified according to the presence or absence of multinodular disease. Perioperative mortality and morbidity, as well as overall survival (OS) and recurrence-free survival (RFS) were compared between the two groups.ResultsAmong 1066 cirrhotic patients, 906 (85.0%) had single- or double-nodular HCC (the non-multinodular group), while 160 (15.0%) had multinodular HCC (the multinodular group). There were no differences in postoperative 30-day mortality and morbidity among non-multinodular versus multinodular patients (1.8% vs. 1.9%, P = 0.923, and 36.0% vs. 39.4%, P = 0.411, respectively). In contrast, 5-year OS and RFS of multinodular patients were worse compared with non-multinodular patients (34.6% vs. 58.2%, and 24.7% vs. 44.5%, both P < 0.001). On multivariable analyses, tumor numbers ≥5, total tumor diameter ≥8 cm and microvascular invasion were independent risk factors for decreased OS and RFS after resection of multinodular HCC in cirrhotic patients.ConclusionsLiver resection can be safely performed for multinodular HCC in the setting of cirrhosis with an overall 5-year survival of 34.6%. Tumor number ≥5, total tumor diameter ≥8 cm and microvascular invasion were independently associated with decreased OS and RFS after resection in cirrhotic patients with multinodular HCC.     

Does the difficulty grade of laparoscopic liver resection for colorectal liver metastases correlate with long-term outcomes?

IntroductionPrognosis of patients with colorectal liver metastases (CRLM) is strongly correlated with the oncological outcome after liver resection. The aim of this study was to analyze the impact of laparoscopic liver resection (LLR) difficulty score (IMM difficulty score) on the oncological results in patients treated for CRLM.MethodsAll patients who underwent LLRs for CRLM from 2000 to 2016 in our department, were retrospectively reviewed. Data regarding difficulty classification, -according to the Institute Mutualiste Montsouris score (IMM)-, recurrence rate, recurrence-free survival (RFS), overall survival (OS) and data regarding margin status were analyzed.ResultsA total of 520 patients were included. Patients were allocated into 3 groups based on IMM difficulty score of the LLR they underwent: there were 227 (43,6%), 84 (16,2%) and 209 (40,2%) patients in groups I, II and III, respectively. The R₁ resection rate in group I, II and III were 8,8% (20/227), 11,9% (10/84) and 12,4% (26/209) respectively (p = 0.841). Three- and 5-year RFS rates were 77% and 73% in group I, 58% and 51% in group II, 61% and 53% in group III, respectively (p = 0.038). Three and 5-year OS rates were 87% and 80% for group I, 77% and 66% for group II, 80% and 69% for group III respectively (p = 0.022).ConclusionThe higher LLR difficulty score correlates with significant morbidity and worse RFS and OS, although the more technically demanding and difficult cases are not associated with increased rates of positive resection margins and recurrence.     

Real-world role of performance status in surgical resection for hepatocellular carcinoma: A multicenter study

BackgroundThe Barcelona Clinic Liver Cancer (BCLC) categorizes a patient with performance status (PS)-1 as advanced stage of hepatocellular carcinoma (HCC) and surgical resection is not recommended. In real-world clinical practice, PS-1 is often not a contraindication to surgery for HCC. The aim of current study was to define the impact of PS on the surgical outcomes of patients undergoing liver resection for HCC.Methods1,531 consecutive patients who underwent a curative-intent resection of HCC between 2005 and 2015 were identified using a multi-institutional database. After categorizing patients into PS-0 (n = 836) versus PS-1 (n = 695), perioperative mortality and morbidity, overall survival (OS) and recurrence-free survival (RFS) were compared.ResultsOverall perioperative mortality and major morbidity among patients with PS-0 (n = 836) and PS-1 (n = 695) were similar (1.4% vs. 1.6%, P = 0.525 and 9.7% vs. 10.2%, P = 0.732, respectively). In contrast, median OS and RFS was worse among patients who had PS-1 versus PS-0 (34.0 vs. 107.6 months, and 20.5 vs. 60.6 months, both P < 0.001, respectively). On multivariable Cox-regression analyses, PS-1 was independently associated with worse OS (HR: 1.301, 95% CI: 1.111–1.523, P < 0.001) and RFS (HR: 1.184, 95% CI: 1.034–1.358, P = 0.007).ConclusionsPatients with PS-1 versus PS-0 had comparable perioperative outcomes. However, patients with PS-1 had worse long-term outcomes as PS-1 was independently associated with worse OS and RFS. Routine exclusion of HCC patients with PS-1 from surgical resection as recommended by the BCLC guidelines is not warranted.     

Association of primary tumor location with long-term oncological prognosis following hepatectomy for hepatocellular carcinoma:A multicenter propensity score matching analysis

PurposeThere is a striking laterality in the site of hepatocellular carcinoma (HCC), with a strong predominance for the right side; however, the impact of primary tumor location on long-term prognosis after hepatectomy of HCC remains unclear. This study aimed to investigate the effect of primary tumor location on long-term oncological prognosis after hepatectomy for HCC.Patients and methodsData of consecutive patients undergoing curative hepatectomy for HCC between 2008 and 2017 were analyzed. Overall survival (OS) and recurrence-free survival (RFS) of left-sided HCC (LS group) and right-sided HCC (RS group) were compared by using propensity score matching (PSM) analysis. COX regression analysis was performed to assess the adjusted effect of tumor location on long-term oncological prognosis.ResultsOf the 2799 included patients, 707 (25.3%) and 2092 (74.7%) were in the LS and RS groups, respectively. Using PSM analysis, 650 matched pairs of patients were created. In the PSM cohort, median OS (66.0 vs. 72.0 months, P = 0.001) and RFS (28.0 vs. 51.0 months, P < 0.001) were worse among patients in the LS group compared to individuals in the RS group. After further adjustment for other confounders using multivariable COX regression analyses, HCC located on the left side remained independently associated with worse OS and RFS.ConclusionTumors located on the left side are associated with poorer OS and RFS after hepatectomy for HCC. Careful surgical options selection and frequent follow-up to improve long-term survival may be justified for HCC patients with left-sided primary tumors.     

Sirolimus-based immunosuppression improves the prognosis of liver Transplantation Recipients with low TSC1/2 expression in hepatocellular carcinoma beyond the Milan Criteria

BackgroundThe use of the immunosuppressive agent sirolimus (SRL) following liver transplantation (LT) in patients with hepatocellular carcinoma (HCC) is controversial. Sirolimus is a typical mammalian target of rapamycin (mTOR) inhibitor, and tuberous sclerosis 1-tuberous sclerosis 2 complex (TSC1/TSC2) is an important negative effector in the mTOR pathway. In this study, we investigated the effect of SRL-based immunosuppression on the prognosis of LT recipients with HCC beyond the Milan criteria based on TSC1/2 expression and explored the effect of TSC1 on HCC in vitro and in vivo.MethodsWe retrospectively analyzed 120 HCC patients who underwent LT in our hospital between January 1, 2015 and December 30, 2018. All patients had HCC beyond the Milan criteria and were divided into the SRL group (n = 50) and non-SRL group (n = 70). TSC1/2 expression levels in paraffin-embedded tissues were determined by immunohistochemistry (IHC) and then analyzed as subgroups. Overall survival (OS) and disease-free survival (DFS) were analyzed using the Kaplan-Meier method. TSC1 expression was silenced in Huh-7 and Bel-7402 cell lines for further cell function experiments.Results88.3% of patients were HBV LT recipients. The SRL group exhibited better DFS and OS compared to the non-SRL group (P = 0.02, P = 0.003). Subgroup (TSC1-based or TSC2-based) analyses revealed that patients with low TSC1 or TSC2 expression benefited from sirolimus (DFS: P = 0.046, OS: P = 0.006 for TSC1; DFS: P = 0.05, OS: P = 0.003 for TSC2) compared with patients with high expression. TSC1 knockdown in Huh-7 and Bel-7402 HCC cell lines activated the mTORC1 pathway and enhanced cell proliferation, migration and sensitivity to SRL in vitro and in vivo.ConclusionTSC1/2 expression could be used to predict the prognosis of patients with HCC beyond the Milan criteria who underwent SRL-based immunosuppression following LT. TSC1 knockdown promoted HCC malignancy and enhanced sensitivity to SRL.     

Preoperative C-reactive protein-to-albumin ratio and clinical outcomes after resection of colorectal liver metastases

PurposeAccumulating evidence suggests that the inflammatory tumor microenvironment can potentiate tumor progression and metastasis. The C-reactive protein-to-albumin ratio (CAR) is a novel inflammation-based prognostic score. This study was performed to examine the associations of the preoperative CAR with clinical outcomes in patients with colorectal liver metastases (CRLM) after curative resection.MethodsWe retrospectively assessed the preoperative CAR in 184 patients who underwent curative resection for CRLM from November 2001 to January 2018 at Kumamoto University (Kumamoto, Japan). The optimal cutoff level of the preoperative CAR was determined by survival classification and regression tree (CART) analysis. We compared clinicopathological factors and prognoses between the high-CAR and low-CAR groups. A Cox proportional hazards model was used to calculate hazard ratios (HRs), controlling for potential confounders.ResultsA higher preoperative CAR was associated with worse overall survival (OS) (p < 0.0001) and recurrence-free survival (RFS) (p = 0.003). Applying survival CART analysis, the high-CAR group comprised 33 patients (17.9%). In the multivariate analyses, a high CAR was independently associated with shorter OS (HR, 2.82; 95% confidence interval, 1.63–4.72; p = 0.0004) and RFS (HR, 1.62; 95% confidence interval, 1.02–2.49; p = 0.040). A high CAR was associated with a large tumor size, high serum carcinoembryonic antigen and carbohydrate antigen 19-9 levels, high intraoperative blood loss, and more postoperative complications.ConclusionA high preoperative CAR is associated with shorter OS and RFS and might serve as a prognostic marker for patients with CRLM after curative resection.     

Transarterial chemoembolization plus immune checkpoint inhibitor as postoperative adjuvant therapy for hepatocellular carcinoma with portal vein tumor thrombus: A multicenter cohort study

PurposeThis study aimed to assess the efficacy and safety of postoperative adjuvant transarterial chemoembolization (PA-TACE) plus immune checkpoint inhibitor (ICI) for hepatocellular carcinoma (HCC) with portal vein tumor thrombus (PVTT).Patients and methodsThis study was conducted on three centers from June 2018 to December 2020. Patients were divided into the PA-TACE (n = 48) and PA-TACE plus ICI groups (n = 42). The recurrence-free survival (RFS) and overall survival (OS) curves were depicted by Kaplan-Meier method, and the differences between the two groups were compared using log-rank test. Univariate and multivariate Cox analyses were performed to identify independent risk factors for RFS and OS. Adverse events (AEs) were assessed according to the Common Terminology Criteria for AEs (CTCAE) version 5.0.ResultsThe median RFS of the PA-TACE plus ICI group was significantly longer than the PA-TACE group (12.76 months vs. 8.11 months; P = 0.038). The median OS of the PA-TACE plus ICI group was also significanfly better than the PA-TACE group (24.5 months vs. 19.1 months; P = 0.032). PA-TACE plus ICI treatment was an independent prognostic factor for RFS (HR: 0.54, 95% CI: 0.32–0.9, P = 0.019) and OS (HR: 0.47, 95% CI: 0.26–0.86, P = 0.014). Only one patient experienced grade ≥3 immune-related AEs in the PA-TACE plus ICI group.ConclusionsPA-TACE plus ICI treatment had better efficacy in preventing recurrence and prolonging survival than PA-TACE alone for HCC patients with PVTT after R0 resection. This novel treatment modality may be an appropriate option for HCC with PVTT.     

Novel implications of combined arterial resection for locally advanced pancreatic cancer in the era of newer chemo-regimens

IntroductionIn this study, we assessed the prognostic efficacy and feasibility of combined arterial resection (AR) for locally advanced pancreatic cancer (LAPC), and aimed to identify significant prognostic factors for patients who underwent combined AR.MethodsBetween 1981 and 2018, 733 consecutive patients who underwent pancreatic surgery for PC were identified. The 730 cases with detailed information were enrolled in the analysis.ResultsAmong 730 resected PC patients, 44 (6%) underwent AR including 21 hepatic (48%), 12 celiac (27%), five splenic (12%), four superior mesenteric (9%), and two other arteries (4%). The combined AR surgery showed significantly longer operative time (median, 608 vs 451 min, P < 0.0001), and the incidence of intraoperative blood transfusion was significantly higher in AR than surgery without AR (P = 0.0002), whereas there was no significant difference in the intraoperative blood loss (970 vs 1200 mL, P = 0.2) and occurrence of major complications (P = 0.5). In prognostic analysis of AR cases, multivariate Cox proportional hazard models revealed preoperative and postoperative therapy were the independent factors for both recurrence-free survival (RFS) and overall survival (OS) (preoperative therapy: RFS, HR = 0.21, P = 0.007; OS, HR = 0.18, P = 0.01; postoperative therapy: RFS, HR = 0.31, P = 0.003; OS, HR = 0.19, P = 0.002).ConclusionThis study showed the feasibility of combined AR for LAPC and robust association of pre- and postoperative therapy and survival after AR surgery. Preoperative therapy following combined AR surgery is potentially powerful strategy for LAPC.     

Long-term outcomes of deceased donor liver transplantation in hepatocellular carcinoma patients with portal vein tumor thrombus: A multicenter study

BackgroundThe incidence of portal vein tumor thrombus (PVTT) has been reported to be as high as approximately 10%–40% in patients with hepatocellular carcinoma (HCC). The long-term prognosis of deceased donor liver transplantation (DDLT) in HCC patients with PVTT remains unknown.MethodsData of 961 HCC patients who underwent DDLT between 2015 and 2018 in six centers were analyzed. Based on the Milan criteria (MC) and Cheng's classification of PVTT, the patients were divided into 4 groups: within MC, beyond MC without PVTT, type 1 PVTT, and type 2 PVTT groups.Results489 (50.9%) were within the MC, 296 (30.8%) beyond the MC but without PVTT, 83 (8.6%) type 1 PVTT, and 93 (9.7%) type 2 PVTT. Kaplan-Meier analysis showed that type 1 or 2 PVTT patients with alpha-fetoprotein (AFP) ≤ 100 ng/mL had overall survival (OS) similar to that of patients within the MC (P = 0.957), and superior OS (P = 0.003 and 0.009) and recurrence-free survival (RFS) (P = 0.038 and <0.001) than those of patients beyond the MC and PVTT patients with AFP > 100 ng/mL. Multivariable Cox-regression analysis identified type 1 and 2 PVTT to be independent risk factor for RFS [hazard ratio (HR) 1.523 95% confidence interval (CI) 1.162–1.997, P = 0.002], but not for OS (HR 1.283, 95%CI 0.922–1.786, P = 0.139).ConclusionHCC patients with type 1 or 2 PVTT may be acceptable candidates for DDLT. To achieve better outcomes, preoperative AFP levels should be seriously considered when selecting patients with PVTT for DDLT.     

Technical,functional, and oncological validity of robot-assisted total-intersphincteric resection (T-ISR) for lower rectal cancer

BackgroundFew studies fairly compared anorectal function and prognostic outcomes between patients undergoing abdominoperineal resection (APR) and anorectal-function-saving operations (ASO) under the equivalent conditions. By contrast, surgeons used to be somewhat hesitant to conduct total intersphincteric resection (T-ISR) as maximal ASO, due to its technical complexity and potential anorectal dysfunction.MethodsPropensity-score matched cohorts undergoing robot-assisted R0 surgery [T-ISR vs APR vs partial-subtotal ISR (PS-ISR)/lower anterior resection (LAR)] for rectal cancer (n = 1361) were included. Operative outcomes, recurrence, and disease-free/overall survival (DFS/OS) were analyzed. Anorectal function was evaluated based on fecal incontinence score and high-resolution manometry between the T-ISR and other ASO groups.ResultsFew differences were detected between the T-ISR and APR groups. More patients undergoing APR had T4 stage disease, while the lowest tumor margin was the same in both groups (mean, 1.5 cm from anal verge). Prognostic outcomes did not differ between the T-ISR and APR groups, including local (5.1% vs 7.7%, p = 1) or systemic (15.4% vs 25.6%, p = 0.401) recurrence, and 5-year DFS (78.7% vs 61.5%, p = 0.1) and OS (89% vs 82.1%, p = 0.434) rates, nor were there differences between the T-ISR and PS-ISR/LAR groups. The PS-ISR group generally showed less anorectal dysfunction than the T-ISR group, but maximal tolerance volume did not differ between these two groups and was within the range for the healthy population.ConclusionsT-ISR can replace most traditional APR, except for advanced T4 disease with aggressive infiltration into the levator-sphincters, and can provide tolerable anorectal dysfunction.     

Trans-arterial chemoembolization + radiofrequency ablation versus surgical resection in hepatocellular carcinoma – A meta-analysis

BackgroundHepatocellular Carcinoma (HCC) remains the third most common cause of cancer death worldwide, with countries in Asia being affected the most. The mainstay of curative therapy for early HCC is radiofrequency ablation (RFA) or surgery; either surgical resection (SR) or liver transplantation. Latest evidence however suggests that combination of TACE+ RFA may provide outcomes comparable to SR.AimTo compare oncologic outcomes and safety profile of TACE + RFA to SR alone in HCC.Materials and methodsA systematic review was conducted through Pubmed, EMBASE and Cochrane Library for literature published before April 2019. Outcomes measured were disease-free survival(DFS), overall survival(OS) and major complications. DFS was further divided into local tumour progression(LTP), intrahepatic distant recurrence(IDR) and distant metastasis(DM).ResultsEight retrospective studies and one randomized controlled trial, involving 1892 patients met eligibility criteria and were included. Unadjusted pooled analysis demonstrated no significant difference in 1-year, 3-year and 5-year OS and 1-year DFS between TACE+RFA and SR. SR had superior 3-year DFS (OR 0.78, 95% CI 0.62–0.98, p = 0.03) and 5-year DFS (OR 0.74, 95% CI 0.58–0.95, p = 0.02) compared to TACE+RFA. When analysing only the propensity matched data, the difference in 3-year DFS and 5-year DFS was not significant. TACE+RFA had a higher LTP rate (OR 2.48, 95% CI 1.05–5.86, p = 0.04) compared to SR but IDR and DM rates were not significant.Discussion and conclusionTACE+RFA offer comparable oncologic outcomes in patients with HCC as compared with SR and with added benefit of lower morbidity.     

Upfront surgery or definitive radiotherapy for p16+ oropharyngeal cancer. A GETTEC multicentric study

BackgroundThe aim of this study was to assess the impact of the initial therapeutic strategy on oncologic outcomes in patients with HPV-positive OPSCC.MethodsAll p16-positive OPSCCs treated from 2009 to 2014 in 7 centers were retrospectively included and classified according to the therapeutic strategy: surgical strategy (surgery ± adjuvant radiotherapy and chemotherapy) vs. non-surgical strategy (definitive radiotherapy ± chemotherapy). Univariate, multivariate propensity score matching analyses were performed to compare overall (OS), disease-specific (DSS) and recurrence-free survival (RFS).Results382 patients were included (surgical group: 144; non-surgical group: 238). Five-year OS, DSS and RFS were 89.2, 96.8 and 83.9% in the surgical group and 84.2, 87.1 and 70.4% in the non-surgical group, respectively. These differences were statistically significant for DSS and RFS after multivariate analysis, but only for RFS after propensity score matching analysis.ConclusionIn p16+ OPSCC patients, upfront surgery results in higher RFS than definitive radiotherapy ± chemotherapy but does not impact OS.     

Prognostic value of primary tumor sidedness in patients with non-metastatic IBD related CRC – Is it the exception to the rule?

BackgroundAlthough primary tumor sidedness (PTS) has a known prognostic role in sporadic colorectal cancer (CRC), its role in Inflammatory Bowel Disease related CRC (IBD-CRC) is largely unknown. Thus, we aimed to evaluate the prognostic role of PTS in patients with IBD-CRC.MethodsAll eligible patients with surgically treated, non-metastatic IBD-CRC were retrospectively identified from institutional databases at ten European and Asian academic centers. Long term endpoints included recurrence–free (RFS) and overall survival (OS). Multivariable Cox proportional hazard regression as well as propensity score analyses were performed to evaluate whether PTS was significantly associated with RFS and OS.ResultsA total of 213 patients were included in the analysis, of which 32.4% had right-sided (RS) tumors and 67.6% had left-sided (LS) tumors. PTS was not associated with OS and RFS even on univariable analysis (5-year OS for RS vs LS tumors was 68.0% vs 77.3%, respectively, p = 0.31; 5-year RFS for RS vs LS tumors was 62.8% vs 65.4%, respectively, p = 0.51). Similarly, PTS was not associated with OS and RFS on propensity score matched analysis (5-year OS for RS vs LS tumors was 82.9% vs 91.3%, p = 0.79; 5-year RFS for RS vs LS tumors was 85.1% vs 81.5%, p = 0.69). These results were maintained when OS and RFS were calculated in patients with RS vs LS tumors after excluding patients with rectal tumors (5-year OS for RS vs LS tumors was 68.0% vs 77.2%, respectively, p = 0.38; 5-year RFS for RS vs LS tumors was 62.8% vs 59.2%, respectively, p = 0.98).ConclusionsIn contrast to sporadic CRC, PTS does not appear to have a prognostic role in IBD-CRC.     

Spontaneous rupture of hepatocellular carcinoma: Optimal timing of partial hepatectomy

BackgroundPartial hepatectomy has been used to treat patients with resectable hepatocellular carcinoma (HCC) which spontaneously ruptured. It is still controversial as to whether emergency partial hepatectomy (EmPH) should be carried out at the time of rupture, or the patients should initially be managed by operative or non-operative treatment to stop the bleeding, followed by staged early or delayed partial hepatectomy when the patient's condition becomes stable.MethodsConsecutive 10-year patients with ruptured HCC managed at our center were included in this study. Patients who underwent partial hepatectomy were further subdivided into the EmPH group, the staged early partial hepatectomy (SEPH) group, and the staged delayed partial hepatectomy (SDPH) group. Univariate and multivariate analyses of factors affecting overall survival(OS) were conducted before and after propensity score matching analyses amongst the included patients. OS, postoperative mortality, recurrence free survival (RFS), and peritoneal metastatic rates were compared. The risk factors of peritoneal metastases were determined using the COX regression analysis.ResultsThe 130 patients who underwent partial hepatectomy were subdivided into the EmPH group (surgery at the time of rupture, n = 30), the SEPH group (surgery ≤ 8 days of rupture, n = 67), and the SDPH group (surgery > 8 days of rupture, n = 33). The remaining 86 patients underwent non-surgical treatment. Partial hepatectomy was an independent predictor of better OS (HR 2.792, P < 0.001). For resectable HCC, the 30-day mortality, OS, and RFS were similar between the EmPH group, and the staged partial hepatectomy (SPH) group which included the patients who underwent SEPH and SDPH. The SEPH group had significantly better OS and RFS. Multivariate COX regression analysis demonstrated that SDPH was strongly associated with postoperative peritoneal dissemination (OR 28.775, P = 0.003).ConclusionPartial hepatectomy provided significantly better survival than non-surgical treatment for patients who presented with ruptured HCC. Early partial hepatectomy within 8 days of rupture which included EmPH (carefully selected) and SEPH, resulted in significantly less patients with peritoneal dissemination and better long-term survival outcomes (especially RFS) than SDPH.     

Survival of surgical and non-surgical older patients with non-metastatic colorectal cancer: A population-based study in the Netherlands

BackgroundSurgery is the primary treatment for non-metastatic colorectal cancer (CRC) but is omitted in a proportion of older patients. Characteristics and prognosis of non-surgical patients are largely unknown.ObjectiveTo examine the characteristics and survival of surgical and non-surgical older patients with non-metastatic CRC in the Netherlands.MethodsAll patients aged ≥70 years and diagnosed with non-metastatic CRC between 2014 and 2018 were identified in the Netherlands Cancer Registry. Patients were divided based on whether they underwent surgery or not. Three-year overall survival (OS) and relative survival (RS) were calculated for both groups separately. Relative survival and relative excess risks (RER) of death were used as measures for cancer-related survival.ResultsIn total, 987/20.423 (5%) colon cancer patients and 1.459/7.335 (20%) rectal cancer patients did not undergo surgery. Non-surgical treatment increased over time from 3.7% in 2014 to 4.8% in 2018 in colon cancer patients (P = 0.01) and from 17.1% to 20.2% in rectal cancer patients (P = 0.03). 3 year RS was 91% and 9% for surgical and non-surgical patients with colon cancer, respectively. For rectal cancer patients this was 93% and 37%, respectively. In surgical patients, advanced age (≥80 years) did not decrease RS (colon; RER 0.9 (0.7–1.0), rectum; RER 0.9 (0.7–1.1)). In non-surgical rectal cancer patients, higher survival rates were observed in patients treated with chemoradiotherapy (OS 56%, RS 65%), or radiotherapy (OS 19%, RS 27%), compared to no treatment (OS 9%, RS 10%).ConclusionNon-surgical treatment in older Dutch CRC patients has increased over time. Because survival of patients with colon cancer is very poor in the absence of surgery, this treatment decision must be carefully weighed. (Chemo-)radiotherapy may be a good alternative for rectal cancer surgery in older frail patients.     

Impact of concurrent splenectomy and esophagogastric devascularization on surgical outcomes of partial hepatectomy for hepatocellular carcinoma in patients with clinically significant portal hypertension: A multicenter propensity score matching analysis

PurposePortal hypertension due to cirrhosis is common among patients with hepatocellular carcinoma (HCC). This study aimed to compare the outcomes of partial hepatectomy in patients with HCC and clinically significant portal hypertension (CSPH) with or without concurrent splenectomy and esophagogastric devascularization (CSED).Patients and methodsFrom a multicenter database, patients with HCC and CSPH who underwent curative-intent hepatectomy were identified. Postoperative morbidity and mortality, and long-term overall survival (OS) were compared in patients with and without CSED before and after propensity score matching (PSM).ResultsOf the 358 enrolled patients, 86 patients underwent CSED. Before PSM, the postoperative 30-day morbidity and mortality rates were comparable between the CSED and non-CSED group (both P > 0.05). Using PSM, 81 pairs of patients were created. In the PSM cohort, the 5-year OS rate of the CSED group were significantly better than the non-CSED group (52.9% vs. 36.5%, P = 0.046). The former group had a significantly lower rate of variceal bleeding on follow-up (7.4% vs. 21.7%, P = 0.014). On multivariate analysis, CSED was associated with significantly better OS (HR: 0.39, P < 0.001).ConclusionHepatectomy and CSED can safely be performed in selected patients with HCC and CSPH, which could improve postoperative prognosis by preventing variceal bleeding, and prolonging long-term survival.     

Upfront surgery or definitive radiotherapy for patients with p16-negative oropharyngeal squamous cell carcinoma. A GETTEC multicentric study

IntroductionTherapeutic management of oropharyngeal squamous cell carcinomas (OPSCC) is still debated. Since the role of HPV was demonstrated, few studies have focused on HPV-negative OPSCC. The aim of our study was to assess the impact of therapeutic strategy (surgical vs. non-surgical) on oncologic outcomes in patients with HPV-negative OPSCC.Material and methodAll p16-negative OPSCCs treated from 2009 to 2014 in 7 tertiary-care centers were included in this retrospective study and were classified according to the therapeutic strategy: surgical strategy (surgery ± adjuvant radiotherapy and chemotherapy) vs. non-surgical strategy (definitive radiotherapy ± chemotherapy). Patients not eligible for surgery (unresectable tumor, poor general-health status) were excluded. Univariate, multivariate and propensity score matching analyses were performed to compare overall (OS), disease-specific (DSS) and recurrence-free survival (RFS).ResultsFour hundred seventy-four (474) patients were included in the study (surgical group: 196; non-surgical group: 278). Five-year OS, DSS and RFS were 76.5, 81.3 and 61.3%, respectively, in the surgical group and 49.9, 61.8 and 43.4%, respectively, in the non-surgical group. The favorable impact of primary surgical treatment on oncologic outcomes was statistically significant after multivariate analysis. This effect was more marked for locally-advanced than for early-stage tumors. Propensity score matching analysis confirmed the prognostic impact of primary surgical treatment for RFS.ConclusionTherapeutic strategy is an independent prognostic factor in patients with p16-negative OPSCC and primary surgical treatment is associated with improved OS, DSS and RFS. These results suggest that surgical strategy is a reliable option for advanced stage OPSCC.     

Borderline or locally advanced pancreatic adenocarcinoma: A single center experience on the FOLFIRINOX induction regimen

IntroductionThis study aimed to determine the impact of FOLFIRINOX neoadjuvant therapy on patients with non-metastatic borderline/locally advanced (BL/LA) pancreatic ductal adenocarcinoma (PDAC), in current practice.Material and methodsFrom 2010 to 2017, 258 patients with BL/LA PDAC from a single high-volume institution received FOLFIRINOX neoadjuvant treatment.ResultsThe 258 patients received a median number of 6 cycles of FOLFIRINOX (range, 3–16); 98 (38%) patients underwent curative surgery, and 160 (62%) continued medical treatment. A venous resection was performed in 57 patients (58%), and an arterial resection in 12 (12%). The postoperative 30- and 90-day mortality rates were 6.1% and 8.2%, respectively. Adjuvant chemotherapy was performed in 57 patients (59%). The median overall survival (OS) in patients who did (n = 98) or did not (n = 160) undergo surgical resection were 39 months and 19 months, respectively (P < 0.001). In resected patients, the ASA 3 score (P < 0.01), venous resection (P < 0.01), hemorrhage (P < 0.01), and R1 margin status (P = 0.03) were found to negatively influence the OS. The median OS was significantly higher in patients who did not require a venous resection (not reached vs. 26.5 months, P < 0.001).ConclusionsNeoadjuvant FOLFIRINOX provided a survival benefit in BL/LA PDAC patients, particularly in those who did not ultimately require venous resection.     

Minimum radial margin in pelvic exenteration for locally advanced or recurrent rectal cancer

PurposeThe aim of this study was to clarify the suitable radial margin (RM) for favourable outcomes after pelvic exenteration (PE), focusing on the discrepancy between the concepts of circumferential resection margin (CRM) and traditional R status.MethodsSeventy-three patients with locally advanced (LARC, n = 24) or locally recurrent rectal cancer (LRRC, n = 49) who underwent PE between 2006 and 2018 were retrospectively analysed. Patients were histologically classified into the following 3 groups; wide RM (≥1 mm, n = 45), narrow RM (0–1 mm, n = 10), and exposed RM (n = 18). The analysis was performed not only in the entire cohort but also in each disease group separately.ResultsThe rates of traditional R0 (RM > 0 mm) and wide RM were 75.3% and 61.6%, respectively, resulting in the discrepancy rate of 13.7% between the two concepts. Preoperative radiotherapy was given in 12.3%. In the entire cohort, the local recurrence and overall survival (OS) rates for narrow RMs were significantly worse than those for wide RMs (p < 0.001 and p = 0.002), but were similar to those for exposed RMs. In both LARC and LRRC, RM < 1 mm resulted in significantly worse local recurrence and OS rates compared to the wide RMs. Multivariate analysis showed that RM < 1 mm was an independent risk factor for local recurrence in both LARC (HR 15.850, p = 0.015) and LRRC (HR 4.874, p = 0.005).ConclusionsNarrow and exposed RMs had an almost equal impact on local recurrence and poor OS after PE. Preoperative radiotherapy might have a key role to ensure a wide RM.