Primary tumor location and the prognosis of patients after local treatment of colorectal liver metastases: a systematic review and meta-analysis

BackgroundRecently numerous studies have reported primary tumor location as a potential prognostic factor after surgery for colorectal liver metastases (CRLM). The aim of this study was to comprehensively review and analyze all the available literature on the impact of primary tumor location in patients after local treatment of CRLM.MethodsStudies examining the association of right- and left-sided colorectal cancer and overall survival (OS) and recurrence free survival (RFS) after local treatment (resection and/or ablation) of CRLM were identified. Random-effects models were used for both clinicopathological and outcome variables. Pooled hazard ratios (HR) with 95% confidence intervals (95% CI) were shown for both OS and RFS.ResultsTen studies (including 11 patient cohorts) were eligible for inclusion, representing 3962 patients. Right-sided tumors (i.e. proximal to the splenic flexure) were observed in 1340 patients (33.8%). Median follow-up ranged from 25 to 137 months. Patients with right-sided tumors had a significantly decreased OS (HR 1.60, 95% CI 1.30–1.98, p < 0.001) and RFS (HR 1.35, 95% CI 1.04–1.77, p = 0.03), when compared to patients with left-sided tumors.ConclusionThis meta-analysis suggests that patients with right-sided primaries suffer from a worse prognosis, compared to patients with left-sided primaries in patients after local treatment of CRLM.     

Prognostic significance of primary tumor sidedness in patients undergoing liver resection for metastatic colorectal cancer

BackgroundApproximately 38% of patients with colorectal cancer will develop isolated liver metastases. Sidedness of colon tumor is identified in non-metastatic and unresected metastatic cancers as predictive of survival, yet its dedicated analysis in resected liver metastases is minimal. Our primary aim was to assess whether left-sided primary tumors improve prognosis in stage IV cancer patients undergoing curative-intent liver metastasectomy; it was hypothesized that it would.MethodsThis is a retrospective, observational cohort study from 1996 to 2016 in a single tertiary-care facility. Survival from diagnosis was calculated via Kaplan–Meier method and compared between the right and left sides via log-rank analysis.ResultsMedian survival differs significantly between colorectal tumors of the right and left origins after hepatic metastasectomy in 612 patients. In patients with right-sided tumors, median survival from diagnosis was 4.5 years (IQR 4.1–5.3), and 6.3 years (IQR 5.6–6.9) in those with left tumors (HR 1.5, 95% CI 1.38–1.60, p < 0.001).ConclusionAs in studies on earlier-stage or unresected metastatic disease, tumor sidedness is an important prognostic factor in patient survival with liver metastasectomy. Clinical risk scores should include side of primary tumor. Further work is needed to determine the molecular basis for this difference.     

Prognostic impact of primary tumor location in Stage III colorectal cancer-right-sided colon versus left-sided colon versus rectum: a nationwide multicenter retrospective study

Background

Previous studies investigating the impact of tumor location on colorectal cancer prognosis only compared two groups by location, e.g., ‘right-sided colon vs. left-sided colon,’ ‘colon vs. rectum,’ and ‘right-sided (right-sided colon) vs. left-sided (left-sided colon and rectum).’ This nationwide multicenter retrospective study aimed to clarify the prognostic impact of tumor location in patients with stage III colorectal cancer by classifying tumors into three groups: right-sided colon, left-sided colon, and rectum.

Methods

Subjects were 9194 patients with stage III colorectal cancer who underwent curative surgery from 1997 to 2012. Relapse-free survival (RFS) after primary surgery and overall survival (OS) after recurrence were examined.

Results

Rectal cancer (n = 2922) was associated with worse RFS compared to right-sided colon cancer (n = 2362) (hazard ratio (HR) 0.65; 95% CI 0.59–0.72; p < 0.001) and left-sided colon cancer (n = 3910) (HR 0.72; 95% CI 0.66–0.78; p < 0.001) after adjusting for key clinical factors (i.e., sex, age, histological type, CEA, adjuvant therapy, T category, and N category). Among patients with recurrence (n = 2823), rectal cancer was associated with better OS compared to right-sided colon cancer (HR 1.23; 95% CI 1.08–1.40; p = 0.002) and worse OS compared to left-sided colon cancer (HR 0.88; 95% CI 0.79–0.99; p = 0.029). Twenty percent of right-sided colon cancer recurrences exhibited peritoneal dissemination, 42% of left-sided colon cancer recurrences were liver metastases, and 33% of rectal cancer recurrences were local recurrences.

Conclusions

The three tumor locations (right-sided colon, left-sided colon, rectum) had different prognostic implications for recurrence after curative resection and overall mortality, suggesting that tumor location serves as a prognostic biomarker in stage III colorectal cancer.

     

Impact of primary tumor location on patterns of recurrence and survival of patients undergoing resection of liver metastases from colon cancer

BackgroundSeveral studies have described a worse prognosis for right-sided colon cancer compared to left-sided. The aim of this study was to compare patterns of recurrence and survival following resection of liver metastases (LM) from right-sided (RS) versus left-sided (LS) colon cancer.MethodsPatients undergoing resection for colon cancer LM between 2000 and 2017 were analyzed. Rectal cancer, multiple primaries and unknown location were excluded.ResultsOut of 995 patients, 686 fulfilled inclusion criteria (RS-LM = 322, LS-LM = 364). RS colon cancer had higher prevalence of metastatic lymph nodes (67.4% vs. 57.1%, P = 0.008). RS-LM were more often mucinous (16.8% vs. 8.5%, P = 0.001) and G3 (58.3% vs. 48.9%, P = 0.014). 451 (65.7%) patients experienced recurrence (RS-LM 68.9% vs. LS-LM 62.9%). In RS-LM group, recurrence was more often encephalic (2.3% vs. 0%, P = 0.029) and at multiple sites (34.2% vs. 23.5%, P = 0.012). The rate of re-resection was lower in RS-LM patients (27.9% vs. 37.5%, P = 0.024). Multivariate analysis showed RS-LM to have worse 5-year overall (35.8% vs. 51.2%, P = 0.002) and disease-free survival (26% vs. 43.6%, P = 0.002).ConclusionsRS-LM is associated with worse survival and aggressive recurrences, with lower chance of re-resection.     

Simultaneous or staged resection of synchronous colorectal cancer liver metastases: a 13-year institutional follow-up

BackgroundThis study compared postoperative outcomes and survival rates of patients who underwent simultaneous or staged resection for synchronous colorectal cancer liver metastases.MethodsBetween 2005 and 2018, 126 patients were registered prospectively at a university hospital in Sweden, 63 patients who underwent simultaneous resection were matched against 63 patients who underwent staged resection.ResultsThe length of hospital stay was shorter for the simultaneous resection group, at 11 vs 16 days, p = <0.001. Fewer patients experienced recurrence in the simultaneous resection group 39 vs 50 patients, p = 0.012. There were no significant differences in disease-free survival and overall survival between the groups. Age (hazard ratio [HR] 1.72; 95% CI 1.01–2.94; p = 0.049) and Clavien-Dindo score (HR 2.22; 95% CI 1.06–4.67; p = 0.035) had impact on survival.ConclusionColorectal cancer with synchronous liver metastases can be resected simultaneously, and enables a shorter treatment time without jeopardizing oncological outcomes.     

Outcomes of liver resection for hepatocellular carcinoma in octogenarians

BackgroundThere is a dearth of information about operative outcomes in patients ≥80 years for hepatocellular carcinoma (HCC) from Western institutions. We compare the result of HCC resections in patients <80 years vs. patients ≥80 years from our institution in the UK.MethodsWe conducted a retrospective review of all patients undergoing liver resections for HCC between 2005 and 2015. Demographics, comorbidities, morbidity, mortality and survival were compared between the two age groups.Results200 patients underwent resection for HCC in this time period. Nineteen patients were ≥80 years and 181 were <80 years. Comorbidities measured by the Charlson Comorbidity Index were significantly higher in the ≥80 group (p < 0.0001). There was no significant difference in the extent of resection in the two groups. Morbidity and mortality between the <80 years and the ≥80 years group were not significantly different (morbidity 27% vs.16%; p = 0.29) (mortality 7% vs. 0%; p = 0.11). The one-year (83.4% vs. 88.2%; p = 0.83), five-year (56.3% vs. 55.8%; p = 0.83) and the overall survival rate rates (887 days vs. 1035 days; p = 0.66) were not significantly different between the groups.DiscussionLiver resection should not be precluded based on age alone; with good outcomes in patients ≥80 years justifying surgery.     

The effects of resection margin and KRAS status on outcomes after resection of colorectal liver metastases

BackgroundThe aim of this study was to investigate the influence of resection margin status in patients with KRAS mutations (mt-KRAS) when compared to those with wild-type KRAS (wt-KRAS) on long-term outcomes in patients with resected CRLM.MethodsAll patients who underwent resection of CRLM with curative intent between January 2011 and December 2016 and had a KRAS type recorded were included in the study. Overall survival (OS), as well as death-censored overall (RFS) and liver-specific (LS-RFS) recurrence-free survival between KRAS types and the margin status within KRAS subgroups were compared using Cox regression models.ResultsData were available for N = 500 patients (30.4% mt-KRAS). mt-KRAS status was independently associated with significantly shorter OS. Within the wt-KRAS subgroup, smaller margins were found to be associated with significantly shorter death-censored LS-RFS (p < 0.001), with HRs of 1.93 (p = 0.005) for 1–4 mm margins and 2.83 (p < 0.001) for <1 mm margins, relative to those with clear margins. No such association was observed in the mt-KRAS subgroup (p = 0.721).ConclusionThe resection margin status is of greater importance in patients with wt-KRAS. Such information could be useful in the operative planning, especially for those with multiple metastatic deposits, and also in the post-operative counselling and surveillance based on the margin and KRAS status.     

Hepatic arterial infusion chemotherapy for colorectal liver metastases revisited

BackgroundRecent reports indicate improved survival in patients undergoing surgical treatment for colorectal liver metastases (CRLM) with hepatic arterial infusion (HAI) pump chemotherapy compared to surgery alone.MethodsPatients who underwent resection and/or ablation of CRLM between 1996 and 2016 were included from a single-institution prospectively maintained database. Proportional hazards regression analysis was performed to determine predictors of overall survival (OS) and 3:1 propensity score analysis (PSA).ResultsOf 349 patients included, 36 had HAI pumps placed (HAI group) and 313 did not (no-HAI group). There was no difference in primary tumor grade (p = 0.24), ECOG status (p = 0.44), tumor number (p = 0.1), tumor size (p = 0.56), margin status (p = 0.76) between the two groups.Median overall survival was 44.7months vs 37.1months for the HAI versus no-HAI group (p = 0.01). Cox proportional hazards regression analysis demonstrated positive margin status (HR:2.47,p < 0.0001), HAI therapy (HR:0.56,p = 0.02), preoperative chemotherapy (HR:0.69,p = 0.02) and tumor diameter (HR:1.07,p = 0.005) as predictors of OS. In 3:1 PSA, 32 HAI subjects were matched with 87 non-HAI subjects balancing all covariates. Median OS was 42.4 months versus 35.6 months for the HAI versus no-HAI group (p = 0.03).ConclusionSurgical treatment of CRLM combined with HAI chemotherapy is associated with improved OS compared to surgery alone. Further study of this treatment approach is indicated.     

Hyaluronan heterogeneity in pancreatic ductal adenocarcinoma: Primary tumors compared to sites of metastasis

BackgroundPancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive cancers with poor survival. The dense desmoplastic stroma in PDAC contributes to treatment resistance. Among the components comprising the tumor stroma, hyaluronan (HA) has been demonstrated to play a critical role in tumor progression and survival. Previous preliminary studies have suggested differences in HA expression in primary and metastatic foci of PDAC. However, the effects of treatment and location of HA expression as a biomarker signature remain unknown; this study sought to compare HA expression in primary and metastatic sites of PDAC.MethodsTissue from primary and metastatic PDACs were obtained from Cedars-Sinai Medical Center along with associated clinical data. Tissue slides were stained for H&E, HA, and CD44. Associations between HA levels and the evaluated variables were examined including progression free survival and overall survival.ResultsHA score was significantly higher in primary PDACs compared to sites of metastases (p = 0.0148). Within the metastases, HA score was significantly higher in liver metastases compared to metastases at other sites (p = 0.0478). In the treatment-naive liver metastasis cohort, patients with HA high status had decreased progression free survival and overall survival compared to patients with HA low status (p = 0.0032 and p = 0.0478, respectively).ConclusionsHA score is variable between primary PDAC, PDAC metastatic to the liver, and PDAC metastatic to other sites. Within liver metastases, patients with HA high status had decreased progression free survival and overall survival compared to patients with HA low status. HA levels can serve as a potential biomarker to guide pancreatic cancer treatments and trial design for agents targeting the stroma.     

Synchronous resection of colorectal cancer primary and liver metastases: an outcomes analysis

BackgroundConcurrent resection of the primary cancer and synchronous colorectal cancer liver metastases (CRCLM) was evaluated for differences in outcomes following stratification of both the liver and colorectal resection.MethodsConsecutive cases of synchronous resection of both the CRC primary and CRCLM were reviewed retrospectively at a single, high-volume institution over a 17-year period (2000–2017).Results273 patients underwent simultaneous resection of CRCLM. The distribution of the primary lesion was similar between the colon (52.4%) and rectum (47.6%), while 46.9% of patients had bilobar liver disease. Major liver/major colorectal resection (n = 24) were significantly more likely to experience colorectal specific morbidity (OR 3.98, 95% CI 1.56–10.15, p = 0.004), liver specific morbidity (OR 7.4, 95% CI 2.22–24.71, p = 0.001), total morbidity (OR 2.91, 95% CI 1.18–7.18, p = 0.020) and 90-day mortality (OR 5.50, 95% CI 1.27–23.81, p = 0.023). Failure to receive adjuvant chemotherapy secondary to postoperative morbidity was associated with significantly worsened survival (HR for death 5.91, 95% CI 1.59–22.01, p = 0.008).ConclusionsPostoperative morbidity precluding the administration of adjuvant chemotherapy is associated with an increase in mortality. Combining a major liver with major colorectal resection is associated with a significant increase in major morbidity and 90-day mortality, and should be avoided.     

Feasibility and safety of liver transplantation or resection after transarterial radioembolization with Yttrium-90 for unresectable hepatocellular carcinoma

BackgroundThe benefit of transarterial radioembolization (TARE) in patients with unresectable hepatocellular carcinoma (HCC) is increasingly evidenced. However, data on outcome of liver transplantation or resection after TARE remain scarce. This study aimed to assess the safety and feasibility of surgery after TARE in patients with unresectable HCC.MethodsPatients exclusively undergoing TARE followed by either orthotopic liver transplantation (OLT) or liver resection (LR) for HCC between 2012 and 2016 were included. Primary outcomes were postoperative morbidity and mortality. Secondary outcomes were overall survival (OS) and response to TARE.ResultsAmong 349 patients with HCC treated with TARE, 32 (9%) underwent either OLT (n = 22) or LR (n = 10), which represent the study cohort. In this group, TARE induced decreased viable nodules (p < 0.001), an efficient downsizing (p < 0.001) as well as a significant downstaging based on BCLC classification (p < 0.001). Overall, major complications and mortality after surgery occurred in 5 (16%) and 1 (3%) patients, respectively. For the whole study cohort, OS was 47 months while survival rates at 1-, 3- and 5-years reached 97%, 86% and 86%, respectively.DiscussionLiver surgery after TARE is feasible and safe. This strategy allows to offer a curative treatment in a subset of patients with unresectable HCC.     

Left lateral segment pediatric liver transplantation: a 25 year experience at Mount Sinai

BackgroundOutcomes of left lateral segment (LLS) grafts in pediatric recipients were compared between living (LD-LLS) and deceased donor (DD-LLS) grafts.Methods195 LLS grafts (99DD-LLS-96LD-LLS) were analyzed with a median follow-up of 9.1years. The primary endpoints were overall patient/graft survival.ResultsLD-LLS grafts were younger (0.9vs.1.4years, p = 0.039), more likely to have a fulminant liver failure (17.9%vs.5.3%,p = 0.002), less likely to have a metabolic disorder (6.3%vs.25.5%,p = 0.002), and less likely to be undergoing retransplantation (5.3% vs.16.2%,p = 0.015). There was a trend toward decreased hepatic artery thrombosis in LD-LLS grafts (6.6% vs. 15.5%,p = 0.054). No differences in the overall biliary complications occurred. The LD-LLS group had prolonged survival compared to the DD-LLS group with 10-year survival rates of 81%, and 74% (p = 0.005), respectively. LD-LLS grafts had longer graft survival compared to DD-LLS grafts (10-year graft survival 85%vs.67%,p = 0.005). Recipient age >1year (HR 2.39,p = 0.026), aortic reconstruction (HR 2.12,p = 0.046) and vascular complication (HR 3.12,p < 0.001) were independent predictors of poor patient survival. Non-biliary liver disease (HR 2.17,p = 0.015), DD-LLS (HR 2.06,p = 0.034) and vascular complication (HR 4.61,p < 0.001) were independent predictors of poor graft survival.ConclusionThe use of SLT remains a viable option with excellent long-term outcomes. We show improved graft and patient survival with living donor grafts.     

Circulating metabolites as a concept beyond tumor biology determining disease recurrence after resection of colorectal liver metastasis

BackgroundMicro-metastatic growth is considered the main source of early cancer recurrence. Nutritional and microenvironmental components are increasingly recognized to play a significant role in the liver. We explored the predictive potential of preoperative plasma metabolites for postoperative disease recurrence in colorectal cancer liver metastasis (CRCLM) patients.MethodsAll included patients (n = 71) had undergone R0 liver resection for colorectal cancer liver metastasis in the years between 2012 and 2018. Preoperative blood samples were collected and assessed for 180 metabolites using a preconfigured mass-spectrometry kit (Biocrates Absolute IDQ p180 kit). Postoperative disease-free (DFS) and overall survival (OS) were prospectively recorded. Patients that recurred within 6 months after surgery were defined as “high-risk” and, subsequently, a three-metabolite model was created which can assess DFS in our collective.ResultsMultiple lysophosphatidylcholines (lysoPCs) and phosphatidylcholines (PCs) significantly predicted disease recurrence within 6 months (strongest: PC aa C36:1 AUC = 0.83, p = 0.003, PC ae C34:0 AUC = 0.83, p = 0.004 and lysoPC a C18:1 AUC = 0.8, p = 0.006). High-risk patients had a median DFS of 183 days versus 522 days in low-risk population (p = 0.016, HR = 1.98 95% CI 1.16–4.35) with a 6 months recurrence rate of 47.6% versus 4.7%, outperforming routine predictors of oncological outcome.ConclusionCirculating metabolites identified CRCLM patients at highest risk for 6 months disease recurrence after surgery. Our data also suggests that circulating metabolites might play a significant pathophysiological role in micro-metastatic growth and concomitant early tumor recurrences after liver resection. However, the clinical applicability and performance of this proposed metabolomic concept needs to be independently validated in future studies.     

Absence of association between CT-assessed skeletal muscle mass and long-term oncological outcomes after curative therapy for colorectal liver metastasis

BackgroundSarcopenia is associated with impaired short- and long-term outcomes in gastrointestinal cancers. Whether sarcopenia is associated with impaired survival after local therapy of Colorectal Cancer Liver Metastases (CRLM) remains controversial. This study aimed to determine the influence of sarcopenia on long-term outcomes after curative-intent therapy for CRLM.MethodsPatients undergoing local therapy for CRLM between 2003 and 2019 were retrospectively analyzed using the skeletal muscle index at the level of the third lumbar vertebra as an indicator of sarcopenia. Factors associated with overall (OS) and disease-free (DFS) survival were analyzed using univariable and multivariable cox regression.ResultsIn total 213/465 patients (46%) were considered sarcopenic. Sarcopenic patients had no impaired 5-year OS or DFS compared to non-sarcopenic patients, 38% vs 44% (p = 0.153) and 19 vs 23% (p = 0.339) respectively. Sarcopenia was not associated with impaired OS (HR = 1.11, 95%CI = 0.85–1.46, p = 0.43) or DFS (HR = 0.99, 95%CI = 0.77–1.28, p = 0.96) in multivariable analysis. There were no significant differences in postoperative complications (p = 0.47), the incidence (p = 0.65) and treatment (p = 0.37) of recurrent metastases. Five-year OS after resection for recurrences was 14% (sarcopenic) and 22% (non-sarcopenic) p 0.716.ConclusionSarcopenia assessed by computed tomography was not associated with impaired survival outcomes in the group of CRLM patients overall.     

Oncologic impact of preoperative prognostic nutritional index change in resected pancreatic cancer following neoadjuvant chemotherapy

BackgroundAlthough several studies have focused on the oncologic impact of the preoperative prognostic nutritional index (PNI), there is no study correlating the preoperative PNI changes with the oncologic outcome of resected pancreatic cancer following neoadjuvant chemotherapy (NAC).MethodsWe retrospectively analyzed 107 pancreatic ductal adenocarcinoma patients who underwent NAC followed by surgical resection. ΔPNI was defined as post-NAC PNI subtracted from pre-NAC PNI. Patients were divided into high (≥-1.94, n = 54) and low ΔPNI groups (<-1.94, n = 53). Long-term oncologic outcomes, such as overall survival (OS) and disease-free survival (DFS), were compared. Univariate and multivariate analysis were used to identify independent prognostic factors.ResultsThe high ΔPNI group correlated with lower pre-NAC PNI (46.96 ± 4.68 vs. 51.77 ± 5.63, p < 0.001) and higher post-NAC PNI (50.05 ± 4.80 vs. 42.56 ± 7.44, p < 0.001) more than the low ΔPNI group. The high ΔPNI group was also associated with longer OS compared with the low ΔPNI group (mean OS: 63.97 months [95% CI: 49.95–77.99] vs. 41.16 months [95% CI: 27.66–54.66], p = 0.003); there was no significant difference in DFS (p > 0.05). Multivariate analysis revealed that low ΔPNI was an independent risk factor for OS (HR, 3.516; 95% CI, 1.885–6.558; p < 0.001), but not for DFS (p > 0.05).ConclusionsLow ΔPNI (<-1.94) was an independent risk factor for the overall survival of resected pancreatic cancer patients following NAC. In the preoperative setting, improving the PNI can better the long-term oncologic outcome of this condition.     

Phase III randomized trial comparing systemic versus intra-arterial oxaliplatin,combined with LV5FU2 +/- irinotecan and a targeted therapy,in the first-line treatment of metastatic colorectal cancer restricted to the liver (OSCAR): PRODIGE 49

IntroductionIn patients with unresectable liver metastases from colorectal cancer (CRCLM), systemic doublet or triplet chemotherapy and targeted therapy is considered a standard first-line treatment. Hepatic arterial infusion of oxaliplatin (HAI-ox) generates a high response rate, but this still needs to be confirmed in a randomized trial. We incorporated HAI-ox in doublet or triplet + targeted therapy to validate its efficacy.AimThe OSCAR study is an ongoing randomized phase III trial comparing FOLFOX + targeted therapy according to RAS status, or FOLFOXIRI + bevacizumab in patients eligible for triplet therapy, with the same regimen but with HAI-ox instead of IV-ox as the first-line treatment for CRCLM.Materials and methodsMain eligibility criteria are colorectal cancer, unresectable liver metastasis, no extra-hepatic metastases except pulmonary nodules if ≤3 and <10 mm, ECOG performance status 0 or 1.EndpointThe primary endpoint is progression-free survival (PFS). A difference of 4 months for the median PFS in favor of HAI-ox is expected (HR = 0.73). Secondary endpoints include overall survival, overall response rate, secondary liver resection, safety, and quality of life.ConclusionThis study is planned to include 348 patients to demonstrate the superiority of HAI-ox over systemic oxaliplatin in first-line CRCLM treatment (NCT02885753).     

Radical antegrade modular pancreatosplenectomy enhances local control of the disease in patients with left-sided pancreatic cancer

BackgroundRadical antegrade modular pancreatosplenectomy (RAMPS) was developed to enhance curability in patients with left-sided pancreatic cancer. However, no evidence is available regarding the prognostic superiority of RAMPS compared with conventional distal pancreatectomy (cDP). Here, we aimed to assess the oncological benefit of RAMPS by comparing surgical outcomes between patients who underwent cDP and RAMPS with propensity score (PS) adjustment.MethodsClinical data of 174 patients undergoing cDP and RAMPS between 2009 and 2016 at two high-volume centers were analyzed with PS matching. Recurrence-free survival (RFS), overall survival (OS), and local recurrence rates were compared between patients who underwent cDP and RAMPS.ResultsThe cDP and RAMPS groups were successfully matched with baseline characteristics. No differences were found in the 3-year RFS and OS rates between the two groups (3-year RFS: cDP 46% vs RAMPS 40%, p = 0.451, 3-year OS: cDP 57% vs RAMPS 53%, p = 0.692). However, the 3-year local recurrence rate was lower in the RAMPS (10%) than that in the cDP group (34%) (hazard ratio 0.275, 95% confidence interval 0.090–0.842, p = 0.02).ConclusionRAMPS is oncologically superior to conventional procedure in achieving local control of the disease in patients with left-sided pancreatic cancer.     

Adjuvant therapy for margin positive pancreatic cancer: A propensity score matched analysis

BackgroundAdjuvant chemotherapy or chemoradiation is often recommended for resected pancreatic adenocarcinoma. We sought to examine the impact of these therapies on R1 resected pancreatic cancer.MethodsUtilizing the National Cancer Database we identified patients who underwent pancreatic resection for adenocarcinoma. Patients were stratified by resection status and adjuvant therapy.ResultsWe identified 28,440 patients who underwent pancreatic resection. Patients with tumor size >2 cm were more likely to undergo R1 resections, p < 0.001. Adjuvant therapy improved survival in all patients with median and 5-year survival: adjuvant chemotherapy (21.7 months, 17.45%), chemoradiation (23.3 months, 20.9%) vs no adjuvant therapy (19.5 months, 19.1%), p < 0.001. In the R1 resection cohort survival was also improved with adjuvant therapy with chemoradiation demonstrating the most significant improvement: adjuvant chemotherapy (15.9 months, 6.5%), chemoradiation (18.7 months, 11.2%) vs no adjuvant therapy (12.5 months, 8.7%), p < 0.001. Chemoradiation but not adjuvant chemotherapy improved survival in the R1 node negative, p < 0.004, and node positive, p < 0.001. Adjuvant chemotherapy benefited survival in R1 node positive patients, p < 0.001.ConclusionsPatients with pancreatic cancer who undergo R1 resection have significant improvement in survival when treated with adjuvant chemoradiation and adjuvant chemotherapy. However, benefits were greater in those receiving adjuvant chemoradiation.     

Systematic review and meta-analysis of survival outcomes in T2a and T2b gallbladder cancers

BackgroundThe 8th edition of AJCC TNM staging of Gallbladder cancer subdivided T2 stage into T2a and T2b based on tumour location. This meta-analysis aimed to investigate the long-term outcomes in T2a and T2b gallbladder cancers.MethodsLiterature search of Medline, Web of science, Embase and Cochrane databases was performed. Study characteristics, survival and recurrence data were extracted for meta-analysis of effect estimates and of individual patient data.ResultsFifteen retrospective studies (2531 patients, T2a = 1332, T2b = 199) were included in the meta-analysis. Overall survival (OS) was significantly worse in patients with T2b compared to T2a tumours (HR 2.18, 95% CI 1.67–2.86, p < 0.0001). Meta-analysis of individual patient data (n = 629) showed similar results (HR 1.92, 95% CI 1.43–2.58, p < 0.00001). Patients with T2b tumours had higher risk of recurrence compared to T2a (OR 3.19, 95% CI 1.40–7.28, p = 0.006) and were more likely to receive adjuvant chemotherapy (OR 1.76, 95% CI 1.12–2.84, p = 0.014). Liver resection improved OS in T2b tumours (HR 2.99, CI 1.73–5.16, p < 0.0001).ConclusionT2b gallbladder tumours have worse overall survival and increase risk of recurrence compared to T2a. Liver resection appears to improve OS in patients with T2b tumours. However, high quality multicenter data is required to confirm these results.