Locally advanced gallbladder cancer: Which patients benefit from resection?

Objectives

Patients with T3–4 gallbladder cancers (GBCs) often require extended surgical procedures, and up to 30% of patients have N2 metastases. This study investigated which patients with T3–4 GBC benefit from resection.

Methods

Consecutive patients (n = 78) with T3–4 GBC who underwent resection between 1990 and 2011 were analysed (38 before 2003, 40 in 2003–2011). Forty patients required common bile duct (CBD) resection, 10 pancreatoduodenectomy, 4 right colectomy and 2 gastric resection. Fifty-two (67%) patients had LN metastases, including 22 with N2 metastases.

Results

The in-hospital mortality rate was 8%, 11% before 2003 vs. 5% in 2003–2011. The morbidity rate (47%) remained stable during the study. Undergoing liver and pancreatic resection did not increase severe morbidity (0%) or mortality (10%). Sixty-seven (86%) patients had R0 resection. The 5-year survival rate was 17% (median follow-up, 65 months). Survival improved after 2002 (26% vs. 9%, p = 0.04). R1 patients had poor 3-year survival (0% vs. 32%, p = 0.001). N+ patients also had low survival (5-year survival, 10% vs. 32% in N0, p = 0.019), but N1 and N2 patients had similar outcomes. CBD resection and major hepatectomy did not worsen prognosis. Patients requiring pancreatoduodenectomy, gastric or colonic resection had 0% 3-year survival (p = 0.036 in multivariate analysis).

Conclusions

Resection of T3–4 GBC is worthwhile only if R0 surgery is achievable. Outcomes improved in most recent years. N2 metastases should not preclude surgery. Good results are possible even with CBD resection or major hepatectomy, while benefits from surgery are doubtful if pancreatoduodenectomy or other organ resection is needed.     

Lessons learnt from 1300 consecutive gallbladder cancer surgeries: Evolving role of peri-operative chemotherapy in the treatment paradigm

BackgroundLevel I evidence for multi-modality management of gallbladder cancers (GBC) is evolving.MethodsProspectively maintained operative GBC database of 1307 patients (year 2010–2019) was analysed to study the impact of peri-operative chemotherapy (PCT) on survival outcomes.Results1040 patients had pathologically confirmed GBC. Stage distribution showed: Stage I(85,8.2%), II(247,23.8%), III(460,44.2%), IV(248, 23.8%). PCT was used as follows: in stage II, 164 patients received adjuvant chemotherapy(ACT); in stage III, ACT was given to 444 patients, either operated upfront(244 patients) or after neoadjuvant chemotherapy (NACT)(216 patients); in stage IV, 32 patients (11 received NACT) underwent radical surgery followed by ACT and 216 patients had inoperable disease (77 received NACT) upon exploration. With a median follow-up of 30 months, the 3-year OS for stage I, II and III was 94.1%, 82.6% and 48.2% respectively. Corresponding DFS was 93.8%, 67.3% and 38.3%. Upon reassessment for surgery after NACT (n = 332), patients who underwent radical surgery (n = 235) had superior OS (p = 0.000) and DFS (p = 0.000) in comparison to those who had inoperable disease (n = 97). Amongst stage III and IV patients with operable disease (n = 492), those who were operated upfront (n = 238) had equivalent survival as those operated after NACT (n = 254). This was also confirmed by a 1:1 propensity matched analysis (118 patients each), matching for T and N stage.ConclusionThe role of peri-operative chemotherapy in management of GBC is evolving. While the role of NACT for locally advanced GBC is unsettled and merits testing prospectively, it helps in selection of patients with favourable disease biology for radical surgery.     

The effect of trans arterial chemoembolization in the management of intrahepatic cholangiocarcinoma. A systematic review and meta-analysis

BackgroundA comprehensive re-evaluation on the role of trans-arterial chemoembolization (TACE) in patients with intrahepatic cholangiocarcinoma.MethodsA thorough database searching was performed in PubMed, EMBASE, and the Cochrane Library. Eligible studies were restricted to comparative studies between TACE and non-TACE cohorts. RevMan5.3 software and Stata 13.0 software were used for statistical analyses. The primary endpoint of our study was long-term survival.ResultsA total of 11 studies with 2036 patients were finally identified. Pooled results revealed that patients receiving TACE had a significantly better overall survival (OS) versus those without TACE (P < 0.05). Subgroup analyses were performed according to different types of TACE. Prophylactic post-surgical TACE (PPTACE) was associated with a significantly better OS versus those without PPTACE (P < 0.05). Palliative TACE (PTACE) also achieved a significantly better OS compared with those with supportive treatment (ST) only (P < 0.00001). However, TACE had no impact on disease-free survival (P = 0.87) and was less effective than surgical resection (P = 0.003).ConclusionPPTACE has a remarkable impact on OS versus those with surgical resections only and should be regularly performed. Regarding patients with unresectable disease, apart from conventional ST, adjuvant PTACE is also recommended. Upcoming prospective randomized controlled trials are warranted for further validation.     

The role of extra-hepatic bile duct resection in patients with gallbladder carcinoma with peri-neural invasion: A ten-year experience in China

BackgroundPeri-neural invasion (PNI) in gallbladder carcinoma (GBC) has been demonstrated as a vital prognostic factor. However, whether PNI in patients with GBC can be regarded as a surgical indication of bile duct resection (BDR) remains controversial.MethodsGBC patients with pathologically-confirmed PNI between September 2010 and September 2020 were retrospectively reviewed. Comparative analyses were performed in patients with PNI according to the performance of BDR. SPSS 25.0 software and Graph pad PRISMA 7.0 software were used for statistical analyses.ResultsA total of 70 patients GBC patients with PNI were incorporated. The results of comparative analyses indicated that patients who received BDR were generally in a more advanced stage and often required a more extended radical cholecystectomy. Higher incidences of preoperative jaundice (48.6% vs 2.9%, P < 0.0001), major hepatectomy (25.7% vs 8.6%, P = 0.055), combined multi-visceral resections (48.6% vs 5.7%, P < 0.0001), combined major vascular reconstruction (22.9% vs 2.9%, P = 0.014), and a lower R0 rate (68.6% vs 88.6%, P = 0.039) were detected in patients who received BDR. Even after propensity score matching (PSM), BDR still had no significant survival advantage but only increased the length of postoperative stay and the frequency of postoperative morbidities.ConclusionBDR seemed to have no significant survival advantage in GBC patients with PNI and was only correlated with a longer postoperative hospital stay and a higher rate of morbidities. PNI should not be regarded as a surgical indication of BDR in patients with GBC.     

Validation of a supplementary condition of eighth AJCC staging system for stage II hepatocellular carcinoma

IntroductionThe eighth American Joint Committee on Cancer (AJCC) staging system was flawed regarding the prognosis of stage II hepatocellular carcinoma (HCC). The aims of this study were to reveal the defect and make updates.MethodsClinical and survival data of HCC patients from the Surveillance, Epidemiology, and End Results database were used. We re-classified stage II into T2aN0M0 (tumors >2 cm with vascular invasion) and T2bN0M0 (multiple tumors ≤5 cm). The Kaplan–Meier method and log-rank test were used to estimate differences in overall survival (OS). Three propensity score matching analyses without (PSM1) or with (PSM2 and PSM3) consideration of surgical treatment were performed. Cox regression was used to reveal risk factors.ResultsHCC patients identified as T1bN0M0, T2aN0M0, T2bN0M0, and T3N0M0 were recruited. OS in T2N0M0 was consistent with the eighth AJCC staging system after PSM1. T2bN0M0 had increased OS compared with T2aN0M0 after PSM2 (hazard ratio [HR] = 1.36; 95% confidence interval [CI] = 1.06–1.73; P = 0.0141) or PSM3 (HR = 1.18; 95%CI = 1.01–1.37; P = 0.0283). No survival benefit existed between T1bN0M0 and T2bN0M0 after PSM2 (HR = 0.92; 95%CI = 0.80–1.05; P = 0.2171) or PSM3 (HR = 0.92; 95%CI = 0.84–1.01; P = 0.0888). Compared with T2aN0M0, T3N0M0 had shorter OS after PSM2 (HR = 0.64; 95%CI = 0.50–0.82; P = 0.0003) or PSM3 (HR = 0.63; 95%CI = 0.54–0.73; P < 0.0001). Cox regression analysis revealed that surgical treatment was associated with better prognosis (HR = 0.3; 95%CI = 0.3–0.4; P < 0.001).ConclusionsThe current staging for T2N0M0 is imprecise because surgical treatment is not adequately evaluated and would be ineffective if the proportion of T2bN0M0 patients with surgical treatment was increased.     

Multicenter study of surgical and oncologic outcomes of extra-levator versus conventional abdominoperineal excision for lower rectal cancer

BackgroundThe surgical and oncological outcome of extra-levator abdominoperineal excision (ELAPE) procedure remains unclear in low rectal cancer.MethodsA total of 194 cases of rectal cancer patients underwent ELAPE or conventional abdominoperineal excision (APE) procedure were analyzed in four hospitals’ databases from January 2010 to December 2015. Clinicopathological data, overall survival (OS), disease free survival (DFS) and local recurrence free survival (LRFS) of patients were compared between two groups.ResultsThe operation time spent in perineal phase was significantly shorter in the ELAPE group than that in conventional APE procedure (P < 0.001). There were more specimens with excellent or good quality in ELAPE group compared to conventional APE group (P = 0.033). Patients whom underwent ELAPE procedures showed significantly better OS, DFS and LRFS than those underwent conventional APE procedures. Patients with preoperative stage cT3∼T4 (P = 0.033, P = 0.008, P = 0,033), cN+ (P = 0.002, P < 0.001, P = 0.006) and pathological stage III-IV (P = 0.023, P = 0.008, P = 0.016) were associated with significant benefits from ELAPE procedure in terms of OS, DFS and LRFS. DFS differed significantly between two groups of patients whom got preoperative chemoradiation therapy (P = 0.009) or postoperative chemotherapy (P = 0.029). For patients of pathological stage IIII-IV without preoperative chemoradiation, ELAPE procedures resulted in statistically better OS (P = 0.018) and DFS (P = 0.030). ELAPE procedure was an independent risk factor of OS, DFS and LRFS in multivariate analysis.ConclusionLow rectal cancer patients might benefit from ELAPE procedure on both surgical and oncological outcomes, especially in patients with relatively advanced tumors, inspite of the effects of pre-operative radio- and chemotherapy.     

Laparoscopic versus open distal gastrectomy for advanced gastric cancer: A meta-analysis of randomized controlled trials and high-quality nonrandomized comparative studies

BackgroundControversy persists about the effects of laparoscopic distal gastrectomy (LDG) versus open distal gastrectomy (ODG) on short-term surgical outcomes and long-term survival within the field of advanced gastric cancer (AGC).MethodsStudies published from January 1994 to February 2020 that compare LDG and ODG for AGC were identified. All randomized controlled trials (RCTs) were included. The selection of high-quality nonrandomized comparative studies (NRCTs) was based on a validated tool (Methodological Index for Nonrandomized Studies, MINORS). The short- and long-term outcomes of both procedures were compared.ResultsOverall, 30 studies were included in this meta-analysis, which comprised of 8 RCTs and 22 NRCTs involving 16,029 patients (7864 LDGs, 8165 ODGs). The recurrence, 3-year disease-free survival (DFS), 3-year overall survival (OS), and 5-year OS rates for LDG and ODG were comparable. LDG was associated with a lower postoperative complication rate (OR 0.79; P < 0.00001), lower estimated volume of blood loss (WMD -102.21 mL; P < 0.00001), shorter postoperative hospital stay (WMD -1.96 days; P < 0.0001), shorter time to first flatus (WMD -0.54 day; P = 0.0007) and shorter time to first liquid diet (WMD -0.66 day; P = 0.001). The number of lymph nodes retrieved, mortality, intraoperative complications, intraoperative blood transfusion, and time to ambulation were similar. However, LDG was associated with a longer surgical time (WMD 33.57 min; P < 0.00001).ConclusionsLDG with D2 lymphadenectomy is a safe and effective technique for patients with AGC when performed by experienced surgeons at high-volume specialized centers.     

Adjuvant interferon-α for the treatment of high-risk melanoma: An individual patient data meta-analysis

BackgroundMany randomised trials assessing interferon-α (IFN-α) as adjuvant therapy for high-risk malignant melanoma have been undertaken. To better assess the role of IFN-α, an individual patient data (IPD) meta-analysis of these trials was undertaken.MethodsIPD was sought from all randomised trials of adjuvant IFN-α versus no IFN-α for high-risk melanoma. Primary outcomes were event-free survival (EFS) and overall survival (OS). Standard methods for quantitative IPD meta-analysis were used. Subgroup analyses by dose, duration of treatment and various patient and disease-specific parameters were performed.FindingsFifteen trials were included in the analysis (eleven with IPD). EFS was significantly improved with IFN-α (hazard ratio [HR] = 0.86, CI 0.81–0.91; P < 0.00001), as was OS (HR = 0.90, CI 0.85–0.97; P = 0.003). The absolute differences in EFS at 5 and 10 years were 3.5% and 2.7%, and for OS were 3.0% and 2.8% respectively in favour of IFN-α. There was no evidence that the benefit of IFN-α differed depending on dose or duration of treatment, or by age, gender, site of primary tumour, disease stage, Breslow thickness, or presence of clinical nodes. Only for ulceration was there evidence of an interaction (test for heterogeneity: P = 0.04 for EFS; P = 0.002 for OS); only patients with ulcerated tumours appeared to obtain benefit from IFN-α.ConclusionThis meta-analysis provides clear evidence that adjuvant IFN-α significantly reduces the risk of relapse and improves survival and shows no benefit for higher doses compared to lower doses. The increased benefit in patients with ulcerated tumours, and lack of benefit in patients without ulceration, needs further investigation.     

Management of the positive pathologic circumferential resection margin in rectal cancer: A national cancer database (NCDB) study

BackgroundThe circumferential resection margin (CRM) is a primary predictor of local recurrence and survival in rectal cancer, and an important consideration in guiding treatment. CRM is usually predicted preoperatively, so optimal management of an unexpected pathologic positive CRM involvement is debatable. We aimed to investigate the postoperative management of T3N0 rectal cancers with a positive pathologic CRM, and the impact of each strategy on survival.MethodsThe NCDB was reviewed for pathological T3N0 rectal cancer cases from 2010 to 2015, that received neoadjuvant chemotherapy, had surgical resection with pathological clear margins, but a positive pathologic CRM(disease≤2 mm from radial margin). The main outcomes were the incidence, treatment modalities used, and impact of each modality on survival. Univariate analysis evaluated the demographic and provider characteristics across treatment groups. Kaplan-Meier and Cox regression analysis assessed survival and factors associated with overall survival (OS).ResultsOf 1607 cases with a positive CRM, 65% (1045) received no adjuvant treatment and 35% (n = 562) received adjuvant chemotherapy (AC). After matching, the 1-, 3-, and 5-year OS rates were 98.5%, 88.6% and 76.6% for AC and 96.9%, 84.6% and 68.4% for with no treatment (p = .027). Factors independently associated with improved OS were treatment at an academic/research facility (p = .009), minimally invasive approach (p = .005), well and moderately differentiated tumor (p < .001), absence of perineural invasion (p = .015) and AC administration (p = .047).ConclusionIn T3N0 rectal cancers resected with local clear margins but a positive pathologic CRM, AC improved OS. However, only a third received this option. Further study is needed to investigate the disparities in AC use in these patients with unexpected pathologic results.     

Long-Term Outcomes After Sublobar Resection Versus Lobectomy in Patients With Clinical Stage IA Lung Adenocarcinoma Meeting the Node-Negative Criteria Defined by High-Resolution Computed Tomography and [18F]-Fluoro-2-Deoxy-d-Glucose Positron Emission Tomography

PurposeTo evaluate long-term outcomes after sublobar resection for patients with clinical stage IA lung adenocarcinoma who met our proposed node-negative (N0) criteria, namely solid component size < 0.8 cm on high-resolution computed tomography (HRCT) or a maximum standardized uptake value (SUV_max) of < 1.5 on [¹⁸F]-fluoro-2-deoxy-d-glucose positron emission tomography/computed tomography (FDG-PET/CT).Patients and MethodsBetween April 2006 and December 2010, a total of 347 patients with clinical stage IA lung adenocarcinoma underwent complete resection in two medical centers. Long-term outcomes of patients with disease that met the N0 criteria after sublobar resection were evaluated.ResultsThe disease of 201 patients (57.9%) met the N0 criteria. Meeting N0 criteria was significantly associated with low-grade adenocarcinoma subtype (P < .001) and absence of lymphatic invasion (P < .001), vascular invasion (P < .001), and pleural invasion (P < .001). One patient (0.5%) had lymph node metastasis. The median follow-up period was 86.1 months. There was a significant difference in the overall survival (OS) rates between patients with disease that met the N0 criteria (5-year OS, 93.9%; 10-year OS, 90.3%) and disease that did not (5-year OS, 81.5%; 10-year OS, 64.3%; P < .001). Among patients with disease that met the N0 criteria, there was no significant difference in the OS between those who underwent lobectomy (5-year OS, 94.3%; 10-year OS, 92.6%) and those who underwent sublobar resection (5-year OS, 93.8%; 10-year OS, 89.3%; P = .64).ConclusionsSublobar resection of clinical stage IA lung adenocarcinoma is feasible in selected patients with disease that meets the N0 criteria, with excellent long-term survival.     

Hepatic resection prolongs overall survival in the selected patients with nasopharyngeal carcinoma liver metastases

BackgroundThe role of surgery in nasopharyngeal carcinoma liver metastases (NCLM) remains elusive, and the current application is limited. We aim to investigate whether hepatic resection (HR) of NCLM improves survival compared with non-hepatic resection (NHR) treatment.MethodsOne hundred and thirty-three patients with NCLM from 2007 to 2017 were divided into two groups. Propensity score matching (PSM) analysis was used to compare the clinical outcomes.ResultsAfter PSM the median overall survival (OS) and the 1, 3 and 5-year OS rates in HR group were 32.60 months, 86.2%, 37.3% and 37.3%, respectively; while for NHR group these values were 19.57 months, 61.5%, 12.9% and 2.9%, respectively (P = 0.008). Multivariate analysis indicated hepatitis B virus infection (P = 0.029) and hepatic resection (P = 0.018) were independent prognostic factors.ConclusionOur study revealed that hepatectomy yields a survival benefit safely compared with systemic treatments, especially for patients with the size of largest metastasis < 5 cm, unilobar distribution of liver tumor and received unanatomical hepatectomy.     

Mediastinal Up-Staging During Surgery in Non–Small-Cell Lung Cancer: Which Mediastinal Lymph Node Metastasis Patterns Better Predict The Outcome? A Multicenter Analysis

BackgroundUnexpected N2 involvement occurs in approximately 10% to 20% of patients with non–small-cell lung cancer (NSCLC) and patients’ prognostic factors remain unclear. The aim of this study was to evaluate prognostic factors in these patients.MethodsFrom January 2002 to December 2012, we retrospectively analyzed data of 550 patients with NSCLC with preoperative negative, but pathologic positive N2 involvement, who underwent anatomical lung resection and hilo-mediastinal lymphadenectomy, obtained from 6 institutions. An established prognostic factor panel and N2-type involvement were correlated to overall (OS), cancer-specific (CSS), and disease-free survival (DFS) using multivariate Cox Regression model. The following lymph node patterns were analyzed: number of resected nodes (#RNs), metastatic nodes (#MNs), ratio between #MNs and #RNs (NR), N2 subgroups proposed for the eighth TNM edition, and lobe-specific versus nonspecific metastasis.ResultsRegarding our cohort, 419 patients were staged IIIA (T1-2N2), 131 IIIB (T3-4 N2), 113 pT1, 306 pT2, 94 pT3, and 37 pT4; 5-year OS, DFS, and CSS were 34.1%, 20.1%, and 64.6%, respectively. Independent prognostic factor for OS, in the multivariable analysis, were as follows: NR <17% (P = .009), proposed N2 classification subgroups (P = .014), age <66 (P < .001), and pT (P = .005); for DFS: NR <17% (P = .003), adjuvant treatment (P = .026), and pT (P = .026); and for CSS: NR <17% (P = .008), grading (P = .001), and adjuvant treatment (P < .001).ConclusionOur study confirms that adjuvant therapy is fundamental and NR, in patients with unexpected N2 involvement, has a strong prognostic factor. In particular, a NR cutoff value of 17% could predict OS, DFS, and CSS in patients with NSCLC.     

Recurrent retroperitoneal sarcomas: Clinical outcomes of surgical treatment and prognostic factors

Background and purposeLocoregional recurrence after resection of primary retroperitoneal sarcoma (RPS) is a challenging therapeutic issue. The objective of this study was to identify clinicopathological factors predictive of overall survival (OS) and disease specific survival (DSS) after reoperation for recurrent RPS.Patients and methodsWe retrospectively collected data from the medical records of 800 patients who underwent resection for sarcoma at our Institution, from 1983 to 2015. Among these patients, 120 were treated for retroperitoneal sarcoma and 55 had a locoregional recurrence (LR). Four of them did not undergo surgery and thus were excluded from this study leaving 51 cases available for data analysis. Univariate and multivariate survival analyses were performed to identify prognostic factors.ResultsMedian overall survival was 33 months. The 1-year, 3-year and 5-year OS rates were 75.5%, 47.1% and 31.6% respectively. Multivariate Cox regression analysis suggested that extension of surgery (P = 0.026), surgical margin status (P = 0.015) and histological grade of recurrent tumor (P = 0.047) were independent prognostic factors for OS. Median DSS was 48 months. The 1-year, 3-year and 5-year DSS rates were 79.2%, 53.1% and 40.9%, respectively. At multivariate analysis, predictors of DSS were extension of surgery (P = 0.004), margin status (P = 0.011), histological grade of recurrent tumor (P = 0.008), and disease free interval (DFI) (P = 0.020). As regards histological subtype of recurrent RPS, at univariate analysis, well-differentiated liposarcoma (WDLS) was associated with better OS and DSS (P = 0.052 and P = 0.016 respectively) compared to dedifferentiated liposarcoma (DDLS).ConclusionsAccording to our findings, surgery is more beneficial in patients with low-grade sarcoma, WDLS and long DFI. The achievement of clear resection margins, rather than performing a multivisceral resection, appears to be a key factor to improve OS and DSS.     

Prognostic value of disease-free interval in colorectal cancer: Is it time?

BackgroundPrevious studies have outlined that the onset of synchronous colorectal cancer (CRC) metastases is associated with poor overall survival (OS) compared to patients with metachronous disease. The aim of this study was to evaluate the association of disease-free interval with newly diagnosed CRC scheduled for primary tumor resection.MethodsPatients who underwent primary CRC resection over an 18-year period were identified from a prospective database at a tertiary-care hospital. In this observational study, the cohort was stratified for the onset of metastases, i.e. synchronous, early-onset and late-onset metachronous disease. The OS was compared using Kaplan-Meier estimators and stratified Cox hazard regression analysis.ResultsOf 360 patients, 204 (57%) had synchronous, 61 (17%) had early metachronous, and 95 (26%) had late metachronous metastases, respectively. The onset of synchronous metastases was not associated with worse OS compared to early and late metachronous disease. ASA level > II (P = 0.011), right-sided compared to left-sided cancer (P = 0.032) or rectal cancer (P < 0.001), and high-grade tumors (P = 0.022) were identified as independent predictors of poor OS, whereas the only favorable prognostic factor was surgical resection of metastases (P = 0.047). Additionally, ASA level < III (P = 0.003) and low-grade tumors (P = 0.032) were found to predict resection of metastases.ConclusionIndividual patients' and tumor characteristics rather than the timing of metastases are associated with OS in newly diagnosed CRC. These data support curative treatment strategies even in patients with synchronous metastases.     

Treatment strategies and outcomes of primary Myxofibrosarcomas in a large patients cohort

Backgroundthis study analysed primary myxofibrosarcoma (MFS) to investigate patient outcomes focusing on histopathologic margins and perioperative treatments.Patients and methodsdata from consecutive patients affected by primary and localized MFS of the extremities or trunk wall who underwent surgery (2002–2017) were analysed. Local recurrence (LR), amputation rate, incidence of distant metastasis (DM), and overall survival (OS) were studied.ResultsOf 293 included patients, 52 (17%) patients received perioperative treatments and 54 (18%) had positive microscopic histopathologic margins (R1). Median follow-up was 80 months (IQR, 49–109). 5-yr CCI of LR was 0.12 (SE: 0.02). Status of histopathologic margins (P < 0.001), tumour malignancy grade (P = 0.018) and size (P = 0023) were independent prognostic factor for LR. Nine amputations (amputation rate: 3%) were performed (N = 1 for primary tumour; N = 8 for LR). Larger tumour size (P = 0.015) and higher grade (P = 0.025) were independent prognostic factor for DM. 5-year OS was 0.84 (95%CI 0.79–0.88). Patient age (P = 0.008), tumour size (P = 0.013) and malignancy grade (P = 0.018) were independently associated to OS. In the subgroup of patients who had a re-excision for a primary MFS (N = 116, 40%), the presence of residual disease was not associated with LR, DM, or OS.Conclusionin this study 5-year LR, DM and OS were 12%, 17%, and 84%, respectively. One in six patients had a positive surgical margin, which was a prognostic factor for LR, while DM and OS were predicted by tumour grade and size. Findings from this large patient cohort may set benchmarks for investigating new treatment options for MFS.     

Hepatectomy for ruptured hepatocellular carcinoma classified as Barcelona Clinic Liver Cancer stage 0/A: The optimal treatment

Background and aimsRuptured hepatocellular carcinoma (rHCC) generally has a very poor prognosis and is currently classified as T4 in the tumor–node–metastasis (TNM) staging system. In this study, we aimed to demonstrate the actual impact of rHCC, as well as the positive effect of hepatectomy in patients with Barcelona Clinic Liver Cancer (BCLC) stage 0/A rHCC.MethodsWe enrolled 86 patients with rHCC after surgery and 526 patients with non-rHCC after surgery or transcatheter arterial chemoembolization (TACE). Survival curves were plotted using the Kaplan–Meier method to compare the postoperative prognosis of patients with rHCC with that of patients with non-rHCC. Univariate and multivariate Cox regression analyses were used to identify the risk factors affecting patient survival.ResultsBCLC stage 0/A rHCC treated with surgery had a worse prognosis than BCLC stage 0/A non-rHCC treated with surgery (overall survival [OS]: hazard ratio [HR] = 3.12 [2.24–4.34], P < 0.001; recurrence-free survival [RFS]: HR = 2.26 [1.65–3.09], P < 0.001). Rupture was an independent prognostic factor in patients with BCLC stage 0/A rHCC (OS: HR = 1.685 [1.416–2.006], P < 0.001; RFS: HR = 1.484 [1.267–1.737], P < 0.001), and patients with BCLC stage 0/A rHCC who underwent surgery had a comparable prognosis to patients with BCLC stage B HCC who underwent surgery or TACE (OS: P = 0.78).ConclusionsPatients classified as having BCLC stage 0/A rHCC can achieve comparable outcomes to patients with BCLC stage B HCC after hepatectomy. However, not all patients with rHCC should be classified as T4 in the TNM staging system.     

Neoadjuvant chemotherapy followed by concurrent chemoradiotherapy versus concurrent chemoradiotherapy alone in locoregionally advanced nasopharyngeal carcinoma: A phase III multicentre randomised controlled trial

BackgroundThe role of neoadjuvant chemotherapy (NACT) for locoregionally advanced nasopharyngeal carcinoma (NPC) is unclear. We aimed to evaluate the feasibility and efficacy of NACT followed by concurrent chemoradiotherapy (CCRT) versus CCRT alone in locoregionally advanced NPC.MethodsPatients with stage III–IVB (excluding T3N0-1) NPC were randomly assigned to receive NACT followed by CCRT (investigational arm) or CCRT alone (control arm). Both arms were treated with 80 mg/m² cisplatin every 3 weeks concurrently with radiotherapy. The investigational arm received cisplatin (80 mg/m² d1) and fluorouracil (800 mg/m² civ d1–5) every 3 weeks for two cycles before CCRT. The primary end-point was disease-free survival (DFS) and distant metastasis-free survival (DMFS). Secondary end-point was overall survival (OS). Survival curves for the time-to-event endpoints were analyzed by the Kaplan–Meier method and compared using the log-rank test. The P value was calculated using the 5-year endpoints.ResultsFour hundred seventy six patients were randomly assigned to the investigational (n = 238) and control arms (n = 238). The investigational arm achieved higher 3-year DFS rate (82.0%, 95% CI = 0.77–0.87) than the control arm (74.1%, 95% CI = 0.68–0.80, P = 0.028). The 3-year DMFS rate was 86.0% for the investigational arm versus 82.0% for the control arm, with marginal statistical significance (P = 0.056). However, there were no statistically significant differences in OS or locoregional relapse-free survival (LRRFS) rates between two arms (OS: 88.2% versus 88.5%, P = 0.815; LRRFS: 94.3% versus 90.8%, P = 0.430). The most common grade 3–4 toxicity during NACT was neutropenia (16.0%). During CCRT, the investigational arm experienced statistically significantly more grade 3–4 toxicities (P < 0.001).ConclusionNACT improved tumour control compared with CCRT alone in locoregionally advanced NPC, particularly at distant sites. However, there was no early gain in OS. Longer follow-up is needed to determine the eventual therapeutic efficacy.     

Determining the role of adjuvant therapy in Invasive Intraductal Papillary Mucinous Neoplasms; a systematic review and meta-analysis

BackgroundConflicting evidence exists regarding the role of adjuvant therapy for Invasive Intraductal Papillary Mucinous Neoplasms (i-IPMN). This meta-analysis assessed whether adjuvant therapy improves Overall Survival (OS) in patients with resected i-IPMN.MethodsA systematic review and meta-analysis was performed. The primary endpoint was the effect of adjuvant therapy on OS. Secondary endpoint evaluated adjuvant therapy with regard to nodal disease, positive resection margins, tumour grade and differentiation. A meta-analysis of pooled hazard ratios (HRs) with an inverse variance and a random-effects model was performed. Risk of bias was determined with the GRADE approach and MINORS criteria.ResultsTen articles with a total of 3252 patients were included. No statistically significant difference in the OS was noted with adjuvant therapy for i-IPMN in the entire cohort (HR = 1; 95% CI = 0.75–1.35; P = 0.98). However, a survival benefit was noted in a subgroup of patients with an aggressive disease phenotype; nodal involvement (HR = 0.56; 95% CI = 0.39–0.79; P = 0.001) and advanced staged tumours (≥stage 2, HR = 1.42; 95% CI = 1.11–1.82; P = 0.005)ConclusionsThe concurrent evidence base for adjuvant therapy for i-IPMN is limited. After acknowledging the limitations of the data, the current literature suggests that adjuvant therapy should be reserved for patients with resected i-IPMN that have adverse tumour biology.     

Safety and Efficacy of Reproductive Organ-Sparing Radical Cystectomy in Women With Variant Histology and Advanced Stage

PurposeMuscle invasive bladder cancer surgical management has been historically a radical cystoprostatectomy in males and an anterior exenteration in females. Uterine, ovarian, and vaginal preservation are utilized, but raise concerns regarding risk to oncologic control, especially in variant histopathology or advanced stage.Materials and MethodsA retrospective single institutional analysis identified radical cystectomies performed in women, including those with variant histology, which were defined as reproductive organ sparing (uterine, vaginal, and ovary sparing) or nonorgan sparing. The Kaplan-Meier method was used for recurrence-free survival (RFS), cancer-specific survival (CSS), and overall survival (OS) in patients with advanced disease.ResultsFrom 2000 to 2020, 289 women were identified, 188 underwent reproductive organ-sparing cystectomy. No statistical differences were noted for clinical parameters or presence of variant histology for organ-sparing (ROS) and nonorgan-sparing (non-ROS). Positive margin rates did not differ for ROS and non-ROS; 4.3% vs. 7.9%, P = .19, respectively. Median RFS was not statistically significantly different for ROS vs. non-ROS (26.1 vs. 15.3 months) P = .937 hazard ratio (HR) 1.024. CSS was not statistically different for ROS vs. non-ROS (36.3 vs. 28.6 months), P = .755 HR 0.9. OS was not statistically different for ROS vs. non-ROS (25.8 vs. 23.8 months), P = .5 HR = 1.178. Variant histology did not change survival (HR 1.1, P = .643).ConclusionIn this analysis, ROS in women with advanced disease did not increase positive margin rates or decrease RFS, CSS, or OS compared to non-ROS. Variant histology did not decrease survival odds. Based on preoperative assessment and intraoperative findings, ROS in patients with variant histology and advanced disease should be considered.     

Radical versus partial nephrectomy for T1 non-clear cell renal cell carcinoma

IntroductionNephron-sparing surgery is the recommended surgical management of T1 renal cell carcinoma (RCC). However, non-clear cell RCC (nccRCC) is heterogeneous and included many histological types. Therefore, the present study was performed to compare radical nephrectomy (RN) versus partial nephrectomy (PN) in nccRCC.Materials and methodsWithin the Surveillance, Epidemiology, and End Results registry (2000–2019), the patients with nccRCC were identified. Kaplan-Meier survival curve and the log-rank test were conducted. Univariate analysis and multivariate Cox regression analysis were performed to explore the prognostic factors.ResultsA total of 7575 patients with nccRCC were included, of which papillary RCC (n = 5219) is the major histology. Kaplan-Meier plots and log-rank tests showed that nccRCC patients who underwent RN had significantly worse overall survival (OS) and cancer-specific survival (CSS) than those who received PN (all P < 0.05). Multivariate analysis also revealed that RN was significantly associated with poor OS and CSS in nccRCC patients. Stratified by histological types, the multivariate analysis also revealed that RN was significantly associated with poor OS in papillary and chromophobe (all P < 0.05). Besides, the multivariable analysis indicated that RN was associated with poor CSS in papillary RCC (P < 0.05). For other histology, the patients who received RN had a comparable survival to those who received PN.ConclusionFor patients with T1 nccRCC, our findings revealed that PN was not inferior to RN in OS and CSS. PN may be also the preferred option for T1 nccRCC, but more prospective studies are required to validate this finding.