Evaluation of dual-energy CT derived radiomics signatures in predicting outcomes in patients with advanced gastric cancer after neoadjuvant chemotherapy

BackgroundTo investigate the prognostic value of dual-energy CT (DECT) based radiomics to predict disease-free survival (DFS) and overall survival (OS) for patients with advanced gastric cancer (AGC) after neoadjuvant chemotherapy (NAC).MethodsFrom January 2014 to December 2018, a total of 156 AGC patients were enrolled and randomly allocated into a training cohort and a testing cohort at a ratio of 2:1. Volume of interest of primary tumor was delineated on eight image series. Four feature sets derived from pre-NAC and delta radiomics were generated for each survival arm. Random survival forest was used for generating the optimal radiomics signature (RS). Statistical metrics for model evaluation included Harrell's concordance index (C-index) and the average cumulative/dynamic AUC throughout follow-up. A clinical model and a combined Rad-clinical model were built for comparison.ResultsThe pre-IU (derived from iodine uptake images before NAC) RS performed best for DFS and OS in the testing cohort (C-indices, 0.784 and 0.698; the average cumulative/dynamic AUCs, 0.80 and 0.77). When compared with the clinical model, the radiomics model had significantly higher C-index to predict DFS in the testing cohort (0.784 vs. 0.635, p < 0.001), but no statistical difference was found for OS (0.698 vs. 0.680, p = 0.473). The combined Rad-clinical models showed improved performance in the testing cohort, with C-indices of 0.810 and 0.710 for DFS and OS, respectively.ConclusionDECT-derived radiomics serves as a promising non-invasive biomarker to predict survival for AGC patients after NAC, providing an opportunity for transforming proper treatment.     

Advantages of preoperative localization and surgical resection of metastatic axillary lymph nodes using magnetic seeds after neoadjuvant chemotherapy in breast cancer

PurposeTo assess the safety and effectiveness of magnetic seeds in preoperative localization and surgical dissection of metastatic axillary lymph nodes (LN+) in breast cancer patients with axillary involvement, after neoadjuvant chemotherapy (NAC). In addition, to assess the impact of targeted axillary dissection (TAD) in reducing the rate of false negatives (FN) in sentinel lymph node biopsy (SLNB).Materials and MethodsA cross-sectional prospective cohort study was conducted from April 2017 to September 2019, including breast cancer patients with axillary lymph node involvement treated with NAC. Prior to NAC, the LN+ were marked by ultrasound-guided clip insertion. After NAC, a magnetic seed (Magseed®) was inserted in the clip-marked lymph node (MLN). During surgery, the MLN was located and removed with the aid of a magnetic detection probe (Sentimag®) and the sentinel lymph node was removed. Axillary lymph node dissection (ALND) was used to determine the rate of FN for SLNB alone and the combination of SLNB and MLN dissection, called TAD.ResultsThe study included 29 patients (mean age, 55; range, 30–78 years). Selective preoperative localization and surgical dissection were successful for all 30 MLNs (100%). The MLN corresponded to the SLN in 50% of cases. After ALND, there were 21.4% (3/14) FN with SLNB alone and 5.9% (1/17) with TAD.ConclusionsFollowing NAC, selective surgical removal of MLN by preoperative localization using magnetic seeds is a safe and effective procedure with a success rate of 100%. Adding TAD reduces the rate of FN associated with SLNB alone.     

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.     

Factors associated with sentinel lymph node status and prognostic role of completion lymph node dissection for thick melanoma

IntroductionSentinel lymph node (SLN) biopsy is useful for the prognostic stratification of patients with thick melanoma. Identifying which variables are associated with SLN involvement and establishing risk in different subgroups of patients could be useful for guiding the indication of SLN biopsy. The value of complete lymph node dissection (CLND) in patients with a positive SLN biopsy is currently under debate.Materials and methodsTo identify factors associated with SLN involvement in thick melanoma we performed a multicentric retrospective cohort study involving 660 patients with thick melanoma who had undergone SLN biopsy. To analyze the role of CLND in thick melanoma patients with a positive SLN biopsy, we built a multivariate Cox proportional hazards model for melanoma-specific survival (MSS) and disease-free survival (DFS) and compared 217 patients who had undergone CLND with 44 who had not.ResultsThe logistic regression analysis showed that age, histologic subtype, ulceration, microscopic satellitosis, and lymphovascular invasion were associated with nodal disease. The CHAID (Chi-squared Automatic Interaction Detection) decision tree showed ulceration to be the most important predictor of lymphatic involvement. For nonulcerated melanomas, the histologic subtype lentigo maligna melanoma was associated with a low rate of SLN involvement (4.3%). No significant differences were observed for DFS and MSS between the CLND performed and not-performed groups. Nodal status on CLND was associated with differences in DFS and MSS rates.ConclusionWe identified subgroups of thick melanoma patients with a low likelihood of SLN involvement. CLND does not offer survival benefit, but provides prognostic information.     

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.     

Laparoscopic approach for T4 colon cancer can be associated with poor prognosis in right-sided T4b tumours

IntroductionAlthough recent studies have demonstrated the safety of laparoscopic surgery in T4 colon cancer, some patients could have poor prognosis. In this study, we aimed to analyse the risk factors affecting oncologic outcome of laparoscopic surgery.Materials and methodsAmong the 1033 T4 colon cancer patients collected from a multicentre database (2004–2017), 584 patients (458 T4a and 126 T4b) underwent laparoscopic approach for radical surgery. Risk factors associated with 3-year disease-free survival (DFS) and overall survival (OS) were evaluated through multivariate analysis. In addition, subgroups were classified using a combination of risk factors, and the survival rate was evaluated.ResultsDuring this period, 188 (32.2%) had recurrence, and 151 (25.9%) died. In the multivariate analysis for oncologic outcome, elevated carcinoembryonic antigen level (hazard ratio [HR] 1.37) and absence of adjuvant chemotherapy (HR 1.60) were associated with poor DFS. T4b (HR 1.56, 1.46), right-sided location (HR 1.52, 1.42), and open conversion (HR 2.70, 2.12) were independently associated with both poor DFS and OS. When four subgroups were analysed through the combination of tumour location and T stage, the DFS and OS rates were significantly lower in patients with right-sided T4b cancer than in other groups (log-rank p < 0.001).ConclusionRight-sided T4b colon cancer for laparoscopic surgery may lead to poor oncologic outcome. This approach could be a caution in suspected cases preoperatively.     

Lymph node yield in the pathological staging of resected nonmetastatic colon cancer: The more the better?

IntroductionGuidelines recommend regional lymphadenectomy with a lymph node yield (LNY) of at least 12 lymph nodes (LN) for adequate colon cancer (CC) staging. LNY ≥22LN may improve survival, especially in right-sided CC [Lee et al., Surg Oncol, 27(3), 2018]. This multicentric retrospective cohort study evaluated the impact of LNY and tumor laterality on CC staging and survival.Materials and methodsPatients with stage I-III CC that underwent surgery from 2012 to 2018 were grouped according to LNY: <22 and ≥ 22. Primary outcomes were LN positivity (N+ rate) and disease-free survival (DFS). Overall survival (OS) was the secondary outcome. Exploratory analyses were performed for laterality and stage.ResultsWe included 795 patients (417 < 22LN, 378 ≥ 22LN); 53% had left-sided CC and 29%/37%/38% had stage I/II/III tumors. There was no association between LNY ≥22LN and N+ rate after adjustment for grade, T stage, lymphovascular invasion (LVI) and perineural invasion; a trend for a higher N+ rate in left-sided CC was identified (interaction p = 0.033). With a median follow-up of 63.6 months for DFS and 73.2 months for OS, 254 patients (31.9%) relapsed and 207 (26.0%) died. In multivariate analysis adjusted for age, ASA score, laparoscopic approach, T/N stage, mucinous histology, LVI and adjuvant chemotherapy, LNY ≥22LN was significantly associated with both DFS (HR 0.75, p = 0.031) and OS (HR 0.71, p = 0.025). Restricted cubic spline analysis showed a more significant benefit for right-sided CC.ConclusionLNY ≥22LN was associated with longer DFS and OS in patients with operable CC, especially for right-sided CC.     

Sentinel lymph node procedure in early-stage vulvar cancer: Correlation of lymphoscintigraphy with surgical outcome and groin recurrence

IntroductionIn early-stage vulvar squamous cell carcinoma (VSCC) a sentinel lymph node (SLN) procedure is regarded successful if at least one SLN is removed with minimal residual radioactivity. An inguinofemoral lymphadenectomy is considered if not all SLNs visualized on lymphoscintigraphy can be found, with subsequent increased morbidity. We correlated lymphoscintigraphy findings with surgical outcome and groin recurrence with focus on number of SLNs found.MethodsThis study concerns a retrospective cohort of 171 women treated for early-stage VSCC who underwent a SLN procedure between 2000 and 2020. The risk of groin recurrence was compared after either a successful or complete SLN procedure, i.e. removal of all SLNs that were visualized on lymphoscintigraphy.ResultsIn 13 (7.6%) groins of 171 patients SLN visualization on lymphoscintigraphy failed. In 230 of the 246 (93.5%) groins in which a SLN was visualized, at least one SLN was found during surgery. In 224 of the 246 (91.1%) groins the SLN procedure was regarded either successful (n = 14) or complete (n = 210). An isolated groin recurrence was documented in 5 out of 192 (2.6%, 95%-CI; 0.34 to 4.9) SLN-negative groins after a median follow-up of 47.0 months. All recurrences were noted in the complete SLN group (5/180 groins). The difference with the successful SLN group (0/12 groins) was not significant.ConclusionRisk of groin recurrence was 2.6% after SLN negative biopsy in early-stage VSCC. The risk appeared not increased if at least one SLN was found with minimal residual radioactivity, in case more SLNs were visualized on lymphoscintigraphy.     

Comparison of long term survival outcomes between D1+ and D2 lymph node dissection for ≥ pT2 or pN+ gastric carcinoma: A large scale case-control study using propensity score matching

BackgroundD2 lymph node dissection (LND) is a widely performed as a standard procedure for advanced gastric cancer (AGC). However, there is little evidence supporting D2 over D1+ LND for gastric cancer treatment. This study compared the long-term outcomes of D2 and D1+ LND for AGC.MethodsWe retrospectively reviewed data on 1121 patients who underwent curative distal gastrectomy and had pathologic stage of ≥ pT2 or pN+. The patients were categorized into the D1+ and D2 LND groups, and long-term survival was compared in the original and propensity score matching (PSM) cohorts.ResultsOverall, 909 and 212 patients underwent D2 and D1+ LND, respectively. The D2 group showed more advanced stage and more frequently underwent open surgery. Postoperative morbidity was significantly higher in the D2 group (19.5% vs. 13.2%, p = 0.034); however, mortality or ≥ grade III complications did not significantly differ between the groups. The 5-year overall survival (OS) and disease-free survival (DFS) did not significantly differ between D2 and D1+ groups at the same stage. Multivariate analysis of prognostic factors revealed that the extent of LND did not significantly affect survival, after adjusting for tumor stage and other clinicopathological factors. In the PSM cohort, the D2 and D1 groups showed no significant difference in OS (p = 0.488) and DFS (p = 0.705).ConclusionsLong-term survival with D1+ LND was comparable to that with D2 LND for ≥ pT2 or pN + gastric carcinoma. A large randomized trial is warranted to validate the optimal extent of LND for gastric carcinoma.     

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 hiatal hernia in esophageal adenocarcinoma; does it have an impact on patient outcomes?

BackgroundThe impact of hiatal hernia (HH) on oncologic outcomes of patients with esophageal adenocarcinoma (AC) remains unclear. The aim of this study was to assess the effect of pre-existing HH (≥3 cm) on histologic response after neoadjuvant treatment (NAT), overall (OS) and disease-free survival (DFS).MethodsAll consecutive patients with oncological esophagectomy for AC from 2012 to 2018 in our center were eligible for assessment. Categorical variables were compared with the X² or Fisher's test, continuous ones with the Mann-Whitney-U test, and survival with the Kaplan-Meier and log-rank test.ResultsOverall, 101 patients were included; 33 (32.7%) had a pre-existing HH. There were no baseline differences between HH and non-HH patients. NAT was used in 81.8% HH and 80.9% non-HH patients (p = 0.910), most often chemoradiation (63.6% and 57.4% respectively, p = 0.423). Good response to NAT (TRG 1–2) was observed in 36.4% of HH versus 32.4% of non-HH patients (p = 0.297), whereas R0 resection was achieved in 90.9% versus 94.1% respectively (p = 0.551). Three-year OS was comparable for the two groups (52.4% in HH, 56.5% in non-HH patients, p = 0.765), as was 3-year DFS (32.7% for HH versus 45.6% for non-HH patients, p = 0.283).ConclusionHH ≥ 3 cm are common in patients with esophageal AC, concerning 32.7% of all patients in this series. However, its presence was neither associated with more advanced disease upon diagnosis, worse response to NAT, nor overall and disease-free survival. Therefore, such HH should not be considered as risk factor that negatively affects oncological outcome after multimodal treatment of esophageal AC.     

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.     

The absence of benefit of perioperative chemotherapy in initially resectable peritoneal metastases of colorectal cancer origin treated with complete cytoreductive surgery and hyperthermic intraperitoneal chemotherapy: A retrospective analysis

IntroductionThe aim of this study was to compare the outcome of patients with peritoneal metastasis (PM) of colorectal origin treated with complete cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) with or without perioperative systemic chemotherapy (PCT+/PCT-).Patients and methodsRetrospective analysis of 125 patients treated with complete CRS (R0/R1) and HIPEC for PM from colorectal origin in two Belgian academic centers between 2008 and 2017. Disease-free survival (DFS) and overall survival (OS) were assessed with regard to PCT. Statistical analyses were adjusted for non-balanced survival risk factors.ResultsThe PCT+ group (n = 67) received at least 5 cycles of PCT and the PCT-group (n = 56) did not receive PCT. The groups were well balanced for all prognostic factors except presentation of synchronous disease (more in PCT+). Survival analysis was adjusted to peritoneal cancer index and presentation of synchronous disease. After a median follow-up of 54±5-months, the 1, 3, 5-years OS in the PCT+ group were 98%, 59% and 35% compared to 97%, 77% and 56% in the PCT-group (HR = 1.46; 95% CI:0.87–2.47; p = 0.155). The 1,3 and 5 years DFS in the PCT+ group were 47%, 13% and 6% compared to 58%, 29% and 26% respectively in the PCT- (HR = 1.22; 95% CI:0.78–1.92; p = 0.376).ConclusionThis study does not show any clear benefit of PCT in carefully selected patients undergoing R0/R1 CRS and HIPEC for colorectal PM. The ongoing CAIRO6 trial randomizing CRS/HIPEC versus CRS/HIPEC and PCT will probably clarify the role of PCT in patients with resectable PM.     

Direct surgery with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for patients with colorectal peritoneal metastases

IntroductionNeoadjuvant chemotherapy is widely used in treatment of peritoneal metastases from colorectal cancer, but there is little scientific evidence for this approach. This study aimed to study survival in patients treated with direct surgery with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS-HIPEC), i.e. without neoadjuvant chemotherapy.Material and methodsPatients with histopathologically confirmed peritoneal metastases from colorectal cancer that underwent first-time CRS-HIPEC with complete cytoreduction (CC0 or 1) at Karolinska University Hospital 2012–2019 were included. Patients with synchronous extraperitoneal metastases were excluded if not treated before end of follow-up. Factors associated with overall survival (OS) and disease-free survival (DFS) were evaluated using the Kaplan-Meier method and Cox regression models. The multivariable models were adjusted for sex, age, synchronous/metachronous peritoneal metastases, peritoneal carcinomatosis index (PCI), extraperitoneal metastases and the pathological tumor (T) and lymph node (N) stage of the primary tumor.ResultsIn all, 131 patients underwent complete CRS-HIPEC for peritoneal metastases without neoadjuvant chemotherapy. The median OS and DFS were 40.3 months and 12.5 months, respectively, in patients treated with direct surgery. In the multivariable model, PCI≥16 was the only variable associated with decreased OS, whereas elevated PCI, metachronous development of peritoneal metastases and synchronous extraperitoneal metastases were associated with decreased DFS. Age was not associated with an impaired prognosis.ConclusionPatients who underwent direct surgery with CRS-HIPEC had a good prognosis, with a median OS of more than 3 years. The results from this study question the need of neoadjuvant chemotherapy in all patients eligible for CRS-HIPEC.     

Prognostic factors in patients with oligometastatic breast cancer – A systematic review

AimOligometastatic breast cancer (OMBC) is a disease-entity with potential for long-term remission in selected patients. Those with truly limited metastatic load (rather than occult widespread metastatic disease) may benefit from multimodality treatment including local ablative therapy of distant metastases. In this systematic review, we studied factors associated with long-term survival in patients with OMBC.MethodsEligible studies included patients with OMBC who received a combination of local and systemic therapy as multimodal approach and reported overall survival (OS) or progression-free survival (PFS), or both. The Quality in Prognosis Studies (QUIPS) tool was used to assess the quality of each included study. Independent prognostic factors for OS and/or PFS are summarized.ResultsOf 1271 screened abstracts, 317 papers were full-text screened and twenty studies were included. Eleven of twenty studies were classified as acceptable quality. Definition of OMBC varied between studies and mostly incorporated the number and/or location of metastases. The 5-year OS ranged between 30 and 79% and 5-year PFS ranged between 25 and 57%. Twelve studies evaluated prognostic factors for OS and/or PFS in multivariable models. A solitary metastasis, >24 months interval between primary tumor and OMBC, no or limited involved axillary lymph nodes at primary diagnosis, and hormone-receptor positivity were associated with better outcome. HER2-positivity was associated with worse outcome, but only few patients received anti-HER2 therapy.ConclusionsOMBC patients with a solitary distant metastasis and >24 months disease-free interval have the best OS and may be optimal candidates to consider a multidisciplinary approach.     

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.     

Is bile leakage after hepatic resection associated with impaired long-term survival?

BackgroundBile leakage (BL) is a frequent and severe complication following liver surgery. The aim of this study was to evaluate risk factors for BL, related other complications and association with long-term survival.MethodsThis study included all patients undergoing hepatectomy in a single centre from 2005 to 2016. Perioperative risk factors related to BL were identified using univariable and multivariable analysis. Kaplan-Meier method was used for survival analysis.ResultsBL occurred in 48 of 458 patients (11%). BLs were more frequent in patients after major hepatectomy (p = 0.001). Portal vein embolization, bilioenteric-anastomosis, lymphadenectomy, vascular reconstruction and operative time were significant factors for developing BL. Comparing patients with or without BL, BL was more commonly associated with other postoperative complications (p = 0.001), especially acute kidney failure and surgical-site-infections. There was no difference in 90-day-mortality (p = 0.124). The median disease-free survival was comparable (17 vs. 15 months, p = 0.976), also no difference was observed when stratifying for different tumour entities. There was no difference in median overall survival (OS) among malignant disease (35 vs. 47 months, p = 0.200) and in 3-year OS (46% vs. 59%). Multivariate analysis confirmed that postoperative liver failure and major hepatectomy were risk factors for reduced OS (p = 0.010).ConclusionsMany concerns have been raised regarding tumour progression after major complications. In this study, we only found a relevant influence of BL on OS in pCC, whereas no association was seen in other cancer types, indicating that tumour progression might be triggered by BL in cancer types arising from the bile ducts itself.     

Stereotactic radiofrequency ablation as first-line treatment of recurrent HCC following hepatic resection

BackgroundTo evaluate the therapeutic efficacy, safety and overall clinical outcome of multiprobe stereotactic RF ablation (SRFA) as first-line treatment of HCC recurrence after hepatic resection (HR).Study designIn this retrospective single-center study, 34 consecutive patients with previous HR were treated by SRFA between 2006 and 2018 for 140 HCCs in 60 ablation sessions.ResultsThe median treated tumor size was 3.0 cm (range 0.5–10 cm). SRFA was primarily successful for 133/140 (95%) tumors. Four tumors were successfully retreated, resulting in a secondary technical efficacy rate of 97.9%. Local tumor recurrence developed in 4 of 140 tumors (2.9%). The major complication rate was 4.8% (3 of 60 ablations). No periprocedural deaths occurred.The overall survival (OS) rates at 1-, 3-, and 5- years from the date of the first SRFA were 94.0%, 70.2%, and 53.3%, respectively, with a median OS of 69.1 months (95% CI 18.8–119.3). The disease-free survival (DFS) was 52.6%, 19.7% and 15.8%, at 1-, 3- and 5- years, respectively, with a median DFS of 12.8 months (95% CI 9.0–28.9).ConclusionStereotactic RFA is a safe, feasible and useful option in the management of recurrent HCC following HR with low morbidity paired with good clinical outcome.     

Prognostic significance of CA-125 re-elevation after interval debulking surgery in patients with advanced-stage ovarian cancer undergoing neoadjuvant chemotherapy

AimsWe evaluated the prognostic significance of postoperative re-elevation of cancer antigen-125 (CA-125) levels in patients with ovarian cancer and preoperative normalization of CA-125 levels after neoadjuvant chemotherapy (NAC).MethodsThe data of 103 patients with preoperative CA-125 normalization after NAC at the Yonsei Cancer Hospital (2006–2017) were analyzed. We compared the clinical characteristics and survival outcomes among patients with normal postoperative CA-125 levels and those with re-elevated CA-125 levels after interval debulking surgery (IDS). CA-125 elevation was defined as levels >35 U/mL.ResultsAmong 103 patients, 52 (50.5%) and 51 (49.5%) had normal and re-elevated CA-125 levels after IDS, respectively. Patients with CA-125 re-elevation underwent more radical surgeries during IDS than those with normal CA-125 levels (p = 0.018). We found no significant differences in progression-free survival (PFS; p = 0.726) or overall survival (OS; p = 0.293) between the two groups. Moreover, patients with persistent CA-125 elevation (3 weeks after IDS) did not have inferior PFS (p = 0.171 and p = 0.208, respectively) or OS (p = 0.128 and p = 0.095, respectively) compared to patients with early normalization (within 3 weeks of IDS) or normal CA-125 levels. Multivariate regression showed that CA-125 re-elevation had no effect on recurrence (hazard ratio [HR], 0.75; 95% confidence interval [CI], 0.43–1.30) or death (HR, 0.99; 95% CI, 0.33–2.98).ConclusionAmong patients with preoperative CA-125 normalization after NAC, postoperative CA-125 re-elevation had no prognostic value. Novel and reliable biomarkers reflecting the tumor response after IDS should be identified.