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.     

The different survival impacts of body mass index in elderly and non-elderly patients with gastric carcinoma

BackgroundThe age-dependent survival impact of body mass index (BMI) remains to be fully addressed in patients with gastric carcinoma (GC). We investigated the prognostic impacts of BMI in elderly (≥70 years) and non-elderly patients undergoing surgery for GC.MethodsIn total, 1168 GC patients were retrospectively reviewed. Patients were stratified into 3 groups according to BMI; low (<20), medium (20–25) and high (>25). The effects of BMI on overall survival (OS) and cancer-specific survival (CSS) were assessed using univariate and multivariate Cox hazards models.ResultsThere were 242 (20.7%), 685 (58.7%) and 241 (20.6%) patients in the low-, medium- and high-BMI groups, respectively. The number of patients with high BMI but decreased muscle mass was extremely small (n = 13, 1.1%). Patients in the low-BMI group exhibited significantly poorer OS than those in the high- and medium-BMI group (P < 0.001). Notably, BMI classification significantly demarcated OS and CSS curves (both P < 0.001) in non-elderly patients, while did not in elderly patients (OS; P = 0.07, CSS; P = 0.54). Furthermore, the survival discriminability by BMI was greater in pStage II/III disease (P = 0.006) than in pStage I disease (P = 0.047). Multivariable analysis focusing on patients with pStage II/III disease showed low BMI to be independently associated with poor OS and CSS only in the non-elderly population.ConclusionsBMI-based evaluation was useful for predicting survival and oncological outcomes in non-elderly but not in elderly GC patients, especially in those with advanced GC.     

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

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

Increased expression of thyroid hormone receptor alpha and estrogen receptor alpha in breast cancer associated with thyroid cancer

IntroductionBreast cancer co-occurred with thyroid cancer might be associated with thyroid hormone receptor (TR) and estrogen receptor (ER), but few have been reported. We aimed to investigate the expression and prognostic significance of ERs and TRs in such settings.Material and methodsTissue microarrays were constructed from 75 patients with breast and thyroid cancer (BC + TC) who were retrospectively recruited between 1999 and 2012 and 147 with breast cancer only (BC controls). The ERα, ERβ, TRα, and TRβ expression levels were analyzed by immunohistochemistry.ResultsTRα expression was more frequently observed in the BC + TC group than the BC control group both in the normal (51.5% vs 23.3%, respectively, p = 0.009) and cancer tissues (21.6% vs 6.8%, respectively, p = 0.001). The BC + TC group showed greater ERα-positivity in the cancer tissues (79.7% vs 58.7%, respectively, p = 0.002) than the BC control group. The degree of ERα- and TRα-positivity was unchanged by radioactive treatment or serum thyroid stimulating hormone levels. In the BC + TC group, ERα-positivity was associated with earlier disease stage I/IIA (81.0% vs 50.0%; p = 0.031) and lower recurrence rates (8.5% vs 40.0%; p = 0.002). TRα-positivity alone was not associated with any recurrence-free survival-related differences, and ERα- and TRα-negativity were associated with significantly shorter recurrence-free survival (p < 0.001).ConclusionEnhanced ERα and TRα expression in breast cancer is associated with thyroid cancer occurrence, and the observed association with prognosis suggests the possible role of ERs and TRs in the link between breast cancer and thyroid cancer.     

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

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

Fluorescence ureteral navigation during laparoscopic surgery for clinically suspected stage T4 colorectal cancer: A cohort study

BackgroundApproximately 15% of patients with colorectal cancer present with locally advanced tumors (T4 stage). Laparoscopic surgery for stage T4 disease has not yet been established.The near-infrared ray catheter fluorescent ureteral catheter (NIRFUC) is a new device that uses near-infrared fluorescence resin.We examined the utility of fluorescence ureteral navigation (FUN) with the NIRFUC during laparoscopic surgery for stage T4 colorectal cancer.Materials and methodsPatients with stage T4 colorectal cancer (n = 143, from January 2017 to March 2021) were divided into a T4FUN + group, in which the NIRFUC was used (n = 21), and a T4FUN- group, in which the NIRFUC was not used (n = 122). Short-term outcomes were compared between the groups.Next, the laparoscopic surgery rate and incidence of ureteral injury from January 2017 to March 2021 were compared between the T4FUN- group and the non-stage T4FUN- group (n = 434, from January 2017 to March 2021), in which fluorescence ureter navigation was not used.ResultsRectal cancer, stage T4b disease, and invasion into the urinary tract were observed more often in the T4FUN + group than in the T4FUN- group.In the comparisons of the T4FUN + versus T4FUN- groups, the operative time was 398 (161–1090) vs. 256 (93–839) minutes, the blood loss was 10 (1–710) vs. 25 (0–1360) ml, and the ratio of laparoscopic surgery to open surgery was 21:0 vs. 79:43. Postoperative complications (Clavien-Dindo grade ≥ III) were present in 2 (10%; 0 ureteral injury) patients in the T4FUN + group and 13 (11%; 2 ureteral injury) patients in the T4FUN- group.In the T4FUN + group, the operative time was longer (p < 0.0001), but the laparoscopic ratio was higher (p = 0.0002), and the blood loss volume and incidence of ureteral injury tended to be lower.In the comparisons of the T4FUN- versus non-stage T4FUN- groups, the ratio of laparoscopic surgery to open surgery was 79:43 vs. 384:50, the incidence of open conversion was 8 (6.6%) vs. 15 (3.5%), and the incidence of ureteral injury was 2 (1.6%) vs. 0 (0%). In the T4FUN- group, the open surgery rate (<0.0001), open conversion rate (p = 0.0205) and incidence of ureteral injury (p = 0.0478) were high, with a significant difference observed between the groups.ConclusionPatients with stage T4 disease have an increased risk of ureteral injury and are more likely to be converted to open surgery.FUN can help to safely increase the laparoscopic surgery rate while safely visualizing the ureter. FUN is recommended for laparoscopic surgery in patients with stage T4 colorectal cancer.Clinical trial registrationExamination of fluorescence navigation for laparoscopic colorectal cancer surgery; Research Ethics Committee of the Kawaguchi Municipal Medical Center (Saitama, Japan) approval number: 2020-3. https://kawaguchi-mmc.org/wp-content/uploads/clinical research-r02.pdf;     

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

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

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.     

The Dutch Lung Cancer Audit-Radiotherapy (DLCA-R): Real-World Data on Stage III Non-Small Cell Lung Cancer Patients Treated With Curative Chemoradiation

IntroductionChemoradiotherapy (CRT) is the standard of care in inoperable non–small-cell lung cancer (NSCLC) patients, favoring concurrent (cCRT) over sequential CRT (seqCRT), with adjuvant immunotherapy in responders. Elderly and frail NSCLC patients have generally been excluded from trials in the past. In elderly patients however, the higher treatment related morbidity of cCRT, may outweigh the possible lower tumor control of seqCRT. For elderly patients with locally advanced NSCLC real-world data is essential to be able to balance treatment toxicity and treatment outcome. The aim of this study is to analyze acute toxicity and 3-month mortality of curative chemoradiation (CRT) in patients with stage III NSCLC and to analyze whether cCRT for elderly stage III NSCLC patients is safe.MethodsThe Dutch Lung Cancer Audit-Radiotherapy (DLCA-R) is a national lung cancer audit that started in 2013 for patients treated with curative intent radiotherapy. All Dutch patients treated for stage III NSCLC between 2015 and 2018 with seqCRT or cCRT for (primary or recurrent) stage III lung cancer are included in this population-based study. Information was collected on patient, tumor- and treatment characteristics and the incidence and severity of acute non-hematological toxicity (CTCAE-4 version 4.03) and mortality within 3 months after the end of radiotherapy. To evaluate the association between prognostic factors and outcome (acute toxicity and mortality within 3 months), an univariable and multivariable analysis was performed. The definition of cCRT was:radiotherapy started within 30 days after the start of chemotherapy.ResultsOut of all 20 Dutch departments of radiation oncology, 19 centers participated in the registry. A total of 2942 NSCLC stage III patients were treated with CRT. Of these 67.2% (n = 1977) were treated with cCRT (median age 66 years) and 32.8% (n = 965) were treated with seqCRT (median age 69 years). Good performance status (WHO 0-1) was scored in 88.6% for patients treated with cCRT and in 71.0% in the patients treated with seqCRT. Acute nonhematological 3-month toxicity (CTCAE grade ≥3 or radiation pneumonitis grade ≥2) was scored in 21.9% of the patients treated with cCRT and in 17.7% of the patients treated with seqCRT. The univariable analysis for acute toxicity showed significantly increased toxicity for cCRT (P = .008), WHO ≥2 (P = .006), and TNM IIIC (P = .031). The multivariable analysis for acute toxicity was significant for cCRT (P = .015), WHO ≥2 (P = .001) and TNM IIIC (P = .016). The univariable analysis for 3-month mortality showed significance for seqCRT (P = .025), WHO ≥2 (P < .001), higher cumulative radiotherapy dose (P < .001), higher gross tumor volume total (P = .020) and male patients (p < .001). None of these variables reached significance in the multivariable analysis for 3-month mortality.ConclusionIn this national lung cancer audit of inoperable NSCLC patients, 3-month toxicity was significantly higher in patients treated with cCRT (21.9% vs. 17.7% for seqCRT) higher TNM stage IIIC, and poor performance (WHO≥2) patients.The 3-months mortality was not significantly different for tested parameters. Age was not a risk factor for acute toxicity, nor 3 months mortality.     

An Exploration of Trifluridine/Tipiracil Monotherapy and in Combination With Bevacizumab or Immune Checkpoint Inhibitors for Patients With Metastatic Colorectal Cancer: A Real-World Study

BackgroundTrifluridine/tipiracil (TAS-102) has achieved modest efficacy in the late-line treatment of metastatic colorectal cancer. The present study aimed to explore the clinical efficacy and drug toxicities of TAS-102 for patients with metastatic colorectal cancer in real-world clinical setting.MethodsFrom October 2020 to February 2022, patients with metastatic colorectal cancer who failed from 2 or more lines of prior therapy and treated with TAS-102 monotherapy, in combination with bevacizumab or immune checkpoint inhibitors (ICIs) were analyzed. The evaluation indicators were progression free survival (PFS), objective response rate , disease control rate (DCR), overall survival (OS) and drug toxicities.ResultsA total of 70 patients were enrolled. The objective response rate and DCR were 1.4% and 68.6%. The median PFS and OS were 6.0 (95% CI: 4.1-7.9) and 10.0 (95% CI: 8.3-11.7) months. Compared with TAS-102 monotherapy and TAS-102 plus ICIs, TAS-102 plus bevacizumab obtained superior DCR (75.9% vs. 50% vs. 40%, P = .047), PFS (6.3m vs. 3.0 m vs. 3.0 m, P = .041) and OS (12.0 m vs. 6.5 m vs. 6.0m, P = .013). Patients without prior regorafenib or fruquintinib therapy obtained better median PFS (6.3 vs. 4.3 m, P = .031) and OS (NR vs. 9.0 m, P = .036). Other indicators, including age, tumor site, KRAS status and use of fluoropyrimidine as last regimen before TAS-102, did not affect the clinical efficacy of TAS-102. The most frequent adverse events were leukopenia, neutropenia, anemia, fatigue, nausea, and vomiting.ConclusionIn real-world clinical setting, TAS-102 showed consistent clinical efficacy and manageable safety with previous prospective clinical studies. Compared with monotherapy and TAS-102 plus ICIs, TAS-102 plus bevacizumab demonstrated better clinical efficacy for metastatic colorectal cancer.     

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 role of surgery for locally recurrent and second recurrent rectal cancer with metastatic disease

BackgroundThe role of surgery for locally recurrent rectal cancer (LRRC) with resectable distant metastases or second LRRC remains unclear. This study aimed to clarify the influence of synchronous distant metastases (SDMs), a history of distant metastasis resection (HDMR), and a second LRRC on the outcome.MethodsThe long-term outcomes of 70 surgically treated patients with LRRC between 2006 and 2018 were compared by SDM (n = 10), HDMR (n = 17), and second LRRC (n = 7).ResultsAmong the 10 patients with SDM, 4 patients underwent simultaneous resection, whereas the other 6 underwent staged resection with distant first approach. Recurrence developed in 9 patients, of which 2 patients with liver re-resection achieved long-term survival without cancer. The patients with and without SDM had equivalent 5-year overall survival rate (40.5% vs. 53.3%, p = 0.519); however, patients with SDM had a worse 3-year recurrence-free survival rate than those without SDM (10.0% vs. 37.5%, p = 0.031). Multivariate analysis showed that primary non-sphincter-preserving surgery, second LRRC, and R1 resection were independent risk factors for overall survival. Similarly, primary non-sphincter-preserving surgery, second LRRC, SDM, and R1 resection were risk factors for recurrence-free survival.ConclusionsPatients with SDM might still be suitable to undergo salvage surgery and achieve favourable overall survival. Distant metastasectomy should be performed first, followed by a sufficient interval to avoid unnecessary LRRC resection in uncurable patients. An HDMR should not be taken into consideration when making surgical plans. Surgical indication of second LRRC should be strict, especially in referred patients.     

Postoperative morbidity adversely impacts long-term oncologic prognosis following hepatectomy for hepatocellular carcinoma: A multicenter observational study

Background & aimsPostoperative morbidity following hepatectomy for hepatocellular carcinoma (HCC) is common and its impact on long-term oncological outcome remains unclear. This study aimed to investigate if postoperative morbidity impacts long-term survival and recurrence following hepatectomy for HCC.MethodsThe data from a multicenter Chinese database of curative-intent hepatectomy for HCC were analyzed, and independent risks of postoperative 30-day morbidity were identified. After excluding patients with postoperative early deaths (≤90 days), early (≤2 years) and late (>2 years) recurrence rates, overall survival (OS), and time-to-recurrence (TTR) were compared between patients with and without postoperative morbidity.ResultsAmong 2,161 patients eligible for the study, 758 (35.1%) had postoperative 30-day morbidity. Multivariable logistic regression analysis showed that diabetes mellitus, obesity, Child-Pugh grade B, cirrhosis, and intraoperative blood transfusion were independent risks of postoperative morbidity. The rates of early and late recurrence among patients with postoperative morbidity were higher than those without (50.7% vs. 38.8%, P < 0.001; and 41.7% vs. 34.1%, P = 0.017). Postoperative morbidity was associated with decreased OS (median: 48.1 vs. 91.6 months, P < 0.001) and TTR (median: 19.8 vs. 46.1 months; P < 0.001). After adjustment of confounding factors, multivariable Cox-regression analyses revealed that postoperative morbidity was associated with a 27.8% and 18.7% greater likelihood of mortality (hazard ratio 1.278; 95% confidence interval: 1.126–1.451; P < 0.001) and recurrence (1.187; 1.058–1.331; P = 0.004).ConclusionThis large multicenter study provides strong evidence that postoperative morbidity adversely impacts long-term oncologic prognosis after hepatectomy for HCC. The prevention and management of postoperative morbidity may be oncologically important.     

Partial hepatectomy vs. transcatheter arterial chemoembolization for multiple hepatocellular carcinomas of BCLC-B stage: A meta-analysis of high-quality studies

Background/aimThe Barcelona Clinic Liver Cancer (BCLC) recommends that transcatheter arterial chemoembolization (TACE) are indicated in patients with multiple hepatocellular carcinomas (HCCs) of BCLC-B stage. However, partial hepatectomy (PH) has increasely performed in these patients. The purpose of this meta-analyses is to illustrate the comparative survival benefits of PH and TACE for patients with multiple HCCs of BCLC-B stage.MethodElectronic databases were systematically searched for eligible studies that compared PH and TACE performed in patients with multiple HCCs of BCLC-B stage. Studies that met the inclusion criteria were reviewed systematically. The reported data were aggregated statistically using the RevMan5.3 software. Primary endpoint was overall survival (OS), and secondary endpoint were the 1-, 3-, and 5-year survival rates, postoperative 30-day mortality and postoperative complications.ResultsA total of seven high-quality studies (one randomized controlled trial [RCT], six propensity-score matching (PSM) nonrandomized comparative trials [non-RCTs] that met the inclusion criteria, which comprised of 2487 patients (1245 PH and 1242 TACE) in the meta-analysis. When compared with the TACE group, the PH group had a significantly higher OS (HR, 1.65; 95% CI, 1.48–1.84; P = 0.26; I² = 22%) and 1-, 3-, 5-year survival rates (OR, 1.96; 95% CI, 1.59–2.41; P = 0.0005; I² = 75%; P < 0.00001; OR, 2.92; 95% CI, 1.94–4.42; P = 0.0001; I² = 78%; P < 0.00001; OR, 2.60; 95% CI, 2.17–3.11; P = 0.13; I² = 44%; P < 0.00001; respectively). Survival benefits persisted across sensitivity and subgroup analyses; High heterogeneity remained after sensitivity and subgroup analyses for 3-year survival rates.ConclusionPH can provide more survival benefit for patients with multiple HCCs of BCLC-B stage compared with TACE.     

Intra-abdominal recurrence from colorectal carcinoma: Differences and similarities between local and peritoneal recurrence

BackgroundPeritoneal recurrences from colo-rectal cancer can be isolated (PR) or associated with local recurrences (LR). The purpose of this study was to analyze patterns and outcomes of LR and PR.MethodsAnalyze from a prospective database of 108 patients treated with CCS plus HIPEC at two cancer centers between 2008 and 2015.ResultsThe population was divided into an LPR group (presence of LR with or without PR, n = 56) and a PR group (isolated PR, n = 52). The patients characteristics (age, sex, Charlson score, PCI) or perioperative treatments were comparable between the groups. The median number of resected organs for tumor involvement (respectively, 2 vs 1; p < 0.001), the percentage of patients with metastatic lymph nodes (LN+) from the resected specimen (respectively, 25% vs 7%; p = 0.016) and the mortality rate (respectively, 9% vs 0%; p = 0.023) were significantly higher in the LPR group. After a median follow-up of 32 (1–108) months, median overall survival was comparable between the two groups (respectively, 46 vs 42 months; p = 0.262).ConclusionsLR is associated with a higher incidence of organ invasion, LN involvement (25%) and postoperative mortality. Optimal surgical resection of LR with systematic lymphadenectomy of invaded organs seems mandatory.     

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.     

Complications and risk factors in vulvar cancer surgery – A population-based study

IntroductionPrimary surgery for vulvar cancer has become less radical in past decades. This study investigates risk factors and prevalence of short-and long-term complications after up-to-date vulvar cancer surgery.MethodsPopulation-based cohort study of surgically treated primary vulvar cancer at a national center of vulvar cancer, assessing surgical outcome. The Swedish Quality Registry for Gynecological Cancer was used for identification, journals reviewed and surgical outcome including complications within 30 days and one year registered. Multivariable logistic regression analysis comprising risk factors of short-term complications; age>80 years, BMI, smoking, diabetes, lichen sclerosus and FIGO stage was performed.Results182 patients were identified, whereas 55 had vulvar surgery only, 53 surgery including sentinel lymph node biopsy (SLNB) and 72 surgery including inguinofemoral lymphadenectomy (IFL), with short-term complication rates of 21.8%, 39.6% and 54.2% respectively. Vulvar wound dehiscence was reported in 6.0% and infection in 13.7%. Complication rates were lower after SLNB than IFL (wound dehiscence 0% vs 8.3%; p = 0.04, infection 15.1% vs 36.1%; p = 0.01 and lymphocele 5.7% vs 9.7%; p = 0.52). Severe complications were rare. Persisting lymphedema evolved in 3.8% after SLNB and in 38.6% after IFL (p = 0.001), ubiquitous after adjuvant radiotherapy. In multivariable regression analysis, no associations between included risk factors and complications were found.ConclusionSurgical complications are still common in vulvar cancer surgery and increase with the extent of groin surgery. To thrive for early diagnosis and to avoid IFL seem to be the most important factors in minimizing short-and long-term complications.     

Second invasive breast cancers in patients treated with breast-conserving therapy

ObjectiveSecond breast cancers after breast-conserving therapy (BCT) include ipsilateral breast tumor recurrence (IBTR) and metachronous contralateral breast cancer (CBC). Each IBTR is further classified as true recurrence (TR) or new primary tumor (NP). We aim to compare survival outcomes of TR, NP and CBC, and explore the optimal treatments.Methods168,427 patients with primary breast cancer who underwent BCT between 1990 and 2005 were identified in the SEER database. The risks of IBTR and CBC were estimated by annual hazard rate. The breast cancer-specific survival (BCSS) were assessed using multivariable Cox regression analysis.ResultsWith median follow-up of 13 years after BCT, 5413 patients developed an IBTR and 4050 patients had a CBC. The risk of IBTR peaked between 10 and 15 years after BCT, while the risk of CBC distributed evenly. 45.9% of IBTRs were classified as a TR and 54.1% as an NP. The time interval from primary breast cancer to NP was longer than to TR and CBC (P < 0.001). Patients with TR had a poorer BCSS than NP (P = 0.003) and CBC (P = 0.002). There was no difference in BCSS between mastectomy and repeat BCT for treating TR (P = 0.584) or NP (P = 0.243). The BCSS of CBCs treated with BCT was better than mastectomy (P = 0.010). Chemotherapy didn't improve the survival of patients with TR (P = 0.058). However, TRs with grade III or negative hormone receptors benefited from chemotherapy significantly.ConclusionPatients with TR had a poorer BCSS than NP and CBC. Classifying IBTR may provide clinical significance for treatments.     

Systemic Chemotherapy With or Without Hepatic Arterial Infusion Chemotherapy for Liver Metastases From Pancreatic Cancer: A Propensity Score Matching Analysis

BackgroundThe significance of systemic chemotherapy (SCT) combined with hepatic arterial infusion (HAI) chemotherapy in the treatment of pancreatic ductal adenocarcinoma with liver metastases (PACLM) remains unclear. Based on previous studies, this single-center propensity score matching (PSM) study aimed to explore the efficacy of SCT with or without HAI for PACLM.Patient and MethodsThe PSM method was used to screen 661 cases of PACLM who received SCT at Tianjin Medical University Cancer Institute and Hospital from 2001 to 2020. According to the 1:6 ratio with PSM, 385 patients were divided into the SCT+HAI group (n = 55) and the SCT group (n = 330). After a median follow-up of 49 (range 7-153) months, overall survival (OS) and survival-related prognostic factors were analyzed.ResultsThe main baseline characteristics of the SCT+HAI group and the SCT alone group were matched appropriately (P > .05). After PSM, the median OS for patients in the 2 groups was 10.6 and 7.6 months, respectively (P = .02). Multivariate analysis revealed that peritoneal metastases (P = .03), CA199 ≥ 500U/mL (P = .03), and lactate dehydrogenase (LDH) ≥ 250U/L (P = .03) were prognostic factors of poor survival, modern SCT plus HAI (P = .04) was a protective factor.ConclusionOur findings indicated that adequate cycles of SCT+HAI result in better survival than SCT alone in patients with PACLM. Patients with peritoneal metastases, markedly elevated CA19-9 and LDH have a poorer prognosis. The conclusion has yet to be validated in randomized controlled clinical trials.     

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.