Wrapping double-mattress anastomosis for pancreaticojejunostomy in minimally invasive pancreaticoduodenectomy can significantly reduce postoperative pancreatic fistula rate compared with conventional pancreaticojejunostomy in open surgery: An analysis of a propensity score-matched sample

BackgroundMinimally invasive pancreaticoduodenectomy (MIPD), including laparoscopic pancreaticoduodenectomy (LPD) and robotic pancreaticoduodenectomy (RPD), is technically demanding because of pancreaticojejunostomy (PJ). Postoperative pancreatic fistula (POPF) is the most serious complication of MIPD and open pancreaticoduodenectomy (OPD). Contrary to expectations, conventional PJ in MIPD did not improve POPF rate and length of hospital stay. High POPF rates are attributed to technical issues encountered during MIPD, which include motion restriction and insufficient water tightness. Therefore, we developed wrapping double-mattress anastomosis, the Kiguchi method, which is a novel PJ technique that can improve MIPD. Herein, we describe the Kiguchi method for PJ in MIPD and compare the outcomes between this technique and conventional PJ in OPD.MethodsThe current retrospective study included 83 patients in whom the complete obstruction of the main pancreatic duct by pancreatic tumors was absent on preoperative imaging. This research was performed from September 2016 to August 2020 at Fujita Health University Hospital. All patients were evaluated as having a soft pancreatic texture, which is the most important factor associated with POPF development. Briefly, 50 patients underwent OPD with conventional PJ (OPD group). Meanwhile, 33 patients, including 15 and 18 who had LPD and RPD, respectively, underwent MIPD using the Kiguchi method (MIPD group). After a 1:1 propensity score matching, 30 patients in the OPD group were matched to 30 patients in the MIPD group.ResultsThe patients’ preoperative data did not differ. The grade B/C POPF rate was significantly lower in the MIPD group than in the OPD group (6.7% vs 40.0%, p = 0.002). The MIPD group had a significantly shorter median length of hospital stay than the OPD group (24 vs 30 days, p = 0.004).ConclusionThe novel Kiguchi method in MIPD significantly reduced the POPF rate in patients without complete obstruction of the main pancreatic duct.     

Clinical presentation and prognosis of adenosquamous carcinoma of the pancreas – Matched-pair analysis with pancreatic ductal adenocarcinoma

IntroductionAdenosquamous carcinoma of the pancreas (ASCP) is a rare subtype of pancreatic adenocarcinoma. The aim of this study was to investigate the characteristics and outcomes of ASCP in comparison to pancreatic ductal adenocarcinoma (PDAC).Materials and methodsAll patients with ASCP treated between December 2001 and December 2017 were identified from a prospective database. Clinicopathological and follow-up data were analyzed. A nested case-control-study with matched-pair analysis was performed to compare overall survival of ASCP and PDAC.ResultsOf 4009 patients undergoing surgery for pancreatic adenocarcinoma 91 patients had ASCP. Compared to PDAC ASCP were larger (4.0 vs. 3.2 cm; p < 0.0001), more frequently involved lymph nodes (88% vs. 78%; p = 0.0216), more frequently showed poor differentiation (G3: 79% vs. 36%; p < 0.0001) and more frequently were located in the pancreatic tail (19% vs. 10%; p = 0.0179). Overall median post-resection-survival was shorter in ASCP (10.8 vs. 20.5 months in PDAC; p = 0.0085), but 5-year survival rates were comparable (18.2% vs. 17.5%). After matching for the unevenly distributed prognostic factors survival after resection of ASCP and PDAC was comparable (p = 0.8301). Localization in the head or several parts of the pancreas, high CA 19-9 levels, and M1 disease were independent predictors of survival in patients with ASCP.ConclusionASCP is more aggressive with poorer differentiation and higher rates of lymph node metastases compared to PDAC. In spite of a shorter median survival, 5-year survival rates after surgical resection of about 18% can be expected in ASCP and support resection as part of a multimodal therapy as the treatment of choice in this rare cancer.     

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

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

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

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

Sarcopenia and primary tumor location influence patients outcome after liver resection for colorectal liver metastases

IntroductionRight-sided and left-sided colorectal cancer (CRC) is known to differ in their molecular carcinogenic pathways. The prevalence of sarcopenia is known to worsen the outcome after hepatic resection. We sought to investigate the prevalence of sarcopenia and its prognostic application according to the primary CRC tumor site.Methods355 patients (62% male) who underwent liver resection in our center were identified. Clinicopathologic characteristics and long-term outcomes were stratified by sarcopenia and primary tumor location (right-sided vs. left-sided). Tumors in the coecum, right sided and transverse colon were defined as right-sided, tumors in the left colon and rectum were defined as left-sided. Sarcopenia was assessed using the skeletal muscle index (SMI) with a measurement of the skeletal muscle area at the level L3.ResultsPatients who underwent right sided colectomy (n = 233, 65%) showed a higher prevalence of sarcopenia (35.2% vs. 23.9%, p = 0.03). These patients also had higher chances for postoperative complications with Clavien Dindo >3 (OR 1.21 CI95% 0.9–1.81, p = 0.05) and higher odds for mortality related to CRC (HR 1.2 CI95% 0.8–1.8, p = 0.03).On multivariable analysis prevalence of sarcopenia remained independently associated with worse overall survival and disease free survival (overall survival: HR 1.47 CI 95% 1.03–2.46, p = 0.03; HR 1.74 CI95% 1.09–3.4, p = 0.05 respectively).ConclusionSarcopenia is known to have a worse prognosis in patients with CRLM and CRC. Depending on the primary location sarcopenia has a variable effect on the outcome after liver resection.     

Spinal metastases from thyroid cancer: Some prognostic factors

BackgroundSpinal metastases (SpMs) from thyroid cancers (TC) significantly reduce quality of life by causing pain, neurological deficits in addition to increasing mortality. Moreover, prognosis factors including surgery remain debated.MethodsData were stored in a prospective French national multicenter database of patients treated for SpM between January 2014 and 2017. Fifty-one consecutive patients affected by TC with 173 secondary SpM were included.ResultsMean overall survival (OS) time for all patients from the diagnosis of a thyroid SpM event was 9.1 years (SD 8.7 months). The 1-year, 5-year and 10-year survival estimates were 94% (SD 3.3), 83.8.0% (SD 5.2), and 74.5% (SD 9.9). The median period of time between primary thyroid tumor diagnosis and the SpM event was 31.4 months (SD 71.6). In univariate analysis, good ECOG-PS (status 0 and 1) (p < 0.0001), ambulatory status (Frankel score) (p < 0.0001) and no epidural involvement (p = 0.01), were associated with longer survival, whereas cancer subtype (p = 0.436) and spine surgery showed no association (p = 0.937). Cox multivariate proportional hazard model only identified good ECOG-PS: 0 [HR: 0.3, 95% CI 0.1–0.941; p < 0.0001], 1 [HR: 0.8, 95% CI 0.04–2.124; p = 0.001] and ambulatory neurological status: Frankel E [HR: 0.262, 95% CI 0.048–1.443; p = 0.02] to be independent predictors of better survival.ConclusionFor cases presenting SpM from TC, we highlighted that the only prognostic factors were the progression of the cancer (ECOG-PS) and the clinical neurological impact of the SpM (Frankel status). Surgery should be discussed mainly for stabilization and neurological decompression.     

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.     

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

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

Utility of a new prognostic score based on the Comprehensive Complication Index (CCI®) in patients operated on for colorectal cancer (S-CRC-PC score)

BackgroundPostoperative complications after colorectal cancer surgery have been associated with poor long-term prognosis. The aim of the present study was to investigate the prognostic impact of postoperative complications after colorectal cancer surgery assessed by the Comprehensive Complication Index (CCI®) and designing a new prognostic score based on this index.MethodsThis observational longitudinal study included a series of 604 patients who underwent colorectal surgery for cancer. Demographic data, comorbidity measured by Charlson Index, tumor characteristics, surgical data and postoperative complications were recorded as predictors. Univariate and multivariate analysis were performed and long-term survival was the output variable. Based on Hazard Ratios obtained on multivariate analysis, a new score, S-CRC-PC, was created for predicting long-term survival.ResultsTwo-hundred and twelve (35.1%) patients developed some postoperative complication. The mean CCI was 11.6 (±19.19). Mild complications (CCI <26.2) were detected in 95 (15.7%) patients. Moderate complications (CCI 26.2–42.2) were detected in 64 (10.6%) patients. Severe complications (CCI >42.3) were detected in 53 patients (8.8%) patients. Mortality rate was 1.7%. In multivariate analysis, age (p < 0.001), Charlson score (p = 0.014), CCI (p < 0.001), and TNM stage (p < 0.001) were statistically significantly in relation to long-term survival rate. S-CRC-PC score was statistically associated with survival rate (HR: 1.34–95% CI: 1.27–1.41). Patients with S-CRC-PC values from 0 to 8 points (low risk), 8.1–16 points (medium risk), and scores above 16 points (high risk) had a cumulative survival rate at five-years of 98%, 83%, and 31% respectively.ConclusionsPostoperative complications after colorectal cancer surgery assessed by CCI are an independent prognostic factor of survival rate. The S-CRC-PC score may be helpful in predicting long-term cancer outcomes.     

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.     

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.     

Prognostic factor analysis of irreversible electroporation for locally advanced pancreatic cancer – A multi-institutional clinical study in Asia

IntroductionIrreversible electroporation (IRE) is a modality that utilizes high electric voltage to cause cell apoptosis. IRE has been used to treat locally advanced pancreatic cancer (LAPC). However, studies of IRE via surgical approaches for LAPC are limited. This study aims to analyse the outcomes and related prognostic factors of IRE for Asian patients with LAPC.Materials and methodsFrom 2012 to 2017, this prospective trial for using IRE through surgical approaches for LAPC was conducted in 11 medical centres in Asia. All related and treatment outcomes were analysed from a prospective database.ResultsSeventy-four patients were enrolled. Thirty complications occurred in thirteen (17.6%) patients without mortality. The electrode placement direction (anteroposterior vs. craniocaudal, HR = 14.2, p < 0.01) and gastrointestinal invasion (HR = 15.7, p < 0.01) were significant factors for complications. The progression-free survival (PFS) rate in one year, three years, and five years were 69.1%, 48.7%, and 28.8%, and the overall survival (OS) rate in one year, three years, and five years were 97.2%, 53%, and 31.2%. In univariate analysis, the chemotherapy regimen, local tumour recurrence, axial tumour length, tumour volume, and serum carbohydrate antigen 19-9 levels were all significantly associated with PFS and OS. In multivariate analysis, the chemotherapy regimen was the only significant factor associated with PFS and OS. TS-1 (Tegafur, gimeracil, and oteracil) group has superior survival outcome than gemcitabine group.ConclusionThis study showed that combined induction chemotherapy and surgical IRE for LAPC is safe. For well-selected patients, IRE can achieve encouraging survival outcomes.     

Prognostic value of preoperative inflammatory markers in resectable biliary tract cancer – Validation and comparison of the Glasgow Prognostic Score and Modified Glasgow Prognostic Score in a Western cohort

IntroductionEstablished preoperative prognostic factors for risk stratification of patients with biliary tract cancer (BTC) are lacking. A prognostic value of the inflammation-based Glasgow Prognostic Score (GPS) and Modified Glasgow Prognostic Score (mGPS) in BTC has been indicated in several Eastern cohorts. We sought to validate and compare the prognostic value of the GPS and the mGPS for overall survival (OS), in a large Western cohort of patients with BTC.Material and methodsWe performed a retrospective single-center study for the period 2009 until 2017. 216 consecutive patients that underwent surgical exploration with a diagnosis of perihilar cholangiocarcinoma (PHCC), intrahepatic cholangiocarcinoma (IHCC), or gallbladder cancer (GBC) were assessed. GPS and mGPS were calculated where both CRP and albumin were measured pre-operatively (n = 168/216). Survival was analyzed by Kaplan-Meier estimate and uni-/multivariate Cox regression.ResultsGPS and mGPS were negatively associated with survival (p < 0.001/p < 0.001), and the association was significant in all three subgroups. GPS, but not the mGPS, identified an intermediate risk group: with GPS = 1 having better OS than GPS = 2 (p = 0.003), but worse OS than GPS = 0 (p = 0.008). In multivariate analyses of resected patients, GPS (p = 0.001) and mGPS (p = 0.03) remained significant predictors of survival, independent of postoperatively available risk factors.ConclusionsPreoperative GPS and mGPS are independent prognostic factors in BTC. The association to OS was shown in all patients undergoing exploration, in resected patients only, and in both cholangiocarcinoma and gallbladder cancer. Furthermore, GPS – which weights hypoalbuminemia higher – could identify an intermediate risk group.     

The prognostic role of in-hospital transfusion of fresh frozen plasma in patients with cholangiocarcinoma undergoing curative-intent liver surgery

IntroductionMajor hepatectomy for perihilar and intrahepatic cholangiocarcinoma (CCA) is often associated with a significant intraoperative blood loss and the requirement for perioperative transfusion of blood products. The aim of this study was to investigate the oncological impact of fresh frozen plasma (FFP) transfusion during hospitalization in patients undergoing hepatectomy for CCA as adverse effects have been described in other malignancies.Material and methodsPatients undergoing hepatectomy for CCA from 2010 to 2019 at a single institution were eligible for this study. Survival analysis was carried out according to Kaplan-Meier and the associations of cancer-specific (CSS) and recurrence-free survival (RFS) with in-hospital application of FFP and other clinico-pathological characteristics were assessed using Cox regression models. Perioperatively deceased patients were excluded from the analysis.ResultsA total of 219 CCA patients were included in this survival analysis of which 53.0% (116/219) received FFP during hospitalization. Patients receiving in-hospital FFP showed a median CCS of 33 months (3-year-CSS = 46%, 5-year-CSS = 29%) compared to 83 months (3-year-CSS = 55%, 5-year-CSS = 53%) in patients who did not receive in-hospital FFP (p = 0.006 log rank). Further, in-hospital FFP was identified as an independent predictor of oncological outcome in multivariable analysis (CSS: HR = 1.71, p = 0.016; RFS: HR = 1.89, p = 0.003).ConclusionIn a large European cohort of patients, in-hospital transfusion of FFP was identified as a novel independent prognostic marker in CCA patients undergoing curative-intent liver surgery. A restrictive transfusion policy is therefore recommended to improve long-term outcome in these patients.     

R1 pancreatic cancer patients benefit from chemoradiation when initiation of adjuvant therapy is delayed

BackgroundAdjuvant chemotherapy (AC) following pancreaticoduodenectomy (PD) for pancreas cancer (PDAC) has been demonstrated to improve survival. However, the optimal adjuvant treatment (AT) regimen for R1-margin patients remains unclear. This retrospective study investigates the impact of AC vs. adjuvant chemoradiotherapy (ACRT) on survival (OS).Material and methodsThe NCDB was queried for patients with PDAC who underwent PD between 2010 and 2018. Patients were divided into, (A) AC<60 days, (B) ACRT<60 days, (C) AC≥60 days, and (D) ACRT≥60 days. Kaplan-Meier survival analyses and Cox multivariable regression analyses were performed.ResultsAmong 13 740 patients, median OS was 23.7 months. For R1 patients, median OS for timely AC and ACRT, and delayed AC and ACRT was 19.91, 19.19, 15.24, 18.96 months, respectively. While time of AC initiation was an insignificant factor for R0 patients (p = 0.263, CI 0.957–1.173), a survival benefit was found for R1 patients who received AC<60 vs. ≥60 days (p = 0.041, CI 1.002–1.42). Among R1 patients, administration of delayed ACRT achieves the same survival benefit of timely AC initiation (p = 0.074, CI 0.703–1.077).ConclusionThe study suggests value in ACRT for patients with R1 margins when delay of AT≥60 days cannot be avoided. Hence, ACRT may mitigate the negative impact of delayed AT initiation for R1-patients.     

Comparing surgical and oncologic outcomes between laparoscopic gastrectomy and open gastrectomy in advanced gastric cancer with serosal invasion: A retrospective study with propensity score matching

PurposeLaparoscopic gastrectomy (LG) has gradually increased for treating advanced gastric cancer (AGC). However, there is a lack of evidence on oncologic safety for AGC, especially with serosal invasion. This study evaluates the surgical and oncologic outcomes between laparoscopic and open gastrectomy (OG) for gastric cancer with serosal invasion.MethodsWe retrospectively reviewed 256 patients who underwent OG and 147 patients who underwent LG for gastric cancer with serosal invasion between August 2005 and December 2017. Finally, 124 patients in the LG group and 124 in the OG group were enrolled according to one-to-one propensity score matching (PSM) analysis. We evaluated surgical and oncological outcomes, including overall survival (OS) and recurrence-free survival (RFS).ResultsThere were no statistical differences in hospital stay and major complications between the two groups. The retrieved lymph nodes of the LG group were similar to those of OG (40 ± 16.23 vs. 38 ± 14.42, p = 0.306), and it showed a similar operation time compared with the other (164 ± 43.86 vs. 156 ± 37.66, p = 0.063). There was no statistical difference in OS (p = 0.761) and RFS (p = 0.121) for survival analysis between the two groups.ConclusionLG for gastric cancer with serosal invasion is feasible and could be considered as a standard treatment.     

Utility of a modified age-adjusted Charlson Comorbidity Index in predicting cause-specific survival among patients with gastric cancer

IntroductionThe current study aimed to evaluate the ability of a modified version of the age-adjusted Charlson Comorbidity Index (mACCI) in predicting cause-specific survival (CSS) among patients with gastric cancer who underwent curative gastrectomy and compared it with the conventional ACCI.Materials and methodsPatients who underwent gastrectomy for gastric cancer from 2007 to 2016 (n = 2885) were included. A mACCI was established by excluding scores for other malignancies, such as other cancers, leukemia, and lymphoma. After determining the optimal cutoff ACCI and mACCI values for CSS, clinicopathological factors and survival outcomes were assessed according to the ACCI and mACCI.ResultsBoth ACCI and mACCI were identified as independent prognostic factors for overall survival (p < 0.001 and p < 0.001, respectively). However, only mACCI was identified as an independent prognostic factor for CSS (p < 0.001). The present study suggested that mACCI was a better indicator of CSS in patients with gastric cancer who underwent curative gastrectomy than ACCI.ConclusionOur findings showed that the mACCI was a strong predictor of CSS in patients with gastric cancer who underwent curative gastrectomy. We believe that the mACCI will become a novel marker that would guide treatment decisions for patients with gastric cancer suffering from comorbidities.     

Circulating tumor DNA detection after neoadjuvant treatment and surgery predicts recurrence in patients with early-stage and locally advanced rectal cancer

IntroductionPatients with early-stage and locally advanced rectal cancer are often treated with neoadjuvant therapy followed by surgery or watch and wait. This study evaluated the role of circulating tumor DNA (ctDNA) to measure disease after neoadjuvant treatment and surgery to optimize treatment choices.Materials and methodsPatients with rectal cancer treated with both chemotherapy and radiotherapy were included and diagnostic biopsies were analyzed for tumor-specific mutations. Presence of ctDNA was measured in plasma by tracing the tumor-informed mutations using a next-generation sequencing panel. The association between ctDNA detection and clinicopathological characteristics and progression-free survival was measured.ResultsBefore treatment ctDNA was detected in 69% (35/51) of patients. After neoadjuvant therapy ctDNA was detected in only 15% (5/34) of patients. In none of the patients with a complete clinical response who were selected for a watch and wait strategy (0/10) or patients with ypN0 disease (0/8) ctDNA was detected, whereas it was detected in 31% (5/16) of patients with ypN + disease. After surgery ctDNA was detected in 16% (3/19) of patients, of which all (3/3) developed recurrent disease compared to only 13% (2/16) in patients with undetected ctDNA after surgery. In an exploratory survival analysis, both ctDNA detection after neoadjuvant therapy and after surgery was associated with worse progression-free survival (p = 0.01 and p = 0.007, respectively, Cox-regression).ConclusionThese data show that in patients with early-stage and locally advanced rectal cancer tumor-informed ctDNA detection in plasma using ultradeep sequencing may have clinical value to complement response prediction after neoadjuvant therapy and surgery.     

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.     

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.