5-year Cumulative Recurrence Rate Research Articles

Transanal total mesorectal excision: short- and long-term results of four certified colorectal cancer centers in Germany

BackgroundTransanal total mesorectal excision (TaTME), a novel approach for treating low rectal cancer, holds promise. However, concerns exist in certain countries about their oncologic safety due to less-than-optimal outcomes on global studies. This research seeks to evaluate the long-term oncologic outcomes focusing on local recurrence rate and overall survival after TaTME surgery in Germany.Patients and methodsThis study analyzed data from patients who underwent elective TaTME surgery between 2014 and 2021 in four certified colorectal cancer centers in Germany. Primary endpoints were 3-year local recurrence rate and local recurrence-free survival (LRFS). Secondary outcomes encompassed overall survival (OS), operative time, completeness of local tumor resection, lymph node resection, and postoperative complications.ResultsA total of 378 patients were analyzed (mean age 61.6 years; 272 males, 72%). After a median follow-up period of 2.5 years, 326 patients with UICC-stages I–III and tumor operability included in survival analyses. Local recurrence was observed in 8 individuals, leading to a 3-year cumulative local recurrence rate of 2.2% and a 3-year LRFS rate of 88.1%. The 3-year OS rate stood at 88.9%. Within 30 days after surgery, anastomotic leakage occurred in 19 cases (5%), whereas a presacral abscess was present in 12 patients (3.2%).ConclusionTaTME proves effective in addressing the anatomical and technical challenges of low rectal surgery and is associated with pleasing short- and long-term results. However, its safe integration into surgical routine necessitates sufficient knowledge and a previously completed training program.

Identifying prognostic predictors for postoperative pituitary neuroendocrine tumour recurrence: an integrated clinical, radiological, and immunohistochemistry assessment

Objective Pituitary neuroendocrine tumours (PitNETs) are the second most common type of intracranial tumour. Several studies have explored the prognostic factors for PitNETs. However, prognostic factors for postoperative PitNET recurrence remain not fully understood. This study aimed to explore potential prognostic factors for PitNET recurrence, such as surrounding tissue invasion and the extent of surgical resection in patients with postoperative PitNETs. Methods We included 106 patients who underwent PitNET surgery between 2013 and 2018, dividing them into two groups: those with recurrence and those without recurrence. Tumours were classified based on demographics, neuroradiological, and immunohistological characteristics. Univariate and multivariate analyses were used to determine factors predicting recurrence. Kaplan–Meier plots and log-rank tests were used to analyse each independent factor based on the cumulative 5-year recurrence rate. Results During the 5-year follow-up period, 29.2% of the patients (n = 31) had disease recurrence. Univariate analysis showed that predictors of recurrence included cavernous and sphenoid sinus invasions, optic chiasm compression, larger tumour volume, giant adenoma >4 cm, and gross total resection (GTR). Multivariate analysis showed that lactotroph tumour type, sphenoid sinus invasion, and GTR were independent predictors. Kaplan–Meier analysis revealed significant differences in the 5-year recurrence rate among the three independent predictors, with significantly lower recurrence rate in patients with lactotroph tumours and GTR, and a significantly higher recurrence risk in patients with sphenoid sinus invasion. Conclusions Lactotroph tumour type, sphenoid sinus invasion, and GTR are independent predictors of postoperative PitNET recurrence. This study provides insights into the factors affecting postoperative PitNET recurrence.

Assessing the Adequacy of Traditional Vertebral Landmarks as Upper Border of Whole Pelvic Radiotherapy Field for Stage IB2-IIB Cervical Cancer.

This study investigates the impact of insufficient common iliac lymph node (CIN) irradiation on treatment outcomes in patients with stage IB2-IIB cervical cancer receiving concurrent chemoradiotherapy (CCRT). We retrospectively analyzed 68 patients with Federation of Gynecology and Obstetrics stage IB2-IIB, treated with weekly cisplatin-based CCRT from 2008 to 2018. Patients received external-beam whole pelvic radiotherapy (WPRT) and concurrent cisplatin chemotherapy, followed by high-dose-rate brachytherapy. The WPRT upper border was at L4-5 in 61 patients and L3-4 in 7 patients. Thirty-seven patients had the CIN area fully included (full-CIN group), while 31 had partial inclusion (partial-CIN group). Recurrence rates and survival outcomes were analyzed over a median follow-up of 111 months. Patient characteristics and the irradiated dose were comparable. Treatment failure occurred in three patients (8.1%) in the full-CIN group and in six patients (19.4%) in the partial-CIN group, with CIN and para-aortic lymph node recurrence in two and one patients, respectively. The 5-year cumulative recurrence rate was 0% for the full-CIN group and 11.4% for the partial-CIN group (p = 0.04). Cause-specific survival was 100% vs. 87.1% (p = 0.025), and the overall survival was 94.3% vs. 87.1% (p = 0.44). Fully including the CIN area in WPRT is crucial for stage IB2-IIB cervical cancer. Vascular anatomical margins should be considered over vertebral landmarks.

Effect of donor and recipient HLA mismatched locus on the prognosis of childhood with leukemia after umbilical cord blood transplantation

Objective: The aim of the study was to investigate the impact of the sites of high-resolution human leukocyte antigen (HLA) mismatch on the prognosis of children with leukemia undergoing umbilical cord blood transplantation (UCBT). Methods: Clinical data and high-resolution HLA-A, HLA-B, HLA-C, HLA-DRB1 and HLA-DQB1 locus gene information were collected in the children who underwent the UCBT for the first time at Children's Hospital of Soochow University between January 2016 and June 2023. In each locus, according to whether the two genes were compatible, they were divided into a compatible group (two genes were perfectly matched) and a non-compatible group (one gene was not matched). In different loci, the differences in occurrence, recurrence, non-recurrence death and survival of acute graft versus host disease (aGVHD) were compared between the two groups. Multivariate Cox regression was employed to analyzed the influencing factors for overall survival rate, and Fine-Gray proportional hazards model was employed to analyze the influencing factors of other outcome events. Results: A total of 100 patients were enrolled (55 males and 45 females), whose age [M (Q1, Q3)] at the time of transplantation was 3.9 (2.0, 6.5) years. There were 55 cases in the HLA-A matched group and 45 cases in the mismatched group. The 5-year non-recurrence mortality (NRM) in the HLA-A matched group was lower than that in the mismatched group (P=0.024). The cumulative incidence of aGVHD within 100 days after transplantation in the HLA-A matched group was lower than that in the mismatched group (P=0.017), and there were no statistically significant differences in other outcome events between the groups (all P>0.05). There were 70 cases in the HLA-B matched group and 30 cases in the mismatched group. The 5-year cumulative recurrence rate in the HLA-B matched group was higher than that in the mismatched group (P=0.027). There were 79 cases in the HLA-C matched group and 21 cases in the mismatched group, and there were no statistically difference in the outcome events between the groups (P>0.05). There were 73 cases in HLA-DRB1 matched group and 27 cases in mismatched group. The 5-year overall survival rate in HLA-DRB1 matched group was higher than that in mismatched group (P=0.036), the 5-year cumulative recurrence rate in HLA-DRB1 matched group was higher than that in mismatched group (P=0.028), and the 5-year NRM in HLA-DRB1 matched group was lower than that in mismatched group (P=0.008). The cumulative incidence of aGVHD within 100 days after transplantation in the matched group was lower than that in the mismatched group (P=0.010), and and there were no statistically significant difference in other outcome events between the groups (P>0.05). There were 68 cases in HLA-DQB1 matched group and 32 cases in mismatched group. There was no statistical difference in outcome events between the two groups (all P>0.05). The risk of aGVHD in HLA-A mismatched group was higher than that in HLA-A matched group (HR=1.25, 95%CI: 1.12-1.38). The risk of recurrence in HLA-B mismatched group was lower than that in HLA-B matched group (HR=0.77, 95%CI: 0.63-0.91). Mismatched group at HLA-DRB1 compared with matched group at HLA-DRB1, had a higher risk of aGVHD (HR=1.37, 95%CI: 1.26-1.48), a higher risk of non-recurrence death (HR=1.39, 95%CI: 1.28-1.50), and a higher risk of death (HR=1.27, 95%CI: 1.18-1.36). No association was found between HLA-C and HLA-DQB1 locus with the risk of aGVHD, recurrence, non-recurrence death, and survival (all P>0.05). Conclusions: In UCBT, the risk of aGVHD in children with matching HLA-A sites of donor and recipient is lower than that in children with incompatible HLA-A sites. Compared with children with incompatible HLA-DRB1 sites, children with HLA-DRB1 matched sites has a lower risk of acute GVHD, a lower 5-year NRM, and a higher risk of death. The recurrence rate of children with matching HLA-B loci is higher than that of children without matching HLA-B loci.

Subdivision of pT1N0 (American Joint Committee on Cancer 8th edition) distal cholangiocarcinoma for adjuvant chemotherapy consideration.

The adjuvant S-1 trial affirmed adjuvant chemotherapy for biliary tract cancer but excluded pT1N0 distal cholangiocarcinoma (DCC) according to the seventh edition of the American Joint Committee on Cancer (AJCC) classification. The introduction of tumor depth of invasion (DOI) for T-classification in the eighth edition complicates identifying DCC patients less likely to benefit from adjuvant chemotherapy. Our cohort consisted of 185 patients with DCC who underwent pancreaticoduodenectomy between 2002 and 2019. We compared clinicopathological factors and survival outcomes between pT1N0 patients in the seventh edition and those in the eighth edition. New DOI cutoffs for subdividing pT1N0 (8th edition) patients were evaluated to identify patients less likely to benefit from adjuvant chemotherapy. Transitioning to the eighth edition increased in pT1N0 cases from eight to 46. The 5-year cumulative recurrence rates of them were 14.3% for the seventh edition and 28.3% for the eighth edition. We proposed a DOI cutoff of <2 mm, at which the 5-year cumulative recurrence rate was 11.5%. The eighth AJCC classification revealed that a significant proportion of pT1N0 DCC patients were at risk for recurrence. A DOI cutoff of <2 mm may be considered to potentially improve patient selection for adjuvant chemotherapy.

Association of Pringle maneuver with postoperative recurrence and survival following hepatectomy for hepatocellular carcinoma: a multicenter propensity score and competing-risks regression analysis.

The application of Pringle maneuver (PM) during hepatectomy reduces intraoperative blood loss and the need for perioperative transfusion, but its effect on long-term recurrence and survival for patients with hepatocellular carcinoma (HCC) remains controversial. We sought to determine the association between the application of PM and post-hepatectomy oncologic outcomes for patients with HCC. Patients who underwent curative hepatectomy for HCC at 9 Chinese hospitals from January 2010 to December 2018 were identified. Using two propensity score methods [propensity score matching (PSM) and inverse probability of treatment weight (IPTW)], cumulative recurrence rate and cancer-specific mortality (CSM) were compared between the patients in the PM and non-PM groups. Multivariate competing-risks regression models were performed to adjust for the effect of non-cancer-specific mortality and other prognostic risk factors. Of the 2,798 included patients, 2,404 and 394 did and did not adopt PM (the PM and non-PM groups), respectively. The rates of intraoperative blood transfusion, postoperative 30-day mortality and morbidity were comparable between the two groups (all P>0.05). In the PSM cohort by the 1:3 ratio, compared to 382 patients in the non-PM group, 1,146 patients in the PM group also had the higher cumulative 5-year recurrence rate and CSM (63.9% and 39.1% vs. 55.3% and 31.6%, both P<0.05). Similar results were also yielded in the entire cohort and the IPTW cohort. Multivariate competing-risks regression analyses demonstrated that no application of the PM was independently associated with lower recurrence rate and CSM based on various analytical cohorts [hazard ratio (HR), 0.82 and 0.77 in the adjusted entire cohort, HR 0.80 and 0.73 in the PSM cohort, and HR 0.80 and 0.76 in the IPTW cohort, respectively]. The findings suggested that no application of PM during hepatectomy for patients with HCC reduced the risk of postoperative recurrence and cancer-specific death by approximately 20-25%.

Robotic versus laparoscopic distal gastrectomy for resectable gastric cancer: a randomized phase 2 trial

Robotic surgery may be an alternative to laparoscopic surgery for gastric cancer (GC). However, randomized controlled trials (RCTs) reporting the differences in survival between these two approaches are currently lacking. From September 2017 to January 2020, 300 patients with cT1-4a and N0/+ were enrolled and randomized to either the robotic (RDG) or laparoscopic distal gastrectomy (LDG) group (NCT03313700). The primary endpoint was 3-year disease-free survival (DFS); secondary endpoints reported here are the 3-year overall survival (OS) and recurrence patterns. The remaining secondary outcomes include intraoperative outcomes, postoperative recovery, quality of lymphadenectomy, and cost differences, which have previously been reported. There were 283 patients in the modified intention-to-treat analysis (RDG group: n = 141; LDG group: n = 142). The trial has met pre-specified endpoints. The 3-year DFS rates were 85.8% and 73.2% in the RDG and LDG groups, respectively (p = 0.011). Multivariable Cox regression model including age, tumor size, sex, ECOG PS, lymphovascular invasion, histology, pT stage, and pN stage showed that RDG was associated with better 3-year DFS (HR: 0.541; 95% CI: 0.314-0.932). The RDG also improved the 3-year cumulative recurrence rate (RDG vs. LDG: 12.1% vs. 21.1%; HR: 0.546, 95% CI: 0.302-0.990). Compared to LDG, RDG demonstrated non-inferiority in 3-year DFS rate.

Analysis of the efficacy and prognostic factors of allogeneic hematopoietic stem cell transplantation in patients with myelodysplastic syndrome with blastomycosis and survival comparison of different subtypes after the WHO 2022 reclassification

Objective: To evaluate the efficacy and prognostic factors of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in patients with myelodysplastic syndrome accompanied by myelodysplasia (MDS-EB) and to compare the prognosis of different subtypes of patients classified by World Health Organization (WHO) 2022. Methods: A total of 282 patients with MDS-EB who underwent allo-HSCT at the Hematology Hospital of the Chinese Academy of Medical Sciences from October 2006 to December 2022 were included in the study. The WHO 2022 diagnostic criteria reclassified MDS into three groups: myelodysplastic tumors with type 1/2 of primitive cell proliferation (MDS-IB1/IB2, 222 cases), MDS with fibrosis (MDS-f, 41 cases), and MDS with biallelic TP53 mutation (MDS-biTP53, 19 cases). Their clinical data were retrospectively analyzed. Results: ① The median age of 282 patients was 46 (15-66) years, with 191 males and 91 females. Among them, 118 (42% ) and 164 (58% ) had MDS-EB1 and MDS-EB2, respectively. ②Among the 282 patients, 256 (90.8% ) achieved hematopoietic reconstruction after transplantation, with 11 (3.9% ) and 15 (5.3% ) having primary and secondary implantation dysfunctions, respectively. The cumulative incidence of acute graft-versus-host disease (GVHD) 100 days post-transplantation was (42.6±3.0) %, and the cumulative incidence of grade Ⅱ-Ⅳ acute GVHD was (33.0±2.8) %. The cumulative incidence of chronic GVHD 1 year post-transplantation was (31.0±2.9) %. Post-transplantation, 128 (45.4% ), 63 (22.3% ), 35 (12.4% ), and 17 patients (6.0% ) developed cytomegalovirus infection, bacteremia, pulmonary fungal infection, and Epstein-Barr virus infection. ③The median follow-up time post-transplantation was 22.1 (19.2-24.7) months, and the 3-year overall survival (OS) and disease-free survival (DFS) rates were 71.9% (95% CI 65.7% -78.6% ) and 63.6% (95% CI 57.2% -70.7% ), respectively. The 3-year non-recurrent mortality rate (NRM) is 17.9% (95% CI 13.9% -22.9% ), and the 3-year cumulative recurrence rate (CIR) is 9.8% (95% CI 6.7% -13.7% ). The independent risk factors affecting OS post-transplantation include monocyte karyotype (P=0.004, HR=3.26, 95% CI 1.46-7.29), hematopoietic stem cell transplantation complication index (HCI-CI) of ≥3 points (P<0.001, HR=2.86, 95% CI 1.72-4.75), and the occurrence of acute gastrointestinal GVHD of grade Ⅱ-Ⅳ (P<0.001, HR=5.94, 95% CI 3.50-10.10). ④The 3-year OS and DFS rates in the MDS-IB1/IB2 group post-transplantation were better than those in the MDS-biTP53 group [OS: 72.0% (95% CI 63.4% -80.7% ) vs 46.4% (95% CI 26.9% -80.1% ), P=0.020; DFS: 67.4% (95% CI 60.3% -75.3% ) vs 39.7% (95% CI 22.3% -70.8% ), P=0.015]. The 3-year CIR was lower than that of the MDS-biTP53 group [7.3% (95% CI 4.3% -11.4% ) vs 26.9% (95% CI 9.2% -48.5% ), P=0.004]. The NRM at 3 years post-transplantation in the MDS-IB1/IB2, MDS-f, and MDS-biTP53 groups were 16.7% (95% CI 12.1% -22.1% ), 20.5% (95% CI 9.4% -34.6% ), and 26.3% (95% CI 9.1% -47.5% ), respectively (P=0.690) . Conclusion: Allo-HSCT is an effective treatment for MDS-EB, with monomeric karyotype, HCI-CI, and grade Ⅱ-Ⅳ acute gastrointestinal GVHD as independent risk factors affecting the patient's OS. The WHO 2022 classification helps distinguish the efficacy of allo-HSCT in different subgroups of patients. Allo-HSCT can improve the poor prognosis of patients with MDS-f, but those with MDS-biTP53 have a higher risk of recurrence post-transplantation.

Laparoscopic Spleen-Preserving Hilar Lymphadenectomy for Advanced Proximal Gastric Cancer Without Greater Curvature Invasion

Splenic hilar lymphadenectomy has been recommended for locally advanced proximal gastric cancer (APGC) involving the greater curvature. However, it is unclear whether laparoscopic spleen-preserving splenic hilar lymphadenectomy (LSPSHL) is associated with a long-term survival benefit for APGC without greater curvature invasion. To present the 5-year follow-up data from a randomized clinical trial that compared laparoscopic total gastrectomy (D2 group) with D2 plus LSPSHL (D2 + No. 10 group) among patients with resectable APGC. This is a post hoc secondary analysis of a randomized clinical trial that enrolled 536 patients with potentially resectable APGC (cT2-4a, N0 or N+, and M0) without greater curvature invasion from January 5, 2015, to October 10, 2018. All patients were tracked for at least 5 years. The final follow-up was on October 30, 2023. Patients were randomly assigned in a 1:1 ratio to the D2 + No. 10 or D2 groups. The 5-year disease-free survival (DFS) and overall survival (OS) rates were measured. Recurrence patterns and causes of death were compared. A total of 526 patients (392 men [74.5%]; mean [SD] age, 60.6 [9.6] years) were included in the modified intent-to-treat analysis, with 263 patients in each group. The 5-year DFS rate was 63.9% (95% CI, 58.1%-69.7%) for the D2 + No. 10 group and 55.1% (95% CI, 49.1%-61.1%) for the D2 group (log-rank P = .04). A statistically significant difference was observed in the 5-year OS between the D2 + No. 10 group and the D2 group (66.2% [95% CI, 60.4%-71.9%] vs 57.4% [95% CI, 51.4%-63.4%]; log-rank P = .03). The No. 10 lymph node exhibited a therapeutic value index (TVI) of 6.5, surpassing that of Nos. 8a (TVI, 3.0), 11 (TVI, 5.8), and 12a (TVI, 0.8). A total of 86 patients in the D2 + No. 10 group (cumulative incidence, 32.7%) and 111 patients in the D2 group (cumulative incidence, 42.2%) experienced recurrence (hazard ratio, 0.72; 95% CI, 0.54-0.95; P = .02). The multivariable competing risk regression model demonstrated that D2 + No. 10 remained an independent protective factor for a lower 5-year cumulative recurrence rate after surgery (hazard ratio, 0.75; 95% CI, 0.56-1.00; P = .05). There was a significant difference in the 5-year cumulative recurrence rate at the No. 10 lymph node area between the 2 groups (D2 + No. 10 group vs D2 group: 0% vs 2.3% [n = 6]; P = .01). This post hoc secondary analysis of a randomized clinical trial found that laparoscopic total gastrectomy with LSPSHL can improve the prognosis and reduce recurrence for APGC without greater curvature invasion. Future multicenter studies are warranted to validate these findings. ClinicalTrials.gov Identifier: NCT02333721.

Long-term survival and functional outcomes of laparoscopic surgery for clinical stage I ultra-low rectal cancers located within 5 cm of the anal verge: A prospective phase II trial (Ultimate trial).

To clarify the long-term oncological outcomes and postoperative anal, urinary, and sexual functions after laparoscopic surgery for clinical stage I very low rectal carcinoma located near the anal canal. Laparoscopic surgery is widely applied for rectal cancer; however, concerns remain, with some studies showing poorer outcomes compared to open surgery. This single-arm, phase II trial included patients registered preoperatively from 47 institutions in Japan. The planned sample size was 300. The primary endpoint was the 3-year local recurrence rate. Anal, urinary, and sexual functions were evaluated using a prospective questionnaire. Three-hundred patients were registered between January 2014 and March 2017. Anus-preserving surgery was performed in 278 (93%), including 172 who underwent intersphincteric resection (58%) and 106 (36%) who underwent low anterior resection. The 3-year cumulative local recurrence rate was 6.3%. At 3 years postoperatively, 87% of patients used their own anus, and the median incontinence score improved from 12 at 3 months to 8 at 3 years. Only 5% of patients had severe incontinence (incontinence score of 16 points). Postoperative urinary function evaluation showed that International Prostate Symptom Score and Overactive Bladder Symptom Score decreased 1 week after surgery, but recovered to preoperative level 1 month after surgery. International Consultation on Incontinence Questionnaire-Sort Form remained almost stable after surgery. Sexual function evaluation using the International Index of Erectile Function-5 and International Index of Erectile Function-15 revealed that the patients had deteriorated 3 months after surgery but had recovered only slightly by 6 months. Laparoscopic surgery achieves feasible long-term oncological outcomes and a high rate of anus preservation with moderate anal function, and an acceptable incontinence score. While urinary function recovered rapidly, sexual function showed poor recovery.

The impact of Karnofsky performance status on prognosis of patients with hepatocellular carcinoma in liver transplantation

BackgroundFunctional performance as measured by the Karnofsky Performance Status (KPS) scale has been linked to the outcomes of liver transplant patients; however, the effect of KPS on the outcomes of the hepatocellular carcinoma (HCC) liver transplant population has not been fully elucidated. We aimed to investigate the association between pre-transplant KPS score and long-term outcomes in HCC patients listed for liver transplantation.MethodsAdult HCC candidates listed on the Scientific Registry of Transplant Recipients (SRTR) database from January 1, 2011 to December 31, 2017 were grouped into group I (KPS 80–100%, n = 8,379), group II (KPS 50–70%, n = 8,091), and group III (KPS 10–40%, n = 1,256) based on percentage KPS score at listing. Survival was compared and multivariable analysis was performed to identify independent predictors.ResultsPatients with low KPS score had a higher risk of removal from the waiting list. The 5-year intent-to-treat survival was 57.7% in group I, 53.2% in group II and 46.7% in group III (P < 0.001). The corresponding overall survival was 77.6%, 73.7% and 66.3% in three groups, respectively (P < 0.001). Multivariable analysis demonstrated that KPS was an independent predictor of intent-to-treat survival (P < 0.001, reference group I; HR 1.19 [95%CI 1.07–1.31] for group II, P = 0.001; HR 1.63 [95%CI 1.34–1.99] for group III, P < 0.001) and overall survival(P < 0.001, reference group I; HR 1.16 [95%CI 1.05–1.28] for group II, P = 0.004; HR 1.53 [95%CI 1.26–1.87] for group III, P < 0.001). The cumulative 5-year recurrence rates was higher in group III patients (7.4%), compared with 5.2% in group I and 5.5% in group II (P = 0.037). However, this was not significant in the competing regression analysis.ConclusionsLow pre-transplant KPS score is associated with inferior long-term survival in liver transplant HCC patients, but is not significantly associated with post-transplant tumor recurrence.

The clinical value of a nomogram constructed from CEA, CA199, PT, FIB, tumor differentiation and TNM stage in colorectal cancer.

The accurate Tumor-Node-Metastasis (TNM) staging of colorectal cancer (CRC) is of great guiding significance for the judgment of tumor progression and prognosis, and the formulation of treatment strategies. The aim of this study was to construct a recurrence risk scoring (RRS) system and prognostic prediction model to improve the accuracy of staging, prognosis prediction, and clinical decision making in resectable CRC. CRC patients who underwent radical resection were retrospectively enrolled into study. Multivariable Cox regression model was applied to screen for independent prognostic factors. The RRS system is composed of independent prognostic factors which was awarded 1point each. A prognostic model composed of RRS and TNM staging system (RRS-TNM model) was applied to predict postoperative recurrence. TNM stage, tumor differentiation, preoperative elevated Carcinoembryonic Antigen, Carbohydrate Antigen 199, Prothrombin Time and Fibrinogen were the independent prognostic biomarkers. 173 of 540 patients had recurrence. The 5-year cumulative recurrence rate (5-y CRR) and disease-free survival (DFS) of postoperative p-TNM stage I, II, and III were 12.7% and 104.8 months, 26.5% and 89.3 months, and 55.5% and 57.3 months, respectively. The 5-y CRR and DFS of preoperative Low-risk (RRS 0-1score), Middle-risk (RRS 2-3scores), and High-risk (RRS 4-5scores) groups were 13.9% and 101.1 months, 40.9% and 75.5 months, and 70.2% and 41.1 months. The AUC (area under ROC curve) of RRS system was not inferior to that of TNM staging system (0.713 vs. 0.666; P= 0.093). The AUC (0.770) and C-index value (0.721) of RRS-TNM model were significantly better than both RRS and TNM staging system (P< 0.001). The RRS system accurately identifies CRC patients with high-risk recurrence preoperatively. Constructing a nomogram using the RRS system and TNM staging significantly improves the accuracy of staging and prognosis prediction, which is of great clinical significance for individualized clinical treatment and follow-up of CRC.

Risk factors for postoperative recurrence in patients with stage II colorectal cancer

BackgroundRecurrences are the main reasons for unfavorable outcomes for patients with stage II colorectal cancer (CRC). To obtain a clear understanding of the high-risk factors, further investigation is warranted. The present study aimed to analyze the risk factors associated with postoperative recurrence in patients with stage II CRC.MethodsEligible patients with pathologically confirmed stage II CRC were enrolled in the study retrospectively based on a prospectively maintained database from April 2008 to March 2019. The Kaplan–Meier method were used to calculate the overall survival (OS) rate and the cumulative recurrence rate. Univariate and multivariable Cox regression analyses were performed to identify risk factors for recurrence.ResultsThere were 2515 patients included, of whom 233 (9.3%) developed local or distant recurrence. Recurrence was associated with a significantly worse 5-year OS (45.4% vs. 95.5%, p < 0.0001). The 5-year cumulative recurrence rate was 13.0% in patients with stage II CRC. On multivariable Cox analysis, tumor size (Hazard Ratio (HR) [95% confidence interval (CI)] = 1.79[1.38, 2.33]), preoperative carbohydrate antigen (CA) 125 level (HR [95% CI] = 1.78[1.17, 2.70]), preoperative CA 199 level (HR [95% CI] = 1.56[1.09, 2.22]), and ulcerating tumor (HR [95% CI] = 1.61[1.19, 2.17]) were found to be associated with postoperative recurrence. Adjuvant chemotherapy was associated with a lower cumulative recurrence rate in patients with these risk factors (p = 0.00096).ConclusionThe tumor diameter, preoperative CA125 level, preoperative CA199 level, and an ulcerative tumor can predict postoperative recurrence in patients with stage II CRC, and postoperative chemotherapy could reduce the cumulative recurrence rate in patients with these high-risk factors.

Preoperative Prediction of Microvascular Invasion with Gadoxetic Acid-Enhanced Magnetic Resonance Imaging in Patients with Single Hepatocellular Carcinoma: The Implication of Surgical Decision on the Extent of Liver Resection

Introduction: Microvascular invasion (MVI) is one of the most important prognostic factors for hepatocellular carcinoma (HCC) recurrence, but its application in preoperative clinical decisions is limited. This study aimed to identify preoperative predictive factors for MVI in HCC and further evaluate oncologic outcomes of different types and extents of hepatectomy according to stratified risk of MVI. Methods: Patients with surgically resected single HCC (≤5 cm) who underwent preoperative gadoxetic acid-enhanced magnetic resonance imaging (MRI) were included in a single-center retrospective study. Two radiologists reviewed the images with no clinical, pathological, or prognostic information. Significant predictive factors for MVI were identified using logistic regression analysis against pathologic MVI and used to stratify patients. In the subgroup analysis, long-term outcomes of the stratified patients were analyzed using the Kaplan-Meier method with log-rank test and compared between anatomical and nonanatomical or major and minor resection. Results: A total of 408 patients, 318 men and 90 women, with a mean age of 56.7 years were included. Elevated levels of tumor markers (alpha-fetoprotein [α-FP] ≥25 ng/mL and PIVKA-II ≥40 mAU/mL) and three MRI features (tumor size ≥3 cm, non-smooth tumor margin, and arterial peritumoral enhancement) were independent predictive factors for MVI. As the MVI risk increased from low (no predictive factor) and intermediate (1–2 factors) to high-risk (3–4 factors), recurrence-free and overall survival of each group significantly decreased (p = 0.001). In the high MVI risk group, 5-year cumulative recurrence rate was significantly lower in patients who underwent major compared to minor hepatectomy (26.6 vs. 59.8%, p = 0.027). Conclusion: Tumor markers and MRI features can predict the risk of MVI and prognosis after hepatectomy. Patients with high MVI risk had the worst prognosis among the three groups, and major hepatectomy improved long-term outcomes in these high-risk patients.

Predictors and Prognostic Significance of Postoperative Complications for Patients with Intrahepatic Cholangiocarcinoma.

The prognostic impact of major postoperative complications (POCs) for intrahepatic cholangiocarcinoma (ICC) remains ill-defined. We sought to analyze the relationship between POCs and outcomes relative to lymph node metastases (LNM) and tumor burden score (TBS). Patients who underwent resection of ICC between 1990-2020 were included from an international database. POCs were defined according to Clavien-Dindo classification ≥ 3. The prognostic impact of POCs was estimated relative to TBS categories (i.e., high and low) and lymph node status (i.e., N0 or N1). Among 553 patients who underwent curative-intent resection for ICC, 128 (23.1%) individuals experienced POCs. Low TBS/N0 patients who experienced POCs presented with a higher risk of recurrence and death (3-year cumulative recurrence rate; POCs: 74.8% vs. no POCs: 43.5%, p = 0.006; 5-year overall survival [OS], POCs 37.8% vs. no POCs 65.8%, p = 0.003), while POCs were not associated with worse outcomes among high TBS and/or N1 patients. The Cox regression analysis confirmed that POCs were significant predictors of poor outcomes in low TBS/N0 patients (OS, hazard ratio [HR] 2.91, 95%CI 1.45-5.82, p = 0.003; recurrence free survival [RFS], HR 2.42, 95%CI 1.28-4.56, p = 0.007). Among low TBS/N0 patients, POCs were associated with early recurrence (within 2years) (Odds ratio [OR] 2.79 95%CI 1.13-6.93, p = 0.03) and extrahepatic recurrence (OR 3.13, 95%CI 1.14-8.54, p = 0.03), in contrast to patients with high TBS and/or nodal disease. POCs were independent, negative prognostic determinants for both OS and RFS among low TBS/N0 patients. Perioperative strategies that minimize the risk of POCs are critical to improving prognosis, especially among patients harboring favorable clinicopathologic features.

Laparoscopic versus open pelvic exenteration for locally advanced rectal cancer: analysis of short- and long-term effects

Objective: To explore the feasibility, safety, and short- and long-term efficacy of laparoscopic pelvic exenteration (LPE) in treating locally advanced rectal cancer. Methods: The clinical data of 173 patients who had undergone pelvic exenteration (PE) for locally advanced rectal cancer that had been shown by preoperative imaging or intraoperative exploration to have invaded beyond the mesorectal excision plane and adjacent organs in the Cancer Hospital, Chinese Academy of Medical Sciences (n=64) and Peking University First Hospital (n=109) from 2010 January to 2021 December were collected retrospectively. Laparoscopic PE (LPE) had been performed on 82 of these patients and open PE (OPE) on 91. Short- and long-term outcomes (1-, 3-, and 5-year overall and disease-free survival and 1- and 3-year cumulative local recurrence rates) were compared between these groups. Results: The only statistically significant difference in baseline data between the two groups (P>0.05) was administration of neoadjuvant therapy. Compared with OPE, LPE had a significantly shorter operative time (319.3±129.3 minutes versus 417.3±155.0 minutes, t=4.531, P<0.001) and less intraoperative blood loss (175 [20-2000] ml vs. 500 [20-4500] ml, U=2206.500, P<0.001). The R0 resection rates were 98.8% and 94.5%, respectively (χ2=2.355, P=0.214). At 18.3% (15/82), and the incidence of perioperative complications was lower in the LPE group than in the OPE group (37.4% [34/91], χ2=7.727, P=0.005). The rates of surgical site infection were 7.3% (6/82) and 23.1% (21/91) in the LPE and OPE group, respectively (χ2=8.134, P=0.004). The rates of abdominal wound infection were 0 and 12.1% (11/91) (χ2=10.585, P=0.001), respectively, and of urinary tract infection 0 and 6.6% (6/91) (χ2=5.601, P=0.030), respectively. Postoperative hospital stay was shorter in the LPE than OPE group (12 [4-60] days vs. 15 [7-87] days, U=2498.000, P<0.001). The median follow-up time was 40 (2-88) months in the LPE group and 59 (1-130) months in the OPE group. The 1-, 3-, and 5-year overall survival rates were 91.3%, 76.0%, and 62.5%, respectively, in the LPE group, and 91.2%, 68.9%, and 57.6%, respectively, in the OPE group. The 1, 3, and 5-year disease-free survival rates were 82.8%, 64.9%, and 59.7%, respectively, in the LPE group and 76.9%, 57.8%, and 52.7%, respectively, in the OPE group. The 1- and 3-year cumulative local recurrence rates were 5.1% and 14.1%, respectively, in the LPE group and 8.0% and 15.1%, respectively, in the OPE group (both P>0.05). Conclusions: In locally advanced rectal cancer patients, LPE is associated with shorter operative time, less intraoperative blood loss, fewer perioperative complications, and shorter hospital stay compared with OPE. It is safe and feasible without compromising oncological effect.

AFP Response to Locoregional Therapy Can Stratify the Risk of Tumor Recurrence in HCC Patients after Living Donor Liver Transplantation

(1) Background: Alpha-fetoprotein (AFP) has been incorporated into the selection criteria of liver transplantation and been used to predict the outcome of hepatocellular carcinoma (HCC) recurrence. Locoregional therapy (LRT) is recommended for bridging or downstaging in HCC patients listed for liver transplantation. The aim of this study was to evaluate the effect of the AFP response to LRT on the outcomes of hepatocellular carcinoma patients after living donor liver transplantation (LDLT). (2) Methods: This retrospective study included 370 HCC LDLT recipients with pretransplant LRT from 2000 to 2016. The patients were divided into four groups according to AFP response to LRT. (3) Results: The nonresponse group had the worst 5-year cumulative recurrence rates whereas the complete-response group (patients with abnormal AFP before LRT and with normal AFP after LRT) had the best 5-year cumulative recurrence rate among the four groups. The 5-year cumulative recurrence rate of the partial-response group (AFP response was over 15% lower) was comparable to the control group. (4) Conclusions: AFP response to LRT can be used to stratify the risk of HCC recurrence after LDLT. If a partial AFP response of over 15% declineis achieved, a comparable result to the control can be expected.

Long-term outcomes of upfront robotic rectal cancer surgery: a single-center, retrospective cohort study in Japan.

The purpose of this study was to evaluate the long-term outcomes of robotic rectal cancer surgery and to examine the risk factors for recurrence. In a high-volume center in Japan, we retrospectively enrolled patients with pStage I-III rectal cancer within 15cm of the anal verge who underwent robotic surgery from 2011 to 2017. Almost all patients underwent upfront surgery, and lateral lymph-node dissection (LLND) was performed for patients with locally advanced lower rectal cancer. We evaluated the 5-year overall survival (OS), relapse-free survival (RFS), and cumulative local recurrence (LR) rates and examined the risk factors for the RFS. We evaluated 488 patients who underwent robotic rectal cancer surgery, including 5.1% who underwent preoperative chemoradiotherapy to obtain clear resection margins and 33.6% who underwent LLND. There were 203, 87, and 198 patients with pStage I, II, and III, respectively, and the positive resection margin rate was 1.0%. The 5-year OS, RFS, and LR rates were 95.5%, 81.7%, and 2.2%, respectively. The independent risk factors for the RFS were the presence of venous invasion, extramural tumor deposits without lymph-node structure, and pT ≥ 3. This study demonstrated the favorable long-term outcomes of robotic rectal cancer surgery.

Identifying Recurrences Among Non-Metastatic Colorectal Cancer Patients Using National Health Data Registries: Validation and Optimization of a Registry-Based Algorithm in a Modern Danish Cohort.

Colorectal cancer (CRC) recurrence is not routinely recorded in Danish health data registries. Here, we aimed to revalidate a registry-based algorithm to identify recurrences in a contemporary cohort and to investigate the accuracy of estimating the time to recurrence (TTR). We ascertained data on 1129 patients operated for UICC TNM stage I-III CRC during 2012-2017 registered in the CRC biobank at the Department of Molecular Medicine, Aarhus University Hospital, Denmark. Individual-level data were linked with data from the Danish Colorectal Cancer Group database, Danish Cancer Registry, Danish National Registry of Patients, and Danish Pathology Registry. The algorithm identified recurrence based on diagnosis codes of local recurrence or metastases, the receipt of chemotherapy, or a pathological tissue assessment code of recurrence more than 180 days after CRC surgery. A subgroup was selected for validation of the algorithm using medical record reviews as a reference standard. We found a 3-year cumulative recurrence rate of 20% (95% CI: 17-22%). Manual medical record review identified 80 recurrences in the validation cohort of 522 patients. The algorithm detected recurrence with 94% sensitivity (75/80; 95% CI: 86-98%) and 98% specificity (431/442; 95% CI: 96-99%). The positive and negative predictive values of the algorithm were 87% (95% CI: 78-93%) and 99% (95% CI: 97-100%), respectively. The median difference in TTR (TTRMedical_chart-TTRalgorithm) was -8 days (IQR: -21 to +3 days). Restricting the algorithm to chemotherapy codes from oncology departments increased the positive predictive value from 87% to 94% without changing the negative predictive value (99%). The algorithm detected recurrence and TTR with high precision in this contemporary cohort. Restriction to chemotherapy codes from oncology departments using department classifications improves the algorithm. The algorithm is suitable for use in future observational studies.

Longitudinal Change of Serum Inter-α-Trypsin Inhibitor Heavy Chain H4 and its Relation with Inflammation, Disease Recurrence, and Mortality in Acute Ischemic Stroke Patients.

Inter-α-trypsin inhibitor heavy chain H4 (ITIH4) modulates atherosclerosis, lipid, and inflammation, which is involved in the development of acute ischemic stroke. Hence, this study aimed to investigate the longitudinal change and prognostic role of ITIH4 in acute ischemic stroke. In 267 patients with acute ischemic stroke, serum ITIH4 after admission (baseline), the 1st day after admission (D1), D3, D7, and D30, and inflammatory cytokines at baseline were detected by enzyme-linked immunosorbent assay (ELISA). Additionally, serum ITIH4 of 30 controls after enrollment was detected by ELISA. ITIH4 was reduced in acute ischemic stroke patients than controls [median (interquartile range, IQR): 131.0 (95.5-194.3) vs. 418.6 (241.5-506.8) ng/mL] (P < 0.001). Among acute ischemic stroke patients, ITIH4 was negatively associated with tumor necrosis factor-alpha (r = -0.211, P = 0.001), interleukin (IL)-1β (r = -0.164, P = 0.007), IL-6 (r = -0.121, P = 0.049), and IL-17A (r = -0.188, P = 0.002). ITIH4 presented a decreased trend from admission to D3, then increased from D3 to D30 (P < 0.001). The 1-year, 2-year, and 3-year cumulative recurrence rate was 7.5%, 18.0%, and 19.1%, respectively; meanwhile, 1-year, 2-year, and 3-year cumulative death rate was 2.2%, 7.1%, and 7.1%, accordingly. The further analysis presented that ITIH4 at baseline (P = 0.002), D1 (P = 0.049), D3 (P = 0.003), D7 (P < 0.001), and D30 (P < 0.001) was decreased in recurrent patients than non-recurrent patients; besides, ITIH4 at D3 (P = 0.017), D7 (P = 0.004), and D30 (P = 0.002), but not at baseline (P = 0.151) or D1 (P = 0.013), was decreased in deaths than survivors. Serum ITIH4 declines at first and then elevates with time, and its reduction is correlated with higher inflammation, increased risk of recurrence and mortality in acute ischemic stroke patients.