Laparoscopic vs open abdominoperineal resection in the multimodality management of low rectal cancers

AIM: To evaluate the safety and feasibility of laparoscopic abdominoperineal resection compared with the open procedure in multimodality management of rectal cancer.METHODS: A total of 106 rectal cancer patients who underwent open abdominoperineal resection(OAPR) were matched with 106 patients who underwent laparoscopic abdominoperineal resection(LAPR) in a 1 to 1 fashion, between 2009 and 2013 at Fudan University Shanghai Cancer Center. Propensity score matching was carried out based on age, gender, pathological staging of the disease and administration of neoadjuvant chemoradiation. Data regarding preoperative staging, surgical technique, pathologicalresults, postoperative recovery and complications were reviewed and compared between the LAPR and OAPR groups. Perineal closure around the stoma and pelvic floor reconstruction were performed only in OAPR, not in LAPR. Therefore, abdominoperineal resection procedure-specific surgical complications including parastomal hernia and perineal wound complications were compared between the open and laparoscopic procedure. Regular surveillance of the two cohorts was carried out to gather prognostic data. Diseasefree survival was analyzed using Kaplan-Meier estimate and log-rank test. Subgroup analysis was performed in patients with locally advanced disease treated with preoperative chemoradiation followed by surgical resection. RESULTS: No significant difference was found between the LAPR group and the OAPR group in terms of clinicopathological features. The operation time(180.8 ± 47.8 min vs 172.1 ± 49.2 min, P = 0.190), operative blood loss(93.9 ± 60.0 m L vs 88.4 ± 55.2 m L, P = 0.494), total number of retrieved lymph nodes(12.9 ± 6.9 vs 12.9 ± 5.4, P = 0.974), surgical complications(12.3% vs 15.1%, P = 0.549) and pathological characteristics were comparable between the LAPR and OAPR group, respectively. Compared with OAPR patients, LAPR patients showed significantly shorter postoperative analgesia(2.4 ± 0.7 d vs 2.7 ± 0.6 d, P < 0.001), earlier first flatus(57.3 ± 7.9 h vs 63.5 ± 9.2 h, P < 0.001), shorter urinary drainage time(6.5 ± 3.4 d vs 7.8 ± 1.3 d, P < 0.001), and shorter postoperative admission(11.2 ± 4.7 d vs 12.6 ± 4.0 d, P = 0.014). With regard to APR-specific complications(perineal wound complications and parastomal hernia), there were no significant differences between the two groups. Similar results were found in the 26 pairs of patients administered neoadjuvant chemoradiation in subgroup analysis. During the follow-up period, no port site recurrences were observed. CONCLUSION: Laparoscopic abdominoperineal resection for multidisciplinary management of rectal cancer is safe, and is associated with earlier recovery and shorter admission time in combination with neoadjuvant chemoradiation.

Whole-genome sequencing reveals the evolutionary trajectory of HBV-related hepatocellular carcinoma early recurrence

Patients with hepatocellular carcinoma(HCC)have poor long-term survival following curative resection because of the high rate of tumor early recurrence.Little is known about the trajectory of genomic evolution from primary to early-recurrent HCC.In this study,we performed whole-genome sequencing(WGS)on 40 pairs of primary and early-recurrent hepatitis B virus(HBV)-related HCC tumors from patients who received curative resection,and from four patients whose primary and recurrent tumor were extensively sampled.We identified two recurrence patterns:de novo recurrence(18/40),which developed genetically independently of the primary tumor and carried different HCC drivers,and ancestral recurrence(22/40),which was clonally related to the primary tumor and progressed more rapidly than de novo recurrence.We found that the recurrence location was predictive of the recurrence pattern:distant recurrence tended to display the de novo pattern,whereas local recurrence tended to display the ancestral pattern.We then uncovered the evolutionary trajectories based on the subclonal architecture,driver-gene mutations,and mutational processes observed in the primary and recurrent tumors.Multi-region WGS demonstrated spatiotemporal heterogeneity and polyclonal,monophyletic dissemination in HCC ancestral recurrence.In addition,we identified recurrence-specific mutations and copy-number gains in BCL9,leading to WNT/β-catenin signaling activation and an immuneexcluded tumor microenvironment,which suggests that BCL9 might serve as a new therapeutic target for recurrent HCC.Collectively,our results allow us to view with unprecedented clarity the genomic evolution during HBV-related HCC early recurrence,providing an important molecular foundation for enhanced understanding of HCC with implications for personalized therapy to improve patient survival.