Phosphoinositide-3 kinase/protein kinase-B/mammalian target of rapamycin (PI3K/Akt/mTOR) signaling pathway is involved in many important biological processes such as cell metabolism, growth, proliferation, and angiogenesis. And its high-level activation is closely related to the development and progression of many malignant tumors. In this paper, mTOR and PI3K/Akt/mTOR signaling pathway are introduced, and their action mechanisms in the development and progression of hepatocellular carcinoma, cholangiocellular carcinoma, cholangiocarcinoma, and gallbladder carcinoma are expounded, and then the role of mTOR inhibitors in the treatment of malignant hepatobiliary tumors is briefly described. It is thought that the PI3K/Akt/mTOR signaling pathway provides new therapeutic targets for malignant hepatobiliary tumors in advanced stage and the constant development of new mTOR inhibitors provides some new hope for the patients with malignant hepatobiliary tumors in advanced stage.

Liver cancer is one of the common malignant tumors in clinic, and the incidence rate has been increasing year by year. Most patients are diagnosed at the advanced stage, and the prognosis is poor. The occurrence and development of hepatocellular carcinoma is closely associated with immune elimination, balance and escape. In recent years, checkpoint inhibitors have been used in clinic and immune checkpoint inhibitors have made extensive progress and application in clinical research, which has brought a significant opportunity to improve the survival rate of patients with advanced liver cancer. However, HCC patients develop immunotherapy resistance afterwords. The poor drug response to tumor cells is a serious problem affecting the clinical prognosis. This review briefly summarizes the potential mechanism of innate resistance and acquired resistance in immunotherapy of liver cancer.

Objective To investigate the risk factors of intrahepatic recurrence after resection for Barcelona Clinic Liver Cancer (BCLC) stage 0 hepatocellular carcinoma (HCC).Methods 58 patients with pathologically confirmed BCLC stage 0 HCC treated with liver resection at the Zhongshan Hospital,Fudan University from January to December 2011 were included in this study.The male/female ratio was 50/8.The age ranged from 31 to 72 years.The clinical,pathological and MR imaging features of these patients were analyzed.The recurrence-free survival rates between patients with HCC ≤ 1.5 cm (n=27) and ＞ 1.5 cm (n=31) were compared.The risk factors of intrahepatic recurrence for HCCs were compared using the Cox regression analysis.Results Intrahepatic recurrence was identified in 25 patients,and the median recurrence time was 33 months.The 3-and 5-year cumulative recurrence-free survival rates were 73.0％ (95％CI:60.7％～85.3％) and 52.3％ (95％CI:37.2％～67.4％).No significant differences were found in the recurrence-free survival rates between tumors ≤ 1.5 cm and ＞ 1.5 cm (P＞0.05).Multivariate analyses demonstrated that serum alpha-fetoprotein level ＞20 g/L (HR 3.773,95％CI:1.628～8.745;P＜0.05) and irregular tumor shape (HR 4.584,95％CI:1.485～ 14.155;P＜0.05) were independent risk factors of intrahepatic recurrence.Conclusions Elevated serum alpha-fetoprotein level and irregular tumor shape were associated with an increased risk of intrahepatic recurrence for BCLC stage 0 HCC patients after resection.They could be used as early prognostic indicators in clinical practice.

Objective:To investigate the effect of modified York-Mason technique on urethrorectal fistula after radical prostatectomy.Methods:A retrospective analysis of clinical data from 20 patients with urethrorectal fistula after radical prostatectomy admitted to Shanghai Sixth People's Hospital from May 2016 to October 2022 was conducted. Patients’ average age was (76.6±4.2) years. The etiology was rectal injury during radical prostatectomy. Patients present urine leakage from the anus during micturition. 2 cases also had bladder neck stenosis, and 1 case had urinary incontinence.3 cases had radiotherapy history because of prostate cancer. The average duration of urethrorectal fistula was (1.8±2.3)years. Preoperative imaging confirmed the presence of contrast agent flowing from the bladder neck into the rectum. Three suspicious patients also underwent CT three-dimensional reconstruction. Urethroscopy revealed a depression at the bladder neck in five cases. Anorectal examination in five cases showed the formation of gas bubbles in the lower anterior wall of the rectum, along with a concave anterior wall. The distance from the fistula to the anal margin was (6.0±2.1) cm, with fistula diameters ≥1 cm in twelve cases, <1 cm in eight cases. Twelve patients had previously undergone cystotomy, and seventeen patients had undergone colostomy. The modified York-Mason procedure was adopted for all 20 cases. The patients were under general anesthesia and placed in the prone jackknife position, with the buttocks spread and fixed to the sides to expose the anus. An 8 cm-long incision was made from two points near the sacrococcygeal joint to the anal edge, representing the modified York-Mason approach. After dividing the anal sphincter muscle, both sides were marked using 3-0 chromium thread for subsequent anal reconstruction. The urethrorectal fistula was exposed, and the urethral side of the fistula was sutured with 4-0 absorbable thread, while the anterior rectal wall side was sutured with 3-0 absorbable thread. In cases of bladder neck stenosis, urethral internal incision was performed, and a urethral catheter was retained for 3 weeks postoperatively. Perianal incision drainage tubes were removed after three days. Patients had colostomy repair could eat the day after surgery, while those who didn’t were fast for five days and received intravenous nutrition.Results:All 20 cases in this group were successfully completed without complications during surgery. Follow-up ranged from 10 to 48 months after surgery. Seventeen (17/20)cases had unobstructed urination, with a maximum urine flow rate >15 ml, and no urine leakage from the anus. Postoperative urethrography and cystourethroscopy showed there were no urethrorectal fistulas in 15 cases. None of the patients experienced fecal incontinence after the surgery, except for three patients with a history of radiotherapy who continued to experience anal leakage. One patient underwent a second modified York-Mason procedure and achieved complete recovery three months after the second surgery. Another patient had anal discharge, and the fistula healed after two weeks of urethral catheter retention. One patient refused further treatment due to advanced age and frailty but still had anal leakage. Another patient experienced regular urethral dilation for urination difficulties, while one patient continued to have urinary incontinence.Conclusions:The modified York-Mason technique could be an effective method for urethrorectal fistula after radical prostatectomy with high success rate and few side effects.

Objective:To investigate the effect of gracilis flap in repair of radiation-induced vesicovaginal fistula.Methods:The data of 18 patients with radiation-induced vesicovaginal fistula treated in the Sixth People’s Hospital Affiliated to Shanghai Jiaotong University School of Medicine from March 2021 to August 2022 were retrospectively reviewed. Their age was (57.3±10.4) years. All patients underwent radical surgery for cervical cancer, and received (24.6±2.8)(range from 20 to 30)times of radiotherapy after surger. The median time between the end of radiotherapy and the onset of vesicovaginal fistula was 14.0(7.8, 18.2)months. The median duration of fistula urine was 12.0(9.8, 18.0)months. All patients were required to use median 19.5(15.8, 27.5) pads per day before surgery. The life quality score(QOL)of 18 cases was median 5.0(5.0, 6.0) points. Three cases had performed laparoscopic vesicovaginal fistula repair, two cases had underwent transvaginal vesicovaginal fistula repair, one case had underwent transvaginal and laparoscopic vesicovaginal fistula repair successively, and the remaining 12 cases were new vesicovaginal fistulas. Two cases were combined with rectovaginal fistulas. All patients underwent the repair of vesicovaginal fistula with gracilis flap interposition in prone and folded knife position, by transvaginal route, the vesicovaginal fistula was mobilized and the two layers were closed, and the vascular pedicle gracilis flap of left inner leg was romoved under the skin tunnel to repair the vesicovaginal fistula. Meanwhile, two cases combined rectovaginal fistulas were repaired and closed the rectovaginal fistulas. The urinary catheters were removed at 3 weeks after the operation and urination was recorded.Results:All patients underwent smooth surgery in (96.6±13.2) minutes. The median follow-up was 13.0(9.8, 20.2)(range from 6 to 24)months. The median number of urine pads used per day in 18 patients was 2.0(1.0, 11.8), and significantly reduced ( P<0.01).QOL score was median 1.0(0, 4.2) point and significantly reduced ( P<0.01).Successful outcome was achieved in 12 patients with no leakage of urine in the vagina. Two cases developed urinary incontinence and required conservative treatment, but the curative effect was poor. Two cases still had vaginal urine leakage performed vesicovaginal fistula repair again. One case was successfully repaired without significant urine leakage.The other case still had significant urine leakage and the QOL score was 3 points. She refused further treatment for self-satisfied. Two cases still had vesicovaginal fistula and rectovaginal fistula after the surgery, and refused further surgery. Conclusions:Repair with gracilis flap interposition is a surgical method with few complications and reliable surgical effect for patients with radiation-induced vesicovaginal fistula.