[Pelvic exenteration for late complications of radiation-induced pelvic injury: a preliminary study].

Objective: To investigate the safety and efficacy of total pelvic exenteration (TPE) for treating late complications of radiation-induced pelvic injury. Methods: This was a descriptive case series study. The inclusion criteria were as follows: (1) confirmed radiation-induced pelvic injury after radiotherapy for pelvic malignancies; (2) late complications of radiation-induced pelvic injury, such as bleeding, perforation, fistula, and obstruction, involving multiple pelvic organs; (3) TPE recommended by a multidisciplinary team; (4) patient in good preoperative condition and considered fit enough to tolerate TPE; and (5) patient extremely willing to undergo the procedure and accept the associated risks. The exclusion criteria were as follows: (1) preoperative or intraoperative diagnosis of tumor recurrence or metastasis; (2) had only undergone diversion or bypass surgery after laparoscopic exploration; and (3) incomplete medical records. Clinical and follow-up data of patients who had undergone TPE for late complications of radiation-induced pelvic injury between March 2020 and September 2022 at the Sixth Affiliated Hospital of Sun Yat-sen University were analyzed. Perioperative recovery, postoperative complications, perioperative deaths, and quality of life 1 year postoperatively were recorded. Results: The study cohort comprised 14 women, nine of whom had recto-vagino-vesical fistulas, two vesicovaginal fistulas, one ileo-vesical fistula and rectal necrosis, one ileo-vesical and rectovaginal fistulas, and one rectal ulcer and bilateral ureteral stenosis. The mean duration of surgery was 592.1±167.6 minutes and the median blood loss 550 (100-6000) mL. Ten patients underwent intestinal reconstruction, and four the Hartmann procedure. Ten patients underwent urinary reconstruction using Bricker's procedure and 7 underwent pelvic floor reconstruction. The mean postoperative hospital stay was 23.6±14.9 days. Seven patients (7/14) had serious postoperative complications (Clavien-Dindo IIIa to IVb), including surgical site infections in eight, abdominopelvic abscesses in five, pulmonary infections in five, intestinal obstruction in four, and urinary leakage in two. Empty pelvis syndrome (EPS) was diagnosed in five patients, none of whom had undergone pelvic floor reconstruction. Five of the seven patients who had not undergone pelvic floor reconstruction developed EPS, compared with none of those who had undergone pelvic floor reconstruction. One patient with EPS underwent reoperation because of a pelvic abscess, pelvic hemorrhage, and intestinal obstruction. There were no perioperative deaths. During 18.9±10.1 months of follow-up, three patients died, two of renal failure, which was a preoperative comorbidity, and one of COVID-19. The remaining patients had gradual and significant relief of symptoms during follow-up. QLQ-C30 assessment of postoperative quality of life showed gradual improvement in all functional domains and general health at 1, 3, and 6 months postoperatively (all P<0.05). Conclusions: TPE is a feasible procedure for treating late complications of radiation-induced pelvic injury combined with complex pelvic fistulas. TPE is effective in alleviating symptoms and improving quality of life. However, the indications for this procedure should be strictly controlled and the surgery carried out only by experienced surgeons.

[Clinical features and prognosis of anastomotic leak after anterior resection for rectal cancer following neoadjuvant chemoradiotherapy].

Objective: To explore clinical features and prognosis of anastomotic leak (AL) after anterior resection following neoadjuvant chemoradiotherapy for rectal cancer patients. Methods: A retrospective cohort study was performed. Data were retrieved from colorectal cancer database of the Sixth Affiliated Hospital, Sun Yat-sen University. The clinical data of 470 patients with rectal cancer who underwent anterior resection after neoadjuvant chemoradiotherapy at our department from September 2010 to December 2018 were enrolled. Clinical features and outcome of postoperative AL were analyzed. The primary outcomes were the short-term and long-term incidence and severity of AL (ISREC grading standard was adopted). The secondary outcomes were the prognostic indicators of AL, including the secondary chronic presacral sinus, anastomotic stenosis and persistent stoma. Patients received regular follow-up every 3-6 months after surgery, including physical examination, blood test, colonoscopy and image; those received follow-up once a year after postoperative 2-year; those who did not return to our hospital received telephone follow-up. Data of this study were retrieved up to January 2020. Univariate χ(2) test and multivariate logistic analysis were used to identify risk factors of AL and prognostic factors of persistent stoma. Results: There were 331 males (70.4%) with the average age of (53.5±11.6) years. Distance from tumor to anal verge ≤ 5 cm was found in 228 (48.5%) patients. The diverting stoma was performed in 440 (93.6%) patients. After a median follow-up of 28 months, AL was found in 129 (27.4%) patients, including 67 (14.3%) patients with clinical leak (ISREC grade B-C). The median time for diagnosis of AL was 70 days (2-515 days) after index surgery. Common symptoms included sacrococcygeal pain (27.9%, 36/129), purulent discharge through anus (25.6%, 33/129), and rectal irritation (17.8%, 23/129). Sixty five point one percent (84/129) of the defect site was at the posterior wall of the anastomosis. Transanal incision and drainage or lavage (27.9%, 36/129) and percutaneous drainage under ultrasound or CT (17.1%, 22/129) were the most common management. Chronic presacral sinus tract could not be evaluated in 12 patients because imaging was performed more than 1 year after the operation. Evaluation beyond 1 year showed that 73 of 458 eligible patients (15.9%) were found with chronic presacral sinus, accounting for 62.4% (73/117) of patients with AL; 69 of 454 (15.2%) were diagnosed with anastomotic stenosis, of whom 49 were secondary to AL; 59 of 470 (12.6%) had persistent stoma due to AL. Univariate analysis showed that male, operative duration > 180 minutes, intraoperative blood loss >150 ml, and pelvic radiation injury were associated with AL (all P<0.05). Multivariate analysis showed that male (OR=1.72, 95% CI: 1.04-2.86, P=0.036), intraoperative blood loss > 150 ml (OR=1.82, 95% CI: 1.11-2.97, P=0.017), and pelvic radiation injury (OR=4.90, 95% CI: 3.09-7.76, P<0.001) were independent risk factors of AL after anterior resection. For patients with AL, clinical leak (ISREC grade B-C) (OR=9.59, 95% CI: 3.73-24.69, P<0.001), age ≤55 years (OR=3.35, 95% CI: 1.35-8.30, P=0.009), distance from tumor to anal verge ≤ 5 cm (OR=3.33, 95% CI: 1.25-8.92, P=0.017), and pelvic radiation injury (OR=3.29, 95% CI: 1.33-8.14, P=0.010) were independent risk factors of persistent stoma. Conclusions: AL after anterior resection following neoadjuvant chemoradiotherapy for rectal cancer patients is common. Among patients with AL, the proportion of those needing persistent stoma is high. Pelvic radiation injury is significantly associated with occurrence of AL and subsequent persistent stoma. Sphincter-preserving surgery for rectal cancer should be selectively used based on the risk of pelvic radiation injury, which is beneficial to reduce the incidence of AL and improve the quality of life.

[Feasibility and safety of laparoscopic Parks procedure for chronic radiation proctopathy].

Objective: To preliminarily evaluate the feasibility and safety of laparoscopic Parks procedure for chronic radiation proctopathy (CRP). Methods: A descriptive cohort study was carried out. The clinical and follow-up data of 19 patients who received laparoscopic Parks procedure due to CRP in the Sixth Affiliated Hospital of Sun Yat-sen University from July 2013 to March 2019 were retrospectively analyzed. Inclusion criteria: (1) serious late complications occurred after pelvic radiotherapy, e.g.serious intractable hematochezia (hemoglobin <70 g/L), intractable anal pain (numerical rating scale >7), rectostenosis, perforation, and fistula. (2) imaging examinations including colonoscopy, pelvic MRI and/or chest, abdomen and pelvic CT were performed before surgery to confirm the lesions. Exclusion criteria: (1) preoperative or intraoperative diagnosis of tumor recurrence; (2) only ostomy was performed after laparoscopic exploration; (3) after neoadjuvant radiotherapy for rectal cancer; (4) incomplete medical records. Surgical procedures: (1) Laparoscopic exploration: tumor recurrence was excluded, and the range of radioactive damage in the intestine was determined. Marks were made on the proximal sigmoid colon without grossly obvious edema, thickening or radioactive injuries. (2) Abdominal operation: the right mesentery of sigmoid colon and rectum was opened, inferior mesenteric vein and inferior mesenteric artery were divided and the Toldt gap was expanded inwards and cephalad. The outside of left hemicolon was freed, the gastrocolic ligament was opened, the splenic flexure was fully mobilized, and the rectum was separated from the rear, side and front to the lowest point. Then perineal operation was performed. (3) Perineal operation: the whole layer of rectum wall was cut thoroughly at 1cm below the lesion's lower margin, the space around the rectum was fully separated, the rectum and sigmoid colon was pulled out through the anus and cut off at the site of the grossly normal intestine, the diseased bowel was removed and a coloanal anastomosis was made. (4) A protective stoma was performed. Conditions of operation, complication and symptom relief were summarized. A descriptive statistic method was used to analyze the results. Results: All the 19 patients were female with a median age of 53 (interquartiles, 50, 56) years old, of whom 18 patients had primary cervical cancer. Surgical indications: 9 cases were rectovaginal fistula; 9 cases were intractable anal pain, among whom 7 were complicated with deep rectal ulcer; and 1 case was intractable hematochezia with deep rectal ulcer. Eighteen cases completed laparoscopic Parks procedure, while 1 case was converted to laparotomy. The median operative time was 215 (131, 270) minutes, the median bleeding volume was 50 (50, 100) ml, and the median hospital stay was 12 (11, 20) days. There was no perioperative death. Ten cases had postoperative complications, including 3 cases of serious complications (CD grade IIIb and above) within 30 days after operation, of whom one case developed pelvic infection caused by rectovaginal, rectovesical and rectourethral fistula and acute renal failure (IVa); 2 cases developed orifice prolapse and parastomal hernia (IIIb). Seven cases had anastomosis-related complications, including 4 cases of grade A anastomotic leakage and 3 cases of anastomotic stenosis. Symptoms of CRP in the whole group were significantly relieved or disappeared after one year of the operation. Five cases achieved stoma closure. Conclusions: Laparoscopic Parks procedure for chronic radiation proctopathy is safe and feasible, and can effectively improve symptoms. However, the incidence of anastomotic complications is high, so the surgical indications should be strictly controlled.

[Analysis on operational safety of chronic radiation intestinal injury].

Objective: To investigate the safety and efficacy of surgical treatment for chronic radiation intestinal injury. Methods: A descriptive cohort study was performed. Clinical data of 73 patients with definite radiation history and diagnosed clinically as chronic radiation intestinal injury, undergoing operation at Department of Colorectal Surgery, the Sixth Affiliated Hospital of Sun Yat-sen University from January 1, 2012 to February 28, 2019, were reviewed and analyzed retrospectively. Patients did not undergo operation or only received adhesiolysis were excluded. All the patients had preoperative examination and overall evaluation of the disease. According to severity of intestinal obstruction and patients' diet, corresponding nutritional support and conservative treatment were given. Surgical methods: The one-stage bowel resection and anastomosis was the first choice for surgical treatment of chronic radiation intestinal injury. Patients with poor nutritional condition were given enterostomy and postoperative enteral nutrition and second-stage stoma closure and intestinal anastomosis if nutritional condition improved. For those who were unable to perform stoma closure, a permanent stoma should be performed. Patients with severe abdominal adhesion which was difficult to separate, enterostomy or bypass surgery after adhesiolysis would be the surgical choice. For patients with tumor metastasis or recurrence, enterostomy or bypass surgery should be selected. Observation parameters: the overall and major (Clavien-Dindo grades III to V) postoperative complication within 30 days after surgery or during hospitalization; mortality within postoperative 30 days; postoperative hospital stay; time to postoperative recovery of enteral nutrition; time to removal of drainage tube. Results: Of the 73 patients who had been enrolled in this study, 10 were male and 63 were female with median age of 54 (range, 34-80) years. Preoperative evaluation showed that 61 patients had intestinal stenosis, 63 had intestinal obstruction, 11 had intestinal perforation, 20 had intestinal fistula, 3 had intestinal bleeding, and 6 had abdominal abscess, of whom 64(87.7%) patients had multiple complications. Tumor recurrence or metastasis was found in 15 patients. A total of 65(89.0%) patients received preoperative nutritional support, of whom 35 received total parenteral nutrition and 30 received partial parenteral nutrition. The median preoperative nutritional support duration was 8.5 (range, 6.0-16.2) days. The rate of one-stage intestine resection was 69.9% (51/73), and one-stage enterostomy was 23.3% (17/73). In the 51 patients undergoing bowel resection, the average length of resected bowel was (50.3±49.1) cm. Among the 45 patients with intestinal anastomosis, 4 underwent manual anastomosis and 41 underwent stapled anastomosis; 36 underwent side-to-side anastomosis, 5 underwent end-to-side anastomosis, and 4 underwent end-to-end anastomosis. Eighty postoperative complications occurred in 39 patients and the overall postoperative complication rate was 53.4% (39/73), including 39 moderate to severe complications (Clavien-Dindo grade III-V) in 20 patients (27.4%, 20/73) and postoperative anastomotic leakage in 2 patients (2.7%, 2/73). The mortality within postoperative 30 days was 2.7% (2/73); both patients died of abdominal infection, septic shock, and multiple organ failure caused by anastomotic leakage. The median postoperative hospital stay was 13 (11, 23) days, the postoperative enteral nutrition time was (7.2±6.9) days and the postoperative drainage tube removal time was (6.3±4.2) days. Conclusions: Surgical treatment, especially one-stage anastomosis, is safe and feasible for chronic radiation intestine injury. Defining the extent of bowel resection, rational selection of the anatomic position of the anastomosis and perioperative nutritional support treatment are the key to reduce postoperative complications.

[Clinical features and risk factors of surgical complications after intersphincteric resection for low rectal cancer following neoadjuvant chemoradiotherapy].

Objective: To explore clinical features and prognosis factors of surgical complications after intersphincteric resection (ISR) for low rectal cancer following neoadjuvant chemoradiotherapy. Methods: The clinical data of 132 patients with low rectal cancer who underwent ISR following neoadjuvant chemoradiotherapy from September 2010 to June 2017 at Department of Colorectal Surgery, Sixth Affiliated Hospital, Sun Yat-sen University were retrospectively reviewed. There were 100 males and 32 females, with the age of (52.9±11.4) years and distance to anal verge of 3.9 cm. Records of perioperative complication (POC) within 30 days after surgery, anastomotic leakage (AL), and anastomotic stenosis (AS) were analyzed. POC was recorded according to the Clavien-Dindo classification. AL was graded by ISREC system and classified into the early AL within 30 days after surgery and delayed AL beyond 30 days. AS was defined as narrowing of the bowel lumen at the anastomosis that prevented passage through a colonoscope with a 12 mm diameter. According to the shape of narrowing, AS was recorded as the stenosis in situ or stenosis with long-segment bowel above. Univariate and multivariate analysis were used to identify risk factors of anastomotic complications. Results: Among the 132 patients, full-dose radiotherapy and diverting stoma were performed in 128 (97.0%) patients, respectively. In entire cohort, AL was found in 41 (31.1%) patients, including 32 patients with clinical leakage (24.2%). The median time for diagnosis of AL was 37 days (2 to 214 days) after surgery. There were 25 patients (18.9%) who were diagnosed with delayed AL beyond 30 days. Chronic presacral sinus formation was detected in 22 of 129 (17.1%) patients at 12 months from surgery. Among the 128 eligible patients, 36 (28.1%) were diagnosed as AS, including 24 (18.8%) patients with stenosis in situ and 12 (9.4%) patients with bowel stenosis above. After a median follow-up of 26 months, 7(5.3%) patients received permanent colostomy and the other 20(15.2%) patients retained a persistent ileostomy, owing to anastomotic complications. Results of multivariate analysis showed that radiation colitis was an independent prognosis factor of AL after ISR (OR=5.04, 95% CI: 2.05 to 12.43, P=0.000); male gender (OR=5.19, 95% CI: 1.24 to 21.75, P=0.024) and AL (OR=8.49, 95% CI: 3.32 to 21.70, P=0.000) were independent prognosis factors of AS after ISR. Conclusions: Surgical complications are common after ISR for low rectal cancer patients with neoadjuvant chemoradiotherapy. A high rate of AL is observed after long-term follow-up, which is associated with AS. Increasing awareness of anastomotic complications after ISR should be raised, especially for male patients with radiation colitis.

[Treatment for peritoneal metastasis of colorectal cancer].

Peritoneal metastasis is the second leading cause of death of colorectal cancer patients. Cytoreductive surgery (CRS) combined with hyperthermia intraperitoneal chemotherapy (HIPEC) is the primary method to treat peritoneal metastasis of colorectal cancer, though there remain some controversies. We reviewed current studies of colorectal peritoneal carcinomatosis (PC) and CRS+ HIPEC, and discussed some issues with regard to the scoring system for peritoneal metastasis, selection criteria for CRS+ HIPEC treatment, and the new drug application for colorectal PC. Peritoneal carcinomatosis index (PCI) is the most useful scoring system for peritoneal metastasis and CRS+ HIPEC is the primary treatment for colorectal PC. Patients with PCI<20 should receive thorough assessment on the feasibility of R0 or R1 resection and CRS+ HIPEC treatment. For patients with unresectable PC at the initial stage, active drug therapy should be adopted to achieve tumor regression, so that some of them would have the opportunity to receive CRS+ HIPEC treatment.

[Attach importance to standardized treatment of chronic radiation proctopathy].

Radiation proctopathy represents the feared injury of rectum resulting from radiotherapy to pelvic malignancy. Interstitial fibrosis is the major histopathologic feature of chronic radiation proctopathy, whose symptoms may improve over time without any management. Treatment decisions should be based on the pattern and severity of symptoms and endoscopic findings. Non-surgical interventions are generally used to relieve major symptoms and prevent severe complications. Surgery is reserved for patients with refractory complications. Diverting stoma and restorative resection are suggested for selected patients to promote rehabilitation. Overall management should target on the improvement of patients' long-term quality-of-life.

[Pathological insights of radiotherapy-related damage to surgical margin after preoperative radiotherapy in patients with rectal cancer].

Objective: To investigate the effect of irradiation to anastomosis from preoperative radiotherapy for patients with rectal cancer by studying the pathological changes. Methods: In this retrospective study, patients enrolled in the FOWARC study from January 2011 to July 2014 in the Sixth Affiliated Hospital of Sun Yat-Sen University were included. In the FOWARC study, enrolled patients with local advanced rectal cancer were randomly assigned to receive either neoadjuvant chemo-radiotherapy or chemotherapy. Among these patients, 23 patients were selected as radiation proctitis (RP)group, who fulfilled these conditions: (1) received neoadjuvant chemo-radiotherapy followed by sphincter-preserving surgery; (2) developed radiation proctitis as confirmed by preoperative imaging diagnosis; (3) had intact clinical samples of surgical margins. Twenty-three patients who had received neoadjuvant chemo-radiotherapy but without development of radiation proctitis were selected as non-radiation proctitis (nRP) group. Meanwhile, 23 patients received neoadjuvant chemotherapy only were selected as neoadjuvant chemotherapy (CT) group. Both nRP and CT cases were selected by ensuring the basic characteristics such as sex, age, tumor site, lengths of proximal margin and distal margin all maximally matched to the RP group. Both proximal and distal margins were collected for further analysis for all selected cases. Microscopy slices were prepared for hematoxylin & eosin staining and Masson staining to show general pathological changes, and also for immunohistochemistry with anti-CD-34 as primary antibody to reveal the microvessel. Microvessel counting in submucosal layer and proportion of macrovessel with stenosis were used to evaluate the blood supply of the proximal and distal end of anastomosis. A modified semi-quantitative grading approach was used to evaluate the severity of radiation-induced injury. Either ANOVA analysis, Kruskal-Wallis rank-sum test or χ(2) test was used for comparison among three groups, and Mann-Whitney U test was used for comparison between two groups. Results: Compared to group of neoadjuvant chemotherapy only, patients receiving neoadjuvant chemo-radiotherapy had lower microvessel count in both proximal and distal margins (M(Q(R)): proximal, 25.5 (19.6) vs. 50.0 (25.0), Z=3.915, P=0.000; distal, 20.5 (17.5) vs. 49.0 (28.0), Z=3.558, P=0.000), higher proportions of macrovessel with stenosis (proximal, 9.5% (23.8%) vs. 0, Z=3.993, P=0.000; distal, 11.5%(37.3%) vs. 0 (2.0%), Z=2.893, P=0.004), higher histopathologic score (proximal, 4.0 (2.0) vs. 1.0 (2.0), Z=6.123, P=0.000; distal, 5.0 (3.0) vs. 2.0 (1.0), Z=4.849, P=0.000). In patients receiving neoadjuvant chemo-radiotherapy, compared to nRP group, RP group had lower microvessel count in both proximal and distal margins (proximal, 19.0 (23.0) vs. 30.4 (38.0), Z=2.845, P=0.004; distal, 19.0 (13.0) vs. 30.0(29.1), Z=2.022, P=0.043), higher proportions of macrovessel with stenosis (proximal, 23.0% (40.0%) vs. 0(11.0%), Z=3.248, P=0.001; distal, 27.0% (45.0%) vs. 3.0% (19.0%), Z=2.164, P=0.030). Rate of anastomotic leakage for CT, nRP and RP group were 8.7% (2/23), 30.4% (7/23), and 52.2% (12/23), and the differences among three groups were statistically significant (χ(2)=10.268, P=0.007). Conclusion: Radiation-induced injury existed on both margins of the resected rectal site after preoperative radiotherapy, and those diagnosed as radiation proctitis had more severe microvascular injury.

[Benzoquinone induce autophagy in HL60 cells and the role of reactive oxygen species in induced autophagy].

OBJECTIVE: To investigate whether autophagy can be induced by 1, 4-benzoquinone (1, 4-BQ) in HL60 cells, as well as the role of reactive oxygen species (ROS) in induced autophagy. METHODS: In order to determine a suitable 1, 4-BQ treatment concentration for autophagy detection in HL60 cells, the cell vitality were examined by CCK8 assay. Logarithmic-growth-phased cells were divided into control group, 1, 4-BQ group (10µmol/L 1, 4-BQ, 24 h) , NAC group (antioxidant n-acetyl cysteine, 5mmol/L, 24 h) and the 1, 4-BQ+NAC group (5 mmol/L NAC were preincubated for 1h prior to the treatment with 10 µmol/L 1, 4-BQ for 24 h). The autophagic acidic vesicle were inspected by acridine orange staining, LC3 were detected by immunofluorescence staining, and expressions of LC3 and Beclin1 were quantitatively detected by Western blot. RESULTS: The results from cell viability test indicated that 1, 4-BQ exhibited a dose-dependent toxicity to HL60 cells. Compared with control group.the cell viability in 20.0、40.0µmol/L concentration were decreased obviously, and the differences had statistical significance (P<0.05). Compare with contrd group acidic vesicle, LC3II, LC3II/LC3I and Beclin1 protein expressions were increased in 1, 4-BQ group, after both respectively 12.4% and 27%, the differences had statistital significance. While 1, 4-BQ+NAC group was observed that acidic vesicle, LC3 and Beclin1 protein level were markedly lower than 1, 4-BQ group, after both decreased 12.6% and 22.6% respectively, both the difference were statistically significant (P<0.05). CONCLUSION: 1, 4-BQ can induce autophagy in HL60 cells, the induction of autophagy is at least partly resulted from ROS. Antioxidant can effectively suppress the occurrence of induced autophagy.