[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.

Predictive values of FAP and HGF for tumor angiogenesis and metastasis in colorectal cancer.

This study aims to explore the correlation of hepatocyte growth factor (HGF) and fibroblast activation protein (FAP) expressions with the angiogenesis and metastasis in colorectal cancer (CRC). The immunohistochemical SABC method was used to detect HGF and FAP expressions in 127 CRC tissues, 51 colorectal polyp tissues and 28 normal tissues. HGF and FAP expressions in liver metastasis were detected using western blot to analyze the correlation of their expressions with lymph node metastasis and liver metastasis. Micro-vessel density (MVD) and clinic-pathologic information of CRC patients were recorded and analyzed. In CRC group, HGF and FAP expressions were greatly higher than those in normal group and colorectal polyps group (P < 0.05). Moreover, the positive rates of HGF and FAP expressions in lymph node metastasis were evidently higher than those in non-lymph node metastasis (P < 0.05). In liver metastasis group, HGF and FAP expressions were obviously higher than non-liver metastasis group (P < 0.05). CRC group had much more MVD in comparison with normal group and colorectal polyps group (P < 0.05).When compared with negative group, MVD was significantly higher than that in CRC tissue with positive HGF and FAP (P < 0.05). Spearman rank correlation analysis showed that HGF and FAP were in positive correlation with MVD (r = 0.542, P < 0.001; r = 0.753, P < 0.001). These results indicate that FAP and HGF play an important role in CRC angiogenesis, and their expression levels are valuable to predict CRC liver metastasis and lymph node metastasis.

[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.

Association of T1740C polymorphism of L-FABP with meat quality traits in Junmu No. 1 white swine.

This study was designed to investigate a single nucleotide polymorphism in intron 1 of the liver fatty acid-binding protein (L-FABP) gene in 156 Junmu No. 1 white swine using PCR-single-strand conformational polymorphism. The association between the polymorphism and meat quality traits was also studied. The cloning and sequencing results indicated that the polymorphism in intron 1 was due to a T→C mutation at position 1740 of L-FABP, yielding three genotypes (TT, TC, and CC). Association analysis revealed that the polymorphism had a significant effect on marbling (P < 0.05): genotype CC had more marbling than TC, and TC had more marbling than TT. The polymorphism also had a highly significant effect on intramuscular fat content (P < 0.01). Genotypes CC and TC had higher intramuscular fat content than TT; there was no significant difference between CC and TC (P > 0.05). However, no significant conclusions concerning other traits could be drawn. We tentatively conclude that L-FABP is a candidate gene or a quantitative trait locus-linked gene associated with meat quality traits.

[Clincal practice of pelvic exenteration for late complications of pelvic radiation injury].

Pelvic radiation injury can potentially involve multiple pelvic organs, and due to its progressive and irreversible nature, its late stage can be complicated by fistulas, perforations, obstructions and other complications involved multiple pelvic organs, which seriously affect the long-term survival and the quality of life of patients. As a multidisciplinary surgical approach, pelvic exenteration has potential application in the treatment of late complications of pelvic radiation injury by completely removing the irradiated lesion, relieving symptoms and avoiding recurrence of symptoms. In clinical practice, we should advocate the concept of "pelvic radiation injury", emphasize multidisciplinary collaboration, fully evaluate the overall status of patients, primary tumor and pelvic radiation injury. We should follow the principles of "damage-control" and "extended resection", and follow the principle of enhanced recovery after surgery to achieve the goal of ensuring the surgical safety, relieving patients' symptoms and improving patients' quality of life and long-term survival.

[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.

[Observational study on perioperative outcomes of pelvic exenteration].

Objective: To investigate the surgical indications and perioperative clinical outcomes of pelvic exenteration (PE) for locally advanced, recurrent pelvic malignancies and complex pelvic fistulas. Methods: This was a descriptive study.The indications for performing PE were: (1) locally advanced, recurrent pelvic malignancy or complex pelvic fistula diagnosed preoperatively by imaging and pathological examination of a biopsy; (2)preoperative agreement by a multi-disciplinary team that non-surgical and conventional surgical treatment had failed and PE was required; and (3) findings on intraoperative exploration confirming this conclusion.Contraindications to this surgical procedure comprised cardiac and respiratory dysfunction, poor nutritional status,and mental state too poor to tolerate the procedure.Clinical data of 141 patients who met the above criteria, had undergone PE in the Sixth Affiliated Hospital of Sun Yat-sen University from January 2018 to September 2022, had complete perioperative clinical data, and had given written informed consent to the procedure were collected,and the operation,relevant perioperative variables, postoperative pathological findings (curative resection), and early postoperative complications were analyzed. Results: Of the 141 included patients, 43 (30.5%) had primary malignancies, 61 (43.3%) recurrent malignancies, 28 (19.9%) complex fistulas after radical resection of malignancies,and nine (6.4%)complex fistulas caused by benign disease. There were 79 cases (56.0%) of gastrointestinal tumors, 30 cases (21.3%) of reproductive tumors, 16 cases (11.3%) of urinary tumors, and 7 cases (5.0%) of other tumors such mesenchymal tissue tumors. Among the 104 patients with primary and recurrent malignancies, 15 patients with severe complications of pelvic perineum of advanced tumors were planned to undergo palliative PE surgery for symptom relief after preoperative assessment of multidisciplinary team; the other 89 patients were evaluated for radical PE surgery. All surgeries were successfully completed. Total PE was performed on 73 patients (51.8%),anterior PE on 22 (15.6%),and posterior PE in 46 (32.6%). The median operative time was 576 (453,679) minutes, median intraoperative blood loss 500 (200, 1 200) ml, and median hospital stay 17 (13.0,30.5)days.There were no intraoperative deaths. Of the 89 patients evaluated for radical PE surgery, the radical R0 resection was achieved in 64 (71.9%) of them, R1 resection in 23 (25.8%), and R2 resection in two (2.2%). One or more postoperative complications occurred in 85 cases (60.3%), 32 (22.7%)of which were Clavien-Dindo grade III and above.One patient (0.7%)died during the perioperative period. Conclusion: PE is a valid option for treating locally advanced or recurrent pelvic malignancies and complex pelvic fistulas.

Luteinizing hormone receptor splicing variants in bovine Leydig cells.

The luteinizing hormone receptor (LHR) plays a key role in testosterone production through its interaction with the gonadotropins, LH and chorionic gonadotropin. We examined the LHR splicing pattern in bovine Leydig cells; LH-induced expression of eight cloned splicing variants was detected by real-time PCR. Luteinizing hormone applied to cultured Leydig cells resulted in expression of full-length LHR and the A and B isoforms, as well as secretion of testosterone, which first increased, then declined, and then increased further, with increased LH levels. The secretion of testosterone progressively increased with increasing LH, but the expression levels of LHR (FL, A, and B) did not increase correspondingly. We conclude that the LHR splicing pattern is complex in bovine Leydig cells, and that expression of full-length LHR and isoforms A and B changes when induced with LH.

Micronucleus assays with Tradescantia pollen tetrads: an update.

Micronucleus (MN) assays with early pollen tetrad cells of Tradescantia (Trad-MN assays) are at present the most widely used bioassays with plants for the detection of genotoxins in the environment. So far, ∼ 160 chemicals have been tested and ∼ 100 articles that concern complex environmental mixtures were published. This article summarises the results of Trad-MN studies, which have been carried out during the last 15 years with individual compounds and investigations concerning the pollution of environmental compartments (soil, water and air). The evaluation shows that the effects of certain genotoxins such as heavy metals, radionuclides, pesticides and air pollutants can be easily detected with this test. Comparisons with results obtained in MN studies with mitotic (root tip) cells indicate that meiotic tetrad cells are in general more sensitive. Important issues for future research concern the evaluation of the suitability of wildlife Tradescantia species that are sometimes used instead of specific clones (such as #4430 for which standardised protocols have been developed) as well as the assessment of the predictive value of Trad-MN results in regard to the prediction of cancer hazards in humans and adverse effects at the ecosystem level. The fact that the genotoxic effects of certain compound such as metals, which can be detected with plant bioassays, in particular with the Trad-MN assay but not in other commonly used bioassays (e.g. in bacterial tests) makes them an essential element in the batteries for environmental monitoring.

Molecular cloning and sequence analysis of follicle-stimulating hormone beta polypeptide precursor cDNA from the bovine pituitary gland.

Follicle-stimulating hormone (FSH) plays an essential role in mammalian spermatogenesis and follicular development. In a previous study, we demonstrated that some bulls carry numerous linked mutations in the FSH beta-subunit (FSHB) gene, and that these bulls have poor-quality semen, low fertility, and slightly lower serum FSH concentration compared to those without such mutations. Here, we identified the different FSHB mRNA transcripts in such individuals and analyzed the evolutionary pattern of the FSHB open reading frame (ORF) in different species. Two different lengths of FSHB mRNA transcripts corresponding to two different polyadenylation sites in the 3'-UTR were detected in wild-type bull pituitary glands, and four different mRNA transcripts resulting from the different polyadenylation sites and linked mutations were identified in mutation-bearing bull pituitaries. All transcripts had almost the same putative FSHB precursor molecule. When the ORF sequences of wild-type and mutation-bearing genes were compared with those of other tetrapod species, the leopard frog had the lowest level of homology (57.8 and 58.1%) and the buffalo had the highest level (95.9 and 96.7%), respectively. These results indicated that the bovine FSHB gene transcribes at least two classes of mRNA in the wild-type and four classes of mRNA in the mutation-bearing individuals, which provides a new insight into the bovine FSHB evolutionary pattern. In addition, these findings lay a foundation for further study of gene expression regulation and the effects of mutations on male fertility traits in cattle.

[Interpretation of Chinese expert consensus on multidisciplinary diagnosis and treatment of radiation rectal injury (2021 edition)].

Although pelvic radiotherapy has played an important role in the treatment of malignant tumors, it is still difficult to avoid radiation damage within a certain period of time. In 2021, under the joint promotion of Colorectal Surgery Group of Chinese Medical Association Surgery Branch, Colorectal Surgeons Committee of Chinese Medical Doctor Association Surgeons Branch, Colorectal Surgeons Committee of Chinese Medical Doctor Association, and Colorectal Cancer Professional Committee of Chinese Anti-Cancer Association, Expert Group on Diagnosis and Treatment of Radiation Intestinal Injury has updated and formulated the 2021 edition of the "Chinese expert consensus on the multidisciplinary diagnosis and treatment of radiation rectal injury" (hereinafter referred to as "Consensus"). This Consensus edition has major changes compared with the "Chinese consensus on the diagnosis and treatment of radiation proctitis (2018)", which mainly updates in the following aspects: (1) adjusting the name of radiation rectal injury: the term "radiation proctitis" was adjusted to "radiation rectal injury"; (2) advocating the concept of pelvic integral injury and the multidisciplinary diagnosis and treatment model; (3) putting forward the clinical classification of diseases: the classification of the chronic rectal injury includes telangiectasia, ulcer, stenosis and mixed type; (4) carrying out individualized treatment based on the characteristics of the above-mentioned disease classification, and adjusting the recommended level of non-surgical treatment; (5) proposing specific guiding principles and details of surgical treatment: "damage control" and "expanded resection" principles, etc. This new edition (2021) of Consensus further refines the disease analysis and treatment strategies, which not only improves the guiding value of clinical practice, but also provides an important reference for the standardized diagnosis and treatment of radiation rectal injury in China.

[Meta analysis of diseased bowel resection versus diversion enterostomy in the treatment of late severe complications of chronic radiation-induced rectal injury].

Objective: To investigate the efficacy and safety of diseased bowel resection and diversion enterostomy in the treatment of late severe complications of chronic radiation-induced late rectal injury (RLRI). Methods: Studies about comparison of diseased bowel resection and diversion enterostomy in the treatment of late severe complications of chronic RLRI were screened and retrieved from databases, including PubMed, EMBASE, Scopus, Web of Science, Cochrane Library, CNKI, VIP, CBM and Wanfang. The following terms in Chinese were used to search [Title/Abstract]: radiation-induced intestinal injury, radiation proctitis, surgery. The following English terms were used to search: Radiation-induced intestinal injury, Bowel injury from radiation, Radiation proctitis, Surgery, Colostomy. Literature inclusion criteria: (1) studies with control groups, published at home and abroad publicly, about the postoperative effects of diseased bowel resection vs. diversion enterostomy on RLRI patients with late severe complications; (2) the period of the study performed in the literatures must be clear; (3) patients at the preoperative diagnosis for RLRI with refractory bleeding, narrow, obstruction, perforation or fistula, etc.; (4) diseased bowel resection included Hartmann, Dixon, Bacon and Parks; diversion enterostomy included colostomy and ileostomy; (5) if the studies were published by the same institution or authors at the same time, the study with the biggest sample size was chosen; studies conducted in different time with different subjects were simultaneously included; (6) at least one prognostic indicator of the following parameters should be included: the improvement of symptoms, postoperative complications, mortality, and reversed stomas rate. The stoma reduction rate was defined as the ratio of successful closure of colostomy after diseased bowel resection and diversion enterostomy. The method of direct calculation or the method of convert into direct calculation were used for stoma reduction rate. Exclusion criteria: (1) a single-arm study without control group; (2) RLRI patients did not undergo diseased bowel resection or diversion enterostomy at the first time; (3) RLRI patients with distant metastasis; (4) the statistical method in the study was not appropriate; (5) the information was not complete, such as a lack of prognosis in the observational indexes. After screening literatures according to criteria, data retrieval and quality evaluation were carried out. Review Manager 5.3 software was used for Meta-analysis. Sensitivity analysis was used to exam the stability of results. Funnel diagram was used to analyze the bias of publication. Results: A total of 11 literatures were enrolled, including 426 RLRI patients with late severe complications, of whom 174 underwent diseased bowel resection (resection group) and 252 underwent diversion enterostomy (diversion group), respectively. Compared with diversion group, although resection group had a higher morbidity of complication (35.1% vs. 15.9%, OR=2.67, 95% CI: 1.58 to 4.53, P<0.001), but it was more advantageous in symptom improvement (94.2% vs. 64.1%, OR=6.19, 95% CI: 2.47 to 15.52, P<0.001) and stoma reductions (62.8% vs. 5.1%, OR=15.17, 95% CI: 1.21 to 189.74, P=0.030), and the differences were significant (both P<0.05). No significant difference in postoperative mortality was found between the two groups (10.1% vs. 18.8%, OR=0.74, 95% CI: 0.21 to 2.59, P=0.640). There were no obvious changes between the two groups after sensitivity analysis for the prognostic indicators (the symptoms improved, postoperative complications, mortality, and reversed stomas rate) compared with the meta-analysis results before exclusion, suggesting that the results were robust and credible. Funnel diagram analysis suggested a small published bias. Conclusions: Chronic RLRI patients with late severe complications undergoing diseased bowel resection have higher risk of complication, while their long-term mortality is comparable to those undergoing diversion enterostomy. Diseased bowel resection is better in postoperative improvement of symptoms and stoma reduction rate.

[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.

[Predictive value of magnetic resonance imaging characteristics before and after radiotherapy for the occurrence of severe radiation-induced late rectal injury in patients with rectal cancer].

Objective: Severe radiation-induced late rectal injury (sRLRI) directly affects the quality of life of patients with rectal cancer. Effective prediction of sRLRI before surgery may provide important information for the selection of surgical strategies and perioperative managements. The purpose of this study is to evaluate the feasibility of predicting sRLRI based on magnetic resonance imaging (MRI) features before and after radiotherapy for rectal cancer. Methods: This was a diagnostic study. Clinical and imaging data of 90 patients with rectal cancer receiving long-term radiotherapy from June 2013 to July 2018 in the Sixth Affiliated Hospital of Sun Yat-sen University were collected retrospectively. Case inclusion criteria: (1) rectal cancer was diagnosed by pathology and age of ≥ 18 years old; (2) patients received neoadjuvant chemoradiotherapy and anterior rectal resection; (3) follow up time ≥ 3 years; (4) patients had no history of other neoplasm. Exclusion criteria: (1) patients did not receive MRI examination in our hospital within 2 weeks before and/or 8 weeks after radiotherapy; (2) images were not good enough for evaluation; (3) medical records were incomplete; (4) patients had severe gastrointestinal diseases. According to the RTOG/EORTC classification criteria for radiation reactions, severe complications of grade 3-4 requiring surgical management were defined as sRLRI. T2WI and DWI images before and after radiotherapy were evaluated. The rectal wall thickness, bladder wall thickness, rectal sacral spacing and apparent diffusion coefficient (ADC) were measured. The receiver operating characteristic (ROC) curve was used to evaluate the predictive value of the above indicators for sRLRI. Results: Among the 90 patients with rectal cancer, 34 (37.8%) developed sRLRI. Before radiotherapy, the median rectal wall thickness of sRLRI and non-sRLRI patients was 4.530 mm and 4.355 mm, respectively; the median bladder wall thickness was 3.962 mm and 3.868 mm, respectively; the median rectal sacral spacing was 15.557 mm and 12.433 mm, respectively; the median ADC value of rectal wall was 1.620 ×10(-3) mm(2)/s and 1.653 ×10(-3) mm(2)/s, respectively. There were no significant differences in above indicators between sRLRI and non-sRLRI patients (all P>0.05). After radiotherapy, compared with non-sRLRI patients, sRLRI patients had increased rectal wall thickness (median: 8.239 mm vs. 6.223 mm, Z=-3.512, P=0.001), rectal sacral spacing (median: 17.728 mm vs. 13.885 mm, Z=-2.247, P=0.025), and change of rectal wall thickness after radiotherapy (median: 98.106% vs. 49.584%, Z=-4.169, P<0.001). After radiotherapy, there were no significant differences in the bladder wall thickness and its change value, the ADC value of rectal wall and its change rate before and after radiotherapy between the two groups (all P>0.05). The area under the curve (AUC) of the change rates of rectal wall thickness after radiotherapy, rectal wall thickness and rectal sacral spacing after radiotherapy for predicting sRLRI was 0.763, 0.722 and 0.642, respectively, while the sensitivity was 85.3%, 70.6% and 76.5%, respectively, and the specificity was 64.3%, 71.4% and 57.1%, respectively. Conclusion: Based on MRI examinations, assessments of rectal wall thickness after radiotherapy, the change rate of rectal wall thickness after radiotherapy, and rectal sacral spacing after radiotherapy are helpful for evaluating the risk of sRLRI after radiotherapy for patients with rectal cancer.

[Questionnaire investigation of radiation rectal injury with anxiety, depression and somatic disorder].

Objective: To observe the incidence and treatment of radiation rectal injury complicated with anxiety, depression and somatic symptom disorder. Methods: A cross-sectional survey research method was carried out. Patients with radiation rectal injury managed by members of the editorial board of Chinese Journal of Gastrointestinal Surgery were the subjects of investigation. The inclusion criteria of the survey subjects: (1) patients suffered from pelvic tumors and received pelvic radiotherapy; (2) colonoscopy showed inflammatory reaction or ulcer in the rectum. Exclusion criteria: (1) patient had a history of psycho-somatic disease before radiotherapy; (2) patient was unable to use a smart phone, unable to read and understand the questions in the questionnaire displayed on the phone; (3) patient refused to sign an informed consent form. According to the SOMA self-rating scale, PHQ-15 self-rating scale, GAD-7 and PHQ-9 self-rating scale, the electronic questionnaire of "Psychological Survey of Radiation Proctitis" was designed. The questionnaire was sent to patients with radiation rectal injury managed by the committee through the WeChat group. Observational indicators: (1) radiation rectal injury symptom assessment: using SOMA self-rating scale, radiation rectal injury symptom classification: mild group (≤3 points), moderate group (4-6 points) and severe group (> 6 points); (2) incidence of anxiety, depression and physical disorder: using GAD-7, PHQ-9 and PHQ-15 self-rating scales respectively for assessment; (3) correlation of radiation rectal injury symptom grading with anxiety, depression, and somatic symptom disorder. Results: Seventy-one qualified questionnaires were collected, of which 41 (56.9%) were from Guangzhou. Among the 71 patients, 6 were males and 65 were females; the mean age was (55.7±9.3) years old and 48 patients (67.6%) were less than 60 years old; the median confirmed duration of radiation rectal injury was 2.0 (1.0, 5.0) years. (1) Evaluation of symptoms of radiation rectal injury: 18 cases of mild (25.4%), 27 cases of moderate (38.0%), and 26 cases of severe (36.6%). (2) Incidence of anxiety, depression and somatic disorder: 12 patients (16.9%) without comorbidities; 59 patients (83.1%) with anxiety, depression, or somatic disorder, of whom 2 patients only had anxiety, 1 patient only had depression, 9 only had somatic disorder, 2 had anxiety plus depression, 4 had anxiety plus somatic disorder, 2 had depression plus somatic disorder, and 40 had all three symptoms. (3) correlation of radiation rectal injury grading with anxiety, depression, and somatic symptom disorder: as compared to patients in mild group and moderate group, those in severe group had higher severity of anxiety and somatic symptom disorder (Z=-2.143, P=0.032; Z=-2.045, P=0.041), while there was no statistically significant difference of depression between mild group and moderate group (Z=-1.176, P=0.240). Pearson correlation analysis revealed that radiation rectal injury symptom score was positively correlated with anxiety (r=0.300, P=0.013), depression (r=0.287, P=0.015) and somatic symptom disorder (r=0.344, P=0.003). Conclusions: The incidence of anxiety, depression, and somatic symptom disorder in patients with radiation rectal injury is extremely high. It is necessary to strengthen the diagnosis and treatment of somatic symptom disorder, so as to alleviate the symptoms of patients with pelvic perineum pain and improve the quality of life.

[Dilemma and strategy in surgery of chronic radiation intestinal injury].

Chronic radiation intestinal injury denotes the repeated and prolonged damage of intestine caused by radiotherapy to pelvic malignancy, which usually occurs after three months of radiotherapy. Surgical intervention is indicated when the progressive intestinal injury leads to the development of massive intestinal hemorrhage, obstruction, perforation, fistula and other late complications. However, there is no consensus on the surgical procedures. We illustrate the dilemma in surgical treatment from the points of pathological mechanism and the frequent sites of radiation intestinal injury. Meanwhile, we discuss the surgical alternatives of radiation intestinal injury based on the literature and our experience. The pathological mechanism of chronic radiation injury is progressive occlusive arteritis and parenchymal fibrosis. The frequently involved sites are distal ileum, sigmoid colon and rectum based on the radiotherapy region. The morbidity and mortality are high in surgery of chronic radiation injury due to poor ability of tissue healing, pelvic fibrosis, multiple organ damage, and poor physical condition. Definitive intestinal resection is one of the most common surgical procedures. Extended resection of diseased bowel to ensure that there is no radiation damage in at least one end of the anastomotic bowels is the key to decrease the risk of complications related to anastomotic sites.

Breaking Earth's shell into a global plate network.

The initiation mechanism of Earth's plate tectonic cooling system remains uncertain. A growing consensus suggests that multi-plate tectonics was preceded by cooling through a single-plate lithosphere, but models for how this lithosphere was first broken into plates have not converged on a mechanism or a typical early plate scale. A commonality among prior efforts is the use of continuum mechanics approximations to evaluate this solid mechanics problem. Here we use 3D spherical shell models to demonstrate a self-organized fracture mechanism analogous to thermal expansion-driven lithospheric uplift, in which globe-spanning rifting occurs as a consequence of horizontal extension. Resultant fracture spacing is a function of lithospheric thickness and rheology, wherein geometrically-regular, polygonal-shaped tessellation is an energetically favored solution because it minimizes total crack length. Therefore, warming of the early lithosphere itself-as anticipated by previous studies-should lead to failure, propagating fractures, and the conditions necessary for the onset of multi-plate tectonics.

[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.

Toll-like receptor 2 gene polymorphism and its relationship with SCS in dairy cattle.

Toll-like receptor 2 (TLR2) plays an important role in the innate immune response to a variety of pathogens. In this study, bovine TLR2 gene was taken as a candidate gene for mastitis resistance. Through PCR-SSCP analysis and sequencing, three missense mutations at T385 G, G398A, and G1884A were detected in the coding region that encoded extracellular domain. Altogether 240 dairy cattle of three breeds (Holstein, Simmental, and Sanhe cattle) were genotyped and allele frequencies were determined. The effects of TLR2 polymorphisms on somatic cell score (SCS) were analyzed and significant association was found between T385 G and SCS. The mean of genotype GG was significantly lower than those of genotype TT and TG. No significant associations were found with SCS for G398A and G1884A. Information provided in this research will be useful in further studies to determine the role of TLR2 gene in the mastitis resistance.