[Mechanisms and clinical management of small bowel obstruction caused by kinking of the jejunojejunal anastomosis after laparoscopic Roux-en-Y gastric bypass].

Currently, obesity and its complications have become increasingly serious health issues. Bariatric surgery is an effective method of treating obesity and related metabolic complications. Among them, Roux-en-Y gastric bypass (RYGB) is still considered the "gold standard" procedure for bariatric surgery. Small bowel obstruction is one of the possible complications after RYGB, and in addition to the formation of intra-abdominal hernias, kinking of the jejunojejunal anastomosis is an important cause of small bowel obstruction. The early clinical symptoms of kinking of the jejunojejunal anastomosis often lack clarity in the early stages. Therefore, early diagnosis, prevention, and effective treatment of kinking of the jejunojejunal anastomosis are challenging but crucial. The occurrence of kinking of the jejunojejunal anastomosis may be related to surgical techniques and the surgeon's experience. The use of anti-obstruction stitch, mesenteric division, and bidirectional jejunojejunal anastomosis may be beneficial in preventing kinking of the jejunojejunal anastomosis. If kinking of the jejunojejunal anastomosis occurs, timely abdominal CT scans and endoscopic examinations should be performed. Gastric and intestinal decompression should be initiated immediately, and exploratory surgery should be prepared.

Magnetic resonance Index of Activity (MaRIA) is reliable in assessing response to treatment in patients with Crohn's disease (CD).

AIM: To assess the accuracy of Magnetic Resonance Index of Activity (MaRIA) in evaluating therapeutic efficacy in Crohn's disease (CD) patients with different activity levels using ileocolonoscopy as the reference standard. MATERIALS AND METHODS: Forty-eight patients underwent magnetic resonance enterography (MRE) and ileocolonoscopy at baseline, week 26, and week 52, along with the Simple Endoscopic Score for Crohn's Disease (SES-CD) and MaRIA scores. According to the SES-CD score at baseline, all patients were subdivided into mild, moderate, and severe activity subgroups. The identification of endoscopic mucosal healing (MH) was explored primarily. Moreover, the Crohn's Disease Activity Index (CDAI), C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), procalcitonin (PCT), and interleukin-6 (IL-6) levels were collected and analysed. RESULTS: MaRIA correlated significantly with SES-CD and CRP at baseline, week 26, and week 52. The discrepancies in MaRIA and SES-CD were statistically significant before and after treatment. MaRIA = 24.43 and ΔMaRIA = 12.77 as the cut-off points were found to have high diagnostic accuracy for predicting MH. MaRIA (p<0.001), SES-CD (p<0.001), CRP (p<0.05), ESR (p<0.05), and CDAI score (p<0.05) in patients with MH were considerably decreased compared to those in patients without MH. CONCLUSIONS: MRE has good application value in evaluating the therapeutic response of CD patients treated with biological agents. MaRIA is a reliable indicator in the follow-up of CD patients, which is strongly correlated with SES-CD, and it has high accuracy in predicting endoscopic MH.

[Research progress of bariatric and metabolic surgery in the prevention of gastroesophageal reflux disease].

Gastroesophageal reflux disease (GERD) is a common digestive tract disease. Obesity is an independent risk factor for GERD. Laparoscopic sleeve gastrectomy (laparoscopic sleeve gastrectomy, LSG) is becoming more popular in bariatric metabolic surgery and is simple to perform with fewer complications, but its efficacy in treating postoperative anti-reflux in obese patients remains controversial. LSG has been reported to disrupt anti-reflux barrier function, such as altered cardiac notch, disruption of diaphragmatic continuity, and increased hiatal hernia after surgery. The cardiac notch is one of the important anti-reflux barriers at the gastroesophageal junction, and its accentuation has been shown to be effective in alleviating the symptoms of GERD, and LSG combined with angle of cardiac notch accentuation is expected to be an effective measure to prevent GERD after obesity surgery. Therefore, this article mainly reviews the research on the prevention of GERD by bariatric surgery, aiming to explore the effective treatment of GERD in obese patients after surgery, so as to improve the symptoms and quality of life of patients with GERD, and provide reference for the surgical treatment of GERD.

[Meta-analysis comparing long-term outcomes of intersphincteric resection versus abdominoperineal resection for low rectal cancer].

Objective: To compare the long-term outcomes of intersphincteric (trans-internal and external) sphincter resection (ISR) and abdominoperineal proctocolectomy (APR) for low-grade rectal cancer. Methods: We used a meta-analytic approach to compare these procedures . Published reports comparing ISR and APR for low rectal cancer in Pubmed, Medline, EMBASE and Cochrane, China Knowledge Network (CNKI), China Biomedical Literature Database, and Vipers databases between January 2005 and January 2023 were searched and those meeting the eligibility criteria were selected for extraction of data for analysis. Inclusion criteria were as follows: (1) all reports comparing ISR and APR for low rectal cancer before January 2023; and (2) prospective randomized controlled studies or well-designed cohort studies. Exclusion criteria were as follows: (1) full text not available; (2) duplicate publications, missing primary outcome indicators, and unknown data; and (3) invalid statistical analysis. Results: Sixteen studies with 2498 patients were included in this study. Compared with the APR group, patients in the ISR group were relatively younger (weighted mean difference [WMD]=-1.82, 95%CI=-2.94 to -0.70, P=0.01), had tumors farther from the anal verge (WMD=0.43, 95%CI=0.18 to 0.67, P<0.01), and lower pathological T-stage (T3-4 stage: OR=0.54, 95%CI=0.36 to 0.81, P<0.01). In contrast, there were no statistically significant differences between the two groups in gender (P=0.78), body mass index (P=0.77), or pathological N stage (P=0.09). Compared with the APR group, patients in the ISR group had a lower rate of postoperative complications (OR=0.77, 95%CI=0.60 to 0.99, P=0.04), shorter hospital stay (WMD=-4.30, 95%CI=-7.07 to -1.53, P<0.01), higher 5-year overall survival (HR=0.54, 95%CI=0.33 to 0.88, P=0.01), and higher 5-year disease-free survival (HR=0.65, 95%CI=0.47 to 0.90, P<0.01). Five-year locoregional failure (HR=0.66, 95%CI=0.40 to 1.10, P=0.11) and time to surgery (WMD=-9.71, 95%CI=-41.89 to 22.47, P=0.55) did not differ significantly between the two groups. Conclusion: ISR is a safe and effective alternative to APR for early-stage low-grade rectal cancer.

[Treatment of obstructive colorectal cancer].

Obstructive colorectal cancer is a common malignant bowel obstruction. Colostomy or colostomy following tumor resection may be the first choice for emergency surgery. The intestinal and systemic conditions of patients undergoing emergency surgery are often poor, and patients need to undergo multiple operations, which increase the surgical risk and economic burden and reduce the quality of life of patients. Poor intraoperative visualization may also affect the radical operation of emergency surgery. Transanal decompression tube (TDT) can rapidly decompress and drain the obstructed bowel, effectively relieve obstruction symptoms, and improve the success rate of primary radical resection. The TDT squeeze the tumor lightly, causing no spread of tumor cells, and is cheap, but the cavity of transanal decompression tube is small and easily blocked, and requires tedious flushing or regular replacement. Self-expanding metallic stents (SEMS) can relieve intestinal obstruction effectively, provide sufficient preparation time for preoperative examination and improvement of nutritional status. By improving patient's tolerance to radical surgery, SEMS might be used as an important treatment strategy choice for obstructive colorectal cancer. However, SEMS may squeeze the tumor, leading to the spread of tumor cells, increase the recurrence rate and metastasis rate, and reduce the survival rate. Moreover, intestinal wall edema still existed during the operation following SEMS, and the rate of ostomy after anastomosis was as high as 34%. We hypothesized that prolonging the interval between stent insertion and surgery to 2 months, with neoadjuvant chemotherapy administered during this interval (SEMS-neoadjuvant chemotherapy strategy), would help improve outcomes. The SEMS-neoadjuvant chemotherapy strategy is a safe, effective, and well tolerated treatment approach with a high laparoscopic resection rate, low stoma formation rate and improvement in the overall survival for patients with left-sided colon cancer obstruction. The patient physical status is improved, the primary tumor is downstaged, and intestinal wall edema is relieved during the relatively longer interval between SEMS placement and surgery. The SEMS-neoadjuvant chemotherapy strategy may be a preferred therapeutic strategy for obstructive left colon cancer.

[Effect of intestinal obstruction stent combined with neoadjuvant chemotherapy on the pathological characteristics of surgical specimens in patients with complete obstructive colorectal cancer].

Objective: To compare the effects of three treatment options: emergency surgery, stent-surgery, and stent-neoadjuvant chemotherapy-surgery, on the pathological characteris- tics of surgically-resected specimens from patients with completely obstructive colorectal cancer. Methods: This was a retrospective cohort study analyzing clinicopathological data of patients with complete obstructive colorectal cancer who were admitted to the General Surgery Department of Beijing Chaoyang Hospital, Capital Medical University, between May 2012 and August 2020. The inclusion criteria were diagnosed with complete colorectal obstruction, pathologically confirmed as adenocarcinoma, resectable on imaging assessment, and without distant metastasis, combined with the patients' clinical manifestations and imaging examination findings. Patients with multiple colorectal cancers, refusal to undergo surgery, and concurrent peritonitis or intestinal perforation before stenting of the intestinal obstruction were excluded. Eighty-nine patients with completely obstructive colorectal cancer were enrolled in the study and were divided into emergency surgery group (n=30), stent-surgery group (n=34), and stent-neoadjuvant chemotherapy- surgery group (n=25) according to the treatment strategy. Differences in the pathological features (namely perineural infiltration, lymphovascular infiltration, tumor deposits, specimen intravascular necrosis, inflammatory infiltration, abscesses, mucus lake formation, foreign body giant cells, calcification, and tumor cell ratio) and biomolecular markers (namely cluster of differentiation (CD)34, Ki67, Bcl-2, matrix metalloproteinase-9, and hypoxia-inducible factor alpha) were recorded. Pathological evaluation was based on the presence or absence of qualitative evaluation of pathological features, such as peripheral nerve infiltration, vascular infiltration, and cancer nodules within the specimens. The evaluation criteria for the pathological features of the specimens were as follows: Semi-quantitative graded evaluation based on the proportion of tissue necrosis, inflammatory infiltrates, abscesses, mucus lake formation, foreign body giant cells, calcification, and tumor cells in the field of view within the specimen were classified as: grade 0: not seen within the specimen; grade 1: 0-25%; grade 2: 25%-50%; grade 3: 50%-75%; and grade 4: 75%-100%. The intensity of cellular immunity was classified as none (0 points), weak (1 point), moderate (2 points), and strong (3 points). The two evaluation scores were then multiplied to obtain a total score of 0-12. The immunohistochemical results were also evaluated comprehensively, and the results were defined as: negative (grade 0): 0 points; weakly positive (grade 1): 1-3 points; moderately positive (grade 2): 4-6 points; strongly positive (grade 3): 7-9 points; and very strong positive (grade 4): 10-12 points. Normally-distributed values were expressed as mean±standard deviation, and one-way analysis of variance was used to analyze the differences between the groups. Non-normally-distributed values were expressed as median (interquartile range: Q1, Q3). A nonparametric test (Kruskal-Wallis H test) was used for comparisons between groups. Results: The differences were not statistically significant when comparing the baseline data for age, gender, tumor site, American Society of Anesthesiologists score, tumor T-stage, N-stage, and degree of differentiation among the three groups (all P>0.05). The differences were not statistically significant when comparing the pathological characteristics of the resected tumor specimens, such as foreign body giant cells, inflammatory infiltration, and mucus lake formation among the three groups (all P>0.05). The rates of vascular infiltration were 56.6% (17/30), 41.2% (15/34), and 20.0% (5/25) in the emergency surgery, stent-surgery, and stent- neoadjuvant chemotherapy-surgery groups, respectively, with statistically significant differences between the groups (χ2=7.142, P=0.028). Additionally, the rate of vascular infiltration was significantly lower in the stent-neoadjuvant chemotherapy-surgery group than that in the emergency surgery group (P=0.038). Peripheral nerve infiltration rates were 55.3% (16/30), 41.2% (14/34), and 16.0% (4/25), in the emergency surgery, stent-surgery, and stent-neoadjuvant chemotherapy-surgery groups, respectively, with statistically significant differences (χ2=7.735, P=0.021). The infiltration peripheral nerve rates in the stent-neoadjuvant chemotherapy-surgery group were significantly lower than those in the emergency surgery group (P=0.032). The necrosis grade was 2 (1, 2), 2 (1, 3), and 2 (2, 3) in the emergency surgery, stent- surgery, and stent-neoadjuvant chemotherapy-surgery groups, respectively, with statistically significant differences (H=10.090, P=0.006). Post hoc comparison revealed that the necrosis grade was higher in the stent-surgery and stent-neoadjuvant chemotherapy-surgery groups compared with the emergency surgery group (both P<0.05). The abscess grade was 2 (1, 2), 3 (1, 3), and 2 (2, 3) in the emergency surgery, stent-surgery, and stent-neoadjuvant chemotherapy-surgery groups, respectively, with statistically significant differences (H=6.584, P=0.037). Post hoc comparison revealed that the abscess grade in the emergency surgery group was significantly lower than that in the stent-surgery group (P=0.037). The fibrosis grade was 2 (1, 3), 3 (2, 3), and 3 (2, 3), in the emergency surgery, stent-surgery, and stent-neoadjuvant chemotherapy-surgery groups, respectively, with statistically significant differences (H=11.078, P=0.004). Post hoc analysis revealed that the fibrosis degree was higher in both the stent-surgery group and the stent- neoadjuvant chemotherapy-surgery group compared with the emergency surgery group (both, P<0.05). The tumor cell ratio grades were 4 (3, 4), 4 (3, 4), and 3 (2, 4), in the emergency surgery, stent-surgery, and stent-neoadjuvant chemotherapy-surgery groups, respectively, with statistically significant differences (H=8.594, P=0.014). Post hoc analysis showed that the tumor cell ratio in the stent-neoadjuvant chemotherapy-surgery group was significantly lower than that in the emergency surgery group (P=0.012). The CD34 grades were 2 (2, 3), 3 (2, 4), and 3 (2, 3) in the emergency surgery, stent-surgery, and stent-neoadjuvant chemotherapy-surgery groups, respectively, and the difference was statistically significant (H=9.786, P=0.007). Post hoc analysis showed that the CD34 grades in the emergency surgery, stent-surgery, and stent-neoadjuvant chemotherapy-surgery groups were 2 (2, 3), 3 (2, 4), and 3 (2,3), respectively. Post hoc analysis revealed that the CD34 concentration was higher in the stent-surgery group than that in the emergency surgery group (P=0.005). Conclusion: Stenting may increase the risk of distant metastases in obstructive colorectal cancer. The stent-neoadjuvant chemotherapy-surgery treatment model promotes tumor cell necrosis and fibrosis and reduces the proportion of tumor cells, vascular infiltration, and peripheral nerve infiltration, which may help decrease local tumor infiltration and distant metastasis in completely obstructive colorectal cancer after stent placement.

[Short-term efficacy of laparoscopic sleeve gastrectomy plus uncut jejunojejunostomy (SG-uncut JJB) for treatment of obesity: a prospective study].

Objective: To analyze the short-term efficacy of sleeve gastrectomy plus uncut jejunojejunostomy (SG+uncut JJB) for patients with obesity. Methods: This prospective study was conducted in the General Surgery Department of Beijing Chaoyang Hospital from January to December 2020 (NCT04534504). The inclusion criteria were patients with a body mass index (BMI) of >32.5 kg/m2, type 2 diabetes mellitus (T2DM) or at least two comorbidities with a BMI of 27.5-32.5 kg/m2, a waist circumference of >90 cm (male) or >85 cm (female), and those aged between 16 and 65 years. The exclusion criteria included patients who were pregnant, diagnosed with severe neurological or mental illnesses, long-term users of antidepressants and immunosuppressants, and diagnosed with severe gastroesophageal reflux disease or underwent revision surgery. Patients with incomplete follow-up data or insufficient follow-up time were also excluded. Patients were divided into SG-uncut JJB group and SG group according to doctor's recommendation and patients' wills. The primary endpoint was the percentage of excess weight loss (%EWL), and the secondary endpoints were the percentage of total weight loss (%TWL) and the T2DM remission rate. All patients were regularly followed up until the end of December 2020. Results: After excluding seven patients who did not meet the inclusion criteria, 47 eligible patients were finally identified, with 21 in the SG+uncut JJB group and 26 in the SG group. The operation time (140 [110-180] minutes vs. 90 [70-180] minutes, Z=-3.642, P=0.001) and total cost ([54,000 ± 6000] yuan vs. [49,000 ± 7000] yuan, t=2.590, P=0.013) were slightly higher in the SG+uncut JJB group than in the SG group (all P<0.05). However, no significant differences were observed in terms of postoperative hospital stay, operative blood loss, and postoperative complications between the two groups (all P>0.05). The incidence of nausea and vomiting was significantly lower in the SG+uncut JJB group than in the SG group (9.5% [2/21] vs. 46.2% [12/26], χ2=7.453, P=0.006}. The %EWL and %TWL in the SG+uncut JJB group tended to increase gradually with time. The same trend was also observed in the SG group during the first 6 months of follow-up. The 12-month %EWL and %TWL in the SG group were slightly lower compared with the 6-month %EWL and %TWL (P=0.001). The 12-month %EWL values in the SG+uncut JJB and SG groups were (72.4%±12.3%) and (63.6%±25.7%), respectively. However, no significant differences were observed between the two groups in terms of %EWL. Moreover, the 1-month ([11.1%±2.4%] vs. [8.2%±4.4%], P=0.011) and 12-month %TWL ([29.7%±6.9%] vs. [20.3%±7.2%], P=0.001) were significantly higher in the SG+uncut JJB group than in the SG group. No significant differences were observed in terms of T2DM and hypertension remission (all P>0.05). Conclusion: SG+uncut JJB might achieve a promising weight-loss effect similar to SG with a relatively lower incidence of postoperative nausea and vomiting, and it might be an effective and safe approach for obesity management.

Recommendations for stereotactic body radiation therapy for spine and non-spine bone metastases. A GETUG (French society of urological radiation oncolgists) consensus using a national two-round modified Delphi survey.

Background and purpose: The relevance of metastasis-directed stereotactic body radiation therapy (SBRT) remains to be demonstrated through phase III trials. Multiple SBRT procedures have been published potentially resulting in a disparity of practices. Therefore, the french society of urological radiation oncolgists (GETUG) recognized the need for joint expert consensus guidelines for metastasis-directed SBRT in order to standardize practice in trials carried out by the group. Materials and methods: After a comprehensive literature review, 97 recommendation statements were created regarding planning and delivery of spine bone (SBM) and non-spine bone metastases (NSBM) SBRT. These statements were then submitted to a national online two-round modified Delphi survey among main GETUG investigators. Consensus was achieved if a statement received ≥ 75 % agreements, a trend to consensus being defined as 65-74 % agreements. Any statement without consensus at round one was re-submitted in round two. Results: Twenty-one out of 29 (72.4%) surveyed experts responded to both rounds. Seventy-five statements achieved consensus at round one leaving 22 statements needing a revote of which 16 achieved consensus and 5 a trend to consensus. The final rate of consensus was 91/97 (93.8%). Statements with no consensus concerned patient selection (3/19), dose and fractionation (1/11), prescription and dose objectives (1/9) and organs at risk delineation (1/15). The voting resulted in the writing of step-by-step consensus guidelines. Conclusion: Consensus guidelines for SBM and NSBM SBRT were agreed upon using a validated modified Delphi approach. These guidelines will be used as per-protocole recommendations in ongoing and further GETUG clinical trials.

[Study on the Protective effect and mechanism of Nicotinamide Riboside on lung injury in paraquat intoxicated mice].

Objective: To investigate the protective effect and mechanism of Nicotinamide Riboside (NR) on lung injury caused by Paraquat intoxicated mice. Methods: Eighty clean male BALB/C mice were selected and averagely divided forty mice into 4 groups with 10 mice in each group, PQ group was given 25% PQ solution (60 mg/kg) by one-time gavage. PQ+NR group were intraperitoneally injected with NR solution (300 mg/kg) 1 hour before given the same amount of PQ solution (60 mg/kg) by one-time gavage, The Control group were given the same amount of saline by one-time gavage, The same amount of NR was intraperitoneally injected before NR group were given saline by one-time gavage. Observed and recorded general condition of PQ intoxicated mice. Observed and recorded the death of mice every half an hour and counted the mortality and drew survival curve of each group after 72 hours exposure. another forty mice were averagely divided and treated by the same way. After 24 hours of modelling, mice were anaesthetized and killed. Then blood was extracted after eyeball was removed. The changes of TNF-a、IL-6 and MPO in serum of mice were detected by ELISA.Two lung tissues were removed from the chest and used to measure the D/W ratio of the lung. The pathological changes of lung were observed and scored under light microscope.The levels of SOD, MDA and Caspase-3 in lung tissues were determined by chemical colorimetry. The expression of Sirt1 and Nrf2 in lung tissues was detected by Western-blot. Results: Compared with the Control group and the NR group, the mice in the PQ group had a poor general condition, such as depression, crouching, skin disorder and reduced activity, food, urine and feces. The symptoms in the PQ+NR group were reduced compared with the PQ group. The survival rate at 72 hours after exposure: 80% in the PQ+NR group and 40% higher than that in the PQ group (P=0.029) . Compared with Control group and NR group, the D/W ratio (0.09±0.07) , lung pathology score under light microscope (11.80±0.37) , TNF-a (39.89±1.48) pg/ml、IL-6 (77.29±2.38) pg/ml、MPO (0.31±0.01) µg/ml、SOD (6.62±0.30) U/mgprot、MDA level (1.21±0.14) mmol/mgprot, Caspase-3 activity (356.00± 27.16) %, Sirt1 and Nrf2 protein expression (1.02±0.14、0.82±0.06) were significantly decreased in PQ group (P=0.004、0.023) ; Compared with PQ group, PQ+NR group significantly increased the D/W ratio (0.10±0.10) , decreased the pulmonary pathology score under light microscope (7.400.51) , decreased TNF-a (33.00± 0.65) pg/ml、IL-6 (52.23±4.23) pg/ml、MPO leve (0.23±0.01) µg/mll, increased SOD leve (9.28±0.45) U/mgprotl, decreased MDA level (0.78±0.02) mmol/mgprot, decreased Caspase-3 activity (222.80±7.59) %, and increased the protein expressions of Sirt1 and Nrf2 (1.62±0.16、1.06±0.04) (P=0.048、0.035) . Conclusion: NR can prolong the survival time of PQ poisoned mice; NR intervention can effectively inhibit the inflammatory response, peroxidation injury and apoptosis of PQ poisoned mice; NR intervention can upregulate the expression of Sirt1 and Nrf2 protein and effectively reduce the lung injury of PQ poisoning.

[Comparison study for the proportion of underdiagnosed zonulopathy in angle closure glaucoma].

Objective: To analyze the proportion and clinical characteristics of underdiagnosed zonulopathy in angle closure glaucoma (ACG) patients and to explore the related risk factors. Methods: Case-control study. Continuous cases of ACG patients who underwent phacoemulsification combined with intraocular lens implantation and goniosynechialysis surgery [ACG group, including acute angle closure glaucoma (AACG) and chronic angle closure glaucoma (CACG)] from November 1, 2020 to October 31, 2021 and age-related cataract patients who underwent phacoemulsification combined with intraocular lens implantation surgery in the same period (control group) were included. The diagnosis of zonulopathy was determined according to the intraoperative signs such as wrinkles of the anterior capsule during continuous circular capsulorhexis. The proportion of zonulopathy, preoperative diagnosis rate of zonulopathy, demographic characteristics, anterior chamber depth (ACD), axis length, difference of ACD in both eyes (ACD of the contralateral eye minus ACD of the operated eye) were compared between the two groups. The related risk factors were explored. The paired t-test (comparison between two groups of normally distributed data), non-parametric test (comparison between two groups of non-normally distributed data), Chi-square test (categorical variables), univariate and multivariate logistic regression analysis were used. Results: There were 104 ACG patients (104 eyes), including 63 AACG patients (63 eyes) and 41 CACG patients (41 eyes), and 117 controls (117 eyes). There was no significant difference in age (P=0.29) and gender (P=0.07) between the two groups. The ACG group had shallower anterior chamber (P<0.001), shorter axial length (P<0.001) and more ACD difference in both eyes (P<0.001). In the ACG group, the proportion of zonulopathy was 46.2% (48/104), which was significantly higher than that (6.0%, 7/117) in the control group (P<0.001). In the control group, only zonular laxity was found, while in the ACG group, besides the predominant zonular laxity (68.8%, 33/48), there was zonular dehiscence (31.3%, 15/48). The eyes with AACG (57.1%, 36/63) had a higher proportion of zonulopathy than those with CACG (29.3%, 12/41) (P=0.006). In the ACG group, only 14 cases (29.8%) were diagnosed preoperatively according to slit lamp examination and/or ultrasound biomicroscopy. The proportion of underdiagnosed zonulopathy was 70.8% in the ACG group (34/48). A smaller ACD was found to be related to the zonulopathy in the ACG group. All AACG cases with an ACD ≤2.0 mm and CACG cases with an ACD ≤1.9 mm had zonulopathy. Multivariate logistic regression showed that the ACD difference in both eyes (P=0.025) and the diagnosis of ACG (AACG vs. cataract, P<0.001; CACG vs. cataract, P=0.023) were independent risk factors associated with zonulopathy. Conclusions: The proportion of underdiagnosed zonulopathy among ACG patients is high. Better preoperative diagnostic methods for zonulopathy are needed. Zonulopathy is common in ACG patients, especially in AACG patients, suggesting that zonulopathy may be related to the pathogenesis of ACG. The shallower the ACD, the riskier the zonulopathy. ACD differences between two eyes and ACG types (including AACG and CACG) were related risk factors of zonulopathy.(This article was published ahead of print on the Online-First Publishing Platform for Excellent Scientific Researches of Chinese Medical Association Publishing House on March 11, 2022).

[Patient selection and early tolerance of whole breast irradiation according to the "Fast Forward" protocol: Preliminary results]. / Sélection de patientes et tolérance précoce de l'irradiation mammaire selon le protocole « Fast Forward ¼ : résultats préliminaires.

PURPOSE: Moderate hypofractionated radiotherapy has become routine practice for a selected population of patients treated for early-stage breast cancer. In April 2020, the Fast Forward (FF) study was published which introduced another extreme hypofractionated radiotherapy regimen in five sessions over a week. The aim of this work is to evaluate the population of first patients in whom this regimen was used in our department, as well as the results in terms of early toxicity. MATERIAL AND METHODS: We retrospectively analysed all the patients treated in our department according to the Fast Forward protocol after establishing an institutional consensus regarding the selection of patients with breast cancer without indication for lymph node irradiation. All patients received breast-only irradiation at a total dose of 26Gy in five fractions according to protocol. All patients were treated by modern conformational techniques with planning large volume coverage between 95 and 100%. Acute toxicity of the treatment was assessed using the NCI CTC v4.0 scale and the general condition was assessed according to the WHO classification. RESULTS: Between August 2020 and May 2021, 30 patients were included, treated on the breast alone without complement on the tumour bed or irradiation of the lymph node areas. The median age of the patients was 80years (range: 60-85years) with performance status 2 in 27 cases (89%). Only one patient had metastatic disease (3%), one patient presented locally advanced and 28 (94%) patients had early stage disease. Three patients (10%) were treated in dorsal decubitus according to the "field in the field" technique and 27 patients (90%) in isocentric lateral decubitus, which made it possible to avoid the organs at risk such as the heart (average dose of less than 1Gy) and the lungs. The early toxicity observed was grade I radio dermatitis in 8 patients (27%). No grade 2 and 3 toxicity, as well as radiation-induced pain or lymphedema were observed. CONCLUSIONS: The results of this series of patients treated with hypofractionated radiotherapy according to the Fast Forward protocol on the breast alone with adapted techniques show that the protocol is feasible, with little early toxicity but a greater follow-up is necessary to assess long-term toxicity.

[Concurrent radiation therapy and dual HER2 blockade in breast cancer: Assessment of toxicity]. / Association du double blocage de HER2 et radiothérapie dans la prise en charge du cancer du sein exprimant HER2.

PURPOSE: The tolerance of the concurrent use of radiotherapy, pertuzumab and trastuzumab is unknown. The purpose of this study was to evaluate the toxicity of this association in patients treated for HER2 positive metastatic and/or locally recurrent unrespectable breast cancer. MATERIAL AND METHODS: A retrospective study was performed in our institution for all consecutive patients treated with concurrent irradiation, pertuzumab and trastuzumab. The radiotherapy was performed while pertuzumab and trastuzumab were administrated as a maintenance treatment at the dose of 420mg (total dose) and 6mg/kg respectively every 3 weeks without chemotherapy. Toxicity was assessed according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0. Left ventricular ejection fraction (LVEF) was measured at baseline and then every 3-4 months. RESULTS: We studied 77 patients. treated in between 2013 and 2019 with median follow-up of 38 months (range 0-264 months). Median age was 53 years (33-86). There were 50 patients (64.9%) with metastatic and 27 patients (35.1%) with recurrent disease. All patients received docetaxel followed by P-T as first line treatment and they received 34 cycles (10-85) of pertuzumab and trastuzumab. All patients experienced partial or complete response according to RECIST criteria. Irradiation volumes were whole breast (41 patients, 53.2%) and chest wall (29 patients, 37.7%) at a dose of 50Gy with a median duration of 39 days. Radiotherapy of lymph nodes was performed in 53 patients (68.8%) as following: supraclavicular-infraclavicular and axillary lymph nodes in 52 patients (67.5%), and internal mammary nodes in 31 patients (40.3%). For 20 patients. (26.0%) radiotherapy was palliative: bone irradiation (12 patients, 15.6%), whole-brain radiotherapy (2 patients, 2.6%), cerebral metastasis irradiation (6 patients). As early toxicity we observed: radio dermatitis as following: 36 patients (46.8%) presented grade I, 17 patients (22.1%) presented grade II, and 3 patients (3.9%) presented grade III. One patient (1.3%) presented grade II esophagitis. One patient (1.3%) presented asymptomatic decrease of LVEF during treatment and 6 patients (7.7%) presented a decrease of LVEF. There was no radiation-induced pneumonitis. As late toxicity, we observed 1 (1.3%) case of grade I and 1 (1.3%) with grade II telangiectasia. There was 1 case (1.3%) of grade III cardiac toxicity, 8 months after the concurrent treatment. CONCLUSION: The concurrent use of radiotherapy, pertuzumab and trastuzumab is feasible with good tolerance. Larger prospective data with longer follow-up is needed to confirm these results.

Clinical practice of breast cancer protontherapy: A single-centre experience from selection to treatment.

PURPOSE: Breast protontherapy efficiently limits cardiac, lung and contralateral breast exposure, which may clinically translate into better late tolerance profile compared with classic photon techniques. While breast protontherapy is already implemented in the United States and in some European countries, clinical experience of breast cancer protontherapy is currently limited in France. The aim of this study is to evaluate the clinical practice of breast cancer protontherapy at the Institut Curie in order to implement this technique at a larger scale. MATERIALS AND METHODS: Data from all breast cancer patients that have been addressed to the protontherapy centre of Orsay (CPO, Institut Curie) for adjuvant breast protontherapy were retrieved. We analysed why these patients were ultimately treated with protontherapy or not. RESULTS: Between November 2019 and November 2020, eleven breast cancer patients have been evaluated for adjuvant protontherapy at the CPO. Two of them were ultimately treated with proton beams; adjuvant breast protontherapy therapy was well tolerated. The nine other patients were not treated with protontherapy due to lack of availability of protontherapy treatment rooms in acceptable time limits, at the time of patient evaluation. CONCLUSION: Despite dosimetric advantages and excellent clinical tolerance, lack of availability of protontherapy machines currently limits wider implementation of breast protontherapy.

[The influence of different corneal diameters on Belin/Ambrósio enhanced ectasia display of Pentacam corneal topography].

Objective: To investigate the effect of corneal diameter on Belin/Ambrósio enhanced ectasia display (BAD). Methods: Retrospective case series study. The subjects were 6 744 myopic patients, including 3 341 males and 3 403 females, who had undergone corneal refractive surgery or had completed preoperative examination but had not undergone corneal refractive surgery at the Army Medical Center and Chongqing Vision Institute in Chongqing from June 2017 to June 2019. Age was (23.74±5.73) years old. No patients had keratoconus. One eye of each patient was randomly included, and the patients were divided into groups according to the corneal diameter measured by Pentacam. Group A included 630 patients (630 eyes) with corneal diameter ≤ 11.1 mm. In group B, there were 4 063 patients (4 063 eyes) with corneal diameter of 11.2 to 11.8 mm. In group C, there were 2 051 patients (2 051 eyes) with corneal diameter ≥11.9 mm. Preoperative BAD parameters of deviation of front elevation difference map (Df), deviation of back elevation difference map (Db), deviation of average pachymetric progression index (Dp), deviation of minimum thickness (Dt), deviation of Ambrósio's relational thickness maximum (Da) and overall deviation value (Do) were measured by Pentacam. One-way analysis of variance was used for preoperative BAD parameters comparison between groups. The distribution of normal, suspicious and pathological results of Df, Db, Dp, Dt, Da and Do in each group was tested by chi-square test. Results: In groups A, B and C, Df was 0.73±1.14, 0.48±1.02, and 0.11±0.91, Db was 1.09±1.07, 0.23±0.83, and-0.34±0.62, Dp was 1.57±0.91, 1.14±0.86, and 0.68±0.75, Dt was -0.11±0.84, -0.2±0.82, and 0.03±0.78, Da was 0.78±0.61, 0.64±0.64, and 0.48±0.64, and Do was 1.65±0.64, 1.24±0.60, and 0.86±0.55, respectively. The BAD parameters of Df (F=129.549), Db (F=829.491), Dp (F=344.373), Dt (F=7.249), Da (F=68.637) and Do (F=524.877) were all significantly different between groups (P<0.01). The proportion of suspicious and pathological BAD parameters [Df (χ²=161.8), Db (χ²=611.75), Dp (χ²=478.84), Da (χ²=44.636), and Do (χ²=553.11)] suggested the distribution in each group was significantly different (P<0.01). Conclusions: Corneal diameter had a significant influence on BAD. Compared with eyes with large corneas, the false positive rate of BAD was higher in eyes with small corneas.(Chin J Ophthalmol, 2020, 56: 761-767).

Physiological roles of transverse lipid asymmetry of animal membranes.

The plasma membrane phospholipid distribution of animal cells is markedly asymmetric. Phosphatidylserine (PS) and phosphatidylethanolamine (PE) are concentrated in the inner leaflet, whereas phosphatidylcholine (PC) and sphingomyelin (SM) are concentrated in the outer leaflet. This non-equilibrium situation is maintained by lipid pumps (flippases or floppases), which utilize energy in the form of ATP to translocate lipids from one leaflet to the other. Scramblases, which are activated when physiologically required, transport lipids in both directions across the membrane and can abolish lipid asymmetry. Lipid asymmetry also causes imbalances in the areas occupied by lipid in the two membrane leaflets, contributing to membrane curvature. The asymmetry of PS across the plasma membrane plays a crucial signalling role in numerous physiological processes. Exposure of PS on the external surface of blood platelets stimulates blood coagulation. PS exposure by other cells during apoptosis provides an "eat me" signal to surrounding macrophages. Many peripheral and integral membrane proteins have polybasic PS-binding domains on their cytoplasmic surfaces which either provide a membrane anchor or affect activity. These domains can also determine trafficking within the cell and control regulation via an electrostatic switch mechanism, as well as potentially acting as "death sensors" when cytoplasmic PS is transferred to the extracellular leaflet during apoptosis. Apart from these physiological roles, external PS exposure by microorganisms, viruses and cancer cells allows them to mimic the immunosuppressive anti-inflammatory action of apoptotic cells and proliferate, thus providing a strong medical motivation for future research in the field of lipid asymmetry in membranes.

[Immunotherapy and radiotherapy for management of breast cancer: Rational and overview on clinical practice]. / Immunothérapie et radiothérapie dans la prise en charge du cancer du sein : rationnel et synthèse de la littérature sur les applications cliniques actuelles.

The discovery of immunotherapy led to understand the major role of immune system during the tumor process. Conventional treatments, such as chemotherapy, are directly tumoricidal. New drugs are developed to target specifically the immune system to make it regain its ability to recognize and eliminate cancer cells. Radiotherapy is used for a long time for its local action, but its systemic role, based on its impact on immunity, is now better known. Breast cancer was wrongly considered poorly immunogenic and put aside the amazing progress in this new area of treatment. In this article, we would like to present the pre-clinical and clinical rationales to associate immunotherapy to radiotherapy in the management of breast cancer.

Receptor interacting protein kinase 3 promotes cisplatin-induced necroptosis in apoptosis-resistant HepG2/DDP cells.

Hepatocellular carcinoma is the most common primary malignancy of the liver. The chemotherapeutic drug cisplatin is widely used for advanced liver cancer. However, the development of cisplatin resistance in cancer cells, which is related to the decreased cellular susceptibility to apoptosis, results in a major limitation of cisplatin-based chemotherapy. Recently, triggering necroptosis has been proposed to be a novel therapeutic strategy to eradicate apoptosis-resistant cancer cells. In this study, we provided evidence that cisplatin could induce cell death in HepG2 cells, but not in the apoptosis-resistant HepG2/DDP cells. Ectopic expression of RIP3 promoted cisplatin-induced HepG2/DDP cells death, HMGB1 and LDH release. Moreover, we demonstrated that this type of cell death was necroptosis and depended on RIP1-RIP3-MLKL signaling pathway because inhibition of MLKL activity by necrosulfonamide (NSA) or knockdown of RIP1 significantly attenuated cisplatin-induced cell death in HepG2/DDP-RIP3 cells. Finally, we found that ectopic expression of RIP3 sensitized HepG2/DDP cancer cells to cisplatin treatment in vivo. The findings offer new insights into the molecular mechanisms underlying cisplatin-induced necroptosis in liver cancer cells and suggest that combination of cisplatin with other drugs which can restore RIP3 expression in cancer cells maybe a better choice for therapy of apoptosis-resistant cancer.

Functional, histological and molecular characteristics of human exstrophy detrusor.

INTRODUCTION: Bladder exstrophy is a congenital anomaly involving foetal exposure and protrusion of the open bladder through an incomplete lower abdominal wall. Techniques to surgically correct exstrophy after birth have greatly improved, but it still presents a major challenge to achieve continence and a good quality of life for patients and their families as the pathophysiology of bladder dysfunction is unknown. OBJECTIVES: A multimodal approach was used to characterise the histological and biomechanical properties of exstrophy detrusor. These were correlated with myocyte responses to agonists and an evaluation of developmental signalling pathways to evaluate the cause of bladder dysfunction in exstrophy. STUDY DESIGN: Detrusor muscle specimens were obtained during corrective surgery from four exstrophy groups: neonatal (1-3 days, n = 8), younger children (7 months-5 years, n = 13) and older children (8-14 years, n = 11) undergoing secondary procedures and cloacal exstrophy (16 days-9 years, n = 9); control specimens were obtained from children (3 months-9 years, n = 14) undergoing surgery for other pathologies but with normal bladder function. Five lines of experiments were undertaken: measurement of connective tissue to detrusor muscle ratio, contractile responses to electrical and agonist stimulation; in vitro biomechanical stiffness, intracellular Ca2+ responses to contractile agonists and immunohistochemistry for proteins (MMP-7, cyclinD1, ß-catenin and c-myc) involved in fibrosis generation. Exstrophy data were compared with those from the control group. RESULTS: Exstrophy tissue demonstrated reduced smooth muscle compared with connective tissue, reduced contractile responses and greater mechanical stiffness. However, intracellular Ca2+ responses to agonists were maintained. These changes were greatest in neonatal and cloacal exstrophy samples and least in those from older paediatric bladders. Immunolabelled MMP-7, ß-catenin and c-myc were reduced in exstrophy samples. DISCUSSION: These results highlight the reality that newborns with exstrophy have significantly reduced compliance and bladder underactivity, which may persist or return to normal values with surgery and age. The primary cause of underactivity is increased connective tissue in relation to detrusor muscle; however, detrusor myocyte function remains normal. Finally, the increase of the smooth muscle content in the paediatric bladder group indicates a remodelling response of the bladder to surgical correction and time. Excess gestational fibrosis is associated with changed expression of key proteins in the Wnt-signalling pathway, a potential aetiological factor and therapeutic target. CONCLUSION: Results point to connective tissue deposition as the primary pathological process that determines bladder function with normal myocyte function. Future research that reduces connective tissue deposition may lead to improvement in outcomes for these children.