ICSDA: a multi-modal deep learning model to predict breast cancer recurrence and metastasis risk by integrating pathological, clinical and gene expression data.

Breast cancer patients often have recurrence and metastasis after surgery. Predicting the risk of recurrence and metastasis for a breast cancer patient is essential for the development of precision treatment. In this study, we proposed a novel multi-modal deep learning prediction model by integrating hematoxylin & eosin (H&E)-stained histopathological images, clinical information and gene expression data. Specifically, we segmented tumor regions in H&E into image blocks (256 × 256 pixels) and encoded each image block into a 1D feature vector using a deep neural network. Then, the attention module scored each area of the H&E-stained images and combined image features with clinical and gene expression data to predict the risk of recurrence and metastasis for each patient. To test the model, we downloaded all 196 breast cancer samples from the Cancer Genome Atlas with clinical, gene expression and H&E information simultaneously available. The samples were then divided into the training and testing sets with a ratio of 7: 3, in which the distributions of the samples were kept between the two datasets by hierarchical sampling. The multi-modal model achieved an area-under-the-curve value of 0.75 on the testing set better than those based solely on H&E image, sequencing data and clinical data, respectively. This study might have clinical significance in identifying high-risk breast cancer patients, who may benefit from postoperative adjuvant treatment.

Modified serial techniques "ASTRO" facilitated laparoscopic total mesorectal excision for ultralow-lying rectal cancer in obese male patients: how we do it (with video).

BACKGROUND: Laparoscopic total mesorectal excision (LaTME) is a technically challenging for ultralow-lying rectal cancer in obese male patients. Herein, we introduced modified serial techniques "ASTRO" to facilitate LaTME, and the short-term outcomes were presented. METHODS: A prospective study (NCT05067413) was conducted between December 2020 and January 2022. The modified serial surgical techniques "ASTRO" included 5 key steps: (1) Anterior peritoneal reflection (APR) dissection at the highest line along with a "n"-shaped membrane bridge; (2) suspending the APR with a purse-string suture through the bladder peritoneum to enlarge the operating space of the anterior rectal wall; (3) traction and counter-traction continuously of the rectum applied with a cotton tape around the rectum; (4) resection of the pelvic rectum on tripartition, followed by the sequence of "posterior > anterior > lateral" principle; and (5) the trans-anterior Obturator nerve gateway was adapted to transect the distal rectum. The operative data and postoperative short-term outcomes were collected. RESULTS: Twenty-four consecutive patients underwent this procedure successfully. The average body mass index (BMI) was 29.9±1.3. The average of tumor height from anal verge was 4.0 cm (range, 3.0-4.5 cm). The median operating time and blood loss was 217 min (range, 165-420 min) and 50 ml (range, 20-100 ml) respectively. The anterior operation space at the midsagittal plane of the pelvis inlet was increased by 2.0 ± 0.3 cm. The calculated dominant angle was 20 ± 3°. The length of stapling line was 6.8 ± 1.0 cm with 11 cases by one cartridge and 13 cases by 2 cartridges. Eight patients developed postoperative complications including 4 with anastomosis leakage (16.7%), 2 with urinary retention (8.3%), one with anastomotic stenosis (4.2%) and one with ileus (4.2%). All the complications were relatively mild and the patients recovered well. CONCLUSION: Modified serial techniques "ASTRO" could expand the operating space and facilitate LaTME in obese male patients, thereby reducing the risk of conversion to open and transanal dissection.

Understanding the Adsorption of PFOA on MIL-101(Cr)-Based Anionic-Exchange Metal-Organic Frameworks: Comparing DFT Calculations with Aqueous Sorption Experiments.

To examine the effects of different functionalization methods on adsorption behavior, anionic-exchange MIL-101(Cr) metal-organic frameworks (MOFs) were synthesized using preassembled modification (PAM) and postsynthetic modification (PSM) methods. Perfluorooctanoic acid (PFOA) adsorption results indicated that the maximum PFOA adsorption capacity was 1.19 and 1.89 mmol g(-1) for anionic-exchange MIL-101(Cr) prepared by PAM and PSM, respectively. The sorption equilibrium was rapidly reached within 60 min. Our results indicated that PSM is a better modification technique for introducing functional groups onto MOFs for adsorptive removal because PAM places functional groups onto the aperture of the nanopore, which hinders the entrance of organic contaminants. Our experimental results and the results of complementary density functional theory calculations revealed that in addition to the anion-exchange mechanism, the major PFOA adsorption mechanism is a combination of Lewis acid/base complexation between PFOA and Cr(III) and electrostatic interaction between PFOA and the protonated carboxyl groups of the bdc (terephthalic acid) linker.

Preliminary surgical outcomes of laparoscopic right hemicolectomy with transrectal specimen extraction: a propensity score matching study of 120 cases (with video).

Background: Compared with conventional laparoscopic surgery, natural orifice specimen extraction surgery (NOSES) has many advantages. Laparoscopic right colectomy with transvaginal specimen extraction has been reported, but the safety and feasibility of transrectal specimen extraction in male patients with ascending colon cancer remain to be verified. This study aimed to preliminarily evaluate the feasibility and safety of laparoscopic right hemicolectomy with transrectal specimen extraction. Methods: The study was conducted at a single tertiary medical center in China. A total of 494 consecutive patients who underwent laparoscopic right colectomy between September 2018 and September 2020 were included. Transrectal specimen extraction was performed in 40 male patients (the NOSES group). Patients in the NOSES group were matched to the conventional laparoscopic group using propensity score matching at a 1:2 ratio. Short-term and long-term outcomes between the two groups were compared and evaluated. Results: Forty patients in the NOSES group and 80 patients in the conventional laparoscopic group were matched for analysis. Baseline characteristics were balanced after propensity matching. The operative features, including operating time, intraoperative bleeding, and the number of harvested lymph nodes, were statistically comparable in both groups. In terms of post-operative recovery, patients in the NOSES group showed preferable outcomes, as evidenced by less post-operative pain and faster return to flatus, defecation, and discharge. The post-operative complications rate, according to the Clavien-Dindo classification system, was similar in both groups. No differences in overall survival or disease-free survival were observed between the two groups. Conclusions: Laparoscopic right colectomy with transrectal specimen extraction is oncologically safe. Compared with conventional laparoscopic right colectomy, it can reduce post-operative pain, accelerate post-operative recovery, shorten the hospital stay, and achieve better cosmetic effect.

Pathological and perioperative outcomes of extracorporeal versus intracorporeal anastomosis in laparoscopic transverse colon cancer resection: retrospective multicentre study.

BACKGROUND: The aim of this study was to compare the pathological and perioperative outcomes of extracorporeal versus intracorporeal anastomosis after laparoscopic transverse colon cancer resection. METHODS: In this retrospective study, patients from seven institutions in China who underwent laparoscopic resection of transverse colon cancer between 2019 and 2021 were selected and included. Either extended right hemicolectomy or transverse colectomy/extended left hemicolectomy was performed. The clinical characteristics and the pathological and perioperative outcomes were compared between patients undergoing extracorporeal or intracorporeal anastomosis. Resection margin lengths were measured on formalin-fixed specimens and an inadequate margin was defined as less than 4.2 cm between the division and the tumour. The outcome of interest was the prevalence of specimens with an inadequate margin. Length of incision, bowel function recovery, hospital stay, early postoperative pain (first day after surgery), 30-day complications, and nodal harvest were investigated as secondary outcomes. RESULTS: Of 411 patients treated during the study interval, 370 patients with transverse colon cancer were included (23.2 per cent treated with intracorporeal anastomosis and 76.8 per cent treated with extracorporeal anastomosis). The prevalence of specimens with inadequate margins was lower in the intracorporeal anastomosis group compared with the extracorporeal anastomosis group in patients undergoing extended right hemicolectomy (P = 0.045) and in patients undergoing transverse colectomy/extended left hemicolectomy (P = 0.030). In multivariate analysis, extracorporeal anastomosis (OR 2.94 (95 per cent c.i. 1.33 to 6.49), P = 0.008) and transverse colectomy/extended left hemicolectomy (OR 1.75 (95 per cent c.i. 1.03 to 2.96), P = 0.038) were independent risk factors for specimens with an inadequate margin. Intracorporeal anastomosis was associated with a shorter incision length (P < 0.001), an earlier recovery of bowel function (P = 0.035), a shorter postoperative hospital stay (P = 0.042), less early postoperative pain (P < 0.001), a longer specimen length (P = 0.042), a longer resection margin (P = 0.007), and a greater lymph node harvest (P = 0.036). There was no statistically significant difference in 30-day complications. CONCLUSION: Patients with transverse colon cancer have better perioperative outcomes, fewer margins of less than 4.2 cm, and larger lymph node harvests when the anastomosis is performed intracorporeally. Further studies are needed to confirm these findings. REGISTRATION NUMBER: NCT05061199 (www.clinicaltrials.gov).

Influence of transvaginal laparoscopic surgery on sexual function, life quality and short-term efficacy of patients diagnosed with colorectal cancer.

OBJECTIVE: To analyze the effect of transvaginal specimen removal on sexual function, life quality and short-term efficacy of patients diagnosed with colorectal cancer. METHOD: We retrospectively analyzed the clinical data of 100 patients with colorectal cancer treated in the Cancer Hospital Chinese Academy of Medical Sciences from September 2017 to December 2019. Among them, 52 patients who underwent transvaginal laparoscopic mid-to-high rectal cancer radical resection without assisted abdominal incision who were chosen as the observation group, and 48 patients with conventional laparoscopic-assisted mid-to-high rectal cancer radical resection were set as the control group. Intraoperative blood loss, number of lymph nodes retrieved, operation time, time of urinary catheter removal, drainage tube removal time and postoperative hospital stay were recorded and compared between the two groups. During the process, the Visual Analogue Scale (VAS) was used to assess the pain status of both groups of patients 24 hours after the operation, and the Female Sexual Function Index was used to evaluate the sexual function quality of patients before and 3 months after surgery. Postoperative complications, 2-year survival rate and 6-month postoperative quality of life of both groups of patients were evaluated and compared. RESULTS: In comparison with the control group, the amount of intraoperative blood loss, catheter removal time, drainage tube removal time, and length of postoperative hospital stay were significantly reduced in the observation group, while the number of lymph nodes retrieved was significantly greater. The VAS score 24 hours after operation was lower in the observation group compared with the control group, with statistical significance. There was no significant difference in postoperative sexual function and complication rates between the two groups. However, the 2-year survival rate and the quality of life 6 months after surgery were comparatively higher in the observation group. CONCLUSION: Natural orifice specimen extraction surgery (NOSES) is effective for transvaginal specimen removal of patients with colorectal cancer, and can significantly improve the prognosis and life quality of patients without affecting their sexual function, with a high safety profile, which is worthy of clinical promotion.

Surgical outcomes and sexual function after laparoscopic colon cancer surgery with transvaginal versus conventional specimen extraction: A retrospective propensity score matched cohort study.

BACKGROUND: Natural orifice specimen extraction has been shown to reduce postoperative pain and wound complications, and provide better cosmetic outcome. However, whether transvaginal specimen extraction affects sexual function remains controversial. The purpose of this study was to investigate the short-term outcomes, sexual function, cosmetic outcomes and prognosis after colon cancer surgery with transvaginal specimen extraction. METHOD: This study was a propensity score-matched comparative retrospective study, based on prospectively collected data in a single center. This study included 70 pairs of propensity score-matched female patients who underwent laparoscopic curative resection for stage I-III colon cancer with transvaginal specimen extraction and conventional specimen extraction between November 2015 and November 2020. Covariates used in the propensity score included age, tumor diameter, tumor differentiation, T stage and American Joint Committee on Cancer stage. Outcome measures included postoperative complication, postoperative sexual function, cosmetic result, disease-free survival and overall survival. RESULTS: Patients in transvaginal group were administered with less additional analgesics (P = 0.008), and had fewer wound complications (P = 0.028). None of patient in the two groups underwent anastomotic leakage, incisional disruption or vaginal fistula. The baseline pre-operative Female Sexual Function Index scores in two groups were the same, and no difference was found in postoperative score between the two groups (P = 0.790). The cosmetic score was significantly better in transvaginal group than that of conventional laparoscopy group (P = 0.000). During the follow-up period, there were no differences in OS or DFS between the two groups (P = 0.658, P = 0.663). CONCLUSIONS: Compared with laparoscopic colon cancer radical resection with specimen extraction, transvaginal specimen extraction is oncologically safe, brings better short-term outcomes, improved cosmetic results and has limited adverse effect on female's sexual function. This procedure can be further carried out in more appropriate patients.

Comparison of the short-term outcomes between intracorporeal isoperistaltic and antiperistaltic totally stapled side-to-side anastomosis for right colectomy: A retrospective study on 214 consecutive patients.

Background: Totally laparoscopic right colectomy has been demonstrated to be safe and feasible. Two manners of anastomosis, namely, antiperistaltic and isoperistaltic stapled side-to-side anastomosis, have been described before. However, research concerning the influence of different peristaltic orientations on anastomosis is rare and, if there is, included relatively small cases without long-term outcomes. The aim of this study was to compare the short- and long-term outcomes of intracorporeal isoperistaltic side-to-side anastomosis and antiperistaltic side-to-side anastomosis for right colectomy. Methods: We retrospectively reviewed 214 consecutive patients who underwent totally laparoscopic right colectomy from January 2017 to December 2020 at our medical center. Two modalities of anastomosis were used: isoperistaltic totally side-to-side anastomosis and antiperistaltic totally side-to-side anastomosis. Data on demographics, disease features, pathological characteristics, operative details, and short-term outcomes were collected and analyzed. Results: We found that operative features such as operating time, intraoperative bleeding, length of resected intestine, number of harvested lymph nodes, and length of incision, as well as measures of postoperative recovery such as time to first flatus, time to first defecation, and length of stay, were statistically comparable between the 2 groups. The postoperative complication rate was also similar between the 2 groups. The median follow-up time was 35.6 months, and no differences were observed in the long-term outcomes. Conclusion: Intracorporeal isoperistaltic side-to-side anastomosis can achieve short- and long-term outcomes similar to those of antiperistaltic side-to-side anastomosis. Both techniques are safe and feasible.

Efficient recovery of potent tumour-infiltrating lymphocytes through quantitative immunomagnetic cell sorting.

Adoptive cell therapies require the recovery and expansion of highly potent tumour-infiltrating lymphocytes (TILs). However, TILs in tumours are rare and difficult to isolate efficiently, which hinders the optimization of therapeutic potency and dose. Here we show that a configurable microfluidic device can efficiently recover potent TILs from solid tumours by leveraging specific expression levels of target cell-surface markers. The device, which is sandwiched by permanent magnets, balances magnetic forces and fluidic drag forces to sort cells labelled with magnetic nanoparticles conjugated with antibodies for the target markers. Compared with conventional cell sorting, immunomagnetic cell sorting recovered up to 30-fold higher numbers of TILs, and the higher levels and diversity of the recovered TILs accelerated TIL expansion and enhanced their therapeutic potency. Immunomagnetic cell sorting also allowed us to identify and isolate potent TIL subpopulations, in particular TILs with moderate levels of CD39 (a marker of T-cell reactivity to tumours and T-cell exhaustion), which we found are tumour-specific, self-renewable and essential for the long-term success of adoptive cell therapies.

Comparative short- and long-term outcomes of three techniques of natural orifice specimen extraction surgery for rectal cancer.

BACKGROUND: The aim of this study was to evaluate the safety of natural orifice specimen extraction surgery (NOSES) and to compare the short- and long-term outcomes of three techniques of NOSES for rectal cancer (RC). MATERIALS AND METHODS: A consecutive series of RC patients in stage I-III who underwent laparoscopic NOSES were enrolled. Three main techniques of NOSES included specimen eversion and extra-abdominal resection (EVER), specimen extraction and extra-abdominal resection (EXER) and intra-abdominal resection and specimen extraction (IREX). The postoperative complications, 5-year disease free survival (DFS), 5-year local recurrence rate (LRR) and 5-year distant metastasis rate (DMR) were compared in three techniques. RESULTS: 268 RC patients met inclusion criteria, including 83 patients treated with EVER, 75 patients treated with EXER and 110 patients treated with IREX. Tumor location was the most critical factor associated with technique selection, with P < 0.001. Postoperative complication rate was 12.3% for all patients, and it was 18.1% for EVER, 13.3% for EXER and 7.3% for IREX. There were no significant differences for anastomotic leakage, anastomotic bleeding and intraabdominal abscess among three technique groups, with P > 0.05. For long-term outcomes, the 5-year DFS, 5-year LRR and 5-year DMR were 85.03%, 4.22% and 11.00% for all patients. Patients in advanced tumor stage have worse long-term survival compared with patients in early stage, but no significant survival differences were observed among three technique groups. CONCLUSION: Three techniques of NOSES for RC had acceptable short- and long-term outcomes, and tumor location was a determinant of technique selection.

Cell Type-Specific Gene Expression of Alpha 5 Subunit-Containing Gamma-Aminobutyric Acid Subtype A Receptors in Human and Mouse Frontal Cortex.

Converging evidence suggests that deficits in somatostatin (SST)-expressing neuron signaling contributes to major depressive disorder. Preclinical studies show that enhancing this signaling, specifically at α5 subunit-containing γ-ami-nobutyric acid subtype A receptors (α5-GABAARs), provides a potential means to overcome low SST neuron function. The cortical microcircuit comprises multiple subtypes of inhibitory γ-aminobutyric acid (GABA) neurons and excitatory pyramidal cells (PYCs). In this study, multilabel fluorescence in situ hybridization was used to characterize α5-GABAAR gene expression in PYCs and three GABAergic neuron subgroups - vasoactive intestinal peptide (VIP)-, SST-, and parvalbumin (PV)-expressing cells - in the human and mouse frontal cortex. Across species, we found the majority of gene expression in PYCs (human: 39.7%; mouse: 54.14%), less abundant expression in PV neurons (human: 20%; mouse: 16.33%), and no expression in VIP neurons (0%). Only human SST cells expressed GABRA5, albeit at low levels (human: 8.3%; mouse: 0%). Together, this localization suggests potential roles for α5-GABAARs within the cortical microcircuit: (1) regulators of PYCs, (2) regulators of PV cell activity across species, and (3) sparse regulators of SST cell inhibition in humans. These results will advance our ability to predict the effects of pharmacological agents targeting α5-GABAARs, which have shown therapeutic potential in preclinical animal models.