Robotic versus laparoscopic left colectomy with complete mesocolic excision for left-sided colon cancer: a multicentre study with propensity score matching analysis.

PURPOSE: Robotic surgery for right-sided colon and rectal cancer has rapidly increased; however, there is limited evidence in the literature of advantages of robotic left colectomy (RLC) for left-sided colon cancer. The purpose of this study was to compare the outcomes of RLC versus laparoscopic left colectomy (LLC) with complete mesocolic excision (CME) for left-sided colon cancer. METHODS: Patients who had RLC or LLC with CME for left-sided colon cancer at five hospitals in China between January 2014 and April 2022 were included. A one-to-one propensity score matched analysis was performed to decrease confounding. The primary outcome was postoperative complications occurring within 30 days of surgery. Secondary outcomes were disease-free survival, overall survival and the number of harvested lymph nodes. RESULTS: A total of 292 patients (187 male; median age 61.0 [20.0-85.0] years) were eligible for this study, and propensity score matching yielded 102 patients in each group. The clinicopathological characteristics were well-matched between groups. The two groups did not differ in estimated blood loss, conversion to open rate, time to first flatus, reoperation rate, or postoperative length of hospital stay (p > 0.05). RLC was associated with a longer operation time (192.9 ± 53.2 vs. 168.9 ± 52.8 min, p = 0.001). The incidence of postoperative complications did not differ between the RLC and LLC groups (18.6% vs. 17.6%, p = 0.856). The total number of lymph nodes harvested in the RLC group was higher than that in the LLC group (15.7 ± 8.3 vs. 12.1 ± 5.9, p < 0.001). There were no significant differences in 3-year and 5-year overall survival or 3-year and 5-year disease-free survival. CONCLUSION: Compared to laparoscopic surgery, RLC with CME for left-sided colon cancer was found to be associated with higher numbers of lymph nodes harvested and similar postoperative complications and long-term survival outcomes.

A novel dephosphorylation targeting chimera selectively promoting tau removal in tauopathies.

Intraneuronal accumulation of hyperphosphorylated tau is a hallmark pathology shown in over twenty neurodegenerative disorders, collectively termed as tauopathies, including the most common Alzheimer's disease (AD). Therefore, selectively removing or reducing hyperphosphorylated tau is promising for therapies of AD and other tauopathies. Here, we designed and synthesized a novel DEPhosphorylation TArgeting Chimera (DEPTAC) to specifically facilitate the binding of tau to Bα-subunit-containing protein phosphatase 2A (PP2A-Bα), the most active tau phosphatase in the brain. The DEPTAC exhibited high efficiency in dephosphorylating tau at multiple AD-associated sites and preventing tau accumulation both in vitro and in vivo. Further studies revealed that DEPTAC significantly improved microtubule assembly, neurite plasticity, and hippocampus-dependent learning and memory in transgenic mice with inducible overexpression of truncated and neurotoxic human tau N368. Our data provide a strategy for selective removal of the hyperphosphorylated tau, which sheds new light for the targeted therapy of AD and related-tauopathies.

Comparison of transanal total mesorectal excision (TaTME) versus laparoscopic TME for rectal cancer: A case matched study.

BACKGROUND: Transanal total mesorectal excision (TaTME) has been developed to improve the quality of laparoscopic TME for patients with rectal cancer. Recently, international concern on TaTME was raised by a national cohort study showing an increased rate of local recurrences. This study aimed to compare clinicopathological and mid-term oncological outcomes of TaTME versus laparoscopic TME (LaTME) for mid and low rectal cancer of a high volume center. METHODS: From August 2014 to October 2019, patients with mid or low rectal cancer who received TaTME procedure were identified. The cases were matched with patients treated with LaTME. Data were retrospectively collected including operative details, postoperative morbidity, pathologic results, and oncologic outcomes. Primary endpoint was the local recurrence (LR) rate. RESULTS: Propensity score matching yielded 70 patients in each of the groups. There were no statistically significant differences between the 2 groups in terms of postoperative complications, conversion rate to open surgery and circumferential resection margin. Local recurrence occurred in 2 patients (2.9%) in the transanal group, whereas 1 patient developed a local recurrence in the laparoscopic group (1.4%)(p = 0.559). Kaplan-Meier survival analysis showed a 2 year Local recurrence rate 1.5% VS 1.6%(p = 0.934), DFS 88.0% VS 87.7%, OS 94.0% vs 100% for transanal and laparoscopic group, respectively. CONCLUSIONS: In a high volume center the transanal total mesorectal procedure is feasible, and appears to be safe alternative to laparoscopic surgery. Oncological outcomes were acceptable and no increased multi or unifocal local recurrence rate was found.

Abdominal ventral rectopexy with colectomy for obstructed defecation syndrome: An alternative option for selected patients.

BACKGROUND: Abdominal ventral rectopexy (AVR) with colectomy is controversial in the treatment of obstructed defecation syndrome (ODS). Literature data on this technique for ODS are very limited. AIM: To evaluate the safety and efficacy of AVR with colectomy for selected patients with ODS. METHODS: Consecutive patients who underwent AVR with colectomy for ODS were identified prospectively from 2016 to 2017 in our department. Patient demographics, perioperative surgical results, and postoperative follow-up outcomes were collected and analyzed. Long-term follow-up was evaluated with standardized questionnaires. The severity of symptoms was assessed by the objective Wexner Constipation Score (WCS) and ODS Score. The quality of life was assessed by the Patients Assessment of Constipation Quality of Life score. Functional outcome was compared pre- and post-operatively for each patient. The primary outcomes were determined by the improvement in symptoms and quality of life. Secondary outcome measures were operating time, postoperative length of stay, morbidity and mortality, improvement of pelvic floor structure, and patient satisfaction. RESULTS: Four patients underwent robotic-assisted surgery, and two patients underwent a laparoscopic-assisted procedure. The mean operating time for the robotic approach was 243 min (range 160-300 min), and the mean operating time for the laparoscopic approach was 230 min (range 220-240 min). The mean postoperative length of stay was 8.2 d (range 6-12 d). There was no conversion to open procedure and no postoperative mortality. No urinary retention, wound infection, prolonged ileus, pelvic infection and anastomosis leakage occurred. Six patients were followed up for 36 mo. The WCS, ODS, and Patients Assessment of Constipation Quality of Life score improved significantly postoperatively (P < 0.05). The WCS and ODS scores showed the best remission and stabilization at 6 to 12 mo after surgery. There was no recurrence or novel constipation after surgery. None of the patients used laxative medication. CONCLUSION: Robotic and laparoscopic-assisted ventral rectopexy with colectomy is a safe and effective procedure for selected patients with ODS. However, comprehensive preoperative evaluation and careful patient selection are essential.

Defecation function and quality of life in patients with slow-transit constipation after colectomy.

BACKGROUND: Although total or subtotal colectomy for slow-transit constipation (STC) has been proven to be a definite treatment, the associated defecation function and quality of life (QOL) are rarely studied. AIM: To evaluate the effectiveness of surgery for STC regarding defecation function and QOL. METHODS: From March 2013 to September 2017, 30 patients undergoing surgery for STC in our department were analyzed. Preoperative, intra-operative, and postoperative 3-mo, 6-mo, 1-year, and 2-year follow-up details were recorded. Defecation function was assessed by bowel movements, abdominal pain, bloating, straining, laxative, enema use, diarrhea, and the Wexner constipation and incontinence scales. QOL was evaluated using the gastrointestinal QOL index and the 36-item short form survey. RESULTS: The majority of patients (93.1%, 27/29) stated that they benefited from the operation at the 2-year follow-up. At each time point of the follow-up, the number of bowel movements per week significantly increased compared with that of the preoperative conditions (P < 0.05). Similarly, compared with the preoperative values, a marked decline was observed in bloating, straining, laxative, and enema use at each time point of the follow-up (P < 0.05). Postoperative diarrhea could be controlled effectively and notably improved at the 2-year follow-up. The Wexner incontinence scores at 6-mo, 1-year, and 2-year were notably lower than those at the 3-mo follow-up (P < 0.05). Compared with those of the preoperative findings, the Wexner constipation scores significantly decreased following surgery (P < 0.05). Thus, it was reasonable to find that the gastrointestinal QOL index scores clearly increase (P < 0.05) and that the 36-item short form survey results displayed considerable improvements in six spheres (role physical, role emotional, physical pain, vitality, mental health, and general health) following surgery. CONCLUSION: Total or subtotal colectomy for STC is not only effective in alleviating constipation-related symptoms but also in enhancing patients' QOL.

The impact of sedation on quality metrics of colonoscopy: a single-center experience of 48,838 procedures.

PURPOSE: Investigation of the role of sedation during colonoscopy is meaningful as the advantages of colonoscopy performing with sedation are still controversial. METHODS: Medical records of patients who underwent colonoscopy in our institution were retrospectively analyzed. The sedation rate, adenoma detection rate (ADR), polyp detection rate (PDR), cecal intubation rate (CIR), iatrogenic colonic perforation rate (ICP) were calculated. RESULTS: A total of 48,838 colonoscopies (24,498 in males) dated from July 2007 to February 2017 were analyzed. The median age was 50 years (range 16-85 years). An overall sedation rate was 80.38%. The PDR was 26.77%, and was not statistically different between colonoscopy with or without sedation (26.67% vs 27.22, p = 0.474). ADR was 12.9% regardless of applying sedation or not (13.0% vs 12.44%, p = 0.337). The CIR was 87.42% in all examinations with an adjusted CIR of 90.34%, and was higher when performed with sedation than without sedation (88.92% vs 80.64%, p < 0.0001). Five cases (0.01%) of ICP were reported, all of which occurred in patients under sedation. CONCLUSIONS: The use of sedation is associated with increased CIR, but ADR and PDR remain unchanged with or without sedation. However, perforation rate, albeit very low, is significantly higher in sedated patients.

[Short-term outcomes of robot-assisted transanal total mesorectal excision].

OBJECTIVE: To explore the feasibility and safety of Da Vinci robot-assisted transanal total mesorectal excision (taTME). METHODS: From May 2017 to July 2018, six rectal cancer patients underwent Da Vinci robot-assisted taTME at our hospital. The clinical data and short-term follow-up results were retrospectively analyzed. SURGICAL PROCEDURE: The patient was placed in a Trendelenburg lithotomy position and sutured with purse string 1-2 cm from the anus to the distal end of the tumor. A self-made platform for transanal surgery was installed and the robot was connected. The rectum was transected circumferentially 0.5 cm from the distal end of the purse. The robot entered the " holy plane" and separated upward between the visceral parietal fasciae to the level of the third sacrum posteriorly and the peritoneal refcection anteriorly. The abdominal trocar was repositioned and connected to the robot. Through the abdominal cavity, the Toldt space of the posterior sigmoid mesentery was entered, and the D3 lymph nodes were dissected proximally. Separation was performed distally to join the perineal approach. Specimen was pulled out from the anus and excised. The cut end of sigmoid colon was anastomosed with the distal rectum or anal canal. Operative status, postoperative pathology and short-term efficacy were analyzed. Mesorectum of specimen was evaluated as complete, near complete and incomplete according to the Nagtegaal criteria. Anastomotic leakage was evaluated according to the criteria developed by the International Rectal Cancer Research Group. RESULTS: All the 6 patients received Da Vinci robot-assisted taTME and sigmoid-anal anastomosis. In the 6 patients, 3 were male and 3 female; mean age was (62.6±2.6) years old; body mass index was (20.5±3.0) kg/m2; distance from tumor to anal edge was (39.4±12.0) mm; length of tumor was (33.6±9.2) mm. Four patients received neoadjuvant therapy before surgery. All the patients completed operations successfully without conversion to laparotomy perioperative, severe complications or death. The mean total operative time was (245.8±24.2) minutes; transition interval of two procedures was (21.2±2.6) minutes; time of transanal robotic dissection of mesorectum was (72.3±15.2) minutes; intra-operative blood loss was (86.7±59.9) ml; the height of anastomosis was (16.0±6.1) mm. There were no intra-operative complications including accidental hemorrhage or urethral injury in any patients. The length of the specimens was (177.0±33.3) mm, and the mesorectum was complete in 5 cases, and near complete in 1 case. The mean distal margin was (20.2±3.2) mm, and the proximal, distal and circumferential margins were all negative. Postoperative pathological staging: T0N0 in 1 case, T0N1 in 1 case , T2N0 in 2 cases , T4N1 in 1 case, T3N0 in 1 case. The former 5 cases received clear fluit diet on the first day, and received fluid diet on the second day after operation. The drainage tube was removed 3 to 6 days after operation. The postoperative hospital stay was 5 to 7 days. The sixth case developed grade B anastomotic leakage on the third day after operation and healed by conservative treatment. No postoperative death, and no serious complications such as intra-abdominal hemorrhage, intestinal obstruction were found. All the patients were followed up for 5 to 19 months, and no local recurrence and death were observed. CONCLUSION: The robotic system is safe and feasible for taTME procedure in rectal cancer with good short-term efficacy. However, the long-term outcomes require further observation.

Medicinal supplement genipin induces p53 and Bax-dependent apoptosis in colon cancer cells.

Colorectal cancer (CRC) is the third leading cause of cancer-associated mortality worldwide. Genipin is a medicinal herb compound derived from the gardenia fruit, which has been reported to exhibit antitumor activity against several types of cancer. The aim of the present study was to investigate the antitumor effect of genipin on colon cancer and the underlying molecular mechanisms. Genipin significantly inhibited the viability of HCT116 and SW480 cells in vitro in a dose- and time-dependent manner. Additionally, genipin was able to significantly inhibit tumor growth in nude mice with xenografts of HCT116 and SW480 cells. The inhibition of tumor growth by genipin treatment was coupled with G0/G1 cell cycle arrest, apoptosis induction, increased reactive oxygen species damage and loss of mitochondrial membrane potential. Further investigation of genipin-treated HCT116 cells revealed that the expression of p53, Bax and cleaved caspase-3 in genipin-treated cells was increased compared with the vehicle control, whereas B-cell lymphoma-2 expression appeared to be lower in genipin-treated cells. Collectively, the findings of the present study indicate that genipin was able to decrease proliferation and promote apoptosis in colon cancer cells by inducing the p53/Bax-mediated signaling pathway. Therefore, genipin may be used as a novel therapeutic agent in the treatment of CRC.

[Robotic-assisted transanal total mesorectal excision for lower rectal cancer].

OBJECTIVE: To explore the availability of Da Vinci robotic-assisted transanal total mesorectal excision(taTME) for lower rectal cancer, which have been regarded as challenging situations in rectal cancer surgery. METHODS: The medical records of a patient who underwent robotic-assisted transanal total mesorectal excision, coloanal anastomosis and ileostomy for lower rectal cancer on May 31st 2017 were reported. RESULTS: The case was a sixty-three year-old male patient with a body mass index of 19.1 kg/m2. Preoperative examinations showed the tumor size was 4 cm×4 cm×3 cm. With a distance from the anal verge of 4 cm.The tumor was moderately differentiated and staged as cT3N2M0.taTME was performed successfully and the patient recovered quickly without any complications. The histological report showed a complete mesorectal excision with freee distal and circumferential margins. CONCLUSION: Robotic-assisted taTME is available. Robotics may help to overcome technical difficulties.

[Enhanced recovery after surgery in the west China: problems, strategy and future].

Enhanced recovery after surgery (ERAS) has been widely used in the world for near 20 years, which should be considered as the milestone of modern medicine advancement, changing the routine perioperative principle, accelerating the recovery speed following operation, minimizing the postoperative pain, and saving the medical resources. Despite the remarkable advance, the quality and application of ERAS in the west China needs further improvement if compared with international level or even some domestic hospitals. The postoperative hospital stay in west China is much longer than the reported 3 to 5 days according to published references. Several suggestions can be help: (1) Based on the published consensus and the successful experiences of ERAS in colorectal surgery, the medical institution should make great effort to extend this technique to change the profound traditional idea in medical staffs and patients. (2) The medical administrations should take the application of ERAS as a key performance index and annual work plan in hospital. (3) Multiple disciplinary team including anesthetist, surgeon, dietitian, and nurses is essential for hospital to promote the quality of ERAS. Undoubtedly, ERAS is going to be the conventional medical care in the western area of China. We may look forward to seeing more researches from western China to update the ERAS consensus.

Expression of transient receptor potential ankyrin 1 correlating to the recovery of colonic transit after pelvic nerve denervation in rats.

BACKGROUND: It has been reported that colorectal motility dysfunction due to pelvic nerve (PN) damage is restored overtime. However, the adaptive mechanism is unknown. Previous studies implied that transient receptor potential ankyrin 1 (TRPA1) mediated sensory nerve signal input plays a crucial role in gut motility regulation. The present study aimed to observe the colorectal motility restoration in rats after PN transection and to explore the change of TRPA1 protein expression in this adaptive process. METHODS: Seventy-eight adult rats were divided into two groups randomly: sham and PN cut. Colonic transit function was determined with radioisotope method by calculating the geometric center (GC) of the distribution of 51Cr at postoperative days (POD) 1, 3, and 7. Expression of TRPA1 in the proximal and distal colon mucosa was detected with Western blotting at POD 1, 3, and 7. RESULTS: At POD 1, the colonic transit in PN cut group was significantly delayed (GC = 4.91 ± 0.41, P < 0.05), when compared with the sham group (GC = 5.76 ± 0.85). A significant trend toward recovery was noted in the PN cut group at POD 3 (GC = 5.58 ± 0.36) and POD 7 (GC = 6.44 ± 0.78). Western blot demonstrated attenuated expression of TRPA1 in the distal colon mucosa after PN denervation at POD 1 (0.39 ± 0.12) compared with that of the shams. A significant trend of increasing expression of TRPA1 was demonstrated in the PN cut group at POD 3 (0.78 ± 0.10) and at POD 7 (1.06 ± 0.13). CONCLUSIONS: Delayed colonic motility due to PN denervation gradually restored overtime, which may relate to the corresponding expression of TRPA1 in the distal colonic mucosa of rats.

Biomarkers for Early Diagnostic of Mild Cognitive Impairment in Type-2 Diabetes Patients: A Multicentre, Retrospective, Nested Case-Control Study.

BACKGROUND: Both type 2 diabetes mellitus (T2DM) and Alzheimer's disease (AD) are common age-associated disorders and T2DM patients show an increased risk to suffer from AD, however, there is currently no marker to identify who in T2DM populations will develop AD. Since glycogen synthase kinase-3ß (GSK-3ß) activity, ApoE genotypes and olfactory function are involved in both T2DM and AD pathogenesis, we investigate whether alterations of these factors can identify cognitive impairment in T2DM patients. METHODS: The cognitive ability was evaluated using Minimum Mental State Examination (MMSE) and Clinical Dementia Rating (CDR), and the mild cognitive impairment (MCI) was diagnosed by Petersen's criteria. GSK-3ß activity in platelet, ApoE genotypes in leucocytes and the olfactory function were detected by Western/dot blotting, the amplification refractory mutation system (ARMS) PCR and the Connecticut Chemosensory Clinical Research Center (CCCRC) test, respectively. The odds ratio (OR) and 95% confidence intervals (95% CI) of the biomarkers for MCI diagnosis were calculated by logistic regression. The diagnostic capability of the biomarkers was evaluated by receiver operating characteristics (ROC) analyses. FINDINGS: We recruited 694 T2DM patients from Jan. 2012 to May. 2015 in 5 hospitals (Wuhan), and 646 of them met the inclusion criteria and were included in this study. 345 patients in 2 hospitals were assigned to the training set, and 301 patients in another 3 hospitals assigned to the validation set. Patients in each set were randomly divided into two groups: T2DM without MCI (termed T2DM-nMCI) or with MCI (termed T2DM-MCI). There were no significant differences for sex, T2DM years, hypertension, hyperlipidemia, coronary disease, complications, insulin treatment, HbA1c, ApoE ε2, ApoE ε3, tGSK3ß and pS9GSK3ß between the two groups. Compared with the T2DM-nMCI group, T2DM-MCI group showed lower MMSE score with older age, ApoE ε4 allele, higher olfactory score and higher rGSK-3ß (ratio of total GSK-3ß to Ser9-phosphorylated GSK-3ß) in the training set and the validation set. The OR values of age, ApoE ε4 gene, olfactory score and rGSK-3ß were 1.09, 2.09, 1.51, 10.08 in the training set, and 1.06, 2.67, 1.47, 7.19 in the validation set, respectively. The diagnostic accuracy of age, ApoE ε4 gene, olfactory score and rGSK-3ß were 0.76, 0.72, 0.66, 0.79 in the training set, and 0.70, 0.68, 0.73, 0.79 in the validation set, respectively. These four combined biomarkers had the area under the curve (AUC) of 82% and 86%, diagnostic accuracy of 83% and 81% in the training set and the validation set, respectively. INTERPRETATION: Aging, activation of peripheral circulating GSK-3ß, expression of ApoE ε4 and increase of olfactory score are diagnostic for the mild cognitive impairment in T2DM patients, and combination of these biomarkers can improve the diagnostic accuracy.

[Clinical analysis of 11 cases undergoing transanal minimal invasive or combined laparoscopy total mesorectal excision for rectal cancer].

OBJECTIVE: To explore the feasibility and safety of transanal minimal invasive or combined laparoscopy total mesorectal excision. METHODS: Clinical data of 11 cases with rectal cancer undergoing transanal total mesorectal excision(taTME) in our hospital between September 2014 and May 2015 were analyzed retrospectively. RESULTS: Among 11 patients, 3 underwent pure-taTME successfully without abdominal incision and ileostomy, whose operation time was 210, 230, 215 min respectively, while other 8 patients underwent laparoscopy-assisted taTME(hybrid-taTME) with operation time ranging from 150 to 290 (median 205) min. No patient was transferred to open operation, while larger tumors of two patients were removed from hypogastric 5 cm incision. Postoperative first day VAS score was 1 to 3(2.0±0.6), the first flatus was 6 to 70(30.2±17.3) h, hospital stay was 4 to 12(7.5±2.5) d, the blood loss was (104±127) ml and the liquid food intake was (28.3±6.3) h. Postoperative complications included 1 case of subcutaneous emphysema, 1 case of anastomotic stoma bleeding, 2 cases of dysuria, which were cured by conservative therapy. One patient developed rectovaginal fistula 20 days after operation and then underwent ileostomy. No relapse of tumor or death during follow-up. CONCLUSIONS: For suitable rectal cancer patients, taTME or hybrid-taTME is feasible.