Transvaginal versus transabdominal specimen extraction in minimally invasive surgery: a systematic review and meta-analysis.

AIM: Natural orifice specimen extraction (NOSE) is an alternative to conventional transabdominal retrieval. We aimed to compare outcomes following transvaginal specimen extraction (TVSE) and transabdominal specimen extraction (TASE) in minimally invasive abdominal surgery. METHODS: An electronic database search of PubMed, Embase and CENTRAL was performed from inception until March 2023. Comparative studies evaluating TVSE versus TASE in adult female patients were included. Studies involving transanal NOSE, endoluminal surgery, or TVSE with concomitant hysterectomy were excluded. Weighted mean differences (WMD) and odds ratio were estimated for continuous and dichotomous outcomes respectively. Primary outcomes were postoperative day 1 (POD1) pain and length of stay (LOS). Secondary outcomes were operative time, rescue analgesia, morbidity, and cosmesis. A review of sexual, oncological, and technical outcomes was performed. RESULTS: Thirteen studies (2 randomised trials, 11 retrospective cohort studies), involving 1094 patients (TASE 583, TVSE 511), were included in the analysis. Seven studies involved colorectal disease and six assessed gynaecological conditions. TVSE resulted in significantly decreased POD1 pain (WMD 1.08, 95% CI: 0.49, 1.68) and shorter LOS (WMD 1.18 days, 95% CI: 0.14, 2.22), compared to TASE. Operative time was similar between both groups, with fewer patients requiring postoperative rescue analgesia with TVSE. Overall morbidity rates, as well as both wound-related and non-wound related complication rates were better with TVSE, while anastomotic morbidity rates were comparable. Cosmetic scores were higher with TVSE. TVSE did not result in worse sexual or oncological outcomes. CONCLUSION: TVSE may be feasible and beneficial compared to TASE when performed by proficient laparoscopic operators, using appropriate selection criteria. Continued evaluation with prospective studies is warranted.

Venous thromboembolism among Asian populations with localized colorectal cancer undergoing curative resection: is pharmacological thromboprophylaxis required? A systematic review and meta-analysis.

Purpose: We compared the incidence of venous thromboembolism (VTE) among Asian populations with localized colorectal cancer undergoing curative resection with and without the use of pharmacological thromboprophylaxis (PTP). Methods: A comprehensive literature search was undertaken to identify relevant studies published from January 1, 1980 to February 28, 2022. The inclusion criteria were patients who underwent primary tumor resection for localized nonmetastatic colorectal cancer; an Asian population or studies conducted in an Asian country; randomized controlled trials, case-control studies, or cohort studies; and the incidence of symptomatic VTE, deep vein thrombosis, and/or pulmonary embolism as the primary study outcomes. Data were pooled using a random-effects model. This study was registered in PROSPERO on October 11, 2020 (No. CRD42020206793). Results: Seven studies (2 randomized controlled trials and 5 observational cohort studies) were included, encompassing 5,302 patients. The overall incidence of VTE was 1.4%. The use of PTP did not significantly reduce overall VTE incidence: 1.1% (95% confidence interval [CI], 0%-3.1%) versus 1.9% (95% CI, 0.3%-4.4%; P = 0.55). Similarly, PTP was not associated with significantly lower rates of symptomatic VTE, proximal deep vein thrombosis, or pulmonary embolism. Conclusion: The benefit of PTP in reducing VTE incidence among Asian patients undergoing curative resection for localized colorectal cancer has not been clearly established. The decision to administer PTP should be evaluated on a case-bycase basis and with consideration of associated bleeding risks.

Postoperative outcomes after prehabilitation for colorectal cancer patients undergoing surgery: a systematic review and meta-analysis of randomized and nonrandomized studies.

Purpose: Prehabilitation (PH) is purported to improve patients' preoperative functional status. This systematic review and meta-analysis sought to compare short-term postoperative outcomes between patients who underwent a protocolized PH program and the existing standard of care among colorectal cancer patients awaiting surgery. Methods: A search in MEDLINE/PubMed, the Cochrane Library, Embase, Scopus, and CINAHL was conducted to identify relevant articles. Repetitive and exhaustive combinations of MeSH search terms ("prehabilitation," "colorectal cancer," "colon cancer," and "rectal cancer") were used to identify randomized and nonrandomized studies comparing PH versus standard of care for colorectal cancer patients awaiting surgery. The primary outcomes included postoperative morbidity, length of hospital stay, and readmission rates. Results: Seven studies including 1,042 colorectal cancer patients (PH, 382) were included. No significant differences were found in intraoperative outcomes. The postoperative complication rates were comparable between groups (Clavien-Dindo grades I and II: risk ratio, 0.82; 95% confidence interval, 0.62-1.07; P=0.15; Clavien-Dindo grades ≥III: risk ratio, 1.02; 95% confidence interval, 0.72-1.44; P=0.92). There were also no significant differences in length of hospital stay (P=0.21) or the risk of 30-day readmission (P=0.68). Conclusion: Although PH does not appear to improve short-term postoperative outcomes following colorectal cancer surgery, the quality of evidence is impaired by the limited trials and heterogeneity. Thus, further large-scale trials are warranted to draw definitive conclusions and establish the long-term effects of PH.

Evaluating the surgical trainee ergonomic experience during minimally invasive abdominal surgery (ESTEEMA study).

Minimally invasive abdominal surgery (MAS) can exert a physical cost. Surgical trainees spend years assisting minimally-invasive surgeries, increasing the risk of workplace injury. This prospective questionnaire-based cohort study was conducted amongst general surgery residents in Singapore. Residents assisting major MAS surgery were invited to complete anonymous online survey forms after surgery. The Phase 1 survey assessed physical discomfort scores and risk factors. Intraoperative measures to improve ergonomics were administered and evaluated in Phase 2. During Phase 1 (October 2021 to April 2022), physical discomfort was reported in at least one body part in 82.6% (n = 38) of respondents. Over a third of respondents reported severe discomfort in at least one body part (n = 17, 37.0%). Extremes of height, training seniority, longer surgical duration and operative complexity were significant risk factors for greater physical discomfort. In Phase 2 (October 2022 to February 2023), the overall rate of physical symptoms and severe discomfort improved to 81.3% (n = 52) and 34.4% (n = 22) respectively. The ergonomic measure most found useful was having separate television monitors for the primary surgeon and assistants, followed by intraoperative feedback on television monitor angle or position. Close to 20% of survey respondents felt that surgeon education was likely to improve physical discomfort.

Using heart rate variability to develop a predictive model for post-operative cardiovascular complications following major abdominal surgery: A pilot study.

BACKGROUND: Heart Rate Variability (HRV) is a dynamic reflection of heart rhythm regulation by various physiological inputs. HRV deviations have been found to correlate with clinical outcomes in patients under physiological stresses. Perioperative cardiovascular complications occur in up to 5% of adult patients undergoing abdominal surgery and are associated with significantly increased mortality. This pilot study aimed to develop a predictive model for post-operative cardiovascular complications using HRV parameters for early risk stratification and aid post-operative clinical decision-making. METHODS: Adult patients admitted to High Dependency Units after elective major abdominal surgery were recruited. The primary composite outcome was defined as cardiovascular complications within 7 days post-operatively. ECG monitoring for HRV parameters was conducted at three time points (pre-operative, immediately post-operative, and post-operative day 1) and analyzed based on outcome group and time interactions. Candidate HRV predictors were included in a multivariable logistic regression analysis incorporating a stepwise selection algorithm. RESULTS: 89 patients were included in the analysis, with 8 experiencing cardiovascular complications. Three HRV parameters, when measured immediately post-operatively and composited with patient age, provided the basis for a predictive model with AUC of 0.980 (95% CI: 0.953, 1.00). The negative predictive value was 1.00 at a statistically optimal predicted probability cut-off point of 0.16. CONCLUSION: Our model holds potential for accelerating clinical decision-making and aiding in patient triaging post-operatively, using easily acquired HRV parameters. Risk stratification with our model may enable safe early step-down care in patients assessed to have a low risk profile of post-operative cardiovascular complications.

Stenting as bridge to surgery versus upfront emergency resection for non-metastatic left sided obstructing colorectal cancer: risk of peritoneal recurrence and long-term outcomes.

BACKGROUND: Oncological outcomes of stenting as a bridge to surgery (SBTS) remain a major concern, despite perioperative benefits it offers. This study aims to evaluate the differences in recurrence patterns and survival in patients with non-metastatic, obstructing left sided colon cancers treated by SBTS versus upfront emergency surgery (ES). METHODS: This is a retrospective, single-centre cohort study of 227 consecutive patients with non-metastatic, obstructing left sided colon cancer between 2007 and 2016. Primary outcomes were pattern of recurrence, and survival. Univariate, bivariate and multivariate logistic regression were done to determine relationships between factors and recurrence. Kaplan Meier curves and log rank tests were used to analyse survival outcomes. RESULTS: Of the 227 patients included, 62 underwent SBTS and 165 underwent upfront ES. There was a higher rate of peritoneal recurrence in SBTS group (27.4 vs 15.2% p = 0.034), with no difference observed in overall, liver or lung recurrences. No significant difference in overall survival (p = 0.11), cancer specific survival (p = 0.35), or recurrence free survival (p = 0.107) was observed. Univariate analysis showed that SBTS (OR 2.12, p = 0.036), diabetes mellitus (DM) (OR 2.58, p = 0.013), T4 (OR 2.81, p = 0.001), N + (OR 4.02, p = 0.001), lymphovascular invasion (OR 2.43, p = 0.011) contributed to a higher rate of peritoneal recurrence. Bivariate analysis showed synergistic relationship between T4 tumors and SBTS: in T4 tumors that underwent SBTS, the odds of having peritoneal recurrence was 6.8 times higher when compared to ES (p = 0.004); whilst in T2/3 tumors there was no significant difference observed (OR 1.33, p = 0.55). Multivariable analysis showed SBTS (OR 2.60, p = 0.04), DM (OR 2.88, p = 0.012), N + (OR 2.97, p = 0.026) were significant predictors for peritoneal recurrence. CONCLUSIONS: There are concerns over oncological safety of SBTS even with low rates of stent-related perforation. Higher rates of peritoneal recurrence are seen especially with T4 colon cancers treated with SBTS. SBTS, DM and nodal stage were significant predictors for peritoneal recurrence.

Intracorporeal antimesenteric ancillary trocar: an anastomotic technique facilitating natural orifice specimen extraction in left-sided colorectal surgery.

AIM: Natural orifice specimen extraction (NOSE) in left-sided colorectal surgery requires application of the circular stapler anvil to the proximal bowel without exteriorization through an additional abdominal incision. We describe an intracorporeal method to secure the stapler anvil, termed the intracorporeal antimesenteric ancillary trocar (IAAT) technique. METHOD: The ancillary trocar is attached to the stapler anvil before introduction into the abdominal cavity through the anal or vaginal orifice. The colon is incised before the trocar spike is brought out through the antimesenteric surface 3-4 cm within the cut edge. A linear stapler is used to seal the bowel end. The ancillary trocar is detached and retrieved via the NOSE conduit. Following the NOSE procedure, a side-to-end colorectal anastomosis is performed with the transanal circular stapler. RESULTS: Ten consecutive patients underwent elective left-sided colorectal resection with IAAT for NOSE (seven transanal, three transvaginal) from January to June 2023. Median age and body mass index were 66 (range 47-74) years and 24.3 (range 17.9-30.8) kg/m2 respectively. Two (20%) patients underwent sigmoid colectomy for sigmoid volvulus while eight (80%) underwent anterior resection for colorectal cancer. Median operating time, operative blood loss and postoperative length of hospital stay were 170 (range 140-240) min, 20 (range 10-40) mL and 1 (range 1-3) day respectively. There were no postoperative complications, readmissions or reoperations. Median follow-up duration was 3 (range 1-6) months. CONCLUSION: The IAAT double-stapling side-to-end anastomotic technique is safe and feasible for patients undergoing left-sided colorectal resection with NOSE, resulting in good outcomes.

Patient-reported unmet supportive care needs in long-term colorectal cancer survivors after curative treatment in an Asian population.

OBJECTIVES: Despite an increase in colorectal cancer (CRC) survival, less is known about CRC-specific long-term unmet supportive needs in Asian patients. This study aimed to examine the prevalence of long-term unmet needs and identify clinical and socio-demographic factors associated with increased unmet needs in Asian CRC survivors. DESIGN AND SETTING: We conducted a cross-sectional study that assessed unmet needs using the Cancer Survivors' Unmet Needs scale. CRC survivors of at least two years after undergoing curative surgery were recruited from an outpatient clinic of a large public hospital in Singapore. RESULTS: In total, 400 CRC survivors with a mean age of 64 and a median survival time post-surgery of 78 months participated in the study. Approximately half of patients (52%) reported at least one unmet need. Male gender (RR 1.19, p = 0.01), age greater than 65 years (RR 0.63, p < 0.0001), longer follow up of more than 5 years (RR 0.80, p = 0.009), presence of a permanent stoma (RR 1.78, p < 0.0001), prior radiotherapy in treatment course (RR 1.99, p < 0.0001), higher educational status (RR 1.30, p = 0.0002), currently employed (RR 0.84, p = 0.014), currently married (RR 0.84, p = 0.01) were significant predictors for increased unmet needs. CONCLUSION: There is a high prevalence of unmet needs in long-term Asian CRC survivors, which underscores the importance of screening patients to allow for early detection of unmet needs. Our findings on sociodemographic and clinical predictors can inform the development of targeted interventions tailored to the need domains and improvement of survivorship programmes.

Surgical and short-term oncological safety of total neoadjuvant therapy in high-risk locally advanced rectal cancer.

BACKGROUND: Management for locally advanced rectal cancer (LARC) conventionally comprises long-course chemoradiotherapy (LCCRT), total mesorectal excision (TME), and adjuvant chemotherapy. However, the RAPIDO study published in 2021 showed that total neoadjuvant therapy (TNT) led to better oncological outcomes without increased toxicity. We review the surgical and short-term oncological outcomes of patients with high-risk LARC who underwent TNT or LCCRT before TME. METHODS: Patients with high-risk LARC who underwent TNT or LCCRT before TME between 2021 and 2022 were reviewed. RESULTS: Thirty-five patients (66%) had TNT as per RAPIDO whilst 18 underwent LCCRT. Median follow-up was 16 months (range 5-25). Of the patients who had TNT, median age was 65 years old (range 44-79), 34 (97%) had clinical Stage 3 LARC and median height FAV was 5 cm (range 0.5-14). Nine (26%) required a dose delay/reduction due to treatment toxicity. Seven (50%) showed resolution of previously enlarged lateral nodes. Three (9%) had pathological complete response. Postoperative major morbidity was 23%, of which 4 patients required a reoperation. Six (17%) patients had disease-related treatment failure, with two having disease progression during TNT, two developed local recurrence, and two developed distal metastasis following surgery. Median duration to surgery following completion of chemotherapy was significantly shorter with TNT (36 days versus 74 days) (P < 0.001). There were no other significant differences in outcomes. CONCLUSION: TNT is clinically safe in high-risk LARC patients with no significant difference to surgical and short-term oncological outcomes compared to LCCRT, although a higher incidence of early surgical morbidity was observed.

Transanal Total Mesorectal Excision With Delayed Coloanal Anastomosis (TaTME-DCAA) Versus Laparoscopic Total Mesorectal Excision (LTME) and Robotic Total Mesorectal Excision (RTME) for Low Rectal Cancer: A Propensity Score-Matched Analysis of Short-term Outcomes, Bowel Function, and Cost.

INTRODUCTION: Total mesorectal excision (TME) with delayed coloanal anastomosis (DCAA) is surgical option for low rectal cancer, replacing conventional immediate coloanal anastomosis (ICAA) with bowel diversion. This study aimed to assess the outcomes of transanal TME (TaTME) with DCAA versus laparoscopic TME (LTME) with ICAA versus robotic TME (RTME) with ICAA. METHODS: This was a retrospective propensity score-matched analysis of patients who underwent elective TaTME-DCAA between November 2021 and June 2022. Patients were propensity-score matched in a ratio of 1:3 to patients who underwent LTME-ICAA and RTME-ICAA from January 2019 to December 2020. Outcome measures were histopathologic results, postoperative morbidity, function, and inpatient costs. RESULTS: Twelve patients in the TaTME-DCAA group were compared with 36 patients in the LTME-ICAA and RTME-ICAA groups each after propensity score matching. Histopathologic results and postoperative morbidity rates were statistically similar. Overall stoma-related complication rates in the ICAA groups were 11%. Median total length of hospital stays for TME plus stoma reversal surgery was similar across all techniques (10 vs. 10 vs. 9 days; P =0.532). Despite a significantly shorter duration of follow-up, bowel function after TaTME-DCAA was comparable to that of LTME-ICAA and RTME-ICAA. Overall median inpatient costs of TaTME-DCAA were comparable to LTME-ICAA and significantly cheaper than RTME-ICAA ($31,087 vs. $29,927 vs. $36,750; P =0.002). CONCLUSIONS: TaTME with DCAA is a feasible and safe technique compared with other minimally invasive methods of TME, while avoiding bowel diversion and stoma-related complications, as well as comparing favorably in terms of overall hospitalization costs.

Predictive modeling algorithms for liver metastasis in colorectal cancer: A systematic review of the current literature.

This study aims to assess the quality and performance of predictive models for colorectal cancer liver metastasis (CRCLM). A systematic review was performed to identify relevant studies from various databases. Studies that described or validated predictive models for CRCLM were included. The methodological quality of the predictive models was assessed. Model performance was evaluated by the reported area under the receiver operating characteristic curve (AUC). Of the 117 articles screened, seven studies comprising 14 predictive models were included. The distribution of included predictive models was as follows: radiomics (n = 3), logistic regression (n = 3), Cox regression (n = 2), nomogram (n = 3), support vector machine (SVM, n = 2), random forest (n = 2), and convolutional neural network (CNN, n = 2). Age, sex, carcinoembryonic antigen, and tumor staging (T and N stage) were the most frequently used clinicopathological predictors for CRCLM. The mean AUCs ranged from 0.697 to 0.870, with 86% of the models demonstrating clear discriminative ability (AUC > 0.70). A hybrid approach combining clinical and radiomic features with SVM provided the best performance, achieving an AUC of 0.870. The overall risk of bias was identified as high in 71% of the included studies. This review highlights the potential of predictive modeling to accurately predict the occurrence of CRCLM. Integrating clinicopathological and radiomic features with machine learning algorithms demonstrates superior predictive capabilities.

Transvaginal Natural Orifice Specimen Extraction (NOSE) in Laparoscopic Colorectal Cancer Surgery With New Insights on Technique and Patient Selection.

BACKGROUND: Following laparoscopic colorectal surgery, transabdominal specimen extraction requires a mini-laparotomy or Pfannenstiel incision, associated with increased postoperative pain and wound complications. The vagina has several unique properties that make natural orifice specimen extraction (NOSE) ideal. We report our experience with transvaginal NOSE for colorectal cancer surgery. MATERIALS AND METHODS: A transvaginal sizer allows the posterior vagina to be incised under tension. A transverse or cruciate incision is made, followed by the insertion of a double-ring wound protector. The external ring is opened against the perineum to shorten the length of the conduit for specimen delivery. Vaginotomy closure is performed via laparoscopy using a barbed suture. RESULTS: Seventeen consecutive female patients underwent elective colorectal cancer surgery with attempted transvaginal NOSE. Median age and body mass index was 67 (range: 50 to 82) years and 26.5 (range: 19.7 to 35.8) kg/m 2 , respectively. Fourteen patients (82%) underwent left-sided resections and 3 (18%) underwent right-sided resections. Median operating time, blood loss, and length of hospital stay was 245 (range: 155 to 360) minutes, 30 (range: 10 to 500) mL, and 3 (range: 2 to 9) days, respectively. Transvaginal extraction was unsuccessful in 1 (6%) patient. Two (12%) patients experienced early postoperative morbidity, neither attributable to the extraction procedure. Median tumor circumferential diameter was 3.3 (range: 2.2 to 7.0) cm. Median follow-up duration was 17 (range: 8 to 27) months. There was no instance of sexual dysfunction. CONCLUSIONS: Transvaginal NOSE for colorectal cancer surgery is feasible and safe in selected patients. Overall specimen diameter, inclusive of tumor and mesentery, relative to pelvic outlet and conduit diameter is the most important consideration for transvaginal NOSE.

Effect of preoperative oral antibiotics and mechanical bowel preparation on the prevention of surgical site infection in elective colorectal surgery, and does oral antibiotic regime matter? a bayesian network meta-analysis.

PURPOSE: Surgical site infection (SSI) impacts 5-20% of patients after elective colorectal surgery. There are varying reports on the effectiveness of oral antibiotics (OAB) with preoperative mechanical bowel preparation (MBP) in preventing SSI. We aim to determine the role of OAB and MBP in preventing SSI after elective colorectal surgery. We also determine if a specific OAB regimen will be more effective than others. METHODS: This study investigated the impact of OAB and MBP in patients undergoing elective colorectal surgery. PubMed, MEDLINE, Ovid, Cochrane Central Register of Controlled Trials, ACP Journal Club, and Embase databases were searched for randomized clinical trials (RCTs) published by June 2022. All RCTs comparing various preoperative bowel preparation regimens, including pairwise or multi-intervention comparisons, were included. To establish the role of OAB and MBP in preventing SSI, we conducted a Bayesian network meta-analysis on all RCTs. We further performed subgroup analysis to determine the most effective OAB regimen. RESULTS: Among included 46 studies with a total of 12690 patients, patients in the MBP + OAB group were less likely to have SSI than those having MBP-only (OR 0.55, 95% CrI 0.39-0.76), and without MBP and OAB (OR 0.52, 95% CrI 0.32-0.84). OAB regimen C (kanamycin + metronidazole) and A (neomycin + metronidazole) demonstrated a significantly reduced incidence of SSI, compared to regimen B (neomycin + erythromycin) with OR 0.24 (95% CrI 0.07-0.79) and 0.26 (95% CrI 0.07-0.99) respectively. CONCLUSIONS: OAB with MBP reduces the risk of SSI after elective colorectal surgery. Providing adequate aerobic and anaerobic coverage with OAB may confer better protection against SSI.

The role of magnetic resonance tumour regression grade in the prediction of regression and survival of rectal adenocarcinoma after long-course chemoradiotherapy: a cohort study.

Rectal cancer response to neoadjuvant long-course chemoradiotherapy (LCCRT) is assessed by magnetic resonance tumour regression grade (mrTRG) and this has an impact on surgical management. However, there is limited data on the correlation between mrTRG and pathological tumour regression grade (pTRG). This study aims to evaluate the correlation between mrTRG and pTRG and the prognostic value of mrTRG on survival. Methods: Between 2011 and 2016, patients with rectal cancer who underwent LCCRT and had post-LCCRT MRI were included in the study. Both mrTRG and pTRG were dichotomised into good responders (mrTRG 1-3 and pTRG 0-1) and poor responders (mrTRG 4-5 and pTRG 2-3). Correlation between mrTRG and pTRG was assessed with Cohen κ analysis. Survival analysis was performed with Kaplan-Meier test and Cox proportional hazard models. Results: There were 59 patients included in this study. There were significant reductions in anal sphincter and circumferential resection margin involvement in post-LCCRT MRI. Fair agreement was found between mrTRG and pTRG (κ=0.345). Sensitivity, specificity and accuracy of mrTRG 1-3 to predict good pathological response were 100%, 46.3% and 62.7%, respectively. On survival analysis, mrTRG 1-3 was not associated with improved overall survival and recurrence-free survival. Conclusions: While there is fair agreement in correlation between mrTRG and pTRG, MRI remains an objective, noninvasive assessment of tumour response. Further studies are required to improve the ability of mrTRG to predict good responders to LCCRT and evaluate its role as a prognostic marker for survival.

KRAS-specific antibody binds to KRAS protein inside colorectal adenocarcinoma cells and inhibits its localization to the plasma membrane.

Colorectal cancer (CRC) is the third highest incidence cancer and a leading cause of cancer mortality worldwide. To date, chemotherapeutic treatment of advanced CRC that has metastasized has a dismayed success rate of less than 30%. Further, most (80%) sporadic CRCs are microsatellite-stable and are refractory to immune checkpoint blockade therapy. KRAS is a gatekeeper gene in colorectal tumorigenesis. Nevertheless, KRAS is 'undruggable' due to its structure. Thus, focus has been diverted to develop small molecule inhibitors for its downstream effector such as ERK/MAPK. Despite intense research efforts for the past few decades, no small molecule inhibitor has been in clinical use for CRC. Antibody targeting KRAS itself is an attractive alternative. We developed a transient ex vivo patient-derived matched mucosa-tumor primary culture to assess whether anti-KRAS antibody can be internalized to bind and inactivate KRAS. We showed that anti-KRAS antibody can enter live mucosa-tumor cells and specifically aggregate KRAS in the cytoplasm, thus hindering its translocation to the inner plasma membrane. The mis-localization of KRAS reduces KRAS dwelling time at the site where it tethers to activate downstream effectors. We previously showed that expression of SOX9 was KRAS-mutation-dependent and possibly a better effector than ERK in CRC. Herein, we showed that anti-KRAS antibody treated tumor cells have less intense SOX9 cytoplasmic and nuclear staining compared to untreated cells. Our results demonstrated that internalized anti-KRAS antibody inhibits KRAS function in tumor. With an efficient intracellular antibody delivery system, this can be further developed as combinatorial therapeutics for CRC and other KRAS-driven cancers.

Laser hemorrhoidoplasty versus conventional hemorrhoidectomy for grade II/III hemorrhoids: a systematic review and meta-analysis.

PURPOSE: This study compared the short- and long-term clinical outcomes of laser hemorrhoidoplasty (LH) vs. conventional hemorrhoidectomy (CH) in patients with grade II/III hemorrhoids. METHODS: PubMed/Medline and the Cochrane Library were searched for randomized and nonrandomized studies comparing LH against CH in grade II/III hemorrhoids. The primary outcomes included postoperative use of analgesia, postoperative morbidity (bleeding, urinary retention, pain, thrombosis), and time of return to work/daily activities. RESULTS: Nine studies totaling 661 patients (LH, 336 and CH, 325) were included. The LH group had shorter operative time (P<0.001) and less intraoperative blood loss (P<0.001). Postoperative pain was lower in the LH group, with lower postoperative day 1 (mean difference [MD], -2.09; 95% confidence interval [CI], -3.44 to -0.75; P=0.002) and postoperative day 7 (MD, -3.94; 95% CI, -6.36 to -1.52; P=0.001) visual analogue scores and use of analgesia (risk ratio [RR], 0.59; 95% CI, 0.42-0.81; P=0.001). The risk of postoperative bleeding was also lower in the LH group (RR, 0.18; 95% CI, 0.12- 0.28; P<0.001), with a quicker return to work or daily activities (P=0.002). The 12-month risks of bleeding (P>0.999) and prolapse (P=0.240), and the likelihood of complete resolution at 12 months, were similar (P=0.240). CONCLUSION: LH offers more favorable short-term clinical outcomes than CH, with reduced morbidity and pain and earlier return to work or daily activities. Medium-term symptom recurrence at 12 months was similar. Our results should be verified in future well-designed trials with larger samples.