Alimentação saudável: dicas práticas para variedade e sabor: Reduzir o consumo de carnes vermelhas e evitar carnes processadas é uma das formas de se proteger do câncer de cólon e reto

Reduzir o consumo de carnes vermelhas e evitar carnes processadas é uma das formas de se proteger do câncer de cólon e reto

Comparison of the safety and efficacy of robotic natural orifice specimen extraction surgery and conventional robotic colorectal cancer resection: a propensity score matching study.

Robotic resection is widely used to treat colorectal cancer. Although the novel natural orifice specimen extraction surgery (NOSES) results in less trauma, its safety and effectiveness are relatively unknown. In the present study, we used propensity score matching to compare the effectiveness and safety of NOSES and robotic resection for treating colorectal cancer. Present retrospective cohort study included patients who underwent robotic colon and rectal cancer surgery between January 2016 and December 2019 at the Department of Gastrointestinal Surgery, the Second Xiangya Hospital of Central South University. The intraoperative time, intraoperative bleeding, postoperative recovery, postoperative complications, and survival status of the conventional robotic colorectal cancer resection (CRR) (78 patients) and NOSES (89 patients) groups were compared. These results showed that no significant differences were observed between the two groups in terms of early postoperative complications, operation time, and the number of lymph nodes dissected. Compared with the CRR group, NOSES group had shorter postoperative exhaust time [3.06 (0.76) vs. 3.53 (0.92)], earlier eating time [4.12 (1.08) vs. 4.86 (1.73)], lesser intraoperative bleeding [51.23 (26.74) vs. 67.82 (43.44)], lesser degree of pain [80.8% vs. 55.1%], and shorter length of hospital stay [8.73 (2.02) vs. 9.50 (3.45)]. All these parameters were statistically significant (P < 0.05). However, no significant differences were observed in the 3-year overall survival rate and disease-free survival rate between both groups (P > 0.05). Collectively, robotic NOSES is a safe and effective approach for treating rectal and sigmoid colon cancers, could decrease intraoperative bleeding and postoperative complications, and accelerate the speed of intestinal function recovery.

Convolutional neural network deep learning model accurately detects rectal cancer in endoanal ultrasounds.

BACKGROUND: Imaging is vital for assessing rectal cancer, with endoanal ultrasound (EAUS) being highly accurate in large tertiary medical centers. However, EAUS accuracy drops outside such settings, possibly due to varied examiner experience and fewer examinations. This underscores the need for an AI-based system to enhance accuracy in non-specialized centers. This study aimed to develop and validate deep learning (DL) models to differentiate rectal cancer in standard EAUS images. METHODS: A transfer learning approach with fine-tuned DL architectures was employed, utilizing a dataset of 294 images. The performance of DL models was assessed through a tenfold cross-validation. RESULTS: The DL diagnostics model exhibited a sensitivity and accuracy of 0.78 each. In the identification phase, the automatic diagnostic platform achieved an area under the curve performance of 0.85 for diagnosing rectal cancer. CONCLUSIONS: This research demonstrates the potential of DL models in enhancing rectal cancer detection during EAUS, especially in settings with lower examiner experience. The achieved sensitivity and accuracy suggest the viability of incorporating AI support for improved diagnostic outcomes in non-specialized medical centers.

Preoperative risk factors and cumulative incidence of temporary ileostomy non-closure after sphincter-preserving surgery for rectal cancer: a meta-analysis.

BACKGROUND: Temporary ileostomy (TI) has proven effective in reducing the severity of anastomotic leakage after rectal cancer surgery; however, some ileostomies fail to reverse over time, leading to conversion into a permanent stoma (PS). In this study, we aimed to investigate the preoperative risk factors and cumulative incidence of TI non-closure after sphincter-preserving surgery for rectal cancer. MATERIALS AND METHODS: We conducted a meta-analysis after searching the Embase, Web of Science, PubMed, and MEDLINE databases from their inception until November 2023. We collected all published studies on the risk factors related to TI non-closure after sphincter-preserving surgery for rectal cancer. RESULTS: A total of 1610 studies were retrieved, and 13 studies were included for meta-analysis, comprising 3026 patients. The results of the meta-analysis showed that the identified risk factors included older age (p = 0.03), especially > 65 years of age (p = 0.03), male sex (p = 0.009), American Society of Anesthesiologists score ≥ 3 (p = 0.004), comorbidity (p = 0.001), and distant metastasis (p < 0.001). Body mass index, preoperative hemoglobin, preoperative albumin, preoperative carcinoma embryonic antigen, tumor location, neoadjuvant chemoradiotherapy, smoking, history of abdominal surgery, and open surgery did not significantly change the risk of TI non-closure. CONCLUSION: We identified five preoperative risk factors for TI non-closure after sphincter-preserving surgery for rectal cancer. This information enables surgeons to identify high-risk groups before surgery, inform patients about the possibility of PS in advance, and consider performing protective colostomy or Hartmann surgery.

A comprehensive evaluation of 80 consecutive robotic low anterior resections: impact of not mobilizing the splenic flexure alongside low-tie vascular ligation as a standardized technique.

Rectal cancer surgery represents challenges due to its location. To overcome them and minimize the risk of anastomosis-related complications, some technical maneuvers or even a diverting ileostomy may be required. One of these technical steps is the mobilization of the splenic flexure (SFM), especially in medium/low rectal cancer. High-tie vascular ligation may be another one. However, the need of these maneuvers may be controversial, as especially SFM may be time-consuming and increase the risk of iatrogenic. The objective is to present the short- and long-term outcomes of a low-tie ligation combined with no SFM in robotic low anterior resection (LAR) for mid- and low rectal cancer as a standardized technique. A retrospective observational single-cohort study was carried out at Reina Sofia University Hospital, Cordoba, Spain. 221 robotic rectal resections between Jul-18th-2018 and Jan-12th-2023 were initially considered. After case selection, 80 consecutive robotic LAR performed by a single surgeon were included. STROBE checklist assessed the methodological quality. Histopathological, morbidity and oncological outcomes were assessed. Anastomotic stricture occurrence and distance to anal verge were evaluated after LAR by rectosigmoidoscopy. Variables related to the ileostomy closure such as time to closure, post-operative complications or hospital stay were also considered. The majority of patients (81.2%) presented a mid-rectal cancer and the rest, lower location (18.8%). All patients had adequate perfusion of the anastomotic stump assessed by indocyanine green. Complete total mesorectal excision was performed in 98.8% of the patients with a lymph node ratio < 0.2 in 91.3%. The anastomotic leakage rate was 5%. One patient (1.5%) presented local recurrence. Anastomosis stricture occurred in 7.5% of the patients. The limitations were small cohort and retrospective design. The non-mobilization of the splenic flexure with a low-tie ligation in robotic LAR is a feasible and safe procedure that does not affect oncological outcomes.

Preliminary comparative study of lower extremity pressure measurements under the conditions using former models and new lithotomy stirrups in rectal cancer surgery.

BACKGROUND: This study aimed to investigate the effect of the use of new lithotomy stirrups-2 on the pressure dispersal on lower limbs, which may lead to the prevention of well-leg compartment syndrome (WLCS) and deep venous thrombosis (DVT), which are the most commonly associated adverse events with laparoscopic and robot-assisted rectal surgery. METHODS: A total of 30 healthy participants were included in this study. The pressure (mmHg) applied on various lower limb muscles when using conventional lithotomy stirrups-1 and new type stirrups-2 was recorded in various lithotomy positions; 1) neutral position, 2) Trendelenburg position (15°) with a 0° right inferior tilt, and 3) Trendelenburg position (15°) with a 10° right inferior tilt. Using a special sensor pad named Palm Q®, and the average values were compared between two types of stirrups. RESULTS: The use of new lithotomy stirrups-2 significantly reduced the pressure applied on the lower limb muscles in various lithotomy positions compared with the use of lithotomy stirrups-1. The most pressured lower limb muscle when using both lithotomy stirrups was the central soleus muscle, which is the most common site for the development of WLCS and DVT. In addition, when using the conventional lithotomy stirrups-1, the pressure was predominantly applied to the proximal soleus muscle; however, when using lithotomy stirrups-2, the pressure was shifted to the more distal soleus muscle. CONCLUSION: These results suggest that the new lithotomy stirrups-2 is useful in reducing the pressure load on leg muscles, especially on the proximal to central soleus, and may reduce the incidence of WLCS and DVT after rectal surgery performed in the lithotomy position. Further clinical studies are needed to determine whether the use of lithotomy stirrups-2 prevents these complications in various clinical settings.

Evaluation of the effect of prostate diameters on erectile dysfunction in patients who underwent low-anterior resection.

OBJECTIVE: Male erectile dysfunction is an important complication of rectal surgery. In this research, the effect of prostate dimensions on the development of postoperative erectile dysfunction in patients diagnosed with mid-rectum adenocarcinoma who underwent low anterior resection (LAR) is examined. PATIENTS AND METHODS: Thirty-one male patients diagnosed as mid-rectal adenocancer were included. The International Index of Erectile Function (IIEF) questionnaire was used to determine the patients' pre and postoperative erectile dysfunction levels, and the level of relationship between the change in these IIEF scores and prostate measurements determined by computed tomography were evaluated. RESULTS: There were statistically significant differences between IIEF index score and anterior posterior (AP) and transverse (TR) measurements (p≤0.001; p≤0.001), but no statistically significant difference was found between craniocaudal (CC) measurement values (p=0.169). CONCLUSIONS: The risk of nerve injury will be higher in those with a small prostate transverse diameter. Intraoperative nerve monitoring should be recommended primarily in younger patient groups.

Clinical influence of prophylactic lateral lymph node dissection on oncologic outcomes of patients with mid-low rectal cancer undergoing mesorectal excision: a meta-analysis.

BACKGROUND: Although several recent meta-analyses have investigated the clinical influence of the addition of lateral lymph node dissection (LLND) on oncologic outcomes in patients with mid-low rectal cancer (RC) undergoing mesorectal excision (ME), most studies included in such meta-analyses were retrospectively designed. Therefore, this study aimed to explore the clinical influence of prophylactic LLND on oncologic outcomes in patients with mid-low RC undergoing ME. METHODS: A comprehensive electronic search of the literature up to July 2022 was performed to identify studies that compared oncologic outcomes between patients with mid-low RC undergoing ME who underwent LLND and patients with mid-low RC undergoing ME who did not undergo LLND. A meta-analysis was performed using fixed-effects models and the generic inverse variance method to calculate hazard ratios (HRs) and 95% CIs, and heterogeneity was analyzed using I2 statistics. RESULTS: A total of 6 studies, consisting of 3 randomized and 3 propensity score matching studies, were included in this meta-analysis. The results of the meta-analysis of 2 randomized studies demonstrated no significant effect of prophylactic LLND on improving oncologic outcomes concerning overall survival (OS) (HR, 1.22; 95% CI, 0.89-1.69; I2 = 0%; P = .22) and relapse-free survival (RFS) (HR, 1.03; 95% CI, 0.81-1.31; I2 = 28%; P = .83). CONCLUSION: The results of this meta-analysis revealed no significant influence of prophylactic LLND on oncologic outcomes-OS and RFS-in patients with mid-low RC who underwent ME.

Minor impact of anastomotic leakage in anterior resection for rectal cancer on long-term male urinary and sexual function.

PURPOSE: Anastomotic leakage after anterior resection for rectal cancer induces bowel dysfunction, but the influence on urinary and sexual function is largely unknown. This cross-sectional cohort study evaluated long-term effect of anastomotic leakage on urinary and sexual function in male patients. METHODS: Patients operated with anterior resection for rectal cancer in 15 Swedish hospitals 2007-2013 were identified. Anastomotic leakage and other clinical variables were retrieved from the Swedish Colorectal Cancer Registry and medical records. Urinary and sexual dysfunction were evaluated at 4 to 11 years after surgery using the International Prostate Symptom Score, International Index of Erectile Function, and European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire CR29. The effect of anastomotic leakage on average scores of urinary and sexual dysfunction was evaluated as a primary outcome, and the single items permanent urinary catheter and sexual inactivity as secondary outcomes. The association of anastomotic leakage and functional outcomes was analyzed using regression models with adjustment for confounders. RESULTS: After a median follow-up of 84 months (interquartile range: 67-110), 379 out of 864 eligible men were included. Fifty-nine (16%) patients had anastomotic leakage. Urinary incontinence was more common in the leakage group, with an adjusted mean score difference measured by EORTC QLQ ColoRectal-29 of 8.69 (95% confidence interval: 0.72-16.67). The higher risks of urinary frequency, permanent urinary catheter, and sexual inactivity did not reach significance. CONCLUSION: Anastomotic leakage after anterior resection had a minor negative impact on urinary and sexual function in men.

Switching from FOLFIRI plus cetuximab to FOLFIRI plus bevacizumab based on early tumor shrinkage in RAS wild-type metastatic colorectal cancer: A phase II trial (HYBRID).

BACKGROUND: Long-term anti-EGFR antibody treatment increases the risk of severe dermatologic toxicities. This single-arm, phase II trial aimed to investigate the strategy of switching from cetuximab to bevacizumab in combination with FOLFIRI based on early tumor shrinkage (ETS) in patients with RAS wild-type metastatic colorectal cancer (mCRC). METHODS: Radiologic assessment was performed to evaluate ETS, defined as ≥20% reduction in the sum of the largest diameters of target lesions 8 weeks after the introduction of FOLFIRI plus cetuximab. ETS-negative patients switched to FOLFIRI plus bevacizumab, whereas ETS-positive patients continued FOLFIRI plus cetuximab for eight more weeks, with a switch to FOLFIRI plus bevacizumab thereafter. The primary endpoint was progression-free survival. RESULTS: This trial was prematurely terminated due to poor accrual after a total enrollment of 30 patients. In 29 eligible patients, 7 were ETS-negative and 22 were ETS-positive. Two ETS-negative patients and 17 ETS-positive patients switched to FOLFIRI plus bevacizumab 8 weeks and 16 weeks after initial FOLFIRI plus cetuximab, respectively. Median progression-free and overall survival durations were 13.4 and 34.7 months, respectively. Six (20%) patients experienced grade ≥3 paronychia, which improved to grade ≤2 by 18 weeks. Grade ≥3 acneiform rash, dry skin, and pruritus were not observed in any patients. CONCLUSIONS: Our novel treatment strategy delivered acceptable survival outcomes and reduced severe dermatologic toxicities.

Long-term outcomes of robot-assisted laparoscopic surgery versus conventional laparoscopic surgery for rectal cancer: single-center, retrospective, propensity score analyses.

Although the short-term outcomes of robot-assisted laparoscopic surgery (RALS) for rectal cancer are well known, the long-term oncologic outcomes of RALS compared with those of conventional laparoscopic surgery (CLS) are not clear. This study aimed to compare the long-term outcomes of RALS and CLS for rectal cancer using propensity score matching. This retrospective study included 185 patients with stage I-III rectal cancer who underwent radical surgery at our institute between 2010 and 2019. Propensity score analyses were performed with 3-year overall survival (OS) and relapse-free survival (RFS) as the primary endpoints. After case matching, the 3-year OS and 3-year RFS rates were 86.5% and 77.9% in the CLS group and 98.4% and 88.5% in the RALS group, respectively. Although there were no significant differences in OS (p = 0.195) or RFS (p = 0.518) between the groups, the RALS group had slightly better OS and RFS rates. 3-year cumulative (Cum) local recurrence (LR) and 3-year Cum distant metastasis (DM) were 9.7% and 8.7% in the CLS group and 4.5% and 10.8% in the RALS group, respectively. There were no significant differences in Cum-LR (p = 0.225) or Cum-DM (p = 0.318) between the groups. RALS is a reasonable surgical treatment option for patients with rectal cancer, with long-term outcomes similar to those of CLS in such patients.

Comparison of robotic versus laparoscopic surgery for visceral obesity in mid-low rectal cancer: a propensity-matched analysis.

Obesity is becoming more and more common, and measuring visceral fat area (VFA) is a useful diagnostic technique for visceral obesity (VO). The purpose of this research is to compare the surgical results of robotic versus laparoscopic rectal surgery, with a focus on assessing the benefits of the latter method for treating both VO and mid-low rectal cancer. Patients receiving laparoscopic or robotic anterior rectal excision at Northern Jiangsu People's Hospital's general surgery department were included in the retrospective analysis. 242 people in all took part in the study; 121 cases were assigned to the robotic surgery (RS) group and another 121 cases to the laparoscopic surgery (LS) group. In comparison to LS, our results show that RS led to a shorter period for the recovery of bowel function (p = 0.03), a shorter hospital stay (p < 0.001), a smaller intraoperative blood loss (p < 0.001), and a shorter time until the commencement of oral intake (p = 0.041). However, there were no statistically significant differences between the two groups in terms of the indices of histopathologic specimens, the proportion of temporary loop ileostomy, and the incidence of early postoperative problems (p > 0.05). When patients with VO undergo surgery for rectal cancer, RS has the added benefit of accelerating patient recovery while producing results that are similar to LS in the near run.

Anti-EGFR Rechallenge in Patients With Refractory ctDNA RAS/BRAF wt Metastatic Colorectal Cancer: A Nonrandomized Controlled Trial.

Importance: The available evidence regarding anti-epidermal growth factor receptor (EGFR) inhibitor rechallenge in patients with refractory circulating tumor DNA (ctDNA) RAS/BRAF wild-type (wt) metastatic colorectal cancer (mCRC) is derived from small retrospective and prospective studies. Objective: To evaluate the efficacy of anti-EGFR rechallenge in patients with refractory ctDNA RAS/BRAF wt mCRC. Design, Setting, and Participants: This nonrandomized controlled trial used a pooled analysis of individual patient data from patients with RAS/BRAF wt ctDNA mCRC enrolled in 4 Italian trials (CAVE, VELO, CRICKET, and CHRONOS) and treated with anti-EGFR rechallenge between 2015 and 2022 (median [IQR] follow-up, 28.1 [25.8-35.0] months). Intervention: Patients received anti-EGFR rechallenge therapy, including cetuximab plus avelumab, trifluridine-tipiracil plus panitumumab, irinotecan plus cetuximab, or panitumumab monotherapy. Main Outcomes and Measures: Overall survival (OS), progression-free survival (PFS), overall response rate (ORR), and disease control rate (DCR) were calculated. Exploratory subgroup analysis evaluating several clinical variables was performed. Safety was reported. Results: Overall, 114 patients with RAS/BRAF wt ctDNA mCRC (median [IQR] age, 61 [29-88] years; 66 men [57.9%]) who received anti-EGFR rechallenge as experimental therapy (48 received cetuximab plus avelumab, 26 received trifluridine-tipiracil plus panitumumab, 13 received irinotecan plus cetuximab, and 27 received panitumumab monotherapy) were included in the current analysis. Eighty-three patients (72.8%) had received 2 previous lines of therapy, and 31 patients (27.2%) had received 3 or more previous lines of therapy. The ORR was 17.5% (20 patients), and the DCR was 72.3% (82 patients). The median PFS was 4.0 months (95% CI, 3.2-4.7 months), and the median OS was 13.1 months (95% CI, 9.5-16.7 months). The subgroup of patients without liver involvement had better clinical outcomes. The median PFS was 5.7 months (95% CI, 4.8-6.7 months) in patients without liver metastasis compared with 3.6 months (95% CI, 3.3-3.9 months) in patients with liver metastasis (hazard ratio, 0.56; 95% CI, 0.37-0.83; P = .004). The median OS was 17.7 months (95% CI, 13-22.4 months) in patients without liver metastasis compared with 11.5 months (95% CI, 9.3-13.9 months) in patients with liver metastasis (hazard ratio, 0.63; 95% CI, 0.41-0.97; P = .04). Treatments showed manageable toxic effects. Conclusions and Relevance: These findings suggest that anti-EGFR rechallenge therapy has promising antitumor activity in patients with refractory ctDNA RAS/BRAF wt mCRC. Within the limitation of a subgroup analysis, the absence of liver metastases was associated with significant improved survival. Trial Registration: ClinicalTrials.gov Identifiers: NCT02296203; NCT04561336; NCT03227926; NCT05468892.

The efficacy and safety of short-course radiotherapy followed by sequential chemotherapy and Cadonilimab for locally advanced rectal cancer: a protocol of a phase II study.

BACKGROUND: For patients with locally advanced rectal cancer (LARC), total neoadjuvant therapy (TNT), namely, intensifying preoperative treatment through the integration of radiotherapy and systemic chemotherapy before surgery, was commonly recommended as the standard treatment. However, the risk of distant metastasis at 3 years remained higher than 20%, and the complete response (CR) rate was less than 30%. Several clinical trials had suggested a higher complete response rate when combining single-agent immunotherapy with short-course radiotherapy (SCRT). The CheckMate 142 study had shown encouraging outcomes of dual immunotherapy and seemingly comparable toxicity for CRC compared with single-agent immunotherapy in historical results. Therefore, dual immunotherapy might be more feasible in conjunction with the TNT paradigm of SCRT. We performed a phase II study to investigate whether the addition of a dual immune checkpoint inhibitor bispecific antibody, Cadonilimab, to SCRT combined with chemotherapy might further increase the clinical benefit and prognosis for LARC patients. METHODS: This single-arm, multicenter, prospective, phase II study included patients with pathologically confirmed cT3-T4N0 or cT2-4N + rectal adenocarcinoma with an ECOG performance score of 0 or 1. Bispecific antibody immunotherapy was added to SCRT combined with chemotherapy. Patients enrolled would be treated with SCRT (25 Gy in five fractions over 1 week) for the pelvic cavity, followed by 4 cycles of CAPOX or 6 cycles of mFOLFOX and Cadonilimab. The primary endpoint was the CR rate, which was the ratio of the pathological CR rate plus the clinical CR rate. The secondary endpoints included local-regional control, distant metastasis, disease-free survival, overall survival, toxicity profile, quality of life and functional outcome of the rectum. To detect an increase in the complete remission rate from 21.8% to 40% with 80% power, 50 patients were needed. DISCUSSION: This study would provide evidence on the efficacy and safety of SCRT plus bispecific antibody immunotherapy combined with chemotherapy as neoadjuvant therapy for patients with LARC, which might be used as a candidate potential therapy in the future. TRIAL REGISTRATION: This phase II trial was prospectively registered at ClinicalTrials.gov, under the identifier NCT05794750.

Surgical management of rectal cancer with synchronous treatment of prostate cancer.

PURPOSE: To assess the safety and efficacy of synchronous treatments for rectal (RC) and prostate (PC) cancers. METHODS: Single-center retrospective study (2007-2021) of patients treated with neoadjuvant radiotherapy (RT) and total mesorectal excision (TME) for RC with synchronous PC treatment. The endpoints were 30-day postoperative severe complications, R0 resection rates, 3-year disease-free survival (DFS) and 3-year overall survival (OS). RESULTS: Among the 16 patients, 15 (93.7%) received neoadjuvant pelvic RT (40-50.4 Gray) followed by either transperineal high dose rate prostate brachytherapy (62.5%), prostate external RT boost (25.0%), or androgen deprivation therapy (ADT) alone (6.3%). One (6.3%) patient received neoadjuvant rectal brachytherapy and ADT. Pelvic RT was combined with chemotherapy in 87.5% of cases. TME was performed in all patients with low anterior resection (87.5%) or abdominoperineal resection (12.5%), primarily using minimally invasive surgery (87.5%). The R0 resection rate was 93.8%. Six (37.5%) patients experienced 30-day Clavien-Dindo grade IIIb complications, including one (7.1%) anastomotic leak. After a median follow-up of 39.0 months, 63.6% of diverting ileostomies were reversed. Three-year DFS from RC was 71.4% (CI 40.2-88.3) and 3-year OS was 84.4% (CI 95% 50.4-95.9). No PC recurrence or death occurred. CONCLUSIONS: Synchronous management of RC and PC with pelvic RT followed by curative prostate RT doses and TME showed acceptable morbidity and oncologic results. Prostate brachytherapy, the most commonly used treatment modality, allowed avoidance of prostatectomy and additional external RT to the rectum. PC should not limit the curative intent of RC, as all recurrences were from rectal origin.

New treatment alternatives for primary and metastatic colorectal cancer by an integrated transcriptome and network analyses.

Metastatic colorectal cancer (CRC) is still in need of effective treatments. This study applies a holistic approach to propose new targets for treatment of primary and liver metastatic CRC and investigates their therapeutic potential in-vitro. An integrative analysis of primary and metastatic CRC samples was implemented for alternative target and treatment proposals. Integrated microarray samples were grouped based on a co-expression network analysis. Significant gene modules correlated with primary CRC and metastatic phenotypes were identified. Network clustering and pathway enrichments were applied to gene modules to prioritize potential targets, which were shortlisted by independent validation. Finally, drug-target interaction search led to three agents for primary and liver metastatic CRC phenotypes. Hesperadin and BAY-1217389 suppress colony formation over a 14-day period, with Hesperadin showing additional efficacy in reducing cell viability within 48 h. As both candidates target the G2/M phase proteins NEK2 or TTK, we confirmed their anti-proliferative properties by Ki-67 staining. Hesperadinin particular arrested the cell cycle at the G2/M phase. IL-29A treatment reduced migration and invasion capacities of TGF-ß induced metastatic cell lines. In addition, this anti-metastatic treatment attenuated TGF-ß dependent mesenchymal transition. Network analysis suggests IL-29A induces the JAK/STAT pathway in a preventive manner.

Impact of grade on workup of rectal neuroendocrine tumors: a retrospective cohort study : Grade impact on workup of rectal NETs.

BACKGROUND: Rectal neuroendocrine tumors (RNETs) are often discovered on screening colonoscopy. Indications for staging and definitive resection are inconsistent in current guidelines. We evaluated the role of grade in guiding staging and procedural decision-making. METHODS: Patients with biopsy confirmed RNETs between 2004 and 2015 were reviewed. Baseline characteristics, staging investigations (biochemical and imaging), and endoscopic/surgical treatment were recorded. Associations between grade, preoperative staging, interventions, and survival were determined using Fisher-Freeman-Halton Exact, log-rank, and Kaplan-Meier analysis. RESULTS: Amongst 139 patients with RNETs, 9% were aged ≥ 75 years and 44% female. Tumor grade was: 73% grade 1 (G1), 18%, grade 2 (G2) and 9% grade 3 (G3). Staging investigations were performed in 52% of patients. All serum chromogranin A and 97% of 24-hour urine 5-hydroxyindoleacetic acid tests were normal. The large majority of staging computed tomography (CT) scans were negative (76%) with subgroup analysis showing no G1 patients with CT identified distant disease compared with 38% of G2 and 50% of G3 patients (p < 0.001). G1 patients were more likely to achieve R0/R1 resections compared to G2 (95% vs. 50%, p < 0.001) and G1 patients had significantly better 5-year overall survival (G1: 98%, G2: 67%, G3: 10%, p < 0.001). CONCLUSION: Tumor grade is important in preoperative workup and surgical decision-making. Biochemical staging may be omitted but staging CT should be considered for patients with grade ≥ 2 lesions. Anatomic resections should be considered for patients with grade 2 disease.

Exploring treatment outcomes in Stage II-III rectal cancer patients undergoing neoadjuvant therapy at a tertiary care center in Pakistan: a comprehensive analysis of pathological outcomes.

BACKGROUND: Rectal cancer treatment has transformed in recent years, with neoadjuvant treatment (NT) and total neoadjuvant treatment (TNT) aiming to enhance pathological responses. This pioneering study in our country delves into rectal cancer management, offering crucial insights by examining pathological outcomes in patients treated with the NT and TNT approach, shaping the evolving landscape. METHODS: In this retrospective-cohort study spanning January 2017 to December 2022 at a tertiary care hospital in Pakistan, ethical approval was obtained to examine outcomes of two treatments. Patients were divided into TNT (chemoradiation and pre-surgery 5 FU-based chemotherapy) and NT (chemoradiation, surgery, and subsequent 5 FU-based chemotherapy). The primary end-point was response rates-no response, pathological complete response (pCR), near complete response (near CR), and partial response (PR). The Chi-Square Test for Independence assessed the association between treatment response and type (TNT or NT). Data analysis used STATA MP 64; significance was set at p < 0.05 for all two-tailed tests. RESULTS: We analyzed 77 patients, 60 underwent standard neoadjuvant chemoradiation, and 17 followed the total neoadjuvant approach. Predominantly male, most were > 65 with ECOG 0-1. The TNT group showed higher response rates (76% vs 62%, p = 0.039), with 40.38% achieving pCR. In the overall population, pCR and near-CR were similar (27.2% vs 26%), while PR were 14%. Treatment characteristics correlated significantly with chemotherapy type, concurrent chemoradiation, LVI, PNI, and T, N, M staging (p < 0.05). Median overall survival was not reached, and mean survival was 89.1 months (CI: 95.0 to 83.3). Side effects varied, with notable differences in neuropathy, diarrhea, oral mucositis, and thrombocytopenia between NT and TNT groups. CONCLUSION: Our study adds to evidence favoring neoadjuvant approaches in managing rectal cancer in pakistan. Demonstrating a favorable pcr rate, ongoing research with extended follow-up is essential, given the dynamic landscape of rectal cancer treatment for improved patient outcomes.

Effect of previous abdominal surgery on robotic-assisted rectal cancer surgery.

BACKGROUND: The effect of previous abdominal surgery (PAS) in laparoscopic surgery is well known and significantly adds to longer hospital length of stay (LOS), postoperative ileus, and inadvertent enterotomies. However, little evidence exists in patients with PAS undergoing robotic-assisted (RA) rectal surgery. METHODS: All patients undergoing RA surgery for rectal cancer were reviewed. Patients with PAS were divided into minor and major PAS groups, defined as surgery involving >1 quadrant. The primary outcome was the risk of conversion to open surgery. RESULTS: A total of 750 patients were included, 531 in the no-PAS (NPAS) group, 31 in the major PAS group, and 188 in the minor PAS group. Patients in the major PAS group had significantly longer hospital LOS (P < .001) and lower adherence to enhanced recovery pathways (ERPs; P = .004). The conversion rates to open surgery were similar: 3.4% in the NPAS group, 5.9% in the minor PAS group, and 9.7% in the major PAS group (P = .113). Estimated blood loss (EBL; P = .961), operative times (OTs; P = .062), complication rates (P = .162), 30-day readmission (P = .691), and 30-day mortality (P = .494) were similar. Of note, 53 patients underwent lysis of adhesions (LOA). On multivariate analysis, EBL >500 mL and LOA significantly influenced conversion to open surgery. EBL >500 mL, age >65 years, conversion to open surgery, and prolonged OT were risk factors for prolonged LOS, whereas adherence to ERPs was a protector. CONCLUSION: PAS did not seem to affect the outcomes in RA rectal surgery. Given this finding, the robotic approach may ultimately provide patients with PAS with similar risk to patients without PAS.