Transanal minimally invasive surgery for benign and malignant rectal lesions: midterm outcomes from a tertiary center.

BACKGROUND: Although transanal minimally invasive surgery (TAMIS) for rectal neoplasia has gained wide acceptance, the mid-term and long-term outcomes are not widely reported in the literature. OBJECTIVE: Describe the mid-term outcomes of patients who underwent TAMIS for benign and malignant rectal lesions in a single center. DESIGN: Retrospective cohort study. SETTINGS: Tertiary referral center. PATIENTS AND METHODS: Demographic, clinical, and oncological outcomes of patients who underwent TAMIS between January 2015 and December 2022 were prospectively collected. The indication for TAMIS was based on the National Comprehensive Cancer Network guidelines. The follow up for the cancer patients included clinical examination, tumor markers every 6 months and MRI rectum at the end of one year. In addition, colonoscopy and CT scan at years one and three and a final CT scan and colonoscopy at year five. MAIN OUTCOME MEASURES: Mid-term oncological and clinical outcome. RESULTS: Thirty elective TAMIS procedures included adenocarcinoma for 33.3% (n=10) of the patients, 20% (n=6) neuroendocrine tumor and the 40% (n=12) were adenomatous lesions. Negative resection margins were achieved in all malignant lesions. Perioperative complications occurred in 2 patients (6.6%), one patient had breaching into the peritoneal cavity, and postoperative hypotension occurred in another patient. The median follow-up time was 23 months (range: 5-72 months). Two patients with adenoma and positive margins developed recurrent adenoma (6.6%) and one patient with initial polypectomy biopsy of adenocarcinoma, had TAMIS with histopathology of adenoma and distant metastasis had developed. CONCLUSIONS: TAMIS for local excision of rectal neoplasia is a valid option with favorable mid-term outcomes provided there is adherence to careful selection criteria. LIMITATIONS: Retrospective nature and small number of the patients.

Colonic medullary carcinoma: an exceedingly rare type of colorectal malignancy: a case report and review of the literature.

BACKGROUND: Medullary carcinoma of the colon is a rare subtype of colorectal cancer that has a unique, and sometimes varied, clinical and histologic profile. It usually presents in adult patients older than 50 years. Here, we report a unique case of young male patient who initially presented with abdominal pain followed by a large bowel obstruction. CASE PRESENTATION: A 40-year-old SriLankan male presented with right-sided abdominal pain and on examination, there was a palpable right iliac fossa mass. Colonoscopy and a computed tomography scan revealed cecal mass. Later, while waiting for elective resection, the patient developed symptoms and signs of a large bowel obstruction. He underwent a laparoscopic right hemicolectomy with an uneventful postoperative course. The histopathologic evaluation of the resected specimens showed invasive carcinoma with syncytial growth pattern, foci of lymphoid host response, and dirty necrosis, in keeping with a medullary carcinoma pT4a pN2b. Unlike most reported medullary carcinoma cases, this patient was young and caudal-related homeobox transcription factor 2 positive. CONCLUSION: We have reported another case of medullary carcinoma of the colon in a young patient with unique histologic characteristics. Reporting such cases helps in refine understanding of the histologic and genetic, as well as clinical, phenotypes of medullary carcinoma of the colon.

Textbook Oncological Outcomes for Robotic Colorectal Cancer Resections: An Observational Study of Five Robotic Colorectal Units.

BACKGROUND: The quality of care of patients receiving colorectal resections has conventionally relied on individual metrics. When discussing with patients what these outcomes mean, they often find them confusing or overwhelming. Textbook oncological outcome (TOO) is a composite measure that summarises all the 'desirable' or 'ideal' postoperative clinical and oncological outcomes from both a patient's and doctor's point of view. This study aims to evaluate the incidence of TOO in patients receiving robotic colorectal cancer surgery in five robotic colorectal units and understand the risk factors associated with failure to achieve a TOO in these patients. METHODS: We present a retrospective, multicentric study with data from a prospectively collected database. All consecutive patients receiving robotic colorectal cancer resections from five centres between 2013 and 2022 were included. Patient characteristics and short-term clinical and oncological data were collected. A TOO was achieved when all components were realized-no conversion to open, no complication with a Clavien-Dindo (CD) ≥ 3, length of hospital stay ≤ 14, no 30-day readmission, no 30-day mortality, and R0 resection. The main outcome measure was a composite measure of "ideal" practice called textbook oncological outcomes. RESULTS: A total of 501 patients submitted to robotic colorectal cancer resection were included. Of the 501 patients included, 388 (77.4%) achieved a TOO. Four patients were converted to open (0.8%); 55 (11%) had LOS > 14 days; 46 (9.2%) had a CD ≥ 3 complication; 30-day readmission rate was 6% (30); 30-day mortality was 0.2% (1); and 480 (95.8%) had an R0 resection. Abdominoperineal resection was a risk factor for not achieving a TOO. CONCLUSIONS: Robotic colorectal cancer surgery in robotic centres achieves a high TOO rate. Abdominoperineal resection is a risk factor for failure to achieve a TOO. This measure may be used in future audits and to inform patients clearly on success of treatment.

Short-term outcomes in robotic vs laparoscopic ileal pouch-anal anastomosis surgery: a propensity score match study.

PURPOSE: Laparoscopic ileal pouch-anal anastomosis (IPAA) surgery offers improved short-term outcomes over open surgery but can be technically challenging. Robotic surgery has been increasingly used for IPAA surgery, but there is limited evidence supporting its use. This study aims to compare the short-term outcomes of laparoscopic and robotic IPAA procedures. METHODS: All consecutive patients receiving laparoscopic and robotic IPAA surgery at 3 centres, from 3 countries, between 2008 and 2019 were identified from prospectively collated databases. Robotic surgery patients were propensity score matched with laparoscopic patients for gender, previous abdominal surgery, ASA grade (I, II vs III, IV) and procedure performed (proctocolectomy vs completion proctectomy). Their short-term outcomes were examined. RESULTS: A total of 89 patients were identified (73 laparoscopic, 16 robotic). The 16 patients that received robotic surgery were matched with 15 laparoscopic patients. Baseline characteristics were similar between the two groups. There were no statistically significant differences in any of the investigated short-term outcomes. Length of stay trend was higher for laparoscopic surgery (9 vs 7 days, p = 0.072) CONCLUSION: Robotic IPAA surgery is safe and feasible and offers similar short-term outcomes to laparoscopic surgery. Length of stay may be lower for robotic IPAA surgery, but further larger scale studies are required in order to demonstrate this.

Choice of specimen's extraction site affects wound morbidity in laparoscopic colorectal cancer surgery.

BACKGROUND: The choice for an ideal site of specimen extraction following laparoscopic colorectal surgery remains debatable. However, midline incision (MI) is usually employed for right and left-sided colonic resections while left iliac fossa or suprapubic transverse incision (STI) were reserved for sigmoid and rectal cancer resections. OBJECTIVE: To compare the incidence of surgical site infection (SSI) and incisional hernia (IH) in elective laparoscopic colorectal surgery for cancer and specimen extraction via MI or STI. METHOD: Prospectively collected data of elective laparoscopic colorectal cancer resections between January 2017 and December 2019 were retrospectively reviewed. MI was employed for right and left-sided colonic resections while STI was used for sigmoid and rectal resections. SSI is defined according to the US CDC criteria. IH was diagnosed clinically and confirmed by CT scan at 1 year. RESULTS: A total of 168 patients underwent elective laparoscopic colorectal resections. MI was used in 90 patients while 78 patients had STI as an extraction site. Demographic and preoperative data is similar for two groups. The rate of IH was 13.3% for MI and 0% in the STI (p = 0.001). SSI was seen in 16.7% of MI vs 11.5% of STI (p = 0.34). Univariate and multivariate analysis showed that the choice of extraction site is associated with statistically significant higher incisional hernia rate. CONCLUSION: MI for specimen extraction is associated with higher incidence of both SSI and IH. The choice of incision for extraction site is an independent predicative factor for significantly higher IH and increased SSI rates.

Diagnostic Inflammation Biomarkers for Prediction of 30-Day Mortality Rate in Acute Cholangitis.

Background: Acute cholangitis (AC) is an acute inflammation and infection of the biliary tract, a potentially life-threatening infection, which is usually associated with biliary tree obstruction and impairment of bile flow from the liver to the duodenum. AC is classified by severity from mild, moderate to severe infection (grade I to III, respectively). Methods: This study recruited a retrospective cohort from Jan 2015 to July 2018. Overall, 294 patients of age ≥ 18 years with AC were enrolled. The study was conducted according to the World Medical Association Declaration of Helsinki. Demographic and laboratory data were collected for analysis. T-Bilirubin and other laboratory results were collected and analyzed using independent T-test and ANOVA for continuous values and multivariate COX regression for survival analysis for identifying independent factors for early mortality. The cut-off threshold of T-bilirubin was determined by calculating the area under the receiver operating characteristic (ROC) curve. Results: There were 213 male and 81 female patients and mean age ± SD of patients was 49.57 ± 16.1 and 56.12 ± 20.18 respectively. 31.9% patients were found older than 60 years of age and 35% patients were found between 30-45 years of age. T-bilirubin and length of hospital stay (LOS) were found statistically significant (P < 0.05) in relation to mortality in AC patients. The area under ROC curve for T-bilirubin level (P = 0.017, OR = 1.010) was 0.717 (95% CI, 6.25-168.9) and this is consistent with the Cut-off point for more than or equal to 38.6 µmol/L (2.26 mg/dL). Conclusions: In this study, T-bilirubin level is found to be significantly related to short-term mortality in AC. Further studies are still needed with larger cohorts to shed more light on these findings. Highlights: Herein, we report a retrospective observational study aiming to evaluate biomarkers contributing to mortality in AC and to determine the cut-off diagnostic levels that could be easily used in emergency setting. Overall, 294 patients of age ≥ 18 years with AC were enrolled. The study was conducted according to the World Medical Association Declaration of Helsinki and approved by Institutional Review Board (IRB) with approval: MRC-01-20-823 at Hamad Medical Corporation (HMC). Demographic and laboratory data were collected for analysis. Total-Bilirubin and other laboratory results were collected and analyzed using independent T-test and ANOVA for continuous values and multivariate COX regression for survival analysis for identifying independent factors for early mortality. The cut-off threshold of T-bilirubin was determined by calculating the area under the receiver operating characteristic (ROC) curve. There were 213 male and 81 female patients and mean age ± SD of patients was 49.57 ± 16.1 and 56.12 ± 20.18 respectively. 31.9% patients were found older than 60 years of age and 35% patients were found between 30-45 years of age. T-bilirubin and length of hospital stay (LOS) were found statistically significant (P < 0.05) in relation to mortality in AC patients. The area under ROC curve for T-bilirubin level (P = 0.037, OR = 1.010) was 0.717 (95% CI, 6.25-168.9) and this is consistent with the Cut-off point for more than or equal to 38.6 µmol/L (2.26 mg/dL).

Transcriptome of Tumor-Infiltrating T Cells in Colorectal Cancer Patients Uncovered a Unique Gene Signature in CD4+ T Cells Associated with Poor Disease-Specific Survival.

Colorectal cancer (CRC) is influenced by infiltration of immune cell populations in the tumor microenvironment. While elevated levels of cytotoxic T cells are associated with improved prognosis, limited studies have reported associations between CD4+ T cells and disease outcomes. We recently performed transcriptomic profiling and comparative analyses of sorted CD4+ and CD8+ tumor-infiltrating lymphocytes (TILs) from bulk tumors of CRC patients with varying disease stages. In this study, we compared the transcriptomes of CD4+ with CD8+ TILs. Functional annotation pathway analyses revealed the downregulation of inflammatory response-related genes, while T cell activation and angiogenesis-related genes were upregulated in CD4+ TILs. The top 200 deregulated genes in CD4+ TILs were aligned with the cancer genome atlas (TCGA) CRC dataset to identify a unique gene signature associated with poor prognosis. Moreover, 69 upregulated and 20 downregulated genes showed similar trends of up/downregulation in the TCGA dataset and were used to calculate "poor prognosis score" (ppScore), which was significantly associated with disease-specific survival. High ppScore patients showed lower expression of Treg-, Th1-, and Th17-related genes, and higher expression of Th2-related genes. Our data highlight the significance of T cells within the TME and identify a unique candidate prognostic gene signature for CD4+ TILs in CRC patients.

RNA-Seq Analysis of Colorectal Tumor-Infiltrating Myeloid-Derived Suppressor Cell Subsets Revealed Gene Signatures of Poor Prognosis.

Elevated levels of myeloid-derived suppressor cells (MDSCs), including polymorphonuclear MDSCs (PMN-MDSCs) and immature MDSCs (I-MDSCs), are usually associated with disease progression in cancer patients, including colorectal cancer (CRC). However, biological mechanisms and molecular pathways regulated by MDSC subpopulations in the CRC tumor microenvironment (TME) have not been fully investigated. In this study, we performed transcriptomic analysis of tumor-infiltrating I-MDSCs and PMN-MDSCs isolated from tumor tissues of six CRC patients, compared to antigen-presenting cells (APCs). We also compared the transcriptomic profiles of tumor-infiltrating PMN-MDSCs to I-MDSCs. Our results showed different molecular pathways regulated by each MDSC subset, potentially reflecting their phenotypical/molecular/functional characteristics in the CRC TME. Moreover, we identified gene signatures in PMN-MDSC and I-MDSC of poor overall survival (OS) and disease-free survival (DFS) using the Cancer Genome Atlas (TCGA) dataset from patients with colon adenocarcinoma (COAD). However, functional studies are required to validate these findings.

Differential gene expression of tumor-infiltrating CD8+ T cells in advanced versus early-stage colorectal cancer and identification of a gene signature of poor prognosis.

BACKGROUND: Cytotoxic CD8+ T cell-mediated response is the most important arm of adaptive immunity, which dictates the capacity of the host immune response in eradicating tumor cells. Due to tumor intrinsic and/or extrinsic factors, the density and function of CD8+ tumor-infiltrating lymphocytes (TILs) could be compromised, leading to poor prognosis and survival. METHODS: Using RNA-Seq, transcriptomes of sorted CD3+CD8+ TILs from treatment-naïve colorectal cancer (CRC) patients at advanced stages (III and IV) were compared with those from patients with early stages (I and II). A signature referred to as 'poor prognosis CD8 gene signature (ppCD8sig)' was identified and analyzed in The Cancer Genome Atlas CRC dataset. Scores for the ppCD8sig were calculated and classified as high, intermediate and low, and its prognostic significance was assessed using multivariate analysis and Cox proportional hazard model. Densities of CD3+ and CD8+ T cell infiltration in tumors from patients with high and low ppCD8sig scores were assessed by flow cytometry and immunostaining. RESULTS: Genes related to epigenetic regulation and response to hypoxia were upregulated in CD8+ TILs from patients with advanced stages, while genes related to T cell activation, cell proliferation and cell cycle were downregulated. Patients with high ppCD8sig score had poorer disease-specific survival (DSS) and shorter progression-free interval (PFI). The ppCD8sig was an independent prognostic indicator for DSS (HR 1.83, 95% CI 1.40 to 2.38, p<0.0001) and PFI (HR 1.42, 95% CI 1.04 to 1.93, p=0.026). Additionally, patients with high ppCD8sig score were more likely to have advanced stages (χ2 p<0.0001) and residual disease after primary therapy (χ2 p=0.046). Patients with high ppCD8sig score had reduced levels of CD3+ and CD8+ TILs and low Immunoscores (IS), compared to patients with low ppCD8sig score. CONCLUSIONS: Our data provided insights into the altered regulation of biological mechanisms and signaling pathways in CD8+ TILs during CRC progression, and revealed a gene signature as an independent prognostic indicator. Patients with high ppCD8sig score had lower levels of TILs and low IS. These data further confirm the prognostic value of the identified ppCD8sig and potentially highlight its clinical relevance.

Left iliac fossa mini-incision sigmoidectomy for treatment of sigmoid volvulus. Case series of six patients from Qatar.

BACKGROUND: Midline laparotomy is the definitive treatment for sigmoid volvulus after initial colonoscopic detorsion. We successfully adopted another technique at our center on 6 patients, treating sigmoid volvulus by left iliac fossa mini-incision. PRESENTATION OF CASES: We report our experience of six non-consecutive cases of sigmoid volvulus treated by left iliac fossa mini-incision. The cases were a 33 year old Egyptian female, a 21 year old Bangladeshi male, a 58 year old Qatari male, a 30 year old Ethiopian male, a 36 year old Ugandan male, and a 58 year old Indian male. The six cases are unique in the surgical technique employed in their management. This is possibly the second case series of left iliac fossa mini-incision for sigmoid volvulus in the Middle East and North Africa Region. DISCUSSION: All patients underwent initial colonoscopic detorsion followed by sigmoidectomy and anastomosis. The procedure was successful in treating the volvulus in five patients with no complication or recurrence over a mean follow up of 8 months (range: 1-36 months). One patient required further laparotomy and resection with anastomosis due to incompletely removed sigmoid colon. CONCLUSIONS: Left iliac fossa mini-incision for sigmoid volvulus is safe, feasible, cosmetically appealing and with low morbidity.