Early Surveillance Endoscopy Should Be Performed Selectively After Transanal Endoscopic Microsurgery for Rectal Lesions.

Introduction Local recurrence (LR) rates after transanal endoscopic microsurgery (TEM) are unclear, and the utility of early postoperative surveillance for low-risk lesions is unknown. This study aimed to define LR after TEM for benign polyps and invasive adenocarcinoma, describe risk factors for LR, and evaluate the utility of early surveillance endoscopy. Methods This retrospective cohort study was conducted at two hospitals in Winnipeg, Manitoba, Canada. Adult patients who underwent TEM between 2009 and 2020 were evaluated for inclusion. The primary outcome was the rate of LR on surveillance endoscopy. Other outcomes included risk factors for LR and diagnostic yield of surveillance endoscopy. Results Among 357 patients who underwent TEM for benign polyps, LR was 10.5% (95% confidence interval (CI) 5.8-15.2) at three years. Positive margin was correlated with LR on multivariate analysis (hazard ratio (HR) 8.01, 95% CI 2.78-23.08). TEM defect closure was associated with lower LR on multivariate analysis (HR 0.19, 95% CI 0.06-0.59). Among 124 patients who underwent TEM for rectal adenocarcinoma, LR was 15.0% (95% CI 6.0-24.0) at three years. The first surveillance endoscopy had a 1.4% yield for low-risk patients (benign lesion, negative margins, and closed TEM defect) and 6.9% for all others. Conclusions LR at three years after TEM was 10.5% for benign polyps and 15.0% for adenocarcinomas. Early surveillance endoscopy can be considered low yield in some patients after TEM, which can be informative for shared decision-making regarding whether to proceed with early endoscopy in a low-risk subgroup of patients.

Implementation of Synoptic Reporting for Endoscopic Localization of Complex Colorectal Neoplasms.

Introduction  Lack of documented tattooing of colorectal neoplasms at index colonoscopy results in high repeat preoperative colonoscopy rates. We developed national consensus recommendations for endoscopic localization and piloted an electronic synoptic reporting template. We report on the implementation and perceptions of using synoptic reporting to enhance colorectal lesion marking in a central Canadian healthcare system.  Methods We implemented the template within our endoscopy reporting system and ran an infographic education campaign. We then conducted a follow-up email-based interview with all regional endoscopists. Thematic analysis and a mixed-methods triangulation approach were employed to synthesize qualitative and quantitative data.  Results The interview was completed by 28/52 endoscopists (54%). Most (60.7%; n = 17) completed >100 colonoscopies and 71.4% (n = 20) identified six to 20 neoplasms requiring tattooing since introduction. A total of 50% (n = 14) used the template. Those not using it were unaware of it (42.9%; n = 12), or preferred using narrative text (17.9%; n = 5). Users reported modest mean functionality scores (intuitiveness: 3.56/5; efficiency: 3.7/5) and high impact scores (credible: 4.22/5; informative: 4.21/5). However, the perception of the synoptic template's ability to reduce the repeat preoperative colonoscopy rate was more circumspect (3.76/5). Conclusions Endoscopists believed the synoptic template was a functional, impactful tool that would improve communication and help to decrease the repeat preoperative colonoscopy rate. However, synoptic template uptake was limited by provider awareness, therefore more educational efforts are needed to increase uptake.

Colorectal polyp classification and management of complex polyps for surgeon endoscopists.

Increasing familiarity with advanced endoscopic excision techniques allows for more colorectal lesions to be removed without major surgery. Endoscopic excision with negative margins is adequate for most polyps and low-risk T1 cancers. The use of modern polyp classification techniques based on size, morphology and pit pattern by an experienced endoscopist allow for an optical diagnosis of these lesions and can predict, with high accuracy, which lesions contain malignant disease and the level of invasion. A surgeon endoscopist must be able to recognize which complex polyps can be resected with advanced polypectomy techniques and which require upfront surgery. We aimed to provide an overview of polyp classification techniques to help surgeons select the correct treatment algorithm for advanced colorectal lesions based on their visual characteristics at index endoscopy.

Total neoadjuvant therapy for rectal cancer: a guide for surgeons.

The modern management of rectal cancers continues to evolve. With the release of data from new landmark randomized controlled trials (RAPIDO, PRODIGE-23), total neoadjuvant therapy (TNT) has moved to the forefront of locally advanced rectal cancer treatment and is considered a standard option in selected patients. Total neoadjuvant therapy promises enhanced systemic disease control, better treatment adherence and less time with an ostomy. However, TNT as currently described encompasses a number of different potential treatment options that differ significantly in terms of their radiation dosage, chemotherapy regimen and order of treatments administered. Being familiar with TNT regimens will be important for rectal cancer surgeons to appropriately advocate for their patients and optimize their outcomes. This article serves as a primer for the general surgeon and offers a pragmatic overview of the indications, realistic expected benefits and potential downsides of each TNT regimen.

Routine pathologic evaluation of circular stapler anastomotic rings is not useful after resection for colorectal cancer: retrospective study and systematic review with meta-analysis.

BACKGROUND: Circular staplers are commonly used for reconstruction after radical resection for colorectal cancer. Pathological analysis of the anastomotic rings is common practice, although the benefits are unclear. The purpose of this study was to evaluate the usefulness of routine histopathological analysis of anastomotic rings in an original series and in a systematic review of the literature. METHOD: The retrospective study was performed at two university-associated academic hospitals in Winnipeg, Canada, including patients investigated for colorectal cancers (within 30 cm of the anal verge) who underwent resection between 2007 and 2020. The systematic review involved Ovid MEDLINE, Embase, Scopus, and Web of Science databases, selecting for adult human studies involving analysis of anastomotic rings in elective colorectal cancer resections. The main outcome measure was the proportion of patients with cancer in the anastomotic ring specimens. The frequency of benign pathology findings and changes to patient management were also examined. RESULTS: Out of 673 eligible patients, 487 were included in the retrospective analysis. No patients had cancer within the anastomotic ring specimens. Twenty-five patients (5.1 per cent) had benign pathological findings within the anastomotic ring specimens, and patient management was never affected. In the systematic review, 27 articles were included in the final analysis out of 5848 records reviewed. The rate of cancer within anastomotic ring specimens was 0.34 per cent, and the rate of change in patient management was 0.19 per cent. CONCLUSION: The likelihood of finding cancer within anastomotic rings is rare and their histopathological examination seldom changes patient management.

Rectal Cancer Metastasis to the Anal Verge: An Unusual Case Presentation and Review of the Literature.

BACKGROUND: Anal metastasis of colorectal adenocarcinoma is very rare, represented by only a handful of case reports in the literature. Previously, reports of metastasis to this region had occurred following a history of anorectal disease, such as anal fistulae. Antecedent trauma to the area from hemorrhoidectomy, fissures, or perineal retractor injury have also been implicated. CASE PRESENTATION: Herein we report the case of 69-year-old man without any history of anal disease presenting with a metachronous metastasis of a colorectal-type adenocarcinoma to the anal verge. He was previously treated for T1N0 rectal adenocarcinoma at the rectosigmoid junction with a low anterior resection 5 years prior, then had a T3N0 local recurrence at the colorectal anastomosis treated with neoadjuvant chemoradiation, and eventually a Hartmann's procedure 4 years later. Subsequently, on surveillance flexible sigmoidoscopy, a new tumor was identified on the perianal skin extending from the anal verge. Histopathology demonstrated colorectal-type adenocarcinoma. Flexible endoscopy identified no other residual or recurrent disease in the colon or rectal stump. The patient was treated with wide local excision and advancement flap reconstruction. CONCLUSION: Isolated metastasis to the anus is an extremely rare occurrence for colorectal adenocarcinoma. There exists little evidence to inform management. One option is to treat like a locally recurrent rectal cancer with aggressive tri-modality management consisting of chemoradiation, abdominal perineal resection, and adjuvant chemotherapy. In the absence of metastatic disease, local resection and close surveillance remain an option. As always, patient factors should guide management.

Ruptured Middle Colic Artery Aneurysm Presenting with Symptoms of Acute Cholecystitis: A Case Report and Literature Review.

Background: Ruptured middle colic artery aneurysm is extremely uncommon. Diagnosis can be challenging, as symptomatology can be attributed to more common abdominal pathologies. Due to the rarity of this condition, only case reports are available to inform management. Case Presentation: We present the case of a 72-year-old woman with a ruptured middle colic artery aneurysm presenting with signs and symptoms more suggestive of acute calculous cholecystitis. Her co-existing bleed was confirmed on CT angiogram. Coil embolization was initially attempted unsuccessfully. She underwent laparotomy, a middle colic artery ligation, and extended right hemicolectomy with intra-aortic balloon placement for emergency proximal vascular control. Post-operatively, she had a re-bleed that was successfully managed with covered stent placement in the proximal superior mesenteric artery after an unsuccessful re-attempt at coil embolization. Her apparent associated cholecystitis was managed with antibiotics and resolved uneventfully. Conclusion: A middle colic artery aneurysm can be challenging to diagnose and treat. Management options include endovascular techniques, open surgery, or a combination approach. Intra-aortic balloon placement for emergency vascular control is a novel approach that could avoid hemorrhage when intra-abdominal vascular access is challenging.

Serrated polyps and polyposis of the colon: a brief review for surgeon endoscopists.

Serrated polyps (SPs) were once considered benign, clinically unimportant lesions. However, it is now recognized that through the serrated neoplasia pathway (SNP), SPs play a role in the development of 15%-30% of cases of colorectal cancers (CRC). Furthermore, a high proportion of postcolonoscopy CRCs are believed to arise from SNP. Serrated polyps are classified into hyperplastic polyps, sessile serrated lesions, sessile serrated lesions with dysplasia, traditionally serrated adenomas, and unclassified serrated adenoma, each with a distinct morphological and molecular profile. Despite improved understanding, SPs remain a clinical challenge owing to evolving terminology, frequent pathologic misclassification, endoscopic underdetection, and high rates of incomplete removal. Surgeon endoscopists and surgeons who perform colorectal procedures will undoubtedly come across patients with SPs, and this paper summarizes some of the clinical challenges they will encounter. We also discuss the diagnosis and management of patients with serrated polyposis syndrome (SPS).

The Role of Lung Lobes in Radiation Pneumonitis and Radiation-Induced Inflammation in the Lung: A Retrospective Study.

OBJECTIVE: We examined the relative response to radiation of the upper lung lobes (UL) versus lower lung lobes (LL) of normal lung tissue using normalized [18F]-fluorodeoxyglucose (FDG) uptake per radiation dose received per lung voxel in patients treated with either photons or protons and tested for correlation of the radiation response with clinical pneumonitis. METHODS: Seventy-five patients (photon (n = 51) or proton (n = 24)) treated for esophageal cancer from November 1, 2003 to May 15, 2011 who received restaging FDG-positron emission tomography (PET) imaging 1 to 3 months after chemoradiation were selected. UL and LL were contoured using the major fissure as the boundary, with the right middle lobe being included in the right UL structure. Pneumonitis toxicity was scored using the Common Terminology Criteria for Adverse Events, version 4.0 based on the consensus of 5 clinicians. RESULTS: LL had a higher mean dose (15.6 Gy vs. 10.4 Gy, p<0.001), higher mean standard uptake value (SUV) (0.78 vs. 0.56, p=0.001) and SUV in low dose regions (0.80 vs. 0.66 for 10 to 20 Gy, p=0.001), and lower mean dose response (0.015 vs. 0.019, p=0.003) compared to the UL. The mean dose ratio of UL vs. LL (p < 0.001), and SUV in the region of lung receiving 0-10 Gy (p=0.04), but not the dose response ratio of UL vs. LL (p=0.53) correlated with symptomatic pneumonitis. CONCLUSION: Upper lung lobes had a greater pulmonary metabolic radiation response than lower lung lobes. Greater dose to UL relative to LL and higher SUV in the low dose region (10-20 Gy) on post-treatment PET correlated with symptomatic pneumonitis.

Contribution of bone marrow-derived cells to the pro-inflammatory effects of protease-activated receptor-2 in colitis.

OBJECTIVE: Our aim was to determine the contribution of proteinase-activated receptor-2 (PAR(2))-expressing bone marrow-derived cells on the development of colonic inflammation. MATERIALS: Chimeric mice were generated by injecting bone marrow cells from wildtype (PAR (2) (+/+) ) or PAR(2) knockout mice (PAR (2) (-/-) ) into irradiated PAR (2) (+/+) or PAR (2) (-/-) mice. TREATMENTS: Colitis was induced by giving 2.5% dextran sodium sulfate (DSS) solution for 7 days or by a single intracolonic administration of trinitrobenzene sulphonic acid (TNBS, 2 mg dissolved in 40% ethanol). METHODS: Seven days after the induction of colitis, bowel thickness, inflammatory parameters [myeloperoxidase (MPO) activity, macroscopic/microscopic damage scores], and leukocyte trafficking (visualized via intravital microscopy) were assessed. RESULTS: Total deficiency of PAR(2) resulted in a marked reduction in severity of both TNBS and DSS induced colitis as assessed by MPO activity, macroscopic damage, bowel thickness, and leukocyte adherence. Colitis was attenuated in all chimeric lines in which there was loss of PAR(2) in the host, non-bone marrow-derived tissue, independent of the status of PAR expression by bone marrow-derived cells. Interestingly, TNBS colitis was attenuated in PAR (2) (+/+) chimeric mice with PAR (2) (-/-) derived bone marrow but these animals were not protected from DSS colitis. CONCLUSIONS: Expression of PAR(2) by host-derived tissues plays a dominant role in regulating colonic inflammation. PAR(2) expression by bone marrow-derived cells appears to play a role in TNBS colitis but not in DSS induced injury.

ATAXIN-1 interacts with the repressor Capicua in its native complex to cause SCA1 neuropathology.

Spinocerebellar ataxia type 1 (SCA1) is one of several neurodegenerative diseases caused by expansion of a polyglutamine tract in the disease protein, in this case, ATAXIN-1 (ATXN1). A key question in the field is whether neurotoxicity is mediated by aberrant, novel interactions with the expanded protein or whether its wild-type functions are augmented to a deleterious degree. We examined soluble protein complexes from mouse cerebellum and found that the majority of wild-type and expanded ATXN1 assembles into large stable complexes containing the transcriptional repressor Capicua. ATXN1 directly binds Capicua and modulates Capicua repressor activity in Drosophila and mammalian cells, and its loss decreases the steady-state level of Capicua. Interestingly, the S776A mutation, which abrogates the neurotoxicity of expanded ATXN1, substantially reduces the association of mutant ATXN1 with Capicua in vivo. These data provide insight into the function of ATXN1 and suggest that SCA1 neuropathology depends on native, not novel, protein interactions.

The tumour-suppressor genes NF2/Merlin and Expanded act through Hippo signalling to regulate cell proliferation and apoptosis.

Merlin, the protein product of the Neurofibromatosis type-2 gene, acts as a tumour suppressor in mice and humans. Merlin is an adaptor protein with a FERM domain and it is thought to transduce a growth-regulatory signal. However, the pathway through which Merlin acts as a tumour suppressor is poorly understood. Merlin, and its function as a negative regulator of growth, is conserved in Drosophila, where it functions with Expanded, a related FERM domain protein. Here, we show that Drosophila Merlin and Expanded are components of the Hippo signalling pathway, an emerging tumour-suppressor pathway. We find that Merlin and Expanded, similar to other components of the Hippo pathway, are required for proliferation arrest and apoptosis in developing imaginal discs. Our genetic and biochemical data place Merlin and Expanded upstream of Hippo and identify a pathway through which they act as tumour-suppressor genes.