Simon Bach

A predictive model for local recurrence after transanal endoscopic microsurgery for rectal cancer.

The outcome of local excision of early rectal cancer using transanal endoscopic microsurgery (TEM) lacks consensus. Screening has substantially increased the early diagnosis of tumours. Patients need local treatments that are oncologically equivalent to radical surgery but safer and functionally superior.

Revolution and evolution: 30 years of ileoanal pouch surgery

&NA; Ileal pouch‐anal anastomosis (IPAA) has become the standard of care for the 25% of patients with ulcerative colitis who ultimately require colectomy. IPAA is favored by patients because it avoids the necessity for a long‐term stoma. This review examines how 3 decades of experience with IPAA has molded current practice, highlighting 5‐ and 10‐year follow‐up of large series to determine durability and functional performance, in addition to causes of failure and the management of complications.

A critical appraisal of endorectal ultrasound and transanal endoscopic microsurgery and decision-making in early rectal cancer.

Aim  Transanal endoscopic microsurgery (TEM) for early rectal cancer (ERC) gives results similar to major surgery in selected cases. Endorectal ultrasound (ERUS) is an important part of the preoperative selection process. This study reports its accuracy and impact for patients entered on the UK TEM database.

The relevance of apoptosis for cellular homeostasis and tumorigenesis in the intestine

Intestinal epithelium is a rapidly renewing tissue in which cell homeostasis is regulated by a balance among proliferation, growth arrest, differentiation and apoptosis (programmed cell death). Until recently, studies on oncogenesis have focused on the regulation of cell proliferation. The recognition that apoptosis must be understood to comprehend how appropriate cell numbers are maintained and how alterations in any part of the equation can contribute to malignancy has led to an explosion of research in this field. The first half of this review gives an overview of morphology and mechanisms of apoptosis, emphasizing key areas of genetic control such as the bcl-2 family and p53. The second half of the review focuses on the role of apoptosis in normal cellular homeostasis and tumorigenesis in the gastrointestinal epithelium. The importance of understanding the molecular biology of apoptotic pathways in cancer therapy and future directions are also addressed.

Pyrrolidinedithiocarbamate increases the therapeutic index of 5-fluorouracil in a mouse model

BACKGROUND & AIMS The thiol-containing antioxidant pyrrolidinedithiocarbamate (PDTC) enhances the cytotoxic efficacy of 5-fluorouracil (5-FU) against human colorectal cancer cell lines in vitro and in vivo. This process appears to be mediated by a sustained increase in p21 expression, independent of p53 function, resulting in growth arrest and apoptosis. We determined whether PDTC augmented 5-FU intestinal toxicity in non-tumor-bearing mice. METHODS Apoptotic and mitotic indices were measured in the small and large intestine on a cell positional basis at intervals throughout the 72-hour period after administration of 5-FU (40 mg/kg) and PDTC (250 mg/kg). The proportion of crypts regenerating after 5-FU (600-1200 mg/kg) and PDTC (500 mg/kg) was also measured. RESULTS 5-FU therapy induces substantial apoptotic cell death with simultaneous inhibition of mitotic activity within the small and large intestinal epithelium. PDTC reduces 5-FU-induced apoptotic events in the colon by 49%, predominantly among clonogenic stem and transit cells while promoting the early recovery of mitotic activity. As a consequence, PDTC increased the proportion of regenerating colonic crypts after 5-FU therapy. PDTC did not, however, significantly modulate 5-FU toxicity in the small intestine. CONCLUSIONS PDTC does not augment the intestinal toxicity of 5-FU and actually protects the colonic mucosa. These results support further investigation of PDTC and related compounds as treatments for colorectal cancer.

Methylation profiling of rectal cancer identifies novel markers of early‐stage disease

Radical surgery is the de facto treatment for early rectal cancer. Conservative surgery with transanal endoscopic microsurgery can achieve high rates of cure but the histopathological measures of outcome used to select local treatment lack precision. Biomarkers associated with disease progression, particularly mesorectal nodal metastasis, are urgently required. The aim was to compare patterns of gene‐specific hypermethylation in radically excised rectal cancers with histopathological stage.

Biomarker-based treatment selection in early-stage rectal cancer to promote organ preservation

Total mesorectal excision (TME) remains commonplace for T1–2 rectal cancer owing to fear of undertreating a small proportion of patients with node‐positive disease. Molecular stratification may predict cancer progression. It could be used to select patients for organ‐preserving surgery if specific biomarkers were validated.

Multicentre study of short-course radiotherapy and transanal endoscopic microsurgery for early rectal cancer.

Organ‐preserving treatment for early‐stage rectal cancer may avoid the substantial perioperative morbidity and functional sequelae associated with total mesorectal excision (TME). The initial results of an organ‐preserving approach using preoperative short‐course radiotherapy (SCRT) and transanal endoscopic microsurgery (TEMS) are presented.

Endorectal ultrasonography, strain elastography and MRI differentiation of rectal adenomas and adenocarcinomas.

Strain elastography is a method for recording tissue hardness. Strain in different areas may be compared using strain ratio (SR). The aims of this study were to validate a previously proposed SR cut‐off value of 1.25 for differentiating adenocarcinomas from adenomas and to compare the performance of endorectal ultrasonography (ERUS), strain elastography and MRI in the same patients.

Combined endorectal ultrasonography and strain elastography for the staging of early rectal cancer

AIM Strain elastography is a novel approach to rectal tumour evaluation. The primary aim of this study was to correlate elastography to pT stages of rectal tumours and to assess the ability of the method to differentiate rectal adenomas (pT0) from early rectal cancer (pT1-2). Secondary aims were to compare elastography with endorectal ultrasonography (ERUS) and to propose a combined strain elastography and ERUS staging algorithm. METHOD In all, 120 consecutive patients with a suspected rectal tumour were examined in this staging study. Patients receiving surgery without neoadjuvant radiotherapy were included (n = 59). All patients were examined with ERUS and elastography. Treatment decisions were made by multidisciplinary team (MDT) assessment, without considering the strain elastography examination. RESULTS Histopathology identified 21 adenomas, 13 pT1, 9 pT2, 15 pT3 and one pT4. Mean elastography strain ratios were predictive of T stage (P = 0.01). Differentiation of adenomas from early rectal cancer (pT1-2) had sensitivity, specificity and accuracy of 0.82, 0.86 and 0.84 for elastography and 0.82, 0.62 and 0.72 for ERUS. A combined staging algorithm was developed to identify tumours eligible for local resection. Based on MDT evaluation 32% of tumours later identified as pT0 or pT1 were treated with total mesorectal excision, even though a local excision might have sufficed. Combined ERUS and elastography evaluation would have significantly reduced this number to 9% (P = 0.008). CONCLUSION Elastography may improve the staging of adenomas and early rectal cancer compared with ERUS alone. Combined ERUS and elastography assessment is likely to further improve the selection of patients for local resection.