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Sphincter-saving procedures for distal carcinoma of the rectum.

Methods of sphincter preservation were developed more than a century ago. Combining these techniques with adequate anterior resection has permitted the resurrection of sphincter-saving procedures that are currently being applied in the therapy of cancer at every level of the rectum. Although Miles' abdominoperineal resection still remains the "gold standard" for the treatment of low rectal neoplasms, restorative resection may now be possible with equivalent oncologic disease control and survival. Further, current trends also suggest that the abdominoperineal resection is being used less frequently in the treatment of most rectal cancers and is being replaced with sphincter-preserving techniques that afford excellent functional results. In this review, the pertinent anorectal anatomy, current issues, and sphincter-saving surgical techniques presently available for the treatment of distal cancers of the rectum are presented.

Anal Canal↗

Activity and cellular origin of gelatinases in patients with colon and rectal carcinoma differential activity of matrix metalloproteinase-9.

BACKGROUND: Expression and enzymatic activity of gelatinases were examined in biopsy specimens from patients with colon and rectal neoplasms. The objective of this study was to determine whether the activity of these enzymes is altered between tumor areas compared with areas of noninvolved, normal mucosa and between colon and rectal carcinoma. METHODS: Matrix metalloproteinase (MMP) production was analyzed by Western immunoblot analysis and gelatin zymography. mRNA was determined by quantitative, real-time polymerase chain reaction analysis. RESULTS: Patients with colon carcinoma (n = 20 patients) showed a significant increase in levels of MMP-9 (92 kDa and 88 kDa) and MMP-2 (72 kDa and 62 kDa) in tumor areas compared with noninvolved regions. In contrast, patients with rectal carcinoma (n = 10 patients) had revealed the same high activity of MMP-9 in tumor regions and corresponding healthy tissue. Confirming activity measurements, in colon tumors, but not in rectal tumors, there was significant up-regulation of MMP-9 transcription compared with healthy tissue in the same patients. There were no significant changes in the tissue inhibitor of metalloproteinase-1 protein when colon and rectal tumor tissues were compared with the corresponding noninvolved regions. Cell culture experiments revealed fibroblasts as the cellular origin of MMPs. The findings showed that the secretion and activation of gelatinases depend on soluble factors secreted by tumor cells and are influenced by extracellular matrix components. CONCLUSIONS: This is the first report showing differences in MMP-9 activity between rectal carcinoma and colon carcinoma. Previous results indicating an active involvement of stromal cells in the generation of MMPs during tumor invasion are extended. Because the abundance of gelatinases increases in colorectal carcinoma, inhibitors of these proteases may be of therapeutic value.

Blotting, Western↗

Local recurrence after transanal endoscopic microsurgery for rectal polyps and early cancers.

BACKGROUND: Transanal endoscopic microsurgery (TEM) allows for local excision of rectal neoplasms with greater exposure than transanal excision and less morbidity than transabdominal approaches. This study examines the implications of the procedure with respect to predictors of recurrence. METHODS: We performed a retrospective analysis of 144 consecutive TEMs from 1993 to 2004. RESULTS: The study comprises 107 patients presenting for TEM with benign disease and 32 patients with cancer. Patients had a mean age of 64+/-14 (SD) years. TEM was performed for recurrent lesions in 17% of cases. Pathologic classification of the lesions after TEM was benign adenoma in 45%, adenoma with high-grade dysplasia (HGD) in 17%, cancer in 33%, and other in 4%. Complications occurred in 10%, and local recurrence occurred in 15% of patients. Median follow-up was 44 months, with a median time to recurrence of 14 months. Positive margins did not influence lesion recurrence. Recurrence of cancers correlated with the depth of tumor invasion (P<.05). On multivariate analysis, independent predictors of recurrence were lesion size and the presence of HGD within adenomas (P<.05). Five-year neoplastic recurrence probabilities were 11% for benign adenomas, 35% for adenomas with HGD, and 20% for cancers (P=.31); invasive recurrence probabilities were 0% for benign adenomas, 15% for adenomas with HGD, and 13% for cancers (P<.05). CONCLUSIONS: Close endoscopic follow-up is warranted after TEM for both benign and malignant disease, with special attention to lesions with HGD. TEM can be performed safely for early rectal cancer with careful patient selection.

Adenocarcinoma↗

Transanal endoscopic microsurgery: risk factors for local recurrence of benign rectal adenomas.

OBJECTIVE: Transanal endoscopic microsurgery (TEM) is a minimally invasive technique for excision of selected benign and malignant rectal neoplasms. It is considered a safe and effective treatment but recurrence rates of 1-13% are reported for benign lesions. The aim of this study was to assess risk factors for local recurrence of benign rectal lesions and to evaluate mortality and morbidity following TEM. METHOD: Data were prospectively collected from all patients undergoing TEM for benign adenomas from January 1998 to March 2005. The procedure was performed by a single surgeon and patients were regularly followed up. RESULTS: One hundred and forty-six procedures were included, with a median patient age of 74 years (range 22-92 years). The mean lesion area was 16 cm(2) (range 0.3-150 cm(2)) and the median distance from the dentate line was 9 cm (range 0-17 cm). Immediate complications included bleeding (six) and acute urinary retention (six). There has been one (0.68%) procedure-related death. After a median follow up of 39 months (range 4-89 months) there have been seven recurrences (4.8%), recurring at a mean time of 23.3 months (range 5-48 months). Only microscopic involvement of the circumferential resection margin was found to be significantly associated with recurrence (P = 0.0059). Recurrence was not associated with age, size of lesion, previous treatment, severity of dysplasia or use of the harmonic scalpel. CONCLUSION: TEM is a safe and effective treatment for benign rectal adenomas. Circumferential resection margin involvement is associated with recurrence, which tends to occur late. Therefore extended follow up is recommended.

Adenoma↗

[Synchronous colorectal and renal tumors: two case reports].

The simultaneous presence of more than one primary malignant tumour in the same patient is a relatively rare event, with values going from 2.7% to 6.8%. In this paper two synchronous colorectal-renal cases surgically treated are described; in the first case with only one resolutive operation for the two tumours, in the second with two consecutive operations. In both cases, the patients had no familiarity for colorectal or renal malignant tumours. Both cases have paradigmatic peculiarities: in the first the discovery of the renal neoplasm has been possible in election during the normal execution of the diagnostic protocol for sigmoido-rectal neoplasm. The second case shows the other possible modality of the outset of the two tumours: the occlusive urgency which never allows to discover immediately the renal tumour (unless a laparotomic exploration makes it perceptible).

Adult↗

[Sialomucins in the follow-up of patients surgically treated for colorectal cancer: preliminary results of a prospective study].

Preliminary results of a prospective study on sialomucin content found either at resection margins of colo-rectal cancer after curative surgery or in endoscopic biopsy specimens of colonic mucosa in thirteen patients selected for the follow up are reported. Though not statistically significant because of the small number of cases enrolled, preliminary data indicate that clinical application of differential mucin staining in colo-rectal neoplasms is potentially useful to predict subgroups of patients at risk for local recurrence as well as metachronous colo-rectal cancers.

Adult↗

Transanal endoscopic microsurgery--impact on the practice of a colorectal surgeon in a district general hospital.

INTRODUCTION: The objective was to assess the impact on the management of colorectal patients treated in a district general hospital within the first year after the introduction of transanal endoscopic microsurgery (TEM). PATIENTS AND METHODS: Data were collected for consecutive unselected patients who underwent TEM. Comparative data were derived from a matched group of patients who underwent anterior resection, peranal procedures (PAR) or transanal resection (TAR) in this unit. RESULTS: Twenty-two patients underwent TEM (11 men and 11 women; aged, 29-87 years; median, 75 years). Eighteen patients had a pre-operative diagnosis of benign rectal neoplasms; three were found to have invasive carcinoma, which might have been missed during TAR. Four patients had a pre-operative diagnosis of rectal cancer and TEM provided local tumour control in three cases. The operating time ranged between 20-150 min (mean, 65 min; median, 57 min). Hospital stay ranged between 0-10 days (mean, 3.7 days; median, 3 days), with a total of 97 in-patient days for the entire group of patients. Twenty-four operations were performed (22 TEM and two salvage anterior resections), with an estimated cost of 1544 pounds sterling for consumables used. Alternative treatments in the absence of TEM were considered to involve 10 anterior resections, 5 closures of ileostomy, 30 TAR procedures and one PAR procedure, with an estimated 306 days of in-patient admission, 46 operations and 6245 pounds sterling spent on consumables. CONCLUSIONS: Availability of TEM allows more efficient treatment for a significant number of patients with rectal tumours. The cost of the equipment is offset by a significant decrease in the length of in-patient admissions.

Adenocarcinoma↗

Proliferative patterns of rectal mucosa as predictors of advanced colonic neoplasms in routinely processed rectal biopsies.

OBJECTIVES: We sought to determine whether the evaluation of rectal cell proliferation in routinely processed rectal biopsies of apparently normal mucosa can predict the presence of advanced colonic neoplasms. METHODS: Fifty consecutive patients, who did not meet any of the following exclusion criteria, underwent total colonoscopy. Patients with nonadvanced adenomas, inflammatory bowel disease, hereditary predisposition to colonic cancer, or a history of colonic neoplasms were excluded. Patients with neoplasms in the distal 40 cm of the large bowel were also excluded. An adenoma was considered advanced if it had a diameter > 1 cm, or villous or severe dysplasia histology were present. In 26 of the 50 patients (Group A: 16 men, 10 women; mean age, 65 yr) advanced colonic neoplasms (advanced adenomas or cancer) were detected; in the remaining 24 (Group B: 13 men, 11 women; mean age, 66 yr) the large bowel was free of neoplasms. In all patients the proliferative patterns of apparently normal rectal mucosa were evaluated using the monoclonal antibody MIB-1 to assess the expression of Ki-67 antigen in routinely processed tissues. Proliferation index for the entire crypt, as well as proliferation indices for each of the five equal compartments, into which the crypt had been divided longitudinally, were calculated for each patient. RESULTS: The mean proliferation indices were similar between the two groups compared. The mean proliferation index for the upper crypt compartments (4 + 5) in the Group A patients was significantly higher than for those of the Group B patients (p < 0.01). Multivariate stepwise logistic regression analysis revealed that among gender, age, and proliferative parameters, the pattern of cell proliferation in the upper rectal crypt (4 + 5) compartment was the only predictor of advanced colonic neoplasms (beta = 11.01, p < 0.001). CONCLUSIONS: Our data suggest that the evaluation of the upward expansion of the rectal crypt proliferative zone in routinely processed rectal biopsies of apparently normal mucosa appears to predict the presence of advanced colonic neoplasms. These preliminary results should be confirmed in larger studies.

Adenoma↗

[Use of compression anastomosis devices in digestive surgery].

In this summary the authors report their experience of the clinical utilization in digestive surgery of a new compression anastomosis device consisting of a biofragmentable ring (BAR-Valtrac). From January 1993 through August 1994 26 patients underwent operations with Valtrac application: 22 for malignant colo-rectal neoplasms, 3 for diverticular disease and 1 for Crohn disease. The authors have performed 8 ileo-colic, 16 colo-colic and 2 colo-rectal anastomoses. There was no perioperatively mortality. Valtrac was discharged post-operatively between XVI and XXVIII days. There were no anastomotic leakage, bleeding or obstruction. Six months postoperatively an endoscopic control carried out in the 50% of the patients showed no anastomotic stenoses. These results, in association with those ones reported by the literature, confirm that anastomoses performed with Valtrac are safe, reliable and allow the same of better results than stapled anastomoses.

Adult↗

An unusual hamartomatous malformation of the rectosigmoid presenting as an irreducible rectal prolapse and necessitating rectosigmoid resection in a 14-week-old infant.

A 14-week-old female infant presented with an irreducible rectal prolapse and a large polypoid tumor at the tip of the prolapsed mucosa. The tumor and prolapsed rectum were resected. Four weeks after the operation, profuse rectal bleeding occurred and a second similar tumor was diagnosed by endoscopy in the sigmoid colon. Laparotomy, rectosigmoid resection, and endorectal pull-through were performed. At operation, the serosal surface showed ragged polypoid lesions and an abnormal angiomatous vascularization. The postoperative course was uneventful. The histology suggested a congenital mucosal malformation. This pathology is unique in our experience and we have been unable to find anything resembling it in the literature. At age two years a Sertoli cell tumor developed in the girl with pubertas precox and a recurrent colonic polyp of the Peutz-Jeghers type.

Colon, Sigmoid↗

Histologic parameters and DNA ploidy as predictors of survival in stage B adenocarcinoma of colon and rectum.

Stage B adenocarcinomas of colon (61 carcinomas) and rectum (44 carcinomas) were retrospectively reviewed in order to define prognostic indicators and to determine if they are different for tumors arising at the two sites. Parameters evaluated included the substage of the tumor, histologic grade, presence of vascular/lymphatic invasion, residual adenoma or extracellular mucin, and tumor cell DNA content as determined by flow cytometry of paraffin-embedded tissues. Five-year survival was 81.0% for patients with colonic and 87.5% for those with rectal tumors. DNA ploidy was a significant predictor of overall and disease-free survival in patients with rectal adenocarcinomas (improved survival for those with diploid tumors) but not in those with colonic tumors and not in the two groups combined. The degree of differentiation of the tumor was prognostically significant in the colonic group and for the groups combined but not in the rectal group. There was a trend toward better survival in substage B1 tumors, as compared with substages B2 and B3, particularly in rectal neoplasms. Other histologic parameters did not predict survival. We conclude that the prognostic indicators in colonic adenocarcinoma seem to differ from those of adenocarcinoma arising in the rectum and that DNA ploidy has a significant impact upon outcome in stage B rectal adenocarcinomas.

Adenocarcinoma↗

Folate, DNA methylation and colo-rectal cancer.

Prospective cohort and case-control studies suggest an association between low folate intake and increased risk of colo-rectal adenoma and cancer. Some, but not all, animal studies indicate that folate supplementation protects against the development of colo-rectal neoplasms, although supraphysiological folate doses have been shown to enhance tumour growth. Folate is a methyl donor for nucleotide synthesis and biological methylation reactions, including DNA methylation. A low dietary folate intake may increase the risk of colo-rectal neoplasia by inducing genomic DNA hypomethylation, which can affect the expression of proto-oncogenes and tumour suppressor genes associated with the development of cancer. Common polymorphisms in genes involved in the methylation pathway, such as methylenetetrahydrofolate reductase and methionine synthase, have been shown to influence risk of colo-rectal neoplasia, with interactions dependent on folate status and/or alcohol intake, which is known to antagonise methyl group availability. There is some evidence to show that DNA from normal-appearing colo-rectal mucosa in individuals with colo-rectal cancer is hypomethylated. In a case-control study DNA methylation in normal-appearing colo-rectal mucosa has been shown to be lower in individuals with colo-rectal cancer (P = 0.08) and colo-rectal adenoma (P = 0.009) than in controls free of colo-rectal abnormalities. Human intervention trials to date suggest that supraphysiological doses of folate can reverse DNA hypomethylation in colo-rectal mucosa of individuals with colo-rectal neoplasia. In a double-blind randomised placebo-controlled study folate supplementation at physiological doses has been shown to increase DNA methylation in leucocytes (P = 0.05) and colonic mucosa (P = 0.09). Further studies are required to confirm these findings in larger populations and to define abnormal ranges of DNA methylation.

Adenoma↗

Sodium-glucose cotransporter-2 inhibitors and gastrointestinal neoplasm risk in type 2 diabetes: a systematic review and meta-analysis of randomized controlled trials.

The potential carcinogenic effects of sodium-glucose cotransporter 2 (SGLT2) inhibitors in patients with type 2 diabetes mellitus (T2DM) remain controversial, particularly regarding site-specific gastrointestinal (GI) neoplasms. This systematic review and meta-analysis aimed to determine the relationship between SGLT2 inhibitors and the risk of GI neoplasms in patients with T2DM. We searched PubMed, EMBASE, Cochrane CENTRAL, Scopus, and Web of Science through March 17, 2025, for RCTs in T2DM comparing SGLT2 inhibitors with placebo or active comparators. Two reviewers independently screened studies, extracted data, and assessed the risk of bias. The primary outcome was GI neoplasms reported in publications, supplementary materials, or trial registries, usually as adverse events rather than centrally adjudicated cancer endpoints. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated in Stata 17.0. In 48 RCTs (n&#x2009;=&#x2009;48,765), SGLT2 inhibitor therapy was not associated with overall GI neoplasm risk (OR&#x2009;=&#x2009;1.10, 95% CI: 0.84-1.44; p&#x2009;=&#x2009;0.46; I&#xb2; = 0%). Site-specific analyses showed no statistically significant association for esophageal (OR&#x2009;=&#x2009;1.12, 95% CI 0.37-3.45), gastric (1.20, 0.65-2.23), hepatic (0.62, 0.31-1.22), pancreatic (0.91, 0.51-1.64), colonic (1.28, 0.78-2.08), colorectal (0.76, 0.27-2.17), and rectal neoplasms (0.98, 0.49-1.97), with all p-values&#x2009;>&#x2009;0.05. Subgroup analyses by agents (e.g., canagliflozin, dapagliflozin, empagliflozin), baseline age, body mass index (BMI), HbA1c, treatment duration, and dose were also non-significant (all p&#x2009;>&#x2009;0.05). Approximately half of the trials had follow-up of one year or less, limiting our ability to evaluate long-term risk. Available RCT evidence does not show a clear increase in GI neoplasm risk with SGLT2 inhibitors in T2DM. However, limited follow-up, low event counts, and non-cancer-specific outcome ascertainment, the findings should be interpreted as reassuring but not definitive evidence of long-term oncologic safety.Systematic review registration: PROSPERO No. CRD42024619019.

Humans↗

Asymptomatic renal neoplasms in the rectal cancer patient.

Although cancers of the rectum and kidney are common malignancies the incidence of coexistent rectal and renal primary tumors is unclear. Our objective was to determine the true incidence of synchronous neoplasms of the rectum and kidney. The computed tumor registry database at the City of Hope National Medical Center was queried for patients with synchronous rectal cancer and renal neoplasms presenting between August 1990 and August 2000. During the 10-year period there were 182 patients presenting for treatment of rectal carcinoma. Of these seven (3.8%) were found to have an asymptomatic renal neoplasm. Four patients underwent synchronous resection. Three patients underwent staged renal and rectal resections. The pathology of the renal lesions included renal cell carcinoma in six and an oncocytoma in one patient. Rectal lesions were all adenocarcinomas and all were within 10 cm of the dentate line. Three patients required abdominoperineal resections and four were treated with low anterior resections. Two patients presented with hepatic metastasis at the time of diagnosis. Five patients remain free of disease. Two patients died of persistent and recurrent disease 6 months and 40 months after operation. With the exception of one patient who required prolonged intubation because of severe Parkinson's disease there were no major complications after simultaneous resection of both renal and rectal disease. Simultaneous asymptomatic renal neoplasms may be found in up to 3.8 per cent of patients with rectal cancer. Synchronous lesions may be treated simultaneously without significant morbidity.

Aged↗

Colo-rectal carcinoma 1975 and 1990: no improvement in the stage of disease at resection.

There is no overall consensus as to what screening patterns should be adopted for individuals of average risk for colo-rectal carcinoma. The single most important prognostic factor in survival is the stage of the colo-rectal neoplasm at the time of resection. Consequently significant resources have been directed to early detection while the disease is at a curative stage. To assess the impact of widespread availability of faecal occult blood testing and large bowel endoscopy we prospectively examined all large intestine specimens resected for carcinoma in 1990 and compared them with specimens resected for colonic carcinoma in 1975. We excluded adenomatous polyps with malignant change which had been treated by snaring at colonoscopy, without subsequent colectomy, as their precise Duke's staging was so difficult. In any event, their numbers were small (> 5 in 1990). Our study shows that despite the resources targeted at early diagnosis of colo-rectal carcinoma resection of tumours at a prognostically favourable stage has not been improved in the 25 years since 1975.

Adenocarcinoma↗

[A study of changes in distribution pattern of proliferating cells associated with progression of human colorectal benign and malignant tumor using PCNA immunohistochemistry].

We studied cell kinetics of colo-rectal neoplasms using PCNA (the auxiliary protein of DNA polymerase-delta) immunohistochemistry. We analyzed the distribution pattern of PCNA positive cells on normal colon mucosa, adenoma (6 cases) and cancer (early: 33 cases, advanced: 6 cases). PCNA positive index (PI) was calculated as the percentage of PCNA positive tumor cells in relation to the total number (about 1000) of the tumor cells. PCNA positive indices were 30% in normal colon mucosa, 49% in adenoma and 72% in cancer, respectively. There were statistically significant differences between three mean values (p < 0.01). In normal colon mucosa PCNA positive cells are localized at the lower part of mucosa, but, in adenoma, they are found at the more upper part of mucosa too. In cancer, PCNA positive cells were localized diffusely and their immunoreactivity is higher than those of the normal mucosa and adenoma. In conclusion, our results suggests that the ratio of PCNA positive cells almost equivalents to growth fraction, and is correlated with the histological grading of colo-rectal tumor, but not correlated with depth of carcinoma. It is presumed that carcinoma has a higher ratio of PCNA positive cells than adenoma, and therefore carcinoma has higher proliferating cell density than adenoma.

Adenoma↗