Colon and rectal complications after heart and lung transplantation.

BACKGROUND: Gastrointestinal complications of solid organ transplantation have been well described, but little attention has been paid to colorectal disorders in particular. The purpose of this study was to identify the incidence and severity of colorectal complications among a large cohort of heart and lung transplant recipients. STUDY DESIGN: We reviewed the medical records of heart, lung, and heart-lung transplant recipients at a single institution between 1978 and 2004. Complications were identified based on need for consultation, endoscopy, or operation by a colorectal surgeon after transplantation. RESULTS: Of 1,012 patients who received transplantations (530 heart, 435 lung, 47 heart-lung), 56 patients (6%) required evaluation for 84 colorectal problems. Incidence of complications was 7% in lung transplant recipients, 6% in heart-lung transplant recipients, and 4% in heart transplant recipients. Forty-four events (52%) were considered major (diverticulitis, perforation, malignancy, and other) and 40 (48%) were minor (polyps, pseudo-obstruction treated medically or endoscopically, benign anorectal disease, and other). Twenty-three (27%) required colectomy and 9 (10%) necessitated anal operation. Thirty-six (43%) required less-invasive interventions (endoscopy, minor anorectal procedures, and other). Eighteen (21%) were treated with medical therapy alone. Six patients died from colorectal disease (7%). CONCLUSIONS: Colorectal complications are a considerable source of morbidity and mortality after heart and lung transplantation. These complications occur more frequently in patients who undergo lung and heart-lung transplantation as compared with heart transplantation alone.

An unusual rectosigmoid mass: endometrioid adenocarcinoma arising in colonic endometriosis: case report and literature review.

Malignant transformation is an infrequent complication of endometriosis. The ovary is the primary site in 79 per cent of cases, and extragonadal sites are identified in 21 per cent. Primary involvement of these types of tumors with the colon and/or rectum is a rare clinical entity. Endometrioid carcinoma is a common histologic type that remains a diagnostic challenge-the main differential diagnosis includes colorectal carcinomas. We report a case of malignant transformation arising in colonic endometriosis. The patient had a total abdominal hysterectomy and bilateral salpingo-oophorectomy 10 years before she presented with hematochezia. The patient was ultimately treated by surgical resection. Immunohistochemical staining in addition to the usual histopathology was critical for accurate diagnosis of this endometriosis-associated intestinal tumor.

Primary perineal wound closure after preoperative radiotherapy and abdominoperineal resection has a high incidence of wound failure.

PURPOSE: Neoadjuvant radiation therapy has been used increasingly to downstage rectal cancer and decrease local recurrence. Despite its efficacy, preoperative radiation therapy may inhibit healing and contribute to wound complications. This study was designed to evaluate perineal wound complications after abdominoperineal resection. METHODS: The clinical records of a consecutive series of patients who underwent abdominoperineal resection for rectal carcinoma between 1988 and 2002 were reviewed. Demographic data, disease stage, and use of preoperative radiation therapy were recorded. Major wound complications included delayed wound healing (>1 month), wound infection requiring drainage/debridement, or reoperation. RESULTS: A total of 160 patients underwent abdominoperineal resection with primary closure of the perineal wound (mean age, 63 +/- 12 years); 117 (73 percent) patients received preoperative radiation therapy; 114 received radiation therapy for rectal cancer (radiation therapy + chemotherapy = 107, radiation therapy alone = 7); 3 received radiation therapy for other pelvic malignancies. Median radiation dose was 5,040 (range, 900-5,400) cGY. Overall wound complication rate was 41 percent. Major wound complication rate was 35 percent. Delayed healing was the most common complication (24 percent), followed by infection (10 percent). Radiation therapy increased the risk of any wound complication (47 vs. 23 percent; P = 0.005), risk of a major wound complication (41 vs. 19 percent; P = 0.021), and risk of infection (14 vs. 0 percent; P = 0.015). Risk of wound complications did not correlate with age, gender, disease stage, smoking, or diabetes. CONCLUSIONS: Wound complications are frequent after abdominoperineal resection and primary closure of the perineum. Preoperative radiation therapy doubles the rate of total and major perineal wound complications. Alternatives to primary perineal closure should be considered, particularly after radiation therapy.

Expression of the high-affinity selectin glycan ligand C2-O-sLeX by colon carcinoma cells.

The selectin family of adhesion proteins directs leukocytes in the blood to lymphoid organs and sites of inflammation, and is also thought to be involved in the dissemination of carcinomas expressing sialylated Lewis glycan structures, such as sialyl-Lewis X (sLeX). The expression of core 2 beta1,6 N-acetylglucosaminyltransferase (C2GnT) by leukocytes allows for the biosynthesis of core 2 O-glycans that when terminated by sLeX can serve as high-affinity selectin glycan ligands. In particular, the sLeX-modified core 2 O-glycan structure C2-O-sLeX has been directly demonstrated to confer significantly higher affinity selectin binding than sLeX. We have recently described the reactivity of the mAb CHO-131, which is dependent on the enzymes alpha2,3-sialyltransferase, alpha1,3-fucosyltransferase, and C2GnT, and specifically recognizes the glycan structure C2-O-sLeX. Here we examined a defined pair of colon carcinoma cell lines that are distinct in their capacity to bind E-selectin, as demonstrated by shear flow assays involving whole blood and shear stresses that occur in the microvasculature. CHO-131 demonstrated reactivity with such cancer cells, but only with the cell line that avidly attached to E-selectin. Hence, we demonstrate for the first time the detection of C2-O-sLeX on colon carcinoma cells, which, as with leukocytes, may be directly relevant to the expression of high affinity glycan ligands for the selectins.

Hyaluronan mediates adhesion of metastatic colon carcinoma cells.

BACKGROUND: Hyaluronan (HA) is a cell-surface glycosaminoglycan that has been implicated in cancer progression. Cells isolated from metastatic colon carcinoma (SW620) produce greater amounts of pericellular HA than cells isolated from a primary tumor (SW480). Inhibition of hyaluronan synthases (HAS) by transfection with antisense cDNA decreases HA production. Because adhesion to the extracellular matrix (ECM) is required for invasion and metastasis, we hypothesized that pericellular HA mediates adhesion to ECM proteins such as laminin, collagen, and fibronectin and that inhibition of HA production or removal of HA by digestion with hyaluronidase would impair adhesion. MATERIALS AND METHODS: SW480, SW620, and antisense transfectants (SW620 cells transfected with vector alone, antisense HAS2, antisense HAS3, and both antisense HAS2 and HAS3) were assessed for adhesion to laminin, Type 1 collagen, or fibronectin-coated plates. To confirm that adhesion was mediated by HA, cells were treated with or without hyaluronidase prior to the assays. RESULTS: Metastatic SW620 cells adhered well to laminin; SW480 cells demonstrated 46% less adhesion (P < 0.05; Student's t test). SW620 cell adhesion to Type 1 collagen and fibronectin was >50% less than adhesion to laminin. Inhibition of HAS2 and/or HAS3 or pretreatment with hyaluronidase significantly decreased adhesion of SW620 cells to laminin (P < 0.05), suggesting that adhesion was dependent upon pericellular HA. CONCLUSIONS: Metastatic SW620 cells that produce large amounts of pericellular HA adhered well to laminin. Inhibition of HAS2 and/or HAS3 expression, or hyaluronidase digestion of pericellular HA significantly inhibited adhesion. These data suggest that HA promotes adhesion to laminin and may thereby facilitate invasion of the basement membrane and metastasis in colon carcinoma.

Hyaluronan facilitates invasion of colon carcinoma cells in vitro via interaction with CD44.

Hyaluronan (HA) and its biosynthetic enzymes, HA synthases (HAS1, 2, and 3) are thought to participate in cancer progression. We have shown previously that HA production and HAS3 expression are increased in metastatic colon carcinoma cells (SW620) when compared with cells isolated from a primary tumor (SW480). Because invasion of the extracellular matrix is a fundamental event in tumor growth and metastasis, we hypothesized that SW620 cells would show greater invasive capability than SW480 cells, that invasion is HA dependent, and that HA mediates invasion via interaction with a cell-surface receptor. Invasion into artificial basement membrane (Matrigel) was assessed in vitro. To assess HA functionality, HAS expression was inhibited in SW620 cells by transfection with antisense HAS constructs. Decreased HA secretion and retention in the transfectants were confirmed using competitive binding and particle exclusion assays. SW620 cells demonstrated greater invasion through Matrigel than did SW480 cells. Antisense transfection decreased Matrigel invasion by SW620 cells by >60%; addition of exogenous HA restored invasion. Because the cell-surface HA receptor CD44 has been implicated in cancer progression, HA-CD44 interaction was then inhibited by incubation with an anti-CD44 antibody. Anti-CD44 antibody impaired invasion into Matrigel by 95%. Taken together, these data suggest that pericellular HA is critical for colon carcinoma cell invasion and that this invasive capability is dependent on interaction with CD44.

Hyaluronan synthase-3 is upregulated in metastatic colon carcinoma cells and manipulation of expression alters matrix retention and cellular growth.

HA is a glycosaminoglycan that is synthesized on the inner surface of the plasma membrane and secreted into the pericellular matrix. HA and its biosynthetic enzymes (HAS1, HAS2 and HAS3) are thought to participate in tumor growth and cancer progression. In our study, colon carcinoma cells isolated from a lymph node metastasis (SW620) produced more pericellular HA and expressed higher levels of HAS3 mRNA compared to cells isolated from a primary colon carcinoma (SW480). To assess functionality, HAS3 expression in SW620 cells was inhibited by transfection with an asHAS3 construct. Decreased HA secretion and cell-surface retention by asHAS3 transfectants were confirmed using competitive binding and particle exclusion assays. Anchorage-independent growth, a correlate of tumor growth in vivo, was assessed by colony formation in soft agar. SW620 cells stably transfected with asHAS3 demonstrated significant growth inhibition, as evidenced by fewer colonies and smaller colony area than either SW620 cells or cells transfected with vector alone. Addition of exogenous HA restored growth in asHAS3 transfectants. Thus, we demonstrate that pericellular HA secretion and retention and HAS3 expression are increased in metastatic colon carcinoma cells relative to cells derived from a primary tumor. Inhibition of HAS3 expression in these cells decreased the pericellular HA matrix and inhibited anchorage-independent growth. These data suggest that HA and HAS3 function in the growth and progression of colon carcinoma.

Quality of life after subtotal colectomy for slow-transit constipation: both quality and quantity count.

PURPOSE: Subtotal colectomy reliably increases bowel-movement frequency in patients with slow-transit constipation, but its impact on quality of life is unknown. The purpose of this study was to assess the relationship between functional outcomes and quality of life after subtotal colectomy for slow-transit constipation. METHODS: We reviewed the charts and operative reports of all patients who underwent subtotal colectomy for slow-transit constipation from January 1992 to June 2001. We sent them a 54-question survey that inquired about bowel function and included a modified 36-item gastrointestinal quality-of-life index. Using Pearson's R, we correlated gastrointestinal quality-of-life index scores with specific functional outcomes. RESULTS: Of 112 patients (109 females), 28 had been lost to follow-up and 2 had died. In all, 75 surveys (67 percent) were returned. Most of these 75 patients (81 percent) were at least somewhat pleased with their bowel-movement frequency, but 41 percent cited abdominal pain; 21 percent, incontinence; and 46 percent, diarrhea at least some of the time. The overall mean gastrointestinal quality-of-life index score was 103 +/- 22 of a maximum possible score of 144 (mean score for healthy controls, 126 +/- 13). We found no correlation between frequency of bowel movements and gastrointestinal quality-of-life index score (R = -0.03). Abdominal pain, diarrhea, and incontinence each had a statistically significant negative impact on gastrointestinal quality-of-life index scores (P = 0.01). Patients who required permanent ileostomy had low gastrointestinal quality-of-life index scores (68 +/- 24). The vast majority (93 percent) of patients stated they would undergo subtotal colectomy again if given a second chance. CONCLUSION: Subtotal colectomy for slow-transit constipation increases bowel-movement frequency; however, the persistence of abdominal pain and the development of postoperative incontinence or diarrhea adversely affect quality of life. Although most patients in the present study were satisfied with their results, quality-of-life scores should be used to assess postoperative outcome.

Surgical therapy for anorectal melanoma.

BACKGROUND: Anorectal melanoma is a rare but highly lethal malignancy. Historically, radical resection was considered the "gold standard" for treatment of potentially curable anorectal melanoma. The dismal prognosis of this disease has prompted us to recommend wide local excision as the initial therapeutic approach. The purpose of this study was to review our results in patients who underwent wide local excision or radical surgery (abdominoperineal resection [APR]) for localized anorectal melanoma. STUDY DESIGN: We reviewed the charts of all patients referred for resection of anorectal melanoma between 1988 and 2002. Endpoints included overall survival, disease-free survival, and local, regional, or systemic recurrence. RESULTS: Fifteen patients underwent curative-intent surgery; four underwent APR and 11 underwent wide local excision. Eight patients (53%) are alive; 7 (47%) are disease-free (followup 6 months to 13 years). Of 12 patients who have been followed for more than 2 years, 4 are alive (33%) and 3 are disease-free (25%). Seven patients have been followed for more than 5 years and two are alive and disease-free (29%). All of the longterm survivors underwent local excision as the initial operation. There were no differences in local recurrence, systemic recurrence, disease-free survival, or overall survival between the APR group and the local excision group. Local recurrence occurred in 50% of the APR group and 18% of the local excision group; regional recurrence occurred in 25% versus 27%. Distant metastases were common (75% versus 36%). CONCLUSION: In patients who have undergone resection with curative intent for anorectal melanoma, most recurrences occur systemically regardless of the initial surgical procedure. Local resection does not increase the risk of local or regional recurrence. APR offers no survival advantage over local excision. We advocate wide local excision as primary therapy for anorectal melanoma when technically feasible.

Fetal wound healing: current biology.

The early-gestation fetus heals dermal wounds rapidly and scarlessly. This phenomenon appears to be intrinsic to fetal skin and independent of the intrauterine environment. Unique properties of fetal cells, extracellular matrix, cytokine profile, and gene expression contribute to scarless repair. An intensive research effort has focused on unraveling the mechanisms that underlie scarless fetal wound healing in an attempt to improve the quality of healing in both children and adults.

Is ileoanal pouch function stable with time? Results of a prospective audit.

PURPOSE: Good continence is reported after ileal pouch-anal reconstruction, but little is known about long-term durability. Our aim was to prospectively evaluate long-term function in these patients. METHODS: Surveys were sent to 235 patients who had returned similar surveys in 1992; paired data were then compared with contingency tables. RESULTS: A total of 154 patients (66 percent) returned surveys. Mean age was 47 (range, 25-72) years. Median follow-up was 12 (range, 8-19) years. Sixty-eight patients (44 percent) were female. There were 5 deaths, and 11 patients had pouches removed or were given a defunctioning ileostomy. Bowel movement frequency did not change from 1992 to 2000 (24-hour frequency = 7 in 1992 vs. 7.1 in 2000; night frequency = 2 vs. 1.4; P = NS). Compared with 1992 data, major day incontinence was worse in 18 percent of patients, improved in 1 percent, and unchanged in 81 percent. Minor day incontinence was worse in 32 percent, improved in 9 percent, and unchanged in 59 percent. Major nighttime incontinence was worse in 22 percent, improved in 6 percent, and unchanged in 72 percent of patients, whereas minor night incontinence was worse in 24 percent, improved in 22 percent, and unchanged in 54 percent. Change in continence was unrelated to gender, age, or age at operation but was related to duration of follow-up. Twenty-seven percent of patients 12 or more years after surgery reported worsened major daytime incontinence vs. 9 percent of patients who were <12 years after surgery (P < 0.05); 33 percent reported more major night-time incontinence (vs. 10 percent; P < 0.05). Minor incontinence also worsened after 12 years. Minor daytime incontinence was seen in 48 percent of patients followed up > 12 years vs. 16 percent of those followed up <12 years (P < 0.05); minor nighttime incontinence was 28 vs. 19 percent, respectively. CONCLUSION: Most patients have stable pouch function over time. However, a small number improve and a larger number suffer measurable deterioration, particularly 12 or more years after surgery.