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Biomedical subjects

Pascal Gervaz

Publications and source records attributed to Pascal Gervaz.

At least 19 recordsLinked to original sources

Lymph node retrieval in abdominoperineal surgical specimen is radiation time-dependent.

BACKGROUND: A low yield of lymph nodes (LN) in abdominoperineal resection (APR) specimen has been associated with preoperative radiation therapy (XRT) in population-based studies, which may preclude adequate staging of anorectal carcinomas. We hypothesized that the number of LN retrieved in APR specimen was correlated with the dose and the timing of pelvic irradiation. PATIENTS AND METHODS: We performed a retrospective study of 102 patients who underwent APR in a single institution between 1980 and 2004. Pathological reports were reviewed and the number of lymph nodes retrieved in APR specimens was correlated with: 1) Preoperative radiation; 2) Dose of pelvic irradiation; and 3) Time interval between the end of XRT and surgery. RESULTS: There were 61 men and 41 women, with a median age of 66 (range 25-89) years. There were 12 patients operated for squamous cell carcinoma of the anal canal (SCCA) and 90 for rectal cancer. 83% and 46% of patients with anal and rectal cancer respectively underwent radical/neoadjuvant radiotherapy. The mean +/- SD number of LN in APR specimen was 9.2 +/- 5.9. The mean number of LN in APR specimen was significantly lower in patients who underwent preoperative XRT (8 +/- 5.5 vs. 10.5 +/- 6.1, Mann-Whitney U test, p = 0.02). The mean number of LN was not significantly different after XRT in patients with SCCA than in patients with rectal cancer (6.2 +/- 5.3 vs. 7.8 +/- 5.3, p = 0.33). Finally, there was an inverse correlation between the yield of LN and the time elapsed between XRT and surgery (linear regression coefficient r = -0.32, p = 0.03). CONCLUSION: Our data indicate that: 1) radiation therapy affects the yield of LN retrieval in APR specimen; 2) this impact is time-dependent. These findings have important implications with regard to anatomic-pathological staging of anal and rectal cancers and subsequent decision-making regarding adjuvant chemotherapy.

Journal Article↗

Influence of target gene mutations on survival, stage and histology in sporadic microsatellite unstable colon cancers.

High-frequency microsatellite unstable (MSI-H) colon tumors develop as a consequence of mutations at repetitive sequences in target genes. TGFBR2 and ACVR2, encoding TGFbeta superfamily receptors, and the proapoptotic gene BAX are frequent targets for frameshift mutation. We analyzed the effect of these mutations on survival and histology in 2 separate cohorts. Forty-eight MSI-H Dukes B2 colon tumors from a cohort of 172 patients had mutations in TGFBR2, BAX and ACVR2 correlated with patient survival. Further, 54 population-based MSI-H colon cancers of all stages from a cohort of 503 patients had mutations correlated with tumor stage, grade and size. Of 44 amplifiable MSI-H Dukes B2 tumors, 70% harbored TGFBR2, 63% BAX and only 4.5% ACVR2 mutations. While mutation alone did not influence survival, concomitant mutation of TGFBR2 and BAX was associated with an improved prognosis in Dukes B2 patients (p=0.05). ACVR2 mutations were more frequent in the second, population-based cohort (stage II: 32.5%, p<0.05). While no target gene mutation correlated with stage in this cohort, poor histological grade and large tumor volume were associated with mutant ACVR2, but not TGFBR2 or BAX mutations, and likely accounts for the lower prevalence of ACVR2 mutations in the first, well-differentiated Dukes B2 cohort. Because target gene mutations did not correlate with stage, they likely occur early in the pathogenesis of MSI-H cancers. Mutations in TGFBR2 and BAX may improve survival in MSI-H Dukes B2 patients, and mutations of ACVR2 may augment histological changes consistent with poor tumor grade that is characteristic of MSI-H colon cancers, and increase tumor size.

Activin Receptors, Type II↗

Outcome of surgery for rectal cancer in octogenarians.

INTRODUCTION: The aim of this study was to assess the outcome of surgery for rectal cancer in patients 80 years of age or more. METHODS: A retrospective study of 29 patients older than 80 years, who presented in our institution between 1997 and 2001 with the diagnosis of rectal adenocarcinoma, was undertaken. RESULTS: Median follow-up was 54 (range 27-78) months, and the median age of patients was 85 (range 80-94) years. Twenty-four out of 29 patients (83%) underwent surgery, 23 being operated electively. Twenty out of 24 patients (83%) underwent resection with curative intent, while four patients (17%) had a palliative procedure. Median hospital stay was 13 (range 10-35) days. Postoperative morbidity and mortality were 46% and 12.5%, respectively. However, when considering only elective procedures with curative intent, operative mortality was 5%. At the time of last follow-up, 13 patients were alive, five of them with no evidence of recurrent disease at 5 years, for an overall 2- and 5-year survival rate of 80% and 67%, respectively. Four out of the 7 deaths, which occurred after surgery, were due to medical causes unrelated to cancer. CONCLUSION: In our institution, two thirds of patients older than 80 years who presented with rectal cancer underwent surgery with curative intent. In this selected population, good results in terms of short-term survival can be achieved, at the price of an elevated postoperative morbidity. Whenever possible, treatment with curative intent should be considered in patients with rectal cancer, irrespective of the age.

Aged, 80 and over↗

Morphologic alterations associated with mechanical bowel preparation before elective colorectal surgery: a randomized trial.

PURPOSE: The feasibility and safety of left-sided colorectal procedures with avoidance of mechanical bowel preparation has recently been demonstrated. Moreover, mechanical preparation has been associated with an increased risk for abdominal septic complications, including anastomotic leakage. This study was designed to determine whether mechanical bowel preparation is associated with histologic alterations in the colon. METHODS: Fifty patients (mean age, 61 (range, 45-78) years) scheduled to undergo elective colorectal surgery were prospectively randomized to receive mechanical preparation (polyethylene glycol; Group 1) or no preparation (Group 2) preoperatively. A macroscopically healthy segment of the bowel was excised at the proximal margin of the colectomy piece. A pathologist, blinded to the patient's group allocation, assessed various morphologic parameters. RESULTS: Indications for colectomy (cancer and complicated diverticulosis) did not differ between groups. Bowel wall alterations were more frequent in patients who received a preparation. The most striking alterations associated with mechanical preparation were loss of superficial mucus (moderate-to-severe in 96 and 52 percent in Groups 1 and 2, respectively; P < 0.001) and epithelial cells (moderate-to-severe in 88 and 40 percent in Groups 1 and 2, respectively; P < 0.01). In addition, inflammatory changes, i.e., lymphocytes (severe in 48 and 12 percent in Groups 1 and 2, respectively; P < 0.02) and polymorphonuclear cells infiltration (severe in 52 and 8 percent in Groups 1 and 2, respectively; P < 0.02), were more prevalent after mechanical preparation. CONCLUSIONS: Mechanical bowel preparation is associated with structural alteration and inflammatory changes in the large bowel wall. Although bowel wall inflammation is a known risk factor for anastomotic leak, it remains to be elucidated whether these changes have a direct relation to the deleterious effect of mechanical bowel preparation in terms of abdominal morbidity.

Aged↗

The duration of postoperative ileus after elective colectomy is correlated to surgical specialization.

AIM: Postoperative ileus is an important factor of complications following gastrointestinal procedures. Its pathophysiology and the parameters, which may impact on its duration, remain unclear. The aim of this study was to measure the role of various clinical determinants on restoration of intestinal function after elective colorectal surgery. METHODS: From July 2002 to September 2003, all patients who underwent laparotomy for colectomy (laparoscopic resections excluded) with either an ileotransverse, colocolic, or high colorectal anastomosis were entered in this prospective study. The intervals in hours between the end of the surgical procedure and passing of flatus (PG) and passing of stool (PS) were recorded by an independent investigator. PG and PS were eventually correlated with the following parameters: type of colectomy, early removal of nasogastric tube (NGT), mechanical bowel preparation (MBP), type of underlying disease, systemic administration of opiates, and surgical training (colorectal fellowship or other). RESULTS: One hundred twenty-four patients were entered in this study. Four patients (3.2%) developed septic complications (3 anastomotic leaks and 1 intraabdominal abscess) and were excluded from the analysis. Median age in this population was 68 (range 30-95) years. Mean duration of postoperative ileus was 70+/-28 h (PG) and 99+/-34 h (PS). The type of colectomy, underlying disease, MBP, and early NGT removal failed, in univariate analysis, to correlate with the duration of postoperative ileus. By contrast, time intervals PG and PS were statistically shorter in the group of patients treated by a colorectal surgeon [56+/-23 vs 74+/-28 h (PG); 82+/-26 vs 103+/-35 h (PS), p=0.004], as well as in patients who received systemic opiates for less than 2 days [64+/-27 vs 75+/-28 h (PG), p=0.04; 88+/-32 vs 108+/-33 h (PS), p=001]. CONCLUSION: Restoration of normal intestinal function after elective open colectomy takes 3 (PG) to 4 (PS) days. In our series, specialized training in colorectal surgery has a positive impact on the duration of postoperative ileus. Surgical specialization should be considered an important parameter in future clinical trials aiming to minimize postoperative ileus.

Adult↗

Assessment of quality of life in patients with rectal cancer treated by preoperative radiotherapy: a longitudinal prospective study.

PURPOSE: To assess prospectively the quality of life (QOL) of patients treated by preoperative radiotherapy (RT) and surgery for locally advanced rectal cancer. METHODS AND MATERIALS: We studied 53 patients treated with bi-fractionated RT (50 Gy in 40 fractions within 4 weeks) followed at a median interval of 45 days by abdominoperineal resection in 11 patients and low anterior resection in 42 patients. Their QOL was assessed using two self-rating questionnaires developed by the European Organization for Research and Treatment of Cancer (EORTC): one was cancer specific (EORTC QLQ-C30) and one was site specific (EORTC QLQ-C38). The questionnaires were completed before RT and 12-16 months after RT, at which time 17 patients had undergone colostomy. We hypothesized that at least some scores of the various scales would vary between the two analyses. RESULTS: Compared with the pre-RT scores, at 1 year, patients reported statistically significant improvement in their emotional state (median 75 vs. 100, p <0.0001), perspective of the future (67 vs. 100, p = 0.0004), and their global QOL (75 vs. 83, p = 0.0008), as well as a decrease in GI symptoms (13 vs. 0, p = 0.002). However, the sexual dysfunction score increased significantly, particularly in men (17 vs. 83, p = 0.0045), and a trend toward a lower body image score was observed (100 vs. 89, p = 0.068). At 1 year, patients with colostomies reported similar or significantly improved symptom scores for fatigue, pain, GI problems, and sleep disturbance, but no such improvements were observed in patients without stomas. CONCLUSION: One year after combined treatment for locally advanced rectal cancer, patients exhibited statistically significant improvement in some important QOL outcomes, including global QOL, despite a decrease in sexual function and body image. Any additional improvement in QOL outcome may require refinements in the RT and surgical techniques to reduce late sequelae, particularly sexual dysfunction. Our results suggest that QOL considerations do not justify sphincter-conserving approaches if locoregional tumor control would be compromised.

Combined Modality Therapy↗

Surgical treatment of appendiceal adenocarcinoid (goblet cell carcinoid).

Adenocarcinoid of the appendix is an infrequent tumor with histologic features of both adenocarcinoma and carcinoid tumor. Although its malignant potential remains unclear, adenocarcinoids seem to be biologically more aggressive than conventional carcinoids. The aim of this study was to analyze long-term results of surgical treatment for appendiceal adenocarcinoid. A retrospective review (1991-2003) identified seven patients (median age 72, range 27-81 years) treated for appendiceal adenocarcinoid. The clinical data of these patients were reviewed. Follow-up was complete for all patients (median 60 months, range 24-108 months). Most cases presented with associated acute appendicitis (71%). First intention surgery consisted of appendectomy (m = 6) and right hemicolectomy (m = 1). In three patients, additional surgical procedures were performed (right colectomy). Indications for colectomy were tumor size (three cases) associated with appendectomy margin invasion in one case. One patient with lymph node and peritoneal involvement experienced recurrence 9 months after hemicolectomy and died of the disease at 2 years. One patient subsequently died of colon carcinoma 6 years after adenocarcinoid treatment. Five patients were alive without disease at the time of the last follow-up. Synchronous or metachronous colon carcinomas developed in three patients (43%). Our results suggest that appendectomy alone could be used for appendiceal adenocarcinoid provided that the tumor (1) is less than 1 cm; (2) does not extend beyond the appendix adventitia; (3) has less than 2 mitoses/10 high power fields; and (4) has surgical margins that are tumor free. Otherwise, carcinologic right colectomy seems to be indicated. The risk for developing colorectal adenocarcinoma seems to be extremely high in patients treated for appendiceal adenocarcinoid and warrants close follow-up with colonoscopic screening.

Adult↗

Proximal location of colon cancer is a risk factor for development of metachronous colorectal cancer: a population-based study.

PURPOSE: This study was undertaken to assess the incidence of 1) metachronous colorectal cancer and 2) subsequent extracolonic cancers, in relation to the location (proximal or distal to the splenic flexure) of the first primary colorectal tumor. METHODS: In this population-based study, a cancer registry database was used to identify patients diagnosed with colorectal adenocarcinoma between 1970 and 1999. Patients with familial adenomatous polyposis and those with hereditary nonpolyposis colorectal cancer syndrome were excluded from the study, as were patients with nonepithelial tumors. Location of the first tumor was established according to International Classification of Diseases-Oncology-02 classification. The registry covers a population of 500,000 residents. RESULTS: A total of 5,006 patients had sporadic adenocarcinoma of the colon or rectum during this period of time, with 1,703 first primary tumors (34 percent) being located proximal to the splenic flexure. One hundred twenty occurrences of second primary colorectal cancer were observed in this population (2.39 percent). The risk for developing a second incidence of primary colorectal cancer was higher in patients whose initial tumor was located in the proximal colon (3.4 percent vs. 1.8 percent; odds ratio, 1.92; 95 percent confidence interval, 1.33-2.77; P < 0.001). The risk for each segment of the large bowel was as follows: cecum, 3.4 percent; right colon, 3 percent; transverse colon, 3.8 percent; left colon, 2.8 percent; sigmoid colon, 1.7 percent; and rectum, 1.8 percent. By contrast, the risk for developing a second, extracolonic tumor did not differ between patients with proximal and distal tumors (13.7 percent vs. 13.4 percent, P = 0.73). CONCLUSION: Patients with a first tumor located within the proximal colon are at twice the risk for developing metachronous colorectal cancer. From an epidemiologic standpoint, these data are in accordance with 1) the increasing incidence and 2) the better prognosis of proximal colon cancer in various populations. Our results confirm that proximal colon cancer is a distinct entity, which justifies the reporting of cases of colon cancer according to their location proximal or distal to the splenic flexure.

Adenocarcinoma↗

Two colons-two cancers: paradigm shift and clinical implications.

Embryological and physiological data suggest that proximal (in relation to the splenic flexure) and distal parts of the colon represent distinct anatomical and functional entities. Since 1990, molecular biologists have identified two distinct pathways, microsatellite instability (MSI) and chromosomal instability (CIN), which are involved in the pathogenesis of colon cancer (CC). Thus, a new paradigm has emerged with the discovery that CC is a heterogeneous disease; furthermore recent data have demonstrated that these two distinct pathways in colorectal carcinogenesis are characterized by a different clinical outcome. The implications for the clinicians are twofold; (1) tumors originating from the proximal colon have a better prognosis due to a high percentage of MSI-positive lesions; and (2) location of the neoplasm in reference to the splenic flexure should be documented before group stratification in ongoing trials of adjuvant chemotherapy for CC. In the future, clinical decision-making regarding adjuvant chemotherapy might be stratified according to the MSI status of cancers located proximally to the splenic flexure.

Chemotherapy, Adjuvant↗

Differential expression of anti-apoptotic protein Bcl-2 in keratinizing versus non-keratinizing squamous cell carcinoma of the anus.

BACKGROUND: Histologically, tumors of the anal region are either keratinizing (K) or non-keratinizing (NK) squamous cell carcinomas (SCCA). We hypothesized that these two variants might represent, not only morphologically, but also biologically, dissimilar malignancies. The present study was undertaken to compare the expression of apoptosis-regulating proteins Bcl-2 and p53 in K versus NK SCCA. METHODS: We performed an immunohistochemical analysis on 98 pre-treatment biopsies of patients with anal canal cancers. Tissue sections were examined immunohistochemically for expression of proteins Bcl-2 (clone 124, DAKO, 1:100) and p53 (clone DO7, DAKO, 1:200). Expression of p53 and Bcl-2 was considered positive when >5% of tumor cells were stained. Tumor histology was correlated with protein expression as well as with other clinical variables. RESULTS: There were 64 NK and 34 K SCC. The proportion of Bcl-2 positive tumors was statistically higher in NK carcinomas (51.5 vs. 23.5%, p=0.009). In addition, women were more likely than men to present with NK carcinomas (71 vs. 45%, p=0.03) as well as with Bcl-2 positive tumors (47 vs. 29%, p=0.05). The more distal the tumor is (anal margin), the more frequently the keratinizing subtype is observed (87 vs. 23%, p=0.0002). By contrast, there was no correlation between p53 and tumor histology (p=0.83). CONCLUSIONS: Our data demonstrate that non-keratinizing and keratinizing SCCA differ in their Bcl-2 expression. In addition, significant differences were observed in the distribution of these two histological subtypes according to gender and tumor sublocation. These findings may indicate possible differences in the carcinogenesis process of these two histological subtypes.

Adult↗

Mechanical bowel preparation for elective colorectal surgery: a meta-analysis.

HYPOTHESIS: There is little scientific evidence to support the routine practice of mechanical bowel preparation (MBP) before elective colorectal surgery in order to minimize the risk of postoperative septic complications. DATA SOURCES: Trials were retrieved using a MEDLINE search followed by a manual search of the bibliographic information in select articles. Languages were restricted to English, French, Spanish, Italian, and German. There was no date restriction. STUDY SELECTION: Only prospective randomized clinical trials (RCTs) evaluating MBP vs no MBP before elective colorectal surgery were included. DATA EXTRACTION: Outcomes evaluated were anastomotic leakage, intra-abdominal infection, wound infection, reoperation, and general and extra-abdominal morbidity and mortality rates. Data were extracted by 2 independent observers. DATA SYNTHESIS: Seven RCTs were retrieved. The total number of patients in these RCTs was 1297 (642 who had received MBP and 655 who had not). Among all the RCTs reviewed, anastomotic leak was significantly more frequent in the MBP group, 5.6% (36/642), compared with the no-MBP group, 2.8% (18/655) (odds ratio, 1.84; P = .03). Intra-abdominal infection (3.7% for the MBP group vs 2.0% for the no-MBP group), wound infection (7.5% for the MBP group vs 5.5% for the no-MBP group), and reoperation (5.2% for the MBP group vs 2.2% for the no-MBP group) rates were nonstatistically significantly higher in the MBP group. General morbidity and mortality rates were slightly higher in the MBP group. CONCLUSIONS: There is no evidence to support the use of MBP in patients undergoing elective colorectal surgery. Available data tend to suggest that MBP could be harmful with respect to the incidence of anastomotic leak and does not reduce the incidence of septic complications.

Cathartics↗

Molecular biology of squamous cell carcinoma of the anus: a comparison of HIV-positive and HIV-negative patients.

The molecular mechanisms involved in progression of squamous cell carcinoma of the anus (SCCA) are poorly elucidated, as well as the potential role of HIV infection. Loss of heterozygosity (LOH) is one of the mechanisms responsible for inactivation of tumor suppressor genes. We hypothesized that HIV-induced immunosuppression may contribute to an alternate molecular pathway in SCCA progression, through persistence of human papillomavirus infection within the anal canal. This study was undertaken to compare the molecular biology of SCCA in HIV-positive (HIV+) and HIV-negative (HIV-) patients. We retrieved tumor specimens from 18 HIV- and 10 HIV+ patients diagnosed with SCCA in two institutions. DNA from tumor and normal tissues was extracted and then amplified by polymerase chain reaction. LOH was investigated at 14 loci: three at 18q (DCC), two at 13q (Rb), three at 17p (p53), three at 11q, one at 2p, and two at 5q (APC). LOH was defined by a tumor DNA-to-normal tissue DNA ratio of >2. HIV+ patients were younger (36 +/- 7 years versus 53 +/- 13 years, P=0.001) and showed a trend toward tumors of larger size (3.7 +/- 1.6 cm versus 2.6 +/- 1.5 cm, P=0.09). The median CD4+ count in HIV+ patients at the time of diagnosis was 74 x 10(6)/L (range, 5-900). The overall frequency of LOH was 17.3% (41 LOH of 236 informative loci). Tumors in HIV- patients were more likely to present LOH than were tumors in HIV+ patients (24.1% versus 6.6%, P=0.0004). Differences between the two groups with regard to allelic losses were also observed at specific loci, such as 18q (41% [HIV-] versus 0% [HIV+], P=0.05), 17p (43% versus 10%, P=0.09), and 5q (33% versus 0%, P=0.12). Consistent LOH on chromosomes 17p, 18q, 5q, and 11q were observed in HIV- patients with SCCA. By contrast, allelic losses at 17p, 5q, and 18q seem to be rare in tumors of HIV+ individuals. These data suggest that immunosuppression may promote SCCA progression through an alternate pathway and that persistence of HPV infection within the anal canal may play a central role in this process.

Adult↗

Chemotherapeutic options in the management of anal cancer.

During the past two decades, anal cancer has served as a paradigm for the successful application of chemoradiation to solid tumours; so far, it remains one of the few carcinomas of the gastrointestinal tract which are curable without the need for definitive surgery. Since the original contribution by Nigro in 1974, surprisingly few changes have been made to the standard of care in chemotherapy, which still consists of a combination of 5-fluorouracil and mitomycin C. However, many issues have yet to be clarified, such as the potential role of cisplatin as a substitute to mitomycin, as well as treatment-induced toxicity in HIV-positive patients. In this paper, the management of patients with anal cancer is presented, and new chemotherapeutic options are critically reviewed. Finally, the authors' opinion regarding currently unresolved issues in the treatment of these rare neoplasms is expressed.

Anus Neoplasms↗

Squamous cell carcinoma of the anus: another sexually transmitted disease.

During the past 30 years, there has been remarkable progress in our understanding of the pathogenesis of squamous cell carcinoma of the anus. It is now accepted that anal cancer is a sexually transmitted disease, which can be cured using a combination of chemo- and radiotherapy. The biology of anal cancer remains to be elucidated, as do the molecular mechanisms involved in resistance to chemoradiation. The contribution of HIV infection to tumour progression currently represents an area of intensive investigation. Finally, the growing numbers of AIDS patients who experience prolonged survival represent a population at risk. In the future, cytological screening of male homosexuals with an anal Papanicolaou test may help in identifying high-grade dysplasia and preventing anal cancer.

Acquired Immunodeficiency Syndrome↗

Recovery of the rectoanal inhibitory reflex after restorative proctocolectomy: does it correlate with nocturnal continence?

PURPOSE: The rectoanal inhibitory reflex has an important role in fecal sampling and discrimination of rectal contents. The aim of this study was to determine the significance of rectoanal inhibitory reflex after restorative proctocolectomy with ileal pouch-anal anastomosis for mucosal ulcerative colitis. METHODS: The medical records of 345 patients who underwent ileal pouch-anal anastomosis from September 1988 to May 1999 were retrospectively reviewed. One hundred patients who underwent double-stapled ileal pouch-anal anastomosis and had anorectal physiology testing within 3 months before surgery as well as after ileostomy closure (mean, 23.1; range, 3-77 months) were analyzed. Anorectal physiology testing included detecting the presence of the rectoanal inhibitory reflex, sensory threshold volume, and rectal or pouch capacity and compliance. Parameters to determine incontinence included daytime and nocturnal bowel movement frequency, nocturnal spotting, status of continence for solid or liquid stool, gas, use of pads, and lifestyle alteration were surveyed in 62 of the 100 patients at a mean of 3.9 (range, 1-9.1) years to determine the incontinence score. RESULTS: Whereas the rectoanal inhibitory reflex was noted in 96 (96 percent) patients before surgery, it was found in only 53 (53 percent) after ileostomy closure (P < 0.0001). Incontinence status data was available in only 62 of the 100 patients (32 RAIR-positive; 30 RAIR-negative). There were no significant differences between the rectoanal inhibitory reflex-positive and the rectoanal inhibitory reflex-negative groups relative to the interval between surgery and manometry (22 vs 25 months), postoperative threshold sensation volume (32 vs 31 ml), postoperative compliance (19 vs 12 cm H(2)O/ml), postoperative capacity (85 66 ml), daytime/nighttime stool frequency (6.2/2 vs 5.5/1.5), or postoperative incontinence score (3.9 vs 1.8). However, there were significant differences relative to the incidence of nocturnal soiling (12/30 (40 percent) 23/32 (72 percent), P = 0.0012) favoring the presence of the rectoanal inhibitory reflex. CONCLUSION: Preservation of the rectoanal inhibitory reflex correlated with a decrease in the incidence of nocturnal soiling after double-stapled ileoanal reservoir construction.

Adolescent↗

Histologic analysis of the irradiated anal sphincter.

PURPOSE: There is accumulating evidence, both quantitative and qualitative, that pelvic irradiation adversely affects anorectal function. However, histologic evidence of sphincter injury has not been demonstrated. This study was designed to perform histologic assessment of collagen deposition and nerve alteration in the internal anal sphincters of rectal cancer patients who underwent abdominoperineal resection after adjuvant chemoradiation therapy and to correlate the degree of histologic changes with the time interval between chemoradiotherapy and abdominoperineal resection. METHODS: Anal canal specimens were prospectively collected in patients undergoing abdominoperineal resection. Representative slides were cut transversely at the level of the dentate line. Using trichrome and S-100 protein staining, a single pathologist blinded to the patients' treatment assessed collagen deposition and nerve fiber densities in the internal anal sphincter, respectively. RESULTS: Twelve patients received radiation for rectal cancer (chemoradiotherapy group) and six were treated by surgery alone, including four patients with rectal cancer (1 leiomyosarcoma) and two with Crohn's disease (control group). There was a trend toward increased fibrosis (replacement of >10 percent of normal structures by collagen) and nerve density in the chemoradiotherapy group compared with the control group (P = 0.08 and P = 0.05, respectively). Nerve density significantly increased as chemoradiotherapy to abdominoperineal resection interval increased (P = 0.04). CONCLUSIONS: Pelvic irradiation results in damage to the myenteric plexus of the internal anal sphincter of patients with rectal cancer; these alterations seem to be time-dependent. A trend toward increased collagen deposition also was observed. Together, these results provide a morphologic basis, which concurs to previously described physiologic and clinical alterations in the anal sphincter of patients irradiated for rectal cancer.

Adult↗

Colorectal adenocarcinoma in cirrhotic patients.

BACKGROUND: Colorectal carcinoma in cirrhotic patients is different from that in patients without the liver disease. The aims of this study were to evaluate the incidence of liver metastasis, postoperative mortality, and the predictors of longterm survival. STUDY DESIGN: A retrospective analysis of patients operated on for colorectal adenocarcinoma at the Mayo Clinic, Rochester, MN between 1976 and 2001, with confirmed liver cirrhosis at the time of abdominal exploration. RESULTS: Seventy-two patients were available for analysis. They were 43% Child A, 42% Child B, and 15% Child C. The median age was 70 (range 42 to 89) years, and the mean duration of followup was 46 months. Postoperative death was 13%. The risk factors were an elevated bilirubin (p = 0.01) and prolonged prothrombin time (p = 0.009). Seven patients (10%) developed liver metastases. For the whole group 1-, 3-, and 5-year survival rates were 69%, 49%, and 35%, respectively. Child A patients had a significantly better survival rate than the combined group of Child B and C patients (p = 0.008). The risks for longterm survival were decreased albumin (p = 0.002) and prolonged prothrombin time (p < 0.001). TNM stage of the carcinoma provided no prognostic information (p = 0.51). CONCLUSIONS: Liver metastases from colorectal adenocarcinoma is infrequent (10%) in cirrhotic patients. The Child's classification, and not the TNM stage of the carcinoma, predicts the risk of postoperative death and longterm survival.

Adenocarcinoma↗

Perianal Crohn disease: a new scoring system to evaluate and predict outcome of surgical intervention.

BACKGROUND: Conventional Crohn disease activity indices do not reflect perianal disease activity or allow prognostic implications from surgery. HYPOTHESIS: A new scoring system, based on the patient's disease history and physical examination findings, will allow more accurate use of surgical intervention for perianal Crohn disease. METHODS: A standardized scoring questionnaire was developed and applied to a consecutive group of patients before surgical treatment of perianal Crohn disease. The scoring system included abscess, fistula, ulcer and fissure, stenosis, incontinence, and concomitant disease. Weighted factors included acuity vs chronicity, de novo vs recurrent disease, and concomitant intestinal disease. The scoring system was validated against the surgical outcome, which was classified as poor, satisfactory, or good. RESULTS: Twenty-eight patients with Crohn disease who underwent 33 surgical procedures had a mean score of 16.5 (range, 3-37; possible range, 0-55). Using the Spearman nonparametric correlation test, the scoring system was accurate in predicting the outcome of surgical intervention (correlation coefficient, 0.78, 95% confidence interval, 0.57-0.89; P<.001) at mean follow-up of 20.8 months (range, 6-40 months). Correlation was further validated using a linear regression model (r = 0.75, slope best-fit value, 3.8; 95% confidence interval, 2.46-5.14; P<.001). All patients with a score of 10 or less had a good outcome, whereas all those with a score of 20 or greater had a poor outcome. CONCLUSIONS: The proposed scoring system correlated well with the short-term outcome of surgical intervention in patients with perianal Crohn disease and allowed prediction of surgical success. Ultimately, it may be possible to alter therapy based on preoperative prediction of the expected postoperative outcome.

Adult↗