Anal canal cancer: a population-based reappraisal

PURPOSE: This study was designed to obtain an updated population-based perspective on anal canal cancer incidence rates, demographics, and outcomes using a nationwide database. Eight-five percent of all carcinomas of the anus are anal canal cancers, and previous studies suggest that incidence rates may be rising. Although the most successful treatment for anal canal cancer has been chemoradiation, little information at the population-level exists regarding demographics, treatment, and survival. METHODS: All patients diagnosed with anal canal cancer from 1973 to 1998 in the Surveillance Epidemiology and End Results cancer registry were analyzed. Data regarding demographics, cancer characteristics, treatment, and survival were assessed. Univariate and multivariate survival analyses were performed. RESULTS: A total of 4,841 patients were studied (mean age was 61 years; 62 percent female). Female patients were significantly older than male patients (65 vs. 58 years; P < 0.0001). There was a yearly increase in incidence of anal canal cancers (from 1973-1998). Disease prevalence by stage was localized (53 percent), regional (38 percent), and distant (9 percent). Racial/stage differences were seen, because black patients had less localized disease than white patients (46 vs. 53 percent; P < 0.01). Overall five-year survival for the entire cohort was 53 percent, and cancer-specific survival was 84 percent. Survival improved per decade (based on year of diagnosis). Significant survival differences in race were noted, but were less when the receipt of treatment was considered. CONCLUSION: Although most anal canal cancer reviews are single institutional series, this study was performed with population-based data. The incidence of anal canal cancer is increasing, and overall survival rates are improving. Important disparities in care were identified, which need to be addressed.     

Tumor Site Predicts Outcome After Radiochemotherapy in Squamous-Cell Carcinoma of the Anal Region: Long-Term Results of 101 Patients

PURPOSE This study was designed to assess the long-term results following radiochemotherapy in patients with anal squamous-cell carcinoma and to evaluate the impact of tumor location on response, survival, and colostomy-free survival.PATIENTS AND METHODS Between 1985 and 2001, a total of 101 patients with anal carcinoma were registered for curative treatment, of whom 77 had involvement of the anal canal alone, 10 cases had extension into the perianal skin, and 14 patients had pure anal margin tumors. Small tumors of the anal margin were not included since they were treated by surgical excision only. Among the 101 patients were 74 women and 27 men with a median age of 62 (range, 26–84) years. T categories (International Union against Cancer) were T1 (15), T2 (36), T3 (34), and T4 (16). Seventy-one patients had no evidence of nodal disease, whereas 30 presented with involved regional nodes. Radiation treatment was directed to the primary tumor region and to the inguinal, perirectal, and internal iliac nodes using a three-field to four-field box technique with 10MV photons up to a total dose of 5040 cGy. Lesions greater than 5 cm received an additional boost by interstitial or external radiation depending on circumferential extension of the residual tumor. All patients were scheduled for simultaneous chemotherapy with two cycles of 5-fluorouracil at a dose of 1000 mg/m ²/day as 120 hours of continuous intravenous infusion on Days 1 to 5 and 29 to 33 and mitomycin C at 10 mg/m ²/day on Days 1 and 29. Median follow-up time was was 7.5 (range, 1–16) years.RESULTS Overall survival and colostomy-free survival rates for patients with anal canal cancer were 75 percent and 87 percent at five years, respectively. Patients with anal margin cancer had a less favorable outcome with five-year-overall and colostomy-free survival rates of 54 percent and 69 percent, respectively. After correction for imbalance between anal canal and anal margin tumors, i.e., exclusion of T1 tumors of the anal canal, difference in overall survival remained significant (73 percent vs. 54 percent, P = 0.01). Following multivariate analysis, tumor location (anal canal vs. anal margin, P = 0.02), age (P = 0.003), and dose intensity of chemotherapy (≤75 percent vs. >75 percent, P = 0.03) remained independent significant factors for overall survival. Initial tumor response at six weeks (P = 0.03) was predictive for colostomy-free survival.CONCLUSIONS With colostomy-free survival rates around 85 percent, long-term treatment results for anal canal carcinoma have reached a satisfactory level. However, patients with larger lesions of the perianal skin are at high risk for locoregional recurrence and possible treatment intensification in this subgroup seems desirable.Supported by Grant No. D 15 from the Interdisciplinary Center for Clinical Research of the Medical Faculty of the University of Erlangen-Nuremberg.Presented at the meeting of the American Society for Therapeutic Radiology and Oncology, Denver, Colorado, October 16 to 20, 2005.     

Characteristics and Survival Patterns of Solid Organ Transplant Patients Developing <Emphasis Type="Italic">De Novo</Emphasis> Colon and Rectal Cancer

PURPOSE Immunosuppression used in transplantation is associated with an increased incidence of various cancers. Although the incidence of colorectal cancer in transplant patients seems to be equal to nontransplant population, the effects of immunosuppression on patients who develop colorectal cancer are not well defined. The purpose of this study was to define the characteristics and survival patterns of transplant patients developing de novo colorectal cancer.METHODS The Israel Penn International Transplant Tumor Registry was queried for patients with colorectal cancer. Analysis included patient demographics, age at transplantation and colorectal cancer diagnosis, tumor stage, and survival. Age and survival rates were compared to United States population-based colorectal cancer statistics using the National Cancer Institute Surveillance Epidemiology and End Results database.RESULTS A total of 150 transplant patients with de novo colorectal cancer were identified: 93 kidney, 29 heart, 27 liver, and 1 lung. Mean age at transplantation was 53 years. Age at transplantation and colorectal cancer diagnosis was not significant for gender, race, or stage of disease. Compared to National Cancer Institute Surveillance Epidemiology and End Results database, transplantat patients had a younger mean age at colorectal cancer diagnosis (58 vs. 70 years; P < 0.001), and a worse five-year survival (overall, 44 vs. 62 percent, P < 0.001; Dukes A&B, 74 vs. 90 percent, P < 0.001; Dukes C, 20 vs. 66 percent, P < 0.001; and Dukes D, 0 vs. 9 percent, P = 0.08). CONCLUSIONS Transplant patients develop colorectal cancer at a younger age and exhibit worse five-year survival rates than the general population. These data suggest that chronic immunosuppression results in a more aggressive tumor biology. Frequent posttransplantation colorectal cancer screening program may be warranted.Poster presentation at the meeting of The American Society of Colon and Rectal Surgeons, New Orleans, Louisiana, June 21 to 26, 2003.     

Prognosis of cloacogenic and squamous cancers of the anal canal

From 1968 to 1982, 195 patients with invasive cancer of the anal canal were treated (average age, 67 +/- 11 years; range, 38 to 85 years; sex ratio [women/men]: 5/1). Histology revealed: cloacogenic cancer, 20 cases; squamous cancer, poorly differentiated, 30; moderately differentiated, 68; well differentiated, 77. The initial size of the cloacogenic cancers was smaller than the squamous cancers. Invasion less than half the circumference of the canal was 90 and 74 percent, respectively. No patients with cloacogenic cancer presented with positive inguinal nodes; however, there were 22 unilateral and five bilateral positive nodes in the squamous cancers. All 195 patients received radiotherapy as the first treatment. There were no differences among the patients operated on with respect to sterilized operative specimens, postradiotherapy sequelae, perineal recurrences, and/or visceral metastases in the cloacogenic and squamous cancers. Five-year survival was better in cloacogenic (62 percent) than in squamous cancers (56 percent); this difference was not significant, and was related to the initial size of the tumor. The number of patients with no evidence of disease and good anal function was significantly related to the initial size of the tumor, and was independent of the histologic findings.     

Results of salvage abdominoperineal resection for anal cancer after radiotherapy

PURPOSE: Nonsurgical treatment of anal cancer by radiotherapy alone or combined with chemotherapy is the standard therapy for epidermoid carcinoma of the anal canal. Surgery is only recommended for treatment failures. Very few studies have been devoted to the outcome of this salvage surgery. The aim of this study is to evaluate these results. METHODS: A retrospective review from 1986 to 1995 revealed 21 patients with residual or recurrent anal canal carcinoma after initial radiotherapy, operated on by abdominoperineal resection. Patients were reviewed as to age, gender, initial treatment, any symptoms of recurrence, duration until recurrence, any diagnosis imaging, treatment, and outcome. RESULTS: None of these 21 patients had known lymph node involvement or metastases at radiotherapy or at salvage abdominoperineal resection. Eleven patients had residual disease (positive biopsy less than 6 months after the end of radiotherapy) and 10 had tumor recurrence (more than 6 months after cessation of treatment). Recurrence occurred at a mean of 15 (range, 9–41) months after radiotherapy. All 21 patients underwent an abdominoperineal resection. Pathologic examination of the 21 specimens showed complete excision in all cases except one and lymph node metastases in two cases. There was no perioperative mortality. The mean follow-up after surgery was 40 months; no patients were lost to follow-up. Of the 21 patients, 10 died and 11 lived, of whom 9 are disease free. The overall survival rate at three years after salvage abdominoperineal resection was 58 percent. The overall survival rate for patients with residual disease (vs. recurrence) at three years was 72 percent (vs. 29 percent) and at five years was 60 percent (vs. 0 percent;P=0.06). CONCLUSIONS: Salvage abdominoperineal resection for anal cancer can be expected to yield a number of survivors from residual disease, but the low rate of survival after abdominoperineal resection for recurrent disease suggests the need for additional postoperative treatment if salvage abdominoperineal resection is performed.     

Salvage Abdominoperineal Resection After Failure of Conservative Treatment in Anal Epidermoid Cancer

PURPOSE Radiotherapy alone or with combined chemotherapy is the first therapeutic option for epidermoid carcinoma of the anal canal. Failure of this conservative treatment may benefit of salvage abdominoperineal resection. This study was designed to analyze postoperative outcome and oncologic results in a single anticancer institution.METHODS Medical charts of 36 patients (median age, 57.9 years) who underwent salvage abdominoperineal resection after failure of conservative treatment between 1987 and 2002 were reviewed retrospectively. There were 15 patients treated for immediate failure (Group I) and 21 patients for recurrence (Group II). Twenty-two patients have undergone primary use of flap reconstruction of the perineal wound. There were ten rectus abdominis myocutaneous flaps, nine omental flaps, two gracilis muscular flaps, and one combined flap.RESULTS There was no postoperative mortality. Median follow-up was 67 (range, 15–155) months. Primary closure of the perineum was obtained in 33 patients (92 percent). Secondary wound breakdown occurred in 23 of 33 patients (70 percent). Complications unrelated to the perineal wound occurred in 13 patients. The overall crude five-year survival after salvage abdominoperineal resection was 69.4 percent. The crude five-year survival in Group I and Group II was 60.7 and 71.5 percent respectively (P = 0.28). The crude five-year, disease-free survival in Groups I and II was 31.1 and 48.2 percent respectively (P = 0.10). Twenty-three patients experienced recurrences after salvage abdominoperineal resection (64 percent) with a mean delay of 30 months.CONCLUSIONS Despite high incidence of perineal morbidity, salvage abdominoperineal resection for epidermoid carcinomas of the anal canal has a high long-term survival rate.     

A 10-Year Outcomes Evaluation of Mucinous and Signet-Ring Cell Carcinoma of the Colon and Rectum

PURPOSE Most studies examining mucinous or signet-ring cell colorectal cancers are single institution reports. This study used a national cancer registry to analyze the epidemiology and survival outcomes of these two subtypes of colorectal cancer compared with adenocarcinoma tumors.METHODS All patients diagnosed with mucinous (n = 16,991), signet-ring cell (n = 1,522), or adenocarcinoma (n = 146,115) colorectal cancer in the Surveillance, Epidemiology, and End Results database (1991–2000) were evaluated. Analyses were performed to obtain age-adjusted incidence rates, stage at presentation, tumor grade, and five-year relative survival for each subtype.RESULTS Mucinous were slightly more common in females (53.4 percent). Incidence rates per 100,000 persons were: mucinous, 5.5; signet-ring cell, 0.6; and adenocarcinoma 46.6. The annual percent change during ten years was stable for mucinous, increased for signet-ring cell (4.8 percent; P < 0.05), and decreased for adenocarcinoma (−1.1 percent; P < 0.05). Fewer mucinous (18 percent) and signet-ring cell (21 percent) tumors were located in the rectum compared with adenocarcinoma (29 percent). Signet-ring cell presented at later stage (III/IV, 80.9 percent) more often than mucinous (52.8 percent) and adenocarcinoma (49.5 percent), and also had worse tumor grade (high grade: signet-ring cell, 73.5 percent; mucinous, 20.9 percent; adenocarcinoma, 17.5 percent). Relative five-year survival was worse for signet-ring cell than mucinous or adenocarcinoma.CONCLUSIONS We present a large population-based review of colorectal cancer subtypes by analyzing national data from the past decade. Although the incidence of colorectal adenocarcinoma is decreasing in the United States, mucinous and signet-ring cell subtypes are stable and increasing, respectively. Importantly, it seems that the signet-ring cell subtype has worse outcomes, whereas survival rates for mucinous tumors are similar to adenocarcinomas.Read at the meeting of The American Society of Colon and Rectal Surgeons, Dallas, Texas, May 8 to 13, 2004.Supported in part by a Limited Project Grant from The American Society of Colon and Rectal Surgeons Research Foundation.     

Immunohistochemical detection of mutant P53 protein and human papillomavirus-related E6 protein in anal cancers

PURPOSE: The wild-type P53 protein, a product of the P53 gene, is a normal growth controlling protein. Mutation of the P53 gene generates a mutant P53 protein which promotes tumor formation through loss of growth suppression. Some of the agents responsible for P53 gene mutation are known, one of which may be tumorigenic human papillomavirus (HPV) infection. Anal cancers are demonstrating a changing trend in the affected population, from older females in the older reported series to younger males more recently. This may be a reflection of infection with tumorigenic HPV types 16 and 18. The E6 oncoprotein of these viruses inactivates the growth-controlling wild-type P53 protein. In this study, our purpose was to determine the incidence of mutant P53 and HPV-16 and 18-related E6 protein and their coexpression in anal cancers. METHODS: We examined 29 anal cancers immunohistochemically for mutant P53 protein, HPV 16 and 18 E6 protein, and coexpression of the two. RESULTS: Mutant P53 protein was present in 58.6 percent of anal cancers overall and in 85.7 percent of anal adenocarcinomas. E6 oncoprotein was present in five cases (17.2 percent), all of which were squamous-cell carcinomas. Coexpression of both mutant P53 and E6 proteins was seen in only three cases (10.3 percent). CONCLUSION: Although tumorigenic HPV may be an important cause for P53 gene mutation in anal cancers, perhaps other mutagenic factors play a predominant role.This work was supported in part by the Bowman Research Fund. Read at the meeting of The American Society of Colon and Rectal Surgeons, San Francisco, California, June 7 to 12, 1992.     

Laparoscopic abdominoperineal resection revisited: are there any health–related benefits? A comparative study

Background Laparoscopic colectomy is associated with less overall morbidity and improved survival for patients with colonic cancers. There are unfortunately limited clinical reports on laparoscopic abdominoperineal resection. We therefore designed this study to compare laparoscopic abdominoperineal resection with conventional open surgery, with emphasis on health–related issues from the patients’ perspective in order to justify its role in the management of low rectal or anal canal tumours. Methods We carried out a non–randomized, prospective comparative study on a cohort of patients who underwent either laparoscopic or open abdominoperineal resection between March 1994 and December 2003. Patient demographics, tumour characteristics, operative morbidity and mortality, as well as overall survival were considered. The standard endpoints of last follow–up date and deaths were used. Data was analyzed according to intention–to–treat principle. Results A total of 102 patients were recruited: 31 patients underwent conventional open abdominoperineal resection (OAPR) and 71 patients were treated laparoscopically. Patient demographics, median follow–up period, as well as tumour characteristics were similar between groups. The median operating time was similar among groups (145 min in laparoscopic group vs. 156 min in open group; p=0.62). Patients in the laparoscopic group had significantly less blood loss (p=0.01) and fewer requirements for blood transfusion (p=0.01). Despite similar overall morbidity, the laparoscopic group had a reduced incidence of abdominal wound infections (p=0.01) and chest infections (p=0.01). Overall survival was significantly better in the laparoscopic group (p=0.01). Conclusions Laparoscopic abdominoperineal resection confers definite health–related benefits the over open approach in terms of reduced septic complications and fewer requirements for blood transfusion. It should be considered the procedure of choice for patients with low rectal or anal canal tumour in whom sphincter excision proved inevitable.     

Total Mesorectal Excision for Rectal Cancer: Difference in Outcome for Low and High Rectal Cancer

PURPOSE This prospective study was designed to assess the outcome through the first five years after the introduction of total mesorectal excision in 1993 in a Norwegian central hospital, with special regard to the difference between low (≤6 cm from anal verge) and high (>6 cm) rectal cancers. METHODS A total of 140 patients (81 males; median age, 64 (range, 29–87) years) underwent surgery for rectal cancer under curative intention. RESULTS Local recurrence rates were 8 of 44 (18 percent) for the low cancers and 5 of 96 (5 percent) for the high, a statistically significant difference (P = 0.0014). Corresponding numbers when the R1 resections are excluded were 5 of 36 (13 percent) for the low and 4 of 92 (4 percent) for the high cancers (P = 0.002). The five-year survival after R0 resections of cancers <6 cm was significantly reduced compared with those >6 cm. The five-year overall survival for the whole material was 72 percent. CONCLUSIONS Surgery alone for rectal cancer can achieve overall good results, with five-year overall survival of 72 percent. The prognosis of the cancers of the lower rectum seems to be inherently different from the tumors of the higher level, both concerning local recurrence and five-year survival, suggesting different biologic behavior of the two cancers. Presented at the meeting of the Norwegian Surgical Society, Oslo, Norway, October 18 to 22, 2004.     

Outcome of surgery for colorectal cancer in a defined population in Sweden from 1984 to 1986

PURPOSE: This study was designed to investigate incidence, treatment, and outcome for patients with colorectal cancer. METHODS: From 1984 to 1986 in Östergötland, a county in Sweden with a defined population, a prospective registration using a computerized protocol was undertaken. RESULTS: In the surgical departments 596 cases were diagnosed and 31 more cases were diagnosed in other departments, bringing the incidence to 53 cases per 100,000 inhabitants per year. Of the cases, 14 percent presented as emergencies. The resectability rate was 90 percent, and the rate of curative operations was 74 percent. Postoperative mortality within 30 days was 2.9 percent. Crude five-year survival for all patients was 40 percent, and the corrected survival rate was 53 percent. After curative resection the crude five-year survival rate was 53 percent, and the corrected survival rate was 70 percent. Prognosis was better for colon than for rectal cancer, 76 percent vs.59 percent corrected five-year survival rate. For rectal cancer the local recurrence rate was 20 percent after curative resection. CONCLUSIONS: The prognosis was improved compared with a previous study from the same area because of decreased postoperative mortality, increased rate of operations for cure, and an increased five-year corrected survival rate. Local recurrence after rectal cancer was still high but may be reduced with improved surgical technique.Supported by grants from Östergötlands Läns Landsting (Project 52/82, 49/83, and 51/84).     

Impact of race in lung cancer: analysis of temporal trends from a surveillance, epidemiology, and end results database.

STUDY OBJECTIVES: We analyzed data from a community-based cancer database over a 26-year period in order to characterize clinicopathologic differences between black and white patients with lung cancer, and to identify relevant temporal trends in incidence and survival. DESIGN, SETTING, and PATIENTS: Data on demographics, stage, histology, and survival were obtained on all black and white patients with primary bronchogenic carcinoma registered in the community-based metropolitan Detroit Surveillance, Epidemiology, and End Results database from 1973 to 1998. RESULTS: Of 48,318 eligible patients, 23% were black. Lung cancer incidence rates decreased for men of both races from 1985 to 1998, with a greater decline occurring in black men (p < 0.0001). Although incidence rates declined over time for men of both races < 50 years of age, this decrease was greater in white men, resulting in an increase in the racial differential in younger men. Temporal trends in incidence rates were similar for women of both races. The incidence of distant-stage disease was higher among blacks throughout the study period. The incidence of local-stage disease decreased for both races, though this decline was greater in blacks. A significant racial difference in 2-year and 5-year survival rates developed during the study period, due to a distinct lack of improvement in black patients. In a multivariate model, the relative risks of death for black patients, relative to white patients, were 1.24 (p < 0.0001) for local stage, 1.14 (p < 0.0001) for regional stage, and 1.03 (p = 0.045) for distant stage. CONCLUSION: Significant racial differences exist in the incidence and survival rates for lung cancer in metropolitan Detroit. Since 1973, several disturbing trends have developed, particularly with regard to the lack of improvement in overall survival in black patients. Further study is required to determine the factors responsible for these temporal trends.     

Outcome of HIV-infected patients with invasive squamous-cell carcinoma of the anal canal in the era of highly active antiretroviral therapy

PURPOSE: Before the development of highly active antiretroviral therapy for the treatment of HIV infection, HIV patients diagnosed with invasive squamous-cell carcinoma of the anal canal carried a very poor prognosis. This study was designed to determine the outcome in a similar group of patients in the era of highly active antiretroviral therapy.METHODS: HIV-positive patients treated for invasive squamous-cell carcinoma of the anal canal at the University of Texas Medical Center affiliated hospitals from 1980 to 2001 were identified from operative data and cancer registries. We reviewed these records and collected data regarding age, CD4 count, highly active antiretroviral therapy, cancer treatment, complications, and survival. The patients were divided into two groups based on the presence or absence of highly active antiretroviral therapy and compared using a Kaplan-Meier approach.RESULTS: Fourteen patients with HIV and invasive squamous-cell carcinoma of the anal canal were identified. Six were in the prehighly active antiretroviral therapy group and eight in the highly active antiretroviral therapy group. All were considered for treatment with chemotherapy and radiation. In the prehighly active antiretroviral therapy group, one patient refused therapy and three were unable to complete the squamous-cell carcinoma therapy as planned because of complications. Four of eight highly active antiretroviral therapy patients were unable to complete the squamous-cell carcinoma therapy as planned. The prehighly active antiretroviral therapy patients had a mean age of 40 years and a mean CD4 count of 190 at the time of diagnosis. The highly active antiretroviral therapy patients had a mean age of 44 years and a mean CD4 count of 255 at the time of diagnosis. The 24-month survival was 17 percent in the prehighly active antiretroviral therapy group and 67 percent in the highly active antiretroviral therapy group (P = 0.0524). All six patients in the prehighly active antiretroviral therapy group died with active squamous-cell carcinoma vs. two in the highly active antiretroviral therapy group. Four of the remaining six patients had no evidence of active squamous-cell carcinoma at the last follow-up visit.CONCLUSIONS: A review of patients with HIV and invasive squamous-cell carcinoma of the anal canal suggests a trend toward a higher CD4 count at the time of diagnosis and improved survival in patients receiving highly active antiretroviral therapy. In this new era, HIV-positive patients should be on highly active antiretroviral therapy. If not, highly active antiretroviral therapy should be initiated, and standard multimodality therapies for invasive squamous-cell carcinoma of the anal canal are recommended.Read at the meeting of The American Society of Colon and Rectal Surgeons, New Orleans, Louisiana, June 21 to 26, 2003.     

Sphincter preservation with chemoradiation in anal canal carcinoma

PURPOSE: This study contained herein assessed long-term results, toxicity, and prognostic variables following combined modality therapy of patients with International Union Against Cancer Classification T1–4, N0–3, M0 squamous-cell carcinoma of the anal canal. PATIENTS AND METHODS: Between 1985 and 1996, 62 patients completed treatment with combined modality therapy. A median total dose of 50 Gy was given to the primary, perirectal, presacral, and inguinal nodes followed by a local boost in selected cases. 5-Fluorouracil was scheduled as a continuous infusion of 1,000 mg/m² per 24 hours on days 1 to 5 and 29 to 33 and mitomycin C as a bolus of 10 mg/m² on days 1 and 29. Routinely processed paraffin-embedded sections were stained using monoclonal antibodies for detection of proliferating cell nuclear antigen and MIB1 (Ki-67) antigen to determine the labeling index. In addition, DNA ploidy was assessed after Feulgen staining. RESULTS: Actuarial cancer-related survival, no evidence of disease survival, and colostomy-free survival rates at five years were 81, 76, and 86 percent, respectively. In univariate analysis, T category (T1/2 vs. T3/4) was predictive for no evidence of disease survival (87vs. 59 percent;P=0.03) and colostomy-free survival (94vs. 73 percent;P=0.05). N category (N0vs. N1–3) influenced actuarial cancer-related survival (85vs. 58 percent;P=0.002) and no evidence of disease survival (80vs. 53 percent;P=0.02). A higher proliferative potential as measured by the MIB1 labeling index was associated with a better colostomy-free survival (90vs. 50 percent;P=0.04). In multivariate analysis, actuarial cancer-related survival was only influenced by the N category (P=0.03) and no evidence of disease survival by N category (P=0.03) and mitomycin C dose (P=0.04). Salvage abdominoperineal resection achieved long-term control in only four of seven patients with local failures. CONCLUSION: Treatment with a combination of radiotherapy and chemotherapy is safe and effective for patients with anal canal carcinoma. Abdominoperineal resection is indicated as a salvage procedure in nonresponding and recurrent lesions and may be of benefit in a small subgroup of patients with poor prognostic factors.Supported by a grant from the Wilhelm Sander Foundation (Nr. 94.061.1).Presented at the European Cancer Conference (ECCO9), Hamburg, Germany, September 14 to 18, 1997.     

Colorectal and extracolonic cancer variations in MLH1/MSH2 hereditary nonpolyposis colorectal cancer kindreds and the general population

PURPOSE: This clinical case review aimed to identify phenotypic variations in colorectal and extracolonic cancer expression between hereditary nonpolyposis colorectal cancer (HNPCC) families with MLH1 and MSH2 germline mutations and the general population. METHODS: Colorectal cancer onset and site distribution were compared among 67 members of MLH1 kindreds, 45 members of MSH2 kindreds, and 1,189 patients from the general population. Synchronous and metachronous cancer rates, tumor stage, extracolonic cancer incidence, and survival were also compared. RESULTS: Mean ages of colorectal cancer onset were 44, 46, and 69 years for MLH1, MSH2, and the general population, respectively (P<0.001). More proximal and fewer distal colon cancers were noted in HNPCC than the general population (P<0.001,P=0.04). Site distribution showed disparity of rectal cancers (8 percent MLH1vs. 28 percent MSH2;P=0.01) based on genotypes. Overall, synchronous colorectal cancer rates were 7.4, 6.7, and 2.4 percent for MLH1, MSH2, and the general population, respectively (P=0.016). Annual metachronous colorectal cancer rates were 2.1, 1.7, and 0.33 percent for MLH1, MSH2, and the general population, respectively (P=0.041). Colorectal cancer stage presentation was lower in HNPCC than the general population (P=0.0028). Extracolonic cancers were noted in 33 percent of MSH2 patients, compared with 12 percent of MLH1 patients and 7.3 percent of the general population with colorectal cancers (P<0.001). Combined MLH1 and MSH2 ten-year survival was 68.7 percent compared with 47.8 percent for the general population (P=0.009 stage stratified, hazard ratio 0.57). CONCLUSION: The presence of rectal cancer should not preclude the diagnosis of HNPCC, because the incidence of rectal cancer in MSH2 was comparable with that in the general population. Phenotypic variations, including the preponderance of extracolonic cancers in MSH2 patients, did not result in survival differences between genotypic subgroups. These phenotypic features of HNPCC genotypes may have clinical significance in the design of specific screening, surveillance, and follow-up for affected individuals.     

Are Survival Rates Different for Young and Older Patients With Rectal Cancer?

PURPOSE Although it is generally believed that young patients with rectal cancer have worse survival rates, no comprehensive analysis has been reported. This study uses a national-level, population-based cancer registry to compare rectal cancer outcomes between young vs. older populations.METHODS All patients with rectal carcinoma in the Surveillance, Epidemiology, and End Results cancer database from 1991 to 1999 were evaluated. Young (range, 20–40 years; n = 466) and older groups (range, 60–80 years; n = 11,312) were compared for patient and tumor characteristics, treatment patterns, and five-year overall and stage-specific survival. Cox multivariate regression analysis was performed to identify predictors of survival.RESULTS Mean ages for the groups were 34.1 and 70 years. The young group was comprised of more black and Hispanic patients compared with the older group (P < 0.001). Young patients were more likely to present with late-stage disease (young vs. older: Stage III, 27 vs. 20 percent respectively, P < 0.001; Stage IV, 17.4 vs. 13.6 percent respectively, P < 0.02). The younger group also had worse grade tumors (poorly differentiated 24.3 vs. 14 percent respectively, P < 0.001). Although the majority of both groups received surgery (85 percent for each), significantly more young patients received radiation (P < 0.001). Importantly, overall and stage-specific, five-year survival rates were similar for both groups (P = not significant).CONCLUSIONS Although previous studies have found young rectal cancer patients to have poorer survival compared with older patients, this population-based study shows that young rectal cancer patients seem to have equivalent overall and stage-specific survival.Supported in part by The American Society of Colon and Rectal Surgeons Limited Project Grant.Presented at the meeting of the Association for Academic Surgery, Sacramento, California, November 13 to 15, 2003.     

Colorectal adenocarcinoma in patients under 45 years of age: Comparison with older patients in a well-defined french population

PURPOSE: Little is known about colorectal cancer in young patients at a population level, and the behavior, characteristics, and prognosis of such tumors continue to be debated. METHODS: A population-based series of 4,643 new cases of colorectal adenocarcinomas diagnosed between 1976 and 1996 in C te d'Or, France, was used to describe time trends in incidence, predisposing conditions, location, stage, and treatment and to evaluate the prognosis of such tumors in patients under 45 years of age (n = 146). Prognosis was determined using relative survival rates and predictive factors using a multivariate relative survival model. RESULTS: Before the age of 45 years, age-standardized incidence rates were 1.9 per 100,000 in males and 1.4 per 100,000 in females. Incidence rates almost doubled from 1976 to 1982 and from 1983 to 1989 in both genders and stabilized thereafter. The frequency of predisposing conditions was significantly higher before the age of 45 years (11.7 vs. 0.4 percent; P < 0.001). TNM Stage III tumors were more frequent in younger patients, and Stage II tumors were more frequent in older patients. The postoperative mortality rate was lower in the 0-to-44 age group, 2.1 percent, compared with 8.4 percent for the 45-and-over age group (P = 0.004). Five-year relative survival rates were 51.9, 49.2, and 41.4 percent, respectively. In both overall and stage-for-stage comparisons, patients before the age of 45 years had a better survival rate than older patients. Gender and stage at diagnosis were the only independent prognostic factors of survival for young patients. CONCLUSIONS: This study confirms the high frequency of predisposing conditions in young patients and that young age is not a poor prognostic factor for colorectal cancer. This underlines the importance of family screening, aggressive surveillance, and treatment in the young with known predisposing conditions.     

Formalin Application in the Treatment of Chronic Radiation-Induced Hemorrhagic Proctitis—An Effective But Not Risk-Free Procedure: A Prospective Study of 33 Patients

PURPOSE This prospective study evaluated the efficacy and safety of local formalin application in chronic refractory radiation-induced hemorrhagic proctitis.METHODS All patients were treated under anesthesia by direct application of 4 percent formalin to the affected rectal areas.RESULTS The study included 33 patients (17 women) and was conducted between January 1994 and December 2001. There were 11 anal cancers (33 percent), 11 prostate cancers, 9 cervical or endometrial cancers, 1 bladder cancer, and 1 rectal cancer. The mean number of daily rectal bleeds was 2.7 (range, 0.5–15). Nineteen patients (58 percent) were blood transfusion dependent. Twenty-three patients had only one formalin application and 10 patients required a second application because of the persistent bleeding. The treatment was effective in 23 cases (70 percent): 13 patients had complete cessation of bleeding and 10 patients had only minor bleeding. Six anal or rectal strictures occurred: 4 patients had been treated for anal cancer (36 percent) and 2 patients had been treated for other cancers (9 percent). None of the strictures was malignant. Anal incontinence worsened in 5 patients of the 11 who had been treated for anal cancer (45 percent) and occurred in 4 of the 22 other patients (18 percent).CONCLUSION Formalin application is an effective treatment for chronic radiation-induced hemorrhagic proctitis. However, local morbidity is not negligible. This result may be related to the high proportion of anal cancers in the series. In our opinion, therefore, formalin application should be reserved for severe hemorrhagic proctitis refractory to medical treatment and should be thoroughly discussed in cases of anorectal radiation-induced stricture, prior anal incontinence, or treated anal cancer.Presented at the Journées Francophones de Pathologie Digestive, Paris, France, March 31 to April 2, 2003, and at Digestive Disease Week, New Orleans, Louisiana, May 15 to 20, 2004.     

Anal canal inflammation after ileal pouch-anal anastomosis

One technique used during restorative proctocolectomy to prevent loss of continence involves preservation of the anal canal. This technique retains a small amount of colonic mucosa and transitional mucosa that may become inflamed or develop dysplastic or neoplastic changes. PURPOSE: This study was designed to determine the presence and severity of anal canal inflammation and the need for treatment. METHOD: Records of 217 patients with mucosal ulcerative colitis who underwent restorative proctocolectomy with a stapled ileal pouch-anal anastomosis without anal mucosectomy from 1987 through 1990 were retrospectively reviewed. RESULTS: Anal canal inflammation was evident on both endoscopy and biopsy in 48 patients (22.11 percent); 18 patients (8.29 percent) had a normal ileal pouch (9 had symptoms; 5 required topical treatment), and 30 patients (13.82 percent) had associated ileal pouch inflammation (23 with symptoms requiring systemic treatment because of pouchitis; 10 patients had concomitant topical treatment). CONCLUSION: Symptomatic inflammation of the retained mucosa occurred in 32 (14.7 percent) patients. Nine (4.1 percent) patients had inflammation of the anal canal alone, and 23 (10.6 percent) had pouchitis in addition. The need for treatment occurred in 28 (12.9 percent) of the total ((2.3 percent) patients with anal canal inflammation and 23 (10.6 percent) with anal canal inflammation plus pouchitis).Read at the meeting of The American Society of Colon and Rectal Surgeons, Orlando, Florida, May 8 to 13, 1994.