Identification of Patients with High-Risk Stage II Colon Cancer for Adjuvant Therapy

Purpose Adjuvant therapy for Stage II colon cancer remains controversial but may be considered for patients with high-risk features. The purpose of this study was to assess the prognostic significance of commonly reported clinicopathologic features of Stage II colon cancer to identify high-risk patients. Methods We analyzed a prospectively maintained database of patients with colon cancer who underwent surgical treatment from 1990 to 2001 at a single specialty center. We identified 448 patients with Stage II colon cancer who had been treated by curative resection alone, without postoperative chemotherapy. Results With median follow-up of 53 months, 5-year disease-specific survival for this cohort was 91 percent. Univariate and multivariate analyses identified three independent features that significantly affected disease-specific survival: tumor Stage T4 (hazard ratio (HR), 2.7; 95 percent confidence interval (CI), 1.1–6.2; P = 0.02), preoperative carcinoembryonic antigen >5 ng/ml (HR, 2.1; 95 percent CI, 1.1–4.1; P = 0.02), and presence of lymphovascular or perineural invasion (HR, 2.1; 95 percent CI, 1–4.4; P = 0.04). Five-year disease-specific survival for patients without any of the above poor prognostic features was 95 percent; five-year disease-specific survival for patients with one of these poor prognostic features was 85 percent; and five-year disease-specific survival for patients with ≥2 poor prognostic features was 57 percent. Conclusions Patients with Stage II colon cancer generally have an excellent prognosis. However, the presence of multiple adverse prognostic factors identifies a high-risk subgroup. Use of commonly reported clinicopathologic features accurately stratifies Stage II colon cancer by disease-specific survival. Those identified as high-risk patients can be considered for adjuvant chemotherapy and/or enrollment in investigational trials. Read at the meeting of The American Society of Colon and Rectal Surgeons, St. Louis, Missouri, June 2 to 6, 2007. Reprints are not avaliable.     

Absence of Lymph Nodes in the Resected Specimen After Radical Surgery for Distal Rectal Cancer and Neoadjuvant Chemoradiation Therapy: What does it Mean?

Purpose The number of retrieved lymph nodes during radical surgery has been considered of great importance to ensure adequate staging and radical resection. However, this finding may not be applicable after neoadjuvant therapy in which, not only is there a decrease in lymph nodes recovered, but also a subgroup of patients with absence of lymph nodes in the resected specimen. Methods Patients with absence of lymph nodes were compared with patients with ypN0 disease and patients with ypN+ disease. Results Thirty-two patients (11 percent) had absence of lymph nodes, 171 patients (61 percent) had ypN0 disease, and 78 patients (28 percent) had ypN+ disease. Patients with absence of lymph nodes had significantly lower ypT status (ypT0-1, 40 vs. 13 percent; P < 0.001) and decreased risk of perineural invasion (6 vs. 21 percent; P = 0.04) compared with ypN0 patients. Five-year disease-free survival (74 percent) was similar to patients with ypN0 (59 percent; P = 0.2), and both were significantly better than patients with ypN+ disease (30 percent; P < 0.001). Conclusions Absence of lymph nodes retrieved from the resected specimen is associated with favorable pathologic features (ypT and perineural invasion status) and good disease-free survival rates. In this setting, absence of retrieved lymph nodes may reflect improved response to neoadjuvant chemoradiation therapy rather than inappropriate or suboptimal oncologic radicality. Presented at the meeting of The American Society of Colon and Rectal Surgeons, St. Louis, Missouri, June 2 to 6, 2007.     

Sleep architecture in children and adolescents with cystic fibrosis and the association with severity of lung disease

Previous studies have shown that sleep complaints are common in adult patients with cystic fibrosis (CF). However, there is very little data on sleep in children and adolescents with CF and the association with severity of lung disease. A prospective study was conducted in CF children and age-matched controls. All patients completed sleep questionnaire and underwent an overnight polysomnographic study. Thirty-eight children and adolescents met the criteria for entry into the analysis, 24 children and adolescents with CF (S) and 14 controls (C). Sleep complaints were common in children and adolescents with CF; 43.5% reported sleep onset problem, 39.1% reported sleep maintenance problem, 30.4% were noted to snore at night, and 73.9% reported daytime sleepiness. Children and adolescents with CF had a significant decrease in sleep efficiency [SE; 75.2 ± 2.5% (S) vs 85.6 ± 1.7%(C); P < 0.01], prolonged rapid eye movement (REM) latency [150.5 ± 16.6 min (S) vs 85.6 ± 11.0 min (C); P < 0.05], and reduction in percentage of REM sleep [12.7 ± 1.5% (S) vs 18.3 ± 1.3% (C); P < 0.05]. The degree of sleep disruption as indicated by SE was correlated with forced expiratory volume in one second (FEV₁; r = 0.52, P < 0.05). However, there was no significant correlation between SE and minimum oxygen saturation [r = 0.30, P=not significant (NS)] or SE and maximal end-tidal pCO₂ (r = 0.11, P=NS). It is concluded that children and adolescents with CF have frequent sleep complaints and significant alteration in the sleep architecture. The magnitude of sleep disruption is associated with severity of lung disease, but is not directly correlated with the degree of nocturnal hypoxemia or hypoventilation. It is speculated that sleep disruption in children and adolescents with CF may have an impact on quality of life and clinical outcomes in this population.     

Tumor Pathology and Long-Term Survival in Emergency Colorectal Cancer

PURPOSE Patients who have an emergency operation for colorectal cancer have poorer long-term survival outcomes compared with elective patients. This study was designed to define the role of tumor pathology as a basis for the differences in survival outcomes. METHODS There were 1,537 elective and 286 emergency patients who had an operation for bowel cancer from 1997 to 2003. Tumor pathology and survival data collected prospectively for these patients were compared by modes of presentation. RESULTS Excluding 30-day mortality, emergency patients as a whole had a five-year all-cause survival rate of 39.2 percent compared with 64.7 percent for elective patients P < 0.0001 they also had more advanced Dukes C and D tumors (P < 0.0001). The rates of early T1 and T2 cancers were 4.7 percent for the emergency and 25 percent for the elective group. Emergency cases had more lymph node-positive patients and N2 patients (57.1 vs. 41.8 percent and 26.6 vs. 15.9 percent, respectively; P < 0.0001). Curatively resected emergency colon patients again had more advanced Dukes staged tumors (P < 0.0001) with a five-year survival rate of 51.6 percent compared with 75.6 percent for elective patients P < 0.0001. On stage-for-stage analysis, the survival rates for curatively resected Dukes B and C colon cancers remained worse for emergency patients (P = 0.003 and P = 0.0002, respectively). Both emergency Dukes B and C groups had more T4 cases (21.5 vs. 10.6 percent; P = 0.017 and 26.4 vs. 15 percent; P = 0.016, respectively). CONCLUSION Advanced tumor pathology is a basis for poor long-term survival in emergency colorectal cancers. Reprints are not available.     

Predictors of survival in recurrent rectal cancer after resection and intraoperative radiotherapy

PURPOSE: This study was designed to determine predictors of survival after surgery and intraoperative radiotherapy for recurrent rectal cancer. METHODS: From a prospective database, 634 patients undergoing resection for recurrent rectal cancer between January 1990 and June 2000 were identified. Of these, 111 received intraoperative radiotherapy with curative intent, and 100 were available for follow-up. Clinicopathologic variables from both the primary and recurrent operations were evaluated as predictors of disease-free and disease-specific survival by multivariate Cox regression and log-rank test. RESULTS: There were 54 males and 46 females, with a median age of 57 (range, 37–83) years. With a median follow-up of 23.2 months, 60 patients (60 percent) recurred: 20 (33 percent) locally, 27 (45 percent) distantly, and 13 (22 percent) at both sites. Of all variables analyzed, only complete resection with microscopically negative margins and the absence of vascular invasion in the recurrent specimen predicted improved disease-free and disease-specific survival (P < 0.01 for all). Median disease-free survival and median disease-specific survival were 31.2 and 66.1 months, respectively, for complete resection compared with 7.9 and 22.8 months for resection with microscopic or grossly positive margins (P < 0.01 for both). Median disease-free survival and median disease-specific survival were 6.4 and 16.1 months, respectively, in the presence of vascular invasion in the recurrent specimen compared with 23.3 and 57.3 months in the absence of vascular invasion (P < 0.01 and P < 0.05, respectively). Complete resection and the absence of vascular invasion were the only predictors of improved local control as well (P < 0.05 and P < 0.01, respectively). CONCLUSION: Resection with negative microscopic margins and absence of vascular invasion are independent predictors of local control and improved survival after resection and intraoperative radiotherapy for recurrent rectal cancer.     

Microvessel density of hepatocellular carcinoma: its relationship with prognosis

Purpose: To elucidate the relationship between angiogenesis and prognosis after curative resection of hepatocellular carcinoma (HCC). Methods: An immunohistochemical study using anti-CD34 monoclonal antibody was carried out on surgical specimens from 78 HCC patients who had undergone curative resection; microvessel density (MVD) was counted and the overall survival and disease-free survival were analyzed retrospectively. Results: Blood vessels in the tumor were strongly stained by anti-CD34 antibody, but not those in the surrounding liver parenchyma. There were three types of tumor vessels: capillary-like (n = 59), sinusoid-like (n = 16) and mixed-type (n = 3). The median MVD count was 100 per field. The HCC were designated as hypovascular (n = 36) with an MVD count below 100, and hypervascular (n = 42) with an MVD count of 100 or more per field. The 5-year survival and disease-free survival rates were 49.7% and 42.8% respectively, and statistical analysis showed that the MVD level was not correlated with tumor size, capsule status, Edmondson's grade, α-fetoprotein level, associated cirrhosis, γ-glutamyltransferase, and serum HBsAg status. The sinusoid-like tumor vessels appeared more frequently in the more differentiated tumors (P < 0.05). No statistical difference in overall and disease-free survival between different MVD levels and microvessel types was found. Tumor size was the only predicting factor in the entire series. In patients with small HCC (≤ 5 cm, n = 40), 5-year survival and disease-free survival rates were 58.9% and 52.7% respectively, higher than the values in large HCC (39.8% and 32.0% respectively, P < 0.05). The MVD level was an independent predicting factor of disease-free survival, 5-year disease-free survival in the hypovascular group (74.6%) being better than that in the hypervascular group (34.7%, P < 0.05). Conclusions: The MVD level was not related to tumor size, capsule statuo, Edmondson's grade, α-fetoprotein level, associated cirrhosis, γ-glutamyltransferase and serum HBsAg status. In the entire series, tumor size was the only factor influencing survival after curative resection. However, in patients with small HCC, the MVD level was an independent factor of disease-free survival. The pathological and clinical implications of different types of tumor vessels in HCC remain to be studied. Received: 27 November 1998 / Accepted: 5 January 1999     

Long-Term Quality of Life in Patients with Crohn’s Disease and Perianal Fistulas: Influence of Fecal Diversion

Purpose Symptomatic perianal fistulas impair quality of life in patients with Crohn’s disease. Fecal diversion improves symptoms but may impair quality of life. This study was designed to compare long-term quality of life in patients with Crohn’s disease with symptomatic perianal fistulas who were treated with or without fecal diversion. Methods From 1996 to 2002, perianal fistulas were treated in 116 patients with Crohn’s disease. A questionnaire, including four quality of life instruments, was mailed to each patient (Short-Form General Health Survey, Gastrointestinal Quality of Life Index, Cleveland Global Quality of Life Score, Short Inflammatory Bowel Disease Questionnaire). Results Questionnaires were returned by 77 of 116 patients (66 percent). Thirty-four of these patients had undergone fecal diversion, whereas 43 had not. Median follow-up was 49 (range, 18–97) months in diverted and 44 (range, 14–98) months in undiverted patients (not significant). In the diverted group, 44 percent complained of Crohn’s disease-related symptoms, which was less compared with 79 percent in undiverted patients (P < 0.05). Diverted patients achieved 68 ± 1 percent of the maximum possible score on the Gastrointestinal Quality of Life Index compared with 60 ± 2 percent in undiverted patients (mean ± standard error of the mean; P < 0.001); diverted patients scored better on the subscale “gastrointestinal symptoms” of the Gastrointestinal Quality of Life Index (81 ± 1 percent vs. 67 ± 2 percent; P < 0.001). There was no difference in the Short Inflammatory Bowel Disease Questionnaire between diverted and undiverted patients except for the subscale “bowel function” (91 ± 2 percent vs. 76 ± 2 percent; P < 0.0001). No difference in quality of life was detected by the Short-Form General Health Survey and Cleveland Global Quality of Life Score. Conclusions In the investigated population of patients with Crohn’s disease, quality of life seems to be similar or potentially superior in diverted patients suffering from perianal fistulas compared with undiverted patients. A diverting stoma, therefore, may improve quality of life in patients with severe perianal Crohn’s disease. Presented at the meeting of the American Gastroenterological Association, Digestive Diseases Week, Los Angeles, California, May 20 to 25, 2006, and published in abstract form Gastroenterology 2006;130(Suppl 2):A620.     

Anti-p53 autoantibody in colorectal cancer: prognostic significance in long-term follow-up

Background The prognostic significance of anti-53 autoantibody in colorectal cancer (CRC) patients is unclear due to measurement of overall rather than disease-specific survival and generally short follow-up periods in many studies. We aim to investigate prognostic significance of anti-p53 auto-antibodies in a study with long-term follow-up (minimum 5 years). Methods ELISA for anti-p53 autoantibody was assayed in serum from 92 patients with CRC and 28 controls. Results Anti-p53 autoantibody was found in 20 patients (21.7%) and none of the controls. No difference in Dukes’ (A/B vs. C/D), Stage (I/II vs. III/IV), T1/2 vs. T3/4, N0 vs. N1/2, M0 vs. M1, poor vs. well/moderate differentiation and proximal vs. distal CRC was observed. Median overall survival was 62 months and median disease-specific survival was 73 months. Dukes’ C/D, Stage III/IV, N1/2 and M1 were associated with poor disease-specific survival in univariate analysis. Stage III/IV was an independent prognostic factor in overall and disease-free survival in multivariate analysis. Anti-p53 autoantibody sero-positivity did not influence overall (p = 0.980) or disease-specific survival (p = 0.874). Median overall survival in anti-p53 autoantibody positive patients was 62 months vs. 60 months in anti-53 autoantibody negative patients. Median disease-specific survival in anti-p53 autoantibody positive patients was 73 months vs. 82 months. Conclusion Anti-p53 autoantibody is not related to clinical parameters of CRC and has no prognostic significance in long-term follow-up.     

Levels of vascular endothelial growth factor and hepatocyte growth factor in sera of patients with rheumatic diseases

 Angiogenesis plays an important role in the progression of rheumatic disease. We measured the levels of vascular endothelial growth factor (VEGF) and hepatocyte growth factor (HGF) in sera from patients with rheumatic diseases and investigated whether these angiogenic factors would be useful in the evaluation of rheumatic diseases. Serum VEGF and HGF levels were determined using ELISA in 128 patients with rheumatic diseases and in 11 healthy controls. Serum VEGF and HGF levels were significantly higher in patients with rheumatic diseases compared to healthy controls [VEGF, 312 ± 20 pg/ml versus 61 ± 8 pg/ml (mean ± SE), P < 0.001; HGF, 935 ± 36 pg/ml versus 413 ± 49 pg/ml, P < 0.01]. Serum VEGF and HGF levels were significantly elevated in patients with adult Still's disease (VEGF, 1021 ± 258 pg/ml; HGF, 1500 ± 295 pg/ml) and were relatively increased in patients with active rheumatoid arthritis (RA) (VEGF, 359 ± 94 pg/ml) and systemic sclerosis (SSc) (VEGF, 356 ± 43 pg/ml; HGF, 1294 ± 224 pg/ml). HGF levels correlated with the clinical course and disease severity in rheumatic disease patients. VEGF levels correlated with the presence of Raynaud's phenomenon (P < 0.05), interstitial lung disease (ILD) (P < 0.05), and serum KL-6 levels (P < 0.01), whereas HGF levels correlated with cryoglobulinemia (P < 0.05), ILD (P < 0.05), serum C-reactive protein (CRP) (P < 0.05), thrombomodulin (P < 0.05), and KL-6 levels (P < 0.05) in rheumatic disease patients. VEGF levels correlated with the skin scores and KL-6 levels in SSc patients and also correlated with the disease activity of RA patients. These data suggest that serum VEGF and HGF levels are related to rheumatic disease activity and the presence of complications. Analysis of VEGF and HGF may be useful in the clinical evaluation of rheumatic disease patients. Received: February 19, 2002 / Accepted: August 13, 2002 Acknowledgment We are grateful to Ms. Aki Nomura for assistance with the ELISA of VEGF and HGF.     

Laparoscopic Ileal Pouch-Anal Anastomosis in Patients with Chronic Ulcerative Colitis and Primary Sclerosing Cholangitis: A Case-Matched Study

Purpose This study was designed to compare short-term outcomes after laparoscopic ileal pouch-anal anastomosis with those of open ileal pouch-anal anastomosis in patients with both sclerosing cholangitis and ulcerative colitis. Methods Sixteen patients with sclerosing cholangitis and ulcerative colitis undergoing laparoscopic ileal pouch-anal anastomosis were matched with 16 open ileal pouch control subjects by sex, American Society of Anesthesiologists’ score, age, and body mass index. Results Operative mortality was zero. Operative time was longer in the laparoscopic group (500 ± 125.8 vs. 381.8 ± 60.9 minutes, P = 0.03). Thirty-day complications were not significantly different between groups (laparoscopic 25 percent vs. open 43.7 percent, P = 0.26). Length of stay was significantly shorter in the laparoscopic group (5.3 ± 1.3 days vs. 9.9 ± 3.3 days open, P < 0.001). Average return of gastrointestinal function was 2.5 days in the laparoscopic group and 4.8 days in the open group (P = 0.001). Time to soft diet was three days in the laparoscopic group and six days in the open group (P < 0.001). All patients were alive and all pouches were intact at last follow-up. Conclusions Laparoscopic ileal pouch-anal anastomosis is feasible with apparent safety in patients with primary sclerosing cholangitis, resulting in shorter duration of hospital stay and quicker return of gastrointestinal function compared with the open procedure with no difference in perioperative complications, reoperations, and readmissions.     

Pegylated doxorubicin for primary cutaneous T-cell lymphoma: a report on ten patients with follow-up

Purpose: Pegylated liposomal doxorubicin (PEG-DOXO) was found to be effective in primary cutaneous T-cell lymphomas (CTCL). The present observation reports on follow-up and relapse-free interval in patients with CTCL. Methods: Ten patients (one female, nine male) aged 50–78 years (mean 66.7 years) with relapsing or recalcitrant CTCL, stage I b (n=3), II a (2), II b (3), IV a (1), and IV b (1) were treated with PEG-DOXO 20 mg m⁻² once a month with an upper limit of 400 mg or eight infusions to induce a clinical response. There was one drop out after a single infusion because of a capillary leak syndrome. Results: In nine patients with PEG-DOXO the best response was a complete response (CR) in five patients and a partial response (PR) in four patients. The final outcome was CR in six, PR in two, stable disease (SD) in one, and progressive disease (PD) in another patient. The overall response rate (CR + PR) was 80% (of ten patients). The follow-up was 2–22 months (mean 12.8 ± 7.1 months). The overall survival was calculated as 19.8 ± 7.4 months with eight out of ten patients still alive. Response duration was 15.2 ± 3.9 months, disease-free survival 13.3 ± 6.1 months, event-free survival 16.7 ± 9.0 months, and progression-free survival 18.2 ± 6.5 months. Four patients (stage I b and II b) achieved 12–19 months of disease-free survival. The follow-up after the first course with PEG- DOXO was 2–22 months (mean 12.8 ± 7.1 months). The survival rate after 12 months of follow-up was 80% (n=5). One patient free of relapse died after 12 months because of pulmonary embolism not related to disease or treatment. Another patient died 1 month after a second course of PEG-DOXO in an advanced tumor stage of CTCL. The most frequent side effects of treatment were anemia and lymphopenia without the need of supportive treatment or dose-reduction. Only one patient developed toxicity of grade 4 (anemia). Conclusions: These results indicate that patients with relapsing or recalcitrant CTCL can achieve an 80% response rate with PEG-DOXO and long-term remissions. Received: 26 April 2000 / Accepted: 9 June 2000     

Long-Term Cure in Surgery for Extrarectal Pelvic Recurrence of Rectal Cancer

Purpose Survival benefit of radical surgery for locally recurrent rectal cancer depends on whether disease is cured rather than whether death is delayed. Cured patients gain decades of life and are spared from sufferings with recurrence. Unfortunately, the majority of patients undergoing surgery, particularly those with extrarectal pelvic recurrence, have poor outcomes with occult disseminated disease. This study was designed to identify which of these patients are curable. Methods Of 61 patients with pelvic recurrence treated by radical reexcision more than nine years before, 36 patients whose initial surgery was abdominoperineal resection were examined retrospectively. We used the logistic regression and Gamel-Boag regression models to estimate curability and identify predictors of cure. Results Ten patients survived five years and seven survived ten years. The cumulative disease-specific mortality curve leveled off 6.5 years after reexcision and remained at 74 percent (95 percent confidence interval, 60–89), indicating that the remaining 26 percent are curable. This value is comparable with the 23 percent curability estimated by the Gamel-Boag model, which also found that the disease-free interval from the initial surgery to the first recurrence is the best predictor of cure (P = 0.005). Of 11 patients with disease-free interval three years or more, 6 survived ten years, whereas 8 of 9 patients with disease-free interval less than one year died of second recurrence within three years of reexcision. Conclusions Even patients with extrarectal pelvic recurrence may have isolated disease that is amenable to complete eradication. As a biologic marker, the disease-free interval serves to predict curability and may distinguish isolated disease from occult disseminated disease.     

Local Excision of Distal Rectal Cancer: An Update of Cancer and Leukemia Group B 8984

Purpose  The efficacy of local excision in the treatment of some early-stage distal rectal cancers is still being debated, because few high-quality, long-term prospective data on outcomes are available. Methods  Fifty-nine patients with T1 lesions were treated with local excision alone, whereas 51 patients with T2 lesions received external beam irradiation (5,400 cGY) and 5-fluorouracil (500 mg/m² intravenously Days 1–3, Days 29–31) after local excision. Kaplan-Meier curves were used to estimate the primary outcomes. The log-rank test and Cox’s proportional hazards model were used to compare subgroups relative to these outcomes. Results  With a median follow-up of 7.1 (range, 2.1–11.4) years, ten-year rates of overall survival were 84 percent for patients with T1 and 66 percent for T2 rectal cancer. Disease-free survival was 75 percent for T1 and 64 percent for T2 disease. Local recurrence rates for patients with T1 and T2 lesions were 8 and 18 percent, respectively, and rates of distant metastases were 5 percent for T1 and 12 percent for T2 lesions. T stage was a statistically significant predictor of overall survival (P = 0.04) and approached statistical significance as a predictor of disease-free survival (P = 0.07). Conclusions  Local excision alone for T1 rectal adenocarcinomas is associated with low recurrence and good survival rates that remain durable with long-term follow-up. T2 lesions treated via local excision and adjuvant therapy are associated with higher recurrence rates. Read at the meeting of The American Society of Colon and Rectal Surgeons, St. Louis, Missouri, June 2 to 6, 2007.     

Portal vein thrombosis in hepatocellular carcinoma: age and sex distribution in an autopsy study

The purpose of this work was to investigate the prevalence, associated features and effect on survival of portal vein thrombosis (PVT) complicating hepatocellular carcinoma (HCC). The autopsy data of a series of 72 consecutive patients (57 male, 15 female) with HCC were reviewed. PVT was found in 32/72 patients (44%), and tended to be more common in female patients (10/15 versus 22/57, P = 0.052). Stratifying the data according to gender, it appeared that the mean age of patients with PVT compared to those without was greater in woman (71.9 ± 5.9 versus 63.2 ± 6.9 years, P = 0.024) and younger in men (58.8 ± 8.9 versus 66.0 ± 9.9 years, P = 0.007). When PVT was present, it was more likely that a definite diagnosis of HCC had been obtained before autopsy (P = 0.0001) and that death had been caused by bleeding complications (P = 0.007). Median survival times were similar, irrespective of the presence of PVT. During the natural history of HCC, PVT occurs in a substantial proportion of patients. Hormonal factors may have a permissive role in thrombus formation or neoplastic vascular invasion. Although in the presence of PVT a diagnosis of HCC is rarely missed and bleeding complications are likely to occur, patient survival does not seem to be significantly affected. Received: 30 September 1997 / Accepted: 4 April 1998     

Direct Tumor Invasion in Colon Cancer: Correlation with Tumor Spread and Survival

Purpose  This study examined the correlation between depth of local invasion in colon cancer and tumor spread and patient survival. Methods  A cohort of 796 patients with a complete set of TNM staging information following an elective resection for colon cancer was selected. The rates of lymph node and distant metastasis, tumor differentiation, and extramural venous invasion for different tumor (T) categories were compared. The effects of initial tumor (T) category on overall patient survival were studied. Results  The depth of local tumor invasion correlated strongly with nodal involvement (P = 0.0001), rates of extramural venous invasion (P = 0.0002), poor differentiation (P = 0.0001), and distant metastasis (P = 0.0001). Fifty-seven percent of the patients remained lymph node-negative and distant metastasis-negative irrespective of their depth of tumor invasion had no impact on overall survival (P = 0.49). For patients with lymph node or distant metastasis (43 percent), depth of tumor invasion had significant impact on overall survival (P = 0.001). Thirteen percent of T3N1, 33 percent of T3N2, 40 percent of T4N1, and 68.percent of T4N2 cases had distant metastasis at presentation. Conclusion  Two types of colon cancer were observed: locally active and tendency to metastasize. For the latter, overall mortality and the risk of metastasis increased with depth of tumor invasion. Reprints are not available.     

Prognostic Analysis of Rectal Stromal Tumors by Reference of National Institutes of Health Risk Categories and Immunohistochemical Studies

Purpose  Prognostic analysis of stromal tumors focusing on the rectal area is rarely performed. This study elucidated prognostic factors by referencing biomarkers of Ki67 and p53. Methods  Forty-nine surgically resected rectal stromal tumors were collected from 1986 to 2006. Immunohistochemical studies were performed with antibodies of CD117, CD34, smooth muscle actin, desmin, S100, Ki67, and p53. Results  The immunoreactivities were: CD34, 83.6 percent; smooth muscle actin, 28.5 percent; S100, 4.1 percent; desmin,16.3 percent;, Ki67, 30.6 percent;, and p53 34.7 percent. Both p53+ and Ki67+ tumors were associated with increased tumor mitosis, increased tumor size, nonspindle cell type, and increased cell pleomorphism (P < 0.05). Increased National Institutes of Health risk was associated with old age, nonspindle cell types, and severe nuclear pleomorphism (P < 0.05). Survival analysis demonstrated that older patients (P = 0.0039), large tumor size (P = 0.003), high mitotic count (P < 0.001), increased risk categories (P < 0.001), high cell pleomorphism (P = 0.003), p53+ (P = 0.007), and Ki67 + (P = 0.002) were prognostic factors for poor disease-free survival. An independent prognostic factor was tumor mitotic count. Conclusions  This study demonstrated the prognostic role of Ki67 and p53 in rectal stromal tumors. Notably, tumor mitosis was superior for prognostic prediction compared to National Institutes of Health risk categories. This work was supported in part by grants from National Science Council, Taiwan (NSC 93-2314-B-182A-145- to T. H. H.)     

Fecal Calprotectin as a Predictor of Abnormal Colonic Histology

Purpose Gastroenterologists have been seeking reliable noninvasive indices of inflammatory and malignant bowel disease. This prospective study was to assess the value of fecal calprotectin in predicting abnormal histologic findings in patients undergoing colonoscopy. Methods Stool specimens supplied before colonoscopy by 72 consecutive patients were measured for calprotectin levels, and the findings correlated with the colonoscopy results and other fecal and blood parameters. Receiver operating characteristics curve analysis was used to determine the predictive value of fecal calprotectin for abnormal colonic histology. Results Patients with abnormal histologic findings had significantly higher calprotectin levels (218 ± 125 mg percent) than patients with normal colonoscopy (77 ± 100 mg percent). There was a highly significant correlation between calprotectin levels and erythrocyte sedimentation rate (r = 0.45, P = 0.008), positive fecal occult blood test (r = 0.57, P = 0.0001), and abnormal colonic histology (r = 0.54, P = 0.0001). Patients with active inflammatory bowel disease had higher calprotectin levels than the rest of the study patients (r = 0.3; P = 0.01). On multivariate analysis, calprotectin was a significant predictor of abnormal colonic histology (P = 0.005; odds ratio, 1.007; 95 percent confidence interval, 1.002–1.012). The area under the receiver operating characteristics curve was 0.79. A fecal calprotectin concentration of 150 μg/ml had a sensitivity of 75 percent, specificity of 84 percent, positive predictive value of 80 percent, and negative predictive value of 75 percent in predicting abnormal colonic histology. Conclusions Fecal calprotectin may serve as a simple, noninvasive surrogate marker of abnormal histologic findings in patients scheduled for colonoscopy. Presented at Digestive Disease Week, Los Angeles, California, May 21 to 24, 2006.     

Is C-Reactive Protein a Prognostic Factor of Colorectal Cancer?

Purpose C-reactive protein, a commonly used inflammation marker, has been reported to be a prognostic factor of colorectal cancer. This prospective study was designed to confirm the prognostic value of its preoperative levels and to observe their perioperative change. Methods Between January 2001 and September 2005, preoperative C-reactive protein levels were obtained for 212 consecutive patients (140 males) receiving elective open resection of colorectal cancer. A level higher than 0.5 mg/dl was defined as positive. They were analyzed against clinicopathologic factors. The survival of 158 curative resections was analyzed. Postoperative levels (at months 1, 3, and 6) were collected for analysis of changing trend, from the patients receiving curative surgeries. Results Median value of preoperative C-reactive protein was 0.54 mg/dl (48.6 percent positive). Positive rate was significantly correlated with ulcerative type, larger size, higher stage, and positive carcinoembryonic antigen (>5 ng/ml). In both univariate log-rank test and multiple Cox proportional hazards regression, stage (univariate P = 0.011, and multivariate P = 0.016; hazard ratio, 6.23; 95 percent confidence interval, 1.41–27.54), C-reactive protein (0.5 mg/dl; P = 0.005, and P = 0.016; hazard ratio: 6.51; 95 percent confidence interval: 1.41–30.05), and differentiation (P = 0.006, and P = 0.043; hazard ratio, 3.53; 95 percent confidence interval, 1.04–11.98) were significant factors. Analysis of disease-free interval showed C-reactive protein was significant (P = 0.03): as level rose, prognosis worsened. The quiescent inflammation-response group (≤0.1 mg/dl) had excellent outcomes. Postoperatively, the C-reactive protein levels declined at the third postoperative month. Conclusions Preoperative C-reactive protein is an independent prognostic factor. The levels declined postoperatively, although with a lag. These findings seem to support the response hypothesis regarding C-reactive protein. Supported by Taipei Veterans General Hospital Grant 97.     

Earlier Eradication of Intra-Anal Warts with Argon Plasma Coagulator Combined with Imiquimod Cream Compared with Argon Plasma Coagulator Alone: A Prospective,Randomized Trial

Purpose Despite the increasing incidence of condylomata acuminate, optimal treatment of anal warts is still undecided. This prospective, randomized study was designed to compare the efficacy of combined argon plasma coagulation and imiquimod cream vs. argon plasma coagulation alone in the management of intra-anal warts. Methods From October 2002 to March 2005, 49 patients with intra-anal warts were randomly assigned to argon plasma coagulation plus imiquimod cream (n = 24) vs. argon plasma coagulation alone (n = 25). Therapeutic sessions were repeated until the elimination of the warts. Efficacy of therapy was defined as the time needed for eradication. All patients were followed up for a mean period of 12 months for signs of recurrence. Results Elimination of warts was achieved earlier in patients receiving combination therapy compared with those receiving monotherapy with argon plasma coagulation (62.5 ± 5.4 days vs. 91.2 ± 6.4 days; P = 0.0016). A subgroup analysis performed in HIV-positive patients showed similar results (combination therapy 95 ± 22.6 days; monotherapy 124.3 ± 20.7 days; P = 0.033); however, in HIV-positive patients warts were eradicated later compared with HIV-negative patients (110.8 ± 25.7 days vs. 65 ± 25.4 days; P < 0.0001). No major complications were observed in our study population. After the follow-up period, recurrence of warts was evident in 22.7 percent of patients in the combination group compared with 34.7 percent of patients in the monotherapy group (P = 0.51). Recurrence was significantly higher in HIV-positive patients compared with HIV-negative patients (P = 0.0039). Conclusions Combination therapy with argon plasma coagulator plus imiquimod cream results in earlier clearance of intra-anal warts in both immunocompetent and immunocompromised patients; however, it does not affect the rate of recurrence. Reprints are not available.     

Prognostic significance of DNA cytometry in thymoma

 Purpose: The aim of this work was to evaluate the prognostic significance of DNA image cytometry in thymoma. Patients and methods: Image cytometric studies with an automatic video-based analysis system (LEYTAS) were carried out on 47 archival specimens from 36 patients with thymomas who underwent operation at a single institution from 1954 to 1992. The significance of aneuploidy DNA-content (5c-exceeding events), and nuclear size on stage and survival were evaluated. The median follow-up was 52.7 (6–164) months. Results: Masaoka's stage was predictive of aneuploidy (P < 0.01) and disease-free survival (P < 0.015). In stage I 18% of the tumors were aneuploid, in stage II 78%, in stage III 85% and in stage IV 100%. The occurrence of 5c-exceeding events was associated with both decreased disease-free survival (P < 0.01) and overall survival (P = 0.013). Nuclear size was not significantly correlated to stage. Under multivariate analysis, aneuploidy and DNA content failed to attain independent significance for stage, performance status, and histology. Conclusion: DNA image cytometry may provide additional information about the prognosis of resected thymoma. Received: 25 August 1999 / Accepted: 2 December 1999