Patient expectations of functional outcomes after rectal cancer surgery: a qualitative study.

BACKGROUND: Rectal cancer patients' expectations of health and function may affect their disease- and treatment-related experience, but how patients form expectations of postsurgery function has received little study. OBJECTIVE: We used a qualitative approach to explore patient expectations of outcomes related to bowel function after sphincter-preserving surgery for rectal cancer. DESIGN: This was a cohort study of patients who were about to undergo sphincter-preserving surgery for rectal cancer. SETTINGS: The study was conducted through individual telephone interviews with participants. PATIENTS: Twenty-six patients (14 men and 12 women) with clinical TNM stage I to III disease were enrolled. MAIN OUTCOME MEASURES: The semistructured interview script contained open-ended questions on patient expectations of postoperative bowel function and its perceived impact on daily function and life. Two researchers analyzed the interview transcripts for emergent themes using a grounded theory approach. RESULTS: Participant expectations of bowel function reflected 3 major themes: 1) information sources, 2) personal attitudes, and 3) expected outcomes. The expected outcomes theme contained references to specific symptoms and participants' descriptions of the certainty, importance, and imminence of expected outcomes. Despite multiple information sources and attempts at maintaining a positive personal attitude, participants expressed much uncertainty about their long-term bowel function. They were more focused on what they considered more important and imminent concerns about being cancer free and getting through surgery. LIMITATIONS: This study was limited by context in terms of the timing of interviews (relative to the treatment course). The transferability to other contexts requires further study. CONCLUSIONS: Patient expectations of long-term functional outcomes cannot be considered outside of the overall context of the cancer experience and the relative importance and imminence of cancer- and treatment-related events. Recognizing the complexities of the expectation formation process offers opportunities to develop strategies to enhance patient education and appropriately manage expectations, attend to immediate and long-term concerns, and support patients through the treatment and recovery process.

A phase II, randomized, controlled trial of acupuncture for reduction of Postcolectomy Ileus.

PURPOSE: Postoperative ileus (POI) prolongs hospital stay and increases risk of postoperative complications. We conducted a randomized, sham-controlled trial to evaluate whether acupuncture reduces POI more effectively than sham acupuncture. METHODS: Colon cancer patients undergoing elective colectomy were randomized to receive 30 min of true or sham acupuncture twice daily during their first 3 postoperative days. GI-3 (the later of the following two events: time that the patient first tolerated solid food, AND time that the patient first passed flatus OR a bowel movement) and GI-2 (the later of the following two events: time patient first tolerated solid food AND time patient first passed a bowel movement) were determined. Pain, nausea, vomiting, and use of pain medications were evaluated daily for the first 3 postoperative days. RESULTS: Ninety patients were randomized. Eighty-one received the allocated intervention: 39 in the true acupuncture group and 42 in the sham acupuncture group, all evaluated for the primary endpoint. The mean time to GI-3 was 149 h [standard deviation (SD) 71 h] and 146 (SD 62 h) after surgery for the acupuncture group and the sham acupuncture group (difference between means -2 h; 95 % confidence interval -31, 26; p = 0.9). No significant differences were found between groups for secondary endpoints. CONCLUSIONS: True acupuncture as provided in this study did not reduce POI more significantly than sham acupuncture. The study was limited by a standard deviation much larger than expected, suggesting that a study with a larger sample size might be required.

Pulmonary recurrence predominates after combined modality therapy for rectal cancer: an original retrospective study.

OBJECTIVE: To characterize patterns of recurrence in locally advanced rectal cancer treated with combined modality therapy (CMT): neoadjuvant chemoradiation + total mesorectal excision + adjuvant chemotherapy. METHODS: A total of 593 consecutive rectal cancer patients (1998 to 2007) with locally advanced (stage II/III) disease (noted on endorectal ultrasound or magnetic resonance imaging) who received CMT were analyzed for patterns of recurrence. RESULTS: After median 44-month follow-up (interquartile range, 25 to 64 months), 119 patients (20%) recurred: 105 distant, 7 local, 7 local and distant, and 112 distant-only recurrence. Ninety-three (78%) had single-organ recurrence, and 26 (22%) had multiple-organ recurrence. The most common site of distant recurrence was lung (69% of all patients with distant relapse); 20% had liver recurrence. Fourteen patients (2.4%) recurred locally. Pulmonary metastases were most commonly identified by computed tomographic scan versus abnormal positron emission tomographic (PET) scan or carcinoembryonic antigen (CEA). Risk factors associated with pulmonary recurrence were the following: pathologic stage, tumor distance from anal verge, lymphovascular or perineural invasion. Five-year freedom from pulmonary recurrence for patients with 0, 1, 2, or 3 risk factors was 99%, 90%, 61%, and 42%, respectively. Thirty of 59 patents with pulmonary recurrence underwent lung metastasectomy; 3-year freedom from recurrence was 37%. CONCLUSIONS: Unlike colon cancer, which most frequently recurs in the liver, locally advanced rectal cancer treated with CMT relapses most frequently in the lung. Pulmonary metastasis was associated with advanced pathologic stage, low-lying tumor, lymphovascular invasion, or perineural invasion. Confirmation of pulmonary metastasis usually requires serial imaging because metastases are often small when initially detected, well below the resolution of PET, and not necessarily associated with elevated CEA. Individualized risk-based surveillance strategies are recommended in this patient population.

Whole-mount pathologic analysis of rectal cancer following neoadjuvant therapy: implications of margin status on long-term oncologic outcome.

OBJECTIVE: Extent of distal resection margins in rectal cancer surgery remains controversial. We set out to determine the long-term oncologic impact of resection margins in patients with locally advanced rectal cancer using a comprehensive pathologic whole-mount section analysis. BACKGROUND: It has been demonstrated that there is minimal disease beyond the gross tumor margin after neoadjuvant combined modality therapy (CMT) for rectal cancer. Although this suggests that close resection margins may be used for sphincter preservation, the long-term oncologic impact of this approach is unclear. METHODS: We prospectively enrolled 103 patients with locally advanced rectal cancer after neoadjuvant CMT. Whole-mount pathologic analysis was performed, and clinicopathologic variables were correlated with disease-specific survival (DSS). RESULT: : Sphincter preservation was achieved in 80% of patients, and the median distal margin was 2 cm (0.1 to 10 cm). There were 22 patients (21%) with distal margins 1 cm or less and no patient had a positive distal margin. Median radial margin was 1 cm and 4 patients (4%) had a margin of 1 mm or less. Viable distal intramural tumor spread was found in 3 patients (2.7%) and in all cases was limited to 1 cm or less from the gross tumor edge. At a median follow-up of 68 months, 5-year DSS was 86% and 1 patient experienced a local recurrence. Factors predictive of worse DSS included advanced tumor (T) and nodal (N) stage, tumor progression on neoadjuvant CMT, lack of a complete pathologic response, tumor location of 5 cm or less from the anal verge, and neurovascular invasion. The extent of the distal and radial margins of resection was not associated with DSS. CONCLUSIONS: These results suggest that carefully selected patients with locally advanced rectal cancers who undergo neoadjuvant CMT can achieve excellent local control and DSS with a sphincter-sparing rectal resection and a margin distal clearance of 1 cm.

A predictive model for lymph node yield in colon cancer resection specimens.

OBJECTIVE: To develop a predictive model of lymph node yield in a series of colon cancer resection specimens with detailed anatomic and surgical technique data. BACKGROUND: Lymph node yield in colon resection specimens has been associated with accuracy of staging and cancer outcomes. We hypothesized that lymph node yield is associated with multiple factors including patient, tumor,and surgical variables. METHODS: The pathology specimens from 152 elective colon neoplasm resections were prepared so that the lymph nodes were separated according to their anatomic relationship to the vascular pedicles and to the tumor. Prior to dissection, the specimen was measured. A linear regression analysis of a priori identified predictors and confounders of lymph node quantity was performed. Potential predictors in the model were age, gender, tumor stage, size, location,and differentiation, presence of lymphovascular or perineural invasion,mucinous histology, number of vascular pedicles, and use of endoscopic tattoo. Potential confounders were American Society of Anesthesiologists class, body mass index, count of lymph node metastasis, and specimen length. RESULTS: Tumor size, tumor location, number of resected pedicles, and use of tattoo had a significant linear or quadratic relationship with lymph node yield when controlling other variables. 23% of the variation in lymph node count was explained by the 15 variables in the model. A model with the 4 significant variables explained 19% of the variation. CONCLUSION: Multiple tumor and surgical factors are associated with lymph node yields in colon specimens. A standard minimum of lymph nodes may not be applicable to all colon cancer resections.

Recurrence rates and prognostic factors in ypN0 rectal cancer after neoadjuvant chemoradiation and total mesorectal excision.

BACKGROUND: Neoadjuvant chemoradiation followed by surgery and adjuvant chemotherapy is typically recommended for patients with locally advanced rectal cancer. Patients with pathologically node-negative tumors have an improved prognosis, but recurrence patterns and independent prognostic factors in these patients have been incompletely characterized. METHODS: Using a retrospective cohort study design, we included all rectal cancer patients treated with neoadjuvant chemoradiation and curative surgery from 1993 through 2003, who had ypN0 tumors. We characterized recurrence rates and patterns in patients not treated with adjuvant chemotherapy. Secondarily, we compared them to patients who did receive adjuvant treatment and assessed for independent prognostic factors, using univariate and multivariable survival analyses. RESULTS: Overall, 324 ypN0 patients (ypT0: n = 73; ypT1-2: n = 130; ypT3-4: n = 120) were followed for a median of 5.8 years. The risk of recurrence was associated with pathologic stage-2.7% ypT0, 12.3% ypT1-2, 24.2%ypT3-4. Five-year recurrence-free survival in patients who did not receive adjuvant treatment was 100% (ypT0), 84.4% (ypT1-2) and 75% (ypT3-4). There was no significant difference in 5-year recurrence-free survival between patients who did and did not receive adjuvant treatment. In multivariable analysis, pathologic stage was the factor most strongly associated with recurrence (hazard ratio 3.6 for ypT3-4 vs. ypT0-2, 95% confidence interval 1.9-6.7, P < 0.0001). CONCLUSIONS: The recurrence rates for selected patients with ypT0-2N0 rectal cancer after neoadjuvant chemoradiation and total mesorectal excision are low. Although standard practice remains completion of planned postoperative adjuvant chemotherapy for all patients undergoing chemoradiation, these data suggest prospective trials may be warranted to measure the benefit of adjuvant chemotherapy in favorable subgroups, such as ypT0-2N0.

Impact of a temporary stoma on the quality of life of rectal cancer patients undergoing treatment.

BACKGROUND: Data from randomized controlled trials support use of a diverting stoma in rectal cancer patients with low anastomoses, but there is little data on how this impacts patient quality of life (QOL). This study prospectively evaluates QOL in stage I-III rectal cancer patients undergoing sphincter-preserving surgery (SPS) with a temporary diverting stoma. MATERIALS AND METHODS: Patents were identified from a prospective single-institution study of stage I-III rectal cancer patients undergoing SPS. Patients completed the EORTC C30/CR38 QOL scale preoperatively, at stoma closure, and at 6 months. The Stoma Quality of Life (SQOL) was administered at stoma closure. Subscales of the EORTC hypothesized to be affected by a diverting stoma were identified a priori. Longitudinal trends were analyzed using repeated measures ANOVA. Frequencies for responses on specific SQOL items were tabulated, and correlations between SQOL subscales and EORTC Global QOL assessed with Pearson correlation coefficient. RESULTS: Global QOL was reportedly good (mean score 70.2) and did not change with a temporary stoma (P = .83). Physical (P = .33), role (P = .07), and social function (P = .48) were also stable. Decreased body image was observed (P = .03). Stoma-related difficulties identified by the SQOL included sexual activity (53%), leakage (39%), discomfort in clothing (34%), concerns regarding privacy to empty pouch (32%), and feeling unattractive (31%). "Overall satisfaction with life," Work/social function (P < .001), sexuality/body image (P = .01), and stoma function (P = .01) subscales of the SQOL correlated strongly with the EORTC Global QOL score (P < .001). CONCLUSION: In this longitudinal study of QOL in rectal cancer patients with a temporary stoma, Global QOL was good despite significant stoma-related difficulties. Use of alternative research methodology is necessary to provide insight into why this contradiction exists.

Evaluation of ¹8F-FDG-PET for early detection of suboptimal response of rectal cancer to preoperative chemoradiotherapy: a prospective analysis.

BACKGROUND: Early identification of inadequate response to preoperative chemoradiotherapy (CRT) may spare rectal cancer patients the toxicity of ineffective treatment. We prospectively evaluated tumor response with (18)F-fluorodeoxyglucose (FDG) positron emission tomography (PET) early in the course of preoperative CRT. METHODS: A total of 27 prospectively accrued patients with locally advanced rectal cancer (T(3-4)/N(1)) received preoperative CRT (5040 cGy + 5FU-based chemotherapy). Patients underwent PET scanning before and 8-14 days after commencement of CRT. Scans were interpreted using 3 standard parameters: SUV(max), SUV(avg), and total lesion glycolysis (TLG) as well as an investigational parameter: visual response score (VRS). Percent pathologic response was quantified as a continuous variable. All PET parameters were correlated with pathology. Pathologic complete/near-complete response was defined as ≥95% tumor destruction, suboptimal response as <95%. Statistical analysis was performed using the Wilcoxon rank sum test and receiver operating characteristic (ROC) curve analysis. RESULTS: Of the 27 patients, 11 (41%) had pathologic complete/near-complete response; 16 (59%) had suboptimal response. SUV(max), SUV(avg), and TLG did not discriminate between responders and nonresponders. Visual response score (VRS) was statistically significantly higher for complete/near-complete responders than for suboptimal responders (65 vs. 33%, P = 0.02). Suboptimal responders were identified with 94% sensitivity and 78% accuracy using a VRS cut-off of 50%. CONCLUSIONS: In this pilot study, FDG-PET at 8-14 days after the beginning of preoperative CRT was unsuccessful at predicting pathological response with enough accuracy to justify an early change in therapy.

Surgery and high-dose-rate intraoperative radiation therapy for recurrent squamous-cell carcinoma of the anal canal.

BACKGROUND: Locoregionally recurrent squamous-cell carcinoma of the anal canal is managed with salvage surgery. High-dose-rate intraoperative radiation therapy has been used in selected patients with this disease to reduce the risk of local recurrence. OBJECTIVE: The aim of this article is to present our institutional experience with this technique. DESIGN: Medical records of 14 patients with locoregionally recurrent squamous-cell carcinoma of the anal canal who underwent this technique between 1992 and 2007 were reviewed. SETTING: The study was conducted at an academic cancer center. PATIENTS: The median age was 45 years (range, 36-77), and 13 of the patients were women. All had prior radiation with or without chemotherapy. INTERVENTIONS: The surgical procedures included abdominoperineal resection with or without sacrectomy (n = 8), low anterior resection (n = 2), and pelvic exenteration (n = 4). The median radiation dose was 1500 cGy (range, 1500-1750). All cases of radiographic invasion of adjacent structures correctly predicted pathologic invasion. There was pathologic invasion into adjacent structures in 11 cases (79%), and adherence to the sacrum without invasion in 2 cases (14%). Surgical margins were positive (n = 6), close (<1 mm) (n = 3), and negative (n = 5). RESULTS: The median follow-up from our technique was 17 months (range, 5-145). Subsequent recurrence occurred in 11 cases, at a median of 8 months from treatment. Two-year actuarial control was 7.1%, and the overall survival was 21.4%. Acute toxicities included wound-healing complications (n = 6); gastrointestinal obstruction (n = 5); neurogenic bladder (n = 1); ureteral stricture (n = 3); and peripheral neuropathy (n = 2). LIMITATIONS: This is a small retrospective series in which the meaningful analysis of associations between clinical variables and outcomes was not possible. CONCLUSION: Salvage surgery with high-dose-rate intraoperative radiation therapy did not appear to be associated with a locoregional control or survival benefit in this series. The addition of high-dose-rate intraoperative radiation therapy to salvage surgery is insufficient to compensate for positive surgical margins. Preoperative imaging should be used to aid in patient selection to identify those patients in whom negative margins can be obtained and to aid in the determination of appropriate salvage surgery.

Close distal margin and rectal cancer recurrence after sphincter-preserving rectal resection.

PURPOSE: Negative surgical margins are important for local control of rectal cancer treated with sphincter-preserving surgery. However, the association of rectal cancer recurrence with close distal margin is not well established. METHODS: Data were extracted from a prospective database of patients collected between 1991 and 2003. Included were 627 patients who underwent curative low anterior resection with total mesorectal excision for rectal cancer 2 to 12 cm from the anal verge. Three hundred ninety-nine patients received neoadjuvant therapy, 65 received postoperative adjuvant therapy alone, and 163 were treated with surgery alone. Median follow-up was 5.8 years. RESULTS: On multivariable analysis, overall recurrence was associated with pathologic stage, lymphovascular invasion, and distal margin. Mucosal recurrence was uncommon; only 16 events were recorded, and of those only 8 were at the initial site of isolated tumor recurrence; 7 of the 8 were surgically salvaged. On univariable analysis, mucosal recurrence was associated with close distal margin (5 vs 2% at 5 y) and lymphovascular invasion (7 vs 2%). Pelvic recurrence, other than isolated mucosal recurrence, was associated with distal location (6 vs 4% at 5 y) and lymphovascular invasion (11 vs 4%). Distal margin as a continuous variable was associated with overall recurrence (excluding isolated mucosal recurrence). CONCLUSIONS: Close distal resection margin identifies patients with increased risk of mucosal and overall cancer recurrence. Although neither causality nor a minimally acceptable margin length can be defined, the data support the importance of achieving a clear distal resection margin in the surgical management of rectal cancer.

Sphincter preservation in low rectal cancer is facilitated by preoperative chemoradiation and intersphincteric dissection.

OBJECTIVE: The aim of this study was to evaluate oncologic outcome in patients with locally advanced distal rectal cancer treated with preoperative chemoradiation followed by low anterior resection (LAR)/stapled coloanal anastomosis, LAR/intersphincteric dissection/hand-sewn coloanal anastomosis, or abdominoperineal resection (APR). SUMMARY BACKGROUND DATA: Distal rectal cancer presents a surgical challenge, and the goals of treatment often include tumor eradication without sacrifice of the anal sphincters. The technique of intersphincteric resection removes the internal anal sphincter to gain additional distal rectal margin in hopes of avoiding a permanent stoma. METHODS: We analyzed 148 patients with stage II and III rectal cancers (endorectal ultrasound staged uT3-4 and/or uN1) located < or =6 cm from the anal verge, treated by preoperative chemoradiation and total mesorectal excision from 1998 to 2004. Eighty-five patients (57%) had sphincter-preserving resection (41, LAR/stapled coloanal anastomosis; 44, LAR/intersphincteric resection/hand-sewn coloanal anastomosis); 63 patients had APR. RESULTS: Patients undergoing APR were older, with more poorly differentiated tumors evidencing less response to chemoradiation and more likely to require extended resection. Complete resection with negative histologic margins was achieved in 92%; circumferential margins were positive in 2 (5%) of 44 in the intersphincteric resection group and 8 (13%) of 63 in the APR group. Distal margins were positive in 2 (5%) of 44 in the intersphincteric resection group. With median follow-up of 47 months, there were a total of 7 local recurrences (5%): 1, 0, and 6 in the stapled anastomosis, intersphincteric resection, and APR groups, respectively. Estimated 5-year recurrence-free survival for the stapled anastomosis, intersphincteric resection, and APR groups were 85%, 83%, and 47% respectively (P = 0.001). CONCLUSIONS: In low rectal cancer, sphincter preservation is facilitated by a significant response to preoperative chemoradiation and intersphincteric resection, without compromise of margins or outcome. In those who have a less favorable response, abdominoperineal resection is more likely to be required and is associated with poorer outcome.

Feasibility of ex vivo FDG PET of the colon.

To facilitate future direct correlations between fluorine 18 fluorodeoxyglucose (FDG)-avid colonic lesions and immunohistochemical assay findings, the authors tested the feasibility of ex vivo FDG positron emission tomography (PET) of the colon resected from humans. In this institutional review board-approved, HIPAA-compliant study, the authors, after obtaining informed patient consent, injected FDG intraoperatively in five patients with neoplasms and imaged their resected colons approximately 3 hours later. The colon could be imaged during this fairly limited time interval, and polyps and cancers could be identified. No biologic tissue degradation occurred. The authors concluded that ex vivo FDG PET of the colon is feasible and, when combined with careful histologic and immunohistochemical analyses, may serve as a research tool to determine the mechanisms of the normal colonic uptake of FDG and the localization of FDG in polyps and cancers.

Treatment for patients with rectal cancer and a clinical complete response to neoadjuvant therapy: a decision analysis.

PURPOSE: A clinical complete response to neoadjuvant therapy occurs in a subset of patients with rectal cancer. Management of these patients is controversial and tension exists between the recurrence risk with observation, and the impact of surgery on quality-of-life. Therefore, the objective was to develop a decision-analytic model to evaluate the relative benefits of surgery vs. observation in rectal cancer patients who achieve clinical complete response after neoadjuvant chemoradiation. METHODS: Clinically relevant inputs and events, including the ability to identify complete responders, likelihood of relapse and of salvage surgery after relapse, and utilities for each health state, were simulated by use of a Markov state-transition model. Transition probabilities and health-state utilities were derived from the literature and expert consensus. One-way and two-way sensitivity analyses were performed to assess the robustness of model results to assumptions. The primary outcome was quality-adjusted life expectancy. RESULTS: In the base-case analysis, the quality-adjusted life expectancy with surgery exceeded observation (5.63 vs. 5.34 quality-adjusted life-years). Sensitivity analysis demonstrated that observation was preferred to surgery if the ability to correctly identify patients with true complete responses exceeded 58 percent, if quality-of-life after surgery was poor (utility <0.81), or if the relative reduction in recurrence risk with surgery was <43 percent when compared with observation. CONCLUSIONS: Our model outlines the issues associated with surgery vs. observation, and suggests that surgery is beneficial for the average patient with rectal cancer with a clinical complete response after neoadjuvant therapy. Current limitations in the clinical assessment of patient response to chemoradiation constitute an important factor influencing our results, and therefore warrant further investigation.

Long-term survival after transanal excision of T1 rectal cancer.

PURPOSE: Several series report higher recurrence after transanal excision of T1 rectal cancer than after radical resection. However, the impact of transanal excision on cancer mortality has not been adequately studied. The purpose of this study was to compare oncologic outcomes of transanal excision with those of radical resection. METHODS: Patients with transanal excision or radical resection for T1 rectal cancer treated between 1985 and 2004 were identified from a prospective database. Patients receiving preoperative chemotherapy or radiation or with tumors >12 cm from the anal verge were excluded. RESULTS: The final cohort comprised 145 radical resections and 137 transanal excisions. The transanal excision group was notable for older mean age (64 vs. 59 years), shorter mean distance from anal verge (5.9 vs. 7.8 cm), and smaller tumor size (2.3 vs. 3.1 cm). Lymphovascular invasion and poor differentiation were similar in both groups. Twenty percent of radical resection specimens had lymph node metastasis. Median follow-up was 5.6 years. Local recurrence was noted in a higher proportion of transanal excision patients (13.2 vs. 2.7 percent, P = 0.001). After transanal excision the hazard ratio for local recurrence was 11.3 (95 percent confidence interval, 2.6-49.2), and disease-specific survival was inferior (87 vs. 96 percent at 5 years, P = 0.03, hazard ratio 2.8 [range, 1.04-7.3]). CONCLUSIONS: Transanal excision offers inferior oncologic results, including greater risk of cancer-related death. This procedure should be restricted to patients who have prohibitive medical contraindications to major surgery or have made an informed decision to accept the oncologic risks of local excision and avoid the functional consequences of rectal resection.

Positron emission tomography detection of distant metastatic or synchronous disease in patients with locally advanced rectal cancer receiving preoperative chemoradiation.

BACKGROUND: Patients with locally advanced rectal cancer may present with synchronous distant metastases. Choice of optimal treatment--neoadjuvant chemoradiation versus systemic chemotherapy alone--depends on accurate assessment of distant disease. We prospectively evaluated the ability of [18F]fluorodeoxyglucose ([18F]FDG) positron emission tomography (PET) to detect distant disease in patients with locally advanced rectal cancer who were otherwise eligible for combined modality therapy (CMT). METHODS: Ninety-three patients with locally advanced rectal cancer underwent whole-body [18F]FDG PET scanning 2-3 weeks before starting CMT. Sites other than the rectum, mesorectum, or the area along the inferior mesenteric artery were considered distant and were divided into nine groups: neck, lung, mediastinal lymph node (LN), abdomen, liver, colon, pelvis, peripheral LN, and soft tissue. Two nuclear medicine physicians blinded to clinical information used PET images and a five-point scale (0-4) to determine certainty of disease. A score greater than 3 was considered malignant. Confirmation was based on tissue diagnosis, surgical exploration, and subsequent imaging. RESULTS: At a median follow-up of 34 months, the overall accuracy, sensitivity, and specificity of PET in detecting distant disease were 93.7%, 77.8%, and 98.7% respectively. Greatest accuracy was demonstrated in detection of liver (accuracy = 99.9%, sensitivity = 100%, specificity = 98.8%) and lung (accuracy = 99.9%, sensitivity = 80%, specificity = 100%) disease; PET detected 11/12 confirmed malignant sites in liver and lung. A total of 10 patients were confirmed to have M1 stage disease. All 10 were correctly staged by pre-CMT PET; abdominopelvic computed tomography (CT) scans accurately detected nine of them. CONCLUSION: Baseline PET in patients with locally advanced rectal cancer reliably detects metastatic disease in liver and lung. PET may play a significant role in defining extent of distant disease in selected cases, thus impacting the choice of neoadjuvant therapy.

Immunohistochemical expression of folate receptor alpha in colorectal carcinoma: patterns and biological significance.

Folate receptor alpha (FRalpha) has emerged as a potential cancer therapy target with several folate-linked therapeutic agents currently undergoing clinical trials. In addition, FRalpha expression in tumors may offer prognostic significance. Most studies on FRalpha expression used reverse transcriptase polymerase chain reaction or cytofluorimetric assays. The applicability of such methods to paraffin-embedded tissues is limited. The aims of this study were to assess the feasibility of immunohistochemistry in detecting FRalpha expression and to assess the patterns and clinical significance of FRalpha expression in colorectal tissues. We used tissue microarrays containing 152 normal colorectal mucosa samples, 42 adenomas, 177 primary, and 52 metastatic colorectal carcinomas. Our results showed that staining for FRalpha on colorectal tissues was simple and easy to read. FRalpha positivity was more frequent in carcinomas (33% in primaries and 44% in metastases) than in normal mucosa or adenoma (7% in both) (P < .001). Positive staining in primary carcinomas correlated with younger age (n = 130) (P = .008), presence of distant metastasis (n = 130) (P = .043), and non-high-frequency microsatellite instability status (as detected by the standard polymerase chain reaction method using the 5 National Cancer Institute-recommended markers) (n = 77) (P = .006). Positive staining in primary carcinomas also correlated with a worse 5-year disease-specific survival (P = .04) on univariate but not multivariate analysis. Thus, our data show that there is selective expression of FRalpha in some colorectal cancers, providing a foundation for investigating the use of folate conjugates for imaging and therapy of colorectal tumors. Furthermore, our results suggest that a possible association exists between FRalpha expression and the microsatellite instability status in colorectal carcinoma. The significance of such an association as well as the prognostic value of FRalpha expression deserves further exploration.

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 > or = 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.

A novel method to localize antibody-targeted cancer deposits intraoperatively using handheld PET beta and gamma probes.

BACKGROUND: Assessing cancer margins, lymph nodes, and small cancer deposits intraoperatively can be challenging. A new device has become available that allows the detection of positron emission tomography (PET) radiotracers through both high-energy gamma and short-range beta emissions. These PET probes are handheld, allowing for real-time evaluation of cancer using a tool that provides surgeons with better intraoperative assessment of tumor sites. METHODS: Within the context of two institutional review board (IRB)-approved protocols investigating new applications of antibody-labeled PET scanning, (124)I-labeled humanized monoclonal antibodies specific for colorectal cancer (huA33) and renal tumors (cG250) were constructed. Patients underwent preoperative PET scans, approximately seven days post-tracer infusion, when tumor-to-nontumor ratios were high. Suspected tumor deposits were evaluated intraoperatively with handheld beta and gamma PET probes. RESULTS: Handheld PET probes detected emissions from all tumors. Count rates from the gamma probe on tumor ranged from 48 to 306 cps, and for the beta probe ranged from 18 to 190 cps. Gamma and beta emissions exhibited a strong positive correlation. The ratio of gamma and beta counts was at least twice that of the background counts for all tumors evaluated. CONCLUSIONS: This study is the first to demonstrate the utility of beta probes for the intraoperative detection of radiolabeled antibodies targeting cancer. Importantly, the recorded beta count rates from the beta probe correlate with the count rates from the high-energy gamma probe. Furthermore, the beta probe may offer superior specificity for real-time localization of small tumor deposits, compared to gamma probes. The intraoperative portable PET probe may prove a valuable bridge to combining tumor biology and PET technology to guide surgical therapy.

Differential expression of alpha-methylacyl-coenzyme A racemase in colorectal carcinoma bears clinical and pathologic significance.

alpha-methylacyl-coenzyme A racemase (AMACR) is a recently discovered biomarker that is shown to be overexpressed in some prostatic carcinomas and associated with prostatic cancer progression. Given that AMACR plays an important role in peroxisomal beta-oxidation of branched-chain fatty acids from red meat and dairy products, and that consumption of red meat may increase risk of developing colon cancer as suggested by epidemiological studies, it is plausible to explore the function of AMACR in colorectal carcinoma. A few previous studies have indeed observed overexpression of AMACR in 45% to 69% of the colorectal carcinomas. However, the clinical and pathologic characteristics of such AMACR expressers have not been investigated. In this study, the immunohistochemical expression pattern of AMACR of 163 patients with primary colorectal carcinoma treated primarily with surgical resection was analyzed and correlated with tumor pathologic features (tumor location, histologic type, grade, pathologic stage, lymph node and distant metastasis) and patient outcome (disease-specific survival). The results showed variable positive staining for AMACR in 123 (75%) of 163 tumors, and moderate to strong staining in 63 (39%) of 163. Lack of staining or low-intensity staining appeared to correlate significantly with mucinous histology (P < .001), poor tumor differentiation (P = .021), and presence of lymphovascular invasion (P = .032). Patients whose tumors showed lack of staining or low-intensity staining also had a significantly worse 5-year disease-specific survival (P < .012), as did patients whose tumors had lymphovascular invasion, or were of high American Joint Committee on Cancer (AJCC) stage. On multivariate analysis, AMACR staining and AJCC staging remained independent predictors for patient outcome. Thus, our data suggest that AMACR expression in colorectal carcinoma correlates with certain tumor pathologic characteristics (histologic type, differentiation, and lymphovascular invasion) and patient outcome. Additional confirmatory studies are needed to establish the significance of AMACR as a prognostic marker for colorectal carcinoma. Further investigation on interaction between AMACR and other known colorectal cancer development pathways may provide new insights on colorectal carcinogenesis.

Distal cT2N0 rectal cancer: is there an alternative to abdominoperineal resection?

PURPOSE: Patients with cT2N0 distal rectal cancer do not require adjuvant therapy. However, when a patient refuses an abdominoperineal resection (APR), is there an alternative? The purpose of this trial is to determine whether preoperative external-beam radiation therapy can increase the rate of sphincter preservation for patients with distal cT2N0 adenocarcinoma of the rectum. PATIENTS AND METHODS: Between April 1988 and October 2003, 27 patients with distal rectal adenocarcinoma staged T2 by clinical and/or endorectal ultrasound who were judged by the operating surgeon to require an APR were treated with preoperative pelvic radiation alone (50.4 Gy). Surgery was performed 4 to 7 weeks later. If pathologic positive pelvic nodes were identified, postoperative adjuvant chemotherapy was recommended. The median follow-up was 55 months (range, 9 to 140 months). RESULTS: The pathologic complete response rate was 15% and 78% of patients underwent a sphincter-sparing procedure. The crude incidence of local failure for patients undergoing a sphincter sparing procedure was 10% and the 5-year actuarial incidence was 13%. The actuarial 5-year survival for patients undergoing sphincter preservation was as follows: disease-free, 77%; colostomy-free, 100%; and overall, 85%. Using the Memorial Sloan-Kettering Cancer Center sphincter function score, 54% of those undergoing a sphincter-sparing procedure had good/excellent bowel function at 12 to 24 months after surgery, and 77% had good/excellent function at 24 to 36 months after surgery. CONCLUSION: Our data suggest that for patients with cT2N0 distal rectal cancer who require an APR, preoperative pelvic radiation improves sphincter preservation without an apparent compromise in local control or survival.