Thomas E. Read

Detection of recurrent and metastatic colorectal cancer: Comparison of positron emission tomography and computed tomography

AbstractBackground: This study evaluates the clinical value of positron emission tomography (PET) with 2-[F-18] fluoro-2-deoxy-D-glucose (FDG) as compared to computed tomography (CT) in patients with suspected recurrent or metastatic colorectal cancer (CRC). Methods: A retrospective review of the records of 58 patients who had FDG-PET for evaluation of recurrent or advanced primary CRC was performed. FDG-PET results were compared with those of CT and correlated with operative and histopathologic findings, or with clinical course and autopsy reports. Results: Recurrent or advanced primary CRC was diagnosed in 40 and 11 patients, respectively. The sensitivity and specificity of FDG-PET were 91% and 100% for detecting local pelvic recurrence, and 95% and 100% for hepatic metastases. These values were superior to CT, which had sensitivity and specificity of 52% and 80% for detecting pelvic recurrence, and 74% and 85% for hepatic metastases. FDG-PET correctly identified pelvic recurrence in 19 of 21 patients; CT was negative in 6 of these patients and equivocal in 4. FDG-PET was superior to CT in detecting multiple hepatic lesions and influenced clinical management in 10 of 23 (43%) patients. Conclusion: FDG-PET is more sensitive than CT in the clinical assessment of patients with recurrent or metastatic CRC, and provides an accurate means of selecting appropriate treatment for these patients.

Effect of Laparoscopic-Assisted Resection vs Open Resection of Stage II or III Rectal Cancer on Pathologic Outcomes: The ACOSOG Z6051 Randomized Clinical Trial

IMPORTANCE Evidence about the efficacy of laparoscopic resection of rectal cancer is incomplete, particularly for patients with more advanced-stage disease. OBJECTIVE To determine whether laparoscopic resection is noninferior to open resection, as determined by gross pathologic and histologic evaluation of the resected proctectomy specimen. DESIGN, SETTING, AND PARTICIPANTS A multicenter, balanced, noninferiority, randomized trial enrolled patients between October 2008 and September 2013. The trial was conducted by credentialed surgeons from 35 institutions in the United States and Canada. A total of 486 patients with clinical stage II or III rectal cancer within 12 cm of the anal verge were randomized after completion of neoadjuvant therapy to laparoscopic or open resection. INTERVENTIONS Standard laparoscopic and open approaches were performed by the credentialed surgeons. MAIN OUTCOMES AND MEASURES The primary outcome assessing efficacy was a composite of circumferential radial margin greater than 1 mm, distal margin without tumor, and completeness of total mesorectal excision. A 6% noninferiority margin was chosen according to clinical relevance estimation. RESULTS Two hundred forty patients with laparoscopic resection and 222 with open resection were evaluable for analysis of the 486 enrolled. Successful resection occurred in 81.7% of laparoscopic resection cases (95% CI, 76.8%-86.6%) and 86.9% of open resection cases (95% CI, 82.5%-91.4%) and did not support noninferiority (difference, -5.3%; 1-sided 95% CI, -10.8% to ∞; P for noninferiority = .41). Patients underwent low anterior resection (76.7%) or abdominoperineal resection (23.3%). Conversion to open resection occurred in 11.3% of patients. Operative time was significantly longer for laparoscopic resection (mean, 266.2 vs 220.6 minutes; mean difference, 45.5 minutes; 95% CI, 27.7-63.4; P < .001). Length of stay (7.3 vs 7.0 days; mean difference, 0.3 days; 95% CI, -0.6 to 1.1), readmission within 30 days (3.3% vs 4.1%; difference, -0.7%; 95% CI, -4.2% to 2.7%), and severe complications (22.5% vs 22.1%; difference, 0.4%; 95% CI, -4.2% to 2.7%) did not differ significantly. Quality of the total mesorectal excision specimen in 462 operated and analyzed surgeries was complete (77%) and nearly complete (16.5%) in 93.5% of the cases. Negative circumferential radial margin was observed in 90% of the overall group (87.9% laparoscopic resection and 92.3% open resection; P = .11). Distal margin result was negative in more than 98% of patients irrespective of type of surgery (P = .91). CONCLUSIONS AND RELEVANCE Among patients with stage II or III rectal cancer, the use of laparoscopic resection compared with open resection failed to meet the criterion for noninferiority for pathologic outcomes. Pending clinical oncologic outcomes, the findings do not support the use of laparoscopic resection in these patients. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00726622.

Usefulness of FDG-PET scan in the assessment of suspected metastatic or recurrent adenocarcinoma of the colon and rectum

PURPOSE: The purpose of this study was to evaluate the clinical efficacy of positron emission tomography with 2-[18F] fluoro-2-deoxy-D-glucose compared with computed tomography plus other conventional diagnostic studies in patients suspected of having metastatic or recurrent colorectal adenocarcinoma. METHODS: The records of 105 patients who underwent 101 computed tomography and 109 2-[18F] fluoro-2-deoxy-D-glucose positron emission tomography scans for suspected metastatic or recurrent colorectal adenocarcinoma were reviewed. Clinical correlation was confirmed at time of operation, histopathologically, or by clinical course. RESULTS: The overall sensitivity and specificity of 2-[18F] fluoro-2-deoxy-D-glucose positron emission tomography in detection of clinically relevant tumor were higher (87 and 68 percent) than for computed tomography plus other conventional diagnostic studies (66 and 59 percent). The sensitivity of 2-[18F] fluoro-2-deoxy-D-glucose positron emission tomography in detecting mucinous cancer was lower (58 percent; n=16) than for nonmucinous cancer (92 percent; n=93). The sensitivity of 2-[18F] fluoro-2-deoxy-D-glucose positron emission tomography in detecting locoregional recurrence (n=70) was higher than for computed tomography plus colonoscopy (90vs. 71 percent, respectively). The sensitivity of 2-[18F] fluoro-2-deoxy-D-glucose positron emission tomography in detecting hepatic metastasis (n=101) was higher than for computed tomography (89vs. 71 percent). The sensitivity of 2-[18F] fluoro-2-deoxy-D-glucose positron emission tomography in detecting extrahepatic metastases exclusive of locoregional recurrence (n=101) was higher than for computed tomography plus other conventional diagnostic studies (94vs. 67 percent). 2-[18F] fluoro-2-deoxy-D-glucose positron emission tomography altered clinical management in a beneficial manner in 26 percent of cases (26/101) when compared with evaluation by computed tomography plus other conventional diagnostic studies. CONCLUSION: 2-[18F] fluoro-2-deoxy-D-glucose positron emission tomography is more sensitive than computed tomography for the detection of metastatic or recurrent colorectal cancer and may improve clinical management in one-quarter of cases. However, 2-[18F] fluoro-2-deoxy-D-glucose positron emission tomography is not as sensitive in detecting mucinous adenocarcinoma, possibly because of the relative hypocellularity of these tumors.

Chylomicrons alter the fate of endotoxin, decreasing tumor necrosis factor release and preventing death.

The hypertriglyceridemia of infection was traditionally thought to represent the mobilization of substrate to fuel the bodys response to the infectious challenge. However, we have previously shown that triglyceride-rich lipoproteins can protect against endotoxin-induced lethality. The current studies examine the mechanism by which this protection occurs. Rats infused with a lethal dose of endotoxin preincubated with chylomicrons had a reduced mortality compared with rats infused with endotoxin alone (15 vs. 76%, P < 0.001). Preincubation with chylomicrons increased the rate of clearance of endotoxin from plasma and doubled the amount of endotoxin cleared by the liver (30 +/- 1 vs. 14 +/- 2% of the total infused radiolabel, P < 0.001). In addition, autoradiographic studies showed that chylomicrons directed more of the endotoxin to hepatocytes and away from hepatic macrophages. Rats infused with endotoxin plus chylomicrons also showed reduced peak serum levels of tumor necrosis factor as compared with controls (14.2 +/- 3.3 vs. 44.9 +/- 9.5 ng/ml, mean +/- SEM, P = 0.014). In separate experiments, chylomicrons (1,000 mg triglyceride/kg) or saline were infused 10 min before the infusion of endotoxin. Chylomicron pretreatment resulted in a reduced mortality compared with rats infused with endotoxin alone (22 vs. 78%, P < 0.005). Therefore, chylomicrons can protect against endotoxin-induced lethality with and without preincubation with endotoxin. The mechanism by which chylomicrons protect against endotoxin appears to involve the shunting of endotoxin to hepatocytes and away from macrophages, thereby decreasing macrophage activation and the secretion of cytokines.

Importance of adenomas 5 mm or less in diameter that are detected by sigmoidoscopy.

BACKGROUND The need for colonoscopy in patients with adenomas 5 mm or less in diameter that are detected by sigmoidoscopy is controversial. METHODS We prospectively determined the prevalence of proximal colonic neoplasms in asymptomatic patients at average risk for colorectal cancer, each of whose index lesion on screening fiberoptic sigmoidoscopy was a benign adenoma. Polyps found on sigmoidoscopy underwent biopsy, and colonoscopy was recommended to all patients with neoplastic polyps. Rectosigmoid adenomas were classified as diminutive (< or = 5 mm in diameter), small (6 to 10 mm in diameter), or large (> or = 11 mm in diameter). RESULTS Of 3496 consecutive patients referred for sigmoidoscopy, 311 had neoplastic rectosigmoid polyps; 108 of these patients were excluded from the analysis because of a history of colonic neoplasia, symptoms, prior colonic evaluation, or incomplete follow-up data. The remaining 203 patients made up the study group, and all underwent colonoscopy. Neoplasms were found in the proximal colon in 40 of 137 patients (29 percent) with diminutive index polyps, 15 of 52 patients (29 percent) with small index polyps, and 8 of 14 patients (57 percent) with large index polyps. Advanced neoplasms (adenomas > or = 10 mm in diameter, adenomas with a villous component or moderate-to-severe dysplasia, carcinoma in situ, or frank carcinoma) were found in 8 patients (6 percent), 5 patients (10 percent), and 4 patients (29 percent), respectively. Two patients with diminutive index polyps had proximal carcinoma in situ, and two had proximal stage I carcinomas; one patient with a large index polyp had proximal stage III carcinoma. CONCLUSIONS The substantial prevalence of proximal colonic neoplasms, including advanced lesions, in asymptomatic average-risk patients with rectosigmoid adenomas < or = 5 mm in diameter warrants colonoscopy in these patients.

Confirmation that chromosome 18q allelic loss in colon cancer is a prognostic indicator.

PURPOSE Recent studies suggest that allelic loss of sequences from the long arm of chromosome 18 may be a useful prognostic indicator in colorectal cancer. The aim of the present study was to confirm whether 18q loss of heterozygosity (LOH) is of prognostic value in patients with colon cancer. METHODS Genomic DNA was prepared from archival tumor and corresponding normal tissue specimens from 151 patients who had undergone potentially curative surgery for adenocarcinoma of the colon. Polymerase chain reaction (PCR) was used to assess allelic loss of five chromosome 18q microsatellite markers in the tumors. The relationship between allelic loss and disease-free and disease-specific survival was investigated. RESULTS LOH was detected in 67 of 126 tumors. Chromosome 18q allelic loss was a negative prognostic indicator of both disease-free (relative risk [RR], 1.65; P = .01) and disease-specific survival (RR, 2.0; P = .003). 18q loss was also associated with significantly reduced disease-free and disease-specific survival in patients with stage II (P = .05 and P = .0156) and III (P = .038 and P = .032) disease. CONCLUSION Chromosome 18q allelic loss is a prognostic marker in colorectal cancers. Chromosome 18 LOH studies may be useful in identifying patients with stage II disease who are at high risk for recurrence, and as such might benefit from adjuvant chemotherapy.

Laparoscopic-assisted ileocolic resections in patients with Crohn's disease: are abscesses, phlegmons, or recurrent disease contraindications?

BACKGROUND Because of the inflammatory nature of Crohns disease, ileocolic resections are often difficult to perform, especially if an abscess, phlegmon, or recurrent disease at a previous ileocolic anastomosis is present. Our goal was to determine whether the above factors are contraindications to a successful laparoscopic-assisted ileocolic resection. METHODS Between 1992 and 1996, 46 laparoscopic-assisted ileocolic resections were attempted. Fourteen patients had an abscess or phlegmon treated with bowel rest before operation (group I), 10 patients had recurrent Crohns disease at the previous ileocolic anastomosis (group II), and 22 patients had no previous operation and no phlegmon or abscess associated with their disease (group III). These groups were compared with each other and with 70 consecutive open ileocolic resections for Crohns disease during the same time period (group IV). RESULTS Operative blood loss and time were greater in group IV than in groups I, II, and III (245 versus 151, 131, and 195 ml, respectively, and 202 versus 152, 144, and 139 minutes, respectively). Conversion to open procedure occurred in 5 patients (group I, 1 [7%]; group II, 2 [20%]; group III, 2 [9%]). Morbidity was highest in group IV (21% versus 0%, 10%, and 10%, respectively). Only one patient died (group IV, 1%). Length of hospital stay was longest in group IV (7.9 versus 4.8, 3.9, and 4.5 days, respectively). CONCLUSIONS The laparoscopic-assisted approach to Crohns disease is feasible and safe with good outcomes. Co-morbid preoperative findings such as abscess, phlegmon, or recurrent disease at the previous ileocolic anastomosis are not contraindications to a successful laparoscopic-assisted ileocolic resection in select patients.

Laparoscopic vs. open abdominoperineal resection for cancer.

PURPOSE: The aim of this study was to compare the safety and efficacy of laparoscopic abdominoperineal resection and open abdominoperineal resection for cancer. METHODS: Records of 194 patients who underwent laparoscopic abdominoperineal resection (42 patients) or open abdominoperineal resection (152 patients) at three institutions between 1991 and 1997 were reviewed. Follow-up was through office charts, American College of Surgeons cancer registry, or telephone contact. Tumors included (laparoscopic abdominoperineal resection and open abdominoperineal resection, respectively) adenocarcinoma (86 and 92 percent), squamous (12 and 7 percent), and gastrointestinal stromal (2 and 1.4 percent) types; Stages I (17 and 26 percent), II (24 and 33 percent), III (43 and 32 percent), and IV (14 and 9 percent); and those with invasion of pelvic structures (14 and 16 percent). RESULTS: Laparoscopic abdominoperineal resection was converted to open abdominoperineal resection in 21 percent because of vessel injury (33 percent), poor exposure (22 percent), adhesions (22 percent), inguinal hernia (11 percent), or radiation fibrosis (11 percent). Perineal infections occurred more often in the laparoscopic abdominoperineal resection group (24vs. 8 percent;P=0.02). Late stoma complications were similar. Mean hospital stay was shorter after laparoscopic abdominoperineal resection (7vs. 12 days). Radial margins were positive in 12 percent of laparoscopic abdominoperineal resection and 12.5 percent of open abdominoperineal resection specimens. Tumor recurrence was similar for both local (19 and 14 percent) and distant (38 and 26 percent) recurrence. Survival rates were similar by Kaplan-Meier curves, with median follow-up of 19 and 24 months, respectively (P=0.22; log rank). CONCLUSION: Laparoscopic abdominoperineal resection can be performed safely and results in a shorter hospital stay. A randomized, prospective trial is needed to determine the long-term outcome of cancer treatment.

Hand-Assisted Laparoscopic vs. Laparoscopic Colorectal Surgery: A Multicenter, Prospective, Randomized Trial

PurposeThis study was designed to compare short-term outcomes after hand-assisted laparoscopic vs. straight laparoscopic colorectal surgery.MethodsEleven surgeons at five centers participated in a prospective, randomized trial of patients undergoing elective laparoscopic sigmoid/left colectomy and total colectomy. The study was powered to detect a 30-minute reduction in operative time between hand-assisted laparoscopic and straight laparoscopic groups.ResultsThere were 47 hand-assisted patients (33 sigmoid/left colectomy, 14 total colectomy) and 48 straight laparoscopic patients (33 sigmoid/left colectomy, 15 total colectomy). There were no differences in the patient age, sex, body mass index, previous surgery, diagnosis, and procedures performed between the hand-assisted and straight laparoscopic groups. Resident participation in the procedures was similar for all groups. The mean operative time (in minutes) was significantly less in the hand-assisted laparoscopic group for both the sigmoid colectomy (175 ± 58 vs. 208 ± 55; P = 0.021) and total colectomy groups (time to colectomy completion, 127 ± 31 vs. 184 ± 72; P = 0.015). There were no apparent differences in the time to return of bowel function, tolerance of diet, length of stay, postoperative pain scores, or narcotic usage between the hand-assisted laparoscopic and straight laparoscopic groups. There was one (2 percent) conversion in the hand-assisted laparoscopic group and six (12.5 percent) in the straight laparoscopic group (P = 0.11). Complications were similar in both groups (hand-assisted, 21 percent vs. straight laparoscopic, 19 percent; P = 0.68).ConclusionsIn this prospective, randomized study, hand-assisted laparoscopic colorectal surgery resulted in significantly shorter operative times while maintaining similar clinical outcomes as straight laparoscopic techniques for patients undergoing left-sided colectomy and total abdominal colectomy.

Neoadjuvant Therapy for Rectal Cancer: Histologic Response of the Primary Tumor Predicts Nodal Status

PURPOSE:This study was designed to compare histologic T and N stages in patients with rectal adenocarcinoma undergoing various neoadjuvant radiotherapy regimens and proctectomy, in an attempt to determine if final histologic stage of the mural tumor predicts nodal status.METHODS:Data were collected from computerized databases at two institutions on 649 consecutive patients who underwent neoadjuvant radiotherapy or chemoradiotherapy and proctectomy for primary adenocarcinoma of the rectum from 1990 to 2002.RESULTS:Five patients were excluded because of incomplete pathology data sets, leaving a study population of 644. Patients underwent neoadjuvant radiotherapy alone (2,000 cGy in 5 fractions, n = 191; or 4,500 cGy in 25 fractions, n = 259) or chemoradiation (4,500 cGy in 25 fractions with concurrent 5-fluorouracil, n = 194). Histologic stage of the remaining mural tumor (ypT) correlated with nodal status (ypN). Lymph nodes harboring metastatic tumor were found in 1 of 42 (2 percent) ypT0 patients, 2 of 45 (4 percent) ypT1 patients, 43 of 186 (23 percent) ypT2 patients, 158 of 338 (47 percent) ypT3 patients, and 16 of 33 (48 percent) ypT4 patients (P < 0.001, chi-squared test). The probability of finding ypN+ disease was 3 of 87 (3 percent) in patients with ypT0-1 residual primary tumors vs. 220 of 557 (39 percent) in patients with ypT2-4 residual primary tumors (P < 0.0001; Fisher’s exact test).CONCLUSIONS:Nodal metastases are rare in patients whose mural tumor burden shrinks to ypT0-1 after neoadjuvant radiotherapy. If transanal excision is offered to select patients with distal rectal cancer, it is reasonable to select those who have an excellent clinical response to neoadjuvant therapy for transanal excision, and then reserve proctectomy for patients proven to have residual ypT2-4 disease.