Comparative analysis of various prognostic nodal factors, adjuvant chemotherapy and survival among stage III colon cancer patients over 65 years: an analysis using surveillance, epidemiology and end results (SEER)-Medicare data.

AIM: The prognostic effects of chemotherapy and various lymph node measures [positive nodes, total node count and the positive lymph node ratio (PLNR)] have been established. It is unknown whether the cancer-specific survival benefit of chemotherapy differs across these nodal prognostic categories. METHOD: This retrospective analysis of linked Surveillance, Epidemiology and End Results (SEER) data and Medicare data (SEER-Medicare)included patients ≥ 65 years of age with a diagnosis of stage III colon cancer between 1997 and 2002. We grouped patients according to the number of positive nodes (N1 and N2), total node count (≥ 12 and < 12 total nodes) and PLNR (below the 75th percentile and at least at the 75th percentile of the PLNR). The end point was colon cancer-specific mortality. RESULTS: Fifty-one per cent (3701) of the 7263 patients received adjuvant therapy during the time period 1997-2002. The mean (standard deviation) number of total nodes examined was 13 (9) and the number of positive nodes identified was 3 (3). Patients with N2 disease, < 12 total nodes examined and a high PLNR had a worse survival at 2, 3 and 5 years following colectomy. Utilization of chemotherapy demonstrated a colon cancer-specific survival benefit (hazard ratio at median follow up = 0.7; P < 0.001) that was consistent and statistically significant across the three nodal prognostic categories examined. CONCLUSION: The benefit of chemotherapy did not vary based on N stage, total node count or PLNR. The results favour a broad-based approach towards increasing the chemotherapy treatment rates in stage III patients of ≥ 65 years of age, rather than an approach that targets clinical subgroups.

A phosphatase associated with metastasis of colorectal cancer.

To gain insights into the molecular basis for metastasis, we compared the global gene expression profile of metastatic colorectal cancer with that of primary cancers, benign colorectal tumors, and normal colorectal epithelium. Among the genes identified, the PRL-3 protein tyrosine phosphatase gene was of particular interest. It was expressed at high levels in each of 18 cancer metastases studied but at lower levels in nonmetastatic tumors and normal colorectal epithelium. In 3 of 12 metastases examined, multiple copies of the PRL-3 gene were found within a small amplicon located at chromosome 8q24.3. These data suggest that the PRL-3 gene is important for colorectal cancer metastasis and provide a new therapeutic target for these intractable lesions.

Controlled local delivery of interleukin-2 by biodegradable polymers protects animals from experimental brain tumors and liver tumors.

PURPOSE: The purpose of our study was to develop an injectable polymeric system for the long-term localized delivery of bioactive interleukin-2 for antitumor immunotherapy. METHODS: IL-2 was encapsulated into gelatin and chondroitin-6-sulfate using an aqueous-based complex coacervation. CTLL-2 cells were used to measure the bioactivity of released IL-2 and radiolabeled IL-2 was used for release studies in the rat brain and mouse liver. Antitumor efficacy studies were carried out in primary (9L gliosarcoma) and metastatic (B16-F10 melanoma) brain tumor models in rats and mice, respectively, as well as a murine liver tumor model (CT26 carcinoma). Survivors of the metastatic brain tumor challenge were rechallenged with tumor in the opposite lobe of the brain to confirm that antitumor immunologic memory had developed. RESULTS: Bioactive IL-2 was released for over 2 weeks in vitro and in vivo IL-2 release showed significant IL-2 levels for up to 21 days. Polymeric IL-2 microspheres injected intratumorally were statistically more effective in protecting animals challenged with fatal tumor doses in the brain and the liver than placebo or autologous tumor cells genetically engineered to secrete IL-2. Immunologic memory was induced following IL-2 microsphere therapy in the B16-F10 brain tumor model that was capable of protecting 42% of animals from a subsequent intracranial tumor challenge, suggesting that tumor destruction was mediated by the immune system. CONCLUSIONS: Local IL-2 therapy using novel polymeric carriers. aimed at stimulating long-lasting antitumor immunity, may provide an improved method of treating a variety of cancers.

Vaccines for colorectal cancer.

Despite recent advances in the treatment of colorectal cancer, the overall survival rate for those patients with advanced locoregional disease remains less than 50%. Although adjuvant systemic chemotherapy has improved survival of these patients, more effective therapies are needed. Immunotherapy is an approach that could have a particular role in the adjuvant therapy of colorectal cancer. There is now convincing evidence that the immune system can specifically recognize and destroy malignant cells. Although both antibody- and T-cell-mediated anti-tumor responses have been documented, the cellular immune response with its direct cytotoxic mechanisms is felt to be the principal anti-tumor arm of the immune system. Analysis of the T cells that recognize tumors has led to the identification and characterization of many tumor-associated antigens including several colorectal antigens. Current approaches to developing a vaccine for colorectal cancer use our expanded understanding of these tumor-associated antigens and the conditions that allow development of an effective cellular immune response to them.

Temporal CT changes after hepatic and renal interstitial radiotherapy in a canine model.

PURPOSE: The purpose of this work was to define the temporal CT characteristics of hepatic and renal ablation following point-source radioablation utilizing a low energy, photon X-ray source emitted from a miniature probe. METHOD: Twelve mongrel dogs underwent each of three hepatic and two renal point-source radiation ablations. Animals underwent serial, dual phase, spiral CT scans and were killed at 1, 3, and 6 months after treatment. RESULTS: Ablative lesions were clearly visible at 1 month following therapy and consistently diminished in size over the 6 months of follow-up. Lesion size tended to be proportional to dose delivered. Both hepatic and renal lesions were low in attenuation with frequent rim enhancement that diminished over time. Hepatic lesions frequently showed transient hepatic attenuation differences (THADs). Lesion size appeared independent of proximity to vessels. CONCLUSION: Following hepatic or renal interstitial radiotherapy, lesions are generated that are similar in CT appearance to those produced by other ablative techniques. The presence of rim or THAD enhancement can be seen early on as part of the normal tissue-healing response.

Counting alleles reveals a connection between chromosome 18q loss and vascular invasion.

The analysis of loss of heterozygosity (LOH) is perhaps the most widely used technique in cancer genetics. In primary tumors, however, the analysis of LOH is fraught with technical problems that have limited its reproducibility and interpretation. In particular, tumors are mixtures of neoplastic and nonneoplastic cells, and the DNA from the nonneoplastic cells can mask LOH. We here describe a new experimental approach, involving two components, to overcome these problems. First, a form of digital PCR was employed to directly count, one by one, the number of each of the two alleles in tumor samples. Second, Bayesian-type likelihood methods were used to measure the strength of the evidence for the allele distribution being different from normal. This approach imparts a rigorous statistical basis to LOH analyses, and should be able to provide more reliable information than heretofore possible in LOH studies of diverse tumor types.

Results of salvage abdominoperineal resection for recurrent anal carcinoma following combined chemoradiation therapy.

Combined chemotherapy and radiation therapy is the standard treatment for epidermoid carcinoma of the anal canal. Failures are often not associated with distant recurrence and are therefore potentially amenable to salvage abdominoperineal resection. The aim of this study was to review our experience with abdominoperineal resection following failure of chemoradiation therapy for epidermoid carcinoma of the anus. Between 1980 and 1998, 17 patients underwent salvage abdominoperineal resection following failure of chemoradiation therapy. Four patients were excluded from survival analysis because resection was performed with palliative intent. Survival curves were based on the method of Kaplan and Meier, and univariate analysis of predictive variables was performed using the log-rank test. Twelve patients underwent abdominoperineal resection for persistent disease and five patients for recurrent disease. No operative deaths occurred, but local complications including perineal wound infection and wound breakdown was seen in 8 of 17 patients and 6 of 17 patients, respectively. Patients undergoing omental flap reconstruction (n = 3) or no pelvic reconstruction (n = 5) had a higher incidence of perineal breakdown compared to those undergoing muscle flap reconstruction (n = 9) (P <0.05). The median follow-up time for the patients operated on with curative intent was 53 months. The 5-year actuarial survival was 47%. Potential prognostic factors that were not found to have an impact on survival included margin status of resection, sphincter invasion, and degree of differentiation. Only pathologic tumor size greater than 5.0 cm (P <0.001) and age over 55 years (P <0.05) adversely affected survival. Selected patients with recurrent or persistent anal carcinoma following chemoradiation therapy can be offered salvage abdominoperineal resection. This operation is associated with a high incidence of local wound complications, and muscle flap reconstruction should be considered when possible. Prolonged survival can be achieved in some patients following salvage resection for epidermoid carcinoma of the anal canal.

Detection of hepatic lesions in candidates for surgery: comparison of ferumoxides-enhanced MR imaging and dual-phase helical CT.

OBJECTIVE: The purpose of this study was to compare the use of phased array MR imaging of the liver at 1.5 T with and without ferumoxides with dual-phase helical CT for the detection of hepatic lesions in candidates for hepatic surgery. SUBJECTS AND METHODS: Patients with known or suspected hepatic lesions who were eligible for surgery underwent dual-phase helical CT at 20 and 70 sec after the start of contrast material injection and phased array MR imaging using fast spin-echo T2-weighted imaging and gradient-echo T1-weighted imaging before and after ferumoxides infusion of 0.56 mg of iron per kilogram of body weight. Three observers who were unaware of the surgical findings separately reviewed the CT scans and unenhanced and enhanced MR images of 24 patients who completed the protocol. The observers' findings were compared with results obtained at surgery using intraoperative sonography and having histopathologic confirmation. Statistical analysis was performed using a segment-by-segment analysis. RESULTS: Eighty-two lesions were found at surgery. The sensitivity of CT, unenhanced MR imaging, and enhanced MR imaging for blinded observers was 60.4%, 62.0%, and 68.2%, respectively. The specificity was 89.2%, 81.9%, and 81.6%, respectively. Five lesions in three patients were not detected preoperatively using any of the techniques. MR imaging found additional lesions not detected on CT in four patients; CT detected one additional lesion not seen on MR imaging. CONCLUSION: Ferumoxides-enhanced MR imaging of the liver shows a trend toward increased sensitivity compared with dual-phase helical CT. Specificity of helical CT was superior to that of enhanced MR imaging for most observers.

Local tumor recurrence following hepatic cryoablation: radiologic-histopathologic correlation in a rabbit model.

PURPOSE: To use radiologic-histopathologic correlation in an animal model to distinguish normal postoperative findings from evidence of residual tumor after cryoablation of malignant hepatic tumors. MATERIALS AND METHODS: Hepatic cryoablation was performed in 12 rabbits with VX2 tumors and in two healthy rabbits. Nonenhanced and dynamic contrast material-enhanced computed tomography (CT) and magnetic resonance (MR) imaging and power and color Doppler flow ultrasonography (US) were performed 7-8 days after cryoablation. Histopathologic findings were correlated with imaging findings. RESULTS: Twenty tumors of 5-20 mm (mean, 10 mm) and seven areas of normal liver were treated with cryolesions of 11-21 mm (mean, 15 mm). All cryolesions exhibited arterial phase rim enhancement at CT and MR imaging, and 13 (57%) of 23 lesions demonstrated peripheral flow at US because of granulation tissue. There was macroscopic recurrence in 15 (75%) of 20 treated tumors; 14 (93%) appeared as peripheral nodularity with low-grade enhancement. Necrotic tissue did not enhance. Intact vessels extended up to 6 mm inside cryolesion margins and caused focal internal enhancement and Doppler flow. Areas of high signal intensity on T2-weighted MR images correlated with liquefaction necrosis, granulation tissue, and tumor. CONCLUSION: In this animal model, recurrent tumor typically appeared as focal nodules at the cryolesion periphery. Rim and central foci of enhancement, Doppler flow, and increased signal intensity on T2-weighted MR images can be normal findings after hepatic cryoablation.

Does prophylactic octreotide decrease the rates of pancreatic fistula and other complications after pancreaticoduodenectomy? Results of a prospective randomized placebo-controlled trial.

OBJECTIVE: To evaluate the endpoints of complications (specifically pancreatic fistula and total complications) and death in patients undergoing pancreaticoduodenectomy. SUMMARY BACKGROUND DATA: Four randomized, placebo-controlled, multicenter trials from Europe have evaluated prophylactic octreotide (the long-acting synthetic analog of native somatostatin) in patients undergoing pancreatic resection. Each trial reported significant decreases in overall complication rates, and two of the four reported significantly lowered rates of pancreatic fistula in patients receiving prophylactic octreotide. However, none of these four trials studied only pancreaticoduodenal resections, and all trials had high pancreatic fistula rates (>19%) in the placebo group. A fifth randomized trial from the United States evaluated the use of prophylactic octreotide in patients undergoing pancreaticoduodenectomy and found no benefit to the use of octreotide. Prophylactic use of octreotide adds more than $75 to the daily hospital charge in the United States. In calendar year 1996, 288 patients received octreotide on the surgical service at the authors' institution, for total billed charges of $74,652. METHODS: Between February 1998 and February 2000, 383 patients were recruited into this study on the basis of preoperative anticipation of pancreaticoduodenal resection. Patients who gave consent were randomized to saline control versus octreotide 250 microg subcutaneously every 8 hours for 7 days, to start 1 to 2 hours before surgery. The primary postoperative endpoints were pancreatic fistula, total complications, death, and length of hospital stay. RESULTS: Two hundred eleven patients underwent pancreaticoduodenectomy with pancreatic-enteric anastomosis, received appropriate saline/octreotide doses, and were available for endpoint analysis. The two groups were comparable with respect to demographics (54% male, median age 66 years), type of pancreaticoduodenal resection (60% pylorus-preserving), type of pancreatic-enteric anastomosis (87% end-to-side pancreaticojejunostomy), and pathologic diagnosis. The pancreatic fistula rates were 9% in the control group and 11% in the octreotide group. The overall complication rates were 34% in the control group and 40% in the octreotide group; the in-hospital death rates were 0% versus 1%, respectively. The median postoperative length of hospital stay was 9 days in both groups. CONCLUSIONS: These data demonstrate that the prophylactic use of perioperative octreotide does not reduce the incidence of pancreatic fistula or total complications after pancreaticoduodenectomy. Prophylactic octreotide use in this setting should be eliminated, at a considerable cost savings.

Management of hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is responsible for a significant amount of morbidity and mortality throughout the world. In many countries, including the United States, a definite increase in the incidence of HCC has been reported recently, largely attributable to the increasing incidence of hepatitis C infection. Unfortunately, the current management of HCC is confusing due to the large number of treatment options available. The difficulty of managing a patient with HCC is compounded by the lack of well-designed, randomized clinical trials comparing the various treatment modalities. Nevertheless, many exciting management options are currently available that may prove valuable in the treatment of this disease. Partial hepatic resection or, in some instances, liver transplantation offers the best chance for cure. However, various ablative therapies, including percutaneous ethanol injection, radiofrequency ablation, and cryosurgery, may produce a survival benefit. In the future, systemic chemotherapy and transarterial chemoembolization, employed either alone or as adjuncts to ablation or resection, may play an increasing role in palliating or down-staging a patient with advanced HCC. This overview of the state-of-the-art management of HCC attempts to guide the practicing physician in selecting the best treatment plan for an individual with HCC.

Focal hepatic ablation using interstitial photon radiation energy.

BACKGROUND: Intratumoral ablative therapy is being used increasingly for the treatment of primary and secondary hepatic malignancies. The interstitial point-source photon radiosurgery system (PRS) is a novel ablative technique that uses radiation therapy similar in dosimetry to interstitial brachytherapy. STUDY DESIGN: To determine the feasibility, toxicity, and local tissue destructive capabilities of the PRS in the liver, preliminary studies in a nontumor-bearing canine model were examined. A 6-month survival study was conducted. Each animal received three radiation treatments, in the right, central, and left hepatic regions. Three low-dose treatments were delivered to each of six animals (group A), generating a 2.0-cm-diameter radiated sphere with a dose of 20 Gy at the lesion edge. Three high-dose treatments were delivered to each of six animals (group B), generating a 3.0-cm-diameter radiated sphere with 20 Gy at the lesion edge. RESULTS: The treatment reproducibly generated sharply demarcated hepatic ablative lesions proportional to the administered dose. Mean lesion diameter at 1 month was 1.6+/-0.2 cm in group A and 3.4+/-1.0 cm in group B. Lesion size was independent of intrahepatic location, including near vascular structures. PRS therapy, when applied to portal structures, resulted in hilar damage. Hilar damage appeared to be associated with arteriolar thrombosis and bile duct injury. Treatment of regions adjacent to large hepatic veins and the IVC was not associated with vessel thrombosis or stricture. CONCLUSIONS: PRS ablation is a generally well-tolerated method that results in consistent, well-demarcated, symmetric lesions of complete necrosis with minimal adjacent parenchymal injury. Application of such an approach for the treatment of liver tumors is promising.

Antigen-specific immunotherapy for human papillomavirus 16 E7-expressing tumors grown in the liver.

BACKGROUND/AIMS: We have previously reported a recombinant vaccinia-based vaccine (vac-Sig/E7/LAMP-1) that demonstrated a significant anti-tumor effect in a subcutaneous tumor challenge model. Since the liver is one of the most common sites for tumor metastasis and organ microenvironments may modulate tumor cell responses to therapies, the aim of the present study was to evaluate the potency of vac-Sig/E7/LAMP-1 in treating E7-expressing tumors grown in the liver. METHODS: For in vivo tumor prevention experiments, mice were vaccinated intraperitoneally with vac-Sig/E7/LAMP-1 followed by intrahepatic tumor challenge. For in vivo tumor regression experiments, mice were first challenged with tumor cells and then vaccinated with vac-Sig/E7/LAMP-1 intraperitoneally. In addition, enzyme-linked immunospot assays were used to determine the frequency of E7-specific T cell precursors. RESULTS: For in vivo tumor protection experiments, tumor growth was observed in all of the mice vaccinated with wild-type vaccinia and 60% of the mice vaccinated with wild-type E7 vaccinia. All of the mice vaccinated with vac-Sig/E7/LAMP-1 remained tumor-free 30 days after tumor challenge. For the tumor regression assays, all of the mice vaccinated with vac-Sig/E7/LAMP-1 remained tumor-free 30 days after vaccination. In contrast, all of those mice receiving culture medium, wild-type vaccinia, or wild-type E7 vaccinia developed tumors in the liver. In addition, mice vaccinated with vac-Sig/E7/LAMP-1 had the highest E7-specific CD8+ T cell precursors. CONCLUSIONS: Our data suggest that vac-Sig/E7/LAMP-1 is an effective vaccine for controlling E7-expressing tumors grown in the liver and our model suggests that antigen-specific immunotherapy may represent a powerful tool for treating liver tumors with characterized tumor-specific antigens. In addition, our data indicate that the number of E7-specific CD8+ T cell precursors directly correlated with the anti-tumor effect generated by Sig/E7/LAMP-1 vaccinia.

Feasibility of ablating normal renal parenchyma by interstitial photon radiation energy: study in a canine model.

BACKGROUND AND PURPOSE: A miniature photon radiosurgery system (PRS) has been described as an alternative to surgical resection and external-beam radiation for tumors and may now offer an alternative for ablation of renal lesions. We evaluated the feasibility of ablation by PRS in a normal parenchyma canine model. MATERIALS AND METHODS: Twelve mongrel dogs were used in this survival study. In the left and right kidneys of each animal, a peripheral lesion and central-hilar lesion, respectively, were induced with PRS. The probes were placed in the renal parenchyma, and local radiation of 15 Gy at a radius of 1.3 cm was delivered over 10 minutes. Serum electrolytes were measured serially. Computed tomography scans were obtained, and the animals were sacrificed for pathologic correlation. In a separate study, the liver received three additional treatments of 10 to 20 minutes of radiation. RESULTS: Eleven dogs survived this 6-month study and were sacrificed as scheduled. One animal expired after 2 weeks from radiation-induced fulminant hepatic failure with normal renal function. No other complications were observed. The average lesion size was 2.5 cm in diameter. Histologic analysis confirmed coagulative necrosis with sharp demarcation from the surrounding parenchyma. CONCLUSION: Preliminary studies demonstrate the feasibility of PRS ablation of the renal parenchyma. Further tumor model testing will be important to determine the ultimate efficacy of local photon radiation energy.

Isolated right segmental hepatic duct injury: a diagnostic and therapeutic challenge.

Biliary leaks and injuries are not an uncommon occurrence following laparoscopic cholecystectomy. Bile leaks associated with the biliary anatomic variant of a low-inserting right segmental hepatic duct can be particularly difficult to diagnose in that results of endoscopic retrograde cholangiography (ERC) are usually interpreted as "normal" with no leaks demonstrated. The aim of this study was to describe a single institution's experience with nine patients with biliary leaks associated with this anatomic variant and to discuss their management. A retrospective analysis of the hospital records of all patients with bile duct injuries managed at a single institution between 1980 and July 1998, inclusive, was performed. Nine patients were identified as having an isolated right segmental hepatic duct injury associated with a biliary leak. Seven (78%) of the nine patients had undergone a laparoscopic cholecystectomy, whereas the remaining two patients (22%) had undergone an open cholecystectomy. All of the patients had undergone endoscopic retrograde cholangiography at outside institutions, the results of which had been interpreted as normal with no apparent leaks. The median interval from the time of cholecystectomy to referral was 1.4 months. All patients were managed with initial percutaneous access of the involved right segmental biliary system, with placement of a percutaneous transhepatic stent. After the biliary leak was controlled, all patients underwent Roux-en-Y hepaticojejunostomy to the isolated biliary segment. All patients had an uncomplicated postoperative course. There were no postoperative anastomotic leaks. Postoperative stenting was maintained for a mean of 8 months. Six (67%) of the nine patients had a long-term successful outcome with minimal or no symptoms. In three patients, recurrent symptoms with pain and/or cholangitis developed at a mean of 34 months. All three patients underwent percutaneous cholangiography, which demonstrated an anastomotic stricture, and all were managed with percutaneous balloon dilatation with a successful outcome. Currently eight (89%) of the nine patients are asymptomatic, with a mean follow-up of 70.4 months (range 12 to 226 months). One patient had intermittent right upper quadrant pain with normal liver function tests but has not required intervention. Isolated right segmental hepatic ductal injury with biliary leakage is an uncommon complication following laparoscopic cholecystectomy. A diagnostic dilemma is created by the presence of a bile leak with a normal endoscopic retrograde cholangiogram. Management begins with percutaneous access of the transected isolated ductal system followed by reconstruction as a Roux-en-Y hepaticojejunostomy.

1999 ARRS Executive Council Award. Contrast-enhanced CT of small hypovascular hepatic tumors: effect of lesion enhancement on conspicuity in rabbits. American Roentgen Ray Society.

OBJECTIVE: The purpose of this study was to evaluate the effect of lesion enhancement on the conspicuity of small hypovascular hepatic tumors in an animal model. MATERIALS AND METHODS: Seven VX2 hepatic tumors in five rabbits were imaged. Dynamic contrast-enhanced CT was performed at a single level centered over the lesions at 5-sec intervals for 119 sec after injection of 2 ml/kg i.v. contrast material at 2 ml/sec. Attenuation was measured over time within regions of interest in the tumor and normal liver, aorta, inferior vena cava, and portal vein. Lesion conspicuity, defined as the difference between the attenuation of the uninvolved liver and neoplasm, was calculated. RESULTS: The mean diameter of the tumors on CT was 10 mm (range, 6-15 mm). The tumors appeared as low-attenuation lesions with progressive enhancement during the arterial phase and early portal phase. Peak mean lesion attenuation was 60 +/- 27 H (enhancement, 23 H) at 64 sec. Peak mean lesion conspicuity was 80 +/- 18 H at 39 sec, occurring 10 sec before the peak mean hepatic attenuation of 135 +/- 15 H (enhancement, 67 H) at 49 sec. Relative lesion conspicuity paralleled relative enhancement of the liver throughout the imaging period. CONCLUSION: Although low-level tumor enhancement during the arterial phase and early portal phase reduced the conspicuity of small hypovascular tumors in this animal model, our results support the use of maximum liver enhancement as a marker for peak lesion conspicuity.

Renal ablative cryosurgery in selected patients with peripheral renal masses.

OBJECTIVES: To present the preliminary results of renal ablative cryosurgery in selected patients. METHODS: Seven patients were treated, all of whom had small peripheral tumors and chose not to undergo partial or radical nephrectomy. Four patients underwent a rib-sparing flank incision; the remaining three underwent laparoscopy. All tumors were biopsied before cryoablation. Intraoperative ultrasound was used to monitor the cryolesion. RESULTS: There were no intraoperative complications. The estimated blood loss averaged 111 mL. To date, 6 of the 7 patients have undergone at least one follow-up computed tomography scan (14.2 months average follow-up); all these scans demonstrated partial resolution of the lesion. Clinically, the patients tolerated the procedure without any renal complications or significant changes in creatinine. CONCLUSIONS: This limited clinical trial has demonstrated the feasibility of treating small peripherally located renal tumors with cryosurgery with minimal morbidity and a favorable outcome. Further studies are necessary to determine the long-term efficacy of this treatment modality.

NCCN Practice Guidelines for Colorectal Cancer.

The NCCN Colorectal Cancer Guidelines panel believes that a multidisciplinary approach is necessary for the management of the patient with colorectal cancer. The panel endorses the concept that treatment of patients in a clinical trial has priority over standard or accepted therapy. The recommended surgical procedure for resectable colon cancer is an en bloc resection; laparoscopic surgery should be done only in the context of a clinical trial. For patients with stage III disease, 5-FU-based adjuvant therapy is recommended. A patient who has metastatic disease in the liver or lung should be considered for surgical resection if he or she is a candidate for surgery and if surgery can extend survival. Surgery should be followed by adjuvant chemotherapy. The panel advocates a conservative post-treatment surveillance program for colon and rectal carcinoma patients. Serial CEA determinations are appropriate if the patient is a candidate for aggressive surgical resection, should recurrence be detected. Abdominal and pelvic CT scans should be utilized only when there are clinical indications of possible recurrence. Patients whose disease progresses during 5-FU-based therapy should be treated with irinotecan or encouraged to participate in a phase I or phase II clinical trial.

Treatment of liver metastases from colon carcinoma with autologous tumor vaccine expressing granulocyte-macrophage colony-stimulating factor.

BACKGROUND AND OBJECTIVES: In preclinical studies, tumor cells genetically altered to secrete granulocyte-macrophage colony-stimulating factor (GM-CSF) can generate systemic antitumor immunity. Clinically relevant immunotherapeutic approaches for the treatment of colorectal cancer should address efficacy within the liver, a common site of metastatic disease. We investigated the effect of irradiated colon cancer cells engineered to produce GM-CSF on protecting from and treating established liver metastases. METHODS: Using a model of liver metastasis by intrahepatic injection of CT-26 murine colon carcinoma cells in syngeneic BALB/c mice, GM-CSF-producing irradiated cells were given as an intradermal vaccine either 14 days prior to hepatic challenge or in animals with early established tumor (days 5 and 10). The presence of tumor, tumor volume, and survival were endpoint determinants. RESULTS: Animals receiving GM-CSF-producing vaccination demonstrated significant protection from subsequent hepatic challenge of viable tumor cells, even at the highest challenge doses. In animals with early established tumors, a significant response was seen with prolongation in survival. CONCLUSIONS: We conclude that GM-CSF autologous tumor vaccination was effective for the treatment of hepatic colorectal metastases in this murine model. These findings provide support for immunotherapeutic approaches for metastatic liver cancer.

Hospital volume can serve as a surrogate for surgeon volume for achieving excellent outcomes in colorectal resection.

OBJECTIVE: To examine the association of surgeon and hospital case volumes with the short-term outcomes of in-hospital death, total hospital charges, and length of stay for resection of colorectal carcinoma. METHODS: The study design was a cross-sectional analysis of all adult patients who underwent resection for colorectal cancer using Maryland state discharge data from 1992 to 1996. Cases were divided into three groups based on annual surgeon case volume--low (< or =5), medium (5 to 10), and high (>10)--and hospital volume--low (<40), medium (40 to 70), and high (> or =70). Poisson and multiple linear regression analyses were used to identify differences in outcomes among volume groups while adjusting for variations in type of resections performed, cancer stage, patient comorbidities, urgency of admission, and patient demographic variables. RESULTS: During the 5-year period, 9739 resections were performed by 812 surgeons at 50 hospitals. The majority of surgeons (81%) and hospitals (58%) were in the low-volume group. The low-volume surgeons operated on 3461 of the 9739 total patients (36%) at an average rate of 1.8 cases per year. Higher surgeon volume was associated with significant improvement in all three outcomes (in-hospital death, length of stay, and cost). Medium-volume surgeons achieved results equivalent to high-volume surgeons when they operated in high- or medium-volume hospitals. CONCLUSIONS: A skewed distribution of case volumes by surgeon was found in this study of patients who underwent resection for large bowel cancer in Maryland. The majority of these surgeons performed very few operations for colorectal cancer per year, whereas a minority performed >10 cases per year. Medium-volume surgeons achieved excellent outcomes similar to high-volume surgeons when operating in medium-volume or high-volume hospitals, but not in low-volume hospitals. The results of low-volume surgeons improved with increasing hospital volume but never equaled those of the high-volume surgeons.