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E W Martin

Publications and source records attributed to E W Martin.

At least 19 recordsLinked to original sources
PubMed2001

Age-related hypermethylation of the 5' region of MLH1 in normal colonic mucosa is associated with microsatellite-unstable colorectal cancer development.

Hypermethylation of the MLH1 promoter underlies most sporadic colorectal cancers with microsatellite instability (MSI). To investigate the role of hypermethylation in the normal colonic mucosa as a possible precursor lesion, we studied 700 bp upstream of MLH1 covering 51 CpG sites. We found partially methylated alleles in 15 of 34 (44%) patients <60 years of age and 20 of 24 (83%) patients > or =80 years of age (P = 0.0026). Fully methylated alleles were present in 18 of 33 (55%) patients with MSI+ tumors but in only 18 of 90 (20%) patients with MSI- tumors (P = 0.00019). By in situ analysis, methylation was patchy and located mainly in the cryptal regions close to the lumen. We conclude that the spread of methylation in the MLH1 promoter in the normal colonic mucosa is closely associated with age and the development of sporadic MSI+ colorectal cancers.

Adaptor Proteins, Signal Transducing↗
PubMed2001

18F-labeled fluorodeoxyglucose positron emission tomography-guided surgery for recurrent colorectal cancer: a feasibility study.

OBJECTIVE: Positron emission tomography (PET) scanning is an accepted diagnostic tool for the detection of colorectal cancer (CRC). The purpose of this study was to determine whether diagnostic information offered by preoperative PET scan could be used to detect disease intraoperatively using beta and gamma handheld probes. METHODS: Two studies were carried out. First, tumor "phantoms" were created using 62 microCi fluorodeoxyglucose (FDG) in a saline-filled basin. Gamma and beta handheld probes were used to determine detection characteristics with respect to probe type, distance from source, and isotope half-life. In a second study, probes were used intraoperatively to detect tumor in 10 patients with recurrent colorectal cancer as determined by preoperative PET scan. Counts relative to background were determined for each probe as was histopathologic correlation with probe-positive tissue. RESULTS: Phantom studies documented that FDG detection by each probe was nonlinearly related to source proximity and half-life. In human subjects, abnormal findings on preoperative PET studies were detected by both probes with tumor:normal ratios of 1.6 (beta) and 1.5 (gamma). All probe-positive tissue was histologically confirmed to be recurrent colorectal cancer. CONCLUSIONS: Intraoperative detection of CRC using an FDG source and beta and gamma probes correlates with preoperative PET. With further improvements in probe technology, successful differentiation of normal and tumor tissue as shown here may allow for more precise localization and directed resection.

Beta Particles↗
PubMed2001

Serum pancreastatin levels predict response to hepatic artery chemoembolization and somatostatin analogue therapy in metastatic neuroendocrine tumors.

INTRODUCTION: Neuroendocrine tumors often metastasize to the liver and present with disabling hormonal symptoms. Hepatic artery chemoembolization (HACE) combined with somatostatin therapy, pre-embolization, peri-embolization and post-embolization, at doses to control symptoms, is an aggressive approach that can relieve hormonal symptoms with minimal morbidity and mortality. METHODS: Chemoembolization was performed using 30 mg of adriamycin, 50 mg of mitomycin, 12 ml of hexabrix, 10 ml of ethiodol, and 360-500-microm particles. Pancreastatin, a split product of chromogranin A, was measured pre-HACE and post-HACE in all patients. RESULTS: Forty-three chemoebolization procedures were performed in 34 symptomatic patients from December 1995 to August 1999. Seventeen patients had intestinal primaries (50%), seven had pancreatic primaries (20%), five had bronchial primaries (15%), and five had unknown primaries (15%). Systemic pancreastatin levels were improved or stable in 31 patients (78%). Symptoms were improved in these 31 patients (78%). Systemic serotonin levels were improved or stable in 24 patients (60%). Radiographic improvement or stability was seen in 18 patients (45%). Procedural related morbidity included pain, fevers, nausea, vomiting, and transient elevations of liver function studies in 75-100% of patients. There was one procedural related mortality (2%). Less than 20% improvement in pancreastatin levels from baseline was associated with death in five of five patients (100%). This was not observed with serotonin levels. CONCLUSION: Measurement of serum pancreastatin levels is an easy and useful method to predict success in patients who undergo HACE plus somatostatin therapy for metastatic neuroendocrine tumors to the liver. This therapeutic approach is effective in relieving symptoms in 78% of patients, with minimal major morbidity or mortality.

Adult↗
PubMed2001

Fluorodeoxyglucose positron emission tomography as an adjunct to carcinoembryonic antigen in the management of patients with presumed recurrent colorectal cancer and nondiagnostic radiologic workup.

BACKGROUND: The purpose of this study was to determine the role of fluorodeoxyglucose positron emission tomography (PET) in localizing disease in patients with colorectal cancer with radiologically occult symptomatology or increases in carcinoembryonic antigen (CEA) level. METHODS: Two hundred seventy-seven patients with colorectal cancer underwent PET scanning between November 1998 and September 2000 prompted by (1) increasing CEA level and nondiagnostic imaging or (2) symptoms with normal CEA level and nondiagnostic imaging. PET results were correlated with operative findings/histology, clinical follow-up data, and CEA level to determine PET's accuracy in determining the source of symptoms or CEA. RESULTS: Fifteen patients had increasing CEA levels, and 14 had abnormal PET. Two of these 14 were denied exploration because PET suggested widely metastatic disease. Nine patients underwent exploration with curative intent. In 1 patient, recurrence was not pathologically confirmed (false-positive rate, 8%). Two had disease beyond that predicted by PET, and 6 underwent complete resection and normalized their CEA levels. Four symptomatic patients with normal CEA levels and negative x-rays had abnormal PET; at exploration, 3 had no evidence of recurrence. CONCLUSIONS: PET imaging can often accurately localize the source of radiologically occult increases in CEA level and select that subset of patients eligible for therapeutic laparotomy. Symptomatic, PET-positive patients with normal CEA levels frequently undergo nontherapeutic laparotomy, and PET findings should be interpreted with caution in these patients.

Adult↗
PubMed2000

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.

Colorectal Neoplasms↗
PubMed1999

Three different intraoperative radiation modalities (electron beam, high-dose-rate brachytherapy, and iodine-125 brachytherapy) in the adjuvant treatment of patients with recurrent colorectal adenocarcinoma.

BACKGROUND: Intraoperative electron beam radiation therapy (IOERT) has been used in the treatment of patients with recurrent colorectal adenocarcinoma for the last 2 decades. Other intraoperative radiation modalities, such as intraoperative high-dose-rate brachytherapy (IOHDR) and intraoperative iodine-125 (125I) brachytherapy, present theoretic advantages for selected patients with recurrent colorectal adenocarcinoma. The experience of a single-institution series in which these three intraoperative radiation modalities were used in a nonrandomized manner is discussed in this report. METHODS: Between September 1989 and January 1997, 80 patients with colorectal adenocarcinoma recurrent in the pelvis or in the paraaortic lymph nodes were treated with IOERT (28 patients), IOHDR (23 patients), or 125I brachytherapy (29 patients). RESULTS: The overall 5-year local control rate was 26% (median = 12 months; 95% confidence interval [95%CI], 6-17). Tumors in paraaortic sites had significantly better local control than those in the pelvis (P = 0.03). The 5-year overall survival rate was 4% (median = 20 months; 95% CI, 17-23). Patients with microscopic residual disease (P = 0.02) and those treated with postoperative external beam irradiation (EBRT) (P = 0.0007) had statistically significant longer survival. Forty-one percent of the treated patients experienced complications: These were severe (Radiation Therapy Oncology Group Grade 4-5) in 19% of patients. CONCLUSIONS: Intraoperative radiation can locally control recurrent colorectal adenocarcinoma in a select group of patients. Patients with localized relapses, microscopic residual tumor, and no distant metastases and those receiving additional EBRT are most likely to benefit from intraoperative irradiation. The authors now routinely recommend EBRT to all patients for whom it is suitable (including those who have had prior EBRT) and consider the combination of the intraoperative modalities whenever feasible.

Adenocarcinoma↗
PubMed1999

Cellular immunotherapy for patients with metastatic colorectal carcinoma using lymph node lymphocytes localized in vivo by radiolabeled monoclonal antibody.

BACKGROUND: The authors showed previously that radiolabeled monoclonal antibody (MoAb) and a hand-held, gamma-detecting probe can be used to localize tumor-reactive lymph nodes in vivo. The authors examined the feasibility, safety, and biologic effects of cellular immunotherapy using autologous cells expanded from these lymph nodes in patients with metastatic colorectal carcinoma. METHODS: Tumor-reactive lymph nodes containing radiolabeled MoAb were localized and excised from 32 patients with metastatic, unresectable colorectal carcinoma at laparotomy. Lymph nodes were dissociated, and cells were cultured ex vivo for 10-14 days. Patients received a single infusion of autologous, expanded cells with no systemic interleukin (IL)-2. RESULTS: A mean of 1.6 x 10(10) expanded autologous lymph node cells were infused with toxicity limited to occasional fevers or chills. The cells infused predominately were activated CD3+ T-cells that expressed genes for IL-4, IL-5, interferon-gamma, and granulocyte-macrophage colony stimulating factor (GM-CSF) by using reverse transcriptase-polymerase chain reaction. Indium-111 labeled cells were observed to traffic initially to the lungs, bone marrow, liver, and spleen. One patient on study achieved a partial response (>80% reduction), and mixed or minor responses were noted in 4 other patients. The responding patient's cell characteristics were notable for high levels of GM-CSF and IL-4 secretion on restimulation with immobilized anti-CD3 in vitro, and biopsies of the tumor were characterized by macrophage infiltration. The median survival of the cell-treated group compared favorably with a similar group of patients who underwent radioimmunoguided surgery without cell treatment (12.5 months vs. 5.8 months) CONCLUSIONS: The infusion of cells expanded from tumor-reactive lymph nodes localized with radiolabeled MoAb in vivo is reproducible and safe and has biologic activity, even in the absence of systemic IL-2 infusion. This approach represents a novel application of MoAb technology, in that MoAbs are used not to diagnose or treat disease directly but rather to identify lymph node cells with therapeutic potential.

Adult↗
PubMed1999

Iodine-125 brachytherapy in the treatment of colorectal adenocarcinoma metastatic to the liver.

BACKGROUND: The liver is the site of distant failure in > 33% of patients with colorectal adenocarcinoma. Liver resection is the only potentially curative option in these patients. Patients with incompletely resected liver lesions (due to the proximity to critical vascular structures) are at high risk of dying of progressive disease in the liver. This pilot study was performed to determine whether the intraoperative implantation of iodine-125 (I-125) seeds could reduce the recurrence and improve the survival of patients with incompletely resected liver metastases. METHODS: Fifty-six patients with unresectable or residual disease after surgical resection of liver metastases from colorectal carcinoma underwent permanent implantation with I-125 seeds to deliver 160 gray to the periphery of the target volume. RESULTS: The 1-, 3-, and 5-year actuarial control rates of liver disease were 41%, 23%, and 23%, respectively. The 5-year actuarial control of liver disease was better for patients with a solitary metastasis (39%) than for those with multiple metastases (9%) (P = 0.04). The 1-, 3-, and 5-year actuarial overall survival rates were 71%, 25%, and 8%, respectively (median, 20 months; 95% confidence interval, 17-23). The radiation-related complications were minimal. CONCLUSIONS: I-125 liver brachytherapy is feasible with minimal radiation-related morbidity. Good prognostic factors for long term liver control and survival are the presence of a solitary metastasis, postresection minimal residual disease requiring smaller volume implants, and no prior liver resections. Future prospective trials should be directed toward this patient population, which has the highest probability of obtaining improved results from the local dose escalation provided by brachytherapy. Adjuvant regional chemotherapy clearly is needed due to the high rate of liver recurrence and ultimate death from liver failure observed in spite of liver resection and brachytherapy.

Adenocarcinoma↗
PubMed1999

Intraoperative electron beam radiotherapy in recurrent colorectal carcinoma.

BACKGROUND AND OBJECTIVES: The installation of a dedicated linear accelerator in a shielded operating room in 1992 allowed us to start a feasibility study of intraoperative electron beam radiation therapy (IOERT) in colorectal carcinoma. METHODS: From March 1992 to February 1996, 28 patients with recurrent colorectal carcinoma were treated with maximal surgical resection and IOERT to the pelvis (n = 20) or paraortics (n = 8). IOERT dose ranged from 10 to 20 Gy with electron energies of 6-15 MeV. Postoperative external beam radiation therapy (EBRT) of 45-50 Gy was planned for the previously unirradiated patients. RESULTS: IOERT was well tolerated, but 10 (70%) of 13 patients in the previously unirradiated group did not complete the EBRT per protocol. Eight patients (29%) had some morbidity including surgically related fistula distal from IOERT sites. Two patients developed pelvic pain, which can be attributed to IOERT. Three-year local control at sites treated with IOERT was 40% (53% for previously irradiated patients and 27% for previously unirradiated patients). The 3-year actuarial overall survival was 12% (17% for previously irradiated patients and 8% for previously unirradiated patients). CONCLUSIONS: Our initial experience showed that it was feasible to treat poor prognostic colorectal cancer patients with IOERT. The morbidity observed was mainly related to extensive surgery in high-risk patients. Poor local control was obtained in patients treated with low-dose IOERT alone. Hence, previously unirradiated patients are encouraged to complete the planned EBRT or, alternatively, are considered for EBRT preoperatively or are given a higher IOERT dose (up to 20 Gy) if EBRT will not be given. Since IORT doses >20 Gy are associated with nerve toxicity, we currently add limited dose EBRT in the previously irradiated group. Patients with disease located in multiple abdominal sites are no longer considered candidates for IOERT.

Colonic Neoplasms↗
PubMed1999

Limitations with light microscopy in the detection of colorectal cancer cells.

PURPOSE: The failure of light microscopy to predict individual patient survival accurately in pStage I and II colorectal carcinoma can hinder planning postoperative therapy and follow-up. This study was designed and conducted in two parts to assess the influence of relative sensitivity of the light microscope on the pathologist's ability to detect malignant cells in lymph nodes. METHODS: The first part of the study examined the issue of sampling error as a fraction of the number of lymph node sections examined by asking the question, "Does increasing the number of sections (sampling) taken from the block increase tumor cell detection in a lymph node?" Three levels of five sections 4 to 5 microm thick separated by 15 to 20 microm were obtained from each of 494 blocks from 173 cases of pStage I and II colorectal carcinoma. A total of 1,721 lymph nodes were examined. Sections from each level were stained with hematoxylin and eosin and for the expression of cytokeratin. The second part of the study examined the relative sensitivity of the light microscope to detect tumor cells in a lymph node. To simulate lymph nodes, cell blocks were made that contained 10(6) or 10(7) mononuclear cells admixed with increasing numbers of SW480 tumor cells (0, 50, 10(2), 5 x 10(2), 10(3), and 5 x 10(3)). Three pathologists independently examined sections from ten control and ten experimental blocks. RESULTS: Results from the first part of the study demonstrated cytokeratin-positive cells in 278 lymph nodes from 102 of 172 (59 percent) cases. These cells were identified in the first level in 177 (64 percent) as compared with the second or third level or both in 101 (36 percent) of the lymph nodes. Results from the second part of the study demonstrated an overall sensitivity of light microscopic examination of hematoxylin and eosin-stained sections to be approximately 23 percent, representing tumor cells correctly detected in 7 sections of the 30 sections containing tumor cells. The overall specificity was 87 percent or 26 sections correctly classified as lacking tumor cells of a possible 30. Immunohistochemical staining for cytokeratin expression improved sensitivity of the light microscope to detect tumor cells to 18 of 30 (60 percent) and the specificity to 30 of 30 (100 percent). CONCLUSION: This study demonstrates several sources of variability that can induce errors in pathologic staging. These include 1) inadequate section, i.e., sampling, of lymph nodes, 2) use of only hematoxylin and eosin-stained sections, 3) samples with tumor cells below the level of detection sensitivity of the light microscope, and 4) observer variability.

Colorectal Neoplasms↗
PubMed1999

Is carcino-embryonic antigen useful in the follow-up management of patients with colorectal liver metastases?

BACKGROUND: The role of carcino-embryonic antigen (CEA) in monitoring early detection of recurrent or metastatic colorectal cancer, and its impact on resectability rate and patient survival remains controversial. Our objective was to determine any association between the preoperative level of CEA and prognosis, and the resectability and survival by method of diagnosis of colorectal hepatic metastases. METHODS: We analyzed patients who underwent exploration for hepatic resection for metastatic colorectal cancer over a 15-year period. The patient population consisted of those patients who had undergone primary colon or rectal resection and were followed up with serial CEA levels and of patients who were followed up with physical examination, liver function tests (LFTs) or computed tomography (CT) of the abdomen and pelvis that led to the diagnosis of liver metastases. Also included in the study were patients who were diagnosed with liver metastases at the time of the primary colon or rectal resection and underwent planned hepatic resection at a later time. RESULTS: Three hundred and one (301) patients who underwent a total of 345 planned hepatic resections for metastatic colorectal cancer between January 1978 and December 1993 were included in this analysis. The median preoperative CEA level was 24.8 ng/mL in the resected group, 53.0 ng/mL in the incomplete resection group, and 49.1 ng/mL in the nonresected group (P = 0.02). More of the patients who had a preoperative CEA < or =30 ng/mL were in the resected group, while those who had a preoperative CEA >30 ng/mL were likely to be in the nonresected group (P = 0.002). The median survival was 25 months for patients with a preoperative CEA level < or =30 ng/mL and 17 months for patients with a preoperative CEA >30 ng/mL (P = 0.0005). The resectability rate and the survival of patients by method of diagnosing liver metastases-rising CEA versus history and physical, elevated LFTs, CT scan versus diagnosis at the time of primary resection-was not significant (P = 0.06 and P = 0.19, respectively). Given the nonstandardized retrospective nature of the study cohort and relative small groups of patients, the power to detect small differences in survival by method of diagnosis is limited. In the complete resection group of patients with unilobar liver disease (5-year survival of 28.8%) there was no difference in survival between those patients who had normal preoperative CEA and those who had elevated preoperative CEA, and approximately 90% of them had an abnormal preoperative serum CEA level. CONCLUSIONS: CEA is useful in the preoperative evaluation of patients with hepatic colorectal metastases for assessing prognosis and is complimentary to history and physical examination in the diagnosis of liver metastases. Patients with colorectal liver metastases and preoperative CEA < or =30 ng/mL are more likely to be resectable, and they have the longest survival.

Biomarkers, Tumor↗
PubMed1999

Low-dose monoclonal antibody CC49 administered sequentially with granulocyte-macrophage colony-stimulating factor in patients with metastatic colorectal cancer.

The clinical and immunologic effects of murine monoclonal antibody (mAb) CC49 administered at a low dose sequentially with granulocyte-macrophage colony-stimulating factor (GM-CSF) were examined. Fourteen patients with metastatic colorectal cancer received 1 mg of unconjugated CC49 on day 1; on day 15 they began 125 micrograms/m2 GM-CSF by subcutaneous injection daily for 14 days, followed by 7 days of rest. Another 14 days of GM-CSF were then administered, followed by 7 days of rest. This 56-day cycle was repeated in patients whose cancer did not progress. Therapy was well tolerated; adverse allergic reactions were not observed. Objective tumor responses were not observed. Increases in antiidiotypic (T2) and anti-antiidiotypic (T3) cellular responses were observed, as were increases in human antimouse antibody levels. In contrast, the expression of Fc receptors on CD14+ peripheral blood monocytes decreased. This pilot study demonstrates idiotypic cellular immunologic effects of antitumor murine mAb, even at the doses used for imaging, and supports the sequential administration of GM-CSF as an adjuvant to mAb-based immunogens.

Adult↗
PubMed1998

125Iodine brachytherapy for colorectal adenocarcinoma recurrent in the pelvis and paraortics.

PURPOSE: To evaluate the results of 125I brachytherapy in colorectal cancers recurrent in the pelvis and paraortics. METHODS AND MATERIALS: From September 1989 to January 1997, 29 patients with colorectal adenocarcinoma recurrent in the pelvis or the paraortic nodes were treated intraoperatively with permanent 125iodine seed implantation at the James Cancer Center of The Ohio State University (OSU). All patients had undergone prior surgery; 72% had prior EBRT. The implanted residual tumor volume was microscopic in 38% and gross in 62%. The implanted area (median 25 cc) received a median minimal peripheral dose of 140 Gy to total decay. An omental pedicle was used to minimize irradiation of the bowel. Five patients received additional postimplant EBRT (20-50 Gy; median 30 Gy). RESULTS: The 1-, 2-, and 4-year actuarial local-regional control rates were 38%, 17%, and 17%, respectively, with a median time to local failure of 11 months (95% CI 10-12 months). The first manifestation of disease progression in 52 % of the patients was local-regional. In addition, 22 patients (75%) developed distant metastases. The 1-, 2-, and 4-year actuarial overall survival rates were 70%, 35%, and 21%, (median = 18 months; 95% CI: 14-22 months). Overall survival was better for patients smaller volume implants (p = 0.007), with a lower total activity implanted (p = 0.0003), with a smaller number of implanted sites (p = 0.004), and with microscopic residual disease (p = 0.01). Patients receiving additional EBRT also had a better prognosis (p = 0.005). Local tumor progression was the cause of death in 34% of the patients who have died at the time of this report and 56% died of distant metastases. Of the patients, 13 (45%) experienced 15 toxic events, including 3 patients (10%) with enteric fistula. Neuropathy was not observed. CONCLUSIONS: 125I brachytherapy can be successfully used for salvage in patients with recurrent colorectal cancer. Patients with isolated, microscopic, or minimal gross residual disease requiring small-volume implants and those receiving additional EBRT have a better prognosis. Postimplant EBRT is now routinely added, even for previously irradiated patients, in an attempt to improve local control. Compared to IOERT and IOHDR, 125I brachytherapy is not associated with clinical neuropathy, probably due to the continuous low dose rate irradiation delivered by the 125I seeds.

Adult↗
PubMed1998

Intraoperative radioimmunodetection.

The radioimmunoguided surgery (RIGS) system employs a monoclonal antibody (CC49), a radionuclide (Iodine-125), and a hand-held gamma-detecting probe (the Neoprobe model 1000). The prototype cancer studied has been colorectal cancer. The antibody identifies a type of mucin, the by-product of the adenocarcinoma cancer cell. The RIGS system localizes up to 90% of colorectal cancers and finds additional RIGS-positive tissues in >50% of the patients. More than 90% of the RIGS-positive visceral tumors are identified by routine hematoxylin-and-eosin (H&E) light microscopy, but the RIGS-positive lymph nodes are H&E occult tissues in >70% of the cases. Enhanced, more time-consuming methods have been developed to confirm hidden cancer cells in these lymph node tissues. Survival data confirm the importance of RIGS-positive tissues. RIGS-positive tissues remaining at the completion of the surgical procedure portend a much poorer outcome than if the patient is deemed RIGS-negative at the completion of the surgical procedure (i.e., all RIGS-positive tissue was removed at surgery).

Antibodies, Monoclonal↗
PubMed1998

Staging of colorectal cancer: biology vs. morphology.

PURPOSE: An accurate determination of the extent or staging of a disease is critical, because it provides the basis for making therapeutic decisions. Staging is a collaborative effort by the surgeon and the pathologist. Radioimmunoguided surgery has been evaluated for its ability to help surgeons determine the extent of disease during surgery, when management decisions have the most impact on patient care. This study was done to compare radioimmunoguided surgery "biostaging" with traditional pathologic staging (TNM) as predictors of survival in patients undergoing curative resections for colorectal cancer. METHODS: Ninety-seven patients with colorectal cancer were prospectively enrolled in radioimmunoguided surgery protocols. Evaluation of follow-up survival data was performed. All patients underwent exploratory laparotomy and radioimmunoguided surgery with resection of their primary colorectal tumor. Survival data were analyzed with the Kaplan-Meier method with log-rank comparisons. RESULTS: Of 97 patients enrolled in the study, 59 were evaluable and completely resectable by radioimmunoguided surgery. Mean follow-up was 62 months, with a range of 34 to 89 months. By traditional staging 13 patients were pStage I, 18 patients were pStage II, and 28 patients were pStage III. By radioimmunoguided surgery biostaging, 24 patients were radioimmunoguided surgery-negative whereas 35 patients were radioimmunoguided surgery-positive. Survival rates by pathologic stage approached a significant difference, but did not, as of the conclusion of the study period, reach it (P = 0.12). Survival rates based on radioimmunoguided surgery status demonstrated a highly significant difference (P = 0.0002). CONCLUSIONS: Radioimmunoguided surgery biostaging provides new information intraoperatively on cancer staging that has not been available before. This may lead to new strategies for therapy that can be individualized and optimized for each patient with cancer.

Adult↗
PubMed1998

[Lymphadenectomy in colorectal carcinoma].

Recurrence of colorectal carcinomas occurs in about 50% of the cases with localized neoplasia. It is understood that the tumor recurrence is due to residual micrometastases not found during surgery or extraregional (peripheral blood or bone marrow). We developed a procedure to detect non-visible, abdominal metastases using a radiolabeled anti-tumor cell antibody injected before the operation (radioimmunoguided surgery RIGS). However, even with the best technique, it is not possible to remove all micrometastasis if a hematogenic dissemination happens. Based on the knowledge of disturbing humoral immune reaction is mounted against shed tumor associated antigens (TAA), we developed a new method to reduce and correct the B cell response and B cell recruitment due to chronic TAA immun complex presentation on follicular dendritic cells (immune corrective surgery, ICS). This method is based on a selective lymphadenectomy. The target lymph nodes were those loaded with TAA-immune complex. The detection method used was the injection of radiolabeled antibody able to recognize the immune complex. From 20 patients (stage I, II and III) treated with ICS, 17 survived more than 5 years 'showing a statistically significant increase of survival compared to patients treated with standard procedures. In conclusion, these data show that surgery of colorectal cancer should be selectively extended to specific anatomical regions in order to remove hidden micrometastases, and more importantly, correct postoperative immune processes that could suppress the T cell response against residual tumor cells.

Colorectal Neoplasms↗
PubMed1998

Determinants of survival following hepatic resection for metastatic colorectal cancer.

Hepatic resection remains the only potentially curative treatment for metastatic colorectal cancer. This retrospective review study was undertaken in an attempt to identify factors that influence patient survival following hepatic resection for metastatic colorectal cancer. From January 1978 to December 1993, a total of 301 patients underwent a total of 345 planned hepatic resections for metastatic colorectal cancer. Of those, 245 patients had one resection, 44 had two resections, and 12 had three resections. For all patients the overall median survival was 20.6 months, operative mortality was 1.1%, and overall morbidity was 17.2%. Average hospital stay was 9 days. Statistical analysis included univariate analysis using log rank comparisons, Kaplan-Meier survival curves, and multivariate analysis using Cox proportional hazards regression. The statistically significant factors that influenced survival were distribution of liver metastases, unilobar versus bilobar (p = 0.0001), resected versus nonresected (p < 0.0001), and tumor-free surgical margins versus positive margins (p = 0.001). Surprisingly, the disease-free interval and the original stage of the primary tumor did not predict survival (p = not significant). Other factors that had no influence on survival were type of resection, size and number of liver metastases, ABO blood group, and the number of perioperative blood transfusions. For those patients who underwent resection of unilobar metastases with tumor-free margins, the 5-year survival rate was 29% with a median survival of 35 months and eight survivors > 7 years. In addition, one patient with bilobar disease had survival > 7 years and five patients who had resection of hepatic metastases and extrahepatic cancer simultaneously had survival > 3 years. Our data support the concept that patients with unilobar metastatic disease who undergo surgical resection with tumor-free surgical margins can be afforded a significant opportunity at long-term survival with acceptable morbidity, mortality, and hospital stay. Also, certain patients with bilobar or extrahepatic disease (or both) who undergo complete resection can enjoy a long-term survival. In these subgroups of patients resection should be considered on an individual basis.

Adenocarcinoma↗