Productive research in patients with peritoneal carcinomatosis has moved slowly over several decades. In large part this was due to lack of standardized assessments by which cancer responses could be quantitated in a reliable and statistically evaluable manner. Recently, both laboratory and clinical assessments have been developed. Clinical research has shown that the prognosis of patients with peritoneal carcinomatosis is dependent upon preoperative and intraoperative variables [1]. These are the histologic grade of the malignancy, the preoperative tumor volume as assessed at surgery, the distribution of tumor at surgery, and the completeness of cytoreductive surgery. Also the preoperative abdominal and pelvic computed tomography (CT) scan has shown predictive value in assessment of the completeness of cytoreduction in patients with mucinous carcinomatosis [2]. The clinical research tools that are currently used in peritoneal carcinomatosis studies are reviewed in this manuscript.

Clinical research methodologies in diagnosis and staging of patients with peritoneal carcinomatosis

The incidence of colorectal cancer in the United States is increasing. Because more than half of patients with colorectal cancer have liver metastases develop, the number of patients with hepatic metastases also is increasing. Unfortunately, metastatic disease will be limited to the liver in perhaps 25% of these patients and confined to only one lobe of the liver 25% of this subgroup. Consequently, solitary or unilobar colorectal metastases are found in as few as 5% of patients with colorectal cancer. The median survival of patients with unresected hepatic metastases is approximately 10.6 months. Patients with solitary lesions or small tumor burdens may attain a median survival of 16-20 months, but 5-year survivors are extremely rare. In contrast, rates of 5-year survival average approximately 36% after resections of solitary hepatic lesions and may approach the same level in selected patients with multiple lesions. Factors that appear to adversely effect survival include detection of metastatic disease because of signs or symptoms of disease, an elevated carcinoembryonic antigen (CEA) level, elevated liver function tests, poorly differentiated primary lesions, lymph node-positive primary lesions, extrahepatic sites of metastases, more than four hepatic lesions, bilobar disease, a satellite pattern of metastases in the liver, positive margins of the liver resection, positive extrahepatic lymph nodes, and more than 10 units of blood transfusion during the perioperative period. Operative mortality for liver resections should remain approximately 4%, and major morbidity should be in the range of 20-30%. Modalities other than surgical resection have not improved survival in patients with colorectal hepatic metastases. Thus, when feasible, patients with metastatic colorectal cancer limited to one lobe of the liver should undergo hepatic resection. Unfortunately, only approximately 5% of patients with colorectal cancer fall into this category, so resection of hepatic metastases can improve overall survival of patients with colorectal cancer by only 1-2%.

Surgical treatment of liver metastases in patients with colorectal cancer

There is increasing interest in the use of metal-containing compounds in medicine. This review describes several therapeutic applications, such as the use of platinum complexes in cancer chemotherapy, gold compounds in the treatment of arthritis, gallium in hypercalcemia, bismuth in anti-ulcer medication, and sodium nitroprusside in hypertension. The use of metal radionuclides in diagnosis and radiotherapy and the role of paramagnetic metal complexes as contrast agents in magnetic resonance imaging are also discussed.

https://science.sciencemag.org/content/sci/261/5122/725.full.pdf

Metal compounds in therapy and diagnosis

In rectal cancer, depth of infiltration and metastatic involvement of lymph nodes are important prognostic factors. The correct choice of operative treatment depends on the extent of the disease. In a prospective study, the value of endorectal ultrasound in staging rectal cancer was evaluated, and factors affecting the method's accuracy are discussed. The overall accuracy in staging depth of infiltration was 89 percent. Overstaging occurred in 10.2 percent, understaging in 0.8 percent. Tumors of the lower rectum are incorrectly staged in 16.7 percent, whereas tumors of the middle and upper rectum had an incorrect staging in 6.3 percent (P < 0.001). Compared with computed tomography, endorectal sonography is the more accurate staging method (74.7 vs. 90.8 percent). In staging lymph nodes, the overall accuracy was 80.2 percent, sensitivity was 89.4 percent, specificity was 73.4 percent, positive predictive value (PPV) was 71.2 percent, and negative predictive value (NPV) was 90.4 percent. The staging accuracy depends on the size of the node. Endorectal ultrasound is a safe, inexpensive, and accurate staging method, in the assessment of both depth of infiltration and nodal status. The results are strongly related to the experience of the investigator.

How accurate is endorectal ultrasound in the preoperative staging of rectal cancer

This review summarizes data demonstrating the safety and efficacy of liver resection for colorectal metastases. Hepatic resection in appropriately selected patients remains the only potentially curative treatment for patients with such metastases. Recommendations for preoperative patient evaluation, patient selection, adjuvant therapy, and postoperative follow-up are presented. Other surgical modalities utilized in the treatment of unresectable or recurrent hepatic colorectal metastases, including ablative modalities and surgical delivery of regional chemotherapy, are described.

Surgical therapy of hepatic colorectal metastasis.

Presurgical colorectal cancer patients (n = 116) received single intravenous infusions of 1 mg of CYT-103 (OncoScint CR103), an immunoconjugate of monoclonal antibody B72.3, radiolabeled with 111In. Following gamma camera imaging, 103 patients underwent an operative procedure: 92 had primary or recurrent colorectal carcinoma, 1 patient evaluated for recurrence of colorectal cancer had a second primary malignancy (small cell lung), and 10 patients had no demonstrable evidence of malignancy. 111In-CYT-103 immunoscintigraphic findings were consistent with the pathologic diagnoses for 70% of patients with colorectal cancer and 90% of disease-free patients. Antibody imaging contributed to surgical decision making through the detection of occult disease (12% of patients) and the confirmation of localized, potentially resectable disease without regional or metastatic spread. Seven patients (6%) experienced adverse effects, primarily fevers and itching, and 33% of patients developed antibodies to murine immunoglobulin after administration of 111In-CYT-103. The results of this study suggest that 111In-CYT-103 is a useful diagnostic tool for the presurgical evaluation of colorectal cancer patients.

Radiolabeled antibody imaging in the management of colorectal cancer. Results of a multicenter clinical study.

PURPOSE: The role of immunoscintigraphy with111 Insatumomab pendetide in the medical and/or surgical management of colorectal cancer patients was evaluated in a multicenter trial METHODS: This 103 patient study population included 46 individuals with rising serum carcinoembryonic antigen levels and otherwise negative diagnostic evaluation, 29 patients with known recurrence, presumed to be isolated and resectable, and 28 patients for whom standard diagnostic tests provided equivocal information RESULTS: No adverse reactions were noted following intravenous administration of 1 mg of satumomab pendetide radiolabeled with approximately 5 mCi of111 In Thirty percent of patients developed human anti-mouse antibodies postinfusion In the 84 patients for whom correlation with histopathologic, diagnostic, and/or clinical findings was available, antibody imaging demonstrated a sensitivity of 73 percent in patients with confirmed tumor (36/49) and negative results for all 35 patients with no evidence of malignancy Occult disease was detected in 18 patients CONCLUSION: 111 In-satumomab pendetide immunoscintigraphy was helpful in the medical and/or surgical management of 45 (44 percent) patients and provided information unavailable from other diagnostic modalities

Edith P. Mitchell

Papers

Radiolabeled antibody imaging in the management of colorectal cancer. Results of a multicenter clinical study.

Immunoscintigraphy with111 In-satumomab pendetide in patients with colorectal adenocarcinoma: Performance and impact on clinical management