James L. Weese

Quantitation of Local Cerebral Blood Flow and Partition Coefficient without Arterial Sampling: Theory and Validation:

A new technique that requires neither arterial blood sampling nor prior knowledge of the indicators tissue–blood partition coefficient has been developed for quantitation of local CBF. This technique arises from an existing method that uses the inert, freely diffusible gaseous tracer [18F]methyl fluoride (CH318F) and positron computed tomography. The shape of the arterial blood curve is derived from continuous sampling of expired air. The concentration of CH318F in the arterial blood is assumed to be proportional to the expired gas curve interpolated between end-tidal values. The absolute scale of the blood curve is determined by fitting a series of venous blood samples to a multicompartment model. Four validation studies were performed to compare values derived using the venous scaled expired breath input function with those derived using direct arterial samples. The proposed method gave higher flow values than the standard arterial sampling method by an average of 4.4%. These validation studies and data from both normal and patient scans suggest that the method provides the quantitation necessary for interstudy comparisons yet avoids the trauma of an arterial puncture.

Endoscopic transrectal resection of rectal carcinomas using the urologic resectoscope

We haye described a technique used in ten patients for local control of rectal carcinomas. Transrectal resection of rectal tumors using the urologic endoscopic resectoscope is a technique that allows controlled, safe removal of tumors of the rectum under excellent optical conditions. This technique has been performed safely in elderly and extremely poor-risk patients with minimal complications and side effects. We suggest that this technique offers a reasonable alternative to fulguration in patients with rectal carcinomas who either refuse abdominoperineal resection or who, because of metastatic disease or infirmity, are not considered candidates for the more conventional approach.

Retrorectal cyst-hamartomas: CT diagnosis.

Retrorectal cyst-hamartomas (RRCH) are congenital lesions characterized by the presence of cysts lined by multiple types of epithelium, often predominantly mucin-secreting. Three cases of RRCH are presented with their associated histologic and CT findings. The lesion requires complete surgical excision to prevent complications of recurrence, infection, or metastasis.

Endoscopic transrectal resection of rectal tumors

Transrectal resection of rectal cancers with the use of the urologic resectoscope is a safe, controlled technique that allows good visualization with defined limits of excision. Twenty‐three patients have undergone 50 transrectal resections, with a median survival of 10.8 months. Only 1 of 22 patients required subsequent colostomy before death. Patients, followed as long as 29 months, have had good local control of tumor and excellent palliation of symptoms.

Chemical cholecystitis after intrahepatic chemotherapy: The case for prophylactic cholecystectomy during pump placement

Recent repopularization of intrahepatic infusion chemotherapy has been made possible by the development of the implantable Infusaid® pump. Surgical placement of a catheter into the gastroduodenal artery with division of collaterals to the stomach, duodenum, and pancreas has reduced the incidence of gastroduodenal ulceration and pancreatitis. The risk of chemical cholecystitis similarly demands prevention. Anatomically, the cystic artery is a branch of the right hepatic, artery in over 95 percent of patients. As a result, even a normal gallbladder is subjected to high-dose chemotherapy with the risk of development of drug-induced cholecystitis. In our first six patients undergoing pump implantation who had normal appearing gallbadders at the time of surgery, two developed symptomatic cholecystitis, necessitating cholecystectomy after receiving intrahepatic chemotherapy. As a result, we recommend elective cholecystectomy at the time of arterial catheterization for intrahepatic chemotherapy.

Does omentectomy prevent malignant small bowel obstruction

Because the omentum collects and disseminates cancer cells, omentectomy is an integral part of ovarian cancer surgery. We postulate that the omentum serves a similar function in colon cancer and may contribute to post-operative malignant small bowel obstruction (S.B.O.) and that routine omentectomy during colectomy would reduce the incidence of. S.B.O. Fischer 344 rats and a transplantable carcinogen-induced rat colon cancer were used to test: (1) whether the omentum is a unique site of intra-abdominal colon tumor implantation which contributes to S.B.O.; and (2) whether omentectomy at the time of tumor implantation would reduce the incidence of S.B.O. Statistical analysis confirmed that animals undergoing omentectomy had a significantly lower incidence of omental tumors and malignant S.B.O. (26 per cent and 16 per cent respectively) when compared with sham operated animals (75 per cent and 85 per cent respectively,P < 0·001). These data suggest that the omentum is a source of bowel obstruction from implantation and growth of tumour cells in the rat rnodel. Although this could be tested in other animal systems, the addition of routine omentectomy to colectomy is simple, not time-consuming, and may reduce postoperative morbidity.

Reduced incidence of rat colon cancer metastases by perioperative immunostimulation with maleic anhydride-divinyl ether-2 (MVE-2)

Intra-abdominal operations result in profound immunodepression during a period when tumor cells are released into the systemic and portal circulations. This combination may augment tumor metastases. The authors have developed a model in which rat colon carcinoma cells transplanted into the portal vein consistently induce hepatic metastases by four weeks, and death within nine weeks. Additionally, the authors have shown that perioperative treatment with levamisole significantly reduces the incidence of metastases. This study tested whether maleic anhydride-divinyl ether-2 (MVE-2), a known immunostimulant, would produce similar effects.Rats pretreated with MVE-2 the day before and day of tumor implantation developed fewer metastases (34 percent of animals treated with MVE-2, compared with 5 percent of animals not treated with MVE-2 had≤two liver metastases). Eighteen percent of MVE-2-treated rats developed no hepatic metastases. Comparison of median liver weights between the MVE-2-treated group and the nontreated, tumor-bearing group was significant (P=0.03) and the MVE-2-treated animals had significantly prolonged survival (P=0.04). The authors conclude that the perioperative period is critical for the implantation and growth of metastases and that perioperative immunostimulation may be a factor in decreasing the incidence of metastases. This model may have relevance to the adjuvant treatment of human colonic cancer.

Lysosomal enzyme activity in pulmonary alveolar macrophages, peritoneal macrophages, and blood mononuclear leukocytes in the hypothyroid rat.

Chronic hypothyroidism can result in an increased susceptibility to severe pulmonary or genitourinary tract infections. We postulate that decreased lysosomal activity in the pulmonary alveolar macrophage (PAM), peritoneal macrophage, and mononuclear leukocyte may be a factor which results in the impaired response to infections in hypothyrosis. In this study rats underwent total thyroidectomy and had their PAMs, peritoneal macrophages, and mononuclear leukocytes analyzed after 4, 8, and 12 weeks. The total lysosomal activity (postnuclear homogenate + lysosomal-rich cell fraction) of PAMs was 50% of age-matched controls. Peritoneal macrophage lysosomal enzyme activity was 25-30% of control activity. In separate experiments, rats were administered physiologic replacement of triiodothyronine (T3) 8 weeks after thyroidectomy. This resulted in PAM and peritoneal macrophage lysosomal enzyme activity similar to control activity. Mononuclear leukocyte lysosomal enzyme activity from hypothyroid rats showed decreases in only one of the three enzymes monitored (beta-glucuronidase). Hypothyroidism did result in a decrease in total number of mononuclear leukocytes harvested per animal. Administration of T3 resulted in mononuclear leukocyte beta-glucuronidase activity similar to euthyroid rats (44 +/- 8 U/mg protein vs 42 +/- 3 U/mg protein). In summary, hypothyroidism in the rat results in decreases in subcellular lysosomal enzyme activity in PAMs, peritoneal macrophages, and mononuclear leukocytes.

Development of a carcinogen-induced rat colon cancer with lymph-node metastases

The progression from normal colonic mucosa to invasive adenocarcinoma of the colon with lymph-node metastases was documented in Sprague-Dawley rats receiving 30 mg of N-methyl-N-nitrosourea via intrarectal injections. Histologically, these tumors closely resemble human colonic cancer. This model is predictable and reproducible. It offers a genetically nonidentical rat model for the development of cancer biology and therapy models.

The Development of Techniques That Permit the Selection and Growth of Malignant Cells from Human Colonic Carcinomas

Publisher Summary This chapter discusses the development of techniques that permit the selection and growth of malignant cells from human colonic carcinomas. The technique which, was developed involved a human colon cancer cell line bank utilizing culture methodologies that permit successful establishment of cell lines from the majority of cancer specimens cultured. Cell lines have been established from neoplastic specimens which include the full spectrum of the clinical disease including an adenoma, localized and aggressive primary cancers, and metastases. These cell lines display biologic and pharmacologic diversity, making the VACO cell line bank an attractive disease-specific model for use in drug discovery programs as well as studies to understand the biologic progression of colon cancer. It was recognized that cell lines undergo selective pressures during in vitro cultivation and as a result may not retain all phenotypes present in the individual clinical tissue of origin. On the other hand, the preservation of such diverse characteristics in these established lines suggests that they exhibit at the least a portion of the diversity present in the patients, and they represent a valuable and practical model system for the laboratory investigation of colon cancer.