Laser tumor thermotherapy: Is there a clinically relevant effect on the immune system

Laser thermotherapy is interesting from an immunological point of view since it can reduce tumor volume without causing immunosuppression at the same time as it may induce and/or enhance tumor immunity. In a rat liver tumor model, we have demonstrated that laser thermotherapy 1) is superior to surgical resection, 2) gives a strong rejection immunity associated with an immune cellular response of tumor-infiltrating macrophages and CD8 lymphocytes, 3) results in pronounced suppression of the growth of a simultaneous untreated tumor (distant bystander effect), 4) produces an increased anti-tumor lymphocyte proliferative response in tumor-draining and systemic lymph nodes and spleen, and 5) results in increased HSP70 immunoreactivity in tumors and tumor-infiltrating macrophages. Thus, the evidence for a laser-induced immunologic effect in tumor-bearing rats is strong. Some observations suggest that laser thermotherapy may be used for inducing favorable immunologic effects also in patients. Thus, we have shown a laser-induced bystander effect in a patient with malignant melanoma. In patients with breast cancer we have shown that laser thermotherapy induces intratumoral infiltration of immunocompetent cells like CD68 macrophages and CD8 lymphocytes. Laser thermotherapy is likely to be beneficial mainly when tumor burden is small, that is, when treatment is performed with curative intent, either with laser alone or together with surgical resection. For optimal effect, it appears likely that thermotherapy should be combined with other therapies. Most likely, a clinically meaningful effect can only be proven in prospective randomized studies comparing thermotherapy with other methods, particularly surgical resection

Local Destruction of Tumors and Systemic Immune Effects

Current immune-based therapies signify a major advancement in cancer therapy; yet, they are not effective in the majority of patients. Physically based local destruction techniques have been shown to induce immunologic effects and are increasingly used in order to improve the outcome of immunotherapies. The various local destruction methods have different modes of action and there is considerable variation between the different techniques with respect to the ability and frequency to create a systemic anti-tumor immunologic effect. Since the abscopal effect is considered to be the best indicator of a relevant immunologic effect, the present review focused on the tissue changes associated with this effect in order to find determinants for a strong immunologic response, both when local destruction is used alone and combined with immunotherapy. In addition to the T cell-inflammation that was induced by all methods, the analysis indicated that it was important for an optimal outcome that the released antigens were not destroyed, tumor cell death was necrotic and tumor tissue perfusion was at least partially preserved allowing for antigen presentation, immune cell trafficking and reduction of hypoxia. Local treatment with controlled low level hyperthermia met these requisites and was especially prone to result in abscopal immune activity on its own

Disappearance of esophageal carcinoma after stenting combined with endoscopic laser therapy

A 92-year-old man with dysphagia secondary to squamous cell carcinoma of the esophagus was palliated repeatedly with endoscopic laser therapy and insertion of esophageal stents. During the treatment period of 32 months, the patient could be fed perorally while ingrowth of tumor, development of new stenoses at the edges of the stents, and breakage of one stent were encountered. A tracheoesophageal fistula developed at the upper edge of the first stent. The patient died from aspiration pneumonia. At autopsy, no cancer cells were found in the esophagus. Combined endoscopic laser treatment and stent therapy may keep a patient free from dysphagia during a long period of time and also may result in the complete disappearance of tumor growth in the esophagus

Resection of colorectal liver metastases: 25-year experience

The aim of this retrospective study was to analyze survival and prognostic factors in 111 consecutive patients undergoing curative resection of liver metastases from colorectal cancer. In addition, the time periods 1971-1984 and 1985-1995 were compared; criteria for first liver resection did not change with time, whereas the attitude toward re-resection was more aggressive during the latter period. Operative mortality was 6% during 1971-1984 and 0% during 1985-1995 (3.6% for all patients). The crude 5-year actuarial survivals were 19% and 35% for patients operated during 1971-1984 and 1985-1995, respectively (25% for the whole period). Relapse at any site was observed in 52 patients (81%) operated during the first period and in 29 patients (67%) operated during the second period; re-resection was performed in 12 (23%) and 15 (52%) of these patients, respectively. Five-year survival after hepatic re-resection was 29% (no operative mortality). In the univariate analysis, significant determinants for long-term survival were, in descending order, a clear resection margin, high degree of fibrosis around the tumor, absence of extrahepatic metastases (including metastases to the liver hilum), use of an ultrasound dissector, low preoperative serum carcinoembryonic antigen (CEA) level, year of resection (1985-1995), and low/moderate grade of liver tumor. There were no 5-year survivors when extrahepatic metastases were present, the liver tumor(s) had a low differentiation or satellites, or the resection margin was involved with tumor. In the multivariate analysis, the determinants were grade of liver tumor, absence of extrahepatic tumor, few intraoperative blood transfusions, low preoperative serum CEA level, and year of resection (1985-1995). It is concluded that: (1) an increased rate of hepatic re-resection was partly responsible for the improved outcome after liver resection for colorectal metastases during recent years; (2) patients with extrahepatic metastases did not benefit from liver resection; and (3) surgery should be performed with a clear resection margin and minimal blood loss

Models for the Insulin Response to Intravenous Glucose

The Grodsky packet storage model describes many features of insulin release, but at present more or less arbitrary simplifications are necessary. The consequences of various simplifications are discussed, especially with regard to identification of parameters thought to be of importance for glucose tolerance. In particular, the insulin release dynamics of the ordinary intravenous glucose tolerance test is examined. The proposed model contains the following features: It considers arterial rather than venous blood glucose concentration as the stimulus, it takes the glucose injection time into account, and it contains a positive derivative term during the rise of the glucose concentration. When the insulin elimination-rate time constant is fixed to an a priori value, model fitting gives a clear quantification of the sensitivity of early and late insulin release to glucose