Splenectomy in the accelerated or blastic phase of chronic myelogenous leukemia: a single-institution, 25-year experience.

BACKGROUND: Patients in the accelerated or blastic phases of chronic myelogenous leukemia (CML) often have painful splenomegaly and secondary thrombocytopenia. We tested the hypothesis that splenectomy can be performed with minimal complications in advanced CML, thereby alleviating pain, reversing thrombocytopenia, and minimizing transfusion requirements. METHODS: We reviewed the records of 53 patients in the accelerated or blastic phases of CML who underwent splenectomy between 1970 and 1995 at the U. T. M. D. Anderson Cancer Center. RESULTS: Twenty-eight patients were in accelerated phase and 25 in blastic phase at the time of splenectomy. The most common indications for splenectomy were symptomatic splenomegaly (median splenic weight, 1000 gm; range, 120 to 6700 gm) or thrombocytopenia (platelet count less than 100,000/microliter) or both. There was 1 death within 30 days of splenectomy. The preoperative platelet count increased 3.72-fold +/- 0.53-fold (mean +/- SEM) by postoperative day 7 (p < 0.001; paired t test). Patients with transfusion-dependent thrombocytopenia had significantly fewer platelet and red blood cell transfusions in the 6 months after splenectomy than in the 6 months before splenectomy (p = 0.016; sign test). CONCLUSIONS: Splenectomy can be performed with minimal morbidity and mortality in advanced CML, thereby relieving symptomatic splenomegaly, reversing thrombocytopenia, and minimizing transfusion requirements.

Apoptosis, cancer and cancer therapy.

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis. Apoptosis is essential in the homeostasis of normal tissues of the body, especially those of the gastrointestinal tract, immune system and skin. There is increasing evidence that the processes of neoplastic transformation, progression and metastasis involve alterations in the normal apoptotic pathways. Furthermore, the majority of chemotherapeutic agents as well as radiation utilize the apoptotic pathway to induce cancer cell death. Resistance to standard chemotherapies also seems to be determined by alterations in the apoptotic pathways of cancer cells. Therefore, understanding the signals of apoptosis and the mechanism of apoptosis may allow the development of better chemo- or radiotherapeutic regimens for the treatment of cancer. Finally, components of the apoptotic pathway may represent potential therapeutic targets using gene therapy techniques.

Intraoperative radiation therapy following pancreaticoduodenectomy.

OBJECTIVE: To determine the morbidity and mortality of pancreaticoduodenectomy followed by electron-beam intraoperative radiation therapy (EB-IORT). SUMMARY BACKGROUND DATA: Local recurrence following pancreaticoduodenectomy occurs in 50% to 90% of patients who undergo a potentially curative surgical resection for adenocarcinoma of the pancreatic head. To improve local disease control, a more aggressive retroperitoneal dissection has been combined with adjuvant EB-IORT. METHODS: Forty-one patients with malignant neoplasms of the periampullary region underwent pancreaticoduodenectomy followed by EB-IORT between January 1989 and May 1992. EB-IORT was delivered in a dedicated operative suite, eliminating the need for patient relocation. Electron-beam energies of 6 to 12 MeV were used to deliver 10 to 20 Gy to the treatment field following resection but before pancreatic, biliary, and gastrointestinal reconstruction. RESULTS: Median operative time was 9 hours, blood loss was 1 L, perioperative transfusion requirement was 2 units, and hospital stay was 20 days. One patient died of a postoperative myocardial infarction, and four patients required reoperation, one for an anastomotic leak. No patient failed to receive EB-IORT because of operative complications during the time period of this study. CONCLUSION: Adjuvant EB-IORT after pancreaticoduodenectomy can be delivered safely, with low mortality and acceptable morbidity.

Site-specific differences in pp60c-src activity in human colorectal metastases.

The c-src proto-oncogene has been implicated in the progression of primary human colorectal carcinoma to hepatic metastasis. To determine if increased pp60c-src tyrosine kinase activity is a colon-specific phenomenon present in colorectal metastases to all sites, the pp60c-src-specific kinase activity of noncolon tumor metastases to the liver was compared to that of colorectal liver metastases. Activity of extrahepatic colon carcinoma metastases was compared to that of colorectal liver metastases as well as that of normal colonic mucosa. The specific activity of pp60c-src in multiple synchronous metastases from colon carcinoma was also examined. Tyrosine kinase activity was determined by immune complex kinase assay; protein levels were determined by immunoblotting. Specific activity was calculated for each group by dividing the total activity by protein level. Colon carcinoma metastases to the liver had significantly (P < 0.04) increased pp60c-src activity with an average 2.2-fold increase over normal mucosa. In contrast, noncolon tumor metastases to the liver showed minimal pp60c-src kinase activity. Extrahepatic colorectal metastases demonstrated significantly increased (P < 0.005) pp60c-src activity with an average 12.7-fold increase over normal mucosa. When compared to colon liver metastases, extrahepatic colorectal tumor metastases show a significant difference in activity (P < 0.05) with an average 5.7-fold increase. Examination of multiple synchronous colon carcinoma metastases confirmed these results. In summary, we conclude that (1) the activation of pp60c-src between primary tumors and metastases is specific to colon metastases, and (2) although pp60c-src activity is significantly increased in colorectal metastases, site-specific differences in the magnitude of activity are evident.