Locoregional adoptive immunotherapy resulted in regression in distant metastases of a recurrent esophageal cancer

 Esophageal cancer is one of the most common malignant diseases. However, postoperative recurrences are still resistant to currently available radiochemotherapy. We recently reported a study on the initial clinical efficacy of locoregional adoptive immunotherapy for advanced esophageal cancer. We report here our clinical experience of remarked responses in distant metastatic lesions in a patient with recurrent cancer after receiving this immunotherapy. A male patient underwent curative surgery, and presented with multiple recurrent metastases in the supraclavicular lymph nodes (LNs), liver, and abdominal aortic LNs. Autologous tumor-activated lymphocytes (AuTLs) generated ex vivo were regionally injected into supraclavicular LNs every 2 weeks 13 times. Mean numbers of the administrated cells were 0.8 × 10⁹ cells/injection. AuTLs established from peripheral blood lymphocytes stimulated by autologous tumor cells with interleukin-2 were tested for their cytotoxicity before every treatment. During immunotherapy, Grade 2 diarrhea and fever were observed. The clinical partial responses were obtained in all lesions and were sustained for 11 months. Because clinical toxicity was tolerable, this immunotherapy might be useful for patients with far-advanced esophageal cancers. Received: June 19, 2002 / Accepted: September 26, 2002 Correspondence to:U. Toh     

Indications and limits of breast conserving treatment

In Japan, 41% of surgeries for breast cancer were breast conserving treatment (BCT) in 2000. The indications for BCT in the guidelines of the Japanese Breast Cancer Society (1999) are as follows: (1) tumor size is 3 cm or less, (2) image diagnosis indicates no sign of extensive intraductal spread, (3) cases with multiple tumor are excluded, (4) radiation therapy is possible, (5) the patient wants to receive BCT. The pathological negative margin is favorable in BCT; however, we estimate based on our study that only about 30% of all breast cancers can be completely resected by partial mastectomy. To extend the indications for BCT, the roles of postoperative radiotherapy, endocrine therapy and preoperative chemotherapy will be important. Patients with ipsilateral breast tumor recurrence (IBTR) have increased risk of distant metastases, and the presence of IBTR is an important predictive factor for distant metastases. When we discuss the indications and limits of BCT, we have to take the rate of IBTR into careful consideration.     

Intraarterial cellular immunotherapy for patients with inoperable liver metastases of esophageal cancer

PURPOSE: We report 2 patients with refractory liver metastatic tumor after esophagectomy for advanced esophageal cancer, who responded markedly to locoregional cellular immunotherapy by repeated intraarterial infusions of autologous tumor cell-activated T lymphocytes (AuTL), even after they failed the standard chemotherapy of cisplatin (CDDP) and 5-fluorouracil (5-FU). METHODS: AuTL administrations were made through the hepatic artery via a subcutaneous reservoir located at the right upper leg. Six injections were administered to both patients, repeated at 2-week intervals. The total number of administered T cells reached 2.4 x 10(9) and 3.1 x 10(9), respectively. RESULTS: A 39% and 51% regression in each infused field, compared with the size of liver tumor before treatment, was observed by computed tomography (CT) scan in patient 1 and 2, respectively. The responses continued up to the 10th and 11th month after the intraarterial infusion, confirmed by follow-up CT scan. The adverse effects of intraarterial immunotherapy were tolerable, with grade 1-2 fever and nausea in each patient. CONCLUSIONS: Clinical regression of liver metastases of esophageal cancer was observed in both patients who received this intraarterial cellular immunotherapy. Liver metastases of esophageal cancer may be controlled effectively and safely by repeating the intraarterial AuTL infusion as a locoregional immunotherapy over a long period.     

A case of chronic obstructive pulmonary disease (COPD) followed by pulmonary rehabilition

We report a 75-year-old woman with chronic obstructive pulmonary disease (COPD) suffering from cough, sputum, high-grade fever and dyspnea on effort. Her chest radiograph revealed an infiltrative shadow in the right lower lung field and her laboratory data showed marked inflammatory changes. Her arterial blood gas analysis showed marked hypoxemia and hypercapnia. After her laboratory data and general condition improved, we performed pulmonary rehabilitation for the patient for about 6 weeks. The program consisted of pursed lip breathing, diaphragmatic breathing, muscle stretch gymnastics, and walking. The 6-minute walking test distance increased from 170 m to 280 m. The minimum SpO2 during the 6-minute walking test increased from 88% to 91%. (O2 3 L/m) After discharge, she continued to receive home care from a visiting nurse specialized in respiratory medicine and 24 hour-monitoring of O2-compliance at home. She has not experienced acute exacerbation or re-hospitalization for 1 year. We conclude that home care service is effective to maintain stable conditions such as state of breathing, SpO2, vital signs, and activities of daily living for elderly COPD outpatients.     

Assessment of stage IIB lung cancer from the pathological factors

In our experience, the prognosis of patients with pathological T3N0M0 lung cancer is generally poor, the 5-year survival rate being almost the same as that of patients with stage IIIA disease. Thus, we assessed patients with stage IIB disease by examining the pathological factors, lymphatic invasion, vessel invasion, histological type, differentiation, tumor size, and node dissection. Lymphatic invasion was found to be positive in 20 of 21 cases, patients with T3N0M0 lung cancer, and all of those with positive vessel invasion had a significantly poor prognosis. This indicates that positive lymphatic and vessel invasion could be a prognostic factor predicting a poor outcome. Patients with T3N0M0 lung cancer that are found to have this poor prognostic factor may not be diagnosed as having stage IIB disease.     

Establishment of a Human Small Cell Lung Carcinoma Cell Line Carrying Amplification of c-myc Gene and Chromosomal Translocation of t(3p;6p) and t(12q;17p)

A transplantable tumor and an in vitro culture cell line (GK-T3) were established from metastatic liver tissue of human small cell lung carcinoma (SCLC). Southern blot analysis revealed about 30-fold amplification of c- myc gene in the tumor cells in liver, xenografts, and in vitro cell line. The degree of c- myc amplification was essentially conserved through serial passages in nude mice and cultivation in vitro. The level of c- myc mRNA was significantly increased in these cells. Cytogenetically, numerical and complex structural abnormalities were observed in GK-T3 cells, including t(3p;6p), t(12q;17p), two homogeneously staining regions (hsrs) and several double minutes (dmins). These results suggest that activation of c- myc gene and alteration of gene(s) round these chromosomal breakpoints may play a role in tumorigenesis of GK-T3 SCLC.     

Uncooked cornstarch treatment for hepatic phosphorylase kinase deficiency

A 5-year-old boy with short stature, hepatomegaly and motor weakness due to hepatic phosphorylase kinase deficiency is described. Laboratory data showed mild hypoglycaemia and metabolic acidosis, hepatic dysfunction, and a low insulin-like growth factor-I level. Mild hypoglycaemia, marked ketosis and insufficient growth hormone secretion were revealed at night. Serum total and free carnitine levels were low and the acyl/total carnitine ratio was high. Urinary acylcarnitine profile using fast atom bombardment and tandem mass spectrometry showed increased excretion of acetylcarnitine and dicarboxylylcarnitines. These endocrinological and metabolic abnormalities and clinical symptoms were improved with uncooked cornstarch treatment.