Long-term complete response of multiple hepatic metastases from carcinoma of the papilla of Vater using intrahepatic infusion of 5-FU with low-dose cisplatin following pancreaticoduodenectomy

Of all distant metastases from carcinoma of the papilla of Vater (CPV), the liver is the most frequent site (more than 60%) and should be specifically targeted in the effort to improve the prognosis. However, the optimal chemotherapy regimen for nonresectable liver metastasis has not been clearly established. In this preliminary report, we note a patient with multiple hepatic metastases from CPV successfully treated using intrahepatic infusion of 5-fluorouracil (FU) with low-dose cisplatin. A 62-year-old woman underwent curative pylorus-preserving pancreaticoduodenectomy for CPV. Four months after surgery, followup computed tomography (CT) demonstrated multiple liver metastases. Weekly intrahepatic arterial infusion chemotherapy of 5-FU, 350 mg/m², with low-dose cisplatin (7 mg/m²) was started. Ten months after starting chemotherapy, a complete response was obtained. To date, the patient continues to receive this weekly hepatic arterial infusion chemotherapy without any side effects, and she has successfully maintained a long-term complete response for 20 months. The patient remains well and was able to proceed with daily activity at the last follow up 30 months after starting this chemotherapy regimen. This regimen is safe and effective and is recommended as one of the treatment choices for liver metastases from CPV.     

Early infectious complications after peripheral blood stem cell autografts in children

Seventeen children underwent marrowablative high-dose chemotherapy with peripheral blood stem cell autografts and were studied retrospectively to determine the type, frequency, and outcomes associated with infectious complications 3 months postgraft. The patients were kept in isolated rooms with a laminar air flow facility, but no decontamination procedures, such as gut sterilization with nonabsorbable antibiotics, nonmicrobial diet, and skin cleansing, were used. They were under their mothers' daily care to maintain good psychological conditions. After the completion of marrow-ablative chemotherapy and the infusion of stem cells, the absolute granulocyte count exceeded 0.5 × 10⁹/liter with a mean of 17.9 days (range 6–65 days), Fifteen patients developed a total of 16 febrile episodes during the first 4 week period, and the confirmed diagnoses were mucositis (12), enterocolitis (nine), septicemia (four), central venous catheter-associated infection (three), pneumonia (one), perianal abscess (one), and possible invasive fungal infection (one). All episodes were successfully treated with parenteral antibiotic therapy, and no patient died of infectious complications. The observations suggest that high-dose chemotherapy can be performed safely with simple and efficient patient management protocol followed by peripheral blood stem cell autografts.     

Human T-cell leukemia virus type I infection as an oncogenic and prognostic risk factor in cervical and vaginal carcinoma

The seroprevalence of human T-cell leukemia virus type I (HTLV-I) antibody in 6701 healthy females and 226 women with gynecologic malignancies, all living in an adult T-cell leukemia-endemic area in southwestern Japan, was investigated to determine whether HTLV-I infection was a risk factor influencing oncogenesis and prognosis. The seroprevalences in cervical carcinoma patients younger than 59 years and in vaginal carcinoma patients of all ages were significantly higher than in age-matched healthy controls. The ratios of observed to expected HTLV-I seroprevalence in patients younger than 59 with cervical carcinoma and in vaginal carcinoma patients were 2.92 and 7.36, respectively. Among the patients with cervical carcinoma or vaginal carcinoma, the tumor recurrence rate in HTLV-I carriers was significantly higher than that in HTLV-I seronegative patients. Our results suggest that HTLV-I infection may be oncogenic and may affect the prognosis in some patients with cervical or vaginal carcinoma.     

Angiosarcoma of the vagina. A light and electronmicroscopy study

A 73-year-old woman, whose medical history reported radical hysterectomy and radiotherapy for squamous cell carcinoma of the cervix uteri 20 years earlier, was found to have an angiosarcoma of the vagina. The histological diagnosis was confirmed by immunohistochemical staining of tumor cells for factor VIII-related antigen and ultrastructurally defined vasoformative structures. Primary angiosarcoma of the vagina is quite rare and reported in only two published cases. The present case is a third in general, and the first report confirmed by light microscopy, immunohistochemical, and electronmicroscopy studies.     

Acute Lymphoblastic Leukemia in a Patient with Pituitary Dwarfism under Treatment with Growth Hormone

An 18-year-old male with pituitary dwarfism, who had been on replacement of growth hormone (GH) and thyroxine for 3.5 years, developed acute lymphoblastic leukemia (ALL). The GH replacement was discontinued, and he was treated with a conventional protocol for ALL. A complete remission was obtained after 10 weeks. Maintenance chemotherapy was given with reduced doses (1/4 to 1/2) of cytotoxic drugs. The platelet count soon reached 200,000/μL, but the hemoglobin level and white blood cell count improved only slowly, reaching 10.0 g/dL and 1,500/μL, respectively, after five months. He has been in complete remission with a hypocellular bone marrow for nearly 15 months. Since GH can stimulate the proliferation of some normal and leukemic hemato-lymphoid cells, the slow remission induction and the prolonged anemia and leukocytopenia after remission, may have been related to the absence of GH in this patient.     

Growth Requirements of Normal and Leukemic Human B Cell Progenitors

Leukemic lymphoblasts in B-lineage acute lymphoblastic leukemia (ALL) express morphologic, phenotypic and genotypic features which resemble those of B lymphocyte progenitors in normal bone marrow. Normal immature B cells and cells from most cases of B-lineage ALL rapidly die in vitro unless they are supported by bone marrow-derived stromal feeder layers. Techniques suitable for maintaining normal and leukemic immature B cells in culture have been developed. Thus, the stromal cell types and growth factors that generate a milieu suitable for immature B-cell development can now be elucidated. In addition, the similarities and discrepancies in survival requirements of normal and leukemic B cell precursors can be studied. We postulate that leukemic B cell precursors can survive and expand in microen-vironments incapable of supporting their normal counterparts, and that the study of the survival requirements of ALL cells will provide indications about the aggressivity of the disease in vivo. In this review, we discuss the culture conditions that support in vitro survival of human immature B cells, some of the factors that influence their expansion, and the putative molecular basis for the prolonged life-span of leukemic lymphoblasts.     

Effects of norethisterone on pressor response to angiotensin II in men.

OBJECTIVE: We examined the effects of norethisterone and/or mestranol on the pressor response to angiotensin II in 20 healthy men. METHODS: Four study protocols were used: I) mestranol 0.08 mg/day for 6 days followed by mestranol plus norethisterone 20 mg/day for 6 days, II) mestranol 0.16 mg/day for 6 days followed by norethisterone alone 10 mg/day for 6 days, III) mestranol 0.24 mg/day followed by norethisterone 20 mg/day for 6 days, and IV) norethisterone 20 mg/day for 6 days. The angiotensin II dose to elicit a 20-mmHg rise in diastolic blood pressure was considered the effective pressor dose. This was determined before each protocol, at the end of the mestranol-alone portion, and at the end of the norethisterone portion. Subjects in study III also underwent measurement of plasma prostanoid levels, plasma renin activity and concentration, and estradiol and progesterone just before each angiotensin II infusion. Subjects in studies I and III underwent measurement of mean platelet volume, complete blood counts, liver function tests, and coagulation factors before each angiotensin II infusion. RESULTS: Whereas mestranol had no apparent effect on angiotensin II pressor response, norethisterone at a dose of 20 mg/day (with or without concurrent mestranol administration) caused a significant decrease in pressor responsiveness to angiotensin II. No changes in plasma prostanoids or renin could be found that would account for the change in pressor response. CONCLUSION: These findings indicate that the refractoriness to angiotensin II induced by norethisterone was related to its progestogenic properties.     

Transmandibular transpterygoid approach to the nasopharynx, parapharyngeal space, and skull base.

The nasopharynx, upper part of the parapharyngeal space, and skull base are relatively inaccessible to the surgeon without major postoperative complications. Operative fields reached by conventional approaches through the palate and maxillary sinus are too limited and narrow to remove extensive tumors. The authors applied a transmandibular transpterygoid approach for the removal of five residual nasopharyngeal carcinomas (NPCs) after full doses of irradiation, one pleomorphic adenoma of the nasopharynx, and one large parapharyngeal schwannoma extending into the jugular foramen. This approach offers a wide operative field so that large blood vessels and cranial nerves can be managed easily. All tumors were successfully resected. Two patients with benign neoplasma had uneventful recoveries after treatment. Of five patients with NPC, two are alive with no evidence of disease for 68 months and 50 months, respectively, while two died of metastases to the liver and bones. The other patient is alive with metastases in the lungs. No tumor recurred in the local primary site, however. Since the number of NPC cases is small, the usefulness of surgical removal of the postirradiation residual NPC is not clear. Our experience proved that the transmandibular transpterygoid approach is a practical method in the treatment of neoplastic lesions in the nasopharynx, parapharyngeal space, and skull base.     

Pseudo-Chediak-Higashi Anomaly in Acute Myeloid Leukemia (M2) of Childhood

The frequency and clinical significance of the pseudo-Chediak-Higashi (PCH) anomaly were studied in 20 children with acute myeloid leukemia (AML) M2 in the FAB nomenclature. PCH granules were recognized as giant eosinophilic granules, measuring up to 5μ, in the cytoplasm of leukemic cells on smears. At the electron microscope level, most PCH granules were round to oval and outlined by a limiting membrane, and contained homogeneous, granular, crystalloid, rod-like or myelin-like materials. The PCH anomaly was demonstrable in five (25.0%) of the 20 patients, which indicates that the anomaly is not rare in childhood AML M2. There were no differences between PCH anomaly-positive and PCH anomaly negative groups with regard to hepatosplenomegaly, hemoglobin levels, white blood cell counts, bone marrow cellularity, t(8q-, 21q+) chromosome abnormalities or prognoses. Circulating leukemic cells were observed less frequently in the PCH anomaly-positive group than in the PCH anomaly-negative group (p <0.05); the leukemic cells were not demonstrable in three of the five patients in the former group, although they were detected in all 15 patients in the latter group. The existence of PCH granules and/or a defect of the cytoskeleton responsible for the PCH anomaly in leukemic cells may impede their movement from the bone marrow to the peripheral blood.