Primary chemotherapy for clinical stage II nonseminomatous germ cell testicular tumors: selection criteria and long-term results.

OBJECTIVE: To determine the treatment option for patients with low-volume stage II nonseminomatous germ cell testicular tumors (NSGCTT) that yields the best survival, is associated with the least morbidity, and avoids "double therapy"--that is, chemotherapy and retroperitoneal lymph node dissection (RPLND). DESIGN: We reviewed our institutional experience with 28 patients with stage II NSGCTT who received primary chemotherapy between August 1983 and October 1992. MATERIAL AND METHODS: The 28 study patients (mean age, 28 years; range, 20 to 52) with low-volume stage II NSGCTT were treated with bleomycin, etoposide, and cisplatin. The correlation of response rates with volume of disease and predominant histologic cell type was determined. The duration of survival was measured from the initiation of chemotherapy to the appearance of progressive disease or death or the date of last follow-up visit. RESULTS: Of the 28 patients treated, 27 (96%) achieved a complete response--20 (71%) with only chemotherapy and an additional 7 (25%) with chemotherapy plus surgical treatment. Twenty-seven patients (96%) remained free of disease after a median follow-up of 72 months. The most frequent complication was cisplatin-associated paresthesias or tinnitus which was noted in 13 patients (46%). In 11 of 15 patients (73%), attempts to have children have been successful. CONCLUSION: Excellent long-term survival rates in patients with stage II NSGCTT can be achieved with primary chemotherapy. In this series, 71% of patients were spared RPLND. The need for postchemotherapy RPLND seemed to be related to the initial metastatic tumor volume and possibly the histologic features of the primary tumor. Continued refinement in surgical techniques and chemotherapeutic regimens will necessitate the comparison of these two treatment approaches in a randomized prospective trial.

Primary osteosarcoma of the breast.

Primary osteosarcoma of the breast is a rare malignant tumour. We report such a case in a 77-year-old lady who presented with a hard lump which was clinically and mammographically indistinguishable from a calcified fibroadenoma. Wide local excision of the lesion was carried out. Detailed histological and immunohistochemical features of the tumour are described. Because there was no evidence of metastasis and adequate local excision, no further treatment was considered necessary and she remains disease free at 39 months.

Male infertility and avascular necrosis of the femoral head.

Corticosteroids are an important part of the pharmacological armamentarium against a wide spectrum of diseases. They are powerful drugs that effect all aspects of human metabolism and, although often life-saving, they have a plethora of important side-effects and a narrow therapeutic window. Most side-effects are well known to physicians but we would like to highlight the problem of avascular necrosis associated with cyclical steroid therapy of short duration using moderate doses for an unusual indication.

Patient safety in orthopaedics: state of the art.

We summarise and highlight the safety concerns within the field of trauma and orthopaedic surgery with particular emphasis placed on current controversies and reforms within the United Kingdom National Health Service.

Survivorship of high tibial osteotomy in the treatment of osteoarthritis of the knee: Finnish registry-based study of 3195 knees.

Previous studies from single centres or single-surgeon series report good early and mid-term results for high tibial osteotomy (HTO) in the treatment of osteoarthritis of the knee. However, the survivorship of HTO at a national level is unknown. This registry-based study included 3195 high HTOs performed between 1987 and 2008. Kaplan-Meier analysis revealed an overall survivorship of 89% (95% confidence interval (CI) 88 to 90) at five years and 73% (95% CI 72 to 75) at ten years, when conversion to total knee replacement was taken as the endpoint. Females and patients aged > 50 years had worse survivorship than males or patients aged ≤ 50 years (hazard ratio (HR) 1.26 (95% CI 1.11 to 1.43) and HR 1.41 (95% CI 1.23 to 1.64), respectively). The survivorship of HTOs performed between 1998 to 2008 was worse than for those performed between 1987 and 1997.

The nature of cytoplasmic inclusions in cerebellar haemangioblastomas.

Intracytoplasmic hyaline globules present in stromal cells in eight of a series of ten cerebellar haemangioblastomas have been shown to contain the glycoprotein alpha-1-antitrypsin.

Non-Hodgkin's lymphoma of the skin associated with chronic limb lymphoedema.

Cutaneous non-Hodgkin's lymphoma developed within a leg affected by chronic lymphoedema. The lymphoedema had followed radiotherapy to bony metastases from a carcinoma of the prostate. Eighteen months after the development of the cutaneous tumours, extracutaneous involvement by the lymphoma became apparent. This is the second report of a non-Hodgkin's lymphoma appearing within a lymphoedematous limb. The possible reasons for such an unusual localization are discussed. Our case report illustrates that cutaneous tumours other than lymphangiosarcomas may localize to a lymphoedematous limb and clinically simulate the Stewart-Treves syndrome.

Failure of sputum eosinophilia after eotaxin inhalation in asthma.

BACKGROUND: Eotaxin is a chemokine specific for eosinophils and may play an important role in eosinophil recruitment in asthma. The effects of eotaxin inhalation on sputum and blood eosinophils, exhaled nitric oxide (NO), and bronchial responsiveness were determined. METHODS: Eotaxin was administered by nebulisation to asthma patients in three studies: (1) an open dose finding study with eotaxin (5, 10 and 20 microg) to two asthmatic subjects; (2) a randomised placebo controlled study with 20 microg eotaxin to five asthmatic subjects and five normal volunteers; and (3) a randomised placebo controlled study with 40 microg eotaxin to nine asthmatics. Forced expiratory volume in 1 second (FEV(1)), exhaled NO, and blood eosinophils were measured before and hourly for 5 hours after nebulisation and at 24 and 72 hours. Methacholine bronchial challenge and sputum induction were performed before and at 5, 24, and 72 hours after nebulisation. RESULTS: In the two placebo controlled studies there was no change in sputum eosinophil count and sputum eosinophilic cationic protein concentration after eotaxin inhalation compared with placebo. FEV(1), exhaled NO, and methacholine PC(20) did not change. However, high dose eotaxin (40 microg) induced an increase in sputum neutrophil count compared with placebo (p<0.05). CONCLUSIONS: Inhaled eotaxin up to 40 microg induced no changes in sputum eosinophil count but at 40 microg it increased the sputum neutrophil count. The significance of this finding is unknown.

Malignant lymphoma of uterus: a case report with a review of the literature.

The female genital tract is rarely the initial manifestation site of malignant lymphomas. Most genital lymphomas arise in the vagina or cervix while those of the uterine corpus are extremely rare. Patients usually present with bleeding, abdominal or pelvic discomfort or back pain but, very infrequently, the tumours are discovered as a result of a routine examination. Our patient was a 67-year-old postmenopausal woman presenting with haematuria and upper abdominal pain. She had several investigations for haematuria including cystoscopy, intravenous urography (IVU) and both renal and pelvic scans. The pelvic scan revealed an enlarged uterus with some calcification suggestive of a fibroid uterus. An abdominal hysterectomy was performed. Histopathology revealed non-Hodgkin's malignant lymphoma of the uterine corpus. She subsequently had post-operative chemotherapy.

Can molgramostim enhance the antitumor effects of cytotoxic drugs in patients with advanced sarcomas?

BACKGROUND: A phase I study was designed for the amalgamation of two previously studied antisarcoma regimens (ifosfamide+doxorubicin and mitomycin+doxorubicin+cisplatin) supported by molgramostim. Thus, we hoped to develop a better regimen for the treatment of advanced sarcomas. PATIENTS AND METHODS: Fifteen adult advanced sarcoma patients and six other patients were registered and sequentially assigned to receive three progressively more myelosuppressive levels of chemotherapy: level I-ifosfamide 2500 mg/m2 + doxorubicin 40 mg/m2 + cisplatin 60 mg/m2 all given on day 0, followed by molgramostim 5 micrograms/kg every 12 hours for 14 days; level II-exactly the same chemotherapy from level I given on day 1 preceded on day 0 by ifosfamide 2500 mg/m2 and an additional four days of molgramostim given on days-6 through-3; level III-same as level II except for the addition of mitomycin 4 mg/m2 immediately prior to cisplatin on day 1. MENSA 500 mg/m2 was given five times on each day that involved ifosfamide treatment. For all levels, treatment was repeated at four-week intervals. RESULTS: Preliminary results and toxicity were reported three years ago (J Natl Cancer Inst 86: 312-4, 1994). Mature results confirm these unexpectedly favorable results with five advanced sarcoma patients still surviving after more than three years (four more than four years). HYPOTHESIS: Molgramostim given subcutaneously in a relatively intensive schedule might enhance the antitumor effects initiated by cytotoxic drugs in patients with advanced sarcomas. This idea should be tested formally in phase III studies.

Dedifferentiated chondrosarcoma: use of MRI to guide needle biopsy.

AIM: To describe the use of MRI to identify and biopsy areas of dedifferentiation in patients with a suspected diagnosis of dedifferentiated chondrosarcoma. MATERIALS AND METHODS: Low-grade chondrosarcoma is characterized at magnetic resonance imaging (MRI) as having a lobulate, hyperintense appearance on T2-weighted spin-echo sequences. T2-weighted MR images were assessed in 15 patients with a final pathological diagnosis of dedifferentiated chondrosarcoma for regions of atypical reduced signal intensity. Information regarding the site of ultrasound or computed tomography (CT)-guided biopsy was available in 10 cases. RESULTS: Nine patients were male and six female with a mean age of 60 years (range 25-77 years). The sites involved were the distal femur (n+4) pelvis (n=3) proximal femur (n=4) femoral diaphysis (n=1) proximal humerus (n=2) and proximal tibia (n=1). The dedifferentiated component consisted of osteosarcoma (n=5) malignant fibrous histiocytoma (n=6) spindle cell sarcoma (n=1) leiomyosarcoma (n=1) and pleomorphic sarcoma (n=1). In 14 of the 15 cases, areas of lower signal intensity lacking in lobulation were identified. In nine of the 10 cases, biopsy site included such areas and yielded high-grade sarcoma. CONCLUSIONS: Dedifferentiation within chondrosarcoma may be identified on T2-weighted MRI as areas of reduced signal intensity. These areas should be the preferred site of biopsy.

The herpes simplex virus type 1 immediate-early protein ICP27 is obligately required for the accumulation of a cellular protein during viral infection.

Lytic infection with herpes virus type 1 (HSV-1) causes the accumulation of a 40-kDa cellular protein (p40) which is also overexpressed in cultured cells transformed by HSV or other agents and in human cervical tumors. Accumulation of p40 is dependent upon viral protein synthesis but not viral DNA replication in the infected cell and occurs in the HSV-1 mutants tsK and tsLB2 in which only a defective ICP4 protein and the four other immediate-early proteins are synthesized. By using a panel of HSV-1 strains, each defective in one of these four proteins, we show that only a mutation in the gene encoding ICP27 abolishes p40 accumulation. The defect in this mutant virus can be rescued by a plasmid encoding ICP27 alone indicating that ICP27 is obligately required for p40 accumulation. The significance of this effect as one aspect of the interaction of viral control proteins with cellular genes is discussed.

A clinical assessment of zuclopenthixol dihydrochloride (Clopixol tablets) in the treatment of psychotic illness.

An open, multi-centre study was carried out in 69 patients with an acute psychotic episode to assess the efficacy and side-effects of treatment with oral zuclopenthixol dihydrochloride. Patients were treated until the acute episode was considered terminated by the clinician and, although dosage could be adjusted to allow optimum clinical response, the majority received 25 mg zuclopenthixol dihydrochloride 3-times daily throughout the trial period. Assessments were made before and during treatment using the BPRS and CGI rating scales and a check-list of side-effects. The results showed that 55 (80%) patients had a successful response to treatment. Almost half (33) of the patients responded fully to the drug within 3 weeks and by the end of 5-weeks' treatment this had increased to over 70% (49). A further 6 patients responded after 6 to 9 weeks of treatment. The drug was generally well tolerated and the majority of patients had either no side-effects or side-effects which did not overtly affect performance.