Pattern of Metastases in Relation to Characteristics of Primary Tumor and Treatment in Patients with Disseminated Urothelial Carcinoma

Purpose

The anatomical pattern of recurrence and metastases in patients with urothelial cancer are described, and the relationship between treatment and features of the primary invasive tumor and the subsequent pattern of metastases is analyzed.

Materials and Methods

Between 1976 and 1991, 240 patients with recurrent or metastatic urothelial cancer were admitted to our department.

Results

The majority of the patients had recurrence within 2 years after initial diagnosis. Local recurrences and lung metastases were diagnosed significantly earlier than other metastases. Multiple sites were involved in more than half of the patients. The most common sites of recurrence were local in the bladder in 65 percent of the cases and bone in 35 percent, followed by lymph nodes in 26 percent and lung in 20 percent. The pattern of metastases was similar in patients with different histological findings, grade and location of the primary tumor. Patients younger than 60 years and those with cancer of the renal pelvis more often had distant metastases compared to older patients with bladder cancer. Local recurrences were less frequent in patients who had undergone cystectomy compared to those treated with radiotherapy only. Moreover, patients with local recurrences were likely to have metastases elsewhere.

Conclusions

Bone was the most frequent site of metastases outside the pelvis and all patients suspected to have recurrence should be examined for bone metastases. The results indicate that the pattern of recurrence and metastases are not dependent on the features of the primary tumor.     

Hereditary neuropathy with liability to pressure palsies

Summary Clinical, neurophysiological and pathological investigations were carried out in 11 affected members of 2 families with hereditary neuropathy with liability to pressure palsies (HNPP). The observations were related to findings in 261 cases of 47 families published in the literature. It was concluded that HNPP is a nosological entity characterized by the following diagnostic criteria: (1) an autosomal dominant inheritance; (2) the clinical presentation of a recurrent mononeuropathy simplex or multiplex, frequently related to an inadequate trauma to peripheral nerves; (3) a significant slowing of motor and sensory conduction velocity in clinically affected, but also in clinically unaffected nerves; (4) characteristic morphological findings in sural nerve biopsy featuring tomaculous swellings of myelin sheaths, transnodal myelination and segmental demyelination. The pathogenesis of HNPP is not clear. Hypothetical explanations of the pathogenesis of HNPP are discussed.In memory of Albert Bischoff (1921–1981), Professor of Neurology, University of Berne     

Phase I/II trial of capecitabine, oxaliplatin, and radiation for rectal cancer.

PURPOSE: The purpose of this study was to establish the feasibility and efficacy of preoperative radiotherapy (RT) with concurrent capecitabine and oxaliplatin (XELOX-RT) in patients with rectal cancer. PATIENTS AND METHODS: Thirty-two patients with locally advanced (T3/T4) or low-lying rectal cancer received preoperative RT (total dose, 50.4 Gy). Capecitabine was administered concurrently at 825 mg/m2 bid on days 1 to 14 and 22 to 35, with oxaliplatin starting at 50 mg/m2 on days 1, 8, 22, and 29 with planned escalation steps of 10 mg/m2. End points of the phase II study included downstaging, histopathologic tumor regression, resectability of T4 disease, and sphincter preservation in patients with low-lying tumors. RESULTS: Dose-limiting grade 3 gastrointestinal toxicity was observed in two of six patients treated with 60 mg/m2 of oxaliplatin. Thus, 50 mg/m2 was the recommended dose for the phase II study. Toxicities observed at this dose level were generally mild, with only two cases of short-lived grade 3 diarrhea. Myelosuppression, mainly leukopenia, was restricted to grade 2 in 19% of patients. T-category downstaging was achieved in 17 (55%) of 31 operated patients, and 68% of patients had negative lymph nodes. Pathologic complete response was found in 19% of the resected specimens. Radical surgery with free margins could be performed in 79% of patients with T4 disease, and 36% of patients with tumors < or = 2 cm from the dentate line had sphincter-saving surgery. CONCLUSION: Preoperative XELOX-RT is a feasible and well tolerated treatment. This regimen is proposed for phase III evaluation comparing standard fluorouracil-based therapy with XELOX chemoradiotherapy.     

Implications of the prostate cancer prevention trial: a decision analysis model of survival outcomes.

PURPOSE: To assess the estimated effect of finasteride prevention of prostate cancer on overall survival. METHODS: Data for our decision tree model came from men in the two arms (finasteride or placebo) of the Prostate Cancer Prevention Trial (PCPT) and from clinically localized prostate cancer patients studied for long-term survival outcomes. Our model compared survival outcomes for men treated with finasteride or placebo. Prostate cancer rates were based on the 7-year period prevalence of prostate cancer detected in the PCPT; survival probabilities were abstracted from the long-term outcome studies. We assessed variability in the PCPT and long-term survival studies to test the variability of our model. RESULTS: Survival advantages for a finasteride-treated (v those not treated with finasteride) population include gains of 1.7 months in 15-year cause-specific survival (assuming finasteride-altered Gleason scores and prostate cancer prevalence rates in the PCPT), of up to 3 months for cancers treated conservatively or surgically (assuming finasteride does not alter Gleason scores), and of 0.35 months (assuming the rate of cancers detected by for-cause biopsies in the PCPT), which increased to 1.7 months when assuming a 30% rate of biopsy-detected cancer in the PCPT placebo group. Model-variability analyses support several survival benefits associated with finasteride (eg, the uniform benefits assuming finasteride does not alter Gleason scores) but question certain others (eg, in 15-year recurrence-free survivals assuming finasteride does alter Gleason scores). CONCLUSION: Finasteride can impart survival benefits according to our model, especially when we assume that finasteride does not alter Gleason scores.     

Isolation, structural elucidation and in vitro activity of 2-acetyl-2-decarboxamido-oxytetracycline against environmental relevant bacteria, including tetracycline-resistant bacteria

2-Acetyl-2-decarboxamido-oxytetracycline (ADOTC) is a major impurity of oxytetracycline (OTC) produced as a side product during fermentation. ADOTC was isolated from OTC and other impurities using preparative HPLC. The preparative column was an Xterra MS, C18 chromatographic column (100 mm x 19 mm i.d., 5 microm), and the mobile phase contained methanol-water (27:73 (v/v)) with 0.08 M formic acid added. The flow rate was 9.0 ml/min. It was possible to isolate few milligram ADOTC in a day. The compound was unambiguously identified using NMR and MS-MS. The anti-microbial activity against activated sludge bacteria was determined giving a potency of only 3% of that of OTC. With tetracycline-resistant bacteria, no anti-microbial activity was observed, indicating a mode of action similar to that of OTC.     

Sinecatechins, a defined green tea extract, in the treatment of external anogenital warts: a randomized controlled trial

OBJECTIVE: To estimate the clinical efficacy of topical sinecatechins, a defined green tea extract, in the treatment of external genital and perianal warts. METHODS: This was a randomized, double-blind, vehicle-controlled trial involving 502 male and female patients aged 18 years and older, with 2-30 anogenital warts ranging from 12 to 600 mm(2) total wart area. Patients applied sinecatechins ointment 15% or 10% or vehicle (placebo) three times daily for a maximum of 16 weeks or until complete clearance of all warts, followed by a 12-week treatment-free follow-up to assess recurrence. RESULTS: Complete clearance of all baseline and newly occurring warts was obtained in 57.2% and 56.3% of patients treated with sinecatechins ointment 15% and 10%, respectively, compared with 33.7% for vehicle (both P<.001). Significance was observed at weeks 4 and 6 and all subsequent visits. Numbers needed to treat were 4.3 and 4.4. Partial clearance rates of at least 50% were reported for 78.4% and 74.0% of patients in the sinecatechins ointment 15% and 10% groups compared with 51.5% of vehicle patients. During follow-up, recurrence of any wart was observed in 6.5%, 8.3%, and 8.8% in the sinecatechins ointment 15% group, sinecatechins ointment 10% group, and vehicle patients, respectively. A total of 3.7%, 8.3%, and 0.0% developed new warts, respectively. A total of 87.7% and 87.3% of patients in the sinecatechins ointment 15% and 10% groups, and 72.1% of vehicle patients experienced application site reactions; 49.2%, 46.2%, and 65.4% of those, respectively, were mild or moderate. CONCLUSION: Topical sinecatechins ointments 15% and 10% are effective and well-tolerated in the treatment of anogenital warts. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, www.clinicaltrials.gov, NCT00449982. LEVEL OF EVIDENCE: I.     

STUDIES IN RODENT POLIOMYELITIS : V. INTERFERENCE BETWEEN MURINE AND MONKEY POLIOMYELITIS VIRUS

1. The murine strain of SK poliomyelitis virus interferes with the propagation in rhesus monkeys of SK, Aycock, and RMV poliomyelitis monkey virus. 2. This interference is demonstrable by intracerebral injection of mixtures of murine and monkey virus prepared in vitro as well as by separate injection of the two viruses by diverse routes. 3. Mixture tests carried out with graded doses of murine and monkey virus show that 0.5 cc. of a 10 per cent suspension prepared from the brains of paralyzed mice is capable of counteracting at least 100 minimal paralyzing doses of two strains of monkey virus. 4. No interference was demonstrable with suspensions of brains infected with murine virus which had been inactivated by heating for ½ hour at 75°C., or with suspensions prepared from normal mice, or with brain suspensions prepared from mice infected with herpes virus. 5. When murine virus is introduced into monkeys by the intravenous route, before or after intracerebral infection with monkey virus, distinct prophylactic or therapeutic results may be obtained. 6. Analysis of the figures shows that the success of interference depends upon (a) the size of the infecting dose of monkey virus, (b) the amount of murine virus injected, and (c) the choice of proper intervals between the injection of monkey and murine virus. 7. The mechanism of the interference phenomenon here described is discussed in the light of the available data.     

STUDIES IN RODENT POLIOMYELITIS : I. FURTHER EXPERIMENTS WITH THE MURINE STRAIN OF SK POLIOMYELITIS VIRUS

1. SK murine virus maintained over more than 200 serial mouse passages increased in virulence for mice from an initial intracerebral titer of about 1:1 million to a maximum titer of not less than 1:1 billion dilution activity. 2. Following intracerebral injection with murine virus of remote mouse passages, 5 of 13 rhesus monkeys developed a characteristic encephalitic syndrome. Repeated intravenous injection of massive doses of virus caused localized flaccid paralysis in 2 of 14 monkeys. 3. Intracerebral injection of graded doses of murine virus into mice of different age groups caused fatal paralysis in young and old animals alike. Infection with small doses of virus by peripheral routes, while uniformly fatal to young mice, was followed by survival of almost half of the old mice. 4. The incubation period of the disease in young mice infected intracerebrally with a standard dose of murine virus, when studied throughout the period of 1 year, was found considerably lengthened during the summer months. 5. Cross neutralization tests furnished no evidence for any serological relationship between SK murine virus and lymphocytic choriomeningitis virus. Theiler''s virus was found to be neutralizable by antimurine horse serum and, to a lesser extent, by concentrated antipoliomyelitis horse serum; however, such inactivation, in both cases, was distinctly inferior to that occurring with SK murine virus. On the other hand, no neutralization whatsoever was obtained between SK murine virus and normal adult mouse serum, whereas the same serum completely neutralized Theiler''s virus. Mice surviving infection with Theiler''s virus, though acquiring immunity to this virus, remained fully susceptible to reinfection with SK murine virus. 6. Neutralization tests with SK murine virus against poliomyelitis-convalescent monkey sera gave irregular results, but neutralization of murine virus occurred regularly with a hyperimmune antipoliomyelitis horse serum. Hyperimmune antimurine horse and rabbit sera, on the other hand, failed to inactivate three strains of monkey poliomyelitis virus (SK, RMV, Aycock) by intracerebral tests in monkeys. The same sera inactivated murine virus in mice by intraperitoneal, but not by intracerebral injection of virus-serum mixtures. 7. The identity of SK murine virus and its relation to other rodent strains of poliomyelitis virus is discussed on the basis of the available data.     

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