Neo-adjuvant therapy improves resectability rates for colorectal liver metastases.

PURPOSE: Liver resection improves survival in selected patients with colorectal liver metastases. However, the majority of patients with colorectal liver metastases have inoperable disease at presentation. Neo-adjuvant therapy (systemic or regional chemotherapy and interstitial laser therapy) used singly or in combination may convert a selected group of patients with irresectable liver metastases into an operable state. PATIENTS AND METHODS: We report a series of patients with initially inoperable multiple colorectal liver metastases who became operable after neo-adjuvant therapy. Operability was defined as unilateral disease limited to the liver. Twelve patients (7 female, 5 male, median age 57 years, range 38-69 years) with multiple inoperable colorectal liver metastases (8 synchronous, 4 metachronous) were initially treated with systemic chemotherapy (n = 7), hepatic arterial chemotherapy (n = 2) and chemotherapy plus interstitial laser therapy (n = 3). RESULTS: In all cases, a significant response was achieved which enabled subsequent liver resection to be undertaken. There was only one postoperative complication (8%) and no peri-operative deaths. 3 patients were operated on within the last 12 months and are still alive. Of the remainder, 1 died within 1 year with recurrent disease. The remaining patients have a median survival of 2.5 years, range 1.39-4 years. CONCLUSIONS: These results are similar to those reported for patients undergoing resection for operable metastases without neo-adjuvant therapy. Aggressive multimodality treatment of colorectal liver metastases in specialised centres may improve the resectability rates and survival in a selected group of patients.

Treatment of recurrent colorectal liver metastases by interstitial laser photocoagulation.

BACKGROUND: Hepatic resection improves survival in selected patients with colorectal liver metastases. The treatment of recurrent hepatic metastases after resection is controversial. Interstitial laser photocoagulation, performed under local anaesthesia, offers a minimally invasive option to repeat resection. The first series of patients with recurrent colorectal liver metastases treated with photo- coagulation is reported. METHODS: Nineteen patients (five women and 14 men, median age 57 (range 44-71) years) who developed recurrent colorectal liver metastases after hepatectomy (five with bilateral disease) were treated with photocoagulation between 1993 and 1997. Fifteen patients also received chemotherapy (14 systemic, one hepatic arterial) before photocoagulation. RESULTS: There were no major complications or deaths related to the treatment. Six patients developed minor complications related to the procedure but did not require any form of intervention. Median survival from commencement of photocoagulation was 16 (range 4-36) months. CONCLUSION: Photocoagulation is a safe, minimally invasive therapy that may be used as an adjunct to chemotherapy and repeat resection in the treatment of recurrent colorectal liver metastases, and may lead to improved survival.

All-trans beta-carotene is absorbed preferentially to 9-cis beta-carotene, but the latter accumulates in the tissues of domestic ferrets (Mustela putorius puro).

The algae Dunaliella bardawil and Dunaliella salina naturally contain large concentrations of all-trans and 9-cis beta-carotene (betaC). The purpose of this study was to compare the relative serum and tissue accumulation of all-trans and 9-cis betaC in ferrets fed different ratios of all-trans/9-cis betaC derived from two commercial sources, D. bardawil or D. salina (Betatene). Male ferrets (7 wk old) were fed carotene-free, pelleted diets for 27 d. Beginning on d 18, groups of ferrets (n = 6 or 7) received daily, one of six oral supplements varying in ratios of 9-cis and all-trans betaC mixed with approximately 1.0mL of Ensure. Four supplements containing 5.2-8.3 micromol total betaC were prepared from a 20% Betatene preparation, D. bardawil, a high-cis Betatene preparation, and Betatene further enriched in 9-cis betaC with all-trans betaC/9-cis betaC ratios of 2.2, 1.5, 0.6 and 0.4, respectively. Two control supplements, high and low betaC, were prepared from commercial betaC beadlets. The high control supplement had an all-trans/9-cis ratio of 19.0, whereas 9-cis betaC was not detected in the low supplement. On d 27, serum and tissues were obtained for HPLC analysis of betaC and its isomers. Analysis of livers showed that all-trans betaC was the primary isomer present, but 9-cis and other isomers were also detected in all groups. The hepatic all-trans/9-cis ratios were 5.9, 4.9, 2.5, 1.4, 52.2 and47.5, respectively, for the groups listed above. Lower amounts of all-trans and 9-cis betaC were found in kidneys compared with the liver, but ratios of all-trans/9-cis were not different among groups. Only trace amounts of 9-cis betaC were found in serum. These results demonstrate that the algae D. bardawil and D. salina provide a bioavailable source of betaC isomers, but, as in humans, absorption of 9-cis betaC is poor and any 9-cis betaC absorbed is apparently cleared by the liver.

Ferrets (Mustela putoius furo) inefficiently convert beta-carotene to vitamin A.

The ferret has recently been used as a model to evaluate the absorption and metabolism of several carotenoids; however, little is known about the vitamin A (VA) requirements of this species or the ability of ferrets to convert dietary beta-carotene (betaC) to VA. Three studies were conducted to estimate the daily utilization of VA in ferrets and to determine the effect of prior VA status on the ability of ferrets to utilize betaC as a source of VA. Weanling male ferrets were fed a pelleted, low carotenoid, semipurified diet either with (+VA) or without VA (-VA) for 21- to 35-d prefeeding periods. Upon initiation of the experiments, several ferrets were killed to determine base-line VA status. The remaining ferrets were fed VA, betaC, or VA and betaC in pelleted feed (Studies 1-3) or liquid carrier (Study 3) for 16-21 additional days. Hepatic VA and betaC concentrations were used as the primary indicators of VA status, although serum and adrenal VA and betaC also were measured. The results showed the following: 1) provision of betaC at up to a 15:1 weight ratio of betaC to VA in pelleted feed or liquid carrier was not sufficient to maintain hepatic VA stores after a -VA prefeeding period; 2) the daily utilization rate of VA by ferrets ranged from 80 to 171 microg in the three studies; 3) the ferret was confirmed to be a species that has the majority of its serum VA in ester form; and 4) feeding -VA diets significantly reduced serum retinyl esters but had less effect on serum retinol. We conclude that although ferrets can convert betaC to VA, the process is inefficient. The ferret model can be most appropriately used when studying the biological effect of tissue betaC stores on VA status and is less appropriate for the evaluation of dietary betaC conversion to VA.

The mongolian gerbil (Meriones unguiculatus) is an appropriate animal model for evaluation of the conversion of beta-carotene to vitamin A.

Vitamin A (VA) deficiency is the leading cause of blindness in children in developing countries. Dietary intervention with foods rich in provitamin A carotenoids, such as beta-carotene (betaC), has been suggested as one solution to this problem. The objective of the two studies described in this paper was to examine the utilization of betaC as a source of VA at different stages of VA depletion using the Mongolian gerbil as a model. Male 4- to 5-wk-old Mongolian gerbils were fed powdered betaC-free semipurified diets either with or without VA for 26 d (Study 1), or without VA for 8-10 wk (Study 2). Gerbils were then fed diets with or without VA (20.9 nmol/g diet) and/or betaC [(67.0 micromol/g diet (Study 1) and 145.9 micromol/g diet (Study 2)] for variable periods. Two (Study 1) or three (Study 2) days before termination of the study, 3-4 gerbils per group were dosed orally with 14C-betaC. Tissues were evaluated for VA and betaC content by HPLC. Liver was extracted with and without saponification to evaluate 14C-betaC and 14C-VA content. The results demonstrate the following: 1) the gerbil is an appropriate animal model to study betaC utilization; 2) 20.9 nmol VA/g diet is more than sufficient for this species; 3) the daily VA utilization rate for this species is calculated to be 3.1 microg/100 g body weight; 4) a highly bioavailable source of betaC at a 6:1 weight ratio of betaC:VA is sufficient to reverse marginal VA status in this model; and 5) a highly bioavailable source of betaC fed between a 6:1 and 13:1 weight ratio to VA provides equivalent VA status as preformed VA in Mongolian gerbils.

Atovaquone in the treatment of Babesia microti infections in hamsters.

The traditional therapy for the treatment of human Babesia microti infections has been the combination of clindamycin and quinine. However, in recent years, it has become apparent that some patients have not responded to this regimen. We became involved in the treatment of several cases of babesiosis in which atovaquone was used to treat this infection. Therefore, using the hamster model, we determined the efficacy of atovaquone alone as well as atovaquone plus azithromycin for the treatment of experimental babesiosis. Atovaquone (100 mg/kg/day) and atovaquone (100 mg/kg/day) with azithromycin (150 mg/kg/day) were effective agents for the treatment of experimental babesiosis in hamsters. When atovaquone was used as monotherapy recrudescences occurred. Organisms obtained from recrudescent animals, when inoculated into uninfected animals, proved to be unresponsive to atovaquone therapy, suggesting the emergence of drug resistance. Resistant organisms did not emerge in hamsters treated with the combination of atovaquone and azithromycin. Atovaquone should be considered in the therapeutic regimen of patients with babesiosis who have either failed standard therapy or have become intolerant to such therapy.

Lymphotoxin and tumor necrosis factor-alpha production by myelin basic protein-specific T cell clones correlates with encephalitogenicity.

Lymphokine activity in seven myelin basic protein (MBP)-specific T cell clones was examined. All of the clones recognize MBP peptide 1-9 in the context of I-Au. A strong positive correlation was found between levels of lymphotoxin (LT) and tumor necrosis factor alpha (TNF-alpha) mRNA and biological activity on L929 cells and their capacity to induce paralysis, the clinical hallmark of experimental allergic encephalomyelitis (EAE). No correlation was found between interleukin-2 or gamma interferon production and encephalitogenicity. LT and/or TNF-alpha may play a central role in the pathogenesis of EAE.

Effect of BANS location on the prognosis of clinical stage I melanoma: new data and meta-analysis.

Intermediate thickness (0.76-1.69 mm) clinical stage I melanomas at BANS locations (upper Back, posterior Arm, posterior Neck, posterior Scalp) were initially reported to have worse prognosis than similar thickness lesions at other subsites. Subsequent investigation did not support this observation. We re-examined the hypothesis in 156 consecutive patients with clinical stage I melanomas in this thickness range, who were seen at the Massachusetts General Hospital from 1977 to 1985. Patients with BANS lesions suffered recurrences at twice the rate of those with non-BANS lesions (28% compared with 13% at 5 years after excision of the primary melanoma), but this difference was not statistically significant. A meta-analysis of the effect of BANS subsite on death risk was performed using data from our investigation and five comparable published studies. The original data set which led to the BANS hypothesis was excluded from the meta-analysis in order to avoid bias. BANS location was associated with a 60% increased risk of death (P = 0.002). The difference remained statistically significant after elimination of any two of the six studies from the analysis. This confirms the influence of anatomical subsite on the prognosis of intermediate thickness melanoma.

Alcohol intolerance in the hypereosinophilic syndrome.

Alcohol intolerance presented as an initial symptom in two patients with hypereosinophilic syndrome. In patient 1 alcohol intolerance persisted during the whole course of disease, while in patient 2 all symptoms including alcohol intolerance disappeared after treatment with prednisolone and vincristine. Alcohol intolerance seems to be influenced by hypereosinophilia and may be of clinical value in the evaluation of the activity of the malignant disorder.

A mucocele etmoidal como causa de exoftalmo unilateral / Ethmoidal mucocele as cause of unilateral exophthalmos

As mucoceles säo lesöes císticas, crônicas e expansivas dos seios paranasais. A sintomatologia ocular é muito freqüente, com exoftalmo inferior e lateral. Em nossa experiência, o sinal de massa cística, näo homogênea, extra-conal com alteraçäo da tábua óssea, ao exame ultrassonográfico, é altamente significativo, quase característico do diagnóstico de mucocele

Lymphomatoid papulosis following Hodgkin's disease.

Lymphomatoid papulosis has occurred in association with Hodgkin's disease. In all cases previously described, Hodgkin's disease has developed after, or concurrently with, the onset of lymphomatoid papulosis. Two patients who developed lymphomatoid papulosis 1 and 10 years after the diagnosis and therapy for advanced Hodgkin's disease are reported. The purpose of this report is to document this unusual sequence.

Does wide excision as the initial diagnostic procedure improve prognosis in patients with cutaneous melanoma?

502 patients with clinical stage I cutaneous melanoma were reviewed to determine if performing a wide excision (4-5 cm) at the time when the diagnosis of melanoma is suspected, improves the survival. Patients were divided into two groups based on initial biopsy type and thickness category. Group 1, wide excision; group 2, total excision with narrow margins, incisional, or punch biopsies. There was no evidence that patients who had had a diagnostic and therapeutic procedure (wide excision) as the initial approach had a better survival than those who had had another form of biopsy before definitive surgery. We cannot recommend excision with wide margins as the initial biopsy procedure for a lesion suspected to be melanoma before histologic verification, since it does not increase survival for melanoma and may result in unnecessary aggressive surgery in the case of a misdiagnosed benign lesion.

Does biopsy type influence survival in clinical stage I cutaneous melanoma?

A total of 472 patients with clinical Stage I cutaneous melanoma were analyzed to determine influence of type of diagnostic biopsy on survival. Of these patients, 119 had had an incisional biopsy (either punch or incision) and 353 had an excisional biopsy. Patients were grouped by thickness category and outcome compared between the biopsy types. Within each thickness category, there is no statistically significant difference in survival between the two groups. The observation that none of the seventy-six patients with primary tumors less than 1.70 mm have died following incisional biopsy strongly argues against any deleterious effect of incisional biopsy in this group. Alternatively, if the two highest-risk groups (greater than or equal to 1.70 mm) are analyzed as a single group, an adverse effect is seen in the incisional biopsy group (p less than 0.05). However, when the data from these groups are subjected to multivariate analysis, biopsy type is not a significant factor in the model. This study shows that either biopsy method may be used in first evaluating patients with suspected melanoma.

Melanin macroglobules as a cellular marker of neurofibromatosis: a quantitative study.

To investigate the usefulness of melanin macroglobules (MMG) as a cellular marker for neurofibromatosis, their density was quantified in biopsies of café-au-lait spots (macules) (CALM) from 22 patients with von Recklinghausen's neurofibromatosis, 6 patients with bilateral acoustic neurofibromatosis, and 19 controls. The density of MMG was significantly higher in biopsies of the CALM of patients with von Recklinghausen's neurofibromatosis than in patients with bilateral acoustic neurofibromatosis (p less than .01) or controls (p less than .0008). The mode of acquisition of von Recklinghausen's neurofibromatosis (inherited vs new mutation) was not related to the density of MMG. On light microscopy, 14/22 (64%) patients with von Recklinghausen's neurofibromatosis had 11 or more MMG per 5 high-power fields. In contrast, none of the other two groups had more than 10 MMG per 5 high-power fields.