The assessment of a learning curve should not be limited to measurement of a decrease in operation time but should also include the conversion and complication rates. The cumulative sum technique and moving average method as proposed in this study seem appropriate to evaluate the learning curve in this clinical domain. Our findings might be especially useful for those planning training programs in laparoscopic surgery.
Since July 1986 we started with following all patients with condylomata acuminata including HIV-testing and human papilloma virus (HPV) identification by DNA-DNA-hybridisation (southern blot). Seventy patients are included, 39 of them are seropositive. The ratio male to female is 59 to 11, in seropositives 35 to 4, in negatives 24 to 7. The average age is 28 and 31 years respectively. The number of homosexuals and junkies is significantly higher in seropositives. Seventeen patients are in HIV-stage II, 11 in stage III and 10 in stage IV according to CDC-classification. Characteristic for the seropositives was an extensive growth on the rectal mucosa and the very rapid growth of initially subtotally resected lesions in order to prevent stenosis. Sixty-five patients were treated by one stage radical operation with electrocauter. Surprisingly recurrency is more frequent in seronegatives, however, the lesion is much smaller in this group. A hypothesis to explain this observation is brought forward. Postoperative complications occurred only in HIV-stages III and IV. We therefore recommend single shot antibiotic prophylaxis in these patients. The HPV-identification showed no malignancy associated HPV-types in both groups but a higher incidence of HPV 11 in higher HIV-stages which we cannot explain. We conclude from our series that, if operation is indicated, one stage radical electrocoagulation of condylomata acuminata is a necessary procedure in seropositive patients and a save one in negative patients but antibiotic prophylaxis should be given in stage III and IV. Anal condylomata acuminata are a hint for possible HIV-positivity.
Previous clinical and experimental evidence strongly supports a breast cancer-promoting function of the lysosomal protease cathepsin B. However, the cathepsin B-dependent molecular pathways are not completely understood. Here, we studied the cathepsin-mediated secretome changes in the context of the MMTV-PyMT breast cancer mouse model. Employing the cell-conditioned media from tumor-macrophage co-cultures, as well as tumor interstitial fluid obtained by a novel strategy from PyMT mice with differential cathepsin B expression, we identified an important proteolytic and lysosomal signature, highlighting the importance of this organelle and these enzymes in the tumor micro-environment. The Cellular Repressor of E1A Stimulated Genes 1 (CREG1), a secreted endolysosomal glycoprotein, displayed reduced abundance upon over-expression of cathepsin B as well as increased abundance upon cathepsin B deletion or inhibition. Moreover, it was cleaved by cathepsin B in vitro. CREG1 reportedly could act as tumor suppressor. We show that treatment of PyMT tumor cells with recombinant CREG1 reduced proliferation, migration, and invasion; whereas, the opposite was observed with reduced CREG1 expression. This was further validated in vivo by orthotopic transplantation. Our study highlights CREG1 as a key player in tumor–stroma interaction and suggests that cathepsin B sustains malignant cell behavior by reducing the levels of the growth suppressor CREG1 in the tumor microenvironment.
Anogenital warts of the condyloma acuminatum type seem to occur quite often during HIV infection. These warts – according to our study – are not commonly caused by malignancy-associated human papilloma virus types, but by types 6 and 11 as seen in the nonimmune-compromised population. Widespread condylomata acuminata may appear in rather early stages of HIV infection and they may therefore represent early warning signs of HIV infection.
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