Dermatologic changes associated with interleukin 2 administration

We have prospectively evaluated the skin changes that occurred in ten patients who were undergoing immunotherapy with interleukin 2 (IL-2) and autologous lymphokine-activated killer cells to treat cancer. Serial skin biopsy specimens were obtained before therapy (baseline), during IL-2 administration, and during IL-2/lymphokine-activated killer cell infusion. All patients developed an eruption that was characterized by macular erythema, with burning and pruritus of the skin. It began after two or three days of IL-2 infusion and was usually localized to the head and neck; it occasionally became generalized (ie, erythroderma). The eruption resolved with desquamation within 48 to 72 hours after cessation of infusion of IL-2. Histologically, the changes were not specific. The only consistent immunohistological finding noted was the presence of DR+/Leu-4+ lymphoid cells surrounding blood vessels in the papillary dermis, with fewer of these cells in the epidermis. There was no difference between the clinical or histological features of the eruption that occurred with IL-2 alone and that which occurred with IL-2 and lymphokine-activated killer cell infusion, suggesting that the cutaneous effects were mediated by IL-2 alone.     

High affinity neurotrophin receptors in the human pre-term newborn, infant, and adult cerebellum

The immunohistochemical occurrence of the high affinity neurotrophin (NT) receptors trkA, trkB, and trkC is shown in the pre-term newborn, infant, and adult human post-mortem cerebellum. Immunoreactive neuronal perikarya and processes were observed in all specimens examined, where they appeared unevenly distributed in the cerebellar cortical layers and deep nuclei, and showed regional differences among cerebellar lobules and folia. The trk receptor-antibodies, tested by Western blot on human cerebellum homogenates, revealed multiple immunoreactive bands for trkA and single bands for trkB and trkC. The results obtained show the tissue localization of the trk receptor-like immunoreactivity in the human cerebellum from prenatal to adult age. The analysis for codistribution of the receptors with the relevant ligand and among the receptors in discrete cortical and deep nuclei tissue fields shows a wide variety of conditions, from a good similarity in terms of type and density of labeled structures, to a lack of correspondence, and suggests the possibility of colocalization of trk receptors with the relevant neurotrophin and among them in the cerebellar cortex. These results sustain the concept that the neurotrophin trophic system participates in the development, differentiation, and maintenance of the human cerebellar connectivity and support the possibility of a multifactorial trophic support for the neurotrophins through target-derived and local mechanisms.     

Prognostic relevance of histological grade and its components in node-negative breast cancer patients.

Available results highlight the lack of good level of evidence studies on the pure prognostic value of histological grade. In the present study, the prognostic relevance of histological grade and of its three components, tubule formation, nuclear pleomorphism and mitotic count, was analyzed in a series of 372 patients with node-negative breast cancer treated with locoregional therapy alone until early relapse. Histological grade was determined blindly by two observers and discordance between evaluations was resolved after joint review using a multihead microscope. No relation was observed between histological grade and any of its three components and disease-free survival. Conversely, a significant relation was observed between histological grade and distant metastasis-free survival (at 6 years, 94, 86 and 76% for grades 1, 2 and 3, respectively, P=0.013) as well as overall survival (98, 90 and 86%, P=0.001). A breakdown analysis as a function of the three components showed that neither tubule formation nor nuclear pleomorphism was associated with prognosis, and only mitotic count strongly influenced both distant metastasis-free survival (91, 82 and 74%, P=0.014) and overall survival (97, 87 and 85%, P=0.011). Histological grade suffers from a much higher subjectivity than any other microscopic evaluation of biomarkers as it is the sum of three different morphological features. Within the Italian Network for Quality Assessment of Tumor Biomarkers program we observed that histological grade is an independent prognostic variable, but also that this role is ascribable only to the number of mitotic figures. In conclusion, due to the ever smaller size of diagnosed breast cancers, resulting in less cancer tissue for biofunctional and molecular analysis, mitotic count evaluated under strict quality control conditions seems to be an accurate and feasible prognostic variable.     

Stapled Hemorrhoidopexy: A Prospective Study From Pathology to Clinical Outcome

Stapled hemorrhoidopexy is widely accepted to treat hemorrhoids, but serious complications have been reported. In this prospective audit, we correlated clinical outcome with pathological findings. From January 2003 to April 2007, 94 patients underwent hemorrhoidopexy. Macroscopic appearance of the specimen (shape, size, and depth) was recorded. Microscopically, the presence of columnar, transitional, and squamous epithelium, the involvement of circular/longitudinal smooth muscle, and features of mucosal prolapse were assessed. Clinical outcome was evaluated by a validated questionnaire. Postoperative pain, secretion, and bleeding durations were 12.7 +/− 10.6, 5.6 +/− 9.6, and 6.3 +/− 8.4 days. Patient’s return to work averaged 16.7 +/− 10.7 days. Fissure, skin tags, and anal strictures were observed in 23.4%. Seven patients experienced pain for a significantly longer period of time. All specimens contained columnar mucosa, but 29.8% contained columnar and transitional epithelium and 12.8% contained columnar, anal transitional, and stratified squamous epithelium. Smooth muscle was observed in 62.7%. Pain was significantly increased if transitional epithelium was present in the specimen. No correlation or differences were observed if smooth muscle was present, although postoperative bleeding was more frequent. Hemorrhoidopexy is safe and effective. The specimen should always be sent for pathology examination. Only columnar epithelium should be present and, although the presence of smooth muscle does not influence the outcome in terms of functional results, its presence may play a role in postoperative bleeding. Presented as poster at the Digestive Disease Week, May 2007, Washington, USA     

Treatment of Hemorrhoids in Day Surgery: Stapled Hemorrhoidopexy vs Milligan–Morgan Hemorrhoidectomy

Background Recently, it has been demonstrated that surgical treatment of hemorrhoids in a day-care basis is possible and safe. The aim of this study was to compare the Longo stapled hemorrhoidopexy (SH) and the Milligan–Morgan hemorrhoidectomy (MMH). Methods One hundred seventy one patients (95 cases in SH group and 76 cases in MMH group) entered the study: 83 cases were III degree hemorrhoids, 88 IV degree. A priori and a post hoc power analysis were performed. Results, prospectively collected, were compared using chi squared test and student t test. Visual analog scale was used for pain evaluation. Postoperative pain, duration of pain, wound secretion, bleeding, resumption of a normal lifestyle, and postoperative complication were evaluated. Results Surgical time was 28.41 ± 10.78 for MMH and 28.30 ± 13.28 min in SH (P = 0.94). Postoperative pain was not different between MMH and SH during the first two postoperative days (4.73 ± 2.91 vs 5.1 ± 3.048; P = 0.4), during the following 6 days, patients treated with SH had less pain (4.63 ± 2.04 in MMH vs 3.60 ± 2.35 in SH; P = 0.006). In the SH group, seven patients needed further hospital stay for complicated course. SH showed higher incidence of anal fissure compared with MMH (6.3% vs 0%; P = 0.025) but no differences in urinary retention, anal stricture, urgency, or anal hemorrhage. Conclusions This study confirms that SH is associated with less postoperative pain and shorter postoperative symptoms, compared with MMH. SH may be a viable addition to the therapy for hemorrhoids with some advantages in early postoperative pain and some disadvantages in postoperative complications and costs.