Leg swelling after inguinal sentinel lymph node biopsy and primary melanoma excision with a safety margin

Background: Risk-factors for leg swelling following primary melanoma excision and inguinal sentinel lymphadenectomy (SLNE) have not been sufficiently investigated. Patients and Methods: We prospectively studied three parameters in 105 subjects: 1) subjectively perceived swelling, 2) clinically diagnosed swelling and 3) photo-optical measurement of volume differences between both legs. Results: Perceived swelling, clinically diagnosed swelling, and manifest edema occurred in 31%, 15%, and 7% of patients respectively. Following inguinal SLNE, there was a mean volume increase of 1.5% in the operated leg. Both the lower leg and the thigh increased in volume. Obesity, primary melanoma location on the lower leg, and inguinal seromas were identified as significant risk factors for postoperative swelling. Wider excision margins around a primary melanoma on the thigh were also associated with a significant increase in volume. Age, sex, the number of sentinel lymph nodes, the drainage fluid volume, and the time since SLNE were non-significant. Conclusions: Both inguinal SLNE and primary melanoma excision may contribute to minimal fluid accumulation in the leg. More than two-thirds of patients did not have any swelling. Obesity, location of the primary melanoma at a distal site on the leg, a wide safety margin, and seromas are associated with postoperative leg swelling.     

Adipocyte morphometric evaluation and angiogenesis in the omentum transposed to the breast: a preliminary study

OBJECTIVE:

The purpose of this study was to describe the probable mechanism of the volume increase of laparoscopically harvested omentum flaps used to treat breast deformities.

METHODS:

A histological analysis of omentum samples was performed to study the volume increase of laparoscopically harvested omentum flaps. Samples were harvested immediately after the transposition of the omentum from the abdominal cavity to the breast region and during the second surgical procedure for breast symmetrization of eight patients submitted to the transposition of the omentum flap. Changes in the morphometric measurements of the adipocytes (perimeter, diameter, and area), microvascular density (as measured by the CD31 endothelial marker), and immunohistochemical expression of VEGF were documented.

RESULTS:

The increases in adipocyte size and microvascular density were statistically significant (P ≤ 0.012). The expression levels of VEGF were lower in the second set of samples when compared to the first set, but the differences were not statistically significant (P < 0.093).

CONCLUSION:

These results demonstrate an increase in cellular volume as measured by adipocyte perimeter, diameter, and area. Moreover, the increase in the number of vessels in the second set of samples suggests that neoangiogenesis was stimulated by the initial increase in VEGF expression levels observed in the first set of samples. The increase in VEGF expression in the flap may have been caused by adipocyte hypertrophy resulting from neoangiogenesis.     

Combinatorial RNAi for quantitative protein network analysis

The elucidation of cross-talk events between intersecting signaling pathways is one main challenge in biological research. The complexity of protein networks, composed of different pathways, requires novel strategies and techniques to reveal relevant interrelations. Here, we established a combinatorial RNAi strategy for systematic single, double, and triple knockdown, and we measured the residual mRNAs and proteins quantitatively by quantitative real-time PCR and reverse-phase protein arrays, respectively, as a prerequisite for data analysis. Our results show that the parallel knockdown of at least three different genes is feasible while keeping both untargeted silencing and cytotoxicity low. The technique was validated by investigating the interplay of tyrosine kinase receptor ErbB2 and its downstream targets Akt-1 and MEK1 in cell invasion. This experimental approach combines multiple gene knockdown with a subsequent quantitative validation of reduced protein expression and is a major advancement toward the analysis of signaling pathways in systems biology.     

Effectiveness and tolerability of olanzapine in the treatment of adolescents with schizophrenia and related psychotic disorders: results from a large, prospective, open-label study

OBJECTIVE: The aim of this study was to assess effectiveness and tolerability of oral olanzapine treatment of adolescents with schizophrenic disorders. METHOD: Adolescent patients (12-19 years) with schizophrenia, schizoaffective, or schizophreniform disorders according to the Diagnostic and Statistical Manual of Mental Disorders, 4(th) edition (DSM-IV) were enrolled in a multicenter, prospective, open-label study. Following a 2- to 9-day washout period, patients initially received 10 mg/day olanzapine. Dose modification was allowed during week 2 (dose range 5-15 mg/day) and during weeks 3-6 (dose range, 5-20 mg/day). Responders (improvement > or =30% on the Brief Psychiatric Rating Scale, BPRS) continued olanzapine for additional 18 weeks. Psychopathology was assessed using BPRS and Clinical Global Impressions (CGI) scales; side effects were assessed by adverse event reporting. RESULTS: Out of 96 patients enrolled at 10 sites, 60 (62.5%) met response criteria at week 6. Mean BPRS total scores decreased significantly (p < 0.001) from baseline (39.2 +/- 13.4) to week 6 last observation carried forward (LOCF) (22.2 +/- 14.7). The rate of patients considered markedly ill or worse (CGI-S) decreased from 83.3% (baseline) to 37.5% (week 6, LOCF). The most common reported adverse event was weight gain (30.2%, 29/96). Three patients (3.1%) discontinued due to adverse events. CONCLUSIONS: In this study of young patients with schizophrenia, schizoaffective, or schizophreniform disorders, olanzapine treatment was associated with marked symptom improvement. As changes in weight and prolactin levels may be greater in adolescent than in adult patients, potential risks and benefits of olanzapine treatment in adolescents should be considered carefully.     

In vivo anti-Chagas vinylthio-, vinylsulfinyl-, and vinylsulfonylbenzofuroxan derivatives

New benzofuroxans were developed and studied as antiproliferative Trypanosoma cruzi agents. Compounds displayed remarkable in vitro activities against different strains, Tulahuen 2, CL Brener and Y. Its unspecific cytotoxicity was evaluated using human macrophages being not toxic at a concentration at least 8 times, and until 250 times, that of its T. cruzi IC50. Some biochemical pathways were studied, namely parasite respiration, cysteinyl active site enzymes and reaction with glutathione, as target for the mechanism of action. Not only T. cruzi respiration but also Cruzipain or trypanothione reductase were not affected, however the most active derivatives, the vinylsulfinyl- and vinylsulfonyl-containing benzofuroxans, react with glutathione in a redox pathway. Furthermore, the compounds showed good in vivo activities when they were studied in an acute murine model of Chagas' disease. The compounds were able to reduce the parasite loads of animals with fully established T. cruzi infections.     

Patients' perceptions of spirituality and the nurse as a spiritual care provider

This qualitative study explored patients' perceptions of spirituality and of the nurse as a spiritual care provider. Semistructured interviews were conducted with 8 adults older than 21, who were living at home, and had been discharged from the hospital within the past 3 months having had at least a 5-day length of stay. Participants agreed that during their hospitalization, nurses were kind and caring but these behaviors were not perceived as spiritual care. Study findings suggest that patients do not perceive spiritual care within the role of nursing and therefore they did not share their spiritual concerns with nurses. Study findings are limited by sample size; however, implications for practice are that nurses need to be aware of a patient's spiritual needs to provide spiritual care.     

Exon 11 mutations, Ki67, and p16(INK4A) as predictors of prognosis in patients with GIST

Prognostic biomarkers for GIST are under investigation. The aim of this study was to assess whether exon 11 mutations, Ki67, and p16^INK4A are predictors of prognosis in GIST. Consecutive GIST cases (n = 84) had their specimens evaluated for exon 11 mutations and expression of Ki67 and p16^INK4A. Surgical cases were categorized according to NIH and Miettinen's classification, and survival was analyzed from hospital database. GISTs were predominately gastric (45%) and with spindle cell morphology (74%). The risk category was very low or low in 28%, intermediate in 23%, and high in 49%. Exon 11 mutation was identified in 29 (48%) out of 60 cases studied. There were 12 point mutations, 10 deletions, 4 duplications, and 3 double mutations. A third of GISTs had either high Ki67 index (>3%) or negativity for p16^INK4A. In multivariate analysis, independent predictors of mortality were Ki67 > 3% (HR = 7.3; P = 0.036) and high mitotic index (HR = 10.4; P = 0.043). There was no association between exon 11 mutations and survival. This study suggests that Ki67 > 3% is an independent predictor of poor prognosis in patients with GIST. Exon 11 mutations and negativity for p16^INK4A need further studies to address the prognostic value.     

Automatic replanning of VMAT plans for different treatment machines: A template-based approach using constrained optimization

Purpose

To investigate a new automatic template-based replanning approach combined with constrained optimization, which may be highly useful for a rapid plan transfer for planned or unplanned machine breakdowns. This approach was tested for prostate cancer (PC) and head-and-neck cancer (HNC) cases.

Methods

The constraints of a previously optimized volumetric modulated arc therapy (VMAT) plan were used as a template for automatic plan reoptimization for different accelerator head models. All plans were generated using the treatment planning system (TPS) Hyperion. Automatic replanning was performed for 16 PC cases, initially planned for MLC1 (4?mm MLC) and reoptimized for MLC2 (5?mm) and MLC3 (10?mm) and for 19 HNC cases, replanned from MLC2 to MLC3. EUD, D_mean, D_2%, and D_98% were evaluated for targets; for OARs EUD and D_2% were analyzed. Replanning was considered successful if both plans fulfilled equal constraints.

Results

All prostate cases were successfully replanned. The mean relative target EUD deviation was ?0.15% and ?0.57% for replanning to MLC2 and MLC3, respectively. OAR sparing was successful in all cases. Replanning of HNC cases from MLC2 to MLC3 was successful in 16/19 patients with a mean decrease of ?0.64% in PTV60 EUD. In three cases target doses were substantially decreased by up to ?2.58% (PTV60) and ?3.44% (PTV54), respectively. Nevertheless, OAR sparing was always achieved as planned.

Conclusions

Automatic replanning of VMAT plans for a different treatment machine by using pre-existing constraints as a template for a reoptimization is feasible and successful in terms of equal constraints.