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The aim of this study was to identify the frequency and spectrum of germline BRCA1/2 pathogenic alterations in a cohort of patients with breast carcinoma. In this study, a total of 603 breast cancer subjects from Turkey were screened for BRCA1/BRCA2 mutations using HDA and Sanger sequencing. In the present study, 21 BRCA1 and BRCA2 pathogenic variants were detected in 30 patients and BRCA1/2 mutations were significantly associated with a family history of breast/ovarian cancer. Analysis of overall survival for BRCA1/BRCA2 mutation carriers showed a trend for poor overall survival only in BRCA1 carriers, although this was not statistically significant in BRCA1 and BRCA2 mutation carriers. The c.5266dupC mutation is one of the most frequently reported mutations in BRCA1 and was identified in five breast cancer patients in our study. The most common BRCA2 gene mutations in the present study were c.8940delA and c.9097dupA, which were found in seven patients. We found mostly BRCA1 and BRCA2 mutation carriers in those patients who showed hormone-positive features. In conclusion, our data showed differences in the distribution of the mutation spectrum of BRCA1 and BRCA2 in Turkey.

Blood-based biomarkers reflect systemic inflammation status and have prognostic and predictive value in solid malignancies. As a recently defined biomarker, Pan-Immune-Inflammation-Value (PIV) integrates different peripheral blood cell subpopulations. This retrospective study of collected data aimed to assess whether PIV may predict the pathological complete response (pCR) to neoadjuvant chemotherapy (NAC) in Turkish women with breast cancer. The study consisted of 743 patients with breast cancer who were scheduled to undergo NAC before attempting cytoreductive surgery. A pre-treatment complete blood count was obtained in the two weeks preceding NAC, and blood-based biomarkers were calculated from absolute counts of relevant cell populations. The pCR was defined as the absence of tumor cells in both the mastectomy specimen and lymph nodes. Secondary outcome measures included disease-free survival (DFS) and overall survival (OS). One hundred seven patients (14.4%) had pCR. In receiver operating characteristic analysis, optimal cut-off values for the neutrophile-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), platelet-to-lymphocyte (PLR), PIV, and Ki-67 index were determined as ≥ 2.34, ≥ 0.22, ≥ 131.8, ≥ 306.4, and ≥ 27, respectively. The clinical tumor (T) stage, NLR, MLR, PLR, PIV, estrogen receptor (ER) status, human epidermal growth factor receptor-2 (HER-2) status, and Ki-67 index were significantly associated with NAC response in univariate analyses. However, multivariate analysis revealed that the clinical T stage, PIV, ER status, HER-2 status, and Ki-67 index were independent predictors for pCR. Moreover, the low PIV group patients had significantly better DFS and OS than those in the high PIV group (p = 0.034, p = 0.028, respectively). Based on our results, pre-treatment PIV seems as a predictor for pCR and survival, outperforming NLR, MLR, PLR in predicting pCR in Turkish women with breast cancer who received NAC. However, further studies are needed to confirm our findings.

Self-injurious behaviors (SIBs) in autism spectrum disorder (ASD) are destructive symptoms that can lead to dangerous injuries and life-threatening risks. Agitation and SIBs may not respond to psychopharmacological and behavioral interventions. There are reports in the literature on improvement after electroconvulsive therapy (ECT) in cases not responding pharmacotherapy. However, data on the efficacy of the therapy on the benefiting patients, the course of the treatment and on the use of maintenance ECT (m-ECT) are very limited. This report presents the clinical features and the course of m-ECT on two cases under follow up for pharmacotherapy resistant ASD with significant agitation, mood disorder and SIBs that could cause severe head traumas. The initial stage of therapy consisted of 7 sessions of ECT patients showed improvement after the 5th session. m-ECT were started since the agitation repeated one week after discharge despite ongoing pharmacotherapy. In the first case, m-ECT was continued once every two weeks for a total of 46 sessions; and in the second case a total of 18 weekly sessions were conducted. No significant side effects or complications were observed and the general state of well-being was preserved. Our paper is among the few that reported succesful treatment of agitation with m-ECT. m-ECT should be considered in treatment resistant cases.

Dermatofibrosarcoma protuberans (DFSP) is an uncommon soft tissue sarcoma that originates from the dermis or subcutaneous tissue in the skin. While its prognosis is generally favorable, disease recurrence is relatively frequent. Because morbidity after repeated surgery may be significant, an optimized prediction of recurrence-free survival (RFS) has the potential to improve current management strategies. The purpose of this study was to investigate the prognostic value of the Ki-67 proliferation index with respect to RFS in patients with DFSP. We retrospectively analyzed data from 45 patients with DFSP. We calculated the Ki-67 proliferation index as the percentage of immunostained nuclei among the total number of tumor cell nuclei regardless of the intensity of immunostaining. We constructed univariate and multivariate Cox proportional hazards regression models to identify predictors of RFS. Among the 45 patients included in the study, 8 developed local recurrences and 2 had lung metastases (median follow-up: 95.0 months; range: 5.2−412.4 months). The RFS rates at 60, 120, and 240 months of follow-up were 83.8%, 76.2%, and 65.3%, respectively. The median Ki-67 proliferation index was 14%. Notably, we identified the Ki-67 proliferation index as the only independent predictor for RFS in multivariate Cox proportional hazards regression analysis (hazard ratio = 1.106, 95% confidence interval = 1.019−1.200, p = 0.016). In summary, our results highlight the potential usefulness of the Ki-67 proliferation index for facilitating the identification of patients with DFSP at higher risk of developing disease recurrences.

The present study was designed to determine the protective activity of cinnamic acid against induction by X-rays of genomic instability in normal human blood lymphocytes. This radio-protective activity was assessed by use of the cytokinesis-block micronucleus test and the alkaline comet assay, with human blood lymphocytes isolated from two healthy donors. A Siemens Mevatron MD2 (Siemens AG, USA, 1994) linear accelerator was used for the irradiation with 1 or 2 Gy. Treatment of the lymphocytes with cinnamic acid prior to irradiation reduced the number of micronuclei when compared with that in control samples. Treatment with cinnamic acid without irradiation did not increase the number of micronuclei and did not show a cytostatic effect in the lymphocytes. The results of the alkaline comet assay revealed that cinnamic acid reduces the DNA damage induced by X-rays, showing a significant radio-protective effect. Cinnamic acid decreased the frequency of irradiation-induced micronuclei by 16-55% and reduced DNA breakage by 17-50%, as determined by the alkaline comet assay. Cinnamic acid may thus act as a radio-protective compound, and future studies may focus on elucidating the mechanism by which cinnamic acid offers radioprotection.

Distant organ tumor dissemination is a major cause of breast cancer-related deaths. In 2010, we analyzed the prognostic importance of the circulating tumor markers (CTMs) cytokeratin 19 (CK19), CK20, epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor 2 (HER2) in relation to the clinical and pathological characteristics of patients with breast cancer (BC). To assess the clinical utility of CK19, CK20 and EGFR in predicting distant metastasis in BC, here we report 7-year follow-up results of 77 patients. The patients with at least one positive CTM were classified as CTM(+) and those negative for all CTMs were assigned to CTM(-) group. In patients who received no treatment following CTM analysis, 25.0% had metastasis in CTM(+) and 10.0% in CTM(-) group. In patients who received one of the following therapies: chemotherapy, radiotherapy or hormone therapy, or the combinations of these therapies, the rate of metastasis was 33.3% in CTM(+) and 20.0% in CTM(-) group. Disease-free time was shorter in CTM(+) patients compared to CTM(-) group (28.83 ± 10.76 and 41.38 ± 9.5 months, respectively). According to multivariate Cox proportional hazard regression analysis, the presence of regional lymph node metastasis, Ki-67 expression, higher tumor grade and CTM expression status were predictors of poor prognosis associated with distant metastasis (p < 0.05). Also, CTM positivity was a factor associated with metastasis-related poor prognosis (HR = 0.492, p = 0.026). The mean survival for CTM(+) patients was shorter than that for CTM(-) patients (90.671 ± 2.66 and 101.23 ± 3.92 months, respectively; p > 0.05). Our findings demonstrate that CTM positivity may indicate a high metastasis risk; however, CTM negativity does not guarantee low metastasis risk. These results may encourage further preclinical investigation of CTMs, to evaluate the possible implications of these findings to the clinical setting.

Aims and background To evaluate the effect of bcl-2 expression on the local control and overall survival of patients with early stage laryngeal cancer treated with radiotherapy alone. Methods and study design We included 53 patients with stage Tis, T1, and T2 laryngeal cancer who were irradiated in our department. Paraffin blocks of all biopsy specimens were subjected to immunohistochemical analysis with a bcl-2 oncoprotein mouse clone 124 Scytek kit. Results The mean follow-up time was 61 months (range, 7–166). Local-regional recurrence was observed in 10 (19%) patients. Forty-three patients (81%) had negative bcl-2 staining, 5 patients (9%) had + staining, 3 patients (6%) ++ staining, and 2 patients (4%) +++ staining. No relationship was detected between bcl-2 expression and local control or overall survival. The emergence of a recurrence and a younger age (Conclusions No correlation was observed between bcl-2 expression and local control or overall survival. Whereas hemoglobin level, age and existence of a recurrence had a prognostic impact on overall survival, patient age and smoking status influenced local control rates.

Aims and background To evaluate the efficacy and tolerability of a new treatment approach including induction chemotherapy (CT) and concurrent chemoradiotherapy (CRT) in unresectable, locally advanced pancreatic cancer (LAPC). Patients and methods Twenty-four patients with LAPC were enrolled in the study. They first received induction CT consisting of 5-fluorouracil (5FU) (500 mg/m2) and gemcitabine (1000 mg/m2), which were given weekly for 3 weeks of every 4. Patients showing a response or disease stabilization after 2 cycles of induction CT received CRT consisting of external beam radiotherapy (50.4-54 Gy in fractions of 1.8 Gy/day) and gemcitabine (350 mg/m2, weekly for 6 weeks). Patients without disease progression received 2 additional cycles of CT consisting of 5FU plus gemcitabine with the same doses and schedule as given in the induction CT. Results After the end of the study, 2 (8%) and 5 (21%) patients showed complete and partial responses, respectively. Five patients (21%) had disease stabilization. The grade 3 and 4 toxicities associated with CT were neutropenia (21%) and thrombocytopenia (4%). The grade 3 and 4 toxicities occurring in patients who received CRT were neutropenia (24%), thrombocytopenia (24%), diarrhea (18%), and nausea (12%). The median progression-free survival for all patients was 6 months (95% CI, 3.6-8.4), and the median overall survival was 11 months (95% CI, 8.16-13.84). Conclusions The CRT approach of this study is moderately active and has an acceptable toxicity profile. However, the incor-poration of combination CT into CRT at the present schedule could not produce any additional benefit over CRT alone. Newer agents with more systemic activity are clearly warranted.

Synovial sarcoma (SS) is a type of soft-tissue sarcoma, often linked to poor survival. Although overexpression of enhancer of zeste homologue 2 (EZH2) has been associated with poor prognosis in different tumors, a few studies investigated this link in SS. Here, we analyzed the relationship between EZH2 expression and prognostic factors in SS. We included 29 patients with SS. Immunostaining of EZH2 was performed with (D2C9) XPTM Rabbit mAb antibody, and the results were classified as low EZH2 expression (negative or weak expression) and high EZH2 expression category (moderate or strong expression). Analysis of survival in relation to prognostic factors was performed with Kaplan-Meier survival curves and Cox proportional hazard regression analysis. Our sample included 19/29 female and 10/29 male patients, with age range 16-63 years. The tumor diameter ranged from 2 to 15 cm. Necrosis was observed in 15/29 cases. Sixteen cases had >10 mitoses per 50 high-power fields (HPFs). Out of 29 cases, 14 showed low and 15 had high EZH2 expression. Statistically significant results were obtained for the association between the presence of metastasis and necrosis (p = 0.042), high EZH2 expression and distant metastasis (p = 0.018), high EZH2 expression and necrosis (p = 0.016), and high EZH2 expression and the tumor size >5 cm versus tumor size ≤5 cm (p = 0.014). Patients with all of the following: the tumor size ≤5 cm, low EZH2 expression, and without necrosis and distant metastasis had significantly longer survival time. Our results are consistent with previous studies, suggesting that EZH2 overexpression is an indicator of poor prognosis in SS.

Earlier, more accurate assessment of secondary brain injury is essential in management of patients with traumatic brain injury (TBI). We assessed the accuracy and utility of high-resolution automated intracranial pressure (ICP) and cerebral perfusion pressure (CPP) recording and their analysis in patients with severe TBI.ICP and CPP data for 30 severe TBI patients were collected automatically at 6-second intervals. The degree and duration of ICP and CPP above and below treatment thresholds were calculated as "pressure times time dose" (PTD; mm Hg . h) using automated recordings (PTDa) or manual recordings (PTDm) for early stage (trauma resuscitation unit [TRU]) and total monitoring time (TRU and intensive care unit).Bland-Altman plots showed lack of agreement between PTDa and PTDm. For ICP20 mm Hg and CPP60 mm Hg, PTDa, but not PTDm, was significantly higher in patients with unfavorable outcome (Extended Glasgow Outcome Scale scoreor=4) than in patients with favorable outcome (Extended Glasgow Outcome Scale score4). Total PTDa for ICP20 mm Hg and CPP60 mm Hg had high predictive power for functional outcome (area under the receiver operating characteristics curve: 0.92 +/- 0.05 and 0.82 +/- 0.08, respectively) and inhospital mortality (0.76 +/- 0.15 and 0.79 +/- 0.14, respectively) and were strongly correlated with length of intensive care unit stay (p = 0.009 and 0.007), length of hospital stay (p = 0.009 and 0.005), and discharge Glasgow Coma Scale scores (p = 0.008 and p = 0.038). PTDa of CPP100 mm Hg during TRU monitoring and during the first 24 hours showed highest predictive power for mortality (area under the receiver operating characteristics curve: 0.72 +/- 0.18 and 0.85 +/- 0.13, respectively). PTDa was better than PTDm and the duration of episodes alone in predicting outcome.PTD calculation of high resolution ICP and CPP recording is a reliable and feasible way of monitoring severe TBI patients.

Carcinoma arising from ectopic breast tissue, either supernumerary breast or aberrant breast tissue, is extremely rare. Carcinoma occurs more frequently in the ectopic breast tissue of the axilla than in extra-axillary ectopic breast tissue. Here we report a case of an invasive lobular carcinoma arising from extra-axillary ectopic breast tissue and presenting as a subcutaneous nodule.

Altered mitochondrial energy metabolism contributes to the pathophysiology of acute brain injury caused by ischemia, trauma, and neurotoxins and by chronic neurodegenerative disorders such as Parkinson’s and Huntington’s diseases. Although much evidence supports that the electron transport chain dysfunction in these metabolic abnormalities has both genetic and intracellular environmental causes, alternative mechanisms are being explored. These include direct, reversible inhibition of cytochrome oxidase by nitric oxide, release of mitochondrial cytochrome c, oxidative inhibition of mitochondrial matrix dehydrogenases and adenine nucleotide transport, the availability of NAD for dehydrogenase reactions, respiratory uncoupling by activities such as that of the permeability transition pore, and altered mitochondrial structure and intracellular trafficking. This review focuses on the catabolism of neuronal NAD and the release of neuronal mitochondrial NAD as important contributors to metabolic dysfunction. In addition, the relationship between apoptotic signaling cascades and disruption of mitochondrial energy metabolism is considered in light of the fine balance between apoptotic and necrotic neural cell death.

Although it is well known that numerical and structural chromosomal aberrations are common in leukemic cells, tetraploidy and near-tetraploidy is a rare entity in acute myeloid leukemia (AML) [1-4]. We describe a rare case of AML-M0 with near-tetraploidy and superior vena cava syndrome (SVCS) due to a large mediastinal granulocytic sarcoma (GS). A 25-year-old male was admitted to our hospital with a progressive non-productive cough, dyspnea, pain on the left upper extremity and weight loss. One month ago, he was treated with a diagnosis of venous thrombosis because of the pain and swelling on his left upper extremity. At the time of admittance, physical examination revealed dyspnea, facial edema, swelling of the neck and upper extremities and dilated jugular and superficial veins of the chest. Peripheral lymph node or organomegaly was absent. His hematological findings were: hemoglobin, 14.1 g dl−1; hematocrit, 41.6%; MCV, 87.5 fl; WBC, 15.3 × 109 l−1 with 15% polymorphonuclear cells; 22% bands; 37% lymphocytes; 26% resembling blastic cells; and platelets 284 × 109 l−1. The chest X-ray showed enlarged mediastinum and thorax computed tomography (CT) demonstrated a multi-lobar mass with a diameter of 9 × 5 cm in the anterior mediastinum which also compressed the superior vena cava (Figure 1A). Abdominopelvic CT scan was normal. Mediastinoscopy was performed for definite diagnosis. The biopsy specimens from mediastinal mass revealed diffuse malignant infiltration in lipomatous tissue, which consisted of round, large sized cells. Nuclei were large, vesicular and contained two or three nucleolus. Cytoplasm was moderate in amount and clear. The specimens showed negativity for all of the antibodies and staining except for myeloperoxidase (MPO), CD34 and TdT (Figure 1B). Bone marrow aspirate revealed the presence of large blasts with a relatively low nuclear-cytoplasmic ratio, moderate chromatin pattern, two-to-three prominent nucleoli, no cytoplasmic granules and few cytoplasmic vacuolization. Most of the cells had heterogeneous shaped nuclei. No Auer rod was seen (Figure 1C). Cytochemistry revealed negativity for MPO, Sudan black B, periodic acid Schiff, combined esterase and acid phosphatase. Flow cytometric studies of the bone marrow cells revealed positivity for CD13, CD33, CD34, CD45, CD7 and HLA-DR. Cytogenetic analysis showed near tetraploidy (Figure 1D). Results of cytogenetic analysis of 20 metaphases of the bone marrow cells were as follows; 102, XXYY, +13, +14, +14, +15, +16, +18, +19, +21, +21, +22 [6] / 104, XXYY, +X, +Y, +3, +4, −7, −8, +10, +11, +13, +13, −14, +15, +15, +19, +21, +21, +22, +22 [9] / 98, XXYY, +3, +4, −6, +8, −11, +13, +14, −16, +19, +20, +21, +21 [5]. Neither apparent structural rearrangement nor normal clone was identified. Upon establishing the diagnosis (AML-M0/near tetraploidy+/mediastinal GS+) [5], he was given an induction chemotherapy consisting of daunorubicin (45 mg m−2 per day, days 1–3) and cytarabine (100 mg m−2 per day continuous infusion, days 1–7) and bone marrow remission was achieved. Then, he received the first consolidation chemotherapy consisting of idarubicin (10 mg m−2 per day, days 1–3) and cytarabine (1000 mg m−2 per day, days 1–6), followed by second consolidation chemotherapy consisting of cytarabine (6 gr m−2 per day, days 1–3) and 1800 cGy radiotherapy on mediastinum. The symptoms of SVCS improved gradually after the 5th day of induction chemotherapy. Likewise, the mediastinal mass decreased in size by 30% after induction chemotherapy, 70% after consolidation chemotherapies and disappeared completely after the completion of radiotherapy (Figures 1E and F). Presently, he is in the 10th month of his complete remission without any recurrence in the disease or GS.

The present study was designed to determine the radioprotective effect of two phytochemicals, namely, quinic acid and chlorogenic acid, against X-ray irradiation-induced genomic instability in non-tumorigenic human blood lymphocytes. The protective ability of two phenolic acids against radiation-induced DNA damage was assessed using the alkaline comet assay in human blood lymphocytes isolated from two healthy human donors. A Siemens Mevatron MD2 (Siemens AG, USA, 1994) linear accelerator was used for irradiation. The results of the alkaline comet assay revealed that quinic acid and chlorogenic acid decreased the DNA damage induced by X-ray irradiation and provided a significant radioprotective effect. Quinic acid decreased the presence of irradiation-induced DNA damage by 5.99-53.57% and chlorogenic acid by 4.49-48.15%, as determined by the alkaline comet assay. The results show that quinic acid and chlorogenic acid may act as radioprotective compounds. Future studies should focus on determining the mechanism by which these phenolic acids provide radioprotection.

Background. Numerous studies have recently been conducted to investigate genetic mechanisms in cancer causes and pathogenesis. Some of these studies have shown that there were certain specific chromosomal defects in normal cells of cancer patients and in their first-degree relatives. It was suggested that these individuals were susceptible to cancer development when compared with people without these defects. Materials and Methods. Chromosomal anomalies, such as gaps, breaks, and acentric fragments, and fragile site expression rates were determined in peripheral blood lymphocyte cultures in 14 head and neck cancer patients, 17 first-degree relatives of these patients, and 20 healthy individuals as a control group in this study. RPMI 1640 medium, composed of aphidicolin, 5-bromodeoxyuridine, and caffeine were used for the induction of fragile sites. Results. In cytogenetic and statistical evaluation, it was observed that both chromosomal aberration rates and fragile site expression frequencies in head and neck cancer patients and in their first-degree relatives were significantly greater than the control group (p

Aims and Background The status of the axillary lymph nodes at the time of diagnosis has been accepted as one of the most important prognostic factors for the overall and disease-free survival of patients with breast cancer. The aim of our study was to determine which factors influence axillary node involvement in invasive breast cancer. Methods The data presented here were obtained from 344 patients who were treated for invasive breast cancer at the Department of Radiation Oncology, Uludag University Medical College, Bursa, Turkey. Possible prognostic factors were categorized as patient related and tumor related. The Mann-Whitney U test was used for univariate analysis and logistic regression was used for multivariate analysis. Results In univariate analysis, a familial cancer history (P = 0.0042), age Conclusions In conclusion, absence of familial cancer history, presence of lymphatic vessel invasion, higher T stage, and age below 40 years independently increased the risk of axillary node involvement. Presence of perineural invasion and lymphatic vessel invasion, age below 40, and an extensive intraductal component of more than 25% independently affected the risk of having ≥4 nodes involved. Patients characterized by these factors may be classified into a higher risk group for nodal involvement, but more data are needed to define factors that can help in the decision-making regarding the omission of axillary treatment.

Purpose: We aim to determine infections occuring in patients with non-small cell lung cancer during radiotherapy (RT). Methods and materials: A total of 181 patients had been treated with thoracic radiotherapy between October 1995 and December 1999. Radiotherapy was given using 1.8-3 Gray (Gy) fraction daily, five fractions a week for a total dose of 59.4 Gy (30-70.2 Gy). A complete history was collected retrospectively for each patient. All microbiological examinations were performed according to the routine procedures of the hospital laboratory. Numeric and categoric variables were employed such as sex, age, performance status, histology, stage, chemotherapy, usage of corticosteroids, neutropenia, surgery, hospitalization, associated diseases, smoking during treatment, package per year of cigarette smoking, dose of radiotherapy, and response rates. Results: Infections developed in 84 patients (46%, 84/181) during thoracic radiotherapy. A 101 episodes of infections developed in these patients. Most patients suffered from sputum production (65%), cough (59%), auscultation findings (31%) and fever (31%). Gram-negative bacteria were the most frequently isolated pathogens in the cultures of specimens (70%, 16/23 samples). Neoadjuvant chemotherapy (OR = 4.81; 95% CI, 1.57-9.12; p = 0.003) and neutropenia (OR = 4.25; 95% CI, 1.44-6.89; p = 0.009) were found as risk factors for influencing infection based on logistic regression analyses. Package per year of cigarette smoking was found statistically significantly higher in patients with infections than patients without infections (p = 0.001). A slight increase in infections, which was of borderline statistical significance (p = 0.07), was observed in patients age over 70. Ciprofloxacin and clarithromycin were the most frequently used agents in treatment. Median survival was 9 months in the patients with infection and 13 months in the 97 patients without infection. Overall survival seemed to be statistically significantly better in patients without infection than patients with infection (p = 0.042) calculated using Kaplan-Meier method. Based on Cox regression analyses; overall survival was not correlated to presence of infection but associated with poor performance status ( 5940 cGy (OR = 2.06; 95% CI, 0.72-7.18; p = 0.007) and the absence of response to treatment (OR = 2.45; 95% CI, 0.89-14.23; p < 0.001) were also found to be risk factors for survival. Conclusions: Infections are important causes of morbidity and mortality in lung cancer patients. The control of infection in these patients may improve the survival. Predisposing factors and treatment management approaches in non-small cell lung cancer should be defined carefully.

Background: Data on intracranial pressure (ICP) and cerebral perfusion pressure (CPP) guide therapy in severe traumatic brain injury (TBI), but current linear analytic methods are insufficiently sensitive and specific for prognosis in dynamic situations over time. Methods: We have developed algorithms incorporating continuous, automated, digital ICP and CPP monitoring data into a pressure times time "dose" function. In this study, we calculated cumulative doses using thresholds of ICP >20 mm Hg and CPP

Calculation of integer heart rate variability (HRVi) permits monitoring over extended periods. We asked whether continuous monitoring of HRVi or integer pulse pressure (PP) variability (PPVi) could predict intracranial hypertension, defined as ICP20 mm Hg, cerebral hypoperfusion, defined as CPP60 mm Hg, mortality or functional outcome after severe traumatic brain injury. Dense integer data collected during continuous intensive care unit monitoring for periods of 1 to 11 days on 25 patients admitted to our Level I trauma center with Glasgow Coma Scale9 provided 1,715,000 data points over a mean 106±62 hours. PP, HRVi, and PPVi increased in response to increasing ICP when CPP60 mm Hg (P0.001), but HRVi and PPVi decreased when CPP60 mm Hg and P50 mm Hg, even with ICP20 mm Hg (P0.001). ICP up to 40 mm Hg still evoked an increase in HRVi and PPVi (P0.001), but both were suppressed with CPP50 mm Hg and ICP40 mm Hg (actual or impending brain death). Mean HRVi and PPVi predicted in-hospital mortality (sensitivity, 67%; specificity, 91% to 100%). Combining HRVi and PPVi as an "autonomic index" (AI) best predicted long-term functional outcome [Area Under the Curve: 0.84±0.08 for AI0.5]. Our data show that HRVi and PPVi can be monitored and calculated automatically and can provide useful prognostic information in patients with severe traumatic brain injury, particularly when combined into a single index.

5-Fluorouracil-based chemoradiotherapy is the most widely used treatment modality in the adjuvant treatment of rectal cancer. Capecitabine represents a valuable alternative to 5-Fluorouracil in this situation.Patients with stage II and stage III rectal adenocarcinoma, who were included in this analysis, received adjuvant chemoradiotherapy consisting of external-beam radiotherapy (50.4-54Gy) either with 5-Fluorouracil at a median dose of 300 mg/m2/day by protracted venous infusion for 5 days a week, or capecitabine at a median dose of 1650 mg/m2/day for 5 days a week after surgery. The data concerning the toxicity and the efficacy of the treatments were compared in patients treated with 5-Fluorouracil- and capecitabine-based chemoradiotherapy.Forty-three patients received 5-Fluorouracil, and 24 patients received capecitabine during adjuvant radiotherapy. Although there were no differences between the groups in terms of toxicity rates, distant metastasis-free survival, disease-free survival, and overall survival rates; a trend for improved loco-regional recurrence-free survival rate was observed in the capecitabine arm (p = 0.063).Capecitabine is at least as effective as 5-Fluorouracil in the postoperative treatment of rectal adenocarcinoma. Considering the trend for improved loco-regional recurrence-free survival rate in the capecitabine arm, it seems that the drug exerts better synergy with radiotherapy in this situation.

To determine the percentage of responders and the resectability rate for patients with locally advanced carcinoma of the rectum treated by infusional 5-fluorouracil chemotherapy and pelvic radiation.Twenty-four patients with a diagnosis of locally advanced unresectable rectal cancer received preoperative 5-fluorouracil by intravenous infusion at the dose of 250-300mg/m2/day concurrent with pelvic radiation (median 50.4 Gy/28 fractions). Surgery was performed with a mean delay of 15 days after completion of irradiation and included 11 abdominoperineal resections and five anal sphincter-preserving procedures.The median follow-up was 22 months. Complete histological response occurred in 6%, and tumor down-staging in 58% of cases. There was a significant difference in the rate of local control based on the distance of the tumor from the anal verge (5.4cm; p=0.046). Our results have suggested the importance of the total dose on the local control (p=0.061). Higher local failure rate has been observed with prolonged treatment time (p=0.018). With metastasis-free survival as the endpoint, only stage (p=0.027) was a statistically significant prognostic factor.The favorable influence of higher doses of preoperative radiotherapy on pathologic stage has been observed. Even after preoperative radiotherapy, postoperative staging remained a prognostic factor.

In this case report we present a patient with a painful traumatic neuroma after a finger stick by lancet. The patient benefited from surgical excision of the lesion, and her symptoms were completely abolished with additional sympathetic nerve blocks.

Acquired lymphangiectasis is a dilatation of lymphatic vessels that can result as a complication of surgical intervention and radiation therapy for malignancy. Acquired lymphangiectasis shares clinical and histological features with the congenital lesion, lymphangioma circumscriptum. Diagnosis and treatment of these vesiculobullous lesions is important because they may be associated with pain, chronic drainage, and cellulitis. We describe patient who had these lesions after treatment for cancer. Although a number of treatment options are available, we have found cryosurgery and electrocautery to be particularly effective.

Breast cancer in both spouses is extremely rare. There are 7 metachronous cases and 1 synchronous case in the English literature. No case has been reported in which 1 of the spouses had bilateral breast cancer. In this paper, we report a synchronous pair of cases where 1 of the spouses (wife) had bilateral breast cancer and the other (husband) had breast cancer.