Intracranial Ependymoma: Long-Term Results in a Series of 21 Patients Treated with Stereotactic 125Iodine Brachytherapy

Background

We evaluated the long-term outcome in patients harboring intracranial ependymomas treated with interstitial brachytherapy (IBT).

Methods

Twenty-one patients (M/F = 9/12; median age: 29 years; range: 8–70 years), diagnosed with intracranial ependymoma (1 WHO I, 11 WHO II, 9 WHO III) were treated with IBT using stereotactically implanted ¹²⁵Iodine seeds between 1987 and 2010, either primarily, as adjuvant therapy following incomplete resection, or as salvage treatment upon tumor recurrence. Sixteen of 21 patients underwent microsurgical resection prior to IBT; in 5 patients, IBT was performed primarily after stereotactic biopsy for histological diagnosis. The cumulative tumor surface dose ranged from 50–65 Gy treating a median tumor volume of 3.6 ml (range, 0.3–11.6 ml). A median follow-up period of 105.3 months (range, 12.7–286.2 months) was evaluated.

Results

Actuarial 2-, 5- and 10-years overall- and disease-specific survival rates after IBT were each 90% and 100% at all times for ependymomas WHO I/II, for anaplastic ependymomas WHO III 100%, 100%, 70% and 100%, 100%, 86%, respectively. The neurological status of seven patients improved, while there was no change in 12 and deterioration in 2 patients, respectively. Follow-up MR images disclosed a complete tumor remission in 3, a partial remission in 12 and a stable disease in 6 patients. Treatment-associated morbidity only occurred in a single patient.

Conclusions

This study shows that stereotactic IBT for intracranial ependymomas is safe and can provide a high degree of local tumor control. Due to the low rate of side effects, IBT may evolve into an attractive alternative to microsurgery in ependymomas located in eloquent areas or as a salvage treatment.     

Less Aggressive Surgical Procedure for Treatment of Solid Pseudopapillary Tumor: Limited Experience from a Single Institute

Objectives

To evaluate the clinical characteristics and radiological features of solid pseudopapillary tumor (SPT) and assess surgical therapy strategy.

Methods

A retrospective review was performed in 62 patients pathologically confirmed of SPT treated between 2003 and 2014. The clinical features, radiological examinations and surgical strategies were analyzed.

Results

56 females and 6 males were included in this study, mean age was 26 years old (range: 8–66 years old) with mean size of the tumor was 7.2 cm (range: 3–15 cm), and most tumor were commonly located in the head of pancreas (n = 29). Among all the cases, 3 patients had liver metastasis and underwent resection of SPT and liver metastasis. Furthermore, we performed 29 cases of local tumor excision; other patients underwent pancreaticoduodenectomy, middle pancreatectomy, middle pancreatectomy with splenectomy, distal pancreatectomy with spleen preservation, distal pancreatectomy with splenectomy and duodenum-preserving pancreatic head resection. No patient suffered from lymph node metastases. After median follow-up of 46 months (range: 2–135 months), no mortality or local recurrence or distant metastasis was found.

Conclusions

Solid pseudopapillary tumor is a latent malignant tumor with excellent prognosis. If feasible, less aggressive resection without regular lymphadenectomy is recommended for treatment of patients with SPT.     

In Vivo Tumor Growth Rate Measured by US in Preoperative Period and Long Term Disease Outcome in Breast Cancer Patients

Objective

The aim of our study was to evaluate the effect of tumor growth rate, calculated from tumor size measurements by US, on breast cancer patients’ outcome.

Patients and Methods

Breast cancer patients who received at least two serial breast ultrasonographies (US) in our institution during preoperative period and were surgically treated between 2002 and 2010 were reviewed. Tumor growth rate was determined by specific growth rate (SGR) using the two time point tumor sizes by US.

Results

A total of 957 patients were analyzed. The median duration between initial and second US was 28 days (range, 8–140). The median initial tumor size was 1.7cm (range, 0.4–7.0) and median second size was 1.9cm (range, 0.3–7.2). 523(54.6%) cases had increase in size. The median SGR(x10^-2) was 0.59 (range, -11.90~31.49) and mean tumor doubling time was 14.51 days. Tumor growth rate was higher when initial tumor size was smaller. Lymphovascular invasion, axillary lymph node metastasis, and higher histologic grade were significantly associated with higher SGR. SGR was significantly associated with disease-free survival (DFS) in a univariate analysis (p = 0.04), but not in a multivariate Cox analysis (p>0.05). High SGR was significantly associated with worse DFS in a subgroup of initial tumor size >2cm (p = 0.018), but not in those with tumor size <2cm (p>0.05).

Conclusion

Our results showed that tumor growth rate measured by US in a relatively short time interval was associated with other worse prognostic factors and DFS, but it was not an independent prognostic factor in breast cancer patients.     

The Response,Outcome and Toxicity of Aggressive Palliative Thoracic Radiotherapy for Metastatic Non-Small Cell Lung Cancer Patients with Controlled Extrathoracic Diseases

Background and Purpose

For metastatic non-small cell lung cancer (NSCLC) patients with controlled extrathoracic disease after systemic treatment, stable or progressive primary lung lesions may cause respiratory symptoms and increase comorbidities. In the present study, we sought to investigate whether aggressive palliative thoracic radiotherapy (RT) can enhance local control and improve the survival for this subgroup of patients.

Materials and Methods

Between March 2006 and December 2014, 56 patients with metastatic NSCLC who had responsive or stable extrathoracic diseases after chemotherapy and/or molecular targets, and received thoracic RT for stable and progressive primary lung lesions were included. RT with a median dose of 55 Gy (range, 40–62 Gy) was administered in 1.8–2.5 Gy fractions to primary lung tumor and regional mediastinal lymph nodes using modern RT technique. Overall survival (OS) from diagnosis, and locoregional progression-free survival (LRPFS), and survival calculated from radiotherapy (OS-RT) were estimated using the Kaplan-Meier method.

Results

There were 37 men and 19 women with a median age of 60 years at diagnosis. The median interval from the diagnosis of metastatic disease to thoracic RT was 8 months. Following thoracic RT, 26 patients (46%) achieved complete or partial response (overall response rate, ORR). Patients with squamous cell carcinoma or poorly-differentiated carcinoma had a higher ORR than those with adenocarcinoma (63% vs. 34%, P = 0.034). EGFR mutations was closely associated with a better ORR (45% vs. 29%, P = 0.284). At a median follow-up time of 44 months, the median OS, LRPFS after RT, and OS-RT were 50 months, 15 months, and 18 months.

Conclusion

Radical palliative throractic RT is safe and might be beneficial for primary lung lesions of metastatic NSCLC patients with controlled extrathoracic diseases.     

Influence of Low-Level Prenatal Exposure to PCDD/Fs and PCBs on Empathizing,Systemizing and Autistic Traits: Results from the Duisburg Birth Cohort Study

Background

Polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs) and polychlorinated biphenyls (PCBs) are assumed to act as endocrine disruptor chemicals. Prenatal exposure to these pollutants might influence fetal steroid hormone levels, which are thought to be related to sex-typical development and autistic traits.

Objectives

We examined associations of prenatal levels of PCDD/Fs and PCBs with autism traits and sex-typical behaviour in childhood.

Methods

We measured levels of PCDD/Fs and PCBs in maternal blood samples during pregnancy using gas chromatography/high-resolution mass spectrometry. Sex-typical behaviour was assessed at 9 years of age (n = 96) and autistic traits at 10 years of age using the Social Responsiveness Scale (SRS; n = 100). Multiple regression analyses were conducted to estimate the associations between prenatal exposure and outcome variables.

Results

Blood concentrations (WHO₂₀₀₅-TEq) of ƩPCDD/Fs ranged from 2.93–46.45 pg/g _{lipid base} (median = 12.91 pg/g _{lipid base}) and concentrations of ƩPCBs were in the range of 1.24–25.47 pg/g _{lipid base} (median = 6.85 pg/g _{lipid base}) which is within the range of German background exposure. We found significant negative associations between PCDD/F levels in maternal blood and SRS scores in the whole group (β = -6.66, p < .05), in girls (β = -10.98, p < .05) and, in one SRS subscale, in boys (β = -6.86, p < .05). For PCB levels, associations with one SRS subscale were significant for the whole study group as were associations with two subscales in girls. We did not find significant associations between PCDD/F or PCB levels and sex-typical behaviour for either sex.

Conclusions

In an earlier part of this study, prenatal exposure to PCDD/Fs and PCBs was found to be associated with lower testosterone levels, therefore, our findings are consistent with the idea that autism spectrum conditions are related to fetal androgen levels. Several possible mechanisms, through which PCDD/Fs and PCBs might influence autistic behaviour, are discussed.     

Delay in Diagnosis of Testicular Cancer; A Need for Awareness Programs

Background Aim

To gain insight into patient and doctor delay in testicular cancer (TC) and factors associated with delay.

Materials and Methods

Sixty of the 66 eligible men; median age 26 (range 17–45) years, diagnosed with TC at the University Medical Center Groningen completed a questionnaire on patients’ delay: interval from symptom onset to first consultation with a general practitioner (GP) and doctors’ delay: interval between GP and specialist visit.

Results

Median patient reported delay was 30 (range 1–365) days. Patient delay and TC tumor stage were associated (p = .01). Lower educated men and men embarrassed about their scrotal change reported longer patient delay (r = -.25, r = .79 respectively). Age, marital status, TC awareness, warning signals, nor perceived limitations were associated with patient delay. Median patient reported time from GP to specialist (doctors’ delay) was 7 (range 0–240) days. Referral time and disease stage were associated (p = .04). Six patients never reported a scrotal change. Of the 54 patients reporting a testicular change, 29 (54%) patients were initially ‘misdiagnosed’, leading to a median doctors’ delay of 14 (1–240) days, which was longer (p< .001) than in the 25 (46%) patients whose GP suspected TC (median doctors’ delay 1(0–7 days).

Conclusions

High variation in patients’ and doctors’ delay was found. Most important risk variables for longer patient delay were embarrassment and lower education. Most important risk variable in GP’s was ‘misdiagnosis’. TC awareness programs for men and physicians are required to decrease delay in the diagnosis of TC and improve disease free survival.     

Toxicity outcome in patients treated with modulated arc radiotherapy for localized prostate cancer

Aim

This study evaluates the acute toxicity outcome in patients treated with RapidArc for localized prostate cancer.

Background

Modern technologies allow the delivery of high doses to the prostate while lowering the dose to the neighbouring organs at risk. Whether this dosimetric advantage translates into clinical benefit is not well known.

Materials and methods

Between December 2009 and May 2012, 45 patients with primary prostate adenocarcinoma were treated using RapidArc. All patients received 1.8 Gy per fraction, the median dose to the prostate gland, seminal vesicles, pelvic lymph nodes and surgical bed was 80 Gy (range, 77.4–81 Gy), 50.4 Gy, 50.4 Gy and 77.4 Gy (range, 75.6–79.2 Gy), respectively.

Results

The time between the last session and the last treatment follow up was a median of 10 months (range, 3–24 months). The incidence of grade 3 acute gastrointestinal (GI) and genitourinary (GU) toxicity was 2.2% and 15.5%, respectively. Grade 2 acute GI and GU toxicity occurred in 30% and 27% of patients, respectively. No grade 4 acute GI and GU toxicity were observed. Older patients (>median) or patients with V60 higher than 35% had significantly higher rates of grade ≥2 acute GI toxicity compared with the younger ones.

Conclusions

RapidArc in the treatment of localized prostate cancer is tolerated well with no Grade >3 GI and GU toxicities. Older patients or patients with higher V60 had significantly higher rates of grade ≥2 acute GI toxicity. Further research is necessary to assess definitive late toxicity and tumour control outcome.     

Prognostic Value of the Fibrosis-4 Index in Human Immunodeficiency Virus Type-1 Infected Patients Initiating Antiretroviral Therapy with or without Hepatitis C Virus

Objective

To evaluate the Fibrosis (FIB)-4 index as a predictor of major liver-related events (LRE) and liver-related death (LRD) in human immunodeficiency virus (HIV) type-1 patients initiating combination antiretroviral therapy (cART).

Design

Retrospective analysis of a prospective cohort study.

Setting

Italian HIV care centers participating to the ICONA Foundation cohort.

Participants

Treatment-naive patients enrolled in ICONA were selected who: initiated cART, had hepatitis C virus (HCV) serology results, were HBsAg negative, had an available FIB-4 index at cART start and during follow up.

Methods

Cox regression models were used to determine the association of FIB4 with the risk of major LRE (gastrointestinal bleeding, ascites, hepatic encephalopathy, hepato-renal syndrome or hepatocellular carcinoma) or LRD.

Results

Three-thousand four-hundred seventy-five patients were enrolled: 73.3% were males, 27.2% HCV seropositive. At baseline (time of cART initiation) their median age was 39 years, had a median CD4+ T cell count of 260 cells/uL, and median HIV RNA 4.9 log copies/mL, 65.9% had a FIB-4 <1.45, 26.4% 1.45–3.25 and 7.7% >3.25. Over a follow up of 18,662 person-years, 41 events were observed: 25 major LRE and 16 LRD (incidence rate, IR, 2.2 per 1,000 PYFU [95% confidence interval, CI 1.6–3.0]). IR was higher in HCV seropositives as compared to negatives (5.9 vs 0.5 per 1,000 PYFU). Higher baseline FIB-4 category as compared to <1.45 (FIB-4 1.45–3.25: HR 3.55, 95% CI 1.09–11.58; FIB-4>3.25: HR 4.25, 1.21–14.92) and time-updated FIB-4 (FIB-4 1.45–3.25: HR 3.40, 1.02–11.40; FIB-4>3.25: HR 21.24, 6.75–66.84) were independently predictive of major LRE/LRD, after adjusting for HIV- and HCV-related variables, alcohol consumption and type of cART.

Conclusions

The FIB-4 index at cART initiation, and its modification over time are risk factors for major LRE or LRD, independently of infection with HCV and could be used to monitor patients on cART.     

Outcomes in a Cohort of Patients Started on Antiretroviral Treatment and Followed up for a Decade in an Urban Clinic in Uganda

Background

Short-medium term studies from sub-Saharan Africa show that, despite high early mortality, substantial loss to program, and high rates toxicity, patients on antiretroviral treatment have achieved outcomes comparable to those in developed settings. However, these studies were unable to account for long term outcomes of patients as they stayed longer on treatment.

Objectives

We aim to describe ten years outcomes of one of the first cohort of HIV positive patients started on antiretroviral treatment (ART) in Sub-Saharan Africa.

Methods

We report 10-years outcomes including mortality, retention, CD4-count response, virological outcomes, ART regimens change from a prospective cohort of 559 patients initiating ART and followed up for 10 years Uganda.

Results

Of 559 patients, 69.1% were female, median age (IQR) was 38 (33–44) years, median CD4-count (IQR) 98 (21–163) cell/μL; 74% were started on stavudine, lamivudine and nevirapine, 26% on zidovudine, lamivudine and efavirenz. After 10 years 361 (65%) patients were still in the study; 127 (22.7%) had died; 30 (5%) were lost to follow-up; 27 (5%) transferred; 18 (3%) withdrew consent. The probability of death was high in the first year (0.15, 95%, CI 0.12–0.18). The median CD4 count increased from 98 to 589 cell/μL (IQR: 450–739 cell/μL) with a median increase of 357 cells/μL (IQR: 128–600 cells/μL); 7.4% never attained initial viral suppression and of those who did 31.7% experienced viral failure. Three hundred and two patients had at least one drug substitution while on first line after a median of 40 months; 66 (11.9%) of the patients were switched to a second line PI-based regimen due to confirmed treatment failure.

Conclusions

Despite the high rate of early mortality due to advanced disease at presentation the outcomes from this cohort are encouraging, particularly the remarkable and incremental immune-recovery and a satisfactory rate of virologic suppression.     

The Effects of Anti-Dementia and Nootropic Treatments on the Mortality of Patients with Dementia: A Population-Based Cohort Study in Taiwan

Background

Few studies have examined the contribution of treatment on the mortality of dementia based on a population-based study.

Objective

To investigate the effects of anti-dementia and nootropic treatments on the mortality of dementia using a population-based cohort study.

Methods

12,193 incident dementia patients were found from 2000 to 2010. Their data were compared with 12,193 age- and sex-matched non-dementia controls that were randomly selected from the same database. Dementia was classified into vascular (VaD) and degenerative dementia. Mortality incidence and hazard ratios (HRs) were calculated.

Results

The median survival time was 3.39 years (95% confidence interval [CI]: 2.88–3.79) for VaD without medication, 6.62 years (95% CI: 6.24–7.21) for VaD with nootropics, 3.01 years (95% CI: 2.85–3.21) for degenerative dementia without medication, 8.11 years (95% CI: 6.30–8.55) for degenerative dementia with anti-dementia medication, 6.00 years (95% CI: 5.73–6.17) for degenerative dementia with nootropics, and 9.03 years (95% CI: 8.02–9.87) for degenerative dementia with both anti-dementia and nootropic medications. Compared to the non-dementia group, the HRs among individuals with degenerative dementia were 2.69 (95% CI: 2.55–2.83) without medication, 1.46 (95% CI: 1.39–1.54) with nootropics, 1.05 (95% CI: 0.82–1.34) with anti-dementia medication, and 0.92 (95% CI: 0.80–1.05) with both nootropic and anti-dementia medications. VaD with nootropics had a lower mortality (HR: 1.25, 95% CI: 1.15–1.37) than VaD without medication (HR: 2.46, 95% CI: 2.22–2.72).

Conclusion

Pharmacological treatments have beneficial effects for patients with dementia in prolonging their survival.     

Cumulative Incidence and Predictors of Progression in Corticosteroid-Na?ve Patients with Sarcoidosis

Background

Assessment of the clinical course of sarcoidosis requires long-term observation. However, the appropriate period of follow-up for sarcoidosis remains unclear, especially in patients without indication of corticosteroid therapy at the time of diagnosis.

Objective

This study aimed to clarify the cumulative incidence and identify risk factors for disease progression in corticosteroid-naïve sarcoidosis patients.

Methods

The clinical courses of 150 Japanese patients with sarcoidosis, who were followed for more than 2 years and had no indication for corticosteroid therapy at diagnosis, were retrospectively reviewed. Disease progression was defined as worsening of pulmonary sarcoidosis, development of new organ involvement, or extrapulmonary organ damage. The cumulative incidence of progression was estimated by generating a cumulative incidence curve with the Fine and Gray method.

Results

The median follow-up duration was 7.7 years (interquartile range, 4.7–13.6 years). Thirty-two (21%) patients experienced disease progression. New organ involvement appeared in 16 patients (11%). The 6-month, and 1-, 5-, 10-, and 15-year cumulative incidence of progression was 2%, 5%, 15%, 28%, and 31%, respectively. The number of organs involved at diagnosis was an independent predictor for progression with a multifactorial adjusted hazard ratio of 1.71 (95% confidence interval, 1.11–2.62). The optimal cut-off of the number of organs involved at diagnosis to identify future progression was three.

Conclusions

In corticosteroid-naïve sarcoidosis patients, the risks of disease progression are comparable from 0–5 years and 5–10 years after diagnosis. The number of organs involved at diagnosis is a useful predictor for progression of sarcoidosis.     

Prognostic Role of Adjuvant Chemotherapy in Node-Negative (N0), Triple-Negative (TN), Medullary Breast Cancer (MBC) in the Korean Population

Background

Despite the favorable prognosis for medullary breast cancer (MBC), the guidelines for the use of adjuvant chemotherapy for MBC have not been clearly established. This study investigated the prognostic role of adjuvant chemotherapy in Korean patients with node-negative (N0), triple-negative (TN) MBC patients.

Methods

We included data from 252 patients with N0 TN MBC, obtained from the Korean Breast Cancer Registry database. Patients were categorized as those who did not undergo adjuvant chemotherapy (group I) or those who did (group II). Clinicopathological characteristics, breast cancer-specific survival (BCSS), and overall survival (OS) were compared between the groups. In addition, a subgroup analysis for survival based on tumor size was conducted.

Results

A total of 252 N0 TN MBC patients with tumor sizes >1 cm who were diagnosed between April 1997 and March 2011 were enrolled. The median age was 44.95 years (range, 25–72 years), and the median follow-up period was 93.94 months (range, 23–195 months). Overall, the BCSS and OS in group II (97.3% and 97.3%, respectively) were significantly better compared with those in group I (89.2% and 86.2%, respectively). In the subgroup analysis, in patients with tumors >2 cm in size, those in group II had significant better BCSS and OS (97.5% and 97.5%, respectively) compared with those in group I (78.3% and 73.9%, respectively). In contrast in those with tumors 1–2 cm in size, there were no significant differences in BCSS and OS between the groups (both 97.1% for group I, and 95.2% and 92.9%, respectively for group II). Multivariate analysis revealed that adjuvant chemotherapy significantly improved BCSS (P = 0.009) and OS (P = 0.007), but only for patients with larger tumors (>2 cm).

Conclusions

In patients with N0 TN MBC, adjuvant chemotherapy had a significant clinical survival benefit, but only in those with tumors >2 cm.     

Association between Education Level and Prognosis after Esophageal Cancer Surgery: A Swedish Population-Based Cohort Study

Background

An association between education level and survival after esophageal cancer has recently been indicated, but remains uncertain. We conducted a large study with long follow-up to address this issue.

Methods

This population-based cohort study included all patients operated for esophageal cancer in Sweden between 1987 and 2010 with follow-up until 2012. Level of education was categorized as compulsory (≤9 years), intermediate (10–12 years), or high (≥13 years). The main outcome measure was overall 5-year mortality after esophagectomy. Cox regression was used to estimate associations between education level and mortality, expressed as hazard ratios (HRs) with 95% confidence intervals (CIs), with adjustment for sex, age, co-morbidity, tumor stage, tumor histology, and assessing the impact of education level over time.

Results

Compared to patients with high education, the adjusted HR for mortality was 1.29 (95% CI 1.07–1.57) in the intermediate educated group and 1.42 (95% CI 1.17–1.71) in the compulsory educated group. The largest differences were found in early tumor stages (T-stage 0–1), with HRs of 1.73 (95% CI 1.00–2.99) and 2.58 (95% CI 1.51–4.42) for intermediate and compulsory educated patients respectively; and for squamous cell carcinoma, with corresponding HRs of 1.38 (95% CI 1.07–1.79) and 1.52 (95% CI 1.19–1.95) respectively.

Conclusions

This Swedish population-based study showed an association between higher education level and improved survival after esophageal cancer surgery, independent of established prognostic factors. The associations were stronger in patients of an early tumor stage and squamous cell carcinoma.     

Effect of Prolonged Radiotherapy Treatment Time on Survival Outcomes after Intensity-Modulated Radiation Therapy in Nasopharyngeal Carcinoma

Purpose

To estimate the influence of prolonged radiation treatment time (RTT) on survival outcomes in nasopharyngeal carcinoma after continuous intensity-modulated radiation therapy.

Methods and Materials

Retrospectively review 321 patients with NPC treated between October 2009 and December 2010 and all of them underwent simultaneous accelerated intensity-modulated radiation therapy. The fractionated dose was 2–2.47 Gy/F (median 2.27 Gy), and the total dose for nasopharyngeal region was 64–74 Gy/ 28–33 fractions. The association of prolonged RTT and treatment interruption with PFS, LRFS and DFFS were assessed by univariate analysis and multivariate analysis. Survival analyses were carried out using Kaplan–Meier methodology and the log-rank test was used to assess the difference. The Cox regression proportional hazard model was used for multivariate analyses and evaluating the prognostic parameters for PFS, LRFS and DFFS.

Results

Univariate analysis revealed no significant associations between prolonged RTT and PFS, LRFS, DFFS when dichotomized using various cut-off values (all P>0.05). In multivariate analysis, RTT (range, 36–63 days) as a continuous variable, had no influence on any survival outcome as well (P>0.05). T and N classification were independent prognostic factors for PFS, LRFS and DFFS (all P<0.05, except T classification for LRFS, P = 0.057). Age was an independent prognostic factor for PFS (hazard ratio [HR], 1.033; P = 0.008) and DFFS (HR, 1.032; P = 0.043).

Conclusion

We conclude that no such association between survival outcomes and radiation treatment duration (range: 36–63 days) can be found in the present retrospective study, however, we have to remind that prolongation in treatment should be limited in clinical application and interruptions caused by any reason should be minimized as much as possible.     

3D conformal hypofractionated radical radiotherapy in early glottic cancer

Aim

The purpose of this study was to evaluate acute and late toxicity and the locoregional control in patients treated with hypofractionated radical radiotherapy 2.25 Gy/fraction/day for early glottic carcinoma.

Materials and methods

A retrospective analysis was performed of 27 patients, stage T1–T2 N0 glottic squamous cell carcinoma, that underwent radical RT from April 2008 to October 2011. The mean age was 64.6 years (range 36–81). Seventeen patients were staged T1a, 3 patients T1b and 7 patients T2. All patients were 3D planned and treated in a 6 MV LINAC, 2.25 Gy/fraction/5 days per week, to a total dose between 63 Gy and 67.5 Gy. Biological Effective Dose (BED (α/β = 10)) ranged from 77.18 Gy to 82.69 Gy and EQD2 from 64.31 Gy to 68.91 Gy. Patients were evaluated in periodic follow-up. Toxicity was evaluated according to RTOG Toxicities Scales.

Results

With a median follow-time of 24.7 months (range 3.6–44.2 months), no evidence of locoregional recurrence was observed. The treatment was well tolerated and no unscheduled interruptions in treatments for toxicity were documented, with the median overall treatment time of 41 days (range 38–48). Only grades 1 and 2 acute toxicity were observed and no evidence of severe late toxicity.

Conclusion

The authors believe that this moderately hypofractionated scheme can provide a good locoregional control for T1–T2 glottic carcinomas with no increase of toxicity. As the limitation of this work is the reduced number of patients and the lack of long term follow-up, the authors hope to update this retrospective study in the future in order to improve the power of the results.     

Cholestasis Reveals Severe Cortisol Deficiency in Neonatal Pituitary Stalk Interruption Syndrome

Objectives

Cholestasis has been reported during the course of congenital hypothalamic-pituitary deficiency, but crucial information is lacking regarding both its origin and prognosis. We aimed to characterize the course of cholestasis and factors contributing to it in patients with deficiency due to pituitary stalk interruption syndrome (PSIS).

Methods

We conducted a retrospective single-center, case-cohort study including 16 patients with PSIS diagnosed before one year of age. We collected clinical and biological parameters from medical records and compared the characteristics of the endocrine syndrome in PSIS patients with and without cholestasis.

Results

5/16 patients had cholestasis, all with a neonatal onset and multiple hypothalamic-pituitary deficiency. Patients with cholestasis presented with lower Apgar score and higher rate of ophthalmic malformations: 3/5 vs 1/11, p = 0.03 and 5/5 vs 4/11, p = 0.02, respectively. The plasma cortisol level was strongly decreased in patients with cholestasis: 12.4 ng/mL (8–15 ng/mL) vs 79.4 ng/mL (10–210 ng/mL), p = 0.04. Cholestasis resolved within 9 months following hormone supplementation. No development of chronic liver disease was observed during a median follow-up of 9.4 years (range, 1.3–13.3 years).

Conclusions

Cholestasis is a frequent symptom at presentation of PSIS during the neonatal period that may help earlier diagnosis and that indicates a profound cortisol deficiency.     

Endothelial Nitric Oxide Synthase G894T Polymorphism Associates with Disease Severity in Puumala Hantavirus Infection

Introduction

Hantavirus infections are characterized by both activation and dysfunction of the endothelial cells. The underlying mechanisms of the disease pathogenesis are not fully understood. Here we tested the hypothesis whether the polymorphisms of endothelial nitric oxide synthase, eNOS G894T, and inducible nitric oxide synthase, iNOS G2087A, are associated with the severity of acute Puumala hantavirus (PUUV) infection.

Patients and Methods

Hospitalized patients (n = 172) with serologically verified PUUV infection were examined. Clinical and laboratory variables reflecting disease severity were determined. The polymorphisms of eNOS G894T (Glu298Asp, rs1799983) and iNOS G2087A (Ser608Leu, rs2297518) were genotyped.

Results

The rare eNOS G894T genotype was associated with the severity of acute kidney injury (AKI). The non-carriers of G-allele (TT-homozygotes) had higher maximum level of serum creatinine than the carriers of G-allele (GT-heterozygotes and GG-homozygotes; median 326, range 102–1041 vs. median 175, range 51–1499 μmol/l; p = 0.018, respectively). The length of hospital stay was longer in the non-carriers of G-allele than in G-allele carriers (median 8, range 3–14 vs. median 6, range 2–15 days; p = 0.032). The rare A-allele carriers (i.e. AA-homozygotes and GA-heterozygotes) of iNOS G2087A had lower minimum systolic and diastolic blood pressure than the non-carriers of A-allele (median 110, range 74–170 vs.116, range 86–162 mmHg, p = 0.019, and median 68, range 40–90 vs. 72, range 48–100 mmHg; p = 0.003, respectively).

Conclusions

Patients with the TT-homozygous genotype of eNOS G894T had more severe PUUV-induced AKI than the other genotypes. The eNOS G894T polymorphism may play role in the endothelial dysfunction observed during acute PUUV infection.     

A Phase I Dose-Escalation Study of Lenalidomide in Combination with Gemcitabine in Patients with Advanced Pancreatic Cancer

Purpose

Lenalidomide have both immunomodulatory and anti-angiogenic properties which could confer anti-cancer effects. The aim of this study was to assess the feasibility of combining lenalidomide with the standard treatment gemcitabine in pancreatic cancer patients with advanced disease.

Patients and Methods

Eligible patients had locally advanced or metastatic adenocarcinoma of the pancreas. Patients received lenalidomide days 1–21 orally and gemcitabine 1000 mg/m2 intravenously (days 1, 8 and 15), each 28 day cycle. Three cohorts of lenalidomide were examined (Cohort I = 15 mg, Cohort II = 20 mg and Cohort III = 25 mg daily). The maximum tolerated dose (MTD) of lenalidomide given in combination with gemcitabine was defined as the highest dose level at which no more than one out of four (25%) subjects experiences a dose-limiting toxicity (DLT). Patients should also be able to receive daily low molecular weight heparin (LMWH) (e.g. dalteparin 5000 IU s.c. daily) as a prophylactic anticoagulant for venous thromboembolic events (VTEs). Twelve patients (n = 4, n = 3 and n = 5 in cohort I, II and III, respectively) were enrolled in this study.

Results

Median duration of treatment was 11 weeks (range 1–66), and median number of treatment cycles were three (range 1–14). The only DLT was a cardiac failure grade 3 in cohort III. Frequent treatment-related adverse events (AEs) (all grades) included neutropenia, leucopenia and fatigue (83% each, but there was no febrile neutropenia); thrombocytopenia (75%); dermatological toxicity (75%); diarrhea and nausea (42% each); and neuropathy (42%).

Discussion

This phase I study demonstrates the feasibility of the combination of lenalidomide and gemcitabine as first-line treatment in patients with advanced pancreatic cancer. The tolerability profile demonstrated in the dose escalation schedule of lenalidomide suggests the dosing of lenalidomide to be 25 mg daily on days 1–21 with standard dosing of gemcitabine and merits further evaluation in a phase II trial.

Trial Registration

ClinicalTrials.gov NCT01547260     

Clinical Outcomes for Gastric Cancer following Adjuvant Chemoradiation Utilizing Intensity Modulated versus Three-Dimensional Conformal Radiotherapy

Purpose/Objective(s)

To determine if intensity modulated radiation therapy (IMRT) in the post-operative setting for gastric cancer was associated with reduced toxicity compared to 3D conformal radiation therapy (3DCRT).

Materials/Methods

This retrospective study includes 24 patients with stage IB-IIIB gastric cancer consecutively treated from 2001–2010. All underwent surgery followed by adjuvant chemoradiation. Concurrent chemotherapy consisted of 5-FU/leucovorin (n = 21), epirubicin/cisplatin/5FU (n = 1), or none (n = 2). IMRT was utilized in 12 patients and 3DCRT in 12 patients. For both groups, the target volume included the tumor bed, anastomosis, gastric stump, and regional lymphatics.

Results

Median follow-up for the entire cohort was 19 months (range 0.4–8.5 years), and 49 months (0.5–8.5 years) in surviving patients. The 3DCRT group received a median dose of 45 Gy, and the IMRT group received a median dose of 50.4 Gy (p = 0.0004). For the entire cohort, 3-year overall survival (OS) was 40% and 3-year disease free survival (DFS) was 41%. OS and DFS did not differ significantly between the groups. Acute toxicity was similar. Between 3DCRT and IMRT groups, during radiotherapy, median weight lost (3.2 vs. 3.3 kg, respectively; p = 0.47) and median percent weight loss were similar (5.0% vs. 4.3%, respectively; p = 0.43). Acute grade 2 toxicity was experienced by 8 patients receiving 3DCRT and 11 receiving IMRT (p = 0.32); acute grade 3 toxicity occurred in 1 patient receiving 3DCRT and none receiving IMRT (p = 1.0). No patients in either cohort experienced late grade 3 toxicity, including renal or gastrointestinal toxicity. At last follow up, the median increase in creatinine was 0.1 mg/dL in the IMRT group and 0.1 mg/dL in the 3DCRT group (p = 0.78).

Conclusion

This study demonstrates that adjuvant chemoradiation for gastric cancer with IMRT to 50.4 Gy was well-tolerated and compared similarly in toxicity with 3DCRT to 45 Gy.     

Risk Factors for Hospitalization Due to Community-Acquired Sepsis – A Population-Based Case-Control Study

Background

The aim of the study was to estimate risk factors for hospitalization due to sepsis and to determine whether these risk factors vary by age and gender.

Methods

We performed a population-based case-control study of all adult patients admitted to a medical ED from September 2010 to August 2011. Controls were sampled within the hospital catchment-area. All potential cases were manually validated using a structured protocol. Vital signs and laboratory values measured at arrival were registered to define systemic inflammatory response syndrome and organ dysfunction. Multivariable logistic regression was used to elucidate which predefined risk factors were associated with an increased or decreased risk hospitalization due to sepsis.

Results

A total of 1713 patients were admitted with sepsis of any severity. The median age was 72 years (interquartile range: 57–81 years) and 793 (46.3%) were male. 621 (36.3%) patients were admitted with sepsis, 1071 (62.5%) with severe sepsis and 21 (1.2%) with septic shock. Episodes with sepsis of any severity were associated with older age (85+ years adjusted OR 6.02 [95%CI: 5.09–7.12]), immunosuppression (4.41 [3.83–5.09]), alcoholism-related conditions (2.90 [2.41–3.50]), and certain comorbidities: psychotic disorder (1.90 [1.58–2.27]), neurological (1.98 [1.73–2.26]), respiratory (3.58 [3.16–4.06]), cardiovascular (1.62 [1.41–1.85]), diabetes (1.82 [1.57–2.12]), cancer (1.44 [1.22–1.68]), gastrointestinal (1.71 [1.44–2.05]) and renal (1.46 [1.13–1.89]). The strength of the observed associations for comorbid factors was strongest among younger individuals.

Conclusions

Hospitalization due to sepsis of any severity was associated with several independent risk factors, including age and comorbid factors.