Twice-daily Thoracic Radiotherapy for Limited-stage Small-cell Lung Cancer Does Not Increase the Incidence of Acute Severe Esophagitis.

PURPOSE: Acute esophagitis is common after thoracic radiation therapy (TRT) given with chemotherapy for limited-stage small-cell lung cancer (LS SCLC). Although twice-daily TRT to 45 Gy in 30 fractions is considered standard, some clinicians are reluctant to use this schedule because of its perceived impracticality and risk of severe esophagitis. We reviewed a single-institution experience with severe (grade ≥ 3) esophagitis after TRT with chemotherapy for LS SCLC. PATIENTS AND METHODS: A total of 504 patients were identified as having received TRT (≥45 Gy) with platinum-containing chemotherapy for LS SCLC at MD Anderson Cancer Center in 1987 through 2012. Patients with complete or good partial response were offered prophylactic cranial irradiation. Esophagitis was scored retrospectively with the Common Terminology Criteria for Adverse Events, V3.0. Clinical variables were analyzed for possible association with acute grade ≥ 3 esophagitis. RESULTS: At a median follow-up time of 23.9 months (range, 1.2-240.8 months), 103 (20%) patients had experienced grade ≥ 3 esophagitis. In univariate analysis, TRT dose ≥ 60 Gy was the only factor associated with severe esophagitis (odds ratio [OR], 1.84; 95% confidence interval [CI], 1.02-3.30; P = .043); use of twice-daily TRT was not (OR, 0.96; 95% CI, 0.61-1.52; P = .867). The significance of TRT to ≥ 60 Gy was maintained in multivariate Cox regression analysis adjusted for tumor size (OR, 1.91; 95% CI, 1.05-3.46; P = .034). CONCLUSIONS: TRT to ≥ 60 Gy predicted acute severe esophagitis, but twice-daily fractionation did not. Standard-dose 45-Gy twice-daily TRT should not be avoided for fear of severe esophagitis.

Volume of hospital is important for the prognosis of high-risk patients with nonvariceal upper gastrointestinal bleeding (NVUGIB).

BACKGROUND AND AIM: Nonvariceal upper gastrointestinal bleeding (NVUGIB) is a potentially life-threatening hospital emergency requiring hemodynamic stabilization and resuscitation. This study is carried out to determine whether hospital volume can influence outcome in patients with NVUGIB. METHOD: This is a retrospective study with a prospective cohort database (KCT 0000514. cris.nih.go.kr). Eight teaching hospitals were divided into two different groups: high-volume centers (HVC, ≥60 NVUGIB patients/year, four clinics) and low-volume centers (LVC, <60 NVUGIB patients/year, four clinics). Baseline characteristics of patients, risk stratification, and outcomes between hospitals of different volumes were compared. From February 2011 to December 2013, a total of 1584 NVUGIB patients enrolled in eight clinics were retrospectively reviewed. The main outcome measurements consisted of continuous bleeding after treatment, re-bleeding, necessity for surgical/other retreatments, and death within 30 days. RESULTS: Similar baseline characters for patients were observed in both groups. There was a significant difference in the incidence of poor outcome between the HVC and LVC groups (9.06 vs. 13.69%, P = 0.014). The incidence rate of poor outcome in high-risk patients (Rockall score ≥8) in HVC was lower than that in high-risk patients in LVC (16.07 vs. 26.92%, P = 0.048); however, there was no significant difference in poor outcome in the lower-risk patients in either group (8.72 vs. 10.42%, P = 0.370). CONCLUSIONS: Significant correlation between hospital volume and outcome in NVUGIB patients was observed. Referral to HVC for the management of high-risk NVUGIB patients should be considered in clinical practice.

Early Weight Loss during Chemoradiotherapy Has a Detrimental Impact on Outcome in NSCLC.

OBJECTIVES: The aim of this study was to assess the effect of early weight loss before the onset of radiation esophagitis on overall survival (OS) in patients with non-small cell lung cancer treated with concurrent chemoradiotherapy. METHODS: Characteristics (e.g., patient weight, radiation esophagitis score, sex, World Health Organization performance status, chemotherapy dose, nodal status, and gross tumor volume) of 151 patients who received concurrent chemoradiotherapy (in 2006-2013) were retrospectively correlated with OS. Early weight loss was defined as weight loss of more than 5% between the start and third week of radiotherapy in patients whose weight was stable before treatment initiation. RESULTS: In 17% of the patients early weight loss was observed. Median OS (95% confidence interval [CI]) was significantly shorter in the early weight loss group (OS = 13.0 months, 95% CI: 2.0-24.0) versus in the non-early weight loss group (OS = 23.0 months, 95% CI: 14.7-31.3) (hazard ratio [HR] = 1.8, 95% CI: 1.12-2.96, p = 0.017). On multivariate analysis sex (HR = 2.1, 95% CI: 1.33-3.29, p = 0.001), World Health Organization performance status (HR = 1.9, 95% CI: 1.20-2.97, p = 0.006), nodal status (HR = 2.9, 95% CI: 1.38-6.01, p = 0.005), and early weight loss (HR = 1.9, 95% CI: 1.10-3.19, p = 0.022) were associated with OS. CONCLUSIONS: Early weight loss in patients with non-small cell lung cancer was found to be associated with worse prognosis. These data warrant further investigation into the efficacy of tailored intervention to prevent early weight loss.

Effect of Increased Radiotoxicity on Survival of Patients with Non-small Cell Lung Cancer Treated with Curatively Intended Radiotherapy.

AIM: To elucidate the impact of different forms of radiation toxicities (esophagitis, radiation pneumonitis, mucositis and hoarseness), on the survival of patients treated with curatively intended radiotherapy for non-small cell lung cancer (NSCLC). PATIENTS AND METHODS: Data were individually collected retrospectively for all patients diagnosed with NSCLC subjected to curatively intended radiotherapy (≥50 Gy) in Sweden during the time period 1990 to 2000. RESULTS: Esophagitis was the only radiation-induced toxicity with an impact on survival (hazard ratio=0.83, p=0.016). However, in a multivariate model, with clinical- and treatment-related factors taken into consideration, the impact of esophagitis on survival was no longer statistically significant (hazard ratio=0.88, p=0.17). CONCLUSION: The effect on survival seen in univariate analysis may be related to higher radiation dose and to the higher prevalence of chemotherapy in this group. The results do not suggest that the toxicities examined have any detrimental effect on overall survival.

Clinical three-dimensional conformal radiotherapy research using repeated computed tomography scans for field reduction in older non-small-cell lung cancer patients.

This study investigated the curative and toxic effects of three-dimensional conformal radiotherapy (3D-CRT), using repeated CT scans for field reduction in older non-small-cell lung cancer (NSCLC) patients. 3D-CRT was administered to 36 older patients with NSCLC, and irradiation fields included the primary lesion and metastatic lymph nodes. After CT localization scanning, images were fed into a treatment planning system to delineate the gross tumor volume (GTV)1 and prepare Plan 1. After the DT50 (dose of the tumor is 50 Gy) increased from 50 Gy in 25 fractions to 54 Gy in 27 fractions, secondary CT localization scanning was performed to delineate GTV2 and prepare Plan 2; radiotherapy was administered continuously. When the DT increased to 60-65 Gy, tertiary CT scanning was performed to prepare another plan. The field was reduced to boost irradiation to the residual target volume until the total DT increased to 68-74 Gy. Compared with GTV1, the median absolute volume regression and median relative regression amounts for GTV2 were 68.85 cm(3) and 31.17%, respectively (Z = -2.673, P = 0.021). There were 8 cases of complete remission (22.2%), 20 of partial remission (55.6%), 7 of stable disease (19.4%), and 1 of progressive disease (2.8%). The total effectiveness rate was 77.8% and the 1- and 2-year survival rates were 63.9 and 27.8%, respectively. Radiation esophagitis and radiation pneumonia, the main toxic side effects, were tolerable. 3D-CRT, using repeated CT scans for field reduction in older NSCLC patients, could increase the local control and survival rates and relieve the toxic radiotherapy side effects.

Influence of oral glutamine supplementation on survival outcomes of patients treated with concurrent chemoradiotherapy for locally advanced non-small cell lung cancer.

BACKGROUND: Glutamine (Gln) supplementation during concurrent chemoradiotherapy (C-CRT) effectively reduces the incidence and severity of acute radiation-induced esophagitis (RIE). However, there are concerns that Gln might stimulate tumor growth, and therefore negatively impact the outcomes of anticancer treatment. We retrospectively investigated the effect of co-administration of oral Gln during C-CRT on survival outcomes of patients with stage IIIB non-small cell lung carcinoma (NSCLC). We additionally evaluated role of oral Gln in preventing C-CRT-induced weight change, acute and late toxicities. METHODS: The study included 104 patients: 56 (53.8%) received prophylactic powdered Gln (Gln+) orally at a dose of 10 g/8 h and 48 (46.2%) did not receive Gln (Gln-) and served as controls. The prescribed radiation dose to the planning target volume was 66 Gy in 2-Gy fractions. Primary endpoints of progression-free survival (PFS), local/regional progression-free survival (LRPFS), and overall survival (OS) were correlated with status of Gln supplementation. RESULTS: Oral Gln was well tolerated except for mild nausea/vomiting in 14 (25.0%) patients. There was no C-CRT-related acute or late grade 4-5 toxicity. Administration of Gln was associated with a decrease in the incidence of grade 3 acute radiation-induced esophagitis (RIE) (7.2% vs. 16.7% for Gln+ vs. Gln-; p=0.02) and late-RIE (0% vs. 6.3%; p=0.06), a reduced need for unplanned treatment breaks (7.1% vs. 20.8%; p=0.04), and reduced incidence of weight loss (44.6% vs. 72.9%; p=0.002). At a median follow-up of 24.2 months (range 9.2-34.4) the median OS, LRPFS, and PFS for Gln+ vs. Gln- cohorts were 21.4 vs. 20.4 (p=0.35), 14.2 vs.11.3 (p=0.16), and 10.2 vs. 9.0 months (p=0.11), respectively. CONCLUSION: In our study, supplementation with Gln during C-CRT had no detectable negative impact on tumor control and survival outcomes in patients with Stage IIIB NSCLC. Furthermore, Gln appeared to have a beneficial effect with respect to prevention of weight loss and unplanned treatment delays, and reduced the severity and incidence of acute- and late-RIE.

Mortality from nonulcer bleeding is similar to that of ulcer bleeding in high-risk patients with nonvariceal hemorrhage: a prospective database study in Italy.

BACKGROUND: Nonulcer causes of bleeding are often regarded as minor, ie, associated with a lower risk of mortality. OBJECTIVE: To assess the risk of death from nonulcer causes of upper GI bleeding (UGIB). DESIGN: Secondary analysis of prospectively collected data from 3 national databases. SETTINGS: Community and teaching hospitals. PATIENTS: Consecutive patients admitted for acute nonvariceal UGIB. INTERVENTIONS: Early endoscopy, medical and endoscopic treatment as appropriate. MAIN OUTCOME MEASUREMENTS: Thirty-day mortality, recurrent bleeding, and need for surgery. RESULTS: A total of 3207 patients (65.8% male), mean (standard deviation) age 68.3 (16.4) years, were analyzed. Overall mortality was 4.45% (143 patients). According to the source of bleeding, mortality was 9.8% for neoplasia, 4.8% for Mallory-Weiss tears, 4.8% for vascular lesions, 4.4% for gastroduodenal erosions, 4.4% for duodenal ulcer, and 3.1% for gastric ulcer. Frequency of death was not different among benign endoscopic diagnoses (overall P = .567). Risk of death was significantly higher in patients with neoplasia compared with benign conditions (odds ratio 2.50; 95% CI, 1.32-4.46; P < .0001). Gastric or duodenal ulcer significantly increased the risk of death, but this was not related to the presence of high-risk stigmata (P = .368). The strongest predictor of mortality for all causes of nonvariceal UGIB was the overall physical status of the patient measured with the American Society of Anesthesiologists score (1-2 vs 3-4, P < .001). LIMITATIONS: No data on the American Society of Anesthesiologists class score in the Prometeo study. CONCLUSIONS: Nonulcer causes of nonvariceal UGIB have a risk of death, similar to bleeding peptic ulcers in the clinical context of a high-risk patient.

Laparoscopic antireflux surgery for gastroesophageal reflux disease after lung transplantation.

BACKGROUND: Although gastroesophageal reflux disease (GERD) is highly prevalent in lung transplantation, the pathophysiology of GERD in these patients is unknown. We hypothesize that the pathophysiology of GERD after lung transplantation differs from that of a control population, and that the 30-d morbidity and mortality of laparoscopic antireflux surgery (LARS) are equivalent in both populations. METHODS: We retrospectively compared the pathophysiology of GERD and the 30-d morbidity and mortality of 29 consecutive lung transplant patients with 23 consecutive patients without lung transplantation (control group), all of whom had LARS for GERD between November 2008 and May 2010. RESULTS: Both groups had a similar prevalence of endoscopic esophagitis and Barrett's esophagus , comparable manometric profiles, and similar prevalence of abnormal peristalsis. However, hiatal hernia was more common in controls than in lung transplant patients (57% versus 24%; P = 0.04). Lung transplant patients had a higher prevalence and severity of proximal GERD (65% versus 33%; P = 0.04). The 30-d morbidity and mortality following LARS were similar in both groups regardless of the higher surgical risk of lung transplants (median ASA class: 3 versus 2 for controls, P < 0.001). CONCLUSIONS: These results show that despite similar manometric profiles, lung transplant patients are more prone to proximal reflux than the general population with GERD; the prevalence of endoscopic esophagitis and Barrett's esophagus is the same in both groups of patients; a hiatal hernia is uncommon after lung transplantation; and the morbidity and mortality of LARS are the same for lung transplant patients as the general population with GERD.

Upper gastrointestinal bleeding: risk factors for mortality in two urban centres in Latin America.

OBJECTIVE: To describe the experience with upper gastrointestinal bleeding in two major Latin American hospitals; presenting its main causes, treatment, and prognosis, while exploring some risk factors associated with death. DESIGN: Prospective cohort study. PATIENTS AND METHODS: Four hundred and sixty four patients were admitted into any of the 2 hospitals and were at least 15 years of age. Some variables demographics, clinics and treatment were studied. The association between those variables and the death were explored. RESULTS: Mean age was 57.9 years; the men:women ratio was 1.4:1. Three hundred and fifty nine patients (77.3%) presented as outpatients and 105 patients (22.6%) were inpatients presenting with UGIB. 71.6% of patients had an upper GI endoscopy within 24 hours. The main causes of bleeding were peptic ulcer (190 patients, 41%), erosive disease (162 patients, 34.9%) and variceal bleeding (47 patients, 10.1%). Forty four patients died (9.5%). Bleeding as an inpatient has a higher mortality risk than does bleeding as an outpatient (RR 2.4 IC 95% 1.2-4.6). An increasing number of comorbidities such as those described in the Rockall Score are also associated with a higher risk of dying (RR 2.5 IC 95% 1.1-5.4). CONCLUSION: UGIB as an inpatient and the presence of comorbidities should alert the clinician in identifying patients at higher risk of a fatal outcome, these patients should have a more aggressive management and be entitled to an early intervention.

Life expectancy, complications, and causes of death in patients with achalasia: results of a 33-year follow-up investigation.

BACKGROUND: Patients with achalasia require repeated invasive therapies and may experience multiple complications. The objectives of this study were to determine the incidence of such complications, causes of death, and life expectancy in 253 patients. METHODS: Patients consisted of two groups: group A comprised 177 patients with newly diagnosed achalasia; group B consisted of 76 patients in whom the diagnosis had been established in external institutions. All patients regularly underwent structured interviews and were reinvestigated if changes in health status occurred. Survival rates were determined by Kaplan-Meier estimates and were compared with those of an average German population. Causes of death were determined from hospital records, information supplied by private physicians, and from death certificates. RESULTS: Complete follow-up was obtained in 98.9% (group A) and in 100% (group B) of all patients. The observation period for group A ranged from 2 to 33 years and for group B from 2 to 26 years (disease duration: 4-68 years). The most frequent complications were reflux esophagitis (group A: 6.2%, group B: 19.7%) and megaesophagus (group A: 6.2%, group B: 21.0%). Thirty-six patients had died during follow-up. Five of these deaths were related to achalasia. In group A, the estimated 20-year survival rates in patients with achalasia [76% (95% confidence interval (CI): 66-85%)] did not significantly differ from those in controls 80% (95% CI: 71-89%). In group B, 25-year survival rates were also similar in patients [87% (95% CI: 78-97%)] and controls [86% (95% CI: 76-97%)]. CONCLUSION: Patients with achalasia experience a significant number of complications. Causes of death and life expectancy, however, do not differ from those of the average population.

Enfermedades oportunistas: experiencias en la población sudafricana con SIDA / Opportunistic diseases. experiences in the South African AIDS population

Se sabe que las enfermedades oportunistas liderean las causas de muerte en el SIDA, a pesar de su reducción sustancial tras el uso masivo de profilaxis primaria y de la terapia antirretroviral de alta eficacia. Se estudiaron los casos infectados con el virus de inmunodeficiencia humana, de Bojanala, que acudieron a la clínica del SIDA de Rustenburg entre abril del 2004 y noviembre del 2005. Se realizó una evaluación clínica especializada en búsqueda de enfermedades oportunistas y se individualizaron las investigaciones específicas, para su confirmación diagnóstica para conocer la morbilidad y la letalidad por enfermedades oportunistas en esta población y el impacto de la tuberculosis en la población inmunodeprimida estudiada. Se atendieron 4 339 pacientes, de los cuales 918 casos (21,2 por ciento) desarrollaron enfermedad oportunista y 98 fallecieron (10,7 por ciento). La letalidad en pacientes con enfermedades oportunistas fue 2,8 veces superior a la del resto. La tuberculosis y la candidiasis esofágica fueron las enfermedades oportunistas más frecuentemente asociadas con este virus. Se concluyó que las enfermedades oportunistas son aún causa mayor de morbilidad y letalidad en el SIDA, lidereadas por la tuberculosis y la esofagitis por candida en frecuencia, y por el síndrome de desgaste, el sarcoma de Kaposi y la meningitis criptocóccica en severidad, a pesar de una mejoría en supervivencia tras su atención y tratamiento oportuno.

It is known that opportunistic diseases are the leading causes of death from AIDS, in spite of their substantial reduction after the mass use of primary prophylaxis and of the highly efficient antiretroviral therapy. The AIDS infected cases in Bojanala that attended the AIDS Clinic in Rustenburg from April 2004 to November 2005, were studied. A specialized clinical evaluation was carried out searching opportunistic diseases, and the specific investigations were individualized for their diagnostic confirmation in order to know the morbidity and lethality from opportunistic diseases in this population, and the impact of tuberculosis on the studied immunodepressed population. 4 339 patients received attention, of whom 918 cases (21.2 percent) developed opportunistic diseases and 98 died (10.7 percent). Lethality in patients with opportunistic diseases was 2.8 times higher than that of the rest. Tuberculosis and esophageal candidiasis were the opportunistic diseases most frequently associated with this virus. It was concluded that the opportunistic diseases are still a main cause of morbidity and lethality in AIDS, leaded by tuberculosis and esophagitis produced by Candida as regards frequency, and by the wasting syndrome, Kaposi’s sarcoma and Cryptococcus meningitis in severity, in spite of an improvement attained in survival, resulting from their attention and timely treatment.

Enfermedades oportunistas: experiencias en la población sudafricana con SIDA / Opportunistic diseases. experiences in the South African AIDS population

Se sabe que las enfermedades oportunistas liderean las causas de muerte en el SIDA, a pesar de su reducción sustancial tras el uso masivo de profilaxis primaria y de la terapia antirretroviral de alta eficacia. Se estudiaron los casos infectados con el virus de inmunodeficiencia humana, de Bojanala, que acudieron a la clínica del SIDA de Rustenburg entre abril del 2004 y noviembre del 2005. Se realizó una evaluación clínica especializada en búsqueda de enfermedades oportunistas y se individualizaron las investigaciones específicas, para su confirmación diagnóstica para conocer la morbilidad y la letalidad por enfermedades oportunistas en esta población y el impacto de la tuberculosis en la población inmunodeprimida estudiada. Se atendieron 4 339 pacientes, de los cuales 918 casos (21,2 por ciento) desarrollaron enfermedad oportunista y 98 fallecieron (10,7 por ciento). La letalidad en pacientes con enfermedades oportunistas fue 2,8 veces superior a la del resto. La tuberculosis y la candidiasis esofágica fueron las enfermedades oportunistas más frecuentemente asociadas con este virus. Se concluyó que las enfermedades oportunistas son aún causa mayor de morbilidad y letalidad en el SIDA, lidereadas por la tuberculosis y la esofagitis por candida en frecuencia, y por el síndrome de desgaste, el sarcoma de Kaposi y la meningitis criptocóccica en severidad, a pesar de una mejoría en supervivencia tras su atención y tratamiento oportuno(AU)

It is known that opportunistic diseases are the leading causes of death from AIDS, in spite of their substantial reduction after the mass use of primary prophylaxis and of the highly efficient antiretroviral therapy. The AIDS infected cases in Bojanala that attended the AIDS Clinic in Rustenburg from April 2004 to November 2005, were studied. A specialized clinical evaluation was carried out searching opportunistic diseases, and the specific investigations were individualized for their diagnostic confirmation in order to know the morbidity and lethality from opportunistic diseases in this population, and the impact of tuberculosis on the studied immunodepressed population. 4 339 patients received attention, of whom 918 cases (21.2 percent) developed opportunistic diseases and 98 died (10.7 percent). Lethality in patients with opportunistic diseases was 2.8 times higher than that of the rest. Tuberculosis and esophageal candidiasis were the opportunistic diseases most frequently associated with this virus. It was concluded that the opportunistic diseases are still a main cause of morbidity and lethality in AIDS, leaded by tuberculosis and esophagitis produced by Candida as regards frequency, and by the wasting syndrome, Kaposis sarcoma and Cryptococcus meningitis in severity, in spite of an improvement attained in survival, resulting from their attention and timely treatment (AU)

Postanesthetic esophageal dysfunction in 13 dogs.

Thirteen dogs with postanesthetic esophageal dysfunction were identified; 10 of these animals had esophageal stricture. Regurgitation was noted in six dogs during the inciting anesthetic event. Clinical problems common to all dogs included vomiting/regurgitation and weight loss. Coughing was noted in six dogs, and aspiration pneumonia was present in four of these dogs. The associated mortality rate was 23%. The duration of symptoms ranged from 17 to 150 days, and the diagnosis was often delayed (up to 76 days from onset of clinical signs to diagnosis). Postanesthetic esophageal dysfunction was a debilitating and costly problem that developed in one dog despite current preventative treatment.

Survival differences in Austrian patients with the acquired immunodeficiency syndrome.

We investigated the association of clinical and demographic factors on survival of the 901 AIDS cases diagnosed until 31 December 1992 and reported to the Austrian Health Authorities up to 20 January 1994. The overall estimated median survival of patients with AIDS increased substantially from 8 months in 1987 to 16 months in 1988, although this increase was not significant by the log-rank test. However, the differences in hazard rates were larger at the beginning of the survival curve: between 1987 and 1988 the proportion surviving at 1 year increased from 41 to 62%, compared to an increase of the proportion surviving at 2 years from 30 to 35% (Breslow test, p value 0.008). AIDS patients diagnosed between 1988 and 1992 (n = 755) were analyzed in more detail. Multivariate survival analysis revealed a shorter survival for those with residence in Eastern Austria, recipients of blood products, individuals with unknown transmission risk, those presenting with two AIDS indicator diseases and those with higher age at AIDS diagnosis. Candidal esophagitis as AIDS indicator disease was associated with longer survival. One hundred eighty-eight of the 755 AIDS patients (24.9%) died within the first 3 months after diagnosis of AIDS. We conclude that the survival time for AIDS patients has improved considerably after 1987, but survival is still very poor. Several factors have been shown to predict survival of patients with AIDS in Austria. Death within the first 3 months after the diagnosis of AIDS occurred at a relatively high frequency in Austrian AIDS patients. This may be caused by difficulties in the use of health care facilities or by the lack of awareness of HIV infection before diagnosis of AIDS either by patient or care provider.