Radical Resection of Periampullary Tumors in the Elderly: Evaluation of Long-term Results

Increasingly, patients of advanced age are coming for evaluation of periampullary tumors. Although several studies have demonstrated the safety of resecting periampullary tumors in older patients, few long-term survival data have been reported. Between 1983 and 1992 various periampullary masses were resected in 70 patients over age 65 (range 65–87 years). Total pancreatectomy was performed in 11 patients, and 59 patients underwent pancreaticoduodenectomy. The mean duration of hospitalization was 17 ± 15 days. Major complications occurred in 27 patients (39%), and operative mortality rate was 8.5%. Overall median survival was 24 months; and 5-year survival was 25%. Perioperative outcome was compared in patients aged 65 to 74 years and in patients ≥75 years old. The older age group required longer periods in the surgical intensive care unit postoperatively, but the long-term survival was similar in the two age groups. Radical resection with the intent to cure periampullary tumors is safe in selected patients of advanced age, and long-term survival is in the range of expected survival for younger patients with the same tumors.     

Cyclin d1 is a valuable prognostic marker in oropharyngeal squamous cell carcinoma.

BACKGROUND: The current tumor-node-metastasis system is inadequate to accurately classify patients in terms of prognosis. Thus, with the availability of recently developed molecular tools, considerable interest lies in discovering prognostic markers in order to guide treatment decisions. In this study, we sought to determine the prognostic significance of the cell cycle regulator cyclin D1 in oropharyngeal squamous cell carcinoma (OSCC). EXPERIMENTAL DESIGN: We studied the protein expression levels of cyclin D1 on a tissue microarray composed of 63 OSCCs with long-term follow-up data available. Protein expression was analyzed with an automated in situ quantitative (AQUA) method which allows preservation of tissue morphology while quantifying protein expression in paraffin-embedded tissue. RESULTS: The mean follow-up time was 35 months. High cyclin D1 nuclear expression was associated with increased 5-year local recurrence rate (48% versus 15%), inferior 5-year disease-free survival (16% versus 58%), and inferior 5-year overall survival (17% versus 53%). In multivariate Cox regression, high nuclear cyclin D1 expression was an independent predictor for local recurrence, disease-free survival, and overall survival at 5 years. CONCLUSIONS: Our results indicate that quantitative assessment of nuclear cyclin D1 expression level by automated in situ quantitative analysis is a strong predictor for outcome in OSCC. Thus, cyclin D1 may be a potential target for molecular intervention in patients with oropharyngeal squamous cell cancer.     

18F]fluorodeoxyglucose uptake by positron emission tomography predicts outcome of non-small-cell lung cancer.

PURPOSE: To determine whether the standardized uptake value (SUV) of [(18)F]fluorodeoxyglucose uptake by positron emission tomography could be a prognostic factor for non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: One hundred sixty-two patients with stage I to IIIb NSCLC were analyzed. Overall survival (OS), disease-free survival (DFS), distant metastasis-free survival (DMFS), and local-regional control (LRC) were calculated by the Kaplan-Meier method and evaluated with the log-rank test. The prognostic significance was assessed by univariate and multivariate analyses. RESULTS: There were 93 patients treated with surgery and 69 patients treated with radiotherapy. A cutoff of 5 for the SUV for the primary tumor showed the best discriminative value. The SUV for the primary tumor was a significant predictor of OS (P = .02) in both groups. Low SUVs ( 5.0; surgery group, P = .02; radiotherapy group, P = .0005). Low SUVs ( 5.0; stage I or II, P = .02; stage IIIa or IIIb, P = .004). However, using the same cutoff point of 5, the SUV for regional lymph nodes was not a significant indicator for DFS (P = .19), LRC (P = .97), or DMFS (P = .17). The multivariate analysis showed that the SUV for the primary tumor was a significant prognostic factor for OS (P = .03) and DFS (P = .001). CONCLUSION: The SUV of the primary tumor was the strongest prognostic factor among the patients treated by curative surgery or radiotherapy.     

Chronic inhalation exposure to mainstream cigarette smoke increases lung and nasal tumor incidence in rats.

An animal model of lung carcinogenicity induced by chronic inhalation of mainstream cigarette smoke would be useful for research on carcinogenic mechanisms, smoke composition-response relationships, co-carcinogenicity, and chemoprevention. A study was conducted to determine if chronic whole-body exposures of rats would significantly increase lung tumor incidence. Male and female F344 rats (n = 81 to 178/gender) were exposed whole-body 6 h/day, 5 days/week for up to 30 months to smoke from 1R3 research cigarettes diluted to 100 (LS) or 250 (HS) mg total particulate matter/m(3), or sham-exposed to clean air (C). Gross respiratory tract lesions and standard lung and nasal sections were evaluated by light microscopy. A slight reduction of survival suggested that the HS level was at the maximum tolerated dose as commonly defined. Cigarette smoke exposure significantly increased the incidences of non-neoplastic and neoplastic proliferative lung lesions in females, while nonsignificant increases were observed in males. The combined incidence of bronchioloalveolar adenomas and carcinomas in females were: HS = 14%; LS = 6%; and C = 0%. These incidences represented minima because only standard lung sections and gross lesions were evaluated. Mutations in codon 12 of the K-ras gene occurred in 4 of 23 (17%) tumors. Three mutations were G to A transitions and one was a G to T transversion. The incidence of neoplasia of the nasal cavity was significantly increased at the HS, but not the LS level in both males and females (HS = 6%, LS = 0.3%, C = 0.4% for combined genders). These results demonstrate that chronic whole-body exposure of rats to cigarette smoke can induce lung cancer.     

Previously undescribed palpebral branch from the infraorbital canal: Application to surgery of the eyelid and treatment of orbital floor fractures

The sensory innervation of the inferior eyelid is mainly derived from the inferior palpebral branch (IPb) of the infraorbital nerve (ION). This study aimed to investigate another, to our knowledge, previously unknown branch, and elucidate its location and distribution. Twelve sides from seven fresh frozen cadaveric Caucasian heads were used in this study. The specimens were derived from two male and four female adult cadavers age. The diameter of the IPb of the ION (D1) and branch arising from the upper wall of the infraorbital canal (D2), and distance between the branching points of this branch and the anterior border of the orbit floor (L1) was measured. A branch to the lower eyelid was found arising from the infraorbital canal on the majority of sides. D1 ranged from 0.4 to 1.1 mm. The branch arising from the upper wall of the infraorbital canal was found 10 sides (83%). D2 ranged 0.6 to 1.0 mm. L1 ranged from 10.2 to 19.8 mm. All of the branches arising from the upper wall of the infraorbital canal (10 sides) primarily innervated to the inferior eyelid. We suggest this branch should be named the “posterior IPb” of the ION. Knowledge of this branch might decrease sensory loss following invasive procedures of the lower orbit. Clin. Anat. 30:835–838, 2017. © 2017Wiley Periodicals, Inc.     

Optimized Adenovirus-Antibody Complexes Stimulate Strong Cellular and Humoral Immune Responses against an Encoded Antigen in Na?ve Mice and Those with Preexisting Immunity

The immune response to recombinant adenoviruses is the most significant impediment to their clinical use for immunization. We test the hypothesis that specific virus-antibody combinations dictate the type of immune response generated against the adenovirus and its transgene cassette under certain physiological conditions while minimizing vector-induced toxicity. In vitro and in vivo assays were used to characterize the transduction efficiency, the T and B cell responses to the encoded transgene, and the toxicity of 1 × 10¹¹ adenovirus particles mixed with different concentrations of neutralizing antibodies. Complexes formed at concentrations of 500 to 0.05 times the 50% neutralizing dose (ND₅₀) elicited strong virus- and transgene-specific T cell responses. The 0.05-ND₅₀ formulation elicited measurable anti-transgene antibodies that were similar to those of virus alone (P = 0.07). This preparation also elicited very strong transgene-specific memory T cell responses (28.6 ± 5.2% proliferation versus 7.7 ± 1.4% for virus alone). Preexisting immunity significantly reduced all responses elicited by these formulations. Although lower concentrations (0.005 and 0.0005 ND₅₀) of antibody did not improve cellular and humoral responses in naïve animals, they did promote strong cellular (0.005 ND₅₀) and humoral (0.0005 ND₅₀) responses in mice with preexisting immunity. Some virus-antibody complexes may improve the potency of adenovirus-based vaccines in naïve individuals, while others can sway the immune response in those with preexisting immunity. Additional studies with these and other virus-antibody ratios may be useful to predict and model the type of immune responses generated against a transgene in those with different levels of exposure to adenovirus.     

A 10-year follow up of a paging service for people with memory and planning problems within a healthcare system: How do recent users differ from the original users?

In 2003 Wilson, Scott, Evans, and Emslie published a report of a new healthcare resource; a paging system designed to reduce the everyday problems of people with neurological deficits who experience memory and/or planning problems. The system was established following several research studies carried out to evaluate its effectiveness. Information was collected on the first 40 clients recruited to the service. The purpose of the present study is to determine how the service might have changed over a 10-year period. The most recent users of the service (N?=?40) have been compared with the original cohort of 40 clients. In addition, in 2007 clients were given the opportunity to use their mobile telephones to receive messages; 17 chose to do so. There was no difference in age between the telephone users compared to the pager users, but those using a pager were less likely to have sustained a traumatic brain injury (TBI) and were more likely to be longer post-insult. There were no significant differences in the gender or ages of the people using the pager compared with those using the telephone service. However, the mean overall time since injury for the last 40 referrals was 9.48 years compared to 4.56 years for the original cohort. Both cohorts comprised several diagnostic groups; clients with TBI formed the largest subgroup, followed by those with stroke. This is typical of patients seen for rehabilitation, with other diagnostic groups forming a smaller percentage. We wanted to determine whether the range of diagnoses was similar over the 10-year period. Despite slight differences, we found a similar range of patients referred. In both cohorts the most frequent messages sent each week related to medication (27.9% in the first compared to 28.6% in the second). More messages were sent regarding mood management in the second cohort. No such messages were sent to the first 40 clients, whereas over 27 per week were sent to the last 40. Fewer health authorities (N?=?21) were referring after 10 years in comparison with 26 referrers for the first cohort.     

Responses to Subchronic Inhalation of Low Concentrations of Diesel Exhaust and Hardwood Smoke Measured in Rat Bronchoalveolar Lavage Fluid

Abstract

Air pollution exposure is associated with adverse health effects, but the causal components and mechanisms are unclear. We compared effects of daily exposure for 6 mo to diesel exhaust (DE) or hardwood smoke (HWS) at 4 concentrations between 30 and 1000 μg/³ of total particulate matter, or filtered air, in male and female rats. Lung lavage fluid was assayed for toxicity indicators, cytokines, and glutathione. Statistical analyses included pairwise comparisons with control and exposure-related trends, modeled using techniques that facilitated evaluation of nonlinear exposure effects. Lactate dehydrogenase increased with exposure concentration in DE-exposed females, but in other groups, low exposure concentrations caused increases while higher concentrations had less effect. Total protein in the HWS-exposed males and females followed similar patterns. Alkaline phosphatase increased in DE-exposed females, but decreased in HWS-exposed males and females. β-Glucuronidase decreased in HWS- and DE-exposed males, but HWS-exposed females showed decreases at low exposure concentrations and weak increases at higher exposure concentrations. Macrophage inflammatory protein-2 decreased in HWS-exposed males and females and DE-exposed females. Tumor necrosis factor-α levels decreased in DE-exposed females and males, but HWS-exposed males showed small increases. DE did not affect total glutathione in either gender, but HWS decreased glutathione in females, while in males, increases at low exposure concentrations but not at higher exposure levels were observed. Thus, these two combustion emissions differentially affect lung responses, with gender affecting response patterns. Furthermore, effects may be nonmonotonic functions of exposure levels, with maximal responses in environmentally or occupationally relevant exposure ranges.