Intralesional photodynamic therapy induces apoptosis in basal cell carcinoma and Bowen's disease through caspase 3 and granzyme B.

BACKGROUND: Photodynamic therapy (PDT) is used to treat cutaneous cancers. It may induce cell death through direct and indirect means, including apoptosis, inflammation and certain immune mechanisms, with the depth of penetration as a potential modifying factor. OBJECTIVES: To examine the pathways of apoptosis in the intralesional PDT of basal cell carcinoma (BCC) and intraepidermal squamous cell carcinoma (Bowen's disease). METHODS: Sixteen patients with superficial or nodular BCC and Bowen's disease were treated with intralesional aminolevulinic acid-PDT. Biopsies were taken at baseline and 24 h post-PDT, and sections were examined by immunohistochemistry for the expression of markers of apoptosis, such as caspase 3, involved in the intrinsic apoptotic pathway, granzyme B, a caspase-independent apoptotic mediator, and the proapoptotic markers BAX and BAK. RESULTS: Apoptotic cells stained with TUNEL showed statistically significant staining at 24 h post PDT (p < 0.01 in both BCC and Bowen's lesions). Caspase 3 (p < 0.01 in BCC and p < 0.05 in Bowen's) and granzyme B (p < 0.01 in BCC and p < 0.01 in Bowen's) were significantly increased at 24 h post-PDT. BAX expression was apparently increased compared to baseline in Bowen's lesions at 24 h post-PDT, whereas Bak was upregulated both in BCC and Bowen's disease at baseline and at 24 h post-PDT. CONCLUSION: Intralesional PDT induces apoptosis in BCC and Bowen's disease via common and alternative apoptotic pathways involving granzyme B. Proapoptotic factors Bak in both BCC and Bowen and Bax in Bowen's disease appear to increase by intralesional PDT at 24 h.

A Case Report of Aggressive Chronic Rhinosinusitis with Nasal Polyps Mimicking Sinonasal Malignancy.

INTRODUCTION: Cases of extensive nasal polyps rarely occur and may mimic more aggressive lesions of the nose and paranasal sinuses. A case of extensive nasal polyposis with unusually aggressive behavior and its management is presented. PRESENTATION OF CASE: A 27-year-old male patient visited the emergency department of a tertiary center, complaining of recurrent episodes of epistaxis. The patient presented with a large polypoid lesion protruding from the right nostril and producing asymmetry of the face. Diagnostic imaging illustrated a lesion of the right maxillary sinus producing excessive bone remodeling and extension into neighboring structures in every direction. Fine limits were noted, however, with no invasive characteristics. Biopsy under local anesthesia was performed, showing findings consistent with nonspecific inflammation. Open surgery through a lateral rhinotomy under general anesthesia was performed, and the mass was readily mobilized and removed. No macroscopic invasion of neighboring structures was noted. Permanent histology confirmed the diagnosis of nasal polyposis. Postoperative follow-up has shown no evidence of recurrence after 12 months. CONCLUSION: Nasal polyps do not typically expand in an aggressive manner, producing bone resorption or extending into neighboring structures. However, nasal polyposis should be included in the differential diagnosis of nasal tumors with such behavior.

Surgery for colorectal cancer in elderly patients: is there such a thing as being too old?

INTRODUCTION: The overall increase in life expectancy causes a rapid increase in number of elderly patients needing colorectal surgery. It remains unclear if there is a significant risk factor in patients over 80 years of age for postoperative morbidity and mortality. For this reason we investigated the perioperative, outcome and long-term survival after surgery for colorectal cancer in our hospital. MATERIALS AND METHODS: We retrospectively analysed a database containing information about patients who underwent surgery for colorectal cancer from January 2010 to December 2015 at the St. Bernhard Hospital in Kamp-Lintfort, Germany. The last follow-up date was 31th of December 2017. RESULTS: A total of 232 patients were enrolled and analysed in this study. All patients were separated in tow groups depending in age. The first group was ≥80 years old (n=49). The second group was <80 years old (n=183). High ASA-Scores (≥3) were detectable more often in elderly patients (p<0,05). Elderly and young patients had a similar risk for postoperative anastomosic leakages (p=0,047). Likewise there were no significant differences regarding the Dindo-Clavien-Classification (p=0,13). The mortality within the first 30 days after surgery was significant elevated for elderly patients compared to younger patients (p=0,04). Also the overall 1-year survival was 90% for the younger and 73,5% for the older study group (p<0,05) Conclusion. Both the short-term outcome and long-term survival rate after colorectal surgery for cancer are worse for patients older than 80 years of age. After interpretation of all data it remains unclear if the age itself is still the biggest risk factor. When old patients have a good ASA-Score and no severe comorbidities, colorectal surgery remains safe even for patients older than 80 years.

Primary peritoneal adenocarcinoma as content of an incarcerated umbilical hernia: A case-report and review of the literature.

INTRODUCTION: Umbilical hernia is a common finding in many cases, posing potentially life-threatening complications, such as incarceration or strangulation. The presence of malignancy in hernia sacs is, however, rather rare. PRESENTATION OF CASE: Here we report on a case of primary peritoneal adenocarcinoma found through histological examination of omental tissue, resected due to an incarcerated umbilical hernia of an 84-years-old woman. There was no macroscopic sign of malignancy during operation; only after routine examination of histological sections the diagnosis was found. DISCUSSION: To our knowledge this is the first report of primary peritoneal cancer as content of an umbilical hernia. This is a rare neoplasm and histologically identical to epithelial ovarian carcinoma. For this reason, the diagnosis is usually based on the histological finding and exclusion of a primary ovarian tumor. Primary peritoneal cancer has a poor outcome in general. Early diagnosis is, therefore, essential for effective treatment. CONCLUSION: Histological analysis of resected hernia sac or content should be performed routinely to discover malignant diseases in the background of a hernia.

Follicular variant of papillary thyroid cancer in Alström syndrome.

Alström syndrome (AS) is an autosomal recessive disorder, characterized by cone-rod dystrophy, sensorineural hearing loss, obesity, hyperinsulinemia with insulin resistance, type 2 diabetes mellitus and progressive pulmonary, hepatic and renal dysfunction. AS is caused by mutations in the ALMS1 gene, located on the short arm of chromosome 2. We report a 35-year-old woman with known history of AS, who developed a follicular variant of papillary thyroid carcinoma. To our knowledge this is the first association of AS with thyroid malignancy, among the approximately 450 cases reported since the first description of the syndrome. We conclude that papillary thyroid carcinoma should be considered in the differential diagnosis of thyroid nodules in patients with AS.

Spinal surgery in patients with Parkinson's disease: unsatisfactory results, failure and disappointment.

Previous studies on spinal surgery in PD patients report an exceptionally high rate of complications. Failure and re -operation are frequent outcomes. This is a retrospective case series with the aim of establishing the rate of complications in patients with concomitant Parkinson's disease. Ten patients were subjected to spinal surgery from 2005 to 2009. The indications and type of operation varied. Cases of Failed Back Surgery and re-operation were sought. Follow - up was between 6 - 42 months. All 10 patients presented some clinical or radiological complication. The most common complications were screw pull - out and progressive spinal deformity. Re - operations were performed in 5 patients, while clinical and radiological results were poor in the majority of cases. Patients with Parkinson's disease have a very high complication rate and often have to undergo revision surgery. This particular group of patients should be informed of the increased risk of failure and be closely followed - up on a regular basis.

Cytologic diagnosis of spinal cord ependymoma in cerebrospinal fluid.

Ependymoma cells are known to rarely exfoliate into cerebrospinal fluid (CSF). However, the frequency of CSF involvement in patients with ependymoma is unclear, and to the author's knowledge the cytomorphologic features of tumour cells have not been well described to date. In this study, the CSF findings in a patient with ependymoma and the cytopathological features of this tumor are reported. The patient presented at the University Hospital of Heraklion, Crete, suffering from a chest to back pain. Computed tomography, scanning and magnetic resonance imaging (MRI) were performed and a mass of 3x2 cm in the thoracic aspect of the spinal cord was found. A sample of cerebrospinal fluid (CSF) was sent for cytologic examination and a diagnosis of ependymoma was made. A biopsy was performed and histology confirmed the cytologic diagnosis of ependymoma grade II (WHO). Exfoliated cells from ependymomas of spinal cord are rarely recognizable in CSF samples. Except in patients with myxopapillary tumours and anaplastic tumours, cytomorphologic features of ependymoma have been described only in case reports of intraoperative imprinting or fine needle aspiration biopsies (FNABs) and not in CSF cytology.

Apoptosis and cell proliferation correlated with tumor grade in patients with lung adenocarcinoma.

BACKGROUND: Apoptosis and cell proliferation in patients with adenocarcinoma of the lung have not been well described with relation to fine-needle aspiration biopsies (FNABs). To investigate the contribution of apoptosis to the growth of adenocarcinoma of the lung, both apoptosis and cell proliferation were analysed for correlation with the grade of the tumor. PATIENTS AND METHODS: Fifty tumors from 50 patients with adenocarcinoma of the lung were studied. Twelve tumors were well-differentiated, 22 were moderately differentiated and 16 were poorly differentiated. The detection of DNA fragments in situ using the terminal deoxyribonucleotidyl transferase-mediated dUTP-digoxigenin nick-end labeling (TUNEL) assay was applied to investigate active cell death (apoptosis) and the MIB-1 antigen was used to investigate cell proliferation. RESULTS: The TUNEL indices were 0.55±0.09, 0.90±0.33 and 3.1±0.99 in well-, moderately and poorly differentiated adenocarcinoma of the lung respectively. The MIB-1 antigen labeling indices were 7.1±0.12, 14.3±3.5 and 28.7±6.9, respectively, in the same order of tumor differentiation. The differences in both TUNEL and MIB-1 labeling indices were significant between well-, moderately and poorly differentiated adenocarcinoma of the lung and a positive correlation was found between the TUNEL indices and the MIB-1 indices. CONCLUSION: Apoptosis (cell death) and cell proliferation increases as the grade of differentiation decreases in adenocarcinoma of the lung, suggesting a rapid turn over of the tumor cells in tumors with a lower grade of differentiation.

Ethnic differences in physiological cardiac adaptation to intense physical exercise in highly trained female athletes.

BACKGROUND: Ethnicity is an important determinant of cardiovascular adaptation in athletes. Studies in black male athletes reveal a higher prevalence of electric repolarization and left ventricular hypertrophy than observed in white males; these frequently overlap with those observed in cardiomyopathy and have important implications in the preparticipation cardiac screening era. There are no reports on cardiac adaptation in highly trained black females, who comprise an increasing population of elite competitors. METHODS AND RESULTS: Between 2004 and 2009, 240 nationally ranked black female athletes (mean age 21+/-4.6 years old) underwent 12-lead ECG and 2-dimensional echocardiography. The results were compared with 200 white female athletes of similar age and size participating in similar sports. Black athletes demonstrated greater left ventricular wall thickness (9.2+/-1.2 versus 8.6+/-1.2 mm, P<0.001) and left ventricular mass (187.2+/-42 versus 172.3+/-42 g, P=0.008) than white athletes. Eight black athletes (3%) exhibited a left ventricular wall thickness >11 mm (12 to 13 mm) compared with none of the white athletes. All athletes revealed normal indices of systolic and diastolic function. Black athletes exhibited a higher prevalence of T-wave inversions (14% versus 2%, P<0.001) and ST-segment elevation (11% versus 1%, P<0.001) than white athletes. Deep T-wave inversions (-0.2 mV) were observed only in black athletes and were confined to the anterior leads (V(1) through V(3)). CONCLUSIONS: Systematic physical exercise in black female athletes is associated with greater left ventricular hypertrophy and higher prevalence of repolarization changes than in white female athletes of similar age and size participating in identical sporting disciplines. However, a maximal left ventricular wall thickness >13 mm or deep T-wave inversions in the inferior and lateral leads are rare and warrant further investigation.

Electrocardiographic screening in athletes: the time is now for universal screening.

Regular physical exercise reduces cardiovascular morbidity and mortality. A small proportion of athletes, however, are at increased risk of exercise-related sudden cardiac death (SCD) as a result of quiescent cardiac anomalies. The preventable nature of such deaths has prompted the medical and sporting governing bodies to recommend preparticipation cardiovascular screening (PPS) in young athletes (< or =35 years) to permit the identification of potentially fatal disorders. Although evidence from the Italian experience suggests that electrocardiographic screening of young athletes has led to a significant reduction in SCD from cardiomyopathies, considerable controversy relating to the efficacy, cost-effectiveness and the impact of false-positive results of PPS still exists. This review presents an appraisal of all the available scientific evidence, attempting to resolve the concerns of the antagonists and examine how PPS compares with the World Health Organization screening criteria, providing compelling justifications for the implementation of universal PPS in young, competitive athletes.

Transforming a conventional theatre into a gynaecological endoscopy unit.

OBJECTIVE: Most minimally invasive procedures are now performed in operating rooms that were originally designed for traditional open surgery. We designed an endoscopic theatre based on our experience with special features specific for gynaecological endoscopy. METHOD: We designed a detailed plan with an architect's aid of a gynaecological unit (based on a Greek presidential decree published in 1991). The space utilized was that of a conventional theatre. RESULTS: With the architectural plan we anticipated every area needed in a gynaecological endoscopic theatre. A twin theatre was considered appropriate in order for the surgical team to operate alternatively in one theatre while the other is being cleaned and prepared for use. CONCLUSION: The design of a unit dedicated to gynaecologic laparoscopy is a multidisciplinary task where the endoscopic surgeon undertakes an active and prominent role. It is a project with great benefits and rewards for all parties involved. We present our design for evaluation.

Polymyositis in a patient with recurring ovarian cancer and history of unrelated breast cancer.

BACKGROUND: Polymyositis (PM) is an idiopathic inflammatory myopathy. Occasionally, it may present as a paraneoplastic syndrome and it is strongly associated with ovarian and weakly with breast cancer. We present here a case of a 60-year-old patient with sequential breast and ovarian (second primary) carcinomas followed by PM as a paraneoplastic disorder. CASE REPORT: The patient had been diagnosed with stage I breast carcinoma 3 years ago and had been treated with conservative surgery followed by radiotherapy and six cycles of chemotherapy (CMF). One and a half year later an ovarian carcinoma was diagnosed for which the patient underwent abdominal hysterectomy oophorectomy and omentectomy. The pathological report characterized it as second primary. Adjuvant chemotherapy with carboplatin and taxol was administered. Fourteen months after the initial laparotomy, the patient was re-operated due to ovarian carcinoma recurrence which was involving all lesser pelvis organs. After a successful radical removal of the recurrence the patient developed a fully expressed PM. This case serves to remind that this disease can occur as a paraneoplastic disorder.

Occupational exposures to body fluids among medical students. A seven-year longitudinal study.

BACKGROUND: Medical students may be at high risk for occupational exposures to blood. OBJECTIVE: To measure the frequency of medical students' exposure to infectious body substances, to identify factors that affect the probability of such exposure, and to suggest targets for the prevention of such exposure. DESIGN: Review of all exposures reported by medical students at the University of California, San Francisco, School of Medicine. SETTING: Teaching hospitals affiliated with the University of California, San Francisco. PARTICIPANTS: Third- and fourth-year medical students from the classes of 1990 through 1996 at the University of California, San Francisco, School of Medicine. INTERVENTIONS: A needlestick hotline service was instituted at teaching hospitals affiliated with the University of California, San Francisco, and a required course was created to train students in universal precautions and clinical skills before the beginning of the third-year clerkship. MEASUREMENTS: Reports of exposures made to the needlestick hotline service, including type of exposure, training site, clerkship, and time of year. RESULTS: 119 of 1022 medical students sustained 129 exposures. Of these exposures, 82% occurred on four services: obstetrics-gynecology, surgery, medicine, and emergency medicine. The probability of exposure was not related to graduation year, clerkship location, previous clerkship experience, or training site. Surveys of two graduating classes at the beginning and end of the study showed that the percentage of exposures reported increased from 45% to 65% over the 7-year study period. Thus, the reported injury rates represent minimum estimates of actual occurrences. Human immunodeficiency virus infection and hepatitis were not reported, although follow-up was limited. CONCLUSIONS: Instruction in universal precautions and clinical procedures is not sufficient to prevent exposures to blood during medical training. Medical schools must assume greater responsibility for ensuring that students are proficient in the safe conduct of clinical procedures and must develop systems that protect students so that they can report and learn from their mistakes.

Combination chemotherapy with docetaxel, vinorelbine and cisplatin as first-line treatment of advanced non-small-cell lung cancer: a multicenter phase II study of the Greek Cooperative Group for Lung Cancer.

Vinorelbine, docetaxel and cisplatin have documented single-agent activity in non-small-cell lung cancer (NSCLC); a multicenter phase II trial was initiated in order to evaluate the tolerance and efficacy of their combination. A total of 24 chemotherapy-naive patients with measurable stage IIIB or IV NSCLC and performance status (PS; WHO) 0-2 entered the study. Vinorelbine (20 mg/m2 i.v.) was given on days 1 and 15, cisplatin (60 mg/m2) on day 1, and docetaxel (100 mg/m2) on day 16, in cycles of 28 days. Recombinant human granulocyte colony-stimulating factor (150 microg/m2 s.c.) was administered prophylactically from day 17 to day 27. One pathological complete (4%) and six partial responses (25%) were documented (overall response 29%; 95% CI 11.6-49.2%). A total of five patients (21%) had stable and 12 (50%) progressive disease. The median duration of response was 28 weeks and the median time to tumor progression 36 weeks; the median survival was 20 weeks. Grade 3-4 neutropenia occurred in 16 patients (67%) while 13 of them (54%) developed febrile neutropenia. Grade 4 mucositis occurred in two patients (8%) and one of them also presented grade 4 diarrhea. There were four treatment-related deaths: two from sepsis, one from massive hemoptysis due to a pulmonary abscess and one from acute myocardial ischemia 7 days post-chemotherapy. In conclusion, the high incidence of neutropenic episodes and treatment-related deaths led to an early discontinuation of patient enrollment. This combination, in the schedule and the doses used, could not be recommended for off protocol treatment of patients with advanced NSCLC.

A comparison of two methods to teach smoking-cessation techniques to medical students.

PURPOSE: To evaluate two smoking-cessation practice exercises, one using standardized patients (SPs), the other using role playing by medical students. METHOD: In the spring of 1994 all 120 first-year University of California, San Francisco, School of Medicine Students were given lectures on the health effects of smoking and how physicians can help patients quit. Afterward some of the students were randomly assigned to two groups in which to practice counseling patients: Group 1 (n = 35) used SPs, Group 2 (n = 37) used role playing. Each of the Group 1 students practiced smoking-cessation techniques with an SP; the SP evaluated the student on cognitive and communication skills, assigned an overall rating, and provide feedback using a standardized form. The Group 2 students (as well as the 48 students not assigned to a group) role-played in pairs and used the same form to provide feedback. All the students evaluated their respective practice practices. Two weeks later 24 Group 1 and 31 Group 2 students participated in a clinic-skills-assessment exercise using SPs. As in the Group 1 practice exercise, each student was evaluated by an SP on cognitive and communication skills and assigned an overall rating. Data were analyzed through a number of statistical methods. The cost of the SP program was determined. RESULTS: The Group 1 students rated their practice exercise much more favorably than did the Group 2 students. However, there was no significant difference between the groups in their ratings by the SPs on the clinical-skills-assessment exercise. The use of SPs cost a great deal more than did the use of role playing. CONCLUSION: Although the students rated the SPs higher than they did the role playing, the two tools produced similar levels of skills attainment. The data suggest that having students practice smoking-cessation techniques through role playing may be as effective as using the more extensive SPs.

Effect of growth hormone replacement on wound healing in healthy older men.

The secretion of growth hormone, an important anabolic agent, declines with aging. We hypothesize that growth hormone levels (measured as insulin-like growth factor-1) correlate with postoperative tissue repair in otherwise healthy, elderly persons. The goal was to determine whether growth hormone supplementation can improve wound healing in this circumstance. We conducted a randomized controlled double-blind trial of 6 months of growth hormone replacement or placebo in 28 healthy older men (>69 years of age) with low baseline plasma insulin-like growth factor-1. Growth hormone doses were adjusted to elevate insulin-like growth factor-1 to levels expected in younger adults. Wound healing was tested by implanting 10 cm expanded polytetrafluoroethylene porous tubes for 10 days, then measuring the content of collagen (as hydroxyproline), DNA, and total protein. Hydroxyproline content was 15% greater in the wounds of the growth hormone group (n = 13) compared with the placebo group (n = 15), (4.52 +/- 0.94 versus 3.92 +/- 0.78 microg/cm; p = 0.04). Therefore, healthy older men who took growth hormone had enhanced reparative collagen deposition during the wound healing process. This action may be clinically useful after selected surgery or trauma in the elderly.

Treatable abdominal pathologic conditions and unsuspected malignant neoplasms at autopsy in veterans who received mechanical ventilation.

STUDY OBJECTIVE: To determine, in medical patients who received mechanical ventilation, the frequency and types of major unexpected diagnoses at autopsy that, if known before death, would probably have led to improved survival (class I errors) or substantively changed management but not survival (class IIB errors). DESIGN: Retrospective cohort study. SETTING: Six medical intensive care units in a Department of Veterans Affairs Cooperative Study. PATIENTS: One hundred seventy-two autopsied patients of the 401 veterans who received mechanical ventilation and died in the hospital. RESULTS: The class I error rate was 12%. Abdominal pathologic conditions--abscesses, bowel perforations, or infarction--were as frequent as pulmonary emboli as a cause of class I errors. While patients with abdominal pathologic conditions generally complained of abdominal pain, results of examination of the abdomen were considered unremarkable in most patients, and the symptom was not pursued. Six percent of patients had extensive malignant neoplasms (class IIB errors). CONCLUSIONS: Atypical presentation of potentially treatable abdominal pathologic conditions is a common cause of class I errors in veterans who receive mechanical ventilation. Conversely, several patients with unrecognized terminal conditions underwent intensive intervention. If the information gained at autopsy had been known before death, management would have probably changed substantively in 18% of patients.