Cholesteatoma, attic, ossicles

Extension of cholesteatome in mastoid and middle ear occurs frequently. It is necessary to know the type of cholesteatoma extension and to decide the type of surgery to be done. The cholesteatome of the ear can extend to tie mastoid, attic and middle ear. Extension to intracranial region occurs in some cases but not discussed in the present review. Nowadays patients prefer hearing reconstruction even if only one ear is affected and the operation is modified accordingly.     

Stress,coping, and hope

Hope is discussed in many literatures and from many perspectives. In this essay hope is discussed from the vantage of psychology and stress and coping theory. Hope and psychological stress share a number of formal properties: both are contextual, meaning‐based, and dynamic, and both affect well‐being in difficult circumstances. Two assumptions underlie this essay: (1) hope is essential for people who are coping with serious and prolonged psychological stress; and (2) hope is not a perpetually self‐renewing resource; it has peaks and valleys and is at times absent altogether. The relationship between hope and coping is dynamic and reciprocal; each in turn supports and is supported by the other. This relationship is illustrated with two adaptive tasks common across situations that threaten physical or psychological well‐being—managing uncertainty and coping with a changing reality. The essay describes ways in which coping fosters hope when it is at low ebb as well as ways in which hope fosters and sustains coping over the long term. Copyright © 2010 John Wiley & Sons, Ltd.     

Occurrence,Efficacy, Metabolism,and Toxicity of Triclosan

Triclosan has broad-spectrum anti-microbial activity against most gram-negative and gram-positive bacteria. It is widely used in personal care products, household items, medical devices, and clinical settings. Due to its extensive use, there is potential for humans in all age groups to receive life-time exposures to triclosan, and, indeed, triclosan has been detected in human tissues and the environment. Data gaps exist regarding the chronic dermal toxicity and carcinogenicity of triclosan, which is needed for the risk assessment of triclosan. The US Food and Drug Administration (FDA) nominated triclosan to the National Toxicology Program (NTP) for toxicological evaluations. Currently, the NTP is conducting several dermal toxicological studies to determine the carcinogenic potential of triclosan, evaluate its endocrine and developmental-reproductive effects, and investigate the potential UV-induced dermal formation of chlorinated phenols and dioxins of triclosan. This paper reviews data on the human exposure, environmental fate, efficacy of anti-microbial activity, absorption, distribution, metabolism and elimination, endocrine disrupting effects, and toxicity of triclosan.     

Front Cover Image,Volume 121, Number 6, May 1, 2020

The treatment for perihilar cholangiocarcinoma (PHC) is a challenge for the surgeon requiring complex resections with a reported perioperative mortality rate between 15% and 48%. In PHC patients with future liver remnant (FLR) less than 30%, it is advised that hepatectomy can be safely performed after the FLR is modified. Associating Liver Partition and Portal vein ligation for Staged Hepatectomy (ALPPS) procedure is criticized heavily due to its high morbidity and mortality rate in this setting. Hereby, we are reporting a modification of ALPPS procedure for PHC. Clinical presentation, preoperative work-up as well as operation and postoperative course of two cases were described in detail. Both patients were jaundiced preoperatively, stage 1 partial-ALPPS procedures were performed laparoscopically, there was sufficient remnant hypertrophy during the interval stage and there was no posthepatectomy liver failure after the second stage (Supporting Information Video). We have followed patients with a mean follow up of 35 months without any recurrence. Here we describe the key technical aspects of this approach that are discussed in three parts: minimally invasive first stage, biliary drainage of both FLR, and deportalized liver at first stage and biliary reconstruction at the second stage. This technique, in selected patients, can extend the indication of ALPPS procedure for PHC with preoperative jaundice.     

Pharmacological characterization of teroxirone, a triepoxide antitumor agent, in rats, rabbits, and humans

Teroxirone is an experimental triepoxide antitumor agent currently undergoing evaluation in clinical trials. We have developed an assay based on derivatization with diethyldithiocarbamate followed by normal-phase high-performance liquid chromatographic analysis. When 14C-labeled teroxirone is administered to rabbits by rapid i.v. infusion, plasma disappearance of parent drug is very rapid (t1/2 less than 5 min), while plasma 14C-labeled drug equivalents are eliminated at a much slower rate (t1/2 greater than 60 min). Twenty-four-hr urinary recovery of parent drug is less than 1%, while recovery of 14C total radioactivity is 60 to 70%. Rapid plasma elimination (t1/2 less than 5 min) and total body clearance (greater than 5 liters/min) are observed following rapid i.v. administration of teroxirone to humans. When teroxirone is administered to humans at constant rates of infusion, plateau concentrations are rapidly achieved and maintained during infusion. Plasma concentrations rapidly decrease upon cessation of infusion. Less than 1% parent drug is recovered in 24-hr urine. Teroxirone is relatively stable in fresh human plasma and whole blood. Teroxirone is metabolized by rat liver, but not lung, microsomal preparations by an NADPH-independent pathway. Epoxide hydrolysis metabolites are detected in microsomal incubations, and cyclohexene oxide inhibits teroxirone metabolism, suggesting that epoxide hydrase may be responsible for teroxirone biotransformation. Cytotoxicity of teroxirone against continuous human tumor cell lines is abolished in the presence of 9000 X g rat liver supernatant preparations but partially restored when cyclohexene oxide is added to incubation mixtures.     

Ovarian cancer (review). Etiology, diagnosis, prognosis, surgery, radiotherapy, chemotherapy and endocrine therapy

The increased incidence of ovarian cancer in women whose ovulations were not suppressed by pregnancy or oral contraceptives and the increase in the incidence of the disease with the onset of climacterium support the hypothesis that ovarian cancer is an endocrine-related disease. Animal experimental results further support this contention. However, identification of a population at risk, prevention, and early detection is difficult. At present, tumor markers are useful in monitoring the disease, though cannot be used for screening. Most of the diagnosed cases are of advanced stages. Besides staging, tumor histology, and residual tumor load are of prognostic importance. The need for accurate initial surgical staging with optimal tumor cytoreduction and the importance of second-look surgery to confirm the response to therapy are emphasized. The precise role for radiotherapy in the treatment of ovarian cancer is still to be established. Presently, response rates of 80% are achieved using cisplatin based combination chemotherapy. In spite of this, long term survival has not improved. Endocrine therapy has hitherto been used empirically and mainly as a last resort in the treatment of advanced ovarian cancer. Response rates of about 10% have been reported. Information on tumor predisposition related to hormonal control should be a key parameter in selecting the appropriate therapy. Tumor analysis has shown that androgen receptors predominate in ovarian cancer, compared to estrogen and progestin receptors. A clinical trial based on endocrine parameters is warranted.     

Mortality predictions for esophageal, stomach, and pancreatic cancer, Ireland, up to 2015

Background and Aim of the Study

An analysis was undertaken to predict numbers of esophageal, stomach, and pancreatic cancer deaths and their World age standardized mortality rates (WASMRs) per 100.000 person years (100,000 PY^?1) in Ireland for the years 2005, 2010 and 2015.

Methods

Linear and log-linear Poisson regression models were applied to 1950–2002 Irish cancer mortality data.

Results

By 2015, esophageal cancer WASMR for males is expected to rise to 9.1 100,000 PY^?1, but for females to fall to 2.3 100,000 PY^?1. In women under 65 yr, the WASMR is expected to decline to 0.8 100,000 PY^?1 but to increase to 3.6 100,000 PY^?1 in men. The stomach cancer WASMR for males is predicted to decrease to 5.3 100,000 PY^?1 and for females to 2.9 100,000 PY^?1. In males under 65 yr, the WASMR is predicted to fall to 1.7 100,000 PY^?1 and to 1.0 100,000 PY^?1 in women. The male WASMR for pancreatic cancer is predicted to decrease to 5.9 100,000 PY^?1 and to 4.7 100,000 PY^?1 in women. In men under 65 yr, the WASMR is predicted to drop to 1.7 100,000 PY^?1 and to fall in women to 1.2 100,000 PY^?1.

Conclusions

Apart from male esophageal cancer, the findings would indicate that declines in Irish WASMRs for these three cancer types are expected to occur by 2015.     

Silica, asbestos, man-made mineral fibers, and cancer

Approximately three million workers in the United States are estimated to be exposed to silica, man-made mineral fibers, and asbestos. The lung is the primary target organ of concern. Each of these substances is composed predominantly of silicon and oxygen; asbestos and silica are crystalline, and asbestos and man-made mineral fibers are fibers. Man-made mineral fibers and asbestos are used as insulating agents, with the former having generally replaced the latter in recent years. Silica is used in foundries, pottery, and brick making, and is encountered by miners. A meta-analysis of 16 of the largest studies with well-documented silica exposure and low probability of confounding by other occupational exposures, indicates a relative risk (RR) of 1.3 (95 percent confidence interval [CI] = 1.2-1.4). Lung cancer risks are highest and most consistent for silicotics, who have received the highest doses (RR = 2.3, CI = 2.2-2.4, across 19studies). The data for mineral fibers continue to support the International Association for Research on Cancer's 1988 judgment that mineral fibers are a possible human carcinogen (Group 2B). Recent epidemiologic studies provide little evidence for lung carcinogenicity for either glass wool or rock/slag wool. Ceramic fibers, a much less common exposure than glass wool and rock/slag wool, are of concern because of positive animal studies, but there are insufficient human data. Regarding asbestos, its carcinogenicity for the lung and mesothelium is well established. With regard to the controversy over chrysotile and mesothelioma, the data suggest chrysotile does cause mesothelioma, although it may be less potent than amphibole asbestos.     

Vinblastine, infusion, bleomycin, and cis-dichlorodiammine-platinum chemotherapy in metastatic melanoma

A chemotherapy regimen containing vinblastine-bleomycin-platinum has been studied in 42 patients with advanced malignant melanoma. Forty-seven percent of evaluable and 43% of all patients experienced objective response. Complete responses were seen in visceral sites. Median duration of response has not been reached but will exceed 26 weeks. Toxicity is predominantly marrow suppressive, gastrointestinal, pulmonary, and mucocutaneous. Pulmonary toxicity was never severe when bleomycin dose was limited to less than 300 mg/m2 body surface area. Half of the patients relapsed with CNS metastases as a first presenting sign of recurrence. Because hospitalization is required in this program its dollar cost is high.     

Somatostatinomas, PPomas, neurotensinomas

We have reviewed data pertinent to three tumor syndromes that derive from overproduction of three GEP peptide hormones. The clinical syndrome of somatostatin excess remains well defined with diabetes, diarrhea, steatorrhea being predominant features. With the availability of assays and increasing awareness, more cases are being diagnosed in the intestine and these differ somewhat in their presentation with cholecystitis, GI bleeding, or a mass as the cardinal features. An unusual association with MEN II pheochromacytoma and neurofibromatosis is emerging. PPomas remain enigmatic. Although diarrhea is a feature, these tumors are usually silent and present with hypatomegally, abdominal pain, and jaundice because of the large size and malignant nature. Neurotensinomas remain rare and truly difficult to separate from the symptom complex produced by VIP excess. Edema, hypotension, cyanosis and flushing should alert one to the possibility of a neurotensin-secreting tumor.     

Viruses, oncogenes, and cancer

Our current theories of virus-induced cellular transformation have changed with the emerging recognition that all normal cells contain proto-oncogenes which convert to oncogenes and induce transformation when activated and/or amplified. Cellular oncogenes have been identified by homology to the transforming genes of acute retroviruses and by the transforming activity of tumor cell DNA in transfection assays. More than two dozen cellular oncogenes identified to date constitute a heterogeneous group of genes which are remarkably conserved among highly diverse species. Expression of proto-oncogenes is linked to normal growth and development; whereas their expression as oncogenes due to gene mutation, rearrangement, amplification or other processes leading to altered or overexpression is associated with the development of tumors. Functions of oncogene proteins are being identified. These include unique protein kinase activity, growth factor/growth factor receptor properties, and the presence of DNA-binding polypeptides. It also appears that cooperation between several activated cellular oncogenes may be required in the multistep process of oncogenesis. Our recent in vitro experimental evidence supports that human cell carcinogenesis is indeed a multistep process. In addition, the involvement of the activated cellular transforming genes met and H-ras in chemically induced human cell carcinogenesis has been shown. Advancement in molecular biology of oncogenes and their products is likely to result in improvements in cancer diagnosis and cancer therapy.     

Mesothelioma Epidemiology, Carcinogenesis, and Pathogenesis

OPINION STATEMENT: The incidence of mesothelioma has gone from almost none to the current 2500-3000 cases per year in the USA. This estimate is an extrapolation based on information available from the Surveillance, Epidemiology and End Results (SEER) Program that collects information on approximately 12% of the US population. Mesothelioma is a cancer that is linked to exposure to carcinogenic mineral fibers. Asbestos and erionite have a proven causative role; the possible role of other mineral fibers in causing mesothelioma is being investigated. Asbestos is considered the main cause of mesothelioma in the US and in the Western world. The capacity of asbestos to induce mesothelioma has been linked to its ability to cause the release of TNF-alpha (that promotes mesothelial cells survival), other cytokines and growth factors, and of mutagenic oxygen radicals from exposed mesothelial cells and nearby macrophages. Some investigators proposed that as a consequence of the regulations to prevent exposure and to forbid and/or limit the use of asbestos, the incidence of mesothelioma in the US (and in some European countries) should have started to decline before or around the year 2000, and sharply decline thereafter. Unfortunately, there are no data available yet to support this optimistic hypothesis. Simian virus 40 (SV40) infection and radiation exposure are additional causes, although their contribution to the overall incidence of mesothelioma is unknown. Recent data from several laboratories indicate that asbestos exposure and SV40 infection are co-carcinogens in causing mesothelioma in rodents and in causing malignant transformation of human mesothelial cells in tissue culture. An exciting new development comes from the discovery that genetic susceptibility to mineral fiber carcinogenesis plays a critical role in the incidence of this cancer in certain families. It is hoped that the identification of this putative mesothelioma gene will lead to novel mechanistically driven preventive and therapeutic approaches.     

History, preliminary results, complications, and future prospects of intraoperative radiotherapy

Intraoperative electron beam radiotherapy (IORT) is a new combined modality therapy in the treatment of cancer. IORT is delivered during a surgical procedure to a tumor or tumor bed and areas of possible local regional spread, with the ability to shield or physically move normal tissues and organs out of the treatment volume. IORT is feasible for various intraabdominal, retroperitoneal, pelvic, and other malignancies. It is possible to increase the total radiation dose, thereby improving the therapeutic ratio; a better local control without an increasing morbidity. Although the optimum use of IORT is still unknown, it is believed that its greatest value is in combination with maximal surgical resection of the tumor with or without external beam radiotherapy (EBRT). IORT is still an experimental treatment modality combining surgery, EBRT, and if necessary, chemotherapy. Because IORT is an expensive treatment method, it is important to determine which method is the best and most convenient for the patient. The answer can be given only when prospective, randomized clinical IORT trials and cost-effectiveness studies are initiated.     

Adriamycin, bleomycin, DIC, CCNU, and prednisone (ABDIC) chemotherapy in MOPP-resistant Hodgkin's disease

ABDIC was administered to 32 patients with MOPP-resistant Hodgkin's disease. Three were considered nonevaluable because of early death. All patients had received MOPP (medium of eight cycles), and five had also received other chemotherapy. Major radiotherapy had been used in 18 of the 29. Complete remission (CR) occurred in 10 of 29 (34.5%), partial remissions (PR) in 14 (48.2%), and no remissions (NR) in five (17.2%). Median survival and relapse-free survival for CR patients exceeded 28 months. Two relapsed at 8 and 18 months; one died at 9 1/2 months, and the other is disease-free with other treatment at 35 months. Seven of the remaining eight patients are alive without disease (10-35 months); 4 are on maintenance therapy, and the other died from an infection and eosinophilic granuloma of lung without evidence of recurrent Hodgkin's disease. Median survival of PR patients was eight months. One patient with Hodgkin's disease involving the liver is alive at 36 months with further therapy. Median survival of NR patients is 2.5 months, and all died within seven months. Survival of CR patients is greater than PR and NR patients (P = 0.002), and that of PR is greater than NR (P = 0.01). Four of the 29 patients had nodal relapse, and 25 had parenchymal relapse, with no difference in response rates (P = 0.47). ABDIC is useful in Hodgkin's disease patients who have had extensive prior chemotherapy and radiotherapy.     

Diet, nutrients, phytochemicals, and cancer metastasis suppressor genes

The major factor in the morbidity and mortality of cancer patients is metastasis. There exists a relative lack of specific therapeutic approaches to control metastasis, and this is a fruitful area for investigation. A healthy diet and lifestyle not only can inhibit tumorigenesis but also can have a major impact on cancer progression and survival. Many chemicals found in edible plants are known to inhibit metastatic progression of cancer. While the mechanisms underlying antimetastatic activity of some phytochemicals are being delineated, the impact of diet, dietary components, and various phytochemicals on metastasis suppressor genes is underexplored. Epigenetic regulation of metastasis suppressor genes promises to be a potentially important mechanism by which dietary components can impact cancer metastasis since many dietary constituents are known to modulate gene expression. The review addresses this area of research as well as the current state of knowledge regarding the impact of diet, dietary components, and phytochemicals on metastasis suppressor genes.     

Management of chemotherapy-induced nausea, vomiting, oral mucositis, and diarrhoea

The past 10 years have seen substantial advances in molecularly targeted therapies for treatment of patients with cancer; however, chemotherapy will continue to be used. Therefore, the toxic effects of chemotherapy must be readily managed-especially nausea, vomiting, mucositis, and diarrhoea. For moderately to highly emetogenic chemotherapy, standard prophylactic treatment is an antagonist for 5-hydroxytryptamine 3 receptors (5-HT3R) combined with dexamethasone for the acute phase, and dexamethasone with another agent for prevention of the delayed phase. Palonoestron (a 5-HT3R antagonist) and aprepitant (an antagonist for the protachykinin 1 receptor) have been introduced for the prevention of emesis. Other agents such as cannabinoids, gabapentin, and olanzapine might also be effective. There is no standard prophylactic regimen for chemotherapy-induced mucositis. The most common treatment is optimum care of the mouth by use of mouthwashes. Keratinocyte growth factor, molgromastim, and transforming growth factor beta3 may also reduce chemotherapy-induced mucositis. Severe diarrhoea is another potentially fatal complication of chemotherapy and is most common in patients treated with irinotecan. Several interventions have been assessed for prevention and treatment of diarrhoea such as high-dose loperamide, non-absorbable antibiotics, budesonide, thalidomide, and fish oils, but only loperamide is used routinely. Symptom management has become a focus of clinical research, and development of personalised medicine should identify patients at increased risk of toxic effects because of molecular or biochemical factors, thus leading to changes in dose, early intervention, or use of alternative therapies.