Unknown primary tumors.

An unknown primary tumor (UPT) is defined by the presence of a metastatic cancer without a known primary site of origin despite a standardized diagnostic workup. Clinically, UPTs show rapid progression and early dissemination, with signs and symptoms related to the metastatic site. The molecular bases of their biology remain largely unknown, with no evidence as to whether they represent a distinct biological entity. Immunohistochemistry remain the best diagnostic tool in term of cost-effectiveness, but the time-consuming "algorithmic process" it relies on has led to the application of new molecular techniques for the identification of the primary site of UPTs. For example, several microarray or miRNA classifications of UPTs have been used, with an accuracy in the prediction of the primary site as high as 90%. It should be noted that validating a prediction of tissue origin is challenging in these patients, since most of them will never have a primary site identified. Moreover, prospective studies to determine whether selection of treatment options based on such profiling methods actually improves patient outcome are still missing. In the last few years functional imaging (i.e. FDG-PET/CT) has gained a main role in the detection of the site of origin of UPTs and is currently recommended by the European Association of Nuclear Medicine. However, despite recent refinements in the diagnostic workup, the site of origin of UPT often remains elusive. As a consequence, treatment of patients with UPT is still empirical and inadequate.

Megaduodenum: an unusual presentation of amyloidosis?

Amyloidosis, a potentially fatal disease, is characterized by an abnormal deposition of autologous proteins. Heart, liver, kidneys, lung, thyroid, skin and the gastrointestinal tract can be involved; in this last case mucosal alterations or disturbances of the motility leading to pseudo-obstruction, bleeding, diarrhea and malabsorption can be present. However, the data concerning the possible gastrointestinal presentations of amyloidosis are scanty and heterogeneous. We report the case of a patient presenting severe gastrointestinal symptoms caused by a megaduodenum. The patient was thoroughly investigated and lesions appeared limited to the upper gastrointestinal tract in the absence of a systemic disorder. However, at follow up the patient developed cardiac dilatation and bioptic samples revealed the presence of amyloidosis.

Chemoprophylaxis in gastrointestinal tumors.

Chemoprevention of gastrointestinal tumors uses natural or synthetic agents to arrest, retard or reverse the carcinogenesis process. The prospect of prevention is clearly appealing, especially for colorectal cancer (CRC), that represents the second most common cause of cancer-related death in the Western world. Aspirin is the best studied chemopreventive agent for CRC, with randomized trials demonstrating its efficacy in reducing recurrence of colorectal adenomas in higher risk patients. Optimal chemoprevention requires long-term use and high dose of aspirin that may increase the risk of gastrointestinal bleeding. Other nonsteroidal anti-inflammatory drugs and selective cyclooxygenase-2 inhibitors also reduce the incidence of colonic adenomas, but they are associated with gastrointestinal harms and important cardiovascular events, respectively. Furthermore, cumulative epidemiological and observational data suggest the potential role of hormones as a chemoprotective agent for CRC. The usefulness of folic acid, calcium, and vitamin D awaits further evaluation. Interestingly, combining different agents may maximize effectiveness while limiting drug toxicity. Although many agents have shown positive results in the field of chemoprevention, it cannot yet be accepted as standard medical practice for CRC. In the present review we discuss the most promising agents in CRC chemoprevention, together with their potential mechanisms of action in tumor inhibition.

Discussion about switch strategy in the adjuvant hormonal therapy of breast cancer: psychological aspects of physician-patient communication.

BACKGROUND: A survey of oncologists was conducted in Italy to evaluate the potential problems of physician-patient discussion about hormonal switch in the adjuvant therapy of breast cancer. MATERIALS AND METHODS: A questionnaire, including both closed and open-ended questions, was administered to 70 oncologists. Fifty-one of them returned completely filled questionnaires. RESULTS: Forty-seven percent of the physicians reported difficulties in proposing the hormonal switch, and 60% stated that they found it difficult to make the therapeutic change acceptable to patients. The oncologist's barriers to propose the switch were related mostly to scientific and economic issues, such as the lack of certain advantages of aromatase inhibitors over tamoxifen (28%), their costs (14%) and their side-effects (34%). On the other hand, according to physicians, the patient's barriers to accept the therapeutic change were mainly due to psychological-relational factors, in particular the anxiety produced by the change (40%) and the bad patient-physician communication experienced in the past (26%). CONCLUSIONS: Patient-physician communication difficulties about switch strategy in the adjuvant hormonal treatment of breast cancer are, at least in part, related to psychological and relational factors. It is likely that training programs, improving doctor's communication skills, can overcome these problems.

Biogas production and valorization by means of a two-step biological process.

The scope of this research work was to investigate biogas production and purification by a two-step bench-scale biological system, consisting of fed-batch pulse-feeding anaerobic digestion of mixed sludge, followed by methane enrichment of biogas by the use of the cyanobacterium Arthrospiraplatensis. The composition of biogas was nearly constant, and methane and carbon dioxide percentages ranged between 70.5-76.0% and 13.2-19.5%, respectively. Biogas yield reached a maximum value (about 0.4 m(3)(biogas)/kg COD(i)) at 50 days-retention time and then gradually decreased with a decrease in the retention time. Biogas CO(2) was then used as a carbon source for A. platensis cultivation either under batch or fed-batch conditions. The mean cell productivity of fed-batch cultivation was about 15% higher than that observed during the last batch phase (0.035+/-0.006 g(DM)/L/d), likely due to the occurrence of some shading effect under batch growth conditions. The data of carbon dioxide removal from biogas revealed the existence of a linear relationship between the rates of A. platensis growth and carbon dioxide removal from biogas and allowed calculating carbon utilization efficiency for biomass production of almost 95%.

A phase II study of dose-dense epirubicin plus cyclophosphamide followed by docetaxel plus capecitabine and pegfilgrastim support as preoperative therapy for patients with stage II, IIIA breast cancer.

BACKGROUND: This phase II study was conducted to evaluate tumor response rate and safety profile of dose-dense epirubicin plus cyclophosphamide followed by docetaxel plus capecitabine given preoperatively to patients with stage II or IIIA breast cancer. PATIENTS AND METHODS: Patients underwent four cycles of dose-dense cyclophosphamide 600 mg/m(2) and epirubicin 90 mg/m(2) every 2 weeks followed by two cycles of docetaxel 36 mg/m(2) on days 1, 8, and 15 plus capecitabine 1250 mg/m(2) on days 5-18 every 4 weeks, with prophylactic pegfilgrastim. The primary objective of the study was to determine the incidence of pathologic complete response defined as the absence of invasive or in situ cancer in the breast and the axillary nodes at definitive surgery. RESULTS: Forty-four patients were enrolled in the study and 41 (93%) were assessable for response to chemotherapy. An objective clinical response was observed in 38 (93%) patients. Seven patients (17.1%) exhibited a pathologic complete response. Breast-conserving surgery was carried out in 36 (88%) patients. Grade 3/4 neutropenia occurred in 4.3% of 252 administered chemotherapy cycles. No febrile neutropenia, cardiac toxicity, thrombocytopenia or other serious adverse event was registered. CONCLUSION: The sequential combination of dose-dense epirubicin plus cyclophosphamide followed by docetaxel plus capecitabine is an effective and well-tolerated neo-adjuvant chemotherapy for stage II, IIIA breast cancer.

Synthesis of ethyl phenylacetate by lyophilized mycelium of Aspergillus oryzae.

Lyophilized mycelia of Aspergillus oryzae CBS 102.07, Aspergillus oryzae MIM, Rhizopus oryzae CBS 112.07, Rhizopus oryzae CBS 391.34, Rhizopus oryzae CBS 260.28 and Rhizopus oryzae CBS 328.47 were tested in this study to select the best biocatalysts for ethanol acylation with phenylacetic acid. The mycelium-bound carboxylesterase activity of A. oryzae MIM, which exhibited the best performances, was initially investigated at 50 degrees C, either in 0.1 M phosphate buffer or in n-heptane to catalyse the hydrolysis or the synthesis, respectively, of ethyl phenylacetate. The results in terms of product and substrate concentrations versus time were used to estimate the maximum molar conversions at equilibrium, the equilibrium constants, and the times needed to reach half maximum conversions, thus providing sufficient information about this biotransformation. The values of the apparent equilibrium constants, estimated at 20 degrees C

Role of endoscopic retrograde cholangiopancreatography in the diagnosis and treatment of biliary tract complications after orthotopic liver transplantation.

BACKGROUND: Biliary complications are a major drawback of liver transplantation. AIM: To analyse, in a single centre, experience in endoscopic diagnosis and management of biliary complications after liver transplantation. PATIENTS: A total of 147 consecutive liver transplantations performed on 132 patients over a 5-year period. METHODS: Evaluation of the incidence and type of biliary-related complications and analysis of their diagnosis and endoscopic treatment by cholangiopancreatography in terms of success of the endoscopic approach, conversion to surgery and long-term patient and graft survival. RESULTS: Endoscopic retrograde cholangiopancreatography was performed on 30 patients (23%). Overall incidence of biliary complications as confirmed by endoscopic retrograde cholangiopancreatography was 17% (25 cases). Endoscopic retrograde cholangiopancreatography was negative in 5 cases (16%). Biliary complications were successfully treated by endoscopy in 84% of cases (21 out of 25 patients); 4 cases (16%) required a surgical approach (2 choledochojejunostomy, 2 retransplantation) due to failure to correct the problem endoscopically. Stenoses and biliary sludge associated with retained internal stent were almost always successfully managed by endoscopic retrograde cholangiopancreatography, while anastomotic leakage more frequently required a surgical approach. CONCLUSIONS: Endoscopic retrograde cholangiopancreatography is a safe and effective approach for diagnosis and treatment of biliary-related complications after liver transplantation thereby reducing morbidity and mortality related to re-operation which is, however, required in selected cases.

High-fiber diet supplementation in patients with irritable bowel syndrome (IBS): a multicenter, randomized, open trial comparison between wheat bran diet and partially hydrolyzed guar gum (PHGG).

High-fiber diet supplementation is commonly used in IBS, although it poses several management problems. Partially hydrolyzed guar gum (PHGG) has shown beneficial effects in animal and human studies, but its potential role in IBS symptom relief has not been evaluated yet. We investigated PHGG in IBS patients and compared it to a wheat bran diet. Abdominal pain, bowel habits, and subjective overall rating were longitudinally evaluated in 188 adult IBS patients (139 women and 49 men) for 12 weeks. Patients were classified as having diarrhea-predominant, constipation-predominant, or changeable bowel habits and were randomly assigned to groups receiving fiber (30 g/day of wheat bran) or PHGG (5 g/day). After four weeks, patients were allowed to switch group, depending on their subjective evaluation of their symptoms. Significantly more patients switched from fiber to PHGG (49.9%) than from PHGG to fiber (10.9%) at four weeks. Per protocol analysis showed that both fiber and PHGG were effective in improving pain and bowel habits, but no difference was found between the two groups. Conversely, intention-to-treat analysis showed a significantly greater success in the PHGG group (60%) than in the fiber group (40%). Moreover, significantly more patients in the PHGG group reported a greater subjective improvement than those in the Fiber group. In conclusion, improvements in core IBS symptoms (abdominal pain and bowel habits) were observed with both bran and PHGG, but the latter was better tolerated and preferred by patients, revealing a higher probability of success than bran and a lower probability of patients abandoning the prescribed regimen, suggesting that it can increase the benefits deriving from fiber intake in IBS, making it a valid option to consider for high-fiber diet supplementation.

Sugarcane bagasse as alternative packing material for biofiltration of benzene polluted gaseous streams: a preliminary study.

Removal of benzene vapor from gaseous streams was studied in two identically sized lab-scale biofiltration columns: one filled with a mixture of raw sugarcane bagasse and glass beads, and the other one packed with a mixture of ground sugarcane bagasse and glass beads, in the same volume ratio, as filter materials. Separate series of continuous tests were performed, in parallel, under the same operating conditions (inlet benzene concentration of 10.0, 20.0 or 50.0 mg m(-3), and superficial gas velocity of 30.6, 61.2 or 122.4 m h(-1)) in order to evaluate and compare the influence of the packing material characteristics upon the biofilter effectiveness. The maximum elimination capacities obtained, at an inlet load of 6.12 g m(-3) h(-1), were 3.50 and 3.80 g m(-3)packibng material h(-1) with raw and ground sugarcane bagasse, respectively. This was a preliminary study and the results obtained suggest only a limited application with more work needed.

Ciliary body tumor and cataract: local resection combined with phacoemulsification.

A 57-year-old man developed a ciliary body mass, clinically diagnosed as malignant melanoma of the ciliary body, that produced a cataract in the right eye. Treatment was cataract surgery with sclerouvectomy performed simultaneously. Pathohistologic examination revealed an acquired adenoma of the nonpigmented ciliary epithelium. The clinicopathologic features and treatment of this tumor are discussed.

Metabolic study of the adaptation of the yeast Candida guilliermondii to sugarcane bagasse hydrolysate.

Batch xylitol production from concentrated sugarcane bagasse hydrolysate by Candida guilliermondii was performed by progressively adapting the cells to the medium. Samples were analyzed to monitor sugar and acetic acid consumption, xylitol, arabitol, ethanol, and carbon dioxide production, as well as cell growth. Both xylitol yield and volumetric productivity remarkably increased with the number of adaptations, demonstrating that the more adapted the cells, the better the capacity of the yeast to reduce xylose to xylitol in hemicellulose hydrolysates. Substrate and product concentrations were used in carbon material balances to study in which way the different carbon sources were utilized by this yeast under microaerobic conditions, as well as to shed light on the effect of the progressive adaptation to the medium on its fermentative activity. Such a theoretical means allowed estimation for the first time of the relative contribution of each medium component to the formation of the main products of this fermentation system.

Mycelium-bound carboxylesterase from Aspergillus oryzae: an efficient catalyst for acetylation in organic solvent.

Dry mycelium of a strain of Aspergillus oryzae efficiently catalyzed the esterification between free acetic acid and primary alcohols (geraniol and ethanol) in organic solvent. The growth conditions to obtain high activity of mycelium-bound enzymes were firstly evaluated. A medium containing Tween 80 as carbon source furnished mycelium with the highest activity in the hydrolysis of alpha-naphthyl esters (alpha-N-acetate, butyrate, caprylate). Dry mycelium was employed to select suited conditions for an efficient acetylation of ethanol and geraniol in heptane. Maximum productions were obtained using 30 g l(-)(1) of lyophilized cells: 12.4 g l(-)(1) of geranyl acetate were produced at 80 degrees C starting from 75 mM geraniol and acetic acid (84% molar conversion) and 4.1 g l(-)(1) of ethyl acetate at 50 degrees C from 50 mM ethanol and acetic acid (94% molar conversion) after 24 h. The stability of the mycelium-bound carboxylesterases are notable since only 10-30% loss of activity was observed after 14 days at temperatures between 30 and 50 degrees C.

Toluene vapour removal in a laboratory-scale biofilter.

A bench-scale biofilter with a 0.5-m high filter bed, inoculated with a toluene-degrading strain of Acinetobacter sp. NCIMB 9689, was used to study toluene removal from a synthetic waste air stream. Different sets of continuous tests were conducted at influent toluene concentrations ranging over 0.1-4.0 g m(-3) and at superficial gas velocities ranging over 17.8-255 m h(-1). The maximum volumetric toluene removal rate for the biofilter (242 g m(-3) h(-1)) was obtained at a superficial gas velocity of 127.5 m h(-1) (corresponding to a residence time of 28 s) and a toluene inlet concentration of 4.0 g m(-3). Under these operating conditions, toluene removal efficiency was only 0.238, which suggested that effective operation required higher residence times. Removal efficiencies higher than 0.9 were achieved at organic loads less than 113.7 g m(-3) h(-1). A macro-kinetic study, performed using concentration profiles along the bioreactor, revealed this process was limited by diffusion at organic loads less than 100 g m(-3) h(-1) and by biological reaction beyond this threshold.

Simple and fast chromatographic method for the determination of sotalol in human serum.

We developed a method for the determination of sotalol in human plasma. After a simple deproteinization of the sample, we submit the supernatant to high-performance liquid chromatography with fluorescence detection. A few minutes are necessary to complete the analysis.

Duodenal obstruction from chronic pancreatitis.

The fibrosclerosing process of the pancreas in the chronic pancreatitis may constrict not only the pancreatic duct but also the bile duct, splenoportal venous system and duodenum. In our retrospective study we analysed 24 patients with duodenal obstruction associated with chronic pancreatitis. Duodenal obstruction was suspected whenever repeated vomiting occurred or large volumes of nasogastric aspirate were obtained. The diagnosis was confirmed by barium meal and endoscopic examination. Duodenal obstruction was relieved by gastrojejunostomy in eight patients, gastrojejunostomy and vagotomy in eight patients, gastroduodenostomy and vagotomy in two patients, vagotomy with Finney pyloroplasty in one patient, duodenoplasty with vagotomy in one patient and Whipple procedure in four patients. We concluded that vagotomy and gastroenterostomy are the procedures of choice. Bypass surgery is helpful to relieve the obstruction of the common bile duct and pancreatic duct. Whipple procedure should be reserved for the small duct form of chronic pancreatitis and for the cases in which there is high suspicion of malignancy.

Long-term (12 months) treatment with an anti-oxidant drug (silymarin) is effective on hyperinsulinemia, exogenous insulin need and malondialdehyde levels in cirrhotic diabetic patients.

BACKGROUND/AIMS: Several studies have demonstrated that diabetic patients with cirrhosis require insulin treatment because of insulin resistance. As chronic alcoholic liver damage is partly due to the lipoperoxidation of hepatic cell membranes, anti-oxidizing agents may be useful in treating or preventing damage due to free radicals. The aim of this study was to ascertain whether long-term treatment with silymarin is effective in reducing lipoperoxidation and insulin resistance in diabetic patients with cirrhosis. METHODS: A 12-month open, controlled study was conducted in two well-matched groups of insulin-treated diabetics with alcoholic cirrhosis. One group (n=30) received 600 mg silymarin per day plus standard therapy, while the control group (n=30) received standard therapy alone. The efficacy parameters, measured regularly during the study, included fasting blood glucose levels, mean daily blood glucose levels, daily glucosuria levels, glycosylated hemoglobin (HbA1c) and malondialdehyde levels. RESULTS: There was a significant decrease (p<0.01) in fasting blood glucose levels, mean daily blood glucose levels, daily glucosuria and HbA1c levels already after 4 months of treatment in the silymarin group. In addition, there was a significant decrease (p<0.01) in fasting insulin levels and mean exogenous insulin requirements in the treated group, while the untreated group showed a significant increase (p<0.05) in fasting insulin levels and a stabilized insulin need. These findings are consistent with the significant decrease (p<0.01) in basal and glucagon-stimulated C-peptide levels in the treated group and the significant increase in both parameters in the control group. Another interesting finding was the significant decrease (p<0.01) in malondialdehyde/levels observed in the treated group. CONCLUSIONS: These results show that treatment with silymarin may reduce the lipoperoxidation of cell membranes and insulin resistance, significantly decreasing endogenous insulin overproduction and the need for exogenous insulin administration.

Macro-kinetic investigation on phenol uptake from air by biofiltration: Influence of superficial gas flow rate and inlet pollutant concentration.

The macro-kinetic behavior of phenol removal from a synthetic exhaust gas was investigated theoretically as well as experimentally by means of two identical continuously operating laboratory-scale biological filter bed columns. A mixture of peat and glass beads was used as filter material. After sterilization it was inoculated with a pure strain of Pseudomonas putida, as employed in previous experimental studies. To determine the influence of the superficial gas flow rate on biofilter performance and to evaluate the phenol concentration profiles along the column, two series of continuous tests were carried out varying either the inlet phenol concentration, up to 1650 mg . m(-3), or the superficial gas flow rate, from 30 to 460 m(3) . m(-2) . h(-1). The elimination capacity of the biofilter is proved by a maximum volumetric phenol removal rate of 0.73 kg . m(-3) . h(-1). The experimental results are consistent with a biofilm model incorporating first-order substrate elimination kinetics. The model may be considered a useful tool in scaling-up a biofiltration system. Furthermore, the deodorization capacity of the biofilter was investigated, at inlet phenol concentrations up to 280 mg . m(-3) and superficial gas flow rates ranging from 30 to 92 m(3) . m(-2) . h(-1). The deodorization of the gas was achieved at a maximum inlet phenol concentration of about 255 mg . m(-3), operating at a superficial gas flow rate of 30 m(3) . m(-2) . h(-1). (c) 1996 John Wiley & Sons, Inc.

Phenol removal from waste gases with a biological filter by Pseudomonas putida.

The purpose of this study is to investigate the feasibility of biologically removing phenol from waste gases by means of a biofilter using a Pseudomonas putida strain. Two series of both batch and continuous tests have been performed in order to ascertain the microbial degradation of phenol. For the preliminary batch tests, carried out in order to test the effective feasibility of the process and to investigate their kinetic behavior, two different microbial cultures belonging to the Pseudomonas genus have been employed, a heterogeneous culture and a pure strain of P. putida. The results of these comparative investigation showed that the pure culture is more efficient than the mixed one, even when the latter has undergone three successive acclimatization tests. The continuous experiments have been conducted during a period of about 1 year in a laboratory-scale column, packed with a mixture of peat and glass beads, and utilizing the pure culture of P. putida as microflora and varying the inlet phenol concentration from 50 up to 2000 mg m(-3). The results obtained show that high degrees of conversion can be obtained (0.93/0.996) operating at a residence time of 54 s.