Carcinoma primário do pâncreas

O estudo anatomopatológico baseado em uma coleção de 6823 necrópsias, constantes do arquivo da Seção de Anatomia Patológica do Instituto Oswaldo Cruz, Rio de Janeiro, Brasil, realizadas durante os anos de 1919 a 1944, revelou a existência de 28 casos de carcinoma primário do pâncreas. A incidência deste tipo de tumor entre o total das necropsias examinadas atinge a 0,40% e, entre os casos de câncer observados na referida série de necrópsias, a 4,08%. O tumor localizou-se na cabeça do pâncreas em 20 casos (71,4%); na cauda, em um caso (3,5%); difuso, em cinco casos (17,8%) e sem localização precisada, em dois casos (7,1%). O tipo histológico predominante foi o adenocarcinoma, reconhecido em 2 casos (78,57%); e em seguida o carcinoma acinoso, em seis casos (21,43%). Geralmente se observa o tipo cirrótico e, em alguns casos, era pronunciada a formação de mucina. A incidência das metástases, em relação aos casos de adenocarcinoma, foi de 95,45% (21 vêzes em 22 casos) e, em relação ao carcinoma acinoso, de 100% (6 vêzes em 6 casos). Entre os órgãos atingidos pelas metástases citam-se em ordem decrescente: o fígado e os gânglios linfáticos (70,3%) o peritônio (25,9%), o pulmão (22,2%), a suprarrenal (18,5%), a pleura bago e rim (7,4%), os intestinos, tiróide, pericárdio, epiploon, estomago, ovário e seio venoso longitudinal superior (3,7%).Em um só caso, não houve produção de metástase (3,57%). Em relação às metástases no peritônio, é interessante acentuar a sua maior freqüência nos casos de adenocarcinoma (7 vêzes em 22 casos). A distribuição do tumor, segundo o sexo, foi de 19 casos em indivíduos do sexo masculino (67,8%) e nove casos, para os do sexo feminino (32,1%), fornecendo a relação de cêrca de 2:1. Segundo a nacionalidade, observaram-se 21 casos (75%) em brasileiros e sete casos (25%) em estrangeiros. Segundo a côr, em 15 casos (53,5%) eram indivíduos de côr branca, em oito casos, (28,5%) de côr preta e, em cinco casos (17,8%), de côr parda. O maior número de casos, em referência à idade, ocorreu em indivíduos de 41 a 50 anos, quando a incidência foi de 11 casos ou 39,3% do total dos casos observados. Em referência a ocorrência anual, verifica-se o maior número (22 casos ou 78,9%) nos últimos dez anos, isto e, de 1935 a 1944.

Inhibitory effect of cyclophosphamide on the biosynthesis of a perchloro-soluble protein fraction of ehrlich ascites carcinoma cells

The perchloro-soluble mucroptotein fraction was determined in the cells of Ehrlich ascites carcinoma on the 10th and 12th days post-inoculation of the tumor. After 3 days of a single subcutaneous dose of cyclophosphamide (200 mg/kg) the mucoprotein levels were found considerable lower. This difference was highly significant statistically.

Acute Eosinophilic and Neutrophilic Pneumonia following Transarterial Chemoembolization with Drug-Eluting Beads Loaded with Doxorubicin for Hepatocellular Carcinoma: A Case Report.

At an intermediate or advanced stage, i.e. stage B or C, based on the Barcelona Clinic Liver Cancer classification of hepatocellular carcinoma (HCC), transarterial chemoembolization (TACE) may be offered as a treatment of palliative intent. We report the case of a patient suffering from acute respiratory distress syndrome after TACE with drug-eluting beads loaded with doxorubicin for HCC. To our knowledge, this is the first case described where a bronchoalveolar lavage was performed, and where significant levels of alveolar eosinophilia and neutrophilia were evident, attributed to a pulmonary toxicity of doxorubicin following liver chemoembolization. © 2014 S. Karger AG, Basel.

Gastric supply manipulation to modulate ghrelin production and enhance vascularization to the cardia: proof of the concept in a porcine model.

Introduction. Selective embolization of the left-gastric artery (LGA) reduces levels of ghrelin and achieves significant short-term weight loss. However, embolization of the LGA would prevent the performance of bariatric procedures because the high-risk leakage area (gastroesophageal junction [GEJ]) would be devascularized. Aim. To assess an alternative vascular approach to the modulation of ghrelin levels and generate a blood flow manipulation, consequently increasing the vascular supply to the GEJ. Materials and methods. A total of 6 pigs underwent a laparoscopic clipping of the left gastroepiploic artery. Preoperative and postoperative CT angiographies were performed. Ghrelin levels were assessed perioperatively and then once per week for 3 weeks. Reactive oxygen species (ROS; expressed as ROS/mg of dry weight [DW]), mitochondria respiratory rate, and capillary lactates were assessed before and 1 hour after clipping (T0 and T1) and after 3 weeks of survival (T2), on seromuscular biopsies. A celiac trunk angiography was performed at 3 weeks. Results. Mean (±standard deviation) ghrelin levels were significantly reduced 1 hour after clipping (1902 ± 307.8 pg/mL vs 1084 ± 680.0; P = .04) and at 3 weeks (954.5 ± 473.2 pg/mL; P = .01). Mean ROS levels were statistically significantly decreased at the cardia at T2 when compared with T0 (0.018 ± 0.006 mg/DW vs 0.02957 ± 0.0096 mg/DW; P = .01) and T1 (0.0376 ± 0.008mg/DW; P = .007). Capillary lactates were significantly decreased after 3 weeks, and the mitochondria respiratory rate remained constant over time at the cardia and pylorus, showing significant regional differences. Conclusions. Manipulation of the gastric flow targeting the gastroepiploic arcade induces ghrelin reduction. An endovascular approach is currently under evaluation.

Augmentation cystoplasty using pedicled and de-epithelialized gastric patches in the mini-pig model.

PURPOSE: The most common methods of bladder augmentation are gastrocystoplasty and enterocystoplasty. Gastrocystoplasty is advantageous due to minimal mucous secretion and a well developed muscular wall as well as good urodynamic properties of the patch. However, the permanent contact of urine with the gastric mucosa is not free of complications. We report the urodynamic, macroscopic and histological outcomes of a pedicled de-epithelialized gastric patch incorporated in the bladder. We compared the results to those of our previous study, which sought to analyze these techniques of patch coverage using sigmoid patches. MATERIALS AND METHODS: We performed 20 augmentation cystoplasties in the mini-pig model using a pedicled de-epithelialized gastric patch and 5 techniques of patch coverage. RESULTS: Three months after surgery all bladders had an increase in volume except those in which the auto-augmentation technique was used. However, all gastric patches were smaller compared to preoperative size. Many had irregular fibrosed inner surfaces and histological evaluation revealed a fibrosed newly formed submucosal layer with a complete urothelial coverage in every patch. No gastric mucosal remnant was found. CONCLUSIONS: De-epithelialized gastrocystoplasty is an attractive procedure that can increase bladder capacity as well as provide a complete urothelial lining without mucosal remnants. However, the success of this procedure seems to be limited by increased morbidity and fibrotic changes, and decreased surface of the patch.

Blocked autophagy sensitizes resistant carcinoma cells to radiation therapy.

Autophagy or "self eating" is frequently activated in tumor cells treated with chemotherapy or irradiation. Whether autophagy represents a survival mechanism or rather contributes to cell death remains controversial. To address this issue, the role of autophagy in radiosensitive and radioresistant human cancer cell lines in response to gamma-irradiation was examined. We found irradiation-induced accumulation of autophagosomes accompanied by strong mRNA induction of the autophagy-related genes beclin 1, atg3, atg4b, atg4c, atg5, and atg12 in each cell line. Transduction of specific target-siRNAs led to down-regulation of these genes for up to 8 days as shown by reverse transcription-PCR and Western blot analysis. Blockade of each autophagy-related gene was associated with strongly diminished accumulation of autophagosomes after irradiation. As shown by clonogenic survival, the majority of inhibited autophagy-related genes, each alone or combined, resulted in sensitization of resistant carcinoma cells to radiation, whereas untreated resistant cells but not sensitive cells survived better when autophagy was inhibited. Similarly, radiosensitization or the opposite was observed in different sensitive carcinoma cells and upon inhibition of different autophagy genes. Mutant p53 had no effect on accumulation of autophagosomes but slightly increased clonogenic survival, as expected, because mutated p53 protects cells by conferring resistance to apoptosis. In our system, short-time inhibition of autophagy along with radiotherapy lead to enhanced cytotoxicity of radiotherapy in resistant cancer cells.

ATP-competitive inhibitors of mTOR: new perspectives in the treatment of renal cell carcinoma.

Targeting mTOR (mammalian target of rapamycin) is an effective approach in the treatment of advanced RCC (renal cell carcinoma). Rapamycin-like drugs (rapalogues) have shown clinical activities and have been approved for the treatment of RCC. Recently, with the development of ATP-competitive inhibitors of mTOR, therapies targeting mTOR have entered a new era. Here, we discuss the biological relevance of blocking mTOR in RCC and review the mechanisms of action of rapalogues in RCC. We also advance some perspectives on the use of ATP-competitive inhibitors of mTOR in RCC.

Reduced quality of life associated adverse events in intermediate hepatocellular carcinoma patients treated with PRECISION TACE with drug eluting beads: Results from the PRECISION V randomized trial : B-241

Purpose: To evaluate the extent of quality of life (QoL) associated adverse events (AEs) following PRECISION TACE with DC Bead compared with conventional transarterial chemoembolisation (cTACE). Methods and Materials: 201 intermediate HCC patients were treated with DC Bead (PRECISION TACE) or conventional TACE (cTACE) with doxorubicin in the PRECISION V clinical study. 93 patients were treated with DC Bead and 108 Patients with cTACE every 2 months and followed up for 6 months. AEs were classified according to the South West Oncology Group criteria. QoL associated AEs were defined as alopecia, constipation, nausea, vomiting, pyrexia, chills, asthenia, fatigue, and headache. Results: The biggest difference in QoL associated AEs was for alopecia: 2 patients (2.2%) for DC-Bead versus 21 patients (19.4%) for cTACE. For other clinical symptoms, constipation (n=10; 10.8% vs. n=13; 12%), vomiting (n=10; 10.8% vs. n=14; 13.0%), pyrexia (n=16; 17.2% vs. n=26; 24.1%), chills (n=1; 1.1% vs. n=5; 4.6%), and headache (n=2; 2.2% vs. n=8; 7.4%) showed lower incidence in the DC Bead group versus cTACE. Nausea, n= 15; 13.9% (n=15; 16.1%) and fatigue, n=6; 5.6% (n=13; 14.0%) were lower for cTACE. Total dose of doxorubicin was on average 35% higher in the DC Bead group. Conclusion: Although patients in the DC Bead group received a higher doxorubicin dose, less QoL associated AEs were reported for this group. Alopecia, the most obvious outward sign of toxicity, was only reported in a tenth of DC Bead patients. Thus, PRECISION TACE with DC Bead improves quality of life associated adverse events.

The different types of internal hernia after laparoscopic Roux-En-Y gastric by-bass for morbid obesity : MDCT features : P5

Purpose: 1. To provide an overview of the different types of internal hernia (IH) occurring after laparoscopic Roux-en-Y gastric bypass (LRYGBP) performed for morbid obesity. 2. To describe the correspondent MDCT features in relation with the underlying anatomical landmarks in order to differentiate their localisation and to direct the surgeon during following laparoscopic closure of mesenteric defects. Methods and materials: LRYGBP performed for morbid obesity is associated with less perioperative complications, shorter hospital stay and a more rapid recovery compared with the open surgical procedure. However, a relatively high incidence of IH is seen that may be due to the laparoscopic approach, but also caused by rapid weight loss with consecutive loosening of the mesenteric sutures. Results: After briefly reviewing the surgical procedure of LRYGBP (ante- versus retrocolic) we describe the exact anatomical landmarks of the different types of IH occurring at any time after operation: They are caused by surgical defects either at the level of the transverse colon mesentery, at the Petersen's space, which represents an opening between the mesocolon and jejunal mesentery, or at the enteroenterostomy site. Typical MDCT features of each IH type in axial and coronal plane as well as targeted vascular reconstructions are demonstrated. Conclusion: Exact knowledge about underlying pathophysiology and anatomical landmarks is essential for distinguishing the different types of IH occurring after LRYGBP on MDCT, since radiological features are difficult to recognize and may even overlap. The radiologist should be aware of the potential anatomic sites to ensure subsequent straightforward laparoscopic exploration.

Inhibition of gastric secretion by a water extract from Baccharis triptera, Mart

Baccharus triptera Mart, is a widespread Compositae used in Brazilian folk medicine to treat gastrointestinal disturbances, rheumatic disease, mild fever, diabetes and as an anti-helminthic. Water extract of small branches of the plant (WE) administered to mice and rats (0.1 to 2 g/Kg, p.o) did not alter spontaneous motor activity, sleeping time induced by barbiturates or the tailflick response in mice. The extract decreased by 40 por cento the number of writhings induced by 0.8 por cento scetic acid, i.p., but did not influence paw edema induced by carrageenan or dextran in rats WE (2g/Kg, p.o.) decreased the intestinal transit of charcoal in mice by 20//. Gastric secretion in pylorus ligated rats was reduced after treatment with WE (1 and 2 g/Kg. i.p. or intraduodenal and the gastric pH was raised. The extract (1 g/Kg, p.o.) prevented gastric ulcers induced in rats by immobilization at 4ºC, but not those induced by indomethacin (10 mg/Kg, s.c.). The results indicate that WE may relieve gastrointestinal disorders by reducing acid secretion and gastrointestinal hiperactivity. Neither analgesic nor anti-inflammatory activities were detectable.

The water extract of Coleus barbatus Benth decreases gastric secretion in rats

Coleus barbatus (Labiatae) Benth is popularly used in Brazil "for the healing of liver and stomach diseases". The water extract (WE 1 to 10 g/Kg, p.o.) of stem and leaves given to rats and mice did not induce signs of intoxication. Preveious treatment of mice with WE (1 g/kg, p.o.) shortened the sleeping time induced by pentobarbital (50 mg/Kg, i.p.) by 37 por cento, althoyugh the extract alone did not increase the spontaneous activity nor did it induce hyperexcitability. In mice WE (2 g/Kg, p.o.) increased the intestinal transit of charcoal by 30 por cento, while reduced gastric secretions ion rats treated with WE (2g/Kg intraduodenal) 3,9 ± 1.0 to 0.5 ± 0.2 ml/4h, respectively). The treatment also reduced the total acid secretion from 34.4 ± 11.0 to 2.7 ± 0.5 mEq/l and raisedgastric pH from 2.2 ± 0.3 to 6.5 ± 0.8. Treatment with WE (2g/Kg, p.o.) protected against gastric ulcers induced by stress (5.3 ± 1.6 and 1.5 ± 0.5 ulcers/cm²), but did nor protect against indonethacin induced ulcers. The results show that the water extract of C barbatus Benth produces mild stimulation of thecentral nervous system and increases intestinal movements. The extract also reduces gastric secretion indicating an antidyspeptic activity, and protects against gastric ulcers induced by stress.

Correlation of tumor-associated antigens MAGE, NY-ESO-1 and P53 expression with clinical and pathological relationships of patients with oral squamous cell carcinoma

Despite advances in the diagnosisand treatment of head and neck cancer,survival rates have not improvedover recent years. New therapeuticstrategies, including immunotherapy,are the subject of extensive research.In several types of tumors, the presenceof tumor infiltrating lymphocytes(TILs), notably CD8+ T cellsand dendritic cells, has been correlatedwith improved prognosis. Moreover,some T cells among TILs havebeen shown to kill tumor cells in vitroupon recognition of tumor-associatedantigens. Tumor associated antigensare expressed in a significant proportionof squamous cell carcinoma ofthe head and neck and apparently mayplay a role in the regulation of cancercell growth notably by inhibition ofp53 protein function in some cancers.The MAGE family CT antigens couldtherefore potentially be used as definedtargets for immunotherapy andtheir study bring new insight in tumorgrowth regulation mechanisms. Between1995 - 2005 54 patients weretreated surgically in our institution forsquamous cell carcinoma of the oralcavity. Patient and clinical data wasobtained from patient files and collectedinto a computerized database.For each patient, paraffin embeddedtumor specimens were retrieved andexpression of MAGE CT antigens,p53, NY-OESO-1 were analyzed byimmunohistochemistry. Results werethen correlated with histopathologicalparameter such as tumor depth,front invasion according to Bryne andboth, local control and disease freesurvival. MAGE-A was expressed in52% of patients. NY-ESO-1 and p53expression was found in 7% and 52%cases respectively. A higher tumordepth was significantly correlatedwith expression of MAGE-Aproteins(p = 0.03). No significant correlationcould be made between the expressionof both p53 andNY-OESO-1 andhistopathological parameters. Expressionof tumor-associated antigendid not seem to impact significantlyon patient prognosis. As does thedemonstration of p53 function inhibitionby CT antigens of MAGE family,our results suggest, that tumor associatedantigens may be implicated in tumorprogression mechanisms. Thishypothesis need further investigationto clarify the relationship betweenhost immune response and local tumorbiology.

Continuous Sunitinib treatment in patients with advanced hepatocellular carcinoma: a Swiss Group for Clinical Cancer Research (SAKK) and Swiss Association for the Study of the Liver (SASL) multicenter phase II trial (SAKK 77/06).

BACKGROUND: Sunitinib (SU) is a multitargeted tyrosine kinase inhibitor with antitumor and antiangiogenic activity. The objective of this trial was to demonstrate antitumor activity of continuous SU treatment in patients with hepatocellular carcinoma (HCC). PATIENTS AND METHODS: Key eligibility criteria included unresectable or metastatic HCC, no prior systemic anticancer treatment, measurable disease, and Child-Pugh class A or mild Child-Pugh class B liver dysfunction. Patients received 37.5 mg SU daily until progression or unacceptable toxicity. The primary endpoint was progression-free survival at 12 weeks (PFS12). RESULTS: Forty-five patients were enrolled. The median age was 63 years; 89% had Child-Pugh class A disease and 47% had distant metastases. PFS12 was rated successful in 15 patients (33%; 95% confidence interval, 20%-47%). Over the whole trial period, one complete response and a 40% rate of stable disease as the best response were achieved. The median PFS duration, disease stabilization duration, time to progression, and overall survival time were 1.5, 2.9, 1.5, and 9.3 months, respectively. Grade 3 and 4 adverse events were infrequent. None of the 33 deaths were considered drug related. CONCLUSION: Continuous SU treatment with 37.5 mg daily is feasible and has moderate activity in patients with advanced HCC and mild to moderately impaired liver dysfunction. Under this trial design (>13 PFS12 successes), the therapy is considered promising. This is the first trial describing the clinical effects of continuous dosing of SU in HCC patients on a schedule that is used in an ongoing, randomized, phase III trial in comparison with the current treatment standard, sorafenib (ClinicalTrials.gov identifier, NCT00699374).

Prospective randomized study of doxorubicin-eluting-bead embolization in the treatment of hepatocellular carcinoma: results of the PRECISION V study.

Transcatheter arterial chemoembolization (TACE) offers a survival benefit to patients with intermediate hepatocellular carcinoma (HCC). A widely accepted TACE regimen includes administration of doxorubicin-oil emulsion followed by gelatine sponge-conventional TACE. Recently, a drug-eluting bead (DC Bead) has been developed to enhance tumor drug delivery and reduce systemic availability. This randomized trial compares conventional TACE (cTACE) with TACE with DC Bead for the treatment of cirrhotic patients with HCC. Two hundred twelve patients with Child-Pugh A/B cirrhosis and large and/or multinodular, unresectable, N0, M0 HCCs were randomized to receive TACE with DC Bead loaded with doxorubicin or cTACE with doxorubicin. Randomization was stratified according to Child-Pugh status (A/B), performance status (ECOG 0/1), bilobar disease (yes/no), and prior curative treatment (yes/no). The primary endpoint was tumor response (EASL) at 6 months following independent, blinded review of MRI studies. The drug-eluting bead group showed higher rates of complete response, objective response, and disease control compared with the cTACE group (27% vs. 22%, 52% vs. 44%, and 63% vs. 52%, respectively). The hypothesis of superiority was not met (one-sided P = 0.11). However, patients with Child-Pugh B, ECOG 1, bilobar disease, and recurrent disease showed a significant increase in objective response (P = 0.038) compared to cTACE. DC Bead was associated with improved tolerability, with a significant reduction in serious liver toxicity (P < 0.001) and a significantly lower rate of doxorubicin-related side effects (P = 0.0001). TACE with DC Bead and doxorubicin is safe and effective in the treatment of HCC and offers a benefit to patients with more advanced disease.