Vaginal morcellation: A new strategy for large gynecological malignant tumor extraction A pilot study

Objective. Evaluate feasibility and safety of a novel technique for uterine morcellation in patients scheduled for laparoscopic treatment of gynecologic malignances. Background. The laparoscopic management of uterine malignancies is progressively gaining importance and popularity over laparotomy. Nevertheless, minimal invasive surgery is of limited use when patients have enlarged uterus or narrow vagina. In these cases, conventional uterus morcellation could be a solution but should not be recommended due to risks of tumor dissemination. Methods. Prospective pilot study of women with endometrial cancer in which uterus removal was a realistic concern due to both organ size and proportionality. Brief technique description: after completion of total laparoscopic hysterectomy and bilateral anexectomy, a nylon with polyurethane Lapsac (R) is vaginally inserted into the abdomen; the specimen is placed inside the pouch that will be closed and rotated 180 degrees toward the vaginal vault and, posteriorly, pushed into the vaginal canal; in the transvaginal phase, the surgeon pulls the edges of the bag up to vaginal introitus and all vaginal walls will be covered; inside the pouch, the operator performs a uterus bisection-morcellation. Results. In our series of 8 cases, we achieved successful completion in all patients, without conversion to laparotomy. Average operative time, blood loss and length of hospitalization were favorable. One patient presented with a vesicovaginal fistula. Conclusion. The vaginal morcellation following oncologic principles is a feasible method that permits a rapid uterine extraction and may avoid a number of unnecessary laparotomies. Further studies are needed to confirm the oncological safety of the technique. (C) 2012 Elsevier Inc. All rights reserved.

MYC, FBXW7 and TP53 copy number variation and expression in Gastric Cancer

Abstract Background MYC deregulation is a common event in gastric carcinogenesis, usually as a consequence of gene amplification, chromosomal translocations, or posttranslational mechanisms. FBXW7 is a p53-controlled tumor-suppressor that plays a role in the regulation of cell cycle exit and reentry via MYC degradation. Methods We evaluated MYC, FBXW7, and TP53 copy number, mRNA levels, and protein expression in gastric cancer and paired non-neoplastic specimens from 33 patients and also in gastric adenocarcinoma cell lines. We also determined the invasion potential of the gastric cancer cell lines. Results MYC amplification was observed in 51.5% of gastric tumor samples. Deletion of one copy of FBXW7 and TP53 was observed in 45.5% and 21.2% of gastric tumors, respectively. MYC mRNA expression was significantly higher in tumors than in non-neoplastic samples. FBXW7 and TP53 mRNA expression was markedly lower in tumors than in paired non-neoplastic specimens. Moreover, deregulated MYC and FBXW7 mRNA expression was associated with the presence of lymph node metastasis and tumor stage III-IV. Additionally, MYC immunostaining was more frequently observed in intestinal-type than diffuse-type gastric cancers and was associated with MYC mRNA expression. In vitro studies showed that increased MYC and reduced FBXW7 expression is associated with a more invasive phenotype in gastric cancer cell lines. This result encouraged us to investigate the activity of the gelatinases MMP-2 and MMP-9 in both cell lines. Both gelatinases are synthesized predominantly by stromal cells rather than cancer cells, and it has been proposed that both contribute to cancer progression. We observed a significant increase in MMP-9 activity in ACP02 compared with ACP03 cells. These results confirmed that ACP02 cells have greater invasion capability than ACP03 cells. Conclusion In conclusion, FBXW7 and MYC mRNA may play a role in aggressive biologic behavior of gastric cancer cells and may be a useful indicator of poor prognosis. Furthermore, MYC is a candidate target for new therapies against gastric cancer.

MYC, FBXW7 and TP53 copy number variation and expression in gastric cancer

BACKGROUND: MYC deregulation is a common event in gastric carcinogenesis, usually as a consequence of gene amplification, chromosomal translocations, or posttranslational mechanisms. FBXW7 is a p53-controlled tumor-suppressor that plays a role in the regulation of cell cycle exit and reentry via MYC degradation. METHODS: We evaluated MYC, FBXW7, and TP53 copy number, mRNA levels, and protein expression in gastric cancer and paired non-neoplastic specimens from 33 patients and also in gastric adenocarcinoma cell lines. We also determined the invasion potential of the gastric cancer cell lines. RESULTS: MYC amplification was observed in 51.5% of gastric tumor samples. Deletion of one copy of FBXW7 and TP53 was observed in 45.5% and 21.2% of gastric tumors, respectively. MYC mRNA expression was significantly higher in tumors than in non-neoplastic samples. FBXW7 and TP53 mRNA expression was markedly lower in tumors than in paired non-neoplastic specimens. Moreover, deregulated MYC and FBXW7 mRNA expression was associated with the presence of lymph node metastasis and tumor stage III-IV. Additionally, MYC immunostaining was more frequently observed in intestinal-type than diffuse-type gastric cancers and was associated with MYC mRNA expression. In vitro studies showed that increased MYC and reduced FBXW7 expression is associated with a more invasive phenotype in gastric cancer cell lines. This result encouraged us to investigate the activity of the gelatinases MMP-2 and MMP-9 in both cell lines. Both gelatinases are synthesized predominantly by stromal cells rather than cancer cells, and it has been proposed that both contribute to cancer progression. We observed a significant increase in MMP-9 activity in ACP02 compared with ACP03 cells. These results confirmed that ACP02 cells have greater invasion capability than ACP03 cells. CONCLUSION: In conclusion, FBXW7 and MYC mRNA may play a role in aggressive biologic behavior of gastric cancer cells and may be a useful indicator of poor prognosis. Furthermore, MYC is a candidate target for new therapies against gastric cancer.

IGFBP7 participates in the reciprocal interaction between acute lymphoblastic leukemia and BM stromal cells and in leukemia resistance to asparaginase

The interaction of acute lymphoblastic leukemia (ALL) blasts with bone marrow (BM) stromal cells (BMSCs) has a positive impact on ALL resistance to chemotherapy. We investigated the modulation of a series of putative asparaginase-resistance/sensitivity genes in B-precursor ALL cells upon coculture with BMSCs. Coculture with stromal cells resulted in increased insulin-like growth factor (IGF)-binding protein 7 (IGFBP7) expression by ALL cells. Assays with IGFBP7 knockdown ALL and stromal cell lines, or with addition of recombinant rIGFBP7 (rIGFBP7) to the culture medium, showed that IGFBP7 acts as a positive regulator of ALL and stromal cells growth, and significantly enhances in-vitro resistance of ALL to asparaginase. In these assays, IGFBP7 function occurred mainly in an insulin-and stromal-dependent manner. ALL cells were found to contribute substantially to extracellular IGFBP7 levels in the conditioned coculture medium. Diagnostic BM plasma from children with ALL had higher levels of IGFBP7 than controls. IGFBP7, in an insulin/IGF-dependent manner, enhanced asparagine synthetase expression and asparagine secretion by BMSCs, thus providing a stromal-dependent mechanism by which IGFBP7 protects ALL cells against asparaginase in this coculture system. Importantly, higher IGFBP7 mRNA levels were associated with lower leukemia-free survival (Cox regression model, P = 0.003) in precursor B-cell Ph(-) ALL patients (n = 147) treated with a contemporary polychemotherapy protocol.

Dyspeptic symptoms and delayed gastric emptying of solids in patients with inactive Crohn's disease

Background: Patients with Crohn's disease (CD) have been shown to present dyspeptic symptoms more frequently than the general population. Some of these symptoms could be related to motility disorders to some degree. Then, we propose to investigate whether gastric emptying of solids in patients with inactive CD is delayed and to determine the relationships between gastric emptying and dyspeptic symptoms in inactive CD. Methods: Twenty-six patients with inactive Crohn's disease, as defined by a Crohn's Disease Activity Index (CDAI) < 150, underwent a gastric emptying test by breath test using C-13 octanoic acid coupled to a solid meal and answered a validated questionnaire (The Porto Alegre Dyspeptic Symptoms Questionnaire) to assess dyspeptic symptoms. Patients with scores >= 6 were considered to have dyspepsia. The control group was composed by 19 age-and sex-matched healthy volunteers. Results: Patients with CD had a significantly longer t 1/2 and t lag (p<0.05) than the controls. CD patients with dyspepsia had significantly (p<0.05) prolonged gastric emptying when compared to patients without dyspeptic symptoms. When the individual symptom patterns were analyzed, only vomiting was significantly associated with delayed gastric emptying (p<0.05). There was no difference between the subgroups of patients with respect to gender, CDAI scores, disease location, clinical behavior (obstructive/obstructive) or previous gastrointestinal surgery. Conclusion: Delayed gastric emptying in inactive Crohn's disease patients seems to be associated with dyspeptic symptoms, particularly vomiting, even without any evidence of gastrointestinal obstruction.

Nutrient Intake of Women 3 Years After Roux-en-Y Gastric Bypass Surgery

Nutritional deficiencies, especially micronutrient deficiencies, can occur in obese individuals. Surgical treatment may aggravate or cause these deficiencies, depending on the type of procedure, food intake and the use of multivitamins, minerals or other supplements. The objective of the study was to evaluate the nutrient intake of women who had undergone Roux-en-Y gastric bypass (RYGB) surgery. A cross-sectional, controlled study was conducted among 44 women after RYGB (operated-group, OG; mean years post-operation = 3.4) and a control group of 38 healthy women (non-operated group, NOG) matched by age and economic condition. The women reported their dietary intake using a 4-day record. The Dietary Reference Intakes was used as a reference. The macronutrient contributions to dietary energy intake presented an acceptable distribution for proteins and carbohydrates. Lipid intake was high among women in the OG and the NOG (43.2 and 55.3 %, respectively). In the evaluation of micronutrients, a statistically significant difference was observed between the groups for iron, zinc and vitamins B1 and B12. Both groups were at high risk for inadequate calcium intake, and the OG was at risk for inadequate zinc, iron and vitamin B1 intake. The nutrient intake of women who had undergone RYGB is very similar to that of non-operated women, with the exception of a reduced intake of iron, zinc and vitamins B1 and B12, which may be due to the difficulty of consuming meat and a balanced diet. The findings of this study emphasize the importance of appropriate nutritional intervention and the regular use of multivitamin and mineral supplements for these patients.

Effects of Gastric Bypass Surgery in Patients With Type 2 Diabetes and Only Mild Obesity

OBJECTIVE-Roux-en-Y gastric bypass (RYGB) ameliorates type 2 diabetes in severely obese patients through mechanisms beyond just weight loss, and it may benefit less obese diabetic patients. We determined the long-term impact of RYGB on patients with diabetes and only class 1 obesity. RESEARCH DESIGN AND METHODS-Sixty-six consecutively selected diabetic patients with BMI 30-35 kg/m(2) underwent RYGB in a tertiary-care hospital and were prospectively studied for up to 6 years (median 5 years [range 1-6]), with 100% follow-up. Main outcome measures were safety and the percentage of patients experiencing diabetes remission (HbA(1c) <6.5% without diabetes medication). RESULTS-Participants had severe, longstanding diabetes, with disease duration 12.5 +/- 7.4 years and HbA(1c) 9.7 +/- 1.5%, despite insulin and/or oral diabetes medication usage in everyone. For up to 6 years following RYGB, durable diabetes remission occurred in 88% of cases, with glycemic improvement in 11%. Mean HbA(1c) fell from 9.7 +/- 1.5 to 5.9 +/- 0.1% (P < 0.001), despite diabetes medication cessation in the majority. Weight loss failed to correlate with several measures of improved glucose homeostasis, consistent with weight-independent antidiabetes mechanisms of RYGB. C-peptide responses to glucose increased substantially, suggesting improved beta-cell function. There was no mortality, major surgical morbidity, or excessive weight loss. Hypertension and dyslipidemia also improved, yielding 50-84% reductions in predicted 10-year cardiovascular disease risks of fatal and nonfatal coronary heart disease and stroke. CONCLUSIONS-This is the largest, longest-term study examining RYGB for diabetic patients without severe obesity. RYGB safely and effectively ameliorated diabetes and associated comorbidities, reducing cardiovascular risk, in patients with a BMI of only 30-35 kg/m(2).

Duodenal stenting for malignant gastric outlet obstruction: Prospective study

AIM: To evaluate the results of duodenal stenting for palliation of gastroduodenal malignant obstruction by using a gastric outlet obstruction score (GOOS). METHODS: A prospective, non-randomized study was performed at a tertiary center between August 2005 and April 2010. Patients were eligible if they had malignant gastric outlet obstruction (GOO) and were not candidates for surgical treatment. Medical history and patient demographics were collected at baseline. Scheduled interviews were made on the day of the procedure and 15, 30, 90 and 180 d later or unscheduled as necessary. RESULTS: Fifteen patients (6 male, 9 female; median age 61 years) with GOO who had undergone duodenal stenting were evaluated. Ten patients had metastasis at baseline (66.6%) and 14 were unable to accept oral intake (93.33%), including 7 patients who were using a feeding tube. Laboratory data showed biliary obstruction in eight cases (53.33%); all were submitted to biliary drainage. Two patients developed obstructive symptoms due to tumor ingrowth after 30 d and another due to tumor overgrowth after 180 d. Two cases of stent migration occurred. A good response to treatment was observed, with a mean time of approximately 1 d (19 h) until toleration of a liquid diet and slightly more than 2 d for both soft solids (51 h) and a solid food/normal diet (55 h). The mean time to first failure to maintain liquid intake (GODS >= 1) was 93 d. During follow-up, the mean time to first failure to maintain the previously achieved GODS of 2-3 (solid/semi-solid food), considered technical failure, was 71 d. On the basis of oral intake a GODS is defined: 0 for no oral intake; 1 for liquids only; 2 for soft solids only; 3 for low-residue or full diet. CONCLUSION: Enteral stenting to alleviate gastroduodenal malignant obstruction improves quality of life in patients with limited life expectancy, which can be evaluated by using a GOO scoring system. (C) 2012 Baishideng. All rights reserved.

Protein restriction inhibits gastric cell proliferation during rat postnatal growth in parallel to ghrelin changes

Objective: Gastric development depends directly on the proliferation and differentiation of epithelial cells, and these processes are controlled by multiple elements, such as diet, hormones, and growth factors. Protein restriction affects gastrointestinal functions, but its effects on gastric growth are not fully understood. Methods: The present study evaluated cell proliferation in the gastric epithelia of rats subjected to protein restriction since gestation. Because ghrelin is increasingly expressed from the fetal to the weaning stages and might be part of growth regulation, its distribution in the stomach of rats was investigated at 14, 30, and 50 d old. Results: Although the protein restriction at 8% increased the intake of food and body weight, the body mass was lower (P < 0.05). The stomach and intestine were also smaller but increased proportionately throughout treatment. Cell proliferation was estimated through DNA synthesis and metaphase indices, and lower rates (P < 0.05) were detected at the different ages. The inhibition was concomitant with a larger number of ghrelin-immunolabeled cells at 30 and 50 d postnatally. Conclusion: Protein restriction impairs cell proliferation in the gastric epithelium, and a ghrelin upsurge under this condition is parallel to lower gastric and body growth rates. (C) 2012 Elsevier Inc. All rights reserved.

Gastric Torsion from an Intestinal Hernia Through a Rent in the Gastrosplenic Ligament in a Horse

The present report describes an 8-year-old gelding presenting with signs of severe abdominal pain. After performing a thorough physical examination, including rectal palpation and additional diagnostic tests, an exploratory laparotomy was recommended. The jejunum was found herniated through the gastrosplenic ligament, and the stomach was severely distended with gas. Given a poor prognosis, the horse was euthanized on the table. At necropsy, the stomach appeared dilated, with an 180 horizontal gastric torsion, from left (lateral) to right (medial), dividing the organ into dorsal and ventral compartments. We believe that the chronic traction exerted by an incarcerated and distended loop of jejunum, in the dorsal aspect of the gastrosplenic ligament, associated with trauma during episodes of intense rolling, enlarged the rent until it ruptured. Because of this rupture, the lateral dorsal aspect of the stomach became unattached, predisposing it to the torsion. (C) 2012 Elsevier Inc. All rights reserved.

Human Fallopian Tube Mesenchymal Stromal Cells Enhance Bone Regeneration in a Xenotransplanted Model

We have recently reported that human fallopian tubes, which are discarded during surgical procedures of women submitted to sterilization or hysterectomies, are a rich source of human fallopian tube mesenchymal stromal cells (htMSCs). It has been previously shown that human mesenchymal stromal cells may be useful in enhancing the speed of bone regeneration. This prompted us to investigate whether htMSCs might be useful for the treatment of osteoporosis or other bone diseases, since they present a pronounced capacity for osteogenic differentiation in vitro. Based on this prior knowledge, our aim was to evaluate, in vivo, the osteogenic capacity of htMSCs to regenerate bone through an already described xenotransplantation model: nonimmunosuppressed (NIS) rats with cranial defects. htMSCs were obtained from five 30-50 years old healthy women and characterized by flow cytometry and for their multipotenciality in vitro capacity (osteogenic, chondrogenic and adipogenic differentiations). Two symmetric full-thickness cranial defects on each parietal region of seven NIS rats were performed. The left side (LS) of six animals was covered with CellCeram (Scaffdex)-a bioabsorbable ceramic composite scaffold that contains 60% hydroxyapatite and 40% beta-tricalciumphosphate-only, and the right side (RS) with the CellCeram and htMSCs (10(6) cells/scaffold). The animals were euthanized at 30, 60 and 90 days postoperatively and cranial tissue samples were taken for histological analysis. After 90 days we observed neobone formation in both sides. However, in animals euthanized 30 and 60 days after the procedure, a mature bone was observed only on the side with htMSCs. PCR and immunofluorescence analysis confirmed the presence of human DNA and thus that human cells were not rejected, which further supports the imunomodulatory property of htMSCs. In conclusion, htMSCs can be used successfully to enhance bone regeneration in vivo, opening a new field for future treatments of osteoporosis and bone reconstruction.

Human Adipose-Derived Mesenchymal Stromal Cells Injected Systemically Into GRMD Dogs Without Immunosuppression Are Able to Reach the Host Muscle and Express Human Dystrophin

Duchenne muscular dystrophy (DMD), a lethal X-linked disorder, is the most common and severe form of muscular dystrophies, affecting I in 3,500 male births. Mutations in the DMD gene lead to the absence of muscle dystrophin and a progressive degeneration of skeletal muscle. The possibility to treat DMD through cell therapy has been widely investigated. We have previously shown that human adipose-derived stromal cells (hASCs) injected systemically in SJL mice are able to reach and engraft in the host muscle, express human muscle proteins, and ameliorate the functional performance of injected animals without any immunosuppression. However, before starting clinical trials in humans many questions still need to be addressed in preclinical studies, in particular in larger animal models, when available. The best animal model to address these questions is the golden retriever muscular dystrophy (GRMD) dog that reproduces the full spectrum of human DMD. Affected animals carry a mutation that predicts a premature termination codon in exon 8 and a peptide that is 5% the size of normal dystrophin. These dogs present clinical signs within the first weeks and most of them do not survive beyond age two. Here we show the results of local and intravenous injections of hASCs into GRMD dogs, without immunosuppression. We observed that hASCs injected systemically into the dog cephalic vein are able to reach, engraft, and express human dystrophin in the host GRMD dystrophic muscle up to 6 months after transplantation. Most importantly, we demonstrated that injecting a huge quantity of human mesenchymal cells in a large-animal model, without immunosuppression, is a safe procedure, which may have important applications for future therapy in patients with different forms of muscular dystrophies.

Lean and Fat Mass Loss in Obese Patients Before and After Roux-en-Y Gastric Bypass: A New Application for Ultrasound Technique

This study aims to evaluate the thickness of the femoral quadriceps and biceps brachii and brachialis muscles bilaterally and the adjacent subcutaneous fat in patients undergoing gastric bypass Roux-en-Y before and after surgery, using ultrasound as the diagnostic method of choice. We studied 12 patients undergoing this surgical method preoperatively and during the first, third, and sixth postoperative months. During these periods, patients were evaluated by ultrasound to determine the thickness of subcutaneous adipose tissue and muscle of the upper and lower limbs. Postoperatively, these patients showed a reduction in the thickness of the upper and lower extremities muscle and adipose tissue as compared to their preoperative values. There was a significant difference in the loss of muscle thickness in all postoperative months and in the thickness of fatty tissue in the sixth month after surgery, compared to the preoperative muscle and fatty tissue thickness. Ultrasound can be considered as the diagnostic method of choice when assessment of the fat and lean body mass is required in morbidly obese patients before and after bariatric surgery.

Adjuvant chemoradiotherapy after d2-lymphadenectomy for gastric cancer: the role of n-ratio in patient selection. results of a single cancer center

Background: Adjuvant chemoradiotherapy is part of a multimodality treatment approach in order to improve survival outcomes after surgery for gastric cancer. The aims of this study are to describe the results of gastrectomy and adjuvant chemoradiotherapy in patients treated in a single institution, and to identify prognostic factors that could determine which individuals would benefit from this treatment. Methods: This retrospective study included patients with pathologically confirmed gastric adenocarcinoma who underwent surgical treatment with curative intent in a single cancer center in Brazil, between 1998 and 2008. Among 327 patients treated in this period, 142 were selected. Exclusion criteria were distant metastatic disease (M1), T1N0 tumors, different multimodality treatments and tumors of the gastric stump. Another 10 individuals were lost to follow-up and there were 3 postoperative deaths. The role of several clinical and pathological variables as prognostic factors was determined. Results: D2-lymphadenectomy was performed in 90.8% of the patients, who had 5-year overall and disease-free survival of 58.9% and 55.7%. The interaction of N-category and N-ratio, extended resection and perineural invasion were independent prognostic factors for overall and disease-free survival. Adjuvant chemoradiotherapy was not associated with a significant improvement in survival. Patients with node-positive disease had improved survival with adjuvant chemoradiotherapy, especially when we grouped patients with N1 and N2 tumors and a higher N-ratio. These individuals had worse disease-free (30.3% vs. 48.9%) and overall survival (30.9% vs. 71.4%). Conclusion: N-category and N-ratio interaction, perineural invasion and extended resections were prognostic factors for survival in gastric cancer patients treated with D2-lymphadenectomy, but adjuvant chemoradiotherapy was not. There may be some benefit with this treatment in patients with node-positive disease and higher N-ratio.