Epoxyeicosatrienoic acids protect cardiac cells during starvation by modulating an autophagic response.

Epoxyeicosatrienoic acids (EETs) are cytochrome P450 epoxygenase metabolites of arachidonic acid involved in regulating pathways promoting cellular protection. We have previously shown that EETs trigger a protective response limiting mitochondrial dysfunction and reducing cellular death. Considering it is unknown how EETs regulate cell death processes, the major focus of the current study was to investigate their role in the autophagic response of HL-1 cells and neonatal cardiomyocytes (NCMs) during starvation. We employed a dual-acting synthetic analog UA-8 (13-(3-propylureido)tridec-8-enoic acid), possessing both EET-mimetic and soluble epoxide hydrolase (sEH) inhibitory properties, or 14,15-EET as model EET molecules. We demonstrated that EETs significantly improved viability and recovery of starved cardiac cells, whereas they lowered cellular stress responses such as caspase-3 and proteasome activities. Furthermore, treatment with EETs resulted in preservation of mitochondrial functional activity in starved cells. The protective effects of EETs were abolished by autophagy-related gene 7 (Atg7) short hairpin RNA (shRNA) or pharmacological inhibition of autophagy. Mechanistic evidence demonstrated that sarcolemmal ATP-sensitive potassium channels (pmKATP) and enhanced activation of AMP-activated protein kinase (AMPK) played a crucial role in the EET-mediated effect. Our data suggest that the protective effects of EETs involve regulating the autophagic response, which results in a healthier pool of mitochondria in the starved cardiac cells, thereby representing a novel mechanism of promoting survival of cardiac cells. Thus, we provide new evidence highlighting a central role of the autophagic response in linking EETs with promoting cell survival during deep metabolic stress such as starvation.

Renal cell carcinoma insulated in the renal capsule with calcification and ossification.

We describe a case of renal-cell carcinoma insulated and entrapped in the renal capsule by a calcified and ossified rim. To our knowledge, this is the first time a renal-cell carcinoma of the renal capsule is reported. The fact that the tumor cells originated from the distal/medullary tubules was supported by immunohistochemical studies. The pertinent literature is reviewed.

Neurofilament immunoreactivity in Merkel-cell tumors: a differentiating feature from small-cell carcinoma.

To differentiate Merkel-cell tumor (MCT) from other neuroendocrine (NE) carcinomas, we immunostained (using avidin-biotin-peroxidase method) nine MCT and 37 NE (including 28 small-cell) carcinomas for NE markers (neuron-specific enolase and chromogranin), cytokeratin, neurofilament, vimentin, and a number of other markers. Cytokeratin was positive in 100% of MCT and in 85% of small-cell carcinomas; neurofilament and vimentin were positive in respectively 100% and 22% of MCT and 0% of NE carcinomas. Our data suggest that the coexpression of cytokeratin and neurofilament by an undifferentiated dermal or visceral tumor is of significant help in diagnosing MCT and differentiating it from small-cell carcinomas. The vimentin reactivity is a weak and insignificant discriminant.

The sentinel hyperplastic polyp: a marker for synchronous neoplasia in the proximal colon.

We prospectively screened 129 asymptomatic subjects (mean age 64 yr) with flexible sigmoidoscopy. Colonoscopy was performed at a later date, regardless of the sigmoidoscopic result. Our intent was 1) to establish the prevalence of proximal neoplasms in patients with and without hyperplastic polyps within reach of the 60-cm sigmoidoscope and 2) to determine whether a distal (sentinel) hyperplastic polyp predicts the presence of synchronous neoplastic polyps higher up in the colon. Our results show that 15% of asymptomatic adult subjects without polyps on sigmoidoscopy have adenomas in proximal colonic segments that can be diagnosed only by colonoscopy. By comparison, proximal neoplasms were detected in 32% (p less than 0.05) and 37% (p less than 0.05) of patients when hyperplastic or adenomatous polyps, respectively, were present on the sigmoidoscopic examination. This finding suggests that a distal (sentinel) hyperplastic polyp by itself may be a marker for neoplastic polyps in proximal colonic segments. Also, the "index" adenoma and "sentinel" hyperplastic polyp may be equivalent for predicting the presence of proximal neoplasms. The observed detection rates for these polyps were both significantly higher than expected when compared to patients who did not have polyps in the distal colon or rectum. If these results can be confirmed by a larger prospective trial, then full colonoscopy for detection of proximal neoplasms may be indicated when either an index adenoma or sentinel hyperplastic polyp is detected by sigmoidoscopy.

Prevalence and malignant potential of colorectal polyps in asymptomatic, average-risk men.

Screening colonoscopy was performed on 119 asymptomatic elderly men with no other risk factors for colonic neoplasms. Ninety adenomas were detected in 49 (41%) subjects. Mean adenoma size was 6.5 mm, with 83 (92%) less than or equal to 10 mm. Forty-nine (54%) adenomas were located proximal to the splenic flexure, and 17 (19%) were classified as tubulovillous or villous. Moderate- to high-grade dysplasia was found in 29 (32%) adenomas and was associated with larger size (p less than 0.0001) and villous architecture (p = 0.0038). Two subjects harbored adenomas with invasive cancer. Seventy-one hyperplastic polyps were found in 40 (34%) subjects. The mean size of hyperplastic polyps was 3.4 mm, and 64 (90%) were located in the left colon. We conclude that, in this population, adenomas are common lesions that are frequently small. However, substantial proportions of these adenomas may be at risk for malignant degeneration due to the presence of villous architecture and higher grades of dysplasia. Because adenomas and hyperplastic polyps are endoscopically indistinguishable, all polyps found at endoscopy should be removed or ablated.

Flexible sigmoidoscopy may be ineffective for secondary prevention of colorectal cancer in asymptomatic, average-risk men.

Asymptomatic men (N = 114) 50 years of age or older had screening for colorectal neoplasia with flexible sigmoidoscopy followed by colonoscopy regardless of the sigmoidoscopic result. Our study objective was to determine the prevalence of patients having isolated adenomatous polyps in a proximal colonic segment in the absence of a distal index neoplasm within reach of the sigmoidoscope. Through the combined use of sigmoidoscopy and colonoscopy, adenomatous polyps were detected in 47 of 114 individuals (41%). A total of 88 adenomas was found. Seventeen patients had isolated neoplasms in proximal colonic segments in the absence of distal adenomas. These patients represented 15% of screened subjects (17 of 114) and 20% of individuals who lacked adenomas on sigmoidoscopy (17 of 84). The majority of proximal neoplasms were small (less than 1.0 cm), tubular adenomas. Flexible sigmoidoscopy may be ineffective for screening asymptomatic men for neoplasia. However, it remains to be determined if a 20% miss rate (for those with a normal sigmoidoscopic examination) is significant and whether small proximal adenomas are worth finding.

Endoscopic retrograde wire-guided brush cytology for diagnosis of patients with malignant obstruction of the bile duct.

A brush was adapted for use over a guide wire to facilitate reliable acquisition of cytological specimens from tight and potentially malignant strictures encountered during ERCP. Cells collected in this manner were assessed for abnormalities indicative of cancer. We have called this technique endoscopic retrograde wire-guided brush cytology (ERWBC). Thirty-nine strictures (24 malignant, 15 benign) in 34 patients were brushed. There were no complications, and all specimens were adequate for evaluation. Sixty percent of patients with cancer were diagnosed by ERWBC. Sensitivity was highest for cholangiocarcinoma (100%), intermediate for pancreatic cancer (60%), and lowest for patients with biliary obstruction due to metastatic disease (22%). There were no false-positive results (specificity, 100%). The positive and negative predictive values were 100% and 58%, respectively, and accuracy for the test was 72%. Collection of cytological specimens using a brush with a wire guide is effective especially for diagnosis of cholangiocarcinoma. A positive result is sufficient evidence for malignancy, and other invasive diagnostic tests are unnecessary. We recommend ERWBC for brushing all strictures of unknown cause during ERCP in an effort to make a diagnosis of cancer.

Eradication of diminutive polyps: a prospective evaluation of bipolar coagulation versus conventional biopsy removal.

Bipolar probe coagulation (BICAP) was evaluated and compared with conventional cold biopsy (CBx) as a potential therapeutic modality for eradication of diminutive colonic polyps (DPs). Seventy-seven and 79 DPs were treated with BICAP and CBx, respectively. Twenty-one percent of the BICAP and 29% of the CBx (p greater than 0.05) group had residual polypoid tissue detected at flexible sigmoidoscopy 3 weeks after treatment. Because of incomplete polyp removal, CBx and BICAP coagulation cannot be recommended as definitive therapies for DPs. Neoplasia was present in 22% of DPs located less than 60 cm from the anus, 73% of proximally located small polyps, and 32% of all DPs. Despite apparent eradication at the time of treatment, the incidence of residual polypoid tissue would suggest the need for critical evaluation of other modalities used to eradicate or remove DPs.

Mucinous adenocarcinoma of prostate.

The twenty-eighth case of mucinous adenocarcinoma of the prostate is reported. This microscopic variety of prostatic cancer is rare and aggressive; it metastasizes to bone, does not seem to respond to hormone therapy, and reacts positively to immunoperoxidase stain.

Mucosal pseudolipomatosis: an air pressure-related colonoscopy complication.

Mucosal pseudolipomatosis is a recently described colonoscopic finding, most likely caused by intramucosal air. We describe four asymptomatic patients with this lesion which completely resolved 3 weeks later on repeat colonoscopy. This is a benign, transient lesion with distinct endoscopic and histologic findings. The similarity between mucosal pseudolipomatosis and pneumatosis cystoides intestinalis is supportive of the mechanical theory for pneumatosis cystoides intestinalis.

The pathological, ultrasonographic and computerized tomographic characteristics of chronic hematocele.

We report a case of a chronic hematocele and describe its characteristics. The specific pathological lesion of a chronic hematocele consists of several neovascular formations covered by layers of fibrin. These lesions give characteristic ultrasonic and computerized tomographic images, consisting of several sharply circumscribed small spherical areas of soft tissue. When correctly interpreted before the initiation of surgical treatment, these images will obviate an orchiectomy, which is not always necessary.

Risk factors for blood loss from adenomatous polyps of the large bowel: a colonoscopic evaluation with histopathological correlation.

In 27 patients with 74 colonic polyps we prospectively evaluated polyp-related risk factors and specific histopathological characteristics that might result in blood loss from these lesions. Each polyp was endoscopically bathed in saline which was then aspirated back into a syringe through a catheter and tested for presence of blood on a Hemoccult II slide. Forty-nine polyps were excised. We found the following: 1) A relatively small proportion of adenomas (approximately 11%) have a propensity to bleed. 2) Approximately 22% of polyp-bearing patients have a bleeding adenoma. 3) Risk factors for bleeding include polyp size greater than 1.0 cm, presence of a stalk, and cherry-red color; associated histopathological findings include marked vascular congestion and intramucosal lakes of blood. 4) Clinically detectable bleeding occurs after intramucosal hemorrhage in the polyp head and dissection of blood into the bowel lumen through the glandular or surface epithelium. Most polyps are small, sessile and pink, without histopathological features of hemorrhage and are unlikely to bleed. Therefore, patients with Hemoccult-positive stools in whom such neoplasms are found should undergo further study to detect other causes of gastrointestinal blood loss. High-risk polyps in otherwise asymptomatic patients can be held responsible for bleeding; in them colonoscopic polypectomy with follow-up Hemoccult testing is sufficient management. Only if bleeding persists is study of other parts of the gut essential.

Involvement of the penis by rectocolic adenocarcinoma. Report of a case and review of the literature.

A case report of a rectal carcinoma metastasizing to the penis is reviewed along with a total of 44 similar cases reported in the world literature. Pertinent arguments are presented in favor of yet another possible route of metastases, namely the perineural route, which has not been considered previously. Cavernosography provides valuable information about the extent of tumor spread; used more often, it would lead to recognition of the rare opportunity when an aggressive surgical approach might achieve prolonged survival.

Prostatic tumors with penile secondaries. Review of the literature with a case report.

73 cases of penile metastatic tumors secondary to prostatic cancer have been collected from the literature (including a personal case) and have been thoroughly reviewed.

Coledocolitiase - analise de 162 casos (com enfase especial a diferenciacao entre litiase primaria e secundaria). / Common bile duct lithiasis - analysis of 162 cases (with special emphasis to differentiation between primary and secondary lithiasis)

162 casos de coledocolitiase operados na Clinica de Cirurgia Geral II do Hospital do Andarai foram analisados: 14 foram considerados como litiase primaria do coledoco e as restantes 148 como secundarias. O criterio para considerar a litiase primaria foi a concomitancia de: a) calculos moles, facilmente fragmentados a pressao digital; b) coledoco muito dilatado; c)vesicula sem calculo e cistico fino, ou com calculos duros, diferentes dos do coledoco. Sao analisados a sintomatologia, os achados cirurgicos e as operacoes realizadas nos 2 grupos de coledocolitiase. Houve 7 obitos operatorios (4,3%) e foi conseguido segmento em 88 pacientes operados entre 6 meses e 13 anos. E enfatizada a necessidade da cirurgia de drenagem biliar complementar (esfincteroplastia ou coledocoduodenostomia) em todos os casos de litiase primaria e nos de litiase secundaria quando ha oddite estenosante, grande dilatacao do coledoco ou multiplos calculos nos canais biliares. O seguimento de 88 pacientes operados mostrou otimo resultado em 93,2% dos casos