Impact of procedural multimedia instructions for pH BRAVO testing on patient comprehension: a prospective randomized study.

The positive impact on patient comprehension and improved procedural outcomes when multimedia is utilized to convey instructions preprocedurally has been previously shown for gastrointestinal procedures such as colonoscopy. However, in gastroesophageal reflux testing (GERD), we continue to utilize verbal and written instructions to establish this diagnosis when we use BRAVO pH testing. This is arguably a more complex procedure involving stopping medications, placement of a device, and maintaining an accurate diary for the duration of the testing. We hypothesize that by utilizing multimedia to relay complex textual information, patients will have improved comprehension of periprocedural instructions thereby improving data entry and satisfaction of expectations during the procedure. Prospective randomized study of 120 patients undergoing endoscopic placement of the BRAVO pH monitoring capsule for evaluation of GERD receive either written preoperative instructions (control) or written plus video instructions (video group). A composite comprehension score was calculated using procedure-specific parameters of data entry over the 48-hour monitoring period. Patient satisfaction was evaluated on the basis of a five-point Likert scale. Extent of patient satisfaction was defined by the fulfillment of patient expectations. Exclusion criteria included patients who did not have access to the video or did not complete follow-up. Seventy-eight patients completed all follow-up evaluations. The video group (n = 44) had a significantly higher mean comprehension score when compared to the control group (n = 34) (9.6 ± 1.4 vs. 7.4 ± 2.0, P = 0.01). Overall satisfaction with instructions was significantly higher in the intervention group (91% vs. 47%, p 0.01). We detected no significant difference in comprehension or satisfaction scores in subgroup analyses of the video group comparing patients <65 and ≥65 years of age and by education level. Compared to standard written instructions, video instructions improved patient comprehension based on data evaluation, and satisfaction. Therefore, clinicians should consider incorporation of multimedia instructions to enhance patient periprocedural expectations and understanding of reflux pH testing using the BRAVO procedure.

Clinicopathological and prognostic analysis of follicular thyroid carcinoma in a single institute over a 15-year period.

BACKGROUND: This study was to evaluate the clinicopathological and prognostic features of follicular thyroid carcinoma (FTC) in our institute over a 15-year period. METHODS: The clinical features, management and outcome of 134 consecutive patients were analyzed according to the time of diagnosis: Group I (1997-2001), Group II (2002-2006), and Group III (2007-2011). RESULTS: As time advanced, the ratio of FTC to papillary thyroid carcinoma decreased from 8.7% in group I to 4.3% in group III (p = 0.000). The percentage of patients undergoing total thyroidectomy seemed to be more commonly used in the later periods - from 10.5% in group I to 21.8% in group II and 18.9% in group III. The median diameter of tumors in group I was 4.2 cm and it showed a sharp decrease to 2.8 cm in group II and 2.9 cm in group III respectively. There was a trend towards a higher stage in patients from Group I vs. patients from Groups II and III (stage IV, 15.8% vs. 2.2% and 4.3%, p = 0.072). The outcome was improved in terms of disease-free survival (DFS). The 3-year DFS rate improved from 77.8% in group I to 93.7% in group II and 100% in group III (p = 0.008). CONCLUSIONS: The clinical features, management and outcome of FTC patients changed over 15-year period. Patients diagnosed after 2001 had a better prognosis. This improvement was probably related to earlier diagnosis with smaller tumor size and presentation at earlier tumor stage.

A general method to derive robust organ-specific gene expression-based differentiation indices: application to thyroid cancer diagnostic.

Differentiation is central to development, while dedifferentiation is central to cancer progression. Hence, a quantitative assessment of differentiation would be most useful. We propose an unbiased method to derive organ-specific differentiation indices from gene expression data and demonstrate its usefulness in thyroid cancer diagnosis. We derived a list of thyroid-specific genes by selecting automatically those genes that are expressed at higher level in the thyroid than in any other organ in a normal tissue's genome-wide gene expression compendium. The thyroid index of a tissue was defined as the median expression of these thyroid-specific genes in that tissue. As expected, the thyroid index was inversely correlated with meta-PCNA, a proliferation metagene, across a wide range of thyroid tumors. By contrast, the two indices were positively correlated in a time course of thyroid-stimulating hormone (TSH) activation of primary thyrocytes. Thus, the thyroid index captures biological information not integrated by proliferation rates. The differential diagnostic of follicular thyroid adenomas and follicular thyroid carcinoma is a notorious challenge for pathologists. The thyroid index discriminated them as accurately as did machine-learning classifiers trained on the genome-wide cancer data. Hence, although it was established exclusively from normal tissue data, the thyroid index integrates the relevant diagnostic information contained in tumoral transcriptomes. Similar results were obtained for the classification of the follicular vs classical variants of papillary thyroid cancers, that is, tumors dedifferentiating along a different route. The automated procedures demonstrated in the thyroid are applicable to other organs.

Intercellular adhesion molecule-1 (ICAM-1) is upregulated in aggressive papillary thyroid carcinoma.

BACKGROUND: Intercellular adhesion molecule-1 (ICAM-1) is implicated in carcinogenesis. In this study we examined the expression of ICAM-1 in papillary thyroid cancer (PTC). We hypothesized that ICAM-1 correlates with indicators of tumor aggressiveness in PTC. METHODS: Thirty-five primary and metastatic PTCs, five follicular adenomas, five Hashimoto thyroiditis, five nodular hyperplasia, and eight normal thyroid tissue samples were analyzed for ICAM-1 gene expression using quantitative reverse-transcription polymerase chain reaction (RT-PCR). ICAM-1 gene expression was analyzed at protein level by immunohistochemistry (IHC) using a semiquantitative score. Gene expression and intensity levels were correlated with markers of tumor aggressiveness including BRAF V600E mutation, tumor size, extrathyroidal extension (ETE), angiolymphatic invasion, and lymph node metastasis. RESULTS: ICAM-1 gene expression was higher in PTC (p = 0.01) and lymph node metastases (p = 0.03) when compared with benign tumors and Hashimoto's. Furthermore, PTCs exhibiting BRAF V600E mutation (p = 0.01), ETE (p < 0.01), and lymph node metastasis (p = 0.02) were associated with higher ICAM-1 levels. Gene expression correlated with protein levels on IHC. Additionally, poorly differentiated thyroid carcinoma had a higher ICAM-1 intensity score compared with well-differentiated carcinoma (p = 0.03). CONCLUSIONS: ICAM-1 expression is upregulated in papillary thyroid carcinoma. Furthermore, ICAM-1 upregulation correlated with aggressive tumor features such as BRAF V600E mutation, ETE, and lymph node metastasis, suggesting that ICAM-1 plays a role in thyroid cancer progression.

Laparoscopic distal pancreatectomy for inflammatory pseudotumor of the pancreas.

An 82-year-old woman presented with abdominal pain, nausea, emesis, and weight loss of ~25 lb over 6 months. A CT scan and MRI of the abdomen revealed a mass in the tail of the pancreas that was suspicious for malignancy. The patient underwent successful laparoscopic distal pancreatectomy and was discharged home on the 4th postoperative day after an uneventful course. Pathology revealed an inflammatory pseudotumor of the pancreas (IPT). Pancreatic IPT is a rare entity, and this case represents the first report of laparoscopic resection of this lesion. The presentation, diagnosis, histologic features, and therapy of IPT of the pancreas are reviewed.

Hand-assisted laparoscopic autoaugmentation gastrocystoplasty.

BACKGROUND: Autoaugmentation gastrocystoplasty has been previously performed successfully. This set of experiments was conducted to determine the feasibility of performing autoaugmentation gastrocystoplasty laparoscopically. METHODS: Hand-assisted laparoscopic autoaugmentation gastrocystoplasty was performed on 15 mongrel dogs. The surgery was carried out with two 10-mm trocars and a 6-cm Pfannenstiel incision. The gastric wedge, supplied by the right gastroepiploic artery, was resected with two applications of an endoscopic gastrointestinal anastomosis (GIA) stapler. The pedicle was demucosalized, and the anastomosis to the bladder was completed through the Pfannenstiel incision. RESULTS: All of the dogs were successfully treated laparoscopically and were eating at 48 h. There was no evidence of anastomotic leak dehiscence at the gastric resection staple line. CONCLUSION: Hand-assisted laparoscopic autoaugmentation gastrocystoplasty can be performed successfully in dogs. This operation may offer a superior alternative to standard bladder autoaugmentation procedures in children suffering from congenital bladder disorders.

p44/p42-MAP kinase expression in papillary thyroid carcinomas.

BACKGROUND: Recent studies suggest that mitogen-activated protein (MAP) kinase contributes to the growth and tumorigenesis of human epithelial cancers. Furthermore, blockade of this pathway may inhibit the growth of epithelial cancers. To determine whether MAP kinase is activated in human papillary thyroid carcinomas (PTCs), we analyzed the presence of native MAP kinase (MAPK) and activated phosphorylated MAP kinase (pMAPK) in papillary thyroid cancers and thyroid carcinoma cell lines. METHODS: Protein from paired specimens of 10 patients with PTC was analyzed by immunoblot for MAPK and pMAPK. In addition, MAPK protein expression and cell growth were analyzed in 3 thyroid tumor cell lines treated with a mitogen extracellular kinase inhibitor, U0126. RESULTS: All 10 PTCs had equal expression of MAPK in the tumors and adjacent normal tissue. Six of the 10 tumors demonstrated increased expression of the pMAPK in the tumor specimen compared to the adjacent normal tissue. Interestingly, 3 of 4 patients without differential expression had multifocal PTC. The pMAPK was expressed constitutively in 3 thyroid cancer cell lines. The MAPK inhibitor treatment decreased pMAPK expression and decreased serum-induced growth in all 3 cell lines. CONCLUSIONS: MAP kinase activation is common in PTCs and may offer a potential target for growth inhibition of PTCs.

Characterisitcs of patients having thyroid surgery under regional anesthesia.

BACKGROUND: Recently local/regional anesthesia has been reintroduced as an alternative to general anesthesia for thyroidectomy. This study was undertaken to analyze characteristics and outcomes of patients who had thyroid surgery performed under regional anesthesia compared with those who had thyroidectomy under general anesthesia. STUDY DESIGN: One hundred seventy-five consecutive patients who underwent thyroid surgery under regional or general anesthesia during a 3-year period were analyzed. Fifty-eight operations were performed under regional anesthesia and 116 under general anesthesia. Patient characteristics analyzed included age, gender, obesity, anesthesia class, and tumor pathology. Postoperative complications, including nausea or vomiting, were compared. Additionally, operative times and length of stay in each group were compared. RESULTS: Patient characteristics including age, gender, tumor pathology, and anesthesia class were similar in both groups. But only 2% of patients treated under regional anesthesia were obese compared with 23% under general anesthesia. Although not significant, there was a trend toward decreased incidence of nausea and vomiting in the regional group. Other complications for the regional and general anesthesia groups were equal at 3%. Two patients required conversion to general anesthesia. Complications in the general anesthesia group included one episode of transient symptomatic hypocalcemia, two patients with transient vocal cord paralysis, and one episode of hematoma. Finally, there was a statistically significant increase in total operating room time and length of stay for the general anesthesia group. CONCLUSIONS: Regional anesthesia is a safe alternative to general anesthesia for patients undergoing thyroid surgery. Patients who cannot communicate verbally with the surgical team or who are obese may not be ideal candidates for regional anesthesia. The use of regional anesthesia results in a decreased length of stay and similar operative and operating room times.

Large-volume liposuction complicated by retroperitoneal hemorrhage: management principles and implications for the quality improvement process.

Large-volume liposuction can be associated rarely with major medical complications and death. The case of exsanguinating retroperitoneal hemorrhage that led to cardiopulmonary arrest in an obese 47-year-old woman who underwent large-volume liposuction is described. Extensive liposuction is not a minor procedure. Performance in an ambulatory setting should be monitored carefully, if it is performed at all. Reporting of adverse events associated with outpatient procedures performed by plastic surgeons should be mandated. Hemodynamic instability in the early postoperative period in an otherwise healthy patient may be due to fluid overload, lidocaine toxicity, or to hemorrhagic shock and must be recognized and treated aggressively. Guidelines for the safe practice of large-volume liposuction need to be established.

Cyclooxygenase-2 expression is up-regulated in human pancreatic cancer.

A large body of evidence suggests that cyclooxygenase-2 (COX-2) is important in gastrointestinal cancer. The purpose of this study was to determine whether COX-2 was expressed in adenocarcinoma of the human pancreas. Quantitative reverse transcription-PCR, immunoblotting, and immunohistochemistry were used to assess the expression of COX-2 in pancreatic tissue. Levels of COX-2 mRNA were increased by >60-fold in pancreatic cancer compared to adjacent nontumorous tissue. COX-2 protein was present in 9 of 10 cases of adenocarcinoma of the pancreas but was undetectable in nontumorous pancreatic tissue. Immunohistochemical analysis showed that COX-2 was expressed in malignant epithelial cells. In cultured human pancreatic cancer cells, levels of COX-2 mRNA and protein were induced by treatment with tumor-promoting phorbol esters. Taken together, these results suggest that COX-2 may be a target for the prevention or treatment of pancreatic cancer.

Telomerase activity in the differentiation of benign and malignant adrenal tumors.

BACKGROUND: Telomerase is an RNA-dependent DNA polymerase that extends the ends of chromosomes by synthesizing the 6 oligonucleotide repeat TTAGGG and thus serves as a marker for cellular immortality. Although absent in most adult somatic tissues, telomerase activity is present in stem cells and is reactivated in nearly all primary human malignancies. In this study we sought to determine whether tumors of the adrenal glands contain telomerase activity and whether telomerase activity can be used to differentiate benign and malignant tumors of the adrenal glands. METHODS: Tissue was obtained from 23 specimens at adrenalectomy. Adjacent normal adrenal tissue was obtained for control. All specimens were rapidly frozen and stored at -80 degrees C until assay. Telomerase activity was determined by the telomeric repeat amplification protocol (TRAP). RESULTS: Telomerase activity was present in 5 of 23 (22%) of the adrenal tumors. All 3 malignant tumors were strongly TRAP positive. There was a single cortical adenoma that had very weak telomerase activity. The single TRAP-positive tumor of the adrenal medulla was a ganglioneuroma. CONCLUSIONS: Benign adrenal tumors infrequently contain telomerase activity, whereas telomerase reactivation appears to be common in malignant tumors of the adrenal glands. These data suggest that determination of telomerase activity may offer a novel way to facilitate the differentiation of benign and malignant adrenal tumors.

Immunonutrition: the role of arginine.

Clearly, arginine has great potential as an immunomodulator and may prove useful in catabolic conditions such as severe sepsis and postoperative stress. there is a body of evidence suggesting that supplemental arginine upregulates immune function and reduces the incidence of postoperative infection. More modest improvements in nitrogen balance have been observed. Tumor response to arginine appears to depend on the immunogenicity of the particular tumor and on the requirement of arginine by the tumor as a growth substrate. Of note, ornithine shares the thymotrophic, immunostimulatory and secretagogue effects of arginine. It is, therefore, likely that these compounds share the same cellular mechanism of action or that arginine acts via increasing the concentration of available ornithine. The role of arginine in the injured patient and in the tumor-bearing host demands additional study based on the promising experimental evidence regarding the supplemental use of arginine.

Detection of telomerase activity in breast masses by fine-needle aspiration.

BACKGROUND: Telomerase is an RNA-dependent DNA polymerase that compensates for the telomere shortening that occurs in its absence. Reactivation of telomerase is thought to be an important step in cellular immortalization, and recent studies have indicated that telomerase activity is often detected in primary human malignancies. The clinical implications of telomerase activity in human tumors are currently under investigation. METHODS: Eighty-nine samples (46 FNAs and 43 gross tissue biopsies) from 44 patients with breast masses were analyzed prospectively for the presence of telomerase activity by a modification of the telomere repeat amplification protocol (TRAP). All samples were obtained directly from the excised mass at the time of specimen removal in the operating room. RESULTS: Telomerase activity was detected in 17 of 19 (90%) FNA samples and 15 of 18 (83%) invasive breast cancer tissue biopsies. Telomerase was also detected in 9 of 16 (56%) FNAs and 8 of 15 (53%) tissue biopsies from 16 fibroadenomas. Other benign proliferative lesions (n = 5) did not have detectable telomerase activity in either FNA or tissue specimens. FNA-TRAP results correlated with the gross tissue specimen TRAP results in 95% of all cases. CONCLUSION: The FNA-TRAP assay for telomerase detection is a highly sensitive and accurate method for the detection of telomerase activity in breast masses. Future application of these techniques should facilitate evaluation of telomerase as a tumor marker in the clinical management of breast and other solid malignancies.

Nutritional support of the cancer patient.

Malnutrition, a common problem in cancer patients, adversely affects survival and quality of life. It results from several factors that alter nutritional intake and cause massive metabolic disturbances. Anticancer therapies may compound the malnutrition. Optimal nutrition improves therapeutic modalities and the clinical course and outcome. Oral nutrition should be used whenever possible; in patients unable to ingest adequate amounts orally, enteral and parenteral feedings are safe and effective.

Surgical complications of nonsteroidal antiinflammatory drug-induced small bowel ulceration.

BACKGROUND: The association between nonsteroidal antiinflammatory drug (NSAID) intake and gastroduodenal peptic ulceration is well recognized. Recent experimental data implicate NSAIDs in the development of a similar spectrum of pathologic lesions of the small bowel. However, clinically significant NSAID-induced small bowel ulcerations have been reported infrequently. This study sought to examine small bowel complications of NSAID use requiring surgical intervention. STUDY DESIGN: A retrospective study of all patients (n = 283) who underwent small bowel resection on the general surgery services at the University of Texas Southwestern Medical Center during a 3-year period from 1991 to 1994 was conducted. Patients who had a history of chronic NSAID use, no other predisposing risk factors for gastrointestinal bleeding, and pathologically confirmed small bowel ulcerations complicated by hemorrhage, perforation, or obstruction were included in this study. RESULTS: Eleven patients with 12 surgical complications of NSAID-induced small bowel ulcerations were identified. These 11 patients all underwent emergent laparotomies with small bowel resection (one patient had two separate operations, 8 months apart). Small bowel ulcerations were noted to occur in the jejunum (4) and the ileum (8) and were multiple in half of the cases. Complications included bleeding (50%), perforation (33%), and obstruction (17%). CONCLUSIONS: This report is the first examining a series of surgical complications of NSAID-associated small bowel ulcerations. Our data suggest that small bowel complications of NSAID use requiring surgical intervention may occur more frequently than is currently recognized and, like peptic ulcer disease attributed to NSAIDs, result in significant morbidity and mortality.

Rapid, nonradioactive screening for mutations in exons 10, 11, and 16 of the RET protooncogene associated with inherited medullary thyroid carcinoma.

Germline mutations in exons 10, 11, and 16 of the RET protooncogene are associated with the heritable cancer syndromes multiple endocrine neoplasia (MEN) type 2A, familial medullary thyroid carcinoma (FMTC), and MEN type 2B. Nonradioactive mutation analysis with nondenaturing Phastgels and the Phast System was performed on DNA amplified by the polymerase chain reaction from exons 10, 11, and 16 of the RET protooncogene from patients with MEN 2A, MEN 2B, or FMTC. The analysis requires approximately 45-90 min for electrophoresis and 35 min for staining. This assay detected 20 of 21 different mutations that represented approximately 90% of all known mutations associated with these lesions. A rare silent polymorphism within exon 10 was also detected. This form of mutation analysis provides simple, rapid, and highly sensitive nonradioactive detection of mutations known to be associated with MEN 2A, FMTC, and MEN 2B.

Telomerase activity in benign and malignant thyroid diseases.

BACKGROUND: Telomerase, an enzyme associated with cellular immortality, is expressed by most malignant cells and is inactive in most normal somatic cells, with the excitation of proliferative stem cells, male germ cells, and activated lymphocytes. The measurement of telomerase activity in clinically obtained tissue samples may provide useful information as both a diagnostic and prognostic marker. In this study, we sought to determine whether telomerase activity might prove helpful in the assessment of benign and malignant thyroid tumors. METHODS: A modified, semiquantitative polymerase chain reaction-based telomeric repeat amplification protocol assay was used for detection of telomerase activity in 59 samples obtained at thyroidectomy, including 15 thyroid cancers, 22 benign thyroid diseases, and 22 adjacent normal thyroid tissues. RESULTS: Four of 13 differentiated thyroid carcinomas (30%) and 2 of 2 medullary carcinomas (100%) expressed telomerase activity. Unexpectedly, we also detected activity in 3 of 22 (14%) adjacent normal thyroid tissues and 6 of 22 (28%) benign thyroid diseases. Pathologic review of the telomerase-positive benign specimens revealed that many contained extensive lymphoid infiltrates with germinal centers (six of nine, 67%), as did two of four telomerase-positive papillary carcinomas. CONCLUSIONS: In contradistinction to other epithelial carcinomas, telomerase does not appear to be frequently reactivated in differentiated thyroid carcinomas.

The role of tumor necrosis factor and nitric oxide in the acute cardiovascular response to endotoxin.

OBJECTIVE: This study was designed to examine the differential effects of tumor necrosis factor (TNF) and nitric oxide on the acute cardiovascular changes that occur in response to endotoxemia. SUMMARY BACKGROUND DATA: Recent studies have suggested that some, if not all, of the cardiovascular effects of TNF are mediated through release of nitric oxide. However, the mechanisms through which TNF and nitric oxide induce hypotension and shock in vivo in response to systemic endotoxemia remain poorly characterized, despite current interest in the use of nitric oxide antagonists to ameliorate septic shock. METHODS: A reproducible model of endotoxemia was established in adult Sprague-Dawley rats. The acute cardiovascular changes that occur after bolus infusion of endotoxin was then determined in rats treated with either TNF antibody, N-methyl arginine, or both. RESULTS: Inhibition of either TNF or nitric oxide restores mean arterial blood pressure to normal after endotoxemia (p < 0.05). However, nitric oxide exerts its effects principally on the peripheral vasculature, whereas TNF appears to act on the myocardium. A combination of TNF antiserum pretreatment and N-methyl arginine administration is necessary to return mean arterial blood pressure to normal 60 minutes after endotoxin infusion. CONCLUSION: Tumor necrosis factor and nitric oxide mediate the acute cardiovascular effects of endotoxemia through distinct mechanisms. Nitric oxide is released as a result of both TNF-dependent and TNF-independent mechanisms, whereas the cardiovascular effects of TNF are only partially mediated through nitric oxide.