Subtyping of triple-negative breast cancers: its prognostication and implications in diagnosis of breast origin.

BACKGROUND: Triple-negative breast cancer (TNBC) subtyping by gene profiling has provided valuable clinical information. Here, we aimed to evaluate the relevance of TNBC subtyping using immunohistochemistry (IHC), which could be a more clinically practical approach, for prognostication and applications in patient management. METHODS: A total of 123 TNBC cases were classified using androgen receptor (AR), CD8, Forkhead box C1 protein (FOXC1), and doublecortin-like kinase 1 (DCLK1) into luminal androgen receptor (LAR), basal-like immunosuppressive (BLIS), mesenchymal-like (MES), and immunomodulatory (IM) subtypes. The IM cases were further divided into the IM-excluded and IM-inflamed categories by CD8 spatial distribution. Their clinicopathological and biomarker profiles and prognoses were evaluated. RESULTS: LAR (28.6%) and MES (11.2%) were the most and least frequent subtypes. The IHC-TNBC subtypes demonstrated distinct clinicopathological features and biomarker profiles, corresponding to the reported features in gene profiling studies. IM-inflamed subtype had the best outcome, while BLIS had a significantly poorer survival. Differential breast-specific marker expressions were found. Trichorhinophalangeal syndrome type 1 (TRPS1) was more sensitive for IM-inflamed and BLIS, GATA-binding protein 3 (GATA3) for IM-excluded and MES, and gross cystic disease fluid protein 15 (GCDFP15) for LAR subtypes. CONCLUSIONS: Our findings demonstrated the feasibility of IHC surrogates to stratify TNBC subtypes with distinct features and prognoses. The IM subtype can be refined by its CD8 spatial pattern. Breast-specific marker expression varied among the subtypes. Marker selection should be tailored accordingly.

Paracrine cyclooxygenase-2 activity by macrophages drives colorectal adenoma progression in the Apc Min/+ mouse model of intestinal tumorigenesis.

Genetic deletion or pharmacological inhibition of cyclooxygenase (COX)-2 abrogates intestinal adenoma development at early stages of colorectal carcinogenesis. COX-2 is localised to stromal cells (predominantly macrophages) in human and mouse intestinal adenomas. Therefore, we tested the hypothesis that paracrine Cox-2-mediated signalling from macrophages drives adenoma growth and progression in vivo in the Apc Min/+ mouse model of intestinal tumorigenesis. Using a transgenic C57Bl/6 mouse model of Cox-2 over-expression driven by the chicken lysozyme locus (cLys-Cox-2), which directs integration site-independent, copy number-dependent transgene expression restricted to macrophages, we demonstrated that stromal macrophage Cox-2 in colorectal (but not small intestinal) adenomas from cLys-Cox-2 x Apc Min/+ mice was associated with significantly increased tumour size (P = 0.025) and multiplicity (P = 0.025), compared with control Apc Min/+ mice. Transgenic macrophage Cox-2 expression was associated with increased dysplasia, epithelial cell Cox-2 expression and submucosal tumour invasion, as well as increased nuclear ß-catenin translocation in dysplastic epithelial cells. In vitro studies confirmed that paracrine macrophage Cox-2 signalling drives catenin-related transcription in intestinal epithelial cells. Paracrine macrophage Cox-2 activity drives growth and progression of Apc Min/+ mouse colonic adenomas, linked to increased epithelial cell ß-catenin dysregulation. Stromal cell (macrophage) gene regulation and signalling represent valid targets for chemoprevention of colorectal cancer.

The necessity of voiding cystourethrography in children with prenatally diagnosed hydronephrosis.

The postnatal persistence of fetal hydronephrosis requires further evaluation to establish whether pathological abnormalities are present. This study determined the necessity for voiding cystourethrography (VCUG) to identify vesicoureteral reflux (VUR) in children (n = 195) with prenatally diagnosed hydronephrosis. Among the study population, the prevalence of VUR was 17.4% (24 males, 10 females). There was a poor correlation between the severity of hydronephrosis, ureteral dilatation, presence of bilateral hydronephrosis and presence of VUR. Except for the frequency of urinary tract infections and the presence of renal damage on (99m)Tc-dimercaptosuccinic acid scans, VCUG was the only reliable method for confirming VUR in this study. The diagnosis of VUR is important for the early detection of renal damage. Further information is needed to develop the optimal approach to the evaluation of prenatal hydronephrosis, with reliable parameters that avoid invasive procedures such as VCUG.

Varying postprandial abdominovagal and cardiovagal activity in normal subjects.

BACKGROUND: Several studies have supported the hypothesis of different presentations in the autonomic nervous system (ANS) between cardiac and gastric vagal activity. Due to the regionality of the ANS, different responses among different organ systems to the same stimulation (such as a meal) are quite possible. METHODS: In this study we monitored the postprandial changes of heart rate variability (HRV) and gastrointestinal (GI) hormones to determine whether both responded in a similar pattern. Twenty-two healthy volunteers (6 males and 16 females) were enrolled. After recording a baseline ECG rhythm, further recordings were made at 20 min intervals for 120 min after a test meal. Serum human pancreatic polypeptide (PP), leptin, and total and active ghrelin levels were measured. KEY RESULTS: After the meal, HR increased significantly from baseline at each time point, except for 20 min after the meal. The high frequency (HF) power decreased significantly from 40 min to 120 min after the meal. In addition, the low frequency (LF) power also decreased significantly from 60 min to 120 min. However, the LF:HF ratio increased significantly from 20 min to 120 min. There was a marked increase (>2 fold) of PP at 20 min after the meal, and the increase was sustained throughout the test period. CONCLUSIONS & INFERENCES: These findings suggest that HRV reflects cardiac, but not equivalently, abdominovagal activity. Therefore, HRV as an abdominovagal activity measurement in patients with GI functional problems should be used with caution, and other markers such as PP should be included.

Endoscopic retrograde cholangiopancreatography, but not esophagogastroduodenoscopy or colonoscopy, significantly increases portal venous pressure: direct portal pressure measurements through endoscopic ultrasound-guided cannulation.

BACKGROUND AND STUDY AIMS: Changes in portal pressure during endoscopy have not been previously evaluated. The aims of this study were to assess the effect of esophagogastroduodenoscopy (EGD), colonoscopy, and endoscopic retrograde cholangiopancreatography (ERCP) on portal vein, inferior vena cava (IVC), and systemic pressures. PATIENTS AND METHODS: Five acute experiments were performed on 50-kg pigs utilizing endoscopic ultrasound (EUS)-guided catheterization of the portal vein and IVC. Systemic, intra-abdominal, IVC, and portal vein pressures were monitored during colonoscopy, EGD, and ERCP with endoscopic sphincterotomy. After endoscopy the animals were sacrificed for necropsy. The main outcome measure was pressure change during each type of endoscopic procedure. RESULTS: There were no significant changes in heart rate or systemic pressure during all endoscopic procedures. Intra-abdominal pressure increased during colonoscopy ( P = 0.02) and ERCP ( P = 0.007). However, mean portal venous pressure was significantly elevated only after the injection of contrast into the common bile duct, reaching its peak value at the time of biliary sphincterotomy (39.0 +/- 15.2 mm Hg vs. 13.4 +/- 3.6 mm Hg at baseline, P = 0.006). Mean peak IVC pressure was also elevated during ERCP, but it did not reach statistical significance (24.0 +/- 10.7 mm Hg vs. 12.6 +/- 4.1 mm Hg at baseline, P = 0.06). CONCLUSION: EGD and colonoscopy did not cause significant changes in portal vein, IVC, or systemic pressures. ERCP with biliary sphincterotomy increased portal pressure with only limited effect on IVC and systemic pressures. These new data indicate a possible connection between ERCP with sphincterotomy and portal pressure, and may be clinically important for patients with liver disease and other causes of portal hypertension who undergo this procedure.

In vivo differentiation of aerobic brain abscesses and necrotic glioblastomas multiforme using proton MR spectroscopic imaging.

BACKGROUND AND PURPOSE: Abscesses caused by aerobic bacteria (aerobic abscesses) can simulate intracranial glioblastomas multiforme (GBMs) in MR imaging appearance and single voxel (SV) proton MR spectroscopy of the central cavity. The purpose of our study was to determine whether MR spectroscopic imaging (SI) can be used to differentiate aerobic abscesses from GBMs. Our hypothesis was that metabolite levels of choline (Cho) are decreased in the ring-enhancing portion of abscesses compared with GBMs. MATERIALS AND METHODS: Fifteen patients with aerobic abscesses were studied on a 1.5T MR scanner using an SV method and an SI method. Proton MR spectra of 15 GBMs with similar conventional MR imaging appearances were used for comparison. The resonance peaks in the cavity, including lactate, cytosolic amino acids, acetate, succinate, and lipids, were analyzed by both SV MR spectroscopy and MRSI. In the contrast-enhancing rim of each lesion, peak areas of N-acetylaspartate (NAA), choline (Cho), lipid and lactate (LL), and creatine (Cr) were measured by MRSI. The peak areas of NAA-n, Cho-n, and Cr-n in the corresponding contralateral normal-appearing (-n) brain were also measured. Maximum Cho/Cr, Cho/NAA, LL/Cr-n, and Cho/Cho-n and minimum Cr/Cr-n and NAA/NAA-n ratios in abscesses and GBMs were compared using the Wilcoxon rank sum test. After receiver operating characteristic curve analysis, diagnostic accuracy was compared. RESULTS: Cytosolic amino acid peaks were found in the cavity in 7 of 15 patients with aerobic abscesses. Means and SDs of maximum Cho/Cr, Cho/NAA, LL/Cr-n, and Cho/Cho-n and minimum Cr/Cr-n and NAA/NAA-n ratios were 3.38 +/- 1.09, 3.88 +/- 2.13, 2.72 +/- 1.45, 1.98 +/- 0.53, 0.53 +/- 0.16, and 0.44 +/- 0.09, respectively, in the GBMs, and 1.77 +/- 0.49, 1.48 +/- 0.51, 2.11 +/- 0.67, 0.81 +/- 0.21, 0.48 +/- 0.2, and 0.5 +/- 0.15, respectively, in the abscesses. Significant differences were found in the maximum Cho/Cr (P = .001), Cho/NAA (P = .006), and Cho/Cho-n ratios (P < .001) between abscesses and GBMs. Diagnostic accuracy was higher by Cho/Cho-n ratio than Cho/Cr and Cho/NAA ratios (93.3% versus 86.7% and 76.7%). CONCLUSION: Metabolite ratios and maximum Cho/Cho-n, Cho/Cr, and Cho/NAA ratios of the contrast-enhancing rim were significantly different and useful in differentiating aerobic abscesses from GBMs by MRSI.

Lack of interleukin-4 receptor alpha chain-dependent signalling promotes azoxymethane-induced colorectal aberrant crypt focus formation in Balb/c mice.

Interleukin (IL)-4 receptor (IL-4R) alpha chain-dependent signalling by IL-4 and IL-13 promotes tumour growth and metastasis in mouse models of colorectal cancer. However, the role of IL-4R alpha-dependent signalling during the early, pre-malignant stages of colorectal carcinogenesis has not been investigated. Therefore, we investigated the effect of deletion of the IL-4R alpha gene on azoxymethane-induced colorectal aberrant crypt focus (ACF) multiplicity and size in Balb/c mice. IL-4R alpha(-/-) mice developed significantly more ACFs [median 8, inter-quartile range (IQR) 4-11.5; n = 9] than wild-type (WT) animals (median 4, IQR 1-6; n = 9; p = 0.04, Mann-Whitney U-test). There were significantly higher levels of IL-4 in serum from azoxymethane- and sham-treated IL-4R alpha(-/-) mice than WT animals, but no difference in serum IL-13 levels. In the absence of functional IL-4Rs, IL-13 can also signal via the IL-13R alpha2 receptor, leading to induction of transforming growth factor (TGF) beta, which has pro-tumourigenic activity at early stages of intestinal tumourigenesis. We found that mucosal TGFbeta mRNA levels and intestinal epithelial cell TGFbeta immunoreactivity were significantly higher in IL-4R alpha(-/-) mice than in WT animals. In summary, IL-4R alpha-dependent signalling has a protective, anti-neoplastic role during the post-initiation phase of azoxymethane-induced colorectal carcinogenesis in Balb/c mice. Our data should prompt thorough investigation of the role of IL-4R alpha-dependent signalling during human colorectal carcinogenesis, particularly as antagonism of IL-4R signalling represents a therapeutic strategy for asthma and other allergic diseases.

Preliminary pneumoperitoneum facilitates transgastric access into the peritoneal cavity for natural orifice transluminal endoscopic surgery: a pilot study in a live porcine model.

BACKGROUND AND STUDY AIMS: Safe entrance into the peritoneal cavity through the gastric wall is paramount for the successful clinical introduction of natural orifice transluminal endoscopic surgery (NOTES). The aim of the study was to develop alternative safe transgastric access to the peritoneal cavity. PATIENTS AND METHODS: We performed 11 survival experiments on 50-kg pigs. In sterile conditions, the abdominal wall was punctured with a Veress needle. The peritoneal cavity was insufflated with 2 L carbon dioxide (CO (2)). A sterile endoscope was introduced into the stomach through a sterile overtube; the gastric wall was punctured with a needle-knife; after balloon dilation of the puncture site, the endoscope was advanced into the peritoneal cavity. Peritoneoscopy with biopsies from abdominal wall, liver and omentum, was performed. The endoscope was withdrawn into the stomach. The animals were kept alive for 2 weeks and repeat endoscopy was followed by necropsy. RESULTS: The pneumoperitoneum, easily created with the Veress needle, lifted the abdominal wall and made a CO (2)-filled space between the stomach and adjacent organs, facilitating gastric wall puncture and advancement of the endoscope into the peritoneal cavity. There were no hemodynamic changes or immediate or delayed complications related to pneumoperitoneum, transgastric access, or intraperitoneal manipulations. Follow-up endoscopy and necropsy revealed no problems or complications inside the stomach or peritoneal cavity. CONCLUSIONS: Creation of a preliminary pneumoperitoneum with a Veress needle facilitates gastric wall puncture and entrance into the peritoneal cavity without injury to adjacent organs, and can improve the safety of NOTES.

Hybrid minimally invasive surgery--a bridge between laparoscopic and translumenal surgery.

BACKGROUND: The peroral transluminal approach to the peritoneal cavity appears safe, feasible, and may further reduce the invasiveness of surgery. However, flexible endoscopes have multiple limitations inside the peritoneal cavity, which can potentially be overcome by blending the use of both a laparoscope and a flexible upper endoscope--a hybrid approach. The goal of the present study was to evaluate a hybrid minimally invasive technique for cholecystectomy in a porcine model. METHODS: Hybrid cholecystectomies were performed in acute experiments on 50-kg pigs under general anesthesia. Pneumoperitoneum was created with a Veress needle, and a laparoscopic 10-mm port was inserted. Under laparoscopic observation, the gastric wall incision was done with an endoscopic needle-knife and sphincterotome, and the upper endoscope was advanced into the peritoneal cavity. A laparoscopic 10-mm port was inserted into the right upper quadrant of the abdomen for gallbladder traction to facilitate exposure of the cystic duct and artery. Via the biopsy channel of the flexible endoscope, and using a knife with an isolated tip, a needle knife, and clips, both the cystic duct and artery were identified, clipped, and transected. The gallbladder itself was then dissected and retracted through the mouth, and the gastric wall incision was closed with endoscopic clips. RESULTS: Five hybrid cholecystectomies were performed without complications. The laparoscopic port enabled a stable pneumoperitoneum, good traction and counter-traction, and improved spatial orientation and visualization. Necropsy did not reveal any intraperitoneal complications. CONCLUSIONS: The hybrid approach increases safety of initial gastric puncture and gastric wall incision, improves orientation and navigation of the flexible endoscope inside the peritoneal cavity, simplifies peroral transgastric cholecystectomy, and could be used to decrease invasiveness of laparoscopic surgery and to facilitate development and clinical introduction of transgastric endoscopic procedures. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00464-007-9329-2) contains supplementary material, which is available to authorized users.

Comparison of intraabdominal pressures using the gastroscope and laparoscope for transgastric surgery.

BACKGROUND: The peroral transgastric endoscopic approach for intraabdominal procedures appears to be feasible, although multiple aspects of this approach remain unclear. This study aimed to measure intraperitoneal pressure in a porcine model during the peroral transgastric endoscopic approach, comparing an endoscopic on-demand insufflator/light source with a standard autoregulated laparoscopic insufflator. METHODS: All experiments were performed with 50-kg female pigs under general anesthesia. A standard upper endoscope was advanced perorally through a gastric wall incision into the peritoneal cavity. The peritoneal cavity was insufflated with operating room air from an endoscopic light source/insufflator. Intraperitoneal pressure was measured by three routes: (1) through the endoscope biopsy channel, (2) through a 5-mm transabdominal laparoscopic port, and (3) through a 16-gauge Veress needle inserted into the peritoneal cavity through the anterior abdominal wall. The source of insufflation alternated between on-demand manual insufflation through the endoscopic light source/insufflator using room air and a standard autoregulated laparoscopic insufflator using carbon dioxide (CO(2)). RESULTS: Six acute experiments were performed. Intraperitoneal pressure measurements showed good correlation regardless of measurement route and were independent of the type of insufflation gas, whether room air or CO(2). On-demand insufflation with the endoscopic light source/insufflator resulted in a wide variation in pressures (range, 4-32 mmHg; mean, 16.0 +/- 11.7). Intraabdominal pressures using a standard autoregulated laparoscopic insufflator demonstrated minimal fluctuation (range, 8-15 mmHg; mean, 11.0 +/- 2.2 mmHg) around a predetermined value. CONCLUSION: Use of an on-demand unregulated endoscopic light source/insufflator for translumenal surgery can cause large variation in intraperitoneal pressures and intraabdominal hypertension, leading to the risk of hemodynamic and respiratory compromise. Safety may favor well-controlled intraabdominal pressures achieved with a standard autoregulated laparoscopic insufflator.

Prostaglandin E2-EP4 receptor signalling promotes tumorigenic behaviour of HT-29 human colorectal cancer cells.

The predominant product of cyclooxygenase (COX) activity in the colon, prostaglandin (PG) E2 promotes intestinal tumorigenesis. Expression of the PGE2 receptor EP4 is upregulated during colorectal carcinogenesis. Therefore, we investigated the role of elevated PGE2-EP4 receptor signalling in the protumorigenic activity of PGE2 by increasing EP4 receptor expression in HT-29 human colorectal cancer (CRC) cells (HT-29-EP4) by stable transfection. Elevated PGE2-induced EP4 receptor activity in HT-29 cells increased resistance to spontaneous apoptosis and promoted anchorage-independent growth, but had no effect on proliferation of HT-29-EP4 cells. EP4 receptor activation by PGE2 in HT-29-EP4 cells also led to development of fluid-filled cysts, which was associated with increased tight junction protein (occludin and zonula occludens-1) expression. Overexpression of the EP4 receptor in HT-29 cells led to basal EP4 receptor signalling in the absence of exogenous PGE2, which was explained by autocrine activity of endogenous, COX-2-derived PGE2 and constitutive, ligand-independent EP4 receptor activity. The predominant signalling pathway mediating antiapoptotic activity downstream of PGE2-EP4 receptor activation in HT-29-EP4 cells was elevation of cyclic adenosine monophosphate (cAMP) levels, which was associated with phosphorylation of cAMP-response element binding protein. EP4 receptor activation led to a small increase in phosphorylated extracellular signal-regulated kinase (ERK) 2 protein levels but inhibition of ERK phosphorylation did not abrogate the antiapoptotic activity of PGE2. However, PGE2-EP4 receptor signalling did not lead to trans-activation of the epidermal growth factor receptor in HT-29 cells. Inhibition of protumorigenic PGE2-EP4 receptor signalling represents a potential strategy for anti-CRC therapy that may avoid the toxicity associated with systemic COX inhibition.

A pollen-specific polygalacturonase from lily is related to major grass pollen allergens.

A pollen-specific gene from lily (Lilium longiflorum Thunb. cv. Snow Queen), designated LLP-PG, was characterized. Southern blots of lily genomic DNA indicated that LLP-PG is a member of a small gene family. A thorough sequence analysis revealed that the LLP-PG gene is interrupted by two introns and encodes a protein of 413 amino acids, with a calculated molecular mass of 44 kDa, and a pI of 8.1. Evaluation of the hydropathy profile showed that the protein has a hydrophobic segment at the N-terminus, indicating the presence of a putative signal peptide. A sequence similarity search showed a significant homology of the encoded protein to pollen polygalacturonases (PGs) from various plant species and to an important group (group 13) of grass pollen allergens. The LLP-PG transcript is pollen-specific and it accumulates only at the latest stage during pollen development, in the mature pollen. In contrast to other "late genes" LLP-PG transcript can neither be induced by abscisic acid (ABA) nor by dehydration. Immunoblot analyses of pollen protein extracts from lily, timothy grass and tobacco with IgG antibodies directed against LLP-PG and against the timothy grass pollen allergen, Phl p 13, indicated that lily LLP-PG shares surface-exposed epitopes with pollen PGs from monocotyledonous and dicotyledonous plants. Enzyme-linked immunosorbent assay (ELISA) analyses and inhibition ELISA assays with patients' IgE demonstrated a very low IgE reactivity of lily rLLP-PG and a lack of cross-reactivity between rLLP-PG and the timothy grass pollen allergen, rPhl p 13. These data demonstrated that despite the significant sequence homology and the conserved surface-exposed epitopes LLP-PG represents a low-allergenic member of pollen PGs.

Regulation of stromal cell cyclooxygenase-2 in the ApcMin/+ mouse model of intestinal tumorigenesis.

Cyclooxygenase-2 (Cox-2) is expressed predominantly by stromal cells in intestinal adenomas from the Apc(Min/+) mouse model of familial adenomatous polyposis. We investigated the mechanistic basis of stromal cell Cox-2 expression in Apc(Min/+) mouse adenomas, as well as Cox-2 expression and activity in histologically normal (HN) Apc(Min/+) mouse intestine, in order to gain further insights into regulation of Cox-2 as a potential chemoprevention target. Upregulation of Cox-2 in intestinal tumours is not an intrinsic feature of Apc(Min/+) macrophages as bone marrow-derived Apc(Min/+) macrophages did not exhibit an abnormality in Cox-2 expression or activity. Intestinal permeability to lactulose or mannitol was similar in Apc(Min/+) mice and wild-type littermates, implying that macrophage activation by luminal antigen is unlikely to explain stromal cell Cox-2 induction. Moreover, stromal cells exhibited differential expression of Cox-2 and inducible nitric oxide synthase, suggesting 'alternative' (M2) rather than 'classical' (M1) macrophage activation. Flow cytometric sorting of isolated stromal mononuclear cells (SMNCs), on the basis of M-lysozyme and specific macrophage marker expression, demonstrated that macrophages, neutrophils and non-myelomonocytic cells all contributed to lamina propria prostaglandin (PG) E(2) synthesis. However, the majority of PGE(2) synthesis by macrophages was via a Cox-2-dependent pathway compared with predominant Cox-1-derived PGE(2) production by non-myelomonocytic cells. SMNCs from HN Apc(Min/+) intestinal mucosa exhibited similar levels of Cox-2 mRNA and protein, but produced more Cox-2-derived PGE(2) than wild-type cells at 70 days of age. There was an age-dependent decline in PGE(2) synthesis by Apc(Min/+) SMNCs, despite tumour progression. These data suggest that other Cox-2-independent factors also control PGE(2) levels during Apc(Min/+) mouse intestinal tumorigenesis. Regulation of macrophage Cox-2 expression and other steps in PGE(2) synthesis (e.g. PGE synthase) are valid targets for novel chemoprevention strategies that could minimize or avoid systemic COX-2 inhibition.

Predictive factors of the long-term outcome in reflux esophagitis in a low-prevalence gastroesophageal reflux disease region.

BACKGROUND: There are no data concerning the long-term outcome of patients with reflux esophagitis in Taiwan. In this study the outcome and the specific prognostic indicators associated with outcome in patients were assessed retrospectively, 7 years after diagnosis of esophagitis. METHODS: The study comprised a total of 128 patients with endoscopic esophagitis, diagnosed between January and June 1995, at Taichung Veterans' General Hospital. The outcome at 7 years after diagnosis was assessed by outpatient or telephone interview. Factors associated with requiring long-term acid suppression therapy were analyzed. RESULTS: In all, 105 patients were eligible for analysis: 61 patients (58.1%) with LA (Los Angeles classification) grade A, 29 patients (27.6%) with grade B, 11 patients (10.5%) with grade C and 4 patients (3.5%) with grade D esophagitis. Seven years after diagnosis, there were 52 patients (49.5%) with no or occasional reflux symptoms, 8 patients (7.6%) with occasional symptoms requiring treatment with histamine-2 receptor antagonists (H2RAs), 12 patients (11.4%) with occasional symptoms requiring treatment with proton pump inhibitors (PPIs), as needed, and 33 patients (31.3%) with sustained symptoms needing daily maintenance with PPIs. CONCLUSION: Nearly 50% of patients in Taiwan with endoscopic esophagitis still required treatment 7 years after diagnosis. Approximately 31% of patients still required daily acid suppression therapy. Presence of hiatal hernia and the severity of esophagitis at initial endoscopy independently were predictive of those who would require long-term acid suppression therapy.

Two-port versus four-port laparoscopic cholecystectomy.

BACKGROUND: Two-port laparoscopic cholecystectomy has been reported to be safe and feasible. However, whether it offers any additional advantages remains controversial. This study reports a randomized trial that compared the clinical outcomes of two-port laparoscopic cholecystectomy versus conventional four-port laparoscopic cholecystectomy. METHODS: One hundred and twenty consecutive patients who underwent elective laparoscopic cholecystectomy were randomized to receive either the two-port or the four-port technique. All patients were blinded to the type of operation they underwent. Four surgical tapes were applied to standard four-port sites in both groups at the end of the operation. All dressings were kept intact until the first follow-up 1 week after surgery. Postoperative pain at the four sites was assessed on the first day after surgery using a 10-cm unscaled visual analog scale (VAS). Other outcome measures included analgesia requirements, length and difficulty of the operation, postoperative stay, and patient satisfaction score on surgery and scars. RESULTS: Demographic data were comparable for both groups. Patients in the two-port group had shorter mean operative time (54.6 +/- 24.7 min vs 66.9 +/- 33.1 min for the four-post group; p = 0.03) and less pain at individual subcostal port sites [mean score using 10-cm unscaled VAS: 1.5 vs 2.8 ( p = 0.01) at the midsubcostal port site and 1.3 vs 2.3 ( p = 0.02) at the lateral subcostal port site]. Overall pain score, analgesia requirements, hospital stay, and patient satisfaction score on surgery and scars were similar between the two groups. CONCLUSION: Two-port laparoscopic cholecystectomy resulted in less individual port-site pain and similar clinical outcomes but fewer surgical scars compared to four-port laparoscopic cholecystectomy. Thus, it can be recommended as a routine procedure in elective laparoscopic cholecystectomy.

Two liters of polyethylene glycol-electrolyte lavage solution versus sodium phosphate as bowel cleansing regimen for colonoscopy: a prospective randomized controlled trial.

BACKGROUND AND STUDY AIMS: As a bowel cleansing agent for colonoscopy, sodium phosphate (NaP) has been reported to have equal effectiveness and better patient tolerance in comparison with 4 l polyethylene glycol-electrolyte lavage (PEG-EL) solution. Poor patient tolerance is frequently associated with a large amount of fluid consumed, and better patient tolerance might therefore be expected if the volume of PEG-EL solution could be reduced. This study aimed to compare 2 l PEG-EL solution with NaP in relation to patients' tolerance and its effectiveness as a bowel cleansing agent. PATIENTS AND METHODS: Two hundred consecutive patients admitted to the day-procedure ward for elective colonoscopy were prospectively randomized to receive either a 2-l PEG-EL solution or a 90-ml oral NaP regimen. Patients with a history of congestive heart failure, impaired renal function (creatinine > 1.5 mg/dl), or previous colectomy were excluded from the study. The patients completed a questionnaire to assess their tolerance of bowel preparation before the colonoscopy. Endoscopists, who were blinded to the type of regimen that had been used, scored the adequacy of bowel preparation from the rectum to cecum using a defined endoscopic score. RESULTS: Two hundred patients were included in this randomized trial. Nine patients were excluded, due to either an incomplete questionnaire (two in the PEG-EL group, one in the NaP group) or inability to complete the bowel preparation regimen (four in the PEG-EL group and two in the NaP group). The demographic data were comparable in the two groups. There were no differences between the two groups with regard to willingness to repeat the regimen, ease of consumption, acceptability of the bowel preparation regimen, or the endoscopists' satisfaction with the quality of bowel preparation. The NaP group had a better mean endoscopic score at the cecum compared with the PEG-EL group (1.47 +/- 1.15 vs. 1.05 +/- 0.76; P = 0.007). CONCLUSIONS: The effectiveness and patient tolerance of the 2-l PEG-EL solution is comparable with that of oral NaP. The 2-l PEG-EL solution is therefore an effective alternative as a bowel-cleansing agent for colonoscopy.

Severe gastrointestinal bleeding after hematopoietic cell transplantation, 1987-1997: incidence, causes, and outcome.

OBJECTIVE: Severe GI bleeding after hematopoietic cell transplantation is commonly due to lesions that are unusual in nontransplant patients. The frequency of GI bleeding appears to have decreased over the last decade, but the reasons have not been readily apparent. We sought to determine the incidence of severe bleeding during two time periods, to describe the causes and outcomes of bleeding, and to analyze the reasons behind an apparent decline in severe bleeding over the decade covered. METHODS: During 1986-1987 and 1996-1997, we followed all patients with and without severe bleeding at our institution, a marrow transplant center. RESULTS: Over this decade, the incidence of severe bleeding declined from 50/467 (10.7%) to 15/635 (2.4%) (p < 0.0001). Overall mortality from intestinal bleeding declined from 3.6% to 0.9% (p = 0.002), but mortality in those with bleeding remained high (34% vs 40%). The onset (day 42 vs 47) and platelet counts (35,994 vs 37,600/microl) were similar, but the sites and causes of bleeding were different. During 1986-1987, 27/50 patients bled from multiple GI sites, viral and fungal ulcers, or graft-versus-host disease (GVHD). Over the decade, bleeding from GVHD had decreased 80% (p < 0.0001), and bleeding from viral (p < 0.0001) and fungal (p = 0.023) ulcers almost disappeared. CONCLUSIONS: The incidence of severe GI bleeding has declined significantly over the last decade because of prevention of viral and fungal infections and severe acute GVHD. However, severe bleeding after transplant remains a highly morbid event, particularly among patients with GVHD.

Effect of electrical stimulation on acupuncture points in diabetic patients with gastric dysrhythmia: a pilot study.

BACKGROUND/AIMS: Abnormal gastric slow-wave frequencies have been observed in diabetic gastroparesis and are associated with impaired antral motor activity. In this study, we aimed at evaluating the effect of acupuncture on gastric slow waves in diabetic patients with symptoms suggesting gastric motor dysfunction. METHODS: Fifteen patients with type II diabetes who had had dyspeptic symptoms for more than 3 months were enrolled. Two acupuncture needles were inserted into the subjects' legs at the Zusanli points, and electrical stimulation (2-Hz pulses) was delivered for 30 min. Cutaneous electrogastrography was performed for 30 min at baseline, for 30 min during acupuncture, and for an additional 30 min after acupuncture. Serum gastrin, motilin, and human pancreatic polypeptide levels were also measured. RESULTS: There was a significant increase in the percentages of normal frequency during and after acupuncture (baseline vs. acupuncture and after acupuncture 21.99 +/- 19.38% vs. 45.93 +/- 19.72 and 48.92 +/- 19.56%; p < 0.01). In addition, the percentage of tachygastric frequency was decreased significantly during and after acupuncture. The dominant frequency was also changed significantly. There was an increase of serum human pancreatic polypeptide during acupuncture (baseline vs. acupuncture 56.96 +/- 27.64 vs. 73.11 +/- 22.37 pmol/l; p < 0.05). CONCLUSIONS: The results of this study revealed that electrical stimulation at the Zusanli points could increase the percentage of normal electrogastrography frequency and decrease the percentage of tachygastric frequency in diabetic patients. The data indicate that acupuncture may enhance the regularity of gastric myoelectrical activity in diabetic patients.

Telomere length and telomerase catalytic subunit expression in non-astrocytic gliomas.

Telomerase activation has been implicated as a major factor in the development of cancer. In our previous study we reported on the telomerase activity of a variety of gliomas. To further investigate the role of telomere and telomerase regulation in the pathogenesis of non-astrocytic gliomas, we examined the telomere length and the mRNA expression of telomerase reverse transcriptase gene (hTERT) and telomerase-associated protein (hTEP) in a series of 27 oligodendroglial and 18 ependymal tumors in this study. No statistical difference was found between the mean telomere length in telomerase-positive and telomerase-negative tumors (11.5 kb vs 13.1 kb; p = 0.424), although a slightly shorter length was observed in telomerase-positive oligodendroglial tumors. mRNA expression of hTERT was highly correlated with the telomerase activity status. hTERT was expressed in 8/8 (100%) and 2/2 (100%) telomerase-positive oligodendroglial and ependymal tumors, respectively, whereas 3/6 (50%) telomerase-negative oligodendroglial tumors and no telomerase-negative ependymal tumors showed expression. In contrast, hTEP1 mRNA was widely expressed in both telomerase-positive and telomerase-negative oligodendroglial and ependymal tumors. Our data support the notion that hTERT plays a critical role in determining the enzymatic activity of human telomerase. It has recently been proposed that both p16(INK4)/Rb pathway inactivation and telomerase activity were required for immortalization of epithelial cells. Although lack of p(16INK4a) expression was detected in a substantial proportion of tumors, no correlation between the p16(INK4a) or pRb protein expression and telomerase activity was observed in our series of non-astrocytic tumors.

Detection of chromosomal imbalances in growth hormone-secreting pituitary tumors by comparative genomic hybridization.

Although recent molecular investigations have identified a number of genetic alterations that are associated with the development of pituitary adenomas, the exact pathogenesis mechanism of these tumors remains largely unknown. In this study, we used a genome-wide survey to detect specific genetic changes within the genome of pituitary adenomas. A series of 10 growth hormone-secreting adenomas were analyzed for their genetic imbalances on all 22 autosomes by comparative genomic hybridization (CGH). Chromosomal imbalances were detected in 8 GH-secreting adenomas, whereas 2 tumors had no detectable genetic abnormalities. Chromosome gains were more frequent than losses. Overrepresentation of whole or parts of chromosomes were detected in 5/10 (50%) in 19, 3/10 (30%) in each of 5, 9, and 22q, 2/10 (20%) in 17p12-q21, whereas DNA loss were 3/10 (30%) in 13q and 2/10 (20%) in 18. No detectable gain or loss of genetic material was observed in chromosomes 7, 8, 10, 12, 15, and 20. The findings of overrepresentation of chromosomes 5q, 9p, 17q and DNA loss of chromosome 18 were consistent with those detected in nonfunctioning adenomas (Daniely M, Aviram A, Adams EF, et al:J Clin Endocrinol Metab 83:1801-1805, 1998) suggesting that the development of pituitary tumors, at least in somatotroph and nonfunctioning adenomas, may share common pathway. Frequent amplifications in chromosomes 19 and 22q imply that candidate genes residing in these chromosomal regions may be involved in the pathogenesis of GH-secreting adenomas.