The spiral enteroscopy training initiative: results of a prospective study evaluating the Discovery SB overtube device during small bowel enteroscopy (with video).

BACKGROUND AND AIM: Indications for small-bowel enteroscopy are increasing, but advancing the endoscope to the ileum remains challenging, especially for less experienced operators. The aim was to evaluate the ease of use, safety, and efficacy of the Discovery SB overtube (Spirus Medical, Stoughton, Massachusetts, USA) during SB enteroscopy by physicians with no experience of the device. PATIENTS AND METHODS: Thirty-three "untrained" endoscopists performed spiral enteroscopy during one of four 2-day training modules. Data were prospectively collected. Patient demographics, depth and time to maximal insertion, total procedure time, and findings were recorded. Trauma was documented during scope withdrawal. Day 1 and day 2 results were compared. RESULTS: Ninety procedures were successfully performed in 95 patients (72.6 % women, age = 48.8 +/- 14.2 years). Endoscopists each performed a mean of five procedures. Mean time to maximal insertion was 20.9 +/- 6.4 minutes. Mean depth achieved was 262.0 +/- 57.4 cm. Total procedure time was 33.6 +/- 8.0 minutes. In 90.3 %, 94.6 %, and 83.9 % of patients, respectively, a trauma score less than 3 was recorded in the esophagus, stomach, and intestine (scale = 0 - 5). There were no perforations, nor significant associations between trauma score and patient age, body mass index, depth of insertion, time to maximal insertion, total procedure time, or day 1 vs. day 2 procedures. Depth of insertion was greater on day 2 than on day 1 (276.9 +/- 53.7 cm vs. 252.0 +/- 58.0 cm, P = 0.043). CONCLUSIONS: Discovery SB provides safe advancement of the enteroscope into the distal small bowel. Maximum depth of insertion appears comparable to that of balloon enteroscopy while taking less time. The device is easy to use and may be effectively operated in as few as five training cases.

Spiral enteroscopy with the new DSB overtube: a novel technique for deep peroral small-bowel intubation.

BACKGROUND AND STUDY AIMS: Spiral enteroscopy is a new technique for deep small-bowel intubation that uses a special overtube (Discovery Small Bowel, DSB) to pleat small bowel. The aims of this prospective study were to evaluate the use of a new-design DSB over new, longer and smaller-diameter enteroscopes, the Fujinon EN-450T5 and the Olympus SIF-Q180. PATIENTS AND METHODS: This is a prospective study of 75 patients at two referral centers. All enteroscopies were performed by two experienced endoscopists. Patients underwent spiral enteroscopy perorally with the DSB and either the Fujinon EN-450T5 or the Olympus SIF-Q180 enteroscope. Procedure time and depth of insertion past the ligament of Treitz were determined for all patients. RESULTS: Peroral spiral enteroscopy with DSB was performed in 50 patients with the Fujinon enteroscope and in 25 patients with the Olympus. Average estimated depth of insertion was 243 cm (range 50 - 380 cm) vs. 256 cm (range 50 - 400 cm) and the average time to reach this depth was 18.7 minutes (range 7 - 52 minutes) vs. 16.2 minutes (range 7 - 33 minutes) in the Fujinon and the Olympus groups respectively. Overall findings were 10 angiodysplasias, 2 small-bowel tumors, 1 Peutz-Jeghers polyp, 1 case of celiac sprue, 2 of small-bowel strongyloidiasis, and 2 small-bowel ulcers. All angiodysplasias were treated with bipolar cauterization. Biopsies were taken from the small-bowel tumors. There were no major complications. CONCLUSIONS: The new DSB is a means of rapid, safe, and effective deep small-bowel intubation. Depth of insertion into the small bowel and total procedure time compare favorably with other deep enteroscopy techniques. The DSB performed equally well with both enteroscopes.

Moving towards better health: a survey of transport authorities and primary care trusts in South West England.

OBJECTIVE: Transport, the way we travel and our ability to access amenities, is an important determinant of health. A survey was conducted to: (1) identify past and present joint working arrangements between transport authorities and health authorities; (2) understand the role and impact of transport themes in health improvement programmes (HIMPs) and health themes in local transport plans (LTPs); and (3) raise awareness of transport and health issues. STUDY DESIGN: A questionnaire survey of directors of public health of primary care trusts (PCTs) and local authority transport managers was undertaken in the South West of England, a region of 5 million people with 32 PCTs and 15 transport authorities. RESULTS: All the transport authorities and 66% of PCTs responded. Consultation with the health authority on the LTP had been full in 67% of transport authority areas and more limited in the remainder. Common targets in the LTP and HIMP had been agreed in 33% of transport authority areas, shared programmes or themes in 40%, and a single shared theme in 13%. LTP and HIMP shared themes included walking and cycling initiatives, road safety, school travel and rural access. LTP themes identified as best practice to deliver health gain included walking initiatives, rural access, school travel and road safety. Ongoing links with PCTs were in place in 73% of the transport areas. Of the PCTs that responded, 33% reported that they were working on a travel plan. CONCLUSIONS: The responses in this survey identified strengths and concerns in the way that health and transport issues are handled locally and are reflected in the LTPs and HIMPs. Recommendations were produced by public health and transport managers in government office South West to improve partnership working.

Overexpression of the HER-2/neu oncogene in pancreatic adenocarcinoma.

Novel systemic treatments are needed in pancreatic cancer. The authors sought to establish the frequency of overexpression of the HER-2/neu oncogene in patients with pancreatic adenocarcinoma to determine the potential role of trastuzumab (Herceptin) as a therapeutic agent in this disease. Tumor specimens from patients with pancreatic adenocarcinoma were analyzed by staining for p185HER2 protein using the DAKO immunohistochemical assay. Patients with and without HER-2/neu overexpression by immunohistochemistry were compared with respect to clinical and pathologic characteristics. HER-2/neu gene amplification was also evaluated by fluorescence in situ hybridization (FISH). Thirty-two of 154 patients (21%) had pancreatic adenocarcinoma that demonstrated HER-2/neu overexpression by immunohistochemistry. At initial diagnosis, 16% of resectable cancers, 17% of locally advanced cancers, and 26% of metastatic cancers were determined to have HER-2/neu overexpression. Three of 11 (27%) patients with HER-2/neu overexpression by immunohistochemistry had gene amplification by FISH. HER-2/neu overexpression occurs in a subset of pancreatic cancer. Evaluation of the efficacy of trastuzumab for patients with pancreatic cancer who overexpress HER-2/neu appears indicated.

Paclitaxel, cisplatin, and concurrent radiation for esophageal cancer.

Paclitaxel is an active agent for adenocarcinomas and squamous cell carcinomas of the esophagus and is a radiation sensitizer. We sought to investigate the toxicity and complete response rate of paclitaxel, cisplatin, and concurrent radiation for esophageal cancer. Forty-one patients with esophageal cancer were studied, 29 with adenocarcinomas and 12 with squamous cell cancers. Twelve patients had tumor extension into the proximal stomach and/or abdominal adenopathy. Patients received paclitaxel 60 mg/m2 by 3-hour intravenous (i.v.) infusion, and cisplatin 25 mg/m2 weekly on days 1, 8, 15, and 22. Radiation was administered concurrently to a total dose of 39.60 Gy, in 1.80 Gy fractions, for 22 treatments. Patients with medical or surgical contraindications to esophagectomy received 2 additional weeks of paclitaxel with a radiation boost to 50.4 Gy. Neutropenia was the most common grade 3/4 toxicity occurring in 10 patients (24%). Only 2 patients (5%) had grade 4 esophagitis requiring parenteral nutrition. Twelve patients (29%) obtained a complete response. The 2-year progression-free and overall survival rates were 40% and 42%, respectively. Esophagitis was less severe than expected and prophylactic enteral feeding tubes were not necessary. Additional effective systemic treatments are needed to reduce the development of distant metastases.

Paclitaxel and concurrent radiation for locally advanced pancreatic cancer.

PURPOSE: To determine the activity and toxicity of paclitaxel and concurrent radiation for pancreatic cancer. METHODS AND MATERIALS: Forty-four patients with locally unresectable pancreatic cancer were studied. Patients received paclitaxel, 50 mg/m(2) by 3 h i.v. (IV) infusion, weekly, on Days 1, 8, 15, 22 and 29. Radiation was administered concurrently to a total dose of 50.4 Gy, in 1.80 Gy fractions, for 28 treatments. RESULTS: Nausea and vomiting were the most common toxicities, Grade 3 in five patients (12%). Two patients (5%) had Grade 4 hypersensitivity reactions to their first dose of paclitaxel. Of 42 evaluable patients, the overall response rate was 26%. The median survival was 8 months, and the 1-year survival was 30%. CONCLUSION: Concurrent paclitaxel and radiation demonstrate local-regional activity in pancreatic cancer. Future investigations combining paclitaxel with other local-regional and systemic treatments are warranted.

Role of endoscopic ultrasound in the diagnosis and staging of pancreatic cancer.

Endoscopic Ultrasound (EUS) is a relatively new modality. Its high resolution makes it possible to detect tumors of 5mm in diameter otherwise missed by other imaging modalities. It is more accurate than computerized tomography (CT) scan, Transabdominal Ultrasound (US) and Magnetic Resonance Imaging (MRI) in diagnosing pancreatic lesions, especially those less than 20mm in diameter. EUS can be used to obtain pancreatic and nodal tissue using ultrasound- guided fine needle aspiration increasing the diagnostic yield and helping determining further management. It can also determine vascular involvement by pancreatic cancer with a sensitivity of more than 90%. The current indications for EUS in the diagnosis and management of pancreatic cancer will be reviewed.

Paclitaxel and concurrent radiation for gastric cancer.

PURPOSE: To determine the activity and toxicity of paclitaxel and concurrent radiation for gastric cancer. METHODS AND MATERIALS: Twenty-seven patients were studied. Twenty-five had proximal gastric cancers, two had distal cancers. Eight had esophageal extension, 6 had celiac adenopathy, and 7 had retroperitoneal adenopathy. Patients received paclitaxel, 50 mg/m(2) by 3-hour intravenous (IV) infusion, weekly, on days 1, 8, 15, 22, and 29. Radiation was administered concurrently to a total dose of 45.0 Gy, in 1.80 Gy fractions, for 25 treatments. Patients who were medically or surgically inoperable received a sixth week of paclitaxel with a radiation boost to 50.4 Gy. RESULTS: Esophagitis and gastritis were the most important toxicities, Grade 3 in four patients (15%), and Grade 4 in three patients (11%). Five patients (19%) had Grade 3 nausea. The overall response rate was 56%, including three patients (11%) with a complete response. The 2-year progression-free and overall survival rates were 29% and 31%, respectively. CONCLUSION: Concurrent paclitaxel and radiation demonstrates substantial local-regional activity in gastric cancer. Future investigations combining paclitaxel and radiation with other local-regional and systemic treatments are warranted.

Paclitaxel and concurrent radiation therapy for locally advanced adenocarcinomas of the pancreas, stomach, and gastroesophageal junction.

An effective locoregional therapy is needed for adenocarcinomas of the pancreas, stomach, and gastroesophageal junction. Paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) may enhance the effect of radiation therapy (RT). Paclitaxel synchronizes cells at G2/M, a relatively radiosensitive phase of the cell cycle. We have shown that response to paclitaxel and concurrent RT (paclitaxel/RT) was not affected by p53 mutations in non-small cell lung cancer. This finding suggested that paclitaxel/RT was a rational treatment approach for other malignancies that frequently harbor p53 mutations, such as upper gastrointestinal malignancies. We completed a phase I study of paclitaxel/RT for locally advanced pancreatic and gastric cancer. The maximum tolerated dose of paclitaxel was 50 mg/m2/wk for 6 weeks with abdominal RT. The dose-limiting toxicities were abdominal pain within the radiation field, nausea, and anorexia. Phase II studies are now under way. Twenty-five patients with locally advanced pancreatic cancer have been entered at the phase II dose level of paclitaxel 50 mg/m2/wk with concurrent RT (total dose, 50 Gy). Thus far, the only grade 3/4 toxicities have been hypersensitivity reactions (n = 2), asymptomatic grade 4 neutropenia (n = 3), and nonneutropenic biliary sepsis (n = 1). Of the first 18 assessable patients with pancreatic cancer treated on the phase II study, six obtained a partial response, for a preliminary response rate of 33%. In the phase II study for locally advanced gastric cancer, 20 patients have been enrolled. Of the first 19 patients who have completed treatment, nine (47%) had grade 3/4 toxicities, including nausea, anorexia, esophagitis, and gastritis. Of the first 16 patients with gastric cancer, complete and partial responses have been observed in one and eight patients, respectively, for a preliminary response rate of 56%. We have also completed treatment on 24 patients with potentially resectable adenocarcinomas of the gastroesophageal junction with neoadjuvant paclitaxel 60 mg/m2 and cisplatin 25 mg/m2, weekly for 4 weeks, with concurrent RT (total dose, 40 Gy) followed by surgical resection. Ten patients (41%) had grade 3/4 toxicities, including neutropenia, nausea, and dehydration. Of 24 patients, four complete responses (17%) and 14 partial responses (58%) were observed, for an overall response rate of 75%. Severe esophagitis was uncommon, making this a well-tolerated outpatient regimen for adenocarcinomas of the distal esophagus. These findings demonstrate that paclitaxel-based chemoradiation for locally advanced upper gastrointestinal malignancies is well-tolerated with substantial activity.

Paclitaxel and concurrent radiation for locally advanced pancreatic carcinoma.

An effective local-regional therapy is needed for adenocarcinomas of the pancreas. Paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton NJ) may enhance the effect of radiation therapy. Paclitaxel synchronizes cells at G2/M, a relatively radiosensitive phase of the cell cycle. We have shown that response to paclitaxel and concurrent radiation (paclitaxel/RT) was not affected by p53 mutations in non-small cell lung cancer (NSCLC). This suggested that paclitaxel/RT was a rationale treatment approach for other malignancies which frequently harbor p53 mutations such as upper gastrointestinal malignancies. We have completed a phase I study of paclitaxel/RT for locally advanced pancreatic and gastric cancers. The maximum tolerated dose (MTD) of paclitaxel was 50 mg/m2/week for 6 weeks with abdominal radiation. The dose limiting toxicities were abdominal pain within the radiation field, nausea and anorexia. Twenty-five patients with locally advanced pancreatic cancer have now completed treatment at the phase II dose level of paclitaxel 50 mg/m2/week with 50 Gy concurrent RT. Thus far, the only grade 3/4 toxicities have been hypersensitivity reactions in 2 patients, asymptomatic grade 4 neutropenia in 3 patients, and non-neutropenic biliary sepsis in 1 patient. Of the first 22 assessable patients treated at the phase II study, 8 obtained a partial response (PR) for a preliminary response rate of 36%. These findings demonstrate that paclitaxel/RT is well tolerated with substantial activity for locally advanced pancreatic cancer.

Preoperative nutrition assessment in liver transplantation.

Nutrition assessment and therapy in end-stage liver disease has become increasingly important with the advent of orthotopic liver transplantation. Reduced lean body mass, increased risk of sepsis, and altered metabolism of carbohydrates, protein, and fat are characteristic of patients with liver dysfunction. This study assesses the prevalence of protein-calorie malnutrition and the relative utility of various parameters used to define protein-calorie malnutrition in 104 patients before liver transplantation. Five subgroups were identified for analysis: primary biliary cirrhosis (PBC, n = 21), sclerosing cholangitis (SC, n = 12), chronic active hepatitis (CAH,n = 34), acute hepatitis (AH,n = 11), and other liver diseases (OD,n = 26). Clinical characteristics, anthropometric measurements, secretory protein levels, 24-h urinary creatinine and urea nitrogen, and immunological studies were assessed. Significant differences between groups were noted in age, height, weight, and percentage ideal body weight (IBW), but no differences were noted with respect to triceps skin fold (TSF) and arm muscle circumference (AMC), where uniform depletion of fat and protein stores was found. Overall percentage IBW was significantly elevated (112 +/- 20, mean +/- SD, p < 0.001), whereas TSF and AMC percentage standards were 71 +/- 33 and 89 +/- 11% (respective p < 0.001). With the < 5th percentile of TSF and AMC as markers of malnutrition, 33 and 43% of patients were malnourished, respectively. Hepatic synthetic function was impaired in all groups, with overall albumin 25 +/- 0.6 g/L, transferrin 1.60 +/- 0.66 g/L, and prothrombin 16.8 +/- 6.2 s.(ABSTRACT TRUNCATED AT 250 WORDS)

Long-term ethanol consumption alters the hepatic response to the regenerative effects of tumor necrosis factor-alpha.

The pathogenesis of chronic alcoholic liver disease is uncertain, but it may reflect an impaired wound healing response to ethanol-induced liver injury. Cell-to-cell communication such as that mediated by the cytokine tumor necrosis factor is necessary for successful liver regeneration and complete recovery from liver injury. Hence disruption of intercellular regenerative signaling may contribute to the pathogenesis of chronic alcoholic liver disease. To test this hypothesis, the cytokine and regenerative responses triggered by partial hepatectomy were compared in ethanol-fed rats and isocalorically maintained, pair-fed controls. To further clarify the effect of ethanol on tumor necrosis factor-modulated regenerative effects, we evaluated some of the rats in each feeding group after pretreatment with antibodies to tumor necrosis factor. As expected, ethanol inhibited DNA synthesis and liver cell proliferation after partial hepatectomy. Ethanol-associated inhibition of liver regeneration occurred despite apparently similar serum concentrations of the tumor necrosis factor-inducible cytokine interleukin-6. Treatment with antibodies to tumor necrosis factor 1 hr before partial hepatectomy inhibited post-partial hepatectomy induction of interleukin-6 and liver regeneration in ethanol-fed and pair-fed rats. However, serum interleukin-6 was reduced more in ethanol-fed rats than in control rats (93% vs. 66%; p < 0.05). Antibodies to tumor necrosis factor also inhibited hepatic DNA synthesis more in ethanol-fed rats than in controls (85% vs. 50%; p < 0.05). In ethanol-fed rats, the increased effect of tumor necrosis factor antibody on post-partial hepatectomy DNA synthesis suggests heightened sensitivity of hepatocytes to tumor necrosis factor.(ABSTRACT TRUNCATED AT 250 WORDS)

Antibodies to tumor necrosis factor-alpha inhibit liver regeneration after partial hepatectomy.

Certain cytokines that are produced in liver may act as growth factors to facilitate wound healing and, hence, may influence liver regeneration. However, this hypothesis has not been directly tested. To determine whether the cytokine response evoked by partial hepatectomy (PH) modulates the process of liver regeneration, adult male rats were injected intraperitoneally with either goat polyclonal antibodies to rat tumor necrosis factor (TNF; 15 micrograms/g body wt) or an equal amount of goat anti-rat immunoglobulin G 1 h before PH. Animals were killed at 12, 24, 48, or 72 h post-PH, 1 h after injection with [3H]thymidine. Serum TNF levels were measured with the L929 cytotoxicity assay, titers of antibody to TNF were determined by enzyme-linked immunoabsorbent assay, and interleukin-6 (IL-6) concentrations were measured by B9 cell bioassay. Liver regeneration was assessed by [3H]thymidine incorporation into hepatic DNA and by immunohistochemical evidence of proliferating cell nuclear antigen (PCNA) expression. Antibodies to TNF were detected in treated rats but not in controls. Titers were highest at 12 h and progressively fell. Although TNF was never detected in serum, treatment with anti-TNF pre-PH significantly inhibited increases in serum IL-6 concentration post-PH. Anti-TNF pretreatment also inhibited [3H]thymidine incorporation into DNA, as well as expression of PCNA by both hepatocytes and liver nonparenchymal cells. These data indicate that TNF positively modulates liver regeneration after PH.

Reducing arrhythmias associated with central venous catheter insertion or exchange.

A recent study demonstrated that the incidence of new arrhythmias occurring during central venous catheter insertion or exchange was 41% atrial and 25% ventricular arrhythmias (12% couplets or greater). Over-insertion of the guidewire, causing direct stimulation to the right side of the heart, has been postulated to be the causative factor. A new technique that allows the operator to control the length of guidewire inserted was developed. With this technique on a population of hospitalized patients, similar to those in the previous study, the incidence of atrial arrhythmias decreased to 32% and the incidence of ventricular arrhythmias to 6% (single premature ventricular contractions only). Although this new technique has limitations, there was a dramatic improvement in the incidence of cardiac arrhythmias. These results indicate a need for modifications in the available equipment to avoid the infrequent but life-threatening complication of malignant arrhythmia.

Incidence of arrhythmia with central venous catheter insertion and exchange.

The risk of complication during the insertion or exchange of central venous catheters has been well documented. The majority of complications involve mechanical problems associated with insertion. Although cardiac arrhythmia has been acknowledged as a possible complication, its incidence has never been quantified. We performed cardiac monitoring on patients during 51 central venous catheter insertions or exchanges to determine the incidence of cardiac arrhythmias during guidewire insertion. Forty-one percent of procedures resulted in atrial arrhythmias and 25% produced some degree of ventricular ectopy, 30% of these were ventricular couplets or greater. Ventricular ectopy was significantly more common in shorter patients (160 +/- 8 vs 168 +/- 11 cm, p less than 0.05) and when the catheter was inserted from the right subclavian position (43% ventricular ectopy vs 10% at the other sites). Other variables such as age, cardiac history, serum potassium, type of procedure, and catheter brand were not significant. It is our conclusion that over-insertion of the wire causes this cardiac stimulation. Despite the absence of morbidity or mortality in this study, this incidence of ventricular ectopy indicates that there is a distinct possibility of a malignant arrhythmia being precipitated by a guidewire. Some modification of the current protocol for these procedures seems indicated.