Mean and oscillating plasma flows and turbulence interactions across the L-H confinement transition.

A complex interaction between turbulence driven E × B zonal flow oscillations, i.e., geodesic acoustic modes (GAMs), the turbulence, and mean equilibrium flows is observed during the low to high (L-H) plasma confinement mode transition in the ASDEX Upgrade tokamak. Below the L-H threshold at low densities a limit-cycle oscillation forms with competition between the turbulence level and the GAM flow shearing. At higher densities the cycle is diminished, while in the H mode the cycle duration becomes too short to sustain the GAM, which is replaced by large amplitude broadband flow perturbations. Initially GAM amplitude increases as the H-mode transition is approached, but is then suppressed in the H mode by enhanced mean flow shear.

[When an enterovirus emerges]. / Quand un entérovirus émerge.

Most of enterovirus infections are benign and the rate of mortality is low in countries with temperate climates. But since the late 1990s, Enterovirus 71 (EV-71) has become much more aggressive in Asian countries, with the outcome of a neurogenic pulmonary oedema syndrome and it is responsible for huge epidemics. The virological diagnosis rely upon viral isolation and identification by sero-neutralization, and upon the detection of specific IgM by ELISA and viral RNA by RT-PCR. There is no specific treatment to fight this virus, but innovative strategies, especially based on interfering RNA, are under investigation.

[Fruit of the emergence of an enterovirus: acute haemorrhagic conjunctivitis]. / Fruit de l'émergence d'un entérovirus : la conjonctivite aiguë hémorragique.

First seen in Ghana and Indonesia in the early 70's, acute haemorrhagic conjunctivitis or "Apollo 11" disease is an eye infection caused by Enterovirus type 70 (EV70). The disease appeared to be a highly contagious conjunctivitis which spread rapidly all over the world. EV70 has been considered as an emerging virus and was classified as a new Enterovirus. No human or animal virus genetically similar to EV70 was known before the sudden outcome of the disease in Ghana, West Africa. EV70 appeared as a pretty demonstrative example of virus emergence and virus spreading. Studies of virus genetic mutations emphasized the variations of RNA virus within a short time period. The current review presents the EV70 infection and the genetic profile of the virus from its emergence to nowadays.

Novel allogeneic granulocyte-macrophage colony-stimulating factor-secreting tumor vaccine for pancreatic cancer: a phase I trial of safety and immune activation.

PURPOSE: Allogeneic granulocyte-macrophage colony-stimulating factor (GM-CSF)-secreting tumor vaccines can cure established tumors in the mouse, but their efficacy against human tumors is uncertain. We have developed a novel GM-CSF-secreting pancreatic tumor vaccine. To determine its safety and ability to induce antitumor immune responses, we conducted a phase I trial in patients with surgically resected adenocarcinoma of the pancreas. PATIENTS AND METHODS: Fourteen patients with stage 1, 2, or 3 pancreatic adenocarcinoma were enrolled. Eight weeks after pancreaticoduodenectomy, three patients received 1 x 10(7) vaccine cells, three patients received 5 x 10(7) vaccine cells, three patients received 10 x 10(7) vaccine cells, and five patients received 50 x 10(7) vaccine cells. Twelve of 14 patients then went on to receive a 6-month course of adjuvant radiation and chemotherapy. One month after completing adjuvant treatment, six patients still in remission received up to three additional monthly vaccinations with the same vaccine dose that they had received originally. RESULTS: No dose-limiting toxicities were encountered. Vaccination induced increased delayed-type hypersensitivity (DTH) responses to autologous tumor cells in three patients who had received >or= 10 x 10(7) vaccine cells. These three patients also seemed to have had an increased disease-free survival time, remaining disease-free at least 25 months after diagnosis. CONCLUSION: Allogeneic GM-CSF-secreting tumor vaccines are safe in patients with pancreatic adenocarcinoma. This vaccine approach seems to induce dose-dependent systemic antitumor immunity as measured by increased postvaccination DTH responses against autologous tumors. Further clinical evaluation of this approach in patients with pancreatic cancer is warranted.

The effects of alcohol celiac plexus block, pain, and mood on longevity in patients with unresectable pancreatic cancer: a double-blind, randomized, placebo-controlled study.

OBJECTIVE: This additional analysis of data from a previously reported prospective trial comparing the effect of intraoperative alcohol or saline placebo neurolytic block in patients with pancreatic cancer was conducted in response to the development of a new theory, which explores the relationship of negative mood states to pain, pain-related behavior, and ultimately, longevity. METHODS: The original study used a double-blind procedure to randomly assign 139 patients with histologically proven, unresectable pancreatic cancer to receive either an alcohol or a saline block. Data on visual analog pain, mood, and interference with activity were collected preoperatively and every 2 months postoperatively until death. The current analysis was conducted on the complete data sets received from 130 patients. Demographic data were submitted to chi-square analysis and to univariate and multivariate analysis of variance. Univariate and multivariate analyses of variance also compared 1) the effect of alcohol versus saline on pain, mood, interference of pain with activities, and longevity and 2) the impact of mood on pain with longevity as the dependent variable. Correlation and regression analyses examined the impact of mood on life expectancy. RESULTS: The alcohol intervention had a significant positive effect on life duration and mood scores. High negative mood states correlated significantly with an increase in visual analog pain, the rating of pain intensity at its worse, and pain interference with patients' activities. CONCLUSION: In these subjects, the neurolytic block, as compared with medical management alone, improved pain, elevated mood, reduced pain interference with activity, and was associated with an increase in life expectancy.

Quality of life and long-term survival after surgery for chronic pancreatitis.

The objective of this study was to evaluate the short-term and long-term outcome as well as quality of life in patients undergoing surgical management of chronic pancreatitis. Between January 1980 and December 1996, a total of 255 patients underwent surgery for chronic pancreatitis at The Johns Hopkins Hospital. The etiology of the disease, indications for surgery, patient characteristics, and long-term survival were analyzed. A visual analog quality-of-life questionnaire containing 23 items graded on a scale of 0 to 10 (0 = worst and 10 = best) was sent to patients postoperatively. Visual analog responses relating to before and after the chronic pancreatitis surgery were compared using a paired t test. During the17-year review period, 263 operations were performed for chronic pancreatitis in 255 patients. The most common presenting symptoms were abdominal pain (88%), weight loss (36%), nausea/vomiting (30%), jaundice (14%), and diarrhea (12%). The cause of the pancreatitis was resumed to be alcohol in 43%, idiopathic in 38%, pancreas divisum in 5%, ampullary abnormality in 4%, and gallstones in 3%. Pancreaticoduodenectomy was the most common procedure in 96 patients (37%), followed by distal pancreatectomy in 67 (25%), Puestow procedure in 52 (19%), sphincteroplasty in 37 (14%), and Duval procedure in five (2%). The overall mortality and morbidity rates were 1.9% and 35%, respectively. Two hundred twenty-seven (89%) of the 255 patients were alive at last follow-up. For the entire cohort of patients, the 5- and 10-year actuarial survivals were 88% and 82%, respectively. One hundred six (47%) of the 227 living patients responded to the visual analog quality-of-life questionnaire. Patients reported improvements in all aspects of the quality-of-life survey including enjoyment out of life, satisfaction with life, pain, number of hospitalizations, feelings of usefulness, and overall health (P < 0.005). In addition to improved quality of life after surgery, narcotic use was decreased (41% vs. 21%, P < 0.01) and alcohol use was decreased (59% vs. 33%, P < 0.001). However, patients often became insulin-dependent diabetics (12% vs. 41%, P < 0.0001) and required pancreatic enzyme supplementation (34% vs. 55%, P < 0.01) after surgical intervention. These data suggest that surgery for patients with chronic pancreatitis can be performed safely with minimal morbidity and excellent long-term survival. Moreover, this study evaluates quality of life in a standardized analog fashion, with highly significant improvement reported in all quality-of-life measures. We conclude that surgery remains an excellent option for patients with chronic pancreatitis.

Does prophylactic octreotide decrease the rates of pancreatic fistula and other complications after pancreaticoduodenectomy? Results of a prospective randomized placebo-controlled trial.

OBJECTIVE: To evaluate the endpoints of complications (specifically pancreatic fistula and total complications) and death in patients undergoing pancreaticoduodenectomy. SUMMARY BACKGROUND DATA: Four randomized, placebo-controlled, multicenter trials from Europe have evaluated prophylactic octreotide (the long-acting synthetic analog of native somatostatin) in patients undergoing pancreatic resection. Each trial reported significant decreases in overall complication rates, and two of the four reported significantly lowered rates of pancreatic fistula in patients receiving prophylactic octreotide. However, none of these four trials studied only pancreaticoduodenal resections, and all trials had high pancreatic fistula rates (>19%) in the placebo group. A fifth randomized trial from the United States evaluated the use of prophylactic octreotide in patients undergoing pancreaticoduodenectomy and found no benefit to the use of octreotide. Prophylactic use of octreotide adds more than $75 to the daily hospital charge in the United States. In calendar year 1996, 288 patients received octreotide on the surgical service at the authors' institution, for total billed charges of $74,652. METHODS: Between February 1998 and February 2000, 383 patients were recruited into this study on the basis of preoperative anticipation of pancreaticoduodenal resection. Patients who gave consent were randomized to saline control versus octreotide 250 microg subcutaneously every 8 hours for 7 days, to start 1 to 2 hours before surgery. The primary postoperative endpoints were pancreatic fistula, total complications, death, and length of hospital stay. RESULTS: Two hundred eleven patients underwent pancreaticoduodenectomy with pancreatic-enteric anastomosis, received appropriate saline/octreotide doses, and were available for endpoint analysis. The two groups were comparable with respect to demographics (54% male, median age 66 years), type of pancreaticoduodenal resection (60% pylorus-preserving), type of pancreatic-enteric anastomosis (87% end-to-side pancreaticojejunostomy), and pathologic diagnosis. The pancreatic fistula rates were 9% in the control group and 11% in the octreotide group. The overall complication rates were 34% in the control group and 40% in the octreotide group; the in-hospital death rates were 0% versus 1%, respectively. The median postoperative length of hospital stay was 9 days in both groups. CONCLUSIONS: These data demonstrate that the prophylactic use of perioperative octreotide does not reduce the incidence of pancreatic fistula or total complications after pancreaticoduodenectomy. Prophylactic octreotide use in this setting should be eliminated, at a considerable cost savings.

Postoperative bile duct strictures: management and outcome in the 1990s.

OBJECTIVE: To describe the management and outcome after surgical reconstruction of 156 patients with postoperative bile duct strictures managed in the 1990s. SUMMARY BACKGROUND DATA: The management of postoperative bile duct strictures and major bile duct injuries remains a challenge for even the most skilled biliary tract surgeon. The 1990s saw a dramatic increase in the incidence of bile duct strictures and injuries from the introduction and widespread use of laparoscopic cholecystectomy. Although the management of these injuries and short-term outcome have been reported, long-term follow-up is limited. METHODS: Data were collected prospectively on 156 patients treated at the Johns Hopkins Hospital with major bile duct injuries or postoperative bile duct strictures between January 1990 and December 1999. With the exception of bile duct injuries discovered and repaired during surgery, all patients underwent preoperative percutaneous transhepatic cholangiography and placement of transhepatic biliary catheters before surgical repair. Follow-up was conducted by medical record review or telephone interview during January 2000. RESULTS: Of the 156 patients undergoing surgical reconstruction, 142 had completed treatment with a mean follow-up of 57.5 months. Two patients died of reasons unrelated to biliary tract disease before the completion of treatment. Twelve patients (7.9%) had not completed treatment and still had biliary stents in place at the time of this report. Of patients who had completed treatment, 90. 8% were considered to have a successful outcome without the need for follow-up invasive, diagnos tic, or therapeutic interventional procedures. Patients with reconstruction after injury or stricture after laparoscopic cholecystectomy had a better overall outcome than patients whose postoperative stricture developed after other types of surgery. Presenting symptoms, number of stents, interval to referral, prior repair, and length of postoperative stenting were not significant predictors of outcome. Overall, a successful outcome, without the need for biliary stents, was obtained in 98% of patients, including those requiring a secondary procedure for recurrent stricture. CONCLUSIONS: Major bile duct injuries and postoperative bile duct strictures remain a considerable surgical challenge. Management with preoperative cholangiography to delineate the anatomy and placement of percutaneous biliary catheters, followed by surgical reconstruction with a Roux-en-Y hepaticojejunostomy, is associated with a successful outcome in up to 98% of patients.

Swiss Army Survey in Switzerland to determine the prevalence of Francisella tularensis, members of the Ehrlichia phagocytophila genogroup, Borrelia burgdorferi sensu lato, and tick-borne encephalitis virus in ticks.

A total of 6071 Ixodes ricinus ticks were collected on Swiss Army training grounds in five regions of Switzerland. The aim of the survey was to assess the prevalence of ticks infected with the human pathogens Francisella tularensis, members of the Ehrlichia phagocytophila genogroup, Borrelia burgdorferi sensu lato, and the European tick-borne encephalitis virus. TaqMan PCR (PE Biosystems, USA) and TaqMan RT-PCR (PE Biosystems) analyses were performed on DNA and RNA extracted from pools of ten ticks grouped by gender. Here, for the first time, it is shown that ticks may harbor Francisella tularensis in Switzerland, at a rate of 0.12%. Furthermore, 26.54% of the ticks investigated harbored Borrelia burgdorferi sensu lato, 1.18% harbored members of the Ehrlichia phagocytophila genogroup, and 0.32% harbored the European tick-borne encephalitis virus. A new instrumentation was applied in this study to carry out and analyze more than 2300 PCR reactions in only 5 days. Furthermore, the results reveal that people working in outdoor areas, including army personnel on certain training grounds contaminated with ticks containing tick-borne pathogens, are at risk for different tick-borne diseases.

Quality of life and outcomes after pancreaticoduodenectomy.

OBJECTIVE: To assess the quality of life (QOL) and functional outcome of patients after pancreaticoduodenectomy. SUMMARY BACKGROUND DATA: Pancreaticoduodenectomy is gaining acceptance and is being performed in increasing numbers for various malignant and benign diseases of the pancreas and periampullary region. There is a general impression that pancreaticoduodenectomy can severely impair QOL and alter normal activities. Only a few small studies have evaluated QOL after pancreaticoduodenectomy. METHODS: A standard QOL questionnaire was sent to 323 patients surviving pancreaticoduodenectomy who had undergone surgery at The Johns Hopkins Hospital between 1981 and 1997. Thirty items on a visual analog scale were categorized into three domains: physical (15 items), psychological (10 items), and social (5 items). Scores are reported as a percentile, with 100% being the highest possible score. The same QOL questionnaire was also sent to laparoscopic cholecystectomy patients and healthy controls. A separate component of the questionnaire asked about functional outcomes and disabilities. RESULTS: Overall QOL scores for the 192 responding pancreaticoduodenectomy patients in the three domains (physical, psychological, social) were 78%, 79%, and 81%, respectively. These QOL scores were comparable to those of the 37 laparoscopic cholecystectomy patients and the 31 healthy controls. The pancreaticoduodenectomy patients were subgrouped into chronic pancreatitis, other benign disease, pancreatic adenocarcinoma, and other cancers. Patients who underwent resection for chronic pancreatitis and pancreatic adenocarcinoma had significantly lower QOL scores in the physical and psychological domains compared with the laparoscopic cholecystectomy patients and the healthy controls. Common problems after pancreaticoduodenectomy were weight loss, abdominal pain, fatigue, foul stools, and diabetes. CONCLUSIONS: This is the largest single-institution experience assessing QOL after pancreaticoduodenectomy. These data demonstrate that as a group, patients who survive pancreaticoduodenectomy have near-normal QOL scores. Many patients report weight loss and symptoms consistent with pancreatic exocrine and endocrine insufficiency. Most patients have QOL scores comparable to those of control patients and can function independently in daily activities.

Resected adenocarcinoma of the pancreas-616 patients: results, outcomes, and prognostic indicators.

This large-volume, single-institution review examines factors influencing long-term survival after resection in patients with adenocarcinoma of the head, neck, uncinate process, body, or tail of the pancreas. Between January 1984 and July 1999 inclusive, 616 patients with adenocarcinoma of the pancreas underwent surgical resection. A retrospective analysis of a prospectively collected database was performed. Both univariate and multivariate models were used to determine the factors influencing survival. Of the 616 patients, 526 (85%) underwent pancreaticoduodenectomy for adenocarcinoma of the head, neck, or uncinate process of the pancreas, 52 (9%) underwent distal pancreatectomy for adenocarcinoma of the body or tail, and 38 (6%) underwent total pancreatectomy for adenocarcinoma extensively involving the gland. The mean age of the patients was 64.3 years, with 54% being male and 91% being white. The overall perioperative mortality rate was 2.3%, whereas the incidence of postoperative complications was 30%. The median postoperative length of stay was 11 days. The mean tumor diameter was 3.2 cm, with 72% of patients having positive lymph nodes, 30% having positive resection margins, and 36% having poorly differentiated tumors. Patients undergoing distal pancreatectomy for left-sided lesions had larger tumors (4.7 vs. 3.1 cm, P < 0.0001), but fewer node-positive resections (59% vs. 73%, P = 0.03) and fewer poorly differentiated tumors (29% vs. 36%, P < 0.001), as compared to those undergoing pancreaticoduodenectomy for right-sided lesions. The overall survival of the entire cohort was 63% at 1 year and 17% at 5 years, with a median survival of 17 months. For right-sided lesions the 1- and 5-year survival rates were 64% and 17%, respectively, compared to 50% and 15% for left-sided lesions. Factors shown to have favorable independent prognostic significance by multivariate analysis were negative resection margins (hazard ratio [HR] = 0.64, confidence interval [CI] = 0.50 to 0.82, P = 0.0004), tumor diameter less than 3 cm (HR = 0.72, CI = 0.57 to 0.90, P = 0.004), estimated blood loss less than 750 ml (HR = 0.75, CI = 0.58 to 0.96, P = 0.02), well/moderate tumor differentiation (HR = 0.71, CI = 0.56 to 0.90, P = 0.005), and postoperative chemoradiation (HR = 0.50, CI = 0.39 to 0.64, P < 0.0001). Tumor location in head, neck, or uncinate process approached significance in the final multivariate model (HR = 0.60, CI = 0.35 to 1.0, P = 0.06). Pancreatic resection remains the only hope for long-term survival in patients with adenocarcinoma of the pancreas. Completeness of resection and tumor characteristics including tumor size and degree of differentiation are important independent prognostic indicators. Adjuvant chemoradiation is a strong predictor of outcome and likely decreases the independent significance of tumor location and nodal status.

Is prophylactic gastrojejunostomy indicated for unresectable periampullary cancer? A prospective randomized trial.

OBJECTIVE: This prospective, randomized, single-institution trial was designed to evaluate the role of prophylactic gastrojejunostomy in patients found at exploratory laparotomy to have unresectable periampullary carcinoma. SUMMARY BACKGROUND DATA: Between 25% and 75% of patients with periampullary cancer who undergo exploratory surgery with intent to perform a pancreaticoduodenectomy are found to have unresectable disease. Most will undergo a biliary-enteric bypass. Whether or not to perform a prophylactic gastrojejunostomy remains unresolved. Retrospective reviews of surgical series and prospective randomized trials of endoscopic palliation have demonstrated that late gastric outlet obstruction, requiring a gastrojejunostomy, develops in 10% to 20% of patients with unresectable periampullary cancer. METHODS: Between May 1994 and October 1998, 194 patients with a periampullary malignancy underwent exploratory surgery with the purpose of performing a pancreaticoduodenectomy and were found to have unresectable disease. On the basis of preoperative symptoms, radiologic studies, or surgical findings, the surgeon determined that gastric outlet obstruction was a significant risk in 107 and performed a gastrojejunostomy. The remaining 87 patients were thought by the surgeon not to be at significant risk for duodenal obstruction and were randomized to receive either a prophylactic retrocolic gastrojejunostomy or no gastrojejunostomy. Short- and long-term outcomes were determined in all patients. RESULTS: Of the 87 patients randomized, 44 patients underwent a retrocolic gastrojejunostomy and 43 did not undergo a gastric bypass. The two groups were similar with respect to age, gender, procedure performed (excluding gastrojejunostomy), and surgical findings. There were no postoperative deaths in either group, and the postoperative morbidity rates were comparable (gastrojejunostomy 32%, no gastrojejunostomy 33%). The postoperative length of stay was 8.5+/-0.5 days for the gastrojejunostomy group and 8.0+/-0.5 days for the no gastrojejunostomy group. Mean survival among those who received a prophylactic gastrojejunostomy was 8.3 months, and during that interval gastric outlet obstruction developed in none of the 44 patients. Mean survival among those who did not have a prophylactic gastrojejunostomy was 8.3 months. In 8 of those 43 patients (19%), late gastric outlet obstruction developed, requiring therapeutic intervention (gastrojejunostomy 7 patients, endoscopic duodenal stent 1 patient; p < 0.01). The median time between initial exploration and therapeutic intervention was 2 months. CONCLUSION: The results from this prospective, randomized trial demonstrate that prophylactic gastrojejunostomy significantly decreases the incidence of late gastric outlet obstruction. The performance of a prophylactic retrocolic gastrojejunostomy at the initial surgical procedure does not increase the incidence of postoperative complications or extend the length of stay. A retrocolic gastrojejunostomy should be performed routinely when a patient is undergoing surgical palliation for unresectable periampullary carcinoma.

Pancreaticoduodenectomy with or without extended retroperitoneal lymphadenectomy for periampullary adenocarcinoma: comparison of morbidity and mortality and short-term outcome.

OBJECTIVE: This prospective, randomized, single-institution trial was designed to evaluate the end points of mortality, morbidity, and survival in patients undergoing standard versus radical (extended) pancreaticoduodenectomy (including distal gastrectomy and retroperitoneal lymphadenectomy). SUMMARY BACKGROUND DATA: Numerous retrospective reports and one prospective randomized trial have suggested that the performance of an extended lymphadenectomy in association with a pancreaticoduodenal resection may improve long-term survival for some patients with pancreatic and other periampullary adenocarcinomas. Many of these previously published studies can be criticized for their retrospective and nonrandomized designs, for the inclusion of nonconcurrent control groups, and for their small numbers. METHODS: Between April 1996 and December 1997, 114 patients with periampullary adenocarcinoma were enrolled in an ongoing, prospective, randomized trial at The Johns Hopkins Hospital. After intraoperative verification of completely resected periampullary adenocarcinoma, the patients were randomized to receive either a standard pancreaticoduodenectomy (removing only the peripancreatic lymph nodes en bloc with the specimen) or a radical pancreaticoduodenectomy (standard resection plus distal gastrectomy and retroperitoneal lymphadenectomy). All pathology specimens were reviewed and categorized. The postoperative morbidity, mortality, and short-term outcomes were examined. RESULTS: Of the 114 patients randomized, 56 underwent a standard pancreaticoduodenectomy and 58 a radical pancreaticoduodenectomy. The two groups were statistically similar with regard to age and gender, but there was a higher percentage of white patients in the radical group. All the patients in the radical group underwent distal gastric resection, whereas 86% of the patients in the standard group underwent pylorus preservation. The mean operative time in the radical group was 6.8 hours, compared with 6.2 hours in the standard group. There were no significant differences between the two groups with respect to the intraoperative blood loss, transfusion requirements, location of primary tumor, mean tumor size, positive lymph node status, or positive margin status. There were three deaths in the standard group and two in the radical group. The complication rates were 34% for the standard group and 40% for the radical group. Patients undergoing radical resection had a higher incidence of early delayed gastric emptying but had similar rates of other complications, such as pancreatic fistula, wound infection, intraabdominal abscess, and need for reoperation. The mean total number of lymph nodes resected was higher in the radical group. Of the 58 patients in the radical group, only 10% had metastatic carcinoma in the resected retroperitoneal lymph nodes, and none of those patients had the retroperitoneal nodes as the only site of lymph node involvement. The 1-year actuarial survival rate for patients surviving the immediate postoperative periods was 77% for the standard resection group and 83% for the radical resection group. CONCLUSIONS: These data demonstrate that radical pancreaticoduodenectomy (with the addition of a distal gastrectomy and extended retroperitoneal lymphadenectomy to a standard pancreaticoduodenectomy) can be performed with similar morbidity and mortality to standard pancreaticoduodenectomy. However, the survival data are not sufficiently mature and the numbers of patients enrolled are not adequate to allow firm conclusions to be drawn regarding survival benefit.

Pancreatic cancer: a continuum of care.

OBJECTIVES: To provide information about the etiology, clinical manifestations, treatment, and symptom management of pancreatic cancer. DATA SOURCES: Textbook chapters, research studies, and review articles. CONCLUSIONS: Cancer of the pancreas is a devastating disease. A diagnosis of pancreatic cancer causes a person to consider both quantity as well as quality of life. Hope for improved quality of life and survival relies on the efforts of a co-operative multidisciplinary team approach. IMPLICATIONS FOR NURSING PRACTICE: Numerous nursing challenges exist in providing care for the patient with pancreatic cancer. Treatment, symptom management, and psychological, social, and spiritual support are essential in meeting the needs of the patient and family through the eventuality of the disease.

Outpatient laparoscopic cholecystectomy: patient and nursing perspective.

Outpatient laparoscopic cholecystectomy has become nearly mandatory in the current health care economic environment. This study determined the opinions of patients and their nurses regarding disability and pain after laparoscopic cholecystectomy. Using a 14-point questionnaire, 32 consecutive patients who underwent inpatient LC were surveyed. The nurses caring for these patients were surveyed with a nine-point questionnaire. Seventy-one percent of patients believed that they could not have been discharged the day of surgery; the nurses reported that 81% of the patients could not have gone home. Nausea and vomiting were common. Pain was rated as 9 or 10 in 19% of patients. Nurses reported that 56% of postoperative patients were not receptive to discharge teaching. Morning (16) versus afternoon (16) procedures were not different. Successful programs of outpatient LC must: 1) ensure adequate home support because patient capability will be limited, 2) optimize pain control, 3) minimize nausea and vomiting, and 4) deliver patient education preoperatively.

Should pancreaticoduodenectomy be performed in octogenarians?

As the population in the United States ages, an increasing number of elderly patients may be considered for pancreaticoduodenal resection. This high-volume, single-institution experience examines the morbidity, mortality, and long-term survival of 727 patients undergoing pancreaticoduodenectomy between December 1986 and June 1996. Outcomes of patients 80 years of age and older (n = 46) were compared to those of patients younger than 80 years. In these older patients, pancreaticoduodenectomy was performed for pancreatic adenocarcinoma (n = 25; 54%), ampullary adenocarcinoma (n = 9; 20%) distal bile duct adenocarcinoma (n = 5; 11%), duodenal adenocarcinoma (n = 2; 4%), cystadenocarcinoma; (n = 2; 4%), cystadenoma (n = 1; 2%), and chronic pancreatitis (n = 2; 4%). When compared to the 681 concurrent patients younger than 80 years who were undergoing pancreaticoduodenectomy, the two groups were statistically similar with respect to sex, race, intraoperative blood loss, and type of pancreaticoduodenectomy performed. Patients 80 years of age or older had a shorter median operative time (6.4 hours vs. 7.0 hours; P = 0.02) but a longer postoperative length of stay (median = 15 days vs. 13 days; P = 0.01) and a higher complication rate (57% vs. 41%; P = 0.05) when compared to their younger counterparts. Pancreaticoduodenectomy in the older group resulted in a 4.3% perioperative mortality rate compared to 1.6% in the younger group (P = NS). In the subset of patients undergoing pancreaticoduodenectomy for periampullary adenocarcinoma (n = 495), patients 80 years of age or older (n = 41) had a median survival of 32 months and a 5-year survival rate of 19%, compared to 20 months and 27%, respectively, in patients younger than 80 years (n = 454; P = 0.77). These data demonstrate that pancreaticoduodenectomy can be performed safely in selected patients 80 years of age or older, with morbidity and mortality rates approaching those observed in younger patients. Based on these data, age alone should not be a contraindication to pancreaticoduodenectomy.

Coactivator OBF-1 makes selective contacts with both the POU-specific domain and the POU homeodomain and acts as a molecular clamp on DNA.

The lymphoid-specific transcriptional coactivator OBF-1 (also known as OCA-B or Bob-1) is recruited to octamer site-containing promoters by interacting with Oct-1 or Oct-2 and thereby enhances the transactivation potential of these two Oct factors. For this interaction the POU domain is sufficient. By contrast, OBF-1 does not interact with the POU domains of other POU proteins, such as Oct-4, Oct-6, or Pit-1, even though these factors bind efficiently to the octamer motif. Here we examined the structural requirements for selective interaction between the POU domain and OBF-1. Previous data have shown that formation of a ternary complex among OBF-1, the POU domain, and the DNA is critically dependent on residues within the octamer site. By methylation interference analysis we identified bases that react differently in the presence of OBF-1 compared to the POU domain alone, and using phosphothioate backbone-modified probes in electrophoretic mobility shift assays, we identified several positions influencing ternary complex formation. We then used Oct-1/Pit-1 POU domain chimeras to analyze the selectivity of the interaction between OBF-1 and the POU domain. This analysis indicated that both the POU specific domain (POUS) and the POU homeodomain (POUH) contribute to complex formation. Amino acids that are different in the Pit-1 and Oct-1 POU domains and are considered to be solvent accessible based on the Oct-1 POU domain/DNA cocrystal structure were replaced with alanine residues and analyzed for their influence on complex formation. Thereby, we identified residues L6 and E7 in the POUS and residues K155 and I159 in the POUH to be critical in vitro and in vivo for selective interaction with OBF-1. Furthermore, in an in vivo assay we could show that OBF-1 is able to functionally recruit two artificially separated halves of the POU domain to the promoter DNA, thereby leading to transactivation. These data allow us to propose a model of the interaction between OBF-1 and the POU domain, whereby OBF-1 acts as a molecular clamp holding together the two moieties of the POU domain and the DNA.

Six hundred fifty consecutive pancreaticoduodenectomies in the 1990s: pathology, complications, and outcomes.

OBJECTIVE: The authors reviewed the pathology, complications, and outcomes in a consecutive group of 650 patients undergoing pancreaticoduodenectomy in the 1990s. SUMMARY BACKGROUND DATA: Pancreaticoduodenectomy has been used increasingly in recent years to resect a variety of malignant and benign diseases of the pancreas and periampullary region. METHODS: Between January 1990 and July 1996, inclusive, 650 patients underwent pancreaticoduodenal resection at The Johns Hopkins Hospital. Data were recorded prospectively on all patients. All pathology specimens were reviewed and categorized. Statistical analyses were performed using both univariate and multivariate models. RESULTS: The patients had a mean age of 63 +/- 12.8 years, with 54% male and 91% white. The number of resections per year rose from 60 in 1990 to 161 in 1995. Pathologic examination results showed pancreatic cancer (n = 282; 43%), ampullary cancer (n = 70; 11%), distal common bile duct cancer (n = 65; 10%), duodenal cancer (n = 26; 4%), chronic pancreatitis (n = 71; 11%), neuroendocrine tumor (n = 31; 5%), periampullary adenoma (n = 21; 3%), cystadenocarcinoma (n = 14; 2%), cystadenoma (n = 25; 4%), and other (n = 45; 7%). The surgical procedure involved pylorus preservation in 82%, partial pancreatectomy in 95%, and portal or superior mesenteric venous resection in 4%. Pancreatic-enteric reconstruction, when appropriate, was via pancreaticojejunostomy in 71% and pancreaticogastrostomy in 29%. The median intraoperative blood loss was 625 mL, median units of red cells transfused was zero, and the median operative time was 7 hours. During this period, 190 consecutive pancreaticoduodenectomies were performed without a mortality. Nine deaths occurred in-hospital or within 30 days of operation (1.4% operative mortality). The postoperative complication rate was 41%, with the most common complications being early delayed gastric emptying (19%), pancreatic fistula (14%), and wound infection (10%). Twenty-three patients required reoperation in the immediate postoperative period (3.5%), most commonly for bleeding, abscess, or dehiscence. The median postoperative length of stay was 13 days. A multivariate analysis of the 443 patients with periampullary adenocarcinoma indicated that the most powerful independent predictors favoring long-term survival included a pathologic diagnosis of duodenal adenocarcinoma, tumor diameter <3 cm, negative resection margins, absence of lymph node metastases, well-differentiated histology, and no reoperation. CONCLUSIONS: This single institution, high-volume experience indicates that pancreaticoduodenectomy can be performed safely for a variety of malignant and benign disorders of the pancreas and periampullary region. Overall survival is determined largely by the pathology within the resection specimen.

Pancreaticoduodenectomy for pancreatic adenocarcinoma: postoperative adjuvant chemoradiation improves survival. A prospective, single-institution experience.

OBJECTIVE: This study was designed to evaluate prospectively survival after pancreaticoduodenectomy for pancreatic adenocarcinoma, comparing two different postoperative adjuvant chemoradiation protocol to those of no adjuvant therapy. SUMMARY BACKGROUND DATA: Based on limited data from the Gastrointestinal Tumor Study Group, adjuvant chemoradiation therapy has been recommended after pancreaticoduodenectomy for adenocarcinoma of the head, neck, or uncinate process of the pancrease. However, many patients continue to receive no such therapy. METHODS: From October 1991 through September 1995, all patients with resected, pathologically confirmed adenocarcinoma of the head, neck, or uncinate process of the pancreas were reviewed by a multidisciplinary group (surgery, radiation oncology, medical oncology, and pathology) and were offered three options for postoperative treatment after pancreaticoduodenectomy: 1) standard therapy: external beam radiation therapy to the pancreatic bed (4000-4500 cGy) given with two 3-day fluorouracil (5-FU) courses and followed by weekly bolus 5-FU (500 mg/m2 per day) for 4 months; 2) intensive therapy: external beam radiation therapy to the pancreatic bed (5040-5760 cGy) with prophylactic hepatic irradiation (2340-2700 cGy) given with and followed by infusional 5-FU (200 mg/m2 per day) plus leucovorin (5 mg/m2 per day) for 5 of 7 days for 4 months; or 3) no therapy: no postoperative radiation therapy or chemotherapy. RESULTS: Pancreaticoduodenectomy was performed in 174 patients, with 1 in-hospital death (0.6%). Ninety-nine patients elected standard therapy, 21 elected intensive therapy, and 53 patients declined therapy. The three groups were comparable with respect to race, gender, intraoperative blood loss, tumor differentiation, lymph node status, tumor diameter, and resection margin status. Univariate analyses indicated that tumor diameter < 3 cm, intraoperative blood loss < 700 mL, absence of intraoperative blood transfusions, and use of adjuvant chemoradiation therapy were associated with significantly longer survival (p < 0.05). By Cox proportional hazards survival analysis, the most powerful predictors of outcome were tumor diameter, intraoperative blood loss, status of resection margins, and use of postoperative adjuvant therapy. The use of postoperative adjuvant chemoradiation therapy was a predictor of improved survival (median survival, 19.5 months compared to 13.5 months without therapy; p = 0.003). The intensive therapy group had no survival advantage when compared to that of the standard therapy group (median survival, 17.5 months vs. 21 months, p = not significant). CONCLUSIONS: Adjuvant chemoradiation therapy significantly improves survival after pancreaticoduodenectomy for adenocarcinoma of the head, neck, or uncinate process of the pancreas. Based on these survival data, standard adjuvant chemoradiation therapy appears to be indicated for patients treated by pancreaticoduodenectomy for adenocarcinoma of the head, neck, or uncinate process of the pancreas. Intensive therapy conferred no survival advantage over standard therapy in this analysis.