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Biomedical subjects

T N Pappas

Publications and source records attributed to T N Pappas.

At least 19 recordsLinked to original sources

Impaired gastric motor activity after abdominal surgery in rats.

Postoperative ileus (POI) is a transient bowel dysmotility that occurs following abdominal surgery. Several mechanisms have been proposed such as neural reflex and inflammatory changes. We focused on gastric motility after abdominal surgery in rats. To investigate the time course of gastric motility after surgery, gastric motility was continuously recorded before, during and after surgery. After laparotomy, terminal ileum was manipulated for 10 min. Gastric motility was recorded by a strain gauge transducer implanted on the serosal surface of the stomach. To investigate whether peripheral sympathetic nerve is involved in the pathogenesis of POI, effects of guanethidine and celiac ganglionectomy were tested on the postoperative gastric motility. Although isoflurane anaesthesia reduced the gastric motility to 40%, the motility recovered immediately when isoflurane was withdrawn. Intestinal manipulation reduced the postoperative gastric motility for 3-24 h after surgery, compared with preoperative levels. Guanethidine administration and celiac ganglionectomy restored the impaired gastric motility. Feeding increased the gastric motility in each group. It is suggested that the pathogenesis of postoperative gastric ileus induced by intestinal manipulation involves viscero-sympathetic pathways. Intestinal manipulation causes impaired gastric motility via inhibitory sympathetic efferent pathway. Feeding may improve the postoperative gastric motility.

Adrenergic Agents↗

Percutaneous cervical oesophageal cannulation in the dog for the performance of prolonged oesophageal pH and manometric studies.

Traditional methods for obtaining oesophageal access in experimental animals are unsuitable for prolonged (24 h) oesophageal pH evaluation, a procedure that is commonly employed in the assessment of human patients suspected of having gastroesophageal reflux disease. In the present study, we describe a six-year experience with a technique of percutaneous oesophagostomy for the performance of serial 24 h oesophageal pH and manometric studies involving 62 dogs and a total of 208 oesophageal cannula placement procedures. The results indicate a considerable improvement over previously described techniques with respect to simplicity of surgical technique, associated morbidity, oesophagostomy management, animal conditioning, and avoidance of chemical and excessive physical restraints in animals undergoing oesophageal pH and manometric evaluation.

Animals↗

Magnitude of abdominal incision affects the duration of postoperative ileus in rats.

BACKGROUND: The pathogenesis of reduced postoperative ileus (POI) in laparoscopic gastrointestinal (GI) surgery still remains controversial. The aim of this study was to investigate the effect of surgical incision on postoperative ileus. METHODS: The effects of length, depth, and site of the incision on GI transit were compared using the geometric center of 51Cr in rats. The inhibitory mechanism of abdominal incision on GI transit also was studied. RESULTS: The findings showed that 5 cm of abdominal skin and the 5-cm back muscle incision had no significant effect on GI transit. However, the 5-cm abdominal muscle-fascia incision and a 5-cm laparotomy significantly delayed GI transit. Gastrointestinal transit after a 5-cm laparotomy was significantly delayed, as compared with that of a 1-cm laparotomy regardless whether intestinal manipulation was performed or not. Guanethidine and yohimbine, but not propranolol, significantly improved the impaired GI transit after a 5-cm laparotomy. CONCLUSIONS: The results suggest that the longer and deeper abdominal incision more profoundly inhibits GI transit. The inhibitory effect of abdominal incision is mediated via the activation of the somatosympathetic reflex and alpha-2 adrenoceptors.

Abdominal Injuries↗

Complications of pancreaticoduodenectomy after neoadjuvant chemoradiation in patients with and without preoperative biliary drainage.

BACKGROUND: It has been suggested that preoperative biliary drainage increases the risk of infectious complications of pancreaticoduodenectomy. AIMS: The aim of this study was to assess complications related to biliary stents/drains and postoperative morbidity in patients undergoing neoadjuvant chemoradiotherapy for periampullary cancer. PATIENTS: One hundred and eighty-four patients with periampullary neoplasms were prospectively selected for neoadjuvant external beam radiation therapy and 5-fluorouracil-based chemotherapy between 1995 and 2002. METHODS: The data were retrospectively completed and analysed with respect to biliary drainage, efficacy and complications of endoscopic biliary stents and postoperative morbidity. Patients who had undergone a surgical biliary bypass were excluded. RESULTS: Data were completed in 168 patients. One hundred and nineteen patients were treated with endoscopic biliary stents, 18 patients had a percutaneous biliary drain and 31 patients did not require biliary drainage. Hospitalisation for stent-related complications was necessary in 15% of the patients with endoscopic biliary stents. Seventy-two patients underwent pancreaticoduodenectomy. There was no significant difference in the rate of wound infections, intra-abdominal abscesses and overall complications between the groups with and without preoperative biliary drainage. CONCLUSIONS: Postoperative infectious complications are common in patients both with and without preoperative biliary drainage. A statistically significant difference in complication rates was not observed between these groups.

Adult↗

Vanilloid receptor-1 containing primary sensory neurones mediate dextran sulphate sodium induced colitis in rats.

BACKGROUND AND AIMS: The role of sensory neurones in colitis was studied by chemical denervation of primary sensory neurones as well as antagonism of the vanilloid receptor-1 (VR-1) in rats prior to administration of dextran sulphate sodium (DSS) to induce colitis. METHODS: Neonatal rats were chemically denervated by subcutaneous administration of capsaicin; controls received capsaicin vehicle only. When animals reached maturity, colitis was induced by administration of 5% DSS in drinking water for seven days. Additionally, normal adult rats were treated with a VR-1 antagonist capsazepine (CPZ) or vehicle twice daily via an enema from day 0 to day 6 of the DSS regimen. Control rats were treated with an enema infusion of vehicle and 5% DSS, or without either an enema infusion or DSS in drinking water. For both groups of rats, severity of inflammation was quantitated by disease activity index (DAI), myeloperoxidase (MPO) activity, and histological examination. RESULTS: DSS induced active colitis in all control rats with resultant epithelial ulceration, crypt shortening, and neutrophil infiltration. Both neonatal capsaicinised rats and normal adult rats treated with CPZ enemas exhibited significantly lower levels of DAI, MPO, and histological damage compared with vehicle treated rats (p< 0.05). CONCLUSIONS: Neonatal capsaicinisation and local administration of CPZ prevents intestinal inflammation in a well established model of colitis indicating that primary sensory neurones possessing VR-1 receptors are required in the propagation of colonic inflammation.

Animals↗

Laparoscopic antireflux surgery in the lung transplant population.

BACKGROUND: Lung transplantation has emerged as a viable therapeutic option for patients with a variety of end-stage pulmonary diseases. As immediate posttransplant surgical outcomes have improved, the greatest limitation of lung transplantation remains chronic allograft dysfunction. Gastroesophageal reflux disease (GERD) with resultant aspiration has been implicated as a potential contributing factor in allograft dysfunction. GERD is prevalent in end-stage lung disease patients, and it is even more common in patients after transplantation. We report here on the safety of laparoscopic fundoplication surgery for the treatment of GERD in lung transplant patients. METHODS: Eighteen of the 298 lung transplants performed at Duke University Medical Center underwent antireflux surgery for documented severe GERD. The safety and benefit of laparoscopic fundoplications in this population was evaluated. RESULTS: The antireflux surgeries included 13 laparoscopic Nissen fundoplications, four laparoscopic Toupets, and one open Nissen (converted secondary to extensive adhesions). Two of the 18 patients reported recurrence of symptoms (11%), and two others reported minor GI complaints postoperatively (nausea, bloating). There were no deaths from the antireflux surgery. After fundoplication surgery, 12 of the 18 patients showed measured improvement in pulmonary function (67%). CONCLUSIONS: GERD occurs commonly in the posttransplant lung population. Laparoscopic fundoplication surgery, when indicated, can be done safely with minimal morbidity and mortality. In addition to the resolution of reflux symptoms, improvement in pulmonary function may be seen in this population after fundoplication. Lung transplant patients with severe GERD should be strongly considered for antireflux surgery.

Adolescent↗

A canine model of gastroesophageal reflux disease (GERD).

BACKGROUND: Although a variety of antireflux procedures and medications are used to treat gastroesophageal reflux disease (GERD), reliable large-animal models of GERD that can be used to objectively compare the efficacy of these treatments are lacking. METHODS: Esophageal manometry and 24-h gastroesophageal pH monitoring with event data were performed in 18 mongrel dogs with a cervical esophagopexy. We then calculated a modified DeMeester score: The Duke Canine reflux score (DCR). Thereafter, the animals underwent a 4-cm anterior distal esophageal myotomy, incision of the left diaphragmatic crus, and intrathoracic gastric cardiopexy. Postoperative 24-h pH and manometry were obtained 2 weeks later. RESULTS: The postoperative 24-h pH results showed a significant increase in the mean DCR score (5.9 +/- 4.5 vs 84.9 +/- 56.1, p < 0.0002), and manometry indicated a significant decrease in mean lower esophageal sphincter (LES) pressure (7.1 +/- 2.9 vs 3.2 +/- 2.5 mmHg, p < 0.0001). CONCLUSION: This technique reliably creates a canine model of GERD.

Animals↗

Neoadjuvant chemoradiation for localized adenocarcinoma of the pancreas.

BACKGROUND: The use of neoadjuvant (preoperative) chemoradiotherapy (CRT) for pancreatic cancer has been advocated for its potential ability to optimize patient selection for surgical resection and to downstage locally advanced tumors. This article reports our experience with neoadjuvant CRT for localized pancreatic cancer. METHODS: Since 1995, 111 patients with radiographically localized, pathologically confirmed pancreatic adenocarcinoma have received neoadjuvant external beam radiation therapy (EBRT; median, 4500 cGy) with 5-flourouracil-based chemotherapy. Tumors were defined as potentially resectable (PR, n = 53) in the absence of arterial involvement and venous occlusion and locally advanced (LA, n = 58) with arterial involvement or venous occlusion by CT. RESULTS: Five patients (4.5%) were not restaged due to death (n = 3) or intolerance of therapy (n = 2). Twenty-one patients (19%) manifested distant metastatic disease on restaging CT. Twenty-eight patients with initially PR tumors (53%) and 11 patients with initially LA tumors (19%) were resected after CRT. Histologic examination revealed significant fibrosis in all resected specimens and two complete responses. Surgical margins were negative in 72%, and lymph nodes were negative in 70% of resected patients. Median survival in resected patients has not been reached at a median follow-up of 16 months. CONCLUSIONS: Neoadjuvant CRT provided an opportunity for patients with occult metastatic disease to avoid the morbidity of resection and resulted in tumor downstaging in a minority of patients with LA tumors. Survival after neoadjuvant CRT and resection appears to be at least comparable to survival after resection and adjuvant (postoperative) CRT.

Adenocarcinoma↗

Complete response to neoadjuvant chemoradiation for rectal cancer does not influence survival.

BACKGROUND: Up to 30% of patients with locally advanced rectal cancer have a complete clinical or pathologic response to neoadjuvant chemoradiation. This study analyzes complete clinical and pathologic responders among a large group of rectal cancer patients treated with neoadjuvant chemoradiation. METHODS: From 1987 to 2000, 141 consecutive patients with biopsy-proven, locally advanced rectal cancer were treated with preoperative 5-fluorouracil-based chemotherapy and radiation. Clinical restaging after treatment consisted of proctoscopic examination and often computed tomography scan. One hundred forty patients then underwent operative resection, with results tracked in a database. Standard statistical methods were used to examine the outcomes of those patients with complete clinical or pathologic responses. RESULTS: No demographic differences were detected between either clinical complete and clinical partial responders or pathologic complete and pathologic partial responders. The positive predictive value of clinical restaging was 60%, and accuracy was 82%. By use of the Kaplan-Meier life table analysis, clinical complete responders had no advantage in local recurrence, disease-free survival, or overall survival rates when compared with clinical partial responders. Pathologic complete responders also had no recurrence or survival advantage when compared with pathologic partial responders. Of the 34 pathologic T0 tumors, 4 (13%) had lymph node metastases. CONCLUSIONS: Clinical assessment of complete response to neoadjuvant chemoradiation is unreliable. Micrometastatic disease persists in a proportion of patients despite pathologic complete response. Observation or local excision for patients thought to be complete responders should be undertaken with caution.

Aged↗

Neoadjuvant chemoradiation for rectal cancer: analysis of clinical outcomes from a 13-year institutional experience.

OBJECTIVE: To examine clinical outcomes in patients receiving neoadjuvant chemoradiation for locally advanced rectal adenocarcinoma. SUMMARY BACKGROUND DATA: Preoperative radiation therapy, either alone or in combination with 5-fluorouracil-based chemotherapy, has proven both safe and effective in the treatment of rectal cancer. However, data are lacking regarding which subgroups of patients benefit from the therapy in terms of decreased local recurrence and increased survival rates. METHODS: A retrospective chart review was performed on 141 consecutive patients who received neoadjuvant chemoradiation (5-fluorouracil +/- cisplatin and 4,500-5,040 cGy) for biopsy-proven locally advanced adenocarcinoma of the rectum. Surgery was performed 4 to 8 weeks after completion of chemoradiation. Standard statistical methods were used to analyze recurrence and survival. RESULTS: Median follow-up was 27 months, and mean age was 59 years (range 28-81). Mean tumor distance from the anal verge was 6 cm (range 1-15). Of those staged before surgery with endorectal ultrasound or magnetic resonance imaging, 57% of stage II patients and 82% of stage III patients were downstaged. The chemotherapeutic regimens were well tolerated, and resections were performed on 140 patients. The percentage of sphincter-sparing procedures increased from 20% before 1996 to 76% after 1996. On pathologic analysis, 24% of specimens were T0. However, postoperative pathologic T stage had no effect on either recurrence or survival. Positive lymph node status predicted increased local recurrence and decreased survival. CONCLUSIONS: Neoadjuvant chemoradiation is safe, effective, and well tolerated. Postoperative lymph node status is the only independent predictor of recurrence and survival.

Adenocarcinoma↗

Immediate and long-term outcomes after lateral pancreaticojejunostomy for chronic pancreatitis.

Lateral pancreaticojejunostomy (LPJ) is the recommended surgical treatment of intractable pain from chronic pancreatitis (CP) with obstruction and ductal dilatation. This study evaluated the etiology, morbidity, mortality, hospital costs, and quality of life (QL) for patients with LPJ for CP. Medical records of 60 patients undergoing LPJ for CP between 1988 and 1996 were reviewed. Long-term QL was assessed by the Short Form 36 Health Survey and analyzed against control populations of patients who underwent pancreatic debridement for necrosis and patients with laparoscopic cholecystectomy for cholelithiasis. CP etiologies included 52 per cent alcoholic, 28 per cent idiopathic, 13 per cent pancreatic divisum, and 7 per cent familial pancreatitis. Peri- and postoperative morbidity and mortality were 25 and 0 per cent respectively. Average hospital cost was $13,530 with mean postoperative hospital stay of 12.1 days. Overall physical and mental QL were diminished compared with both the debridement group and cholecystectomy group with particular detriments in areas of physical role (P < 0.05), bodily pain (P < 0.001), social function (P < 0.001), and mental health (P < 0.001). We conclude that LPJ for CP is a relatively safe procedure with low morbidity and mortality but results in a significantly diminished long-term QL relative to other surgical patients with pancreatic or biliary disease. This difference prevails in both physical and mental aspects of health.

Adult↗

Safety and efficacy of India ink and indocyanine green as colonic tattooing agents.

BACKGROUND: Controversy exists concerning the safety and efficacy of colonic tattooing for the intraoperative identification of polypectomy sites. The purpose of this study was to determine (1) the concentrations of India ink and indocyanine green that resulted in high-visibility tattoos without significant tissue inflammation and (2) the India ink injection volume that produces best visibility at colonoscopy, laparoscopy, and laparotomy. METHODS: Twenty-two New Zealand white rabbits (2 kg) were anesthetized and injected with India ink (undiluted 1:10, 1:50, 1:100, 1:1000, 1:10,000) and indocyanine green as an undiluted, concentrated formulation (25 mL/2 mL solvent) or in a diluted form (25 mg/5 mL solvent) at various concentrations (1:10, 1:50, 1:100). Tuberculin syringes were used to create a 0.1 mL serosal bleb at two injection sites 2 cm apart. Laparotomy was repeated at days 1, 3, and 7 after injection. Additionally, 16 rabbits were injected with India ink at laparotomy and re-explored at 1 and 5 months. Twelve mongrel dogs (20 kg) were injected with 1.0 mL volumes. Re-exploration by colonoscopy, laparoscopy, and laparotomy was done at 7 days and 1 month. Tattoo visibility at re-exploration in both animal models was graded on a scale (0 = agent not seen, 1 = seen with difficulty, 2 = easily seen). Histology in the rabbit was judged by degrees of inflammation (0 = no inflammation, 2 = mild inflammation, 4 = moderate inflammation, 6 = severe inflammation). RESULTS: The concentrated indocyanine green solution was easily visible only on day 1 in the rabbit. Injections of both concentrated and diluted indocyanine green caused mucosal ulceration and moderate to severe inflammation. India ink studied at 7 days, 1 month, and 5 months after injection in the rabbit model was visible at all concentrations. The undiluted and 1:10 concentrations were easily seen and showed evidence of mucosal ulceration. Tattoos produced with all other India ink concentrations were visible without gross inflammation. India ink was also studied at 7 days and 1 month in dogs. The tattoo with the 1:100 concentration at 0.5 mL was seen consistently at colonoscopy, laparoscopy, and laparotomy with only a mild submucosal reaction at 7 days. The tattoos produced with the 1:100 and 1:1000 concentrations at 0.5 mL and 1.0 mL injection volumes were easily seen by all methods of intraabdominal visualization at 1 month with similar histology. CONCLUSION: Indocyanine green was an ineffective colonic tattooing agent. India ink was an effective colonic tattooing agent. Dilute concentrations that caused little to no inflammation could be visualized at 7 days and 1 month in rabbits and dogs and at 5 months in rabbits. India ink, at appropriated concentrations, appears to be a safe short- and long-term colonic tattooing agent.

Animals↗

Dextran sulfate sodium-induced colitis in immunodeficient rats.

To examine the morphology of colitis and study the role of the immune system in colitis, we compared colitis in immunocompetent Wistar-Kyoto rats with that in spontaneously hypertensive rats, known to have T-cell dysfunction. Rats were treated with 3% dextran sulfate in drinking water for periods ranging from 3 to 60 days. Diarrhea developed earlier and was associated with a more severe weight loss in Wistar-Kyoto rats than spontaneously hypertensive rats. The morphologic findings (flattening of the gland epithelium, gland dropout and ulceration) in spontaneously hypertensive rats were milder than in Wistar-Kyoto rats. Only spontaneously hypertensive rats survived 60 days of treatment; the findings included ulceration, crypt distortion, and inflammatory pseudopolyp formation. Immunostaining for B-cell, T-cell, and macrophage markers showed no difference in the distribution of these cells in the mucosa of Wistar-Kyoto rats and spontaneously hypertensive rats. Spontaneously hypertensive rats with T-cell dysfunction develop dextran sulfate sodium-induced colitis.

Animals↗

Lack of evidence for MHC-unrestricted (atypical) recognition of mucin by mucinous pancreatic tumour-reactive T-cells.

Cytotoxic T-cells generated against heterologous, mucinous pancreatic tumour cells were shown to recognize mucin in a major histocombatibility complex (MHC)-unrestricted fashion. In contrast, the present study demonstrates a typical allogeneic response of heterologous cytotoxic T-cells established against mucin-expressing pancreatic tumour cells. Heterologous cytotoxic T cells lysed targets that were used as stimulators and other targets that shared human leucocyte antigen (HLA) with the stimulator. These cytotoxic T-cells lysed mucin-expressing stimulator cells but not autologous tumour cells in spite of expressing mucin on their surface. Likewise, tumour-infiltrating CD4+ T-cells proliferated against its own tumour cell target, while such T-cells did not respond to heterologous, mucin-expressing pancreatic tumour cells. Culturing heterologous tumour-specific cytotoxic T-cells with purified pancreatic tumour cell-mucin rendered them unresponsive to their target cells. Furthermore, purified mucin did not produce a mucin-specific response in mucinous pancreatic tumour patients' primary T-cells even in the presence of antigen-presenting cells. Our study finds no evidence for MHC-unrestricted recognition of mucin by pancreatic cancer patients' T-cells.

Flow Cytometry↗

Local ampullary resection with careful intraoperative frozen section evaluation for presumed benign ampullary neoplasms.

BACKGROUND: Frozen section evaluation has been reported to be inaccurate in detecting foci of adenocarcinoma within adenomas of the ampulla of Vater, leading many authors to advocate pancreaticoduodenectomy as the method of treatment for these neoplasms. The authors hypothesized that (1) ampullary resection is less morbid than pancreaticoduodenectomy, and (2) frozen section evaluation following ampullary resection is accurate and allows for a selective application of pancreaticoduodenectomy to those with carcinoma or benign lesions too large to be locally resected. METHODS: A retrospective review of a single-surgeon experience was conducted. Thirty-eight patients who underwent ampullary resection and pancreaticoduodenectomy (39 procedures) for benign and malignant ampullary neoplasms were identified. Our technique of step-frozen section analysis is described. RESULTS: Twenty-one ampullary resections were performed for preoperative diagnoses of benign (16) and malignant (5) ampullary neoplasms. Frozen section evaluation accurately predicted the final histology in all patients undergoing ampullary resection. Ampullary resection (vs pancreaticoduodenectomy) was associated with a statistically lower operative time (169 minutes vs 268 minutes), estimated blood loss (192 mL vs 727 mL), mean length of stay (10 days vs 25 days), and overall morbidity (29% vs 78%). CONCLUSIONS: Frozen section evaluation of ampullary neoplasms is accurate. Because ampullary resection is less morbid than pancreaticoduodenectomy and frozen section evaluation is accurate, ampullary resection with frozen section evaluation is our current approach to the treatment of small benign ampullary neoplasms.

Adenocarcinoma↗

Laparoscopic biliary and enteric bypass.

Very few patients with a periampullary neoplasm present with resectable disease. Consequently, various operative and non-operative techniques have been developed to palliate patients with unresectable periampullary disease. Laparoscopic biliary (cholecystojejunostomy) and enteric bypass (gastrojejunostomy) are reasonable options as compared to their open counterparts for operative palliation. However, only a limited number of carefully selected patients meet selection criteria for laparoscopic palliation.

Bile Duct Neoplasms↗

Laparoscopy and peripancreatic neoplasia.

Since its inception laparoscopy has been a valuable tool for diagnosis, and more recently it has become widely accepted as a medium for surgical intervention. In this light, the addition of minimally invasive techniques to the management of peripancreatic cancer has gained notable attention. Although most practitioners agree that there is some role for minimally invasive therapy, opinions vary as to the extent and significance these applications carry to the overall management of peripancreatic malignancies.

Follow-Up Studies↗