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Biomedical subjects

Mark P Callery

Publications and source records attributed to Mark P Callery.

8 recordsLinked to original sources

Preoperative chemoradiation in resectable pancreatic cancer.

Despite advancements in the field of surgical oncology, the diagnosis of pancreatic cancer still carries a grave and dismal prognosis. Surgery alone for adenocarcinoma of the pancreatic head or uncinate process has a median survival time of 12 months. These grim statistics have led many to study the effects of combined multimodality therapy in the fight against pancreatic cancer. The long recovery time associated with pancreaticoduodenectomy has resulted in as many as 25% of patients unable to proceed with planned adjuvant therapy. For these reasons preoperative or neoadjuvantc hemoradiation therapy (CRT) has been evaluated. Pre-operative CRT ensures that all eligible patients receive the benefits of multimodality therapy, and patients who manifest metastatic disease on restaging evaluations are spared the morbidity of an unnecessary laparotomy. Multimodality therapy appears to lengthen the survival duration in patients with pancreatic cancer. It also affords a selection advantage, in that patients with aggressive disease biology with advanced metastatic disease following CRT are spared the morbidity of surgery. Conversely, a limited subset of patients may even be downstaged, allowing for a potentially curative resection. In this article we review the current status of neoadjuvant chemoradiation in adenocarcinoma of the pancreas. We discuss its rationale in light of the reported strengths and weaknesses of postoperative adjuvant CRT.

Adenocarcinoma↗

Is the use of a bougie necessary for laparoscopic Nissen fundoplication?

HYPOTHESIS: Esophageal intubation with a bougie during laparoscopic Nissen fundoplication (LNF) is commonly used to prevent an excessively tight wrap. However, a bougie may cause intraoperative gastric and esophageal perforations. We hypothesized that LNF is safe and effective when performed without a bougie. DESIGN: Retrospective review of 102 consecutive patients who underwent LNF without a bougie. SETTING: Tertiary care university hospital. PATIENTS: All patients presented with symptoms of reflux disease. Mean (+/- SD) percentage of time with pH of less than 4 was 12.6% +/- 9.4%. Mean DeMeester score was 47.8. Mean (+/- SD) resting lower esophageal sphincter pressure was 15.0 +/- 9.4 mm Hg. Mean (+/- SD) distal esophageal amplitude was 69.4 +/- 39.2 mm Hg. INTERVENTION: During LNF, we obtained 2 to 3 cm of intra-abdominal esophagus, divided all short gastric vessels, reapproximated the crura, and performed a loose 360 degrees fundoplication without a bougie. MAIN OUTCOME MEASURES: Postoperative rates of dysphagia, gas bloat, and recurrent reflux. RESULTS: In the early postoperative period, 50 patients (49.0%) complained of mild, 11 (10.8%) of moderate, and 7 (6.9%) of severe dysphagia. Average (+/- SD) duration of early dysphagia was 4.6 +/- 2.1 weeks. Dysphagia resolved in 61 (89.7%) of 68 patients within 6 weeks. Late resolution of dysphagia was noted in 4 (5.8%) patients. Three patients were successfully treated with esophageal dilatations. Persistent dysphagia was found in 1 patient. Thirty patients (29.4%) had transient gas bloat. Mild persistent reflux, requiring daily medication, was noted in 5 (4.9%) patients. CONCLUSIONS: Performance of LNF without a bougie offers a safe and effective therapy for gastroesophageal reflux disease. While avoiding the potential risks for gastric and esophageal injury, it may provide low rates of long-term postoperative dysphagia and reflux recurrence.

Deglutition Disorders↗

Regulation of NFkappaB in hepatic ischemic preconditioning.

BACKGROUND: The second messengers tyrosine kinase (TK) and protein kinase C (PKC) have been implicated in mediating the cellular signaling cascade during hepatic ischemic preconditioning (IPC). We evaluated the role of TK and PKC on the modulation of the transcription factor nuclear factor kappa B (NFkappaB) and its inhibitor IkappaB alpha during IPC. STUDY DESIGN: Yorkshire pigs underwent routine harvest. IPC livers underwent 15 minutes of ischemia and 15 minutes of in situ perfusion before harvest, with or without pretreatment with a TK inhibitor (genistein) or a PKC inhibitor (chelerythrine). During cold storage and reperfusion, tissue extracts were analyzed for IkappaB alpha phosphorylation and NFkappaB levels and for TK and PKC activity by Western blot. RESULTS: Control pig livers demonstrated no change in the levels of TK, PKC, IkappaB alpha, or NFkappaB before cold ischemia. IPC grafts demonstrated activation of TK and PKC with increased IkappaB alpha phosphorylation and NFkappaB levels before cold ischemia. IPC grafts pretreated with genistein demonstrated inhibition of TK activation but not of PKC activation. Genistein-pretreated grafts also demonstrated inhibition of IkappaB alpha phosphorylation and a lack of NFkappaB translocation to the nucleus throughout the entire experiment. IPC grafts pretreated with chelerythrine demonstrated inhibition of PKC activation but not TK activation. Chelerythrine-pretreated grafts also demonstrated IkappaB alpha phosphorylation before cold ischemia and enhanced nuclear levels of NFkappaB. CONCLUSIONS: Data suggest that the role of TK in IPC might be mediated in part by NFkappaB, but PKC does not depend on NFkappaB for its effect. Two parallel signaling pathways might explain these data.

Alkaloids↗

Chronic cough due to gastroesophageal reflux disease: failure to resolve despite total/near-total elimination of esophageal acid.

BACKGROUND: While medical therapy may fail to improve cough due to gastroesophageal reflux disease (GERD), it is not known if inadequate esophageal acid suppression is responsible. METHODS: In a prospective, before-and-after interventional trial, we assessed the effects of antireflux surgery in eight patients whose chronic coughs were due to GERD resistant to intensive medical therapy. All patients met a profile predicting that cough was likely due to GERD and had an initial positive 24-h esophageal pH monitoring study, and then underwent serial 24-h esophageal pH monitoring on gradually intensified medical therapy until the percentage of time that esophageal pH was < 4 was zero and there were no acid reflux events > 4 min. The effects of medical and surgical therapy on cough were assessed clinically by a visual analog scale (VAS) and the Adverse Cough Outcome Survey (ACOS). RESULTS: Before surgery (median, 23.7 days), patients still complained of cough, VAS score was 73.1 +/- 6.1, and ACOS score was 15.0 +/- 1.1. After surgery (median, 41.2 days and 1 year), cough improved in all, VAS score decreased to 19.1 +/- 8.3 and 22.6 +/- 8.1 (p = 0.001), respectively, and ACOS score decreased to 2.0 +/- 1.3 and 3.6 +/- 2.3, respectively (p = 0.002). CONCLUSIONS: Antireflux surgery can improve chronic cough due to GERD resistant to intensive medical therapy. There is a clinical profile that can predict when GERD is the likely cause of cough. GERD cannot be excluded on clinical grounds as the potential cause of cough. The term acid reflux disease, when applied to chronic cough due to GERD, can be a misnomer.

Adult↗

Donor hepatic function: a factor in postreperfusion syndrome.

Reperfusion of support livers after cold preservation produces hemodynamic instability (i.e., postreperfusion syndrome) in the recipient during both orthotopic liver transplantation and extracorporeal liver perfusion. We evaluated the effect of the normal porcine cold-preserved support liver on healthy recipient hemodynamics and in situ liver function during extracorporeal liver perfusion. Support livers were harvested from Yorkshire pigs and reperfused in an extracorporeal circuit with a healthy, anesthetized recipient pig. Correlation analyses were performed between support liver variables of function (oxygen consumption, bile flow, and biliary phospholipid and cholesterol output) and both recipient hemodynamic stability (heart rate, blood pressure, urine output, and vasopressor use) and hepatic function (bile flow and biliary phospholipid secretion). The data indicate that optimally functioning support livers are associated with improved recipient hemodynamic stability manifested by decreased recipient heart rate and vasopressor use and increased recipient urine output. Support livers exhibiting poor biliary secretory function (i.e., bile flow and phospholipid output) were associated with similarly diminished recipient liver biliary secretory function. These data indicate that the functional condition of the support liver after harvest and cold preservation may influence both recipient hemodynamic parameters and the endogenous function of the recipient liver.

Animals↗