Biomedical subjects

G G Tsiotos

Publications and source records attributed to G G Tsiotos.

At least 19 recordsLinked to original sources

PubMed2001

Molecular biology of pancreatic cancer: potential clinical implications.

The development of cancer involves the accumulation of genetic changes. Over the past decade there has a been spectacular advance in the knowledge of the genetic basis of cancer, mainly as a result of the rapid progression of molecular technology. Pancreatic cancer is one of the most lethal cancers. Conventional therapeutic approaches have not had much impact on the course of this aggressive neoplasm. Knowledge of the molecular biology of pancreatic cancer has grown rapidly. Genetic alterations in pancreatic cancer include oncogene mutations (most commonly K-ras mutations), and tumour suppressor gene alterations (mainly p53, p16, DCC, etc.). These advances have potential implications for the management of this deadly disease. Identification of a hereditary genetic predisposition to pancreatic cancer has led to the formation of pancreatic cancer registries around the world, with voluntary screening of patients and siblings for the hereditary genetic defect. Asymptomatic population screening remains unrealistic, but the recognition of subpopulations at increased risk from pancreatic cancer, along with novel and sensitive detection techniques, means that targeted population screening is a step closer. Intensive research is performed in specialist laboratories to improve the diagnostic approach in patients with pancreatic cancer. The use of such molecular diagnostic methods is likely to expand. Molecular biology may also have a great impact on the treatment of pancreatic cancer, and many therapeutic approaches are being evaluated in clinical trials, including gene replacement therapy, genetic prodrug activation therapy, antisense immunology and peptide technology. The 'molecular age' has the promise of delivering still better results. This review summarises recent data relating to the molecular biology of pancreatic cancer, with emphasis on features that may be of clinical significance for diagnosis and/or therapy.

Genes, Tumor Suppressor↗

PubMed2000

Molecular biology of pancreatic cancer; oncogenes, tumour suppressor genes, growth factors, and their receptors from a clinical perspective.

Pancreatic cancer represents the fourth leading cause of cancer death in men and the fifth in women. Prognosis remains dismal, mainly because the diagnosis is made late in the clinical course of the disease. The need to improve the diagnosis, detection, and treatment of pancreatic cancer is great. It is in this type of cancer, in which the mortality is so great and the clinical detection so difficult that the recent advances of molecular biology may have a significant impact. Genetic alterations can be detected at different levels. These alterations include oncogene mutations (most commonly, K-ras mutations, which occur in 75% to more than 95% of pancreatic cancer tissues), tumour suppressor genes alterations (mainly, p53, p16, DCC, etc.), overexpression of growth factors (such as EGF, TGF alpha, TGF beta 1-3, aFGF, bTGF, etc.) and their receptors (i.e., EGF receptor, TGF beta receptor I-III, etc.). Insights into the molecular genetics of pancreatic carcinogenesis are beginning to form a genetic model for pancreatic cancer and its precursors. These improvements in our understanding of the molecular biology of pancreatic cancer are not simply of research interest, but may have clinical implications, such as risk assessment, early diagnosis, treatment, and prognosis evaluation.

Female↗

PubMed2000

Ischemia/Reperfusion-Induced pancreatitis.

BACKGROUND/AIM: The pancreas is an organ highly susceptible to ischemic damage. This discussion reviews the role of ischemia as an etiologic factor in acute pancreatitis. METHODS: Literature review. RESULTS: The susceptibility of the pancreas to ischemia/reperfusion injury has been demonstrated in experimental studies and in clinical settings such as cardiopulmonary bypass, hemorrhagic shock, and transplantation of the pancreas. Oxygen free radicals, activation of polymorphonuclear leukocytes, failure of microvascular perfusion, cellular acidosis, and disturbance of intracellular homeostasis appear to be important factors/mechanisms in the pathogenesis of ischemia/reperfusion-induced acute pancreatitis. In clinical practice, the diagnosis of ischemic pancreatitis is difficult and often delayed, especially during the postoperative period after cardiac or major vascular surgery. CONCLUSIONS: Ischemia appears to be one important factor in acute pancreatitis. The management of ischemic pancreatitis is similar to that of acute pancreatitis of any etiology.

Acidosis↗

PubMed2000

Adenocarcinoma of the distal bile duct. A clinicopathologic outcome analysis after curative resection.

BACKGROUND/AIMS: Primary distal bile duct adenocarcinomas (DBDAs) are unusual neoplasms, necessitating pancreaticoduodenectomy for cure. The aims of this study were to evaluate the prognostic importance of lymphatic and perineural invasion, long-term outcome of patients after resection, and differences in outcome with hilar cholangiocarcinoma and pancreatic carcinoma. METHODS: The medical records and histopathological slides of 15 patients (8 men and 7 women) with documented DBDA after curative pancreaticoduodenectomy were reviewed. RESULTS: Nine standard and 6 pylorus-preserving pancreaticoduodenectomies were performed. TNM staging included 1, 3, 2, 8, and 1 patient in stages I, II, III, and IVA and IVB, respectively. Lymphatic and perineural invasion was present in 4 (27%) and 9 (60%) patients, respectively. With multivariate analysis only serum bilirubin was a significant prognostic factor. Median survival was 21 months, and 2- and 5-year actuarial survivals were 40 and 20%, respectively. Median survival with adjuvant therapy (n = 6) was 21 months, with 5-year survival of 33%. Five-year actuarial survivals when lymphatic or perineural invasion was present were 0 and 11%, respectively. CONCLUSION: DBDA is aggressive, but entails a better prognosis than pancreatic ductal or more proximal bile duct carcinoma. Lymphatic and/or perineural invasion worsen survival.

Aged↗

PubMed1999

Are the results of pancreatectomy for pancreatic cancer improving?

Although pancreatectomy is still performed in a few patients with pancreatic cancer, and nearly all patients who develop pancreatic cancer eventually die of their disease, significant improvements have been made recently. Pancreatectomy is now safer, with major morbidity (hemorrhage, pancreatic anastomotic leak, intraabdominal sepsis) occurring in only about 20% and operative mortality of less than 5%. Two (seemingly subtle) issues cannot be overemphasized when someone carefully studies the literature: (1) There is a crucial difference between actuarial and actual survival, with the former generally being higher whereas the latter is true; and (2) careful re-review of pathologic specimens (especially in long-term survivors) initially diagnosed as pancreatic cancer, preferably by an independent pathologist before publishing long-term results is essential. (Erroneous inclusion of patients with nonductal carcinoma substantially and artificially increases survival.) After curative resection, 5-year actual survival is realistically about 10% with median survivals of 12 to 18 months. In certain subgroups with favorable pathologic characteristics (neoplasms <2 cm without nodal or perineural invasion) the prognosis appears to be significantly better, with the 5-year survival about 20%. The recent improvements in postoperative morbidity and mortality and long-term outcome (resulting also in decreased cost of care of such patients) have occurred typically in centers with an invested interest in and proven record with pancreatic surgery. Further improvements in survival should be sought at the areas of earlier diagnosis and novel treatments designed to prevent locoregional recurrences; the role of extended resections must be determined by prospective, randomized trials.

Humans↗

PubMed1999

Management of fluid collections and necrosis in acute pancreatitis.

According to the Atlanta classification, the most widely accepted clinically based classification system for acute pancreatitis, four pathologic entities of fluid collections and necrosis are recognized. Acute fluid collections occur early as an exudative reaction to the pancreatic inflammation, have no fibrous wall, and resolve spontaneously. Pancreatic necrosis, the most severe form of acute pancreatitis, is diagnosed on dynamic contrast-enhanced computerized tomography and requires early aggressive cardiorespiratory resuscitation, nutritional support, and appropriate systemic antibiotics to prevent superinfection. Development of infection (infected necrosis) is the indication for operative debridement, preferably as late in the course of the disease as possible. Acute pseudocysts are collections of pancreatic, enzyme-rich fluid caused by pancreatic ductal disruption that occur 3 to 6 weeks after onset of acute pancreatitis and have a well-defined, nonepithelial fibrous wall. If communication with the ductal system is present, internal enteric drainage (either operative or endoscopic) is more effective; if communication is not present, the pseudocysts are amenable to percutaneous drainage. A pancreatic abscess is an infected, circumscribed peripancreatic collection, associated with minimal or no parenchymal necrosis, that occurs late (4 to 6 weeks) after onset of severe pancreatitis and may represent an infected pseudocyst; percutaneous drainage is the treatment of choice.

Abscess↗

PubMed1999

Palliation of pain in chronic pancreatitis. Use of neural blocks and neurotomy.

Effective management of the pain of chronic pancreatitis may require a multidisciplinary approach involving gastroenterologists, anesthesiologists, psychologists or counselors for chemical addiction (alcohol, narcotics), and surgeons. Viable approaches use pharmacologic analgesics with selected psychotropic medications, celiac plexus blocks, and possibly thoracoscopic splanchnic nerve transections. If these management techniques that preserve pancreatic parenchyma and function, fail, resective surgical therapy may be indicated. For most of these patients, all attempts at nonresective therapy should be exhausted before operative intervention.

Analgesics↗

PubMed1999

Fungal infection in acute necrotizing pancreatitis.

BACKGROUND: Anecdotal reports suggest that patients with fungal infection of necrotizing pancreatitis (NP) have worse outcomes than those with bacterial infection. Our aim was to compare the clinical course and outcomes of patients with NP infected with fungal versus nonfungal organisms. STUDY DESIGN: Prospectively collected data on 57 patients with infected NP (1983-1995) were reviewed. RESULTS: Seven patients (12%) developed fungal infection, and 50 (88%) developed bacterial infection. Groups had similar mean ages (60 versus 63 years) and APACHE-II scores on admission (9 each). The cause of NP was ERCP-induced in 3 of 7 with fungal infection versus 3 of 50 with bacterial infection. Patients with fungal infection had been treated with a mean of 4 different antibiotics for a mean of 23 days, and 4 of 7 (57%) required mechanical ventilation preoperatively. In addition, postoperative ICU stays were longer (20 versus 10 days), as were total hospital stays (59 versus 41 days). Mortality was higher with fungal infection; 3 of 7 patients (43%) died versus 10 of 50 patients (20%). CONCLUSIONS: Although NP presents with similar initial severity, patients with fungal infection of NP tend to have a more complicated course and worse outcomes compared with those with bacterial infection. Low-dose antifungal prophylaxis should be added to early management of NP.

Adult↗

PubMed1999

Extrapancreatic necrotizing pancreatitis with viable pancreas: a previously under-appreciated entity.

BACKGROUND: Necrotizing pancreatitis is generally considered to involve the pancreatic parenchyma in all patients, and, as an extension of the necrotic process, the peripancreatic tissues as well. We identified a subgroup of patients in whom the necrotic process involves apparently extrapancreatic tissues alone (EXPN), as opposed to the usual combined parenchymal and peripancreatic necrosis (PN). STUDY DESIGN: The objective of this study was to compare clinical courses of EXPN and PN. Data were reviewed on 82 consecutive patients with necrotizing pancreatitis treated operatively between 1983 and 1997. The extent of pancreatic parenchymal necrosis (expressed as percent of pancreas based on contrast-enhanced CT and operative findings) was estimated in 62 patients. Diagnosis of EXPN required normal enhancement of entire pancreas on dynamic CT and operative documentation of viability of the gland. RESULTS: Twelve patients (19%) had EXPN and 50 (81%) had PN. Gender, age, body mass index, etiology of pancreatitis, prevalence, and type of infection were similar between groups, but APACHE-II scores on admission were less in EXPN (6+/-2 versus 10+/-1, p = 0.02). Patients with EXPN required fewer reoperative necrosectomies (0.7 versus 3.2, p = 0.009) and did not develop pancreatic or gastrointestinal fistulas (0 versus 19 patients) or hemorrhage (0 versus 8 patients). ICU stays were similar, but hospital stays in EXPN were shorter (29+/-6 versus 54+/-5 days, p = 0.01) and mortality was less (8% and 20%, p<0.001). CONCLUSIONS: Necrotizing pancreatitis manifesting as EXPN is not rare. EXPN is a less aggressive form of necrotizing pancreatitis, locally and systemically, and signifies a better prognosis.

Adult↗

PubMed1999

Intra-abdominal complications after cardiac surgery.

Gastrointestinal complications such as peptic ulcer disease, pancreatitis, acute cholecystitis, bowel ischaemia, and diverticulitis are rare after cardiac surgery (< 1%), but are associated with high morbidity and mortality (about 30%). Hypoperfusion during cardiopulmonary bypass seems a possible aetiological factor. As many patients may be mechanically ventilated and sedated, the usual symptoms and signs of an abdominal complication may be masked. It is necessary to keep this possibility in mind in patients with abdominal pain or tenderness, and the usual diagnostic measures should be undertaken if time permits. Initial treatment is usually conservative, but when it fails, prompt intervention is obligatory. Unfortunately surgeons are often reluctant to submit patients to major abdominal operations immediately after cardiac surgery. However, effective and timely intervention may be life-saving in patients who are poorly able to compensate for the major haemodynamic disturbances of the untreated serious bleeding or sepsis. Although the cardiac condition must be taken into consideration, most patients' cardiac function will have improved since their open-heart surgery and they should be able to withstand general anaesthesia and most operations.

Aged↗

PubMed1999

Pancreas regeneration after resection: does it occur in humans?

Although pancreatic regeneration after partial resection or pancreatic injury (restitutio ad integrum) has been demonstrated in animal models, whether regeneration occurs in the human pancreas is unknown. Our aim was to determine whether the human pancreas regenerates after subtotal resection. We reviewed pre- and postoperative computerized tomograms (CTs) of 21 patients after proximal pancreatectomy (50-60% resection) for malignancy with no recurrent disease during follow-up of pancreatic parenchymal abnormalities. Three fixed anatomic measurements (pancreatic body width, tail width, and length) were compared with the same region 10 and 21 months after surgery. Data are expressed as mean +/- SEM. Pancreatic measurements before and 10 months after resection did not differ for body width (2.0+/-0.1 cm vs. 1.8+/-0.1 cm), tail width (2.2+/-0.2 cm vs. 1.8+/-0.2 cm) or length (8.2+/-0.3 vs. 7.4+/-0.4 cm) (p> or =0.1 each). At 21 months after resection, measurements were less for body width and tail width (2.2+/-0.2 cm vs. 1.5+/-0.2 cm and 2.2+/-0.1 cm vs. 1.5+/-0.2 cm, respectively; p = 0.01) and unchanged for length (8.1+/-0.4 cm vs. 8.1+/-0.4 cm; p = 0.9). We conclude that the human pancreas does not regenerate after partial anatomic (50%) resection.

Adult↗

PubMed1999

Experience with duodenal necrosis. A rare complication of acute necrotizing pancreatitis.

Duodenal necrosis is a rare, but very serious complication of acute necrotizing pancreatitis that most likely is the result of vascular compromise and ischemia of the peri-Vaterian aspect of the duodenal wall. In this article, we present three patients with duodenal necrosis complicating acute necrotizing pancreatitis. The diagnosis was made at the time of necrosectomy. Management options of this challenging complication of necrotizing pancreatitis are discussed.

Adult↗

PubMed1999

Laparoscopic splenectomy: evolution and current status.

The aim of this review is to assess the indications for, and surgical approach to, laparoscopic splenectomy (LS) and to propose a recommendation for the surgical approach to LS. The reports of LS were reviewed with a detailed analysis of indications, surgical technique, and clinical outcome. Thirty-two articles including a total of 643 patients (549 adults and 94 children) were published between August 1994 and May 1997, with a mean of 20 cases per report. LS is recommended if the spleen has a maximum diameter of 20 cm. Compared to the open procedure, there are fewer perioperative complications, less morbidity, and a shorter hospital stay. The disadvantages of LS are longer operation times and less sensitivity in identifying accessory spleens. LS is not the operation of choice for hypersplenism and traumatic splenic injury.

Adult↗

PubMed1998

Ischemic necrotizing pancreatitis. Two case reports and review of the literature.

Pancreatic ischemia is a very rare etiology of clinical acute pancreatitis, complicating cardiac surgery, hemorrhagic shock, and transplantation of the pancreas. In this article, we present two patients with acute ischemic necrotizing pancreatitis, complicating a generalized atheromatous disease with extensive lesions in the splanchnic circulation (patient 1) and repair of a descending thoracic aortic aneurysm (patient 2). Diagnostic approach and management of ischemic necrotizing pancreatitis are discussed.

Aged↗

PubMed1998

Management of necrotizing pancreatitis by repeated operative necrosectomy using a zipper technique.

METHODS: From 1983 to 1995, 72 patients with necrotizing pancreatitis were treated with a general approach involving planned reoperative necrosectomies and interval abdominal wound closure using a zipper. RESULTS: Hospital mortality was 25%. Multiple organ failure without sepsis caused early mortality in 3 of 4 patients and sepsis caused late mortality in 11 of the remaining 14. The mean number of reoperative necrosectomies/debridements was 2 (0 to 7). Fistulae developed in 25 patients (35%); 64% were treated conservatively. Recurrent intraabdominal abscesses developed in 9 patients (13%) but were drained percutaneously in 5. Hemorrhage required intervention in 13 patients (18%). Prognostic factors included APACHE-II score on admission < 13 (P = 0.005), absence of postoperative hemorrhage (P = 0.01), and peripancreatic tissue necrosis alone (P < 0.05). CONCLUSIONS: The zipper approach effectively maximizes the necrosectomy and decreases the incidence of recurrent intraabdominal infection requiring reoperation. APACHE-II score > or = 13, extensive parenchymal necrosis, and postoperative hemorrhage signify worse outcome.

APACHE↗

PubMed1998

Long-term outcome of necrotizing pancreatitis treated by necrosectomy.

BACKGROUND: Long-term functional outcome after operative treatment of necrotizing pancreatitis (NP) has not been studied extensively. METHODS: Pancreatic function, performance status, recurrence of symptoms and other related problems were analysed in 44 consecutive patients successfully discharged from hospital after operative necrosectomy (1983-1995) and followed up completely for a mean of 5 years. RESULTS: Clinical pancreatic insufficiency developed in half the patients. Diabetes mellitus (11 patients), steatorrhoea (six) or both (five) were associated with a mean estimate of 52, 66 and 67 per cent parenchymal necrosis respectively. Normal pancreatic function was associated with 27 per cent parenchymal necrosis (P < 0.05). Diabetes worsened while steatorrhoea tended to improve over time. Abdominal pain and pancreatitis recurred in six and two patients respectively. Performance status worsened in four patients because of recurrent pancreatitis and severe steatorrhoea. Poor long-term performance was associated with a higher Acute Physiology And Chronic Health Evaluation II score on admission (mean 14 versus 9). CONCLUSION: NP has prominent effects on long-term pancreatic exocrine and endocrine function in half the patients, but most preserve a good overall functional status. The development of pancreatic insufficiency varies with the extent of pancreatic parenchymal necrosis.

APACHE↗

PubMed1998

Pancreas-preserving total duodenectomy.

The concept of operations to be 'as resective as necessary and as organ-preserving as possible' has led to the novel technique of resection of the entire duodenum, with complete preservation of the head of the pancreas, as a better alternative to the classic pancreaticoduodenectomy. This operation requires meticulous technique and precise knowledge of pancreatic and peripancreatic anatomy. Indications include benign or premalignant conditions confined to the duodenal mucosa, usually familial adenomatous polyposis. When appropriately performed, pancreas-preserving total duodenectomy leads to shorter operative time, requires less and safer anastomoses, and optimizes postoperative endoscopic surveillance. The available long-term results are encouraging.

Adult↗

PubMed1997

Pancreatic ascites: a rare complication of necrotizing pancreatitis. A case report and review of the literature.

We describe a young patient with a family history of hereditary pancreatitis who developed extensive pancreatic necrosis complicated by pancreatic ascites. Because of failure of medical management, he was successfully treated with operative necrosectomy and primary wound closure over peripancreatic drains. A postoperative low-output pancreaticocutaneous fistula resolved with time. Pancreatic ascites, as a result of pancreatic duct disruption, is more common in chronic rather than acute pancreatitis and is exceedingly uncommon in the context of necrotizing pancreatitis. When it complicates the latter, treatment should be guided by the principles of management of necrotizing pancreatitis. However, when true pancreatic ascites persists, the pancreatic duct anatomy and site of leak should be defined with endoscopic retrograde pancreatography (ERP). Treatment options include endoscopic duct dilatation and stent placement (if a stricture exists proximal to the leak), onlay pancreaticojejunostomy, or distal pancreatectomy (especially if the leak is located in the distal pancreas or in an enterically isolated distal pancreas).

Adult↗