New legislative regulations, problems, and future perspectives, with a particular emphasis on surgical education.

Major changes in the residency-training systems are currently under way worldwide. New laws regulating the maximum number of work-hours per week are already enforced in the USA and are soon to be enforced in the European Union (EU); they apply to residents in training, as well as to practising specialists in the USA. These changes are expected to influence training imparted to resident doctors, quality of care given to hospitalised patients and functioning of hospitals, in general. The implications of the new regulations are likely to be magnified by the gradual decrease in the number of young people willing to take up Medicine as a career and even more so by the decrease in the number of medical graduates who choose to take up Surgery as their specialty. This communication describes the new situation that has developed (especially in general surgery) with the recent regulations and intends to suggest possible solution to the important problems that are likely to arise.

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.

Ileal absorptive adaptation to jejunal resection and extrinsic denervation: implications for living-related small bowel transplantation.

Net absorption of water, electrolytes, and simple nutrients decreases early after jejunoileal autotransplantation (extrinsic denervation) in a canine model but recovers toward normal by 8 weeks. However, the ability of the extrinsically denervated ileum to adapt after total jejunectomy, which would be relevant as a model of segmental small bowel transplantation, remains unknown. Two groups of five dogs each were studied before and 2 weeks and 12 weeks after 50% proximal enterectomy. A control group remained neurally intact, whereas the other group underwent extrinsic denervation (Ext Den) of the remaining ileum. Using a perfusion technique, net absorption of water, electrolytes, and five simple nutrients (glucose, arginine, glutamine, and oleic and taurocholic acids) was measured at the three time points. Ileal morphometry was also evaluated. All dogs developed diarrhea, which resolved by 12 weeks in all but two of the Ext Den dogs. Weight in both groups was decreased at 2 weeks (P <0.05), returned to normal at 12 weeks in control dogs, but remained low in Ext Den dogs (P <0.05). Maximal weight loss was greater in the Ext Den group (P <0.05). No consistent or important differences in net absorptive fluxes of water, electrolytes, or simple nutrients were noted either within or between groups at any time point. Villous height, crypt depth, and longitudinal muscle width increased significantly at 12 weeks after jejunectomy in the Ext Den dogs, but not in the control dogs (P <0.05). Extrinsic denervation of the ileum results in persistent weight loss after proximal 50% enterectomy. Despite diarrhea, only minor changes in electrolyte absorption occur, and ileal net absorption of simple nutrients remains unaffected. The ileum of extrinsically denervated dogs undergoes a more prominent morphometric adaptation after jejunectomy. Extrinsic denervation necessitated by small bowel transplantation, independent of immune effects, does not appear to suppress the ileal adaptive response to maintain net absorption of water, electrolytes, and simple nutrients.

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.

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.

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.

Villous tumors of the duodenum: reappraisal of local vs. extended resection.

Benign villous tumors of the duodenum are often managed by transduodenal local excision. Risk of local recurrence, coupled with improving safety of radical pancreaticoduodenectomy, has prompted reexamination of the roles of conservative and radical operations. The aim of this study was to determine long-term outcome after local and extended resection in order to identify factors to consider in planning operative strategy. Eighty-six patients (mean age 64 years) with villous tumors of the duodenum managed surgically from 1980 to 1997 were reviewed. Histologic findings, size, presence of polyposis syndromes, and extent of resection were correlated with outcome. Villous tumors were benign adenomas in 64 patients (74%), contained carcinoma in situ in three (4%), and invasive carcinoma in 19 (22%). The presence of cancer was not known preoperatively in 9 (47%) of the 19 with invasive carcinoma. Operative treatment included transduodenal local excision in 53 patients, pancreaticoduodenectomy in 20, pancreas-sparing duodenectomy in five, full-thickness excision in four, and other in six. Among the 50 patients with benign tumors managed by local excision, 17 had a recurrence with actuarial rates of 32% at 5 years and 43% at 10 years; four of the recurrences (24%) were adenocarcinomas. The recurrence rate was influenced by the presence of a polyposis syndrome but not by tumor size. Recurrence of benign villous tumors after local excision is common and may be malignant. Pancreaticoduodenectomy is appropriate for villous tumors containing cancer and may be considered an alternative for select patients with benign villous tumors of the duodenum. If local excision is performed, regular postoperative endoscopic surveillance is mandatory.

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.

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.

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.

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.

Staging laparoscopy for pancreatic cancer should be used to select the best means of palliation and not only to maximize the resectability rate.

Staging laparoscopy, based on the assumption that endobiliary stenting is the best palliation, allegedly saves an "unnecessary" laparotomy for incurable pancreatic cancer. Our aim was to determine survival of patients with clinically resectable pancreatic cancer that is found to be unresectable intraoperatively and thereby infer appropriate utilization of staging laparoscopy. A retrospective analysis was undertaken of 148 patients with ductal adenocarcinoma (1985 to 1992) with a clinically resectable lesion based on current imaging techniques. All were considered candidates for resection but were deemed unresectable at operation because of metastases to the liver (group I; 29 patients), the peritoneum (group II; 22 patients), or distant lymph nodes (group III; 44 patients) or because of vascular invasion (group IV; 53 patients). Overall median survival was 9 months (range 1 to 53 months), but by group was as follows: group I, 6 months; group II, 7 months; group III, 11 months; and group IV, 11 months. Individual comparisons showed shorter survival for patients with distant nodal, liver, or peritoneal metastases than with nodal or vascular involvement (P<0.03). Staging laparoscopy should be performed to identify patients with liver or peritoneal metastases who have an expected survival of approximately 6 months, in whom short-term endoscopic palliation is satisfactory. Extended laparoscopy to identify lymph node or vascular involvement is contingent upon which palliation (operative vs. endoscopic) is considered most appropriate. Because we believe operative bypass provides better, more durable palliation in this latter group, we have not adopted extended laparoscopy.

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.

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.

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.

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.

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.

Laparoscopic management of small bowel obstruction: indications and outcome.

Our aim was to evaluate the feasibility of a laparoscopic, minimal access approach for the management of patients with small bowel obstruction. Forty patients underwent laparoscopic treatment of radiologically documented or suspected small bowel obstruction based on history and/or motility study. None had chronic abdominal or pelvic pain. The operation was completed laparoscopically in 14 patients (35%) and with laparoscopic-assisted procedures in 12 (30%); 14 (35%) required conversion to open celiotomy because of dense adhesions (precluding complete inspection or adhesiolysis), small bowel necrosis in the setting of small bowel obstruction, or neoplasia. Three iatrogenic enterotomies occurred while "running" the bowel. There were three (7%) postoperative procedure-related complications (wound infection, intra-abdominal abscess, ileus). The combined group of patients treated laparoscopically or with laparoscopic-assisted procedures had a shorter hospital stay than those converted to open celiotomy (4 +/- 0.6 vs. 7 +/- 0.7 days; P <0.003). At median follow-up of 12 months, 21 of 26 patients managed laparoscopically or with laparoscopic-assisted procedures remain asymptomatic; all 21 patients with an operatively confirmed site of mechanical obstruction managed by a minimal access approach remain asymptomatic. Laparoscopic treatment of small bowel obstruction is effective, leads to a shorter hospital stay, and has good long-term results. A minimal access approach to treatment of small bowel obstruction should be considered in selected patients.

Hepatic steatosis as a potential risk factor for major hepatic resection.

Hepatic steatosis is a recognized risk factor for primary nonfunction of hepatic allografts, but the effect of steatosis on postoperative recovery after major liver resection is unknown. Our aim was to determine if hepatic steatosis is associated with increased perioperative morbidity and mortality in patients undergoing major resection. A retrospective review of medical records of 135 patients who had undergone major hepatic resection from 1990 to 1993 was performed. Histopathology of the hepatic parenchyma at the resection margin was reviewed for the presence of macro- or microvesicular steatosis. The extent of steatosis was graded as none (group 1), mild with less than 30% hepatocytes involved (group 2), or moderate-to-severe with 30% or more hepatocytes involved (group 3). Outcome of patients was correlated with extent of steatosis. Patients with moderate-to-severe steatosis were obese (body mass index = 25.8 +/- 0.5 vs. 26.5 +/- 1.0 vs. 33.4 +/- 2.9; P< 0.05 groups 1, 2, and 3, respectively) and had an increased serum bilirubin concentration preoperatively. Hepatectomy required a longer operative time for group 3 (290 +/- 9 minutes vs. 287 +/- 13 minutes vs. 355 +/- 24 minutes; P

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.