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Background/aims: HIPEC has been recently recommended as the 'new standard of care' for advanced ovarian cancer patients to treat residual disease, a recommendation based on the good results reported by many single institution studies. This study aims to elucidate whether cyto-reductive surgery for advanced stage IV ovarian cancer combined with laparoscopic HIPEC has any value in the management of advanced ovarian cancer., Methodology: From January 2007 to October 2011, 31 patients with stage IV ovarian cancer were enrolled. The inclusion criteria were stage IV epithelial ovarian cancer, with no evidence of extra-abdominal metastasis, and without previous systemic chemotherapy. Patients were randomly divided into two groups, group A and group B, which consisted of 12 patients who received laparoscopic HIPEC in a neo-adjuvant setting, and 19 patients who received laparoscopic HIPEC in an adjuvant setting, respectively., Results: Overall response rate after Laparoscopic HIPEC (neo-adjuvant and adjuvant) was 100%. Macroscopic images recorded during initial laparoscopy and subsequent laparoscopies revealed a dramatic decrease in the size of the neoplastic deposits accompanied with a decrease in their absolute number., Discussion: The results of this study indicate that laparoscopic HIPEC preceding multi-organ radical surgery has been seen to be associated with optimal short and long-term results, and promising OS and DFS. They also demonstrate the therapeutical advantage of neo-adjuvant initial approach over adjuvant approach.

Background/aims: The benefits of adjuvant chemotherapy for colorectal cancer has been well accepted over the last decade. Published data so far has been focused in the direction of giving the right chemotherapy dose, schedule, and combinations, in order to increase the efficacy and decrease the toxicity., Methodology: Eighty-seven patients with histological proved stage III rectal carcinoma were subjected to a combined adjuvant modality using laparoscopic heperthermic endoperitoneal chemotherapy (HIPEC) and systemic chemotherapy twenty days following the initial surgery., Results: Seventy patients who completed a one year follow-up had a disease free survival. Among forty patients who completed the two year follow-up, two patients developed local recurrence., Conclusions: Cytoreduction followed by HIPEC improves survival in patients with rectal carcinoma and lymphnode positive and neurovascular involvement.

Colorectal cancer (CRC) caused nearly 204,000 deaths in Europe in 2004. Despite recent advances in the treatment of advanced disease, which include the incorporation of two new cytotoxic agents irinotecan and oxaliplatin into first-line regimens, the concept of planned sequential therapy involving three active agents during the course of a patient's treatment and the integrated use of targeted monoclonal antibodies, the 5-year survival rates for patients with advanced CRC remain unacceptably low. For patients with colorectal liver metastases, liver resection offers the only potential for cure. This review, based on the outcomes of a meeting of European experts (surgeons and medical oncologists), considers the current treatment strategies available to patients with CRC liver metastases, the criteria for the selection of those patients most likely to benefit and suggests where future progress may occur.

Background/aims: Anastomotic leakage is a major problem in colorectal surgery particularly in low rectal cancer. The defunctioning loop ileostomy was introduced as a technique to create a manageable stoma that would divert the fecal stream from a more distal anastomosis in order to reduce the consequences of any anastomotic leakage. Therefore, the use of a defunctioning stoma has been suggested, but limited data exist to clearly determine the necessity of routine diversion. This study was designed to evaluate early morbidity, mortality and hospital stay in patients undergoing lower rectal cancer surgery concerned with or without loop ileostomy., Methodology: This is a prospective randomized study that was performed between May 2001 and March 2008. There were 256 patients who underwent elective low anterior resection and stapler anastomosis. They were divided into two groups. Group A consisted of 120 patients who underwent straight anastomosis without ileostomy and group B consisted of 136 patients who underwent straight anastomosis with loop ileostomy. Data regarding patient demographics, underlying pathology, anastomotic problems, and ileostomy-related problems were gathered. The patients were all monitored closely after surgery for an anastomotic leak and all stoma-related complications were recorded. Inclusion criteria consisted of biopsy proven adenocarcinoma of the rectum located at < or = 5 cm above the anal verge, age > or = 22 years, and informed consent. Exclusion criteria included age more than 90 years, associated co morbid conditions Stage IV with disease spread to liver and peritoneum., Results: Indications for surgery were lower rectal cancer (n=256). Mean age 55.5 years (range 22-90 years) and a male: female ratio of 1.1:1. All patients were undergoing elective surgery for lower rectal cancer. In our study 12 patients in group A developed anastomotic leak, two of them were re-explored for anastomotic leak and Hartman's colostomy was carried out. There were two deaths in Group A. In group B anastomotic leak was seen in three patients. In all three, anastomotic healing took place at a later period of time on the 18th, 20th, and 25th postoperative day respectively without any additional morbidity and mortality. Ileostomy-related problems were minor and limited to the stoma and complaints requiring stoma nurse evaluation (n=8), dehydration requiring outpatient care (n=3), bleeding at the stoma closure site (n=l). No stoma site hernias have been identified so far., Conclusions: The use of defunctioning loop ileostomy in all patients undergoing lower rectal surgery with stapler anastomosis is beneficial and safe. Defunctioning loop ileostomy use has resulted in no anastomotic leak rate and considerable low morbidity. So according to our study, we strongly recommend defunctioning loop ileostomy as a routine procedure in patients undergoing lower rectal cancer surgery.

In recent years, mortality associated with pancreaticoduodenectomy has come down to less than 5% but morbidity still remains high. Pancreatic fistula is one of the most common complications following pancreaticoduodenectomy. Postpancreatectomy hemorrhage is a rare but disastrous complication and associated with poor outcome. Early bleeding is usually due to some surgical mishap, but the management is simpler. Delayed hemorrhage has more complex pathophysiology and requires a multimodality approach for its management. In this paper, we review the recent articles related to postoperative hemorrhage after major pancreatobiliary surgery. Here we discuss the incidence, cause, investigations and management of early and late postoperative hemorrhage.

Background/aims: Pancreatic neuroendocrine tumors constitute a small percentage of pancreatic tumors. Surgical resection is the best treatment for these types of tumors. Aggressive surgical resection including multivisceral resection provides long-term survival. Even palliative resection of the tumor is justifiable. Here we share our experience with the management of pancreatic neuroendocrine tumors., Methodology: Between January 1993 and April 2007 we operated on 54 patients with pancreatic neuroendocrine tumor. We have analyzed our data retrospectively. Patients were analyzed in terms of demographic characteristics, operative procedure, postoperative outcome and survival., Results: Out of 54 patients, 31 patients had nonfunctional tumor and 23 patients had functional tumors. Neuroendocrine carcinoma was found in 19 patients. Pancreaticoduodenectomy was performed in 21 patients. Simultaneous liver resection was performed in 4 patients and multiorgan resection for locally advanced pancreatic tumor was performed in 3 patients., Conclusions: Surgical resection is the best option for the treatment of pancreatic neuroendocrine tumors. Aggressive resection provides survival benefit and a better quality of life. If the entire gross tumor can be resected, multiorgan resection or simultaneous liver resection is justifiable.

Colorectal cancer is one of the most common cancers in the western world. The goal of this review is to outline some of the important surgical issues surrounding the management of rectal cancer. In patients with early rectal cancer (T1), local excision may be an alternative approach in highly selected patients. For more advanced rectal cancer, radical surgical resection is the treatment of choice. Total mesorectal excision and negative radial margin (>1 mm) decreases the local recurrence rate and improves survival. In appropriate patients, laparoscopic resection allows for improved patient comfort, shorter hospital stays, and earlier returns to preoperative activity level. In patients with locally advanced disease, neoadjuvant chemoradiotherapy followed by radical excision according to the principles of TME has become widely accepted. Surgical resection is the treatment of choice for resectable liver metastasis of colorectal origin. Surgical resection improves disease-free and overall survival rate. For patients with unresectable metastatic disease, multimodality approach may increase the resectability rate and hence survival.

Background/aims: Microwave ablation is the most recent development in the field of tumor ablation and is a well established and safe local ablative method available for liver tumors (both primary and secondary tumors). The technique allows for flexible approaches to treatment, including percutaneous, laparoscopic, and open surgical access. Laparoscopic technique has the advantages of accurate tumor staging, better tolerability and low cost. It can be performed in tumors which are close to the vital organs. The aim of this study was to evaluate the feasibility and safety of laparoscopic microwave ablation of liver tumors., Methodology: During January 2001 to December 2005, 57 patients with liver tumors were treated with laparoscopic microwave ablation in the department of Surgical Oncology. There were 34 male and 23 female patients. Out of 57 patients, 11 patients had hepatocellular carcinoma and 46 patients had secondaries in the liver. The most common source of secondaries was colorectal cancers. Laparoscopic microwave ablation of tumors was performed in these patients., Results: During the study period, 57 patients with no evidence of extrahepatic disease underwent laparoscopic microwave ablation of unresectable hepatic tumors. No major intraoperative complications occurred. Postoperatively all the patients did well. Four patients developed liver abscess at the ablation area. Two patients required percutaneous aspiration of the liver abscess. No other major complications occurred. Follow-up CT scan shows complete necrosis of the tumors. Patients were followed-up at regular intervals., Conclusions: Laparoscopic microwave ablation is a feasible and safe alternative to open microwave ablation of the liver tumors. It carries all the advantage of minimal invasive surgery. In experienced hands, microwave ablation using laparoscopic technique can be done safely and effectively.

Metastatic liver disease remains a challenging and life-threatening clinical situation with an obscure and dismal prognosis and outcome. The liver is the most common site of metastatic spread of colorectal cancer and nearly half of the patients with colorectal cancer ultimately develop liver metastasis during the course of their diseases. Death from colorectal cancer is often a result of liver metastases. Over half of these patients die from their metastatic liver diseases. At the time of diagnosis, hepatic metastases are present in 15-25% of patients, and another 25-50% will develop metachronous liver metastases within 3 years following resection of the primary tumor. Over the last decade, there have been tremendous advances in the treatment of metastatic liver disease. Hepatic resection still remains the gold standard for the treatment of metastatic lesions which are amenable to surgery. Unfortunately, up to 40 percent of patients are identified as having additional disease at the time of exploration, and 20 percent are found to be unresectable. Regional therapies such as radiofrequency ablation, microwave ablation and cryotherapy may be offered to patients with isolated unresectable metastases. Other options like hepatic artery chemotherapy and chemoembolization, portal vein embolization and immunotherapy also play a vital role in management of metastatic liver disease when used in combination with other therapies. This article reviews the history of metastatic liver disease, epidemiology, diagnosis and various treatment modalities available for liver metastases along with our experience in management of advance metastatic liver disease.

It is very rare to find large gastrointestinal stromal tumors arising from the gastrohepatic omentum in a patient with neurofibromatosis type 1. We here document a case of two large gastrointestinal stromal tumors arising from the gastrohepatic omentum in a patient with von Recklinghausen's disease. In the present case, two large tumors in the lesser sac were evident on preoperative computed tomography and magnetic resonance imaging and were surgically removed successfully. Biopsy was suggestive of gastrointestinal stromal tumors.

Background/aims: Pancreas-preserving total duodenectomy is a challenging surgical technique with organ preservation and has limited indications. We assessed the safety, feasibility and short-term functional outcome of PPTD without the need of pancreato-enteric anastomosis in our surgical technique., Methodology: During the two-year period from 2005 to 2007, three patients underwent pancreas-preserving total duodenectomy at our center. Two patients had diffuse adenomatous polyposis; another had previous transduodenal excision for polyp with recurrence. In all three patients pancreas-preserving total duodenectomy was performed without the pancreato-jejunal anastomosis and were analyzed prospectively. The surgical procedure and outcome is described., Results: Out of three patients who underwent pancreas-preserving total duodenectomy, one patient had pancreatitis postoperatively and recovered well with conservative line of management. The other two patients had an uneventful postoperative course. All the patients were closely followed up and were symptom free, in a good condition with good functional status., Conclusions: To the best of our knowledge this is the first series of pancreas-preserving total duodenectomy without pancreato-enteric anastomosis ever reported. Although the indication for pancreas-preserving total duodenectomy is limited, it can be performed safely with good surgical expertise and knowledge of pancreato-duodenal anatomy. It can be beneficial in elderly patients with concomitant heart disease and associated risk factors. Although it is technically demanding requiring high surgical skills, it excludes the need of pancreas resection with maintenance of gastrointestinal function and the procedure can be performed safely and in less time. But the procedure should be contraindicated in the presence of malignancy and the operated patient should be under long-term surveillance.

Cytomegalovirus infection of the gastrointestinal tract of normal hosts is very rare. On the other hand, this is a common cause of morbidity in immunocompromised hosts. Herein we describe the case of a 52-year-old male who underwent a gastrectomy due to a severe gastrointestinal hemorrhage. Histological examination showed the characteristic cytomegalovirus inclusion bodies. The diagnosis was confirmed with immunohistochemistry and his immune system revealed no abnormality. We believe that, although it is very rare, cytomegalovirus infection should be kept in mind for non-immunocompromised patients with upper gastrointestinal bleeding or multiple gastric ulcers.

Background/aims: In everyday clinical practice many unfortunate patients present with advanced abdominal malignancies and are referred to a medical oncologist for palliative chemoradiotherapy and very few of them are offered surgical treatment. Many such patients, detected either preoperatively or on exploration, are considered to be inoperable and left to live a short and morbid life. The aim of this study was to assess the feasibility and effect of aggressive surgical management with adjuvant chemotherapy in advanced abdominal malignancies requiring resection of one or more organs along with the primary organ of the disease. We retrospectively analyzed our experience of treating such patients., Methodology: A total of 62 patients were included in this study attending the clinic between January 2001 and January 2006. These patients were diagnosed to have advanced abdominal malignancies because of spread of the disease from the organ of origin to either contiguous or noncontiguous abdominal organ(s). The patients with ovarian and uterine (n=18) malignancy underwent resection of colon (5), omentum (18), distal pancreatectomy and splenectomy (2), cystectomy (4), parietal peritoneal excision (9), small bowel excision in various combinations along with radical hysterectomy. Twelve patients with advanced colorectal carcinoma (n=12) along with abdominoperineal excision, anterior resection or colonic resection underwent cystectomy (3), hysterectomy (4), small bowel resection (4), hepatic resection (7) or parietal peritoneal excision (4) in various combinations. A total of 14 patients with gastric and gastroesophageal junction malignancy (n=14) underwent gastrectomy or gastroesophagectomy with omentectomy (14), distal pancreatico-splenectomy (5), hepatic resection (9), transverse colectomy (2) and parietal peritoneal excision (2) due to advanced disease. Patients with pancreatic carcinoma (n=12) underwent Whipple's pancreaticoduodenectomy or distal pancreatectomy with hepatic resection (6), transverse colectomy (1), splenectomy (3), left nephrectomy and adrenalectomy (3), small bowel excision (1) and parietal peritoneal excision (3). Along with excision of nonsolid organ retroperitoneal tumors (n=6) the organs resected were left kidney with adrenal (2), spleen (2) right kidney and adrenal (2), segmental inferior vena cava (1) and colon (2). All patients (except those who died in the early postoperative period) received adjuvant chemotherapy (43) or chemobiologic therapy (12) or radiotherapy., Results: Out of the total 62 patients who underwent multiorgan resection 7 patients died in the immediate postoperative period due to massive pulmonary embolism (2), cardiorespiratory insufficiency (2) or sepsis (3). Important morbidities seen in the early postoperative period were anastomotic leak (3), hemorrhage (2), pulmonary infection (5), pancreatitis (1), wound infection (4) and urinary tract infection (2). There was 100% postoperative follow-up of the patients. The survival rate was 77% in the first, 56.45% in the second, 47% in the third, 32% in the fourth and 22% at the end of the five-year follow-up., Conclusions: Aggressive surgical intervention by multiorgan resection and adjuvant chemo or chemobiological therapy is a feasible option in patients with advanced abdominal malignancies with statistically improved survival rate. Furthermore, it helps in getting better response to therapeutic manipulations and improved quality of life of the patients.

Background/aims: Pancreatic carcinoma is by far the most common malignancy and is the 5th most lethal cancer in the world and 40% of these carcinomas are locally advanced and unresectable at the time of presentation. Palliative surgery and chemoradiotherapy have not produced significant improvement in survival. The overall prognosis of these pancreatic cancers is poor, if left untreated without any form of palliation. Out of many palliative methods adopted for such locally advanced pancreatic carcinoma, none has shown much survival benefit. Microwave ablation is a well established and safe local ablative method for liver tumors and microwave ablation for locally advanced pancreatic tumors has been extensively used around the world. This is our largest series of microwave ablation in 15 patients with locally advanced pancreatic head carcinoma. The aim of this study was to evaluate the safety, efficacy, feasibility and complications of microwave ablation in unresectable locally advanced pancreatic carcinoma., Methodology: In total, 15 patients, from January 2004 to December 2006, were included in this study all having locally advanced pancreatic tumors which were found to be unresectable on radiological evaluation. The 15 patients (10 male and 5 female) with a mean age of 67 years were subjected to open microwave ablation after laparotomy and additional palliative procedure like biliary bypass (end-to-side hepaticojejunostomy) and gastric obstruction bypass by antecolic gastrojejunostomy was performed in 6 patients. The location of tumor was predominantly in the head and/or uncinate portion of the pancreas (n=12) and head and body (n=3). The average size of tumor was 6cm (range 4-8cm) and almost all had major regional vascular invasion on CT or MR angiogram. All tumors were histologically proven before the procedure by core needle and frozen section biopsy. Patients with distant metastasis were not included in this study., Results: In all 15 patients, partial necrosis was achieved. There was no major procedure-related morbidity or mortality. Minor complications were seen in 6 out of 15 patients, mild pancreatitis (2), asymptomatic hyperamylasia (2), pancreatic ascites (1), and minor bleeding (1). All patients had close follow-up and the longest surviving patient had a follow-up of 22 months., Conclusions: Microwave ablation is a beneficial therapy as a local effective procedure which is feasible and safe with acceptable minor complications in a locally advanced pancreatic tumor which can be used as part of a palliative or multimodality treatment, however, further long-term and properly designed studies are required to prove its usefulness in achieving survival benefit.

Background/aims: Acute abdomen accounts for 13-40% of all emergency surgical admissions. The aim of this prospective randomized controlled study was to examine the role of early laparoscopy in the management of acute abdomen compared with the more traditional active observation., Methodology: From July 1993 to August 2004, 522 patients consecutively, admitted with "acute abdomen", were randomized to either early laparoscopy (260 patients) (group 1) or active observation and non-invasive investigation (262 patients) (group 2). Baseline investigations included a full blood count, a pregnancy test in women of reproductive age, chest and/or abdominal radiograph if indicated clinically., Results: Sixty-two patients in the laparoscopy group underwent a total of 116 radiological investigations compared with a total of 558 investigations in all patients in the observation group (P < 0.05). In the observation group 34.7% of patients remained without a clear diagnosis compared with 4.2% of patients in the early laparoscopic group (P < 0.0001). The morbidity rate was 1.1% in group 1 and 27% in group 2 (P < 0.0001). The duration of hospital stay was significantly shorter in group 1 (3.1 vs. 7.3 days) (P < 0.01). Eight patients in group 1 required readmission (total readmission 46 days) compared with 58 patients in group 2 who stayed a total of 201 days (P < 0.05)., Conclusions: Early laparoscopy is valuable in the management of acute abdomen. It provides a significantly higher diagnostic accuracy and a better improvement in quality of life than the more traditional approach observation.

Background/aims: This study was designed to assess the efficacy of two-stage liver surgery and hepatic directed chemo-biological therapy in treatment of synchronous bilobar hepatic metastases of colorectal origin., Methodology: A total of thirty-two patients were included in this study that were diagnosed to have colorectal carcinoma with synchronous bilobar hepatic metastases. During stage one surgery along with excision of primary colorectal carcinoma; ligation and transection of main portal branch on side of bulky metastases disease (right branch in 28 and left in 4 patients) was performed. The metastatic nodules in the opposite lobe were ablated by microwave therapy and a hepatic arterial jet port catheter was introduced via the gastroduodenal artery for liver directed chemo-biological therapy. The catheter was connected to a subcutaneously placed port. Three cycles of chemotherapeutic drugs and Avastin (Bevacizumab) were given via hepatic arterial infusion (HAI) at intervals of twenty-five days. During the second stage surgery hepatic resection was carried out followed by continuation of hepatic arterial infusion of chemobiological drugs as adjuvant therapy., Results: In the follow-up period of 31 months, 1-year survival of 100% and 2-year survival of 80% with a mean 28 months survival was noted., Conclusions: Combined approach of ligating the portal branch, microwave ablation, hepatic regional chemo-biological therapy and staged liver surgery (a multimodality approach) in the treatment of advanced liver metastatic disease synchronous with colorectal cancer is an effective method of treatment which improves the overall survival and quality of life of the patient with hepatic bilobar metastases synchronous with colorectal carcinoma. Avastin, a monoclonal antibody against vascular endothelial growth factor; used for inhibition of tumor growth has shown its efficacy in early results and holds good promise for the future.

Primary tumors arising from great vessels like the aorta, pulmonary artery or inferior vena cava (IVC) are rare. The latter is the commonest site of its occurrence. It arises from the smooth muscle cells of the vessel wall. Aggressive surgical management should be attempted to excise it whenever possible. We describe a case of primary inferior vena cava tumor involving all three segments of the abdominal inferior vena cava infrarenal, suprarenal and retrohepatic vena cava, along with right kidney, right adrenal as well as right hepatic vein and left renal vein. We resected it completely without reconstruction of the IVC. The patient is doing well seven months after surgery without having any renal insufficiency, hepatic insufficiency or leg edema and having optimum quality of life. To our knowledge, this is the first case of such a long segment IVC leiomyosarcoma treated without IVC reconstruction, and despite its extent and concomitant involvement of the right kidney, right adrenal, right hepatic vein and left renal vein, it had a favorable response combining prolongation of survival and satisfactory quality of life.

Background/aims: Polymorphonuclear leukocytes (PMN) are well recognized as being the principal cells in inflammatory response reaction. During the surgical procedures there is a massive release of elastase (PMN-elastase) from the neutrophils, along with other proteinases. Therefore the measurement of the PMN-elastase might be a useful indicator of the degree of surgical trauma. Laparoscopic cholecystectomy (LC) is a so-called "mini-invasive" surgical procedure and on the basis of this consideration the aim of the present prospective, non-randomized study, is to examine (a) whether the serum levels of PMN-elastase concentration are modified and how, in patients undergoing LC compared to patients undergoing open cholecystectomy (OC), (b) whether these findings are indicative of an increased risk to develop infectious complications and therefore whether they are clinically significant., Methodology: Plasma granulocyte elastase was determined photometrically, using an immune-activation immunoassay, in 86 patients (42 patients underwent OC and 44 LC). The levels of C reactive protein (CRP), an acute phase protein, were measured using a competitive CRP ELISA kit. Blood samples were collected from all patients a day before operation and at days 1, 3, 6 and 12 after operation. We established a reference range for elastase by measuring the serum elastase concentration in 68 normal control patients without gallbladder cholelithiasis or other diseases., Results: On day, 1, 3 and 6 after surgery, patients that underwent OC showed a significant increase (p < 0.05) in plasma elastase concentration, while it was almost unchanged in LC patients. The mean values of the serum CRP on p.o. days 1, 3 and 6 were also significantly lower in the LC group than those in OC group (p < 0.05). We recorded three cases (7.1%) of postoperative infections in the "open" group. The CRP concentration remained high for 1, 3 and 6 days and normalized 10-12 days after surgery while the PMN-elastase normalized after 13, 14 and 16 days., Conclusions: The peripheral leukocyte function may be better preserved after LC in comparison to OC. Laparoscopic surgery, associated with a small skin incision and the avoidance of open laparotomy, can thus minimize surgical stress, and provide more favorable postoperative conditions for patients. Indeed excessive and prolonged post-injury elevations of PMN-elastase and CRP are associated with increased morbidity. Moreover, the PMN-elastase is a more sensible marker of inflammation in comparison to the CRP.

Hepatitis B remains a major problem for public health worldwide and represents a challenging disease for practicing physicians. Of the 2 billion people who have been infected with the hepatitis B virus, more than 350 million have chronic infections. These chronically infected individuals are at high risk of death from cirrhosis and liver cancer. The use of new antiviral drugs, such us nucleotides analogues, offer good hope in the prognosis of patients suffering from chronic hepatitis B.

Background/aims: To evaluate epidermal growth factor receptor (EGFR) gene status in pancreatic ductal adenocarcinoma correlating the results to protein expression and clinicopathological features, Methodology: Using tissue microarray technology (TMArrayer 100), fifty (n = 50) paraffin-embedded tissue samples of histologically-confirmed primary tumors were cored twice at a diameter of 1 mm and re-embedded into the final recipient block. Immunohistochemistry was performed by the use of anti-EGFR monoclonal antibody (31G7). Also, a chromogenic in situ hybridization protocol was applied based on the use of EGFR gene and chromosome 7 centromeric probes, respectively., Results: EGFR protein overexpression was observed in 29/50 (58%) cases and correlated to stage (p = 0.001) but not to grade (p = 0.206). EGFR gene analysis identified numerical alterations in 6/50 (12%), including 2 cases characterized by low-level gene amplification and 4 by absence of one allele. Gene status was associated to tumor grade (p = 0.023) and stage (p = 0.02). Chromosome 7 analysis detected aneuploidy in 14 (28%) cases., Conclusions: A subset of pancreatic ductal adenocarcinomas (PDACs) is characterized by EGFR gene numerical alterations including sporadic cases of amplification or absence of one allele (maybe due to gene deletion or intragenic point mutation and allelic silence). Those alternative mechanisms maybe influence the efficacy of novel targeted therapeutic strategies based on monoclonal antibodies or intracellular tyrosine-kinase inhibitors in PDACs.

Background/aims: Up to 40% of the patients with pancreatic carcinoma are not fit for curative resection due to the locally advanced nature of the disease in the form of vascular involvement. In recent years a more aggressive approach of vascular resection with pancreaticoduodenectomy (PD) has resulted in the increase in resectability rate and survival in this group of patients. The most important determinant of survival in these patients is negative resection margins. The aim of the present study is to present our experience of vascular resection using a modified technique, in patients with pancreatic cancer., Methodology: This is a retrospective study of 48 patients who underwent portal vein/superior mesenteric vein (PV/SMV) resection along with PD using the modified technique of resection, during 1982-2004. The principle modification is the initial extensive retroperitoneal dissection for the assessment of the extent of tumor involvement of the superior mesenteric vessels and division of retroperitoneal margin before the division of the pancreas. All patients also underwent extended lymphadenectomy., Results: The subtotal PD was done in 26 and total PD in 22 patients, with resection of the PV/SMV in all of them. The end-to-end anastomosis was possible after adequate mobilization of the PV and SMV in 40 patients. In 4 patients reconstruction was able to be done with the use of a graft. The portal vein occlusion time was 8-15 minutes. Histopathological examination showed negative margins in all the resected specimens. Postoperative complications occurred in 16.66% with reoperation rate of 8.33%, and mortality of 6.25%. After a mean follow-up of 110 months, mean survival was 40 months with the range of 18-250 months. The five-year and 10-year survival was 18% and 10% respectively. The venous patency rate was 100% at three years., Conclusions: In conclusion, PD with en bloc resection of the PV/SMV confluence can safely be done with morbidity and mortality similar to that of standard PD. The survival advantage is directly related to the attainment of negative resection margins. The modified technique is a useful way of doing vascular resection with the least amount of bowel congestion and securing negative resection margins.

Liver metastases are the major cause of death coloroctal resection for cancer. Colorectal liver metastases are unique because of the potential for cure. Presently surgical resection is the gold standard of treatment. Complete R0 resection gives 5-year survival of up to 24-44%. Over the years there have been extensive efforts in devising new modalities of treatment for this disease. These include methods to increase the resectability such as portal after vein emolization & two-stage surgery, py with newer drugs and methods such chronotherapy & hepatic artery infusion chemotherapy, newer methods of radiotherapy, local ablative therapies such as cryoablation, radiofequency ablation, microwave ablation & laser interstitial thermal therapy, and biological therapy. Biological therapy is largely investigational, but holds great promise for the future.

Adenocarcinoma of the pancreas has always been a disease with a dismal prognosis. Almost every patient with this cancer dies of the tumor. Over the years there has been extensive advancement in the understanding of etiology, molecular biology, diagnosis and treatment of this disease. Presently, surgical resection is the only potentially curative option available for these patients. It is now clear that surgery alone cannot increase the survival of these patients. With the understanding of molecular biology of pancreatic cancer new management strategies are under a preclinical stage of development. These new diagnostic and therapeutic modalities hopefully will improve the outcome of patients with pancreatic cancer.

Background/aims: After pancreatoduodenectomy (PD), pancreatic leak and the functional pancreatic and gastrointestinal disorders are the most important complications. Still there is no single method which takes care of all of them. After identifying the various reasons behind these complications, the senior author started performing the present method in the 1980s. Since then we have been able to bring these complications to a very low incidence. The present study is designed to substantiate the claims of various advantages of this method of PD and reconstruction and to explain the rationale behind this method., Methodology: This is a retrospective study of 225 consecutive PD procedures done for periampullary cancers, during the period of 1993-2004. The shortterm and long-term results assessed were mortality rate, morbidity rate, early reoperation, survival, steatorrhea, pancreatic enzyme supplementation requirement, occurrence of bile gastritis, dumping, new onset of diabetes, marginal ulcers, cholangitis, postoperative weight trends and frequency of hospital readmission for symptom management. Follow-up was done 6 monthly in all the patients with the aim of diagnosis of recurrence and assessment of long-term gastrointestinal and pancreatic function and nutritional status. In addition, in 15 patients, upper gastrointestinal endoscopy (UGIE) with gastric and jejunal biopsy, 99Tc-HIDA scan, determination of fecal fat loss after a standard 100-g fat diet for three days, fecal elastase-1 measurement (ELISA) and MRCP were done to objectively document the changes in gastrointestinal and pancreatic function. The data were compared with the results available in the literature., Results: The mean age was 56 years with a range of 27-85 years. There were 130 males and 95 females. Preoperatively 18 patients had diabetes and preoperative weight loss varied from 5-30 kilograms with a mean of 12 kilograms. Of all the PD cases 57 were for ampullary, 70 were for lower end cholangiocarcinoma and 98 were for pancreatic head cancer. The postoperative complications occurred in the form of intra-abdominal bleed (5), pancreaticojejunostomy leak (12), intra-abdominal abscess (4) and pneumonia (5). Delayed gastric emptying was not seen in any of the patients. In 8/12 patients with PJ leak the closure was achieved with the conservative treatment. The 30-day mortality was 6/225 (2.66%). The causes were sepsis in 3, intra-abdominal bleed in 2 and pulmonary embolism in 1 patient. There was no mortality related to PJ leak. The median follow-up was of 36 months. The overall 5-year survival for ampullary, lower end cholangio- and pancreatic head carcinoma were 65%, 25% and 20% respectively. After surgery none of the patients had clinical evidence of steatorrhea, gastritis, peptic ulcer disease, cholangitis, dumping and there was no new case of diabetes. After 6-12 months 80% of the patients gained weight similar to their preoperative levels. UGIE with gastric and jejunal biopsies, 99Tc-HIDA scan, fecal fat loss estimation, fecal elastase estimation and MRCP were done in 15 patients and were found to be normal., Conclusions: Our method of PD and reconstruction produces encouraging results with respect to PJ leak, mortality, DGE, malabsorption, bile gastritis, dumping, marginal ulcers and diabetes. We recommend this technique as a safe and effective method even to the low volume centers.

Background/aims: Choledochal cysts are congenital malformations of the pancreatico-biliary system. Some aspects of optimal surgical management of choledochal cysts remain controversial. The purpose of this paper is to present our series of 14 patients with choledochal cysts, analyzing surgical management and long-term results., Methodology: Between January 1975 and December 2001, 15 adult patients with choledochal cysts were treated at our Department. Sex, age, clinical symptoms, associated diseases, surgical management and postoperative morbidity and mortality were reviewed. Choledochal cysts were classified according to the Alonso-Lej classification with Todani et al.'s, modification, based on radiographic and operative findings., Results: There were 15 patients, 6 males and 9 females, with an age ranging from 28 to 82 years and a mean age at the time of surgery 58.3 years. Seven patients had a solitary fusiform extrahepatic cyst (Type I), five patients had an extrahepatic supraduodenal diverticulum (Type II), one patient had a choledochocele (Type III), while two patients had a Type IVB cyst. Symptoms were vague and intermittent. Recurrent upper abdominal pain, jaundice, fever, nausea and vomiting were the most common findings, usually occurring in combination. Two patients presented with cholestatic cirrhosis. Five patients had laboratory evidence of hepatocellular dysfunction and two patients had hyperamylasemia. A variety of operations was performed such as cystoduodenostomy, cyst excision and hepaticojejunostomy, cyst excision and choledochoduodenostomy. Postoperative follow-up ranged from 30 months to 12 years in all patients except of two patients who were lost to follow-up., Conclusions: Total or partial excision of the choledochal cysts is the optimal treatment because of the lower incidence of postoperative complications and the better survival rate after the operation.

Background/aims: Carcinoids are relatively rare tumors that arise from neuroendocrine cells and have proved to be slow growing malignancies which involve many organs and most frequently the gastrointestinal (GI) tract. Herein we present in this study 101 pts with carcinoid tumors that originated from the GI tract and pancreas. Also, we analyze the clinical and pathological features, pointing out the characteristics of this group of neoplasms and describing our diagnostic and therapeutical approach, in parallel with a brief review of the literature., Methodology: One hundred and one (66 females and 35 males, aged from 16 to 79 years) pts were included in our study. The primary tumors originated from the GI tract in 97/101 pts (appendix 34%, small intestine 31%, stomach 14%, duodenum 6%, colon 6%, rectum 3%) and from the pancreas in 4/101 (4%). The diagnosis was confirmed histologically in all cases, after surgical excision of the primary tumor or by biopsies taken during endoscopy. All pts were evaluated several times per year with clinical, biochemical and imaging assessments, including neuroendocrine markers [urinary 5-Hydroxyindoleacetic acid (5-HIAA), serum Chromogranin-A (CgA)] and Somatostatin Receptor Scintigraphy (OCTREOSCAN). The follow-up period ranged between 1.5 to 12.5 years (mean time: 5 years and 3 months) and it is still in progress., Results: Patients were referred to us with gastrointestinal symptoms or symptoms of the "carcinoid syndrome" (flushing, and diarrhea), depending mainly on the location of the primary tumors and the existence or not of metastases. CgA and 5-HIAA levels were increased especially in metastatic tumors. Localization of the primary tumors to facilitate surgery was made by many imaging techniques (US, CT, MRI, Enteroclysis, OCTREOSCAN) and endoscopic procedures. OCTREOSCAN was positive in 94% pts with metastatic disease. Furthermore, it revealed the primary and the metastatic lesions in 16% and 33% of pts with carcinoids of the small intestine respectively, while other conventional imaging procedures (including MRI) were negative at the same time. Seventy-four percent of the pts underwent a surgical resection of the primary tumor, while in 21%, an endoscopic polypectomy was performed. All pts with metastatic tumors and positive OCTREOSCAN, were treated with Somatostatin analogues, which resulted in control of symptoms (75%), stabilization of tumor growth (71%) or tumor shrinkage (9%). A combined therapy with the addition of interferon-a was initiated in pts in whom, despite the increase of drug dosage and the shortening of administration intervals, a complete clinical and biochemical response was no more achieved with Somatostatin analogues alone. Pancreatic carcinoids and also those that originated from the proximal colon were found to have worst prognosis., Conclusions: a) Tumor size (especially in appendiceal and gastric carcinoids) and, also, the dispersion of disease, highly predict the evolution of the patients; b) serum Chromogranin-A seems to be a very useful tumor marker for the diagnosis and follow-up of pts with GI carcinoids; c) the introduction of new imaging techniques and especially OCTREOSCAN contributes to a better localization of the primary tumors and their metastases, as well as, to the right decision of the appropriate medical treatment; d) surgical excision is the treatment of choice in nonmetastatic tumors; and e) in pts with metastatic disease, the administration of Somatostatin analogues improves their quality of life.

Background/aims: To evaluate the efficacy and safety of multimodality approach towards advanced rectal cancer., Methodology: In a prospective, randomized trial, two hundred and ten patients with advanced carcinoma of the rectum were studied. Patients were randomly divided in two groups A and B. Patients in group A underwent total mesorectal excision (TME) with adjuvant systemic chemotherapy and radiotherapy. Group B patients underwent TME with adjuvant stop-flow perfusion along with systemic chemotherapy, Results: The five-year survival for Group A patients was 72% and for Group B patients the overall five-year survival was 92% and the disease-free survival was 87%., Conclusions: Multimodality approach to advanced rectal cancer leads to substantial prolongation of survival and optimization of quality of life.

Background/aims: Carcinoid tumors of the appendix are thought to be the most common type of appendiceal neoplasms. Although the vast majority of appendiceal carcinoids behave in a benign fashion, they are considered malignant because they all have the potential for invasion, metastasis and production of physiologically active substances. The aim of our study is to evaluate the gravity of the prognostic factors and the indications for extended surgical treatment., Methodology: Twenty-four patients, six male (aged from 18 to 59 years) and eighteen female (aged from 16 to 27 years) are included in our study. All these patients were managed and followed-up in our section during the last 17 years (follow-up range 10-17 years). Following confirmation of the diagnosis, secretion of 5-HLAA (5-Hydroxy-Inndole-Acetic Acid) was measured after a 24-hour collection of urine. Moreover, ultrasound (US) examination of the liver and computerized tomography (CT) scanning of the upper abdomen were performed after the operation in all patients. Also, patients with tumor size more than 1cm underwent a Somatostatin Receptor Scintigraphy (Octreoscan). The follow-up data of all patients included measurement of 5-HLAA and US examination every six months., Results: The most common site for the tumors was the tip of the appendix (18/22). In the rest of the cases, the neoplasms were located in the base (4/22) and in the body (2/22), while in one patient the mesoappendix was invaded. In sixteen patients the tumor size was less than 1cm, in seven patients the tumor diameter was measured to be 1 to 2cm and in one patient the tumor was 3cm. Most of our patients (16/22) underwent only an appendicectomy, while in the rest of them (in the patients with tumor size between 1-2cm and in the patient with invasion of mesoappendix) a right hemicolectomy was performed. No patient was found to have metastatic disease during the operation, while the patient with invasion of the mesoappendix developed metastases in the lung, two years after the operation., Conclusions: Carcinoid tumors of the appendix, in most cases, are found incidentally during appendicectomies, especially in young females and usually are less than 1cm in size, which is probably the reason of the absence of metastases in all cases. Histological examination and size of the tumor are important factors that contribute to the selection of the surgical treatment and both must be estimated by the surgeons to make the final choice.

Background/aims: Local recurrence is a formidable problem after potentially curative resection for rectal cancer. We attempted to identify possible factors affecting the frequency of local recurrence, focusing on the clearance of the tumor and the margin of resection., Methodology: The clinical cohort consisted of 66 patients suffering from rectal carcinoma. All patients underwent a low anterior resection with meticulous pelvic preparation and dissection. The proximal and distal margins of the tumor were measured before fixing for permanent sections., Results: Analysis by distance of the tumor from the anal verge revealed that 5 out of 33 patients (15.15%) from the upper rectal group and 7 out of 19 patients (36.8%) from the mid rectal group developed local recurrences (36.8% vs. 15.15% P=0.0369). Analysis by distance of the distal resection margins revealed that 8 out of 12 patients with local recurrence had distal margins less than 2cm, whereas 7 out of 40 patients free of local relapse had margins less than 2cm. Therefore 8 out of 15 patients with distal margins less than 2cm developed local recurrence (53.5%) whereas 4 patients among 37 with margins greater than 2cm developed a local failure (10.8%) (53.5% vs. 10.8% P=4.88E-04). The median survival in all patients of our series was 23 months. The median survival in 52 patients who underwent a potentially curative resection was 42 months., Conclusions: Tumors located in the upper portion of the rectum presented a minor tendency for local recurrence compared to tumors located in the middle of the rectum. Our study provides strong indications that high rate of local recurrences are probably related to the limited anatomic margins that can be obtained in the pelvis during primary resections.

Background/aims: Gastrectomy with gastrojejunostomy is a fundamental step used for the restoration of the alimentary tract after pancreaticoduodenectomy or total pancreatectomy. Anastomotic ulcers occurring after pancreaticoduodenectomy, is a well known problem. The aim of our study is to investigate the incidence of anastomotic ulcer after pancreaticoduodenectomy or total pancreatectomy and to elucidate whether vagotomy is necessary., Methodology: In this study we reviewed the medical records of 94 patients who underwent pancreaticoduodenectomy or total pancreatectomy without vagotomy and we report the results after systemic follow-up 3-14 years, emphasizing the cases in which anastomotic ulcer is jeopardized., Results: A total of 78 Whipple procedures and 16 total pancreatectomies without vagotomy were performed. The overall incidence of anastomotic ulceration following pancreatectomy was 11.7%. In our series the symptoms and complications associated with anastomotic ulceration were pain in 6 patients, bleeding in 4 patients and free perforation in one patient. Six patients needed a reoperation, the 4 patients with bleeding that underwent truncal vagotomy, the patient with free perforation in which oversew and bilateral vagotomy was performed and a patient with refractory pain who underwent a bilateral vagotomy. Among the 11 patients with anastomotic ulcer, the overall postoperative mortality rate was 27.3%., Conclusions: It seems reasonable to perform bilateral truncal vagotomy only in patients with a history of peptic ulceration and for patients with favorable prognosis and potential for long survival.

Background/aims: Interleukin-6 (IL-6), a multifunctional cytokine, is expressed by various cells after many stimuli. This cytokine release is related, among other things, to the extent of the surgically-induced trauma. Laparoscopic cholecystectomy (LC) is a so-called "mini-invasive" surgical procedure and, on the basis of this consideration, the aim of the present prospective non-randomized study, is to examine (a) whether the IL-6 is modified and how, in patients after LC compared to patients undergoing open cholecystectomy (OC), (b) whether these findings are indicative of an increased risk to develop infectious complications and whether they are therefore clinically significant., Methodology: Circulating IL-6 level was measured using a random access chemiluminescense-immunoassay system in 71 patients before the operation (time 0) and 1, 2, 3, 6, 24 and 48 hours after the beginning of the operation. Thirty-five patients underwent OC and 36 LC., Results: The increase in the serum IL-6 during LC was found to be significantly smaller than that during OC and resulted in a smaller extent of postoperative elevations for C-reactive protein. We recorded three cases (8.5%) of postoperative infections in the "open" group and IL-6 concentration normalized only 6 days after surgery., Conclusions: An increase in the serum IL-6 level during LC is lower in comparison to OC and results in lower postoperative elevation in C-reactive protein. Laparoscopic surgery, associated with a small skin incision and the avoidance of open laparotomy, can thus minimize surgical stress, and provide more favorable postoperative conditions for patients. Indeed excessive and prolonged post-injury elevations are associated with increased morbidity.

Background/aims: Anastomotic leakage is a major cause of mortality in colorectal surgery. Several methods have been evaluated in order to prevent anastomotic leakage. To decrease the rate and severity of anastomotic leakage, omentoplasty (OP) has been proposed by several authors on the basis of experimental and clinical studies. A prospective, randomized trial was designed to study the influence of omentoplasty on anastomotic leakage after colorectal resection., Methodology: One hundred and twenty-six patients undergoing elective or emergency surgery for malignancy, benign tumor, diverticular disease and other were randomly assigned to omentoplasty (OP group) or not (NO group). The primary end point was the rate of clinical and radiological anastomotic leakage. Both groups were comparable in terms of demographic data, preoperative characteristics and intraoperative findings., Results: Eighteen patients (14.3%) had anastomotic leakage, 4 (6.4%) in the OP group and 14 (21.9%) in the NO group. Significant differences (P<0.05) between the two groups were also found in terms of repeat operation (3.2% vs. 14.1%) and deaths (3.2 vs. 7.8%). Other factors associated with anastomotic leakage were the distal site of anastomosis (<5 cm from anal verge) and the emergency., Conclusions: Omental wrap, with its mechanical and biological properties, seems to be effective in lowering the rate and the severity of anastomotic leakage after colorectal surgery.

Background/aims: To evaluate the long-term outcome of a multidisciplinary approach for advanced Klatskin tumor involving the hepatic hilus., Methodology: A retrospective analysis was undertaken in 110 patients between 1993 and 2003. The patients were divided into Group A (n=42) and Group B (n=58). Group A patients underwent local excision of the tumor and Group B patients underwent combined tumor and liver resection with or without resection of the regional vascular structures. On admission, all patients underwent percutaneous transhepatic biliary drainage. Where hepatectomy was planned, portal vein branch ligation and transection was done ipsilateral to the liver lobe where the tumor was present. An arterial catheter was introduced into the hepatic artery at the end of the surgery, for adjuvant locoregional immunochemotherapy, which was carried out in all patients. The second-stage resectional surgery was carried out 35 days later., Results: The overall mean survival for Group A patients was 29 months (range 14 to 76). The mean disease-free survival was 28 months (range 10-52). Five-year survival rate was 5% and five-year disease-free survival was 0%. The overall mean survival for Group B patients was 39 months (range 28 to 79). The mean disease-free survival was 32 months (range 17-72). Five-year survival rate was 20% and five-year disease-free survival was 10%., Conclusions: The concept of a multidisciplinary approach has significantly improved survival in patients with a grave disease like Klatskin tumor.

Background/aims: To evaluate the efficacy of two-stage surgery and multidisciplinary approach, in the treatment of primary colorectal cancer, synchronous with advanced liver metastases., Methodology: Sixty-two patients who underwent two-stage surgery for advanced metastatic liver disease synchronous with colorectal tumor were studied. In the first-stage surgery, the primary colorectal tumor was resected. Depending on the location of the main tumor mass, ligation and transection of the relevant (right or left) main portal vein branch was done. Subsequently, the metastatic nodules in the contralateral lobe were ablated by microwave therapy. An arterial jet port catheter was also introduced into the hepatic artery via the gastroduodenal artery for locoregional chemoimmunotherapy. Two days after the first-stage surgery locoregional transarterial targeting chemoimmunotherapy was given. The second-stage hemihepatectomy was carried out forty to forty-five days after the initial surgery. As an adjuvant treatment locoregional targeting chemoimmunotherapy was carried out in all patients via the arterial chemoport., Results: Mean survival was 66+/-4 months. There were no operative deaths., Conclusions: Two-stage liver surgery including, portal vein branch ligation, microwave ablative therapy and transarterial targeting locoregional chemoimmunotherapy is the best treatment for advanced, synchronous metastatic liver disease of colorectal origin. It results in an increase in the overall survival of these patients with good postoperative quality of life, which encourages the hepato-biliary surgeon to venture upon this herculean task thus increasing the resectability rate of the tumor.

Background/aims: To evaluate, the early and long-term results of mono-bloc spleno-pancreatic and vascular resection for advanced carcinoma of the head of the pancreas, with portal-mesenteric venous invasion., Methodology: In a prospective, randomized trial, fifty-six patients with advanced carcinoma of the head of the pancreas with vascular invasion were studied. Patients were randomly divided in two groups A and B. Group A patients underwent an en-bloc spleno-pancreatic and vascular resection. Group B patients underwent a palliative gastro-biliary bypass. Patients in both groups were subjected to adjuvant locoregional chemoimmunotherapy, through an arterial catheter introduced into the superior mesenteric artery via a jejunal arterial branch., Results: The 2- and 5-year survival rates for Group A patients were 81.8% and 18.5%. The respective percentages for disease-free survival were 60.6% and 0%. Two-year survival for group B was nil., Conclusions: Mono-bloc spleno-pancreaticoduodenectomy and regional vascular resection and reconstruction, with adjuvant locoregional chemoimmunotherapy leads to substantial prolongation of survival and optimization of quality of life.

Background/aims: To evaluate the benefits of two-stage liver surgery with main portal branch ligation and transection combined with transarterial targeting locoregional neo and adjuvant immunochemotherapy in patients suffering from hepatocellular carcinoma., Methodology: 43 consecutive patients underwent two-stage liver surgery for advanced hepatocellular carcinoma. First we performed ligation and transection of the main portal vein branch corresponding to the liver lobe occupied by the tumor. Subsequently we introduced an arterial jet port catheter towards the hepatic artery via the gastroduodenal artery. After locoregional transarterial targeting immunochemotherapy regimen the patient underwent a second laparotomy for hemihepatectomy. Following surgery, locoregional transarterial targeting immunochemotherapy was given to all patients via the arterial port of the gastroduodenal artery as an adjuvant treatment., Results: Mean survival was 41 months. There were no operative deaths., Conclusions: Two-stage liver surgery and transarterial targeting locoregional immunochemotherapy is the favorable option of treatment for advanced hepatocellular carcinoma. It not only results in an increase in the overall survival of these patients, but also increases the rate of resectability of these tumors by the hepatobiliary surgeon.

Purpose: To evaluate in a prospective randomized study the long-term results of adjuvant locoregional chemoimmunotherapy in a number of patients with stage III pancreatic duct cancer who underwent pancreatic resection between November 1993 and October 2000., Methods: One hundred twenty-eight patients were divided into three groups. Group A (n = 40) patients had surgical resection alone. Group B (n = 45) patients had, using a side arterial branch of the jejunal artery, an arterial catheter advanced under fluoroscopic control into the superior mesenteric artery. Group B patients also received adjuvant chemotherapy. Group C (n = 43) patients had the same kind of arterial catheter and received as an adjuvant treatment locoregional chemoimmunotherapy. During the initial surgical exploration, all patients underwent pancreatic resection. Pancreatic resection involved a standard technique of extended duodenopancreatectomy with regional lymphadenectomy and was carried out in all patients by the first author. At the end of intervention, all patients were randomly assigned to the above-mentioned groups. Randomization was based mainly on histologic evidence of the stage of the disease., Results: The 2- and 5-year survival rates were 29% and 0% for group A, 52% and 10% for group B, and 65% and 18% for group C. The respective percentages for disease-free survival were 20% and 0% for group A, 35% and 7% for group B, and 58% and 11% for group C. Since statistical differences among groups were observed from the second and third years, the study was interrupted early for ethical reasons., Conclusions: When applied regionally, combined chemoimmunotherapy is simple, safe, and effective. This type of therapy offers substantial advantages in terms of prolonging overall survival and improving disease-free survival compared to surgical resection alone or to surgical resection and adjuvant regional chemotherapy.

Background/aims: Liver resection for metastatic liver disease of colorectal origin, although considered as the 'gold standard' of treatment, is associated with limited long-term survival. The aim of this study was to compare overall survival, disease-free survival and the incidence of intra- or extrahepatic recurrence between patients who were randomly assigned to have locoregional chemoimmunotherapy with systemic chemotherapy group A (n = 62 patients) versus those who were treated with systemic immunochemotherapy group B (n = 60 patients)., Methodology: Group A included patients who, after liver resection, received locoregional immunochemotherapy combined with systemic chemotherapy, while group B included patients who had undergone systemic immunotherapy combined with systemic chemotherapy following liver resection. The two groups were matched in terms of sex, age and stage of the disease. Prognostic factors and their impact on disease-free survival were studied in both groups., Results: Two-year survival was 92% for group A versus 75% for group B, 5-year survival was 73% for group A versus 60% for group B. During the two-year period, 34% of the group A patients versus 52% of those of group B developed either intrahepatic or extrahepatic recurrence of the disease (P < 0.00212)., Conclusions: From the analysis of the above results it becomes clear that regional immunochemotherapy combined with systemic chemotherapy leads to a decrease in the incidence of disease recurrence and thus to a significant prolongation of the overall survival and of disease-free survival.

Background/aims: Acute biliary pancreatitis is a clinical entity with a high morbidity rate (15-50%) and mortality rate (20-35%). Early diagnosis has a primary importance for an appropriate treatment (75% of cases of idiopathic acute pancreatitis are of biliary origin)., Methodology: Diagnosis of acute biliary pancreatitis in 78 patients was based on careful clinical and instrumental assessment: ultrasonography (76.9% of cases) and laboratory tests in 23.1% of cases. In our study we used the Ranson and APACHE II scores and 24 of the cases (30.7%) were classified as severe, while 54 (69.2%) were mild. All patients with severe acute biliary pancreatitis underwent emergency endoscopic retrograde cholangiopancreatography + endoscopic sphincterotomy (within 24-48 hours) followed by laparoscopic cholecystectomy (10 days). Patients with mild acute biliary pancreatitis underwent laparoscopic cholecystectomy associated with intraoperative cholangiography, within 10 days., Results: In 19 patients with severe acute biliary pancreatitis operative endoscopy was curative. Subsequent laparoscopic cholecystectomy provoked subcutaneous emphysema only in one case but did not show any other serious morbidity. In the remaining 5 cases laparotomy was required because of necrosis, with a mortality rate of 60%. In all cases of mild acute biliary pancreatitis, laparoscopic cholecystectomy was successfully performed with a morbidity rate of 7.3%. Common bile duct stones were revealed with intraoperative cholangiography in 31.4% of the mild cases and in 75% of the severe cases., Conclusions: In conclusion acute biliary pancreatitis treatment is always surgical; in almost all severe cases it is performed with minimally invasive procedures (endoscopic retrograde cholangiopancreatography + endoscopic sphincterotomy with laparoscopic cholecystectomy < or = 10 days) if surgery is carried out within 24-48 hrs, as well in the mild cases (laparoscopic cholecystectomy + intraoperative cholangiography) when surgery is performed within 10 days.

Recent advances in understanding fundamental mechanisms of regulation of the immune response are throwing light into mechanisms of tumor growth. The understanding of the immunological aspects of tumor expansion is leading to the development of new strategies to stimulate the immune system to mount more effective responses to tumors. This progress as well as some promising results in clinical trials is generating considerable optimism. The goal of this review is to present recent advances concerning tumor immunology, identify some of the pitfalls and problems that still exist and present new areas of immunotherapy that look promising.

Background/aims: The study has been designed to assess the potential advantages of regional targeting chemoimmunotherapy versus systemic chemotherapy and immunotherapy in a number of patients suffering from nonresectable metastatic liver disease of colorectal origin., Methodology: From January 1996 to January 2001 (86) patients with unresectable metastatic liver disease of colorectal origin were randomly assigned to two groups. Group A (n = 44 patients), who received regional targeting chemoimmunotherapy through an arterial catheter introduced subcutaneously under echo guidance into the hepatic artery. Group B (n = 42 patients) received systemic chemoimmunotherapy., Results: Survival of Group A patients ranged from 9 to 48 months (mean: 33 months), while Group B patients' survival ranged from 8 to 18 months (mean: 10 months). Response to treatment was 75% for Group A patients versus 52% for Group B. There were statistically significant differences in survival between the two groups (P = 0.0001)., Conclusions: We believe that the data of this study reconfirms previously reported experience about the advantages of regional chemoimmunotherapy when compared with systemic chemoimmunotherapy for the management of advanced metastatic liver disease.

Background/aims: Laparoscopic cholecystectomy is a so called mini-invasive surgical procedure, and on this basis, we investigated whether and how the immune response is modified in patients after laparoscopic cholecystectomy compared to patients who underwent open cholecystectomy., Methodology: In a prospective, nonrandomized trial, 35 patients underwent laparoscopic cholecystectomy and 31 open cholecystectomy. Immune activity (neutrophils, total lymphocytes, lymphocyte subpopulations, human leukocyte antigen (HLA-DR), interleukin 6, skin Multitest) was evaluated before surgery and respectively, 1, 3, and 6 days postoperatively., Results: One day after surgery, an increase in interleukin 6 (P < 0.01) was noted in patients who had undergone open cholecystectomy, while this parameter was almost unchanged in patients with laparoscopic cholecystectomy. Moreover, skin tests showed a hypo or anergic response in the majority (81.8%) of open cholecystectomy patients compared to laparoscopic cholecystectomy patients (10.5%), (P < 0.01). Finally, monocyte antigen HLA-DR was also reduced in open cholecystectomy patients (P < 0.05). In this group, we noted 2 cases (6.45%) of respiratory tract infection., Conclusions: Even though laparoscopic cholecystectomy requires a longer surgery, it reduces postoperative pain, and hospitalization. It also facilitates rapid recovery, a return to normal activity, avoids postoperative immunosuppression and shows a better postoperative morbidity compared to open surgery.

Following hepatectomy, liver "knows" when to start and when to stop growing, and thereby accurately regulates its mass. Partial hepatectomy triggers hepatocyte proliferation whereas excessive liver mass (transplant) is regulated by apoptosis. Liver regeneration mainly involves the activation of adult hepatocytes and possibly of liver precursor ("stem") cells. The multistep process of liver regeneration comprises at least 2 critical phases: the transition of the quiescent hepatocyte into the cell cycle (priming) and the progression beyond the restriction point in the G1 phase of the cycle. The priming phase is characterized by the expression of immediate early genes. Activation of protooncogenes in the immediate early gene response involves both transcriptional and post-transcriptional mechanisms. Activation of four transcription factors, NF kappa B, STAT3, AP-1, and C/EBP beta, causes secondary activation of multiple genes and plays an important role in the initiation of hepatic regeneration. The passage of primed hepatocytes through the cell cycle is characterized by the expression of cell cycle genes and requires growth factors. An equilibrium between stimulator and inhibitor genes of the cell cycle expressed after hepatectomy, may explain why the liver regeneration is a tightly regulated growth process. Based on the knowledge of the regulation of liver regeneration, several practical considerations and potential therapeutic strategies can be applied in humans with hepatic dysfunction due to liver resection.

Background/aims: The purpose of this study was to assess whether long-term survival in patients suffering from cholangiocarcinomas of the porta hepatis is significantly different when comparing results between local and extended procedures in order to justify increased mortality and morbidity following extensive resections., Methodology: From November 1991 to May 2000, 46 patients with Klatskin tumor were assigned to two groups. Group A patients (n = 25) had local resection and group B patients (n = 21) had local resection plus hemihepatectomy. On admission, all patients were drained via percutaneous transhepatic biliary drainage. In all patients we proceeded with an internal biliary drainage in order to anticipate jaundice and decompensated liver function. Internal biliary drainage was carried out 35-40 days before surgery. At the end of the operation an arterial catheter was introduced into the common hepatic artery for adjuvant locoregional targeting immunochemotherapy, which was initiated 20 days following surgery in all patients., Results: Overall survival for group A patients ranged from 14 months to 76 months (mean: 29). Disease-free survival ranged from 10-52 months (mean: 25). Five-year survival rate was 10%. Five-year disease-free survival was 0%. Overall survival for group B patients ranged from 28 months to 79 months (mean: 39). Disease-free survival ranged from 17-72 months (mean: 32). Five-year survival rate was 20%. Five-year disease-free survival rate was 10%., Conclusions: Combined tumor and liver resection is associated with significantly better results when compared with those following tumor resection alone.

Background/aims: Main portal branch embolization was developed several years before in an attempt to improve prognosis and outcome for patients suffering from advanced liver malignancies., Methodology: From September 1993 to September 2000 43 patients with advanced hepatocellular carcinoma underwent main portal branch transection and neo- and adjuvant transarterial immunochemotherapy. Forty days after initial surgery, all patients underwent a phase II surgical exploration for liver resection., Results: Survival ranged from 18 months to 64 months with a median of 41 months. Two- and 5-year survival was 75% and 57%, respectively., Conclusions: Main portal branch transection combined with major liver resection and neoadjuvant and adjuvant locoregional immunochemotherapy fulfilled our expectations firstly for increasing the resectability rate and secondly for increasing the overall survival and the disease-free survival.