Parecoxib's effects on anastomotic and abdominal wound healing: a randomized Controlled trial.

BACKGROUND: Current evidence regarding the effects of selective cyclooxygenase inhibitors on gastrointestinal anastomoses is controversial. An experimental randomized control study was conducted in our institution to histopathologically evaluate the consequences of parecoxib, on intestinal and abdominal wound healing. METHODS: Twenty-four adult Wistar rats underwent laparotomy, ascending colon transection, and hand-sewn anastomosis. They were randomized to receive either parecoxib (0.5 mg/kg twice daily) or 0.9% normal saline by intraperitoneal injection postoperatively. Animals were euthanatized either on the third or the seventh postoperative day. Semiquantitative methods were used to evaluate both intestinal and abdominal wounds for inflammatory cell composition, angiogenesis, fibroblasts, granular tissue, collagen deposition, epithelization, and presence of necrosis, exudate, and abscess formation. Results are presented as (parecoxib: median [IQR] versus control: median [IQR], P-value). RESULTS: No macroscopic anastomotic leakage or wound dehiscence was observed. Intestinal anastomoses in the parecoxib group, showed significantly decreased epithelization (2 [1] versus 3 [1], [P = 0.004]) and collagen deposition (2 [0] versus 3 [1], [P = 0.041]). No difference was observed in angiogenesis (3 [1] versus 2.5 [1], [P = 0.158]). Abdominal wall specimens appeared to demonstrate decreased epithelization (2 [2] versus 4 [0.5], [P = 0.0004]) in the treatment group. No difference between the two groups was identified regarding collagen deposition (2.5 [1] versus 2 [0.5], [P = 0.280]) and angiogenesis (2.5 [1] versus 2 [1], [P = 0.633]). Necrosis was significantly more present in the parecoxib group in both specimen types, (3.5 [1] versus 2.5 [1], [P = 0.017]) and (3 [1] versus 1 [0.5], [P < 0.0001]). CONCLUSIONS: The present study shows that despite the absence of clinical adverse effects, parecoxib can impair anastomotic and abdominal wound healing on a histopathological level.

Association of FokI and PvuII polymorphisms with breast cancer staging and survival among Caucasian women: a prospective study.

PURPOSE: Both vitamin D and estrogens play an important role in breast cell growth and differentiation. Therefore, we hypothesized that FokI polymorphism in the Vitamin D Receptor (VDR) gene, as well as PvuII polymorphism in the Estrogen Receptor (ESR) gene might be associated with progression of breast cancer. The aim of this study was to prospectively examine the association of these polymorphisms with histopathological features and prognosis among women with histologically proven breast cancer. METHODS: Patient characteristics, tumor histopathology, and genotyping of one VDR polymorphism variant (FokI) and one ER polymorphism variant (PvuII) were recorded. Patients were also routinely followed up. RESULTS: There was a significant difference regarding nodal stage (p<0.001) between the different genotypes of FokI polymorphisms (FF, Ff, ff), even though a trend was also detected in the frequency between ductal and lobular type, as well as tumor size (p=0.077). When further analysis was performed regarding patients whose polymorphism included the f allele, we found statistically significant differences in tumor size (p<0.001), nodal stage (p=0.03), tumor grade (p=0.04) and lymphovascular invasion (p<0.001), while no differences in nodal status, distant metastases and tumor stage were noticed. No significant associations were found between any of the PvuII polymorphism variants and tumor histopathology and stage. No statistical significance was proven between FokI polymorphism's variants or f allele and overall or progression-free survival. Statistically significant associations between overall and progression- free survival and PvuII polymorphism's variants was demonstrated (p<0.001). CONCLUSION: The f allele was associated with the presence of lymphovascular invasion and poorly differentiated tumors, whereas the PP genotype was associated with increased overall and progression-free survival, suggesting that this variant is related to a more favorable prognosis.

Expression of microRNAs, miR-21, miR-31, miR-122, miR-145, miR-146a, miR-200c, miR-221, miR-222, and miR-223 in patients with hepatocellular carcinoma or intrahepatic cholangiocarcinoma and its prognostic significance.

MicroRNAs are a class of non-coding molecules found to regulate a variety of cellular functions in health and disease. Dysregulation of microRNAs is involved in liver disease, especially hepatocarcinogenesis. Since primary hepatic malignancies are typically characterized by late diagnosis, frequent recurrence, and poor response to adjuvant therapy, there is a need for the discovery of novel biomarkers in order to achieve earlier diagnosis, predict tumor aggressiveness and response to adjuvant therapy. The purpose of this study is to evaluate the expression of certain microRNAs (miR-21, -31, -122, -145, -146a, - 200c, -221, -222 and -223) in patients with hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC), as well as to assess their prognostic significance. Micro-RNA expression was assessed by reverse transcription and real-time PCR (RT-PCR). Clinicopathological data and survival rates were retrieved and analyzed. According to our results, miR-21, miR-31, miR-122, miR-221, miR-222 were significantly up-regulated in HCC tissues, whereas miR-145, miR-146a, miR-200c, and miR-223 were found to be down-regulated. Concerning ICC samples, miR-21, miR-31, and miR-223 were found to be over-expressed, whereas miR-122, miR-145, miR-200c, miR-221, and miR-222 were down-regulated. Additionally, expression of miR-21, miR-31, miR-122, and miR-221 in HCC correlated with cirrhosis, while miR-21 and miR-221 associated with tumor stage and poor prognosis. In ICC tissues, miR-21, miR-31, and miR-223 were found to be over-expressed, but no correlation with clinicopathological features was found.

Neuroendocrine differentiation in embryonal type hepatoblastoma.

Hepatoblastoma, a malignant tumor which arises occasionally in older children but very rarely in adults, exhibits divergent differentiation with embryonal cells, fetal hepatocytes and immature elements. This report describes an embryonal type hepatoblastoma with neuroendocrine differentiation in a 16-year-old patient, which was diagnosed postoperatively. Clinical and radiologic work-up failed to reveal a primary gastrointestinal malignancy and no primary lesions were detected in any other organ. This feature of hepatoblastoma is considered to be a multidirectional differentiation of the small epithelial or stem cells of the liver. At 2-year follow up, the patient remains symptom-free, with normal laboratory and diagnostic imaging studies, and no recurrent or metastatic disease identified.

The impact of ischemic preconditioning on hemodynamic, biochemical and inflammatory alterations induced by intra-abdominal hypertension: an experimental study in a porcine model.

PURPOSE: Intra-abdominal hypertension (IAH) has several pathophysiologic implications on human organs and systems. The aim of this experimental study was to investigate whether ischemic preconditioning (IP), namely the application of IAH for a small period of time prior to establish pneumoperitoneum, can attenuate the hemodynamic, biochemical and inflammatory alterations observed during IAH. METHODS: Twenty-four pigs were divided into three groups: group A (control group), group B (pneumoperitoneum of 30 mmHg) and group C (ischemic preconditioning, consisting of pneumoperitoneum of 25 mmHg for 15 min and subsequent pneumoperitoneum of 30 mmHg). Hemodynamic (central venous pressure, cardiac index, mean arterial pressure, heart rate, stroke volume index, systemic vascular resistance index, global end-diastolic index, intrathoracic blood index and extravascular lung water index), biochemical (serum glutamic oxaloacetic transaminase (SGOT), serum glutamic pyruvate transaminase (SGPT), alkaline phosphatase (ALP), γ-glutamyl transpeptidase (γ-GT), urea and creatinine) and inflammatory (tumour necrosis factor-α, interleukin (IL)-6, IL-10 and C-reactive protein) parameters were measured. RESULTS: (a) Hemodynamics: The increase of central venous pressure monitoring and heart rate and the decrease of cardiac index, mean arterial pressure, stroke volume index, global end-diastolic volume index and intrathoracic blood volume index with the establishment of pneumoperitoneum were attenuated by IP. Systemic vascular resistance index and extravascular lung water were not affected. (b) Urea significantly increased with the pneumoperitoneum. IP, however, attenuated this effect. Οther biochemical parameters (SGOT, SGPT, ALP, γ-GT and creatinine) had a similar upward trend during IAH, which was reversed with IP. (c) Inflammatory parameters: CRP was increased with pneumoperitoneum, an effect that was attenuated with the application of IP. Νo significant differences were observed for interleukins. CONCLUSIONS: Ischemic preconditioning seems to attenuate the pathophysiologic alterations of several hemodynamic, biochemical and inflammatory parameters observed during IAH.

The effect of warm liver ischaemia & reperfusion injury on circulating plasma lipid levels & lipolytic enzyme activity in rat & the impact of ischaemic preconditioning.

BACKGROUND & OBJECTIVES: Ischaemia/reperfusion (I/R) associated with major liver surgery compromises liver function. Ischaemic preconditioning (IPC) may be effective in minimizing hepatic I/R injury. This study aimed to investigate the impact of liver ischaemic manipulations on lipid metabolism in rat during the process of liver recovery after liver surgery. METHODS: Sixty three male Wistar rats were assigned to three groups: the sham group, the I/R group which underwent warm ischaemia and reperfusion (I/R), and the IPC group. The animals were subdivided in 3 groups [1 st , 3 rd and 7 th postoperative day (PO)]. Hepatic lipase (HL) and total lipase (TL) activity and the levels of aspartate and alanine transaminases (AST, ALT), triglycerides, HDL and cholesterol were measured in plasma. RESULTS: There was no significant difference in the activity of HL and TL between the groups. Significant higher levels of HDL (P<0.0001) were observed in the IPC group when compared to the other groups on the 3 rd PO day. Triglycerides (P<0.0001) and HDL (P=0.003) in the IPC group were higher than the sham group on the 7 th PO day while HDL was also higher in the I/R group. Significantly higher cholesterol levels were found in the I/R and IPC groups on the 7 th PO day, which were not observed in the sham group. There was a similar curve for triglycerides in the sham and IPC groups while there were significantly higher levels of triglycerides on day 7 for the I/R group. The levels of HDL in the IPC group were higher on the 3 rd and 7 th PO day, compared to day 1. INTERPRETATION & CONCLUSION: Warm ischaemia and I/R injury do not seem to affect lipolytic enzyme activity after the 1 st PO day despite the effects on plasma lipids. IPC seems to prevent accumulation of triglycerides and cholesterol in plasma.

Successful treatment with the mTOR inhibitor everolimus in a patient with perivascular epithelioid cell tumor.

Perivascular epithelioid cell tumor (PEComa) is an extremely rare neoplasm that appears to arise most commonly at visceral (especially gastrointestinal and uterine), retroperitoneal, and abdominopelvic sites. Malignant PEComas exist but are very rare. These tumors represent a family of mesenchymal neoplasms, mechanistically linked through activation of the mTOR signaling pathway. Metastatic PEComa is a rare form of sarcoma for which no effective therapy has been described previously and that has a uniformly fatal outcome. Although there is no known effective therapy, the molecular pathophysiology of aberrant mTOR signaling provides a scientific rationale to target this pathway therapeutically. The difficulty in determining optimal therapy, owing to the sparse literature available, led us to present this case. On this basis, we report a case of metastatic retroperitoneal PEComa treated with an oral mTOR inhibitor, with everolimus achieving significant clinical response.

Concurrent insulinoma and pancreatic adenocarcinoma: report of a rare case and review of the literature.

Pancreatic adenocarcinoma is the 5th leading cause of cancer-related death in Western countries and insulinomas are rare endocrine neoplasms of the pancreas. The concurrent appearance of pancreatic adenocarcinoma and insulinoma is very rare and to the best of our knowledge has never been reported again. Herein, we present such an occurrence in a 74-year-old man. Resection of a mass in the uncinate process of the pancreas revealed pancreatic adenocarcinoma with severe desmoplastic reaction. Two years later, due to symptomatology persistence the patient was re-examined and a new 2 cm mass in the uncinate process was found leading to surgery, which demonstrated a 2 cm endocrine islet-cell tumor. Establishing a diagnosis in patients with insulinoma is difficult and the imaging studies still have low sensitivity and specificity except for intra-operative ultrasonography, which is the most accurate method detecting 90% of these lesions.

The effect of hepatectomy on plasma lipolytic enzyme activity and circulating lipid levels: an experimental study on Wistar rat.

BACKGROUND/AIMS: The aim of this experimental study was to investigate the effect of liver resection and resulting transient hepatic steatosis on circulating lipid levels and plasma lipolytic enzyme activity. METHODOLOGY: Forty-eight male Wistar rats were assigned to the sham (Group A=21) or the hepatectomy group (Group B=27) and were further subdivided according to the day they were sacrificed (POD 1, 3 and 7). We measured hepatic lipase (HL) and total lipase (TL) activity and plasma levels of AST, ALT, triglycerides, HDL and cholesterol. RESULTS: There were no significant differences in the activities of HL and TL between the groups. Nevertheless, significant differences were observed in the levels of HDL (p=0.001) and cholesterol (p=0.001) on the 1st POD, and in triglycerides (p=0.045) on the 7th POD. A significant drop in the levels of HDL and cholesterol on the 1st POD was followed by a rapid recovery (3rd POD) and maintenance of these levels in group B until the 7th POD, while high levels of triglycerides (TG) were observed only on POD 7. CONCLUSIONS: After hepatectomy the activities of the lipolytic enzymes recover early and remain stable during regeneration. HDL and cholesterol levels are reversely proportional to the liver stress.

Ischemia as a possible effect of increased intra-abdominal pressure on central nervous system cytokines, lactate and perfusion pressures.

INTRODUCTION: The aims of our study were to evaluate the impact of increased intra-abdominal pressure (IAP) on central nervous system (CNS) cytokines (Interleukin 6 and tumor necrosis factor), lactate and perfusion pressures, testing the hypothesis that intra-abdominal hypertension (IAH) may possibly lead to CNS ischemia. METHODS: Fifteen pigs were studied. Helium pneumoperitoneum was established and IAP was increased initially at 20 mmHg and subsequently at 45 mmHg, which was finally followed by abdominal desufflation. Interleukin 6 (IL-6), tumor necrosis factor alpha (TNFa) and lactate were measured in the cerebrospinal fluid (CSF) and intracranial (ICP), intraspinal (ISP), cerebral perfusion (CPP) and spinal perfusion (SPP) pressures recorded. RESULTS: Increased IAP (20 mmHg) was followed by a statistically significant increase in IL-6 (p = 0.028), lactate (p = 0.017), ICP (p < 0.001) and ISP (p = 0.001) and a significant decrease in CPP (p = 0.013) and SPP (p = 0.002). However, further increase of IAP (45 mmHg) was accompanied by an increase in mean arterial pressure due to compensatory tachycardia, followed by an increase in CPP and SPP and a decrease of cytokines and lactate. CONCLUSIONS: IAH resulted in a decrease of CPP and SPP lower than 60 mmHg and an increase of all ischemic mediators, indicating CNS ischemia; on the other hand, restoration of perfusion pressures above this threshold decreased all ischemic indicators, irrespective of the level of IAH.

Prevention of Entero-Atmospheric Fistula: The Initial Closure of the Abdomen.

BACKGROUND AND AIMS: The "Open Abdomen" technique for difficult conditions such as trauma, necrotizing pancreatitis, severe peritonitis, reoperations and transplantations have become a very useful way to save patients. The more severe complication of this method are the enteroatmospheric fistulae with a frequency of 5-75% and a mortality up to 42%. So any effort to prevent these is very essential. The aim of this paper is to present methods of the initial (temporary) closure of the abdomen for the prevention of this catastrophe, when early approximation of the abdominal wall is not feasible. METHODS AND MATERIALS: We present two representative case reports and we describe the use of full thickness or split skin grafts as first step for abdominal closure. RESULTS AND CONCLUSIONS: The outcome of our patients by using tissues for temporary abdominal closure seems to have fewer problems than other methods with synthetic materials. We think that this is a reasonable option for the cases where we cannot achieve approximation of the abdominal wall edges in the early days of an open abdomen.

Managing injuries of hepatic duct confluence variants after major hepatobiliary surgery: an algorithmic approach.

AIM: To investigate injuries of anatomy variants of hepatic duct confluence during hepatobiliary surgery and their impact on morbidity and mortality of these procedures. An algorithmic approach for the management of these injuries is proposed. METHODS: During a 6-year period 234 patients who had undergone major hepatobiliary surgery were retrospectively reviewed in order to study postoperative bile leakage. Diagnostic workup included endoscopic and magnetic retrograde cholangiopancreatography (E/MRCP), scintigraphy and fistulography. RESULTS: Thirty (12.8%) patients who developed postoperative bile leaks were identified. Endoscopic stenting and percutaneous drainage were successful in 23 patients with bile leaks from the liver cut surface. In the rest seven patients with injuries of hepatic duct confluence, biliary variations were recognized and a stepwise therapeutic approach was considered. Conservative management was successful only in 2 patients. Volume of the liver remnant and functional liver reserve as well as local sepsis were used as criteria for either resection of the corresponding liver segment or construction of a biliary-enteric anastomosis. Two deaths occurred in this group of patients with hepatic duct confluence variants (mortality rate 28.5%). CONCLUSION: Management of major biliary fistulae that are disconnected from the mainstream of the biliary tree and related to injury of variants of the hepatic duct confluence is extremely challenging. These patients have a grave prognosis and an early surgical procedure has to be considered.

Special problems encountering surgical management of large retroperitoneal schwannomas.

BACKGROUND: Retroperitoneal schwannomas are rare, usually benign tumors that originate in the neural sheath and account for only a small percentage of retroperitoneal tumors. The aim of this clinical study is to present our experience in managing retroperitoneal schwannomas with a review of the current literature and to point out the surgical technical difficulties we faced, due to the tumor's strange behavior that eroded the vertebra in two cases without causing malignant invasion. METHODS: We reviewed the medical files of 69 patients treated in our department for retroperitoneal tumors from January 1991 until December 2006. Five patients had retroperitoneal schwannomas according to pathology report. RESULTS: There were two male and three female patients, with a mean age of 56 years (range 44-67 years). All patients were asymptomatic and none suffered from von Recklinghausen disease. Imaging workup included ultrasonography, computed tomography and magnetic resonance imaging. One patient, after having a non-diagnostic computed tomography fine needle aspiration (CT-FNA), underwent exploratory laparotomy and incisional biopsy that established the diagnosis of schwannoma. After complete excision of the tumors, postoperative course was uneventful in all patients. Tumors' maximum diameter was 12.7 cm (range 7-20 cm). No recurrences were detected during the follow up period (6-75 months). CONCLUSION: Preoperative establishment of diagnosis is difficult in case of retroperitoneal schwannomas, however close relationship of retroperitoneal tumors with adjacent neural structures in imaging studies should raise a suspicion. Complete surgical resection is the treatment of choice. Histology and Immunohistochemistry confirms the diagnosis.

Effect of Increased Intra-abdominal Pressure on Liver Histology and Hemodynamics: An Experimental Study.

BACKGROUND: While reduction of portal venous (PV) blood flow has been described in animal models of intra-abdominal hypertension, reports on compensatory changes in hepatic arterial (HA) flow, known as the hepatic arterial buffer response are controversial. MATERIALS AND METHODS: Pneumoperitoneum with helium was induced in 13 piglets. Hemodynamic measurements and pathological assessment were conducted at baseline and during the three subsequent phases: Phase A: 45 minutes with a stable intra-abdominal pressure of 25 mmHg; phase B: 45 minutes with a stable intra-abdominal pressure of 40 mmHg; and phase C during which the abdomen was re-explored and reperfusion of the liver was allowed to take place. RESULTS: Phase B pressure was significantly greater than phase A pressure in both the PV and the inferior vena cava, demonstrating a positive association between escalating intra-abdominal hypertension and the pressure in these two vessels (all p<0.001). In contrast, HA pressure was comparable between baseline and phase A, while it tended to decrease in phase B. Regarding histology, the most notable abnormality was the presence of inflammatory infiltrates and hepatocyte necrosis. CONCLUSION: Helium-insufflation increased PV pressure with a partial compensatory decrease of HA pressure. Nonetheless, findings consistent with hepatic ischemia were observed on pathology.

Surgical approaches of resectable synchronous colorectal liver metastases: timing considerations.

AIM: To compare the safety and efficacy of simultaneous versus two stage resection of primary colorectal tumors and liver metastases. METHODS: From January 1996 to May 2004, 103 colorectal tumor patients presented with synchronous liver metastases. Twenty five underwent simultaneous colorectal and liver surgery and 78 underwent liver surgery 1-3 mo after primary colorectal tumor resection. Data were retrospectively analyzed to assess and compare the morbidity and mortality between the surgical strategies. The two groups were comparable regarding the age and sex distribution, the types of liver resection and stage of primary tumors, as well as the number and size of liver metastases. RESULTS: In two-stage procedures more transfusions were required (4 +/- 1.5 vs 2 +/- 1.8, pRBCs, P < 0.05). Chest infection was increased after the two-stage approach (26% vs 17%, P < 0.05). The two-stage procedure was also associated with longer hospitalization (20 +/- 8 vs 12 +/- 6 d, P < 0.05). Five year survival in both groups was similar (28% vs 31%). No hospital mortality occurred in our series. CONCLUSION: Synchronous colorectal liver metastases can be safely treated simultaneously with the primary tumor. Liver resection should be prioritized over colon resection. It is advisable that complex liver resections with marginal liver residual volume should be dealt with at a later stage.

Treatment of hydatid liver disease.

BACKGROUND: Echinococcal disease is still a serious problem in certain parts of the world. The liver is the organ affected most frequently. Over recent decades, various reports have been published comparing standard surgical and more conservative modalities for the treatment of the disease. Proper selection among the strategies reported so far could be the most appropriate part of successful patient management. METHODS: A thorough review of the most recent reports on the treatment of liver Echinococcus infection, including percutaneous drainage, medical management, and laparoscopic, endoscopic and open surgical approaches has been conducted, focusing on patient outcomes. RESULTS: The standard surgical approach, namely partial capsectomy, drainage, and epiploplasty, remains the most frequent operative method. Previous problems such as disease recurrence and a residual cavity seem to be managed optimally with more radical operations such as total pericystectomy. Laparoscopic and endoscopic approaches (endoscopic retrograde cholangiopancreatography and sphincterotomy) appear to have a crucial role, especially when the location of the cyst or the patient's status does not permit more radical approaches. Percutaneous computed tomography- or ultrasound-guided drainage appears to be of great value in certain cases. Chemotherapeutic agents remain useful as an adjuvant treatment. CONCLUSIONS: Appropriate patient selection and proper use of the various available treatments are of great importance. A tailor-made approach should be employed for each patient. The surgeon's experience constitutes a principal criterion. To achieve the best possible results, an interdisciplinary approach should be used in the majority of patients.

"Solitary" necrotic nodule of the liver: an enigmatic entity mimicking malignancy.

AIM: The aim of the study is to further investigate the clinicopathological features of solitary necrotic nodules. MATERIAL AND METHODS: Twenty-three archived cases of solitary necrotic nodule of the liver, which were preoperatively misdiagnosed as liver metastases were studied. The pathological findings were correlated with the clinical data of the patients. RESULTS: The nodules were solitary in 20 cases and multiple (2) in three cases, and measured from 0.5-1.5 cm in diameter. Twenty-one cases were located in the right lobe of the liver (91.6%) and two in the left lobe (8.69%). Twenty nodules were found in the subcapsular region (86.95%), while three nodules were located within the hepatic parenchyma (13.04%). More then half of our cases (12) were accompanied by extended calcification. Granulomatous tissue resembling "burnt-out" parasitic granulomas was found in three cases. CONCLUSIONS: Solitary necrotic nodules of the liver often mimic malignancy in abdominal imaging. Thus, permanent histopathology of the operative specimen remains the only accurate method of diagnosis. Their pathogenesis is most likely variable, and most reported cases are linked either to a parasitic or a vascular origin. Despite the designation of these lesions as "solitary" they may occasionally be multiple. In addition to the standard histological criteria of solitary necrotic nodules, the relatively small size (15 mm or less) and the frequent presence of calcifications seem to further characterize this enigmatic entity. Solitary necrotic nodule should be included in the differential diagnosis of small liver lesions with extensive necrosis.

Gemcitabine combined with 5-fluorouracil for the treatment of advanced carcinoma of the pancreas.

BACKGROUND: Gemcitabine is an active agent in pancreatic cancer, showing clinical synergy with 5-fluorouracil (5-FU). The aim of the study was to evaluate the safety and efficacy of the combination of gemcitabine and 5-FU in patients with advanced adenocarcinoma of the pancreas. PATIENTS AND METHODS: Forty-two patients (median age, 62 years), with advanced or metastatic pancreatic adenocarcinoma, were enrolled in the study. The combination of gemcitabine (1000 mg/m2) and 5-FU (600 mg/m2) was administered on days 1, 8 and 15 and repeated every 28 days. RESULTS: A total of 168 cycles (median 4 cycles per patient) were administered. Partial responses were observed in 6 patients (14.2%) and stable disease in 11 (26.2%). The overall clinical benefit was 40.4%. Symptom relief and improvement of performance status were observed in 18 (42.8%) patients. The median time to progression, median duration of response and the median overall survival, were 6, 7 and 13 months, respectively. The most common grade 3 to 4 toxicities were neutropenia, anaemia and diarrhoea. CONCLUSION: The combination of gemcitabine and 5-FU is an active regimen for the treatment of advanced pancreatic cancer with an acceptable toxicity profile.