Challenging diagnosis of ileal gastrointestinal stromal tumor presenting with obscure digestive bleeding.

We report a case of a patient observed in emergency condition for recurrent episodes of massive obscure gastrointestinal bleeding that required surgical control. At laparotomy we found an ileal mass with the characteristics of a gastrointestinal stromal tumor (GIST) at histopathological analysis. GISTs should always be considered as a possible cause of obscure gastrointestinal bleeding, although they are often difficult to diagnose preoperatively. Laparotomy is sometimes the only way to obtain a diagnosis. Starting from this case, we reviewed the literature about GISTs, focusing our attention on their diagnosis and the possible surgical and nonsurgical therapies.

Interleukin-2 immunotherapy action on innate immunity cells in peripheral blood and tumoral tissue of pancreatic adenocarcinoma patients.

BACKGROUND AND AIMS: Innate immunity cells play a crucial role in host anticancer defense: cancer patients with high levels of natural killer (NK) cells and eosinophils have a better prognosis. Recombinant interleukin-2 (rIL-2) immunotherapy stimulates innate immunity cells. This study aims to evaluate the toxicity of pre- and postoperative rIL-2 treatment and the effects on innate immunity both in peripheral blood and in cancer tissue of patients with resectable pancreatic adenocarcinoma. MATERIALS AND METHODS: Seventeen patients received high dose rIL-2 preoperative subcutaneous administration and two low dose postoperative cycles. We evaluated NK cell and eosinophil count in blood and in pancreatic surgical specimens. RESULTS: Toxicity was moderate. In the early postoperative period, blood NK cells and eosinophils significantly increased compared to basal values (p < 0.02). Histopathological analysis did not find significant intratumoral infiltration of NK cells nor of eosinophils. CONCLUSIONS: Preoperative high dose rIL-2 administration is able to counteract surgery-induced deficiency of NK cells and eosinophils in peripheral blood in the early postoperative period, although it cannot overcome local mechanisms of immune tumor escape in cancer tissue. The amplification of innate immunity, induced by immunotherapy, may improve the control of metastatic cells spreading in the perioperative period.

Prolonged survival of a patient affected by pancreatic adenocarcinoma with massive lymphocyte and dendritic cell infiltration after interleukin-2 immunotherapy. Report of a case.

Several studies have shown that there is a paucity of immune cells within the stroma of pancreatic adenocarcinoma, a very aggressive cancer with a median survival of about 18 months. A 65-year-old man presented with jaundice. Abdominal ultrasound revealed intra- and extrahepatic bile duct dilatation and a 45-mm diameter hypoechoic solid mass within the pancreatic head; a computed tomography scan excluded vascular infiltration and metastatic lesions. The patient received immunotherapy consisting of 6,000,000 IU human recombinant interleukin-2 administered subcutaneously twice a day for 3 consecutive days. Thirty-six hours after the last dose, he underwent a pylorus-preserving pancreatoduodenectomy. Because of the presence of high-grade dysplasia detected by intraoperative histological examination of a distal section, a spleen preserving total pancreatectomy was performed. The postoperative course was uneventful. The patient died 32 months after surgery because of local recurrence. Histopathology showed G3 pancreatic ductal adenocarcinoma infiltrating the anterior and posterior peripancreatic tissue, duodenal wall and intrapancreatic common bile duct, with sarcoma-like foci and a component of intraductal tumor involving the common bile duct. In the distal pancreas, widespread foci of pancreatic intraepithelial neoplasia (PanI2-3) were found. The Ki-67 proliferation index was 16%. TNM staging was pT3 pN1 R1. Sections were immunostained for the T-lymphocyte marker CD3 and for the dendritic cell marker CD1a. Intratumoral infiltration was high for CD1a+ cells and mild for CD3+ cells. Preoperative immunotherapy with interleukin-2 may contribute to massive stromal infiltration of immune cells in pancreatic adenocarcinoma. This may prolong the survival even in the presence of negative prognostic factors (age >65 years, tumor diameter >20 mm, R1, tumor grade G3).

A case of pancreatic heterotopy of duodenal wall, intraductal papillary mucinous tumor and intraepithelial neoplasm of pancreas, papillary carcinoma of kidney in a single patient.

We report a case of the contemporaneous presence of two histologically different pancreatic neoplasms, one renal cancer and one embryogenic duodenal anomaly in a single patient. A 66-year-old man underwent ultrasound examination because of urinary disorders; a solid neoformation within the inferior pole of the left kidney was observed. Computed tomography confirmed the renal lesion, but also a heterogeneous mass within the pancreatic head appeared without bile ducts dilatation. Abdominal magnetic resonance revealed a multiloculated cystic component of the pancreatic mass. A second CT scan confirmed the renal and biliary findings, but it revealed a modest enlargement of the pancreatic asymptomatic mass. A resection of the left kidney inferior pole and a pylorus-preserving pancreaticoduodenectomy were performed. Histopathologic analysis of the surgical specimen revealed mild differentiated papillary renal carcinoma, intraductal papillary mucinous adenoma of the pancreatic head, foci of intraepithelial pancreatic neoplasm and pancreatic heterotopy of duodenal muscular and submucosal layers. The coexistence of several primaries and anomalies in one patient led us to suppose a genetic predisposition to different lesions, even in the absence of known familial genetic syndromes. The study of such cases may help to improve the investigation of molecular correlations and etiological factors of different solid tumors. Nowadays, surgery is the only effective cure.

Hepatic surgery using the Ligasure vessel sealing system.

Blood loss, a well-known risk factor for morbidity and mortality during liver resection, occurs during parenchymal transection, so many approaches and devices have been developed to limit bleeding. Surgical technique is an important factor in preventing intraoperative and postoperative complications. The aim of the present study was to determine whether the bipolar vessel sealing device allows a safe and careful liver transection, achieving a satisfactory hemostasis thus reducing blood loss and related complications.A total of 30 consecutive patients (18 male, 12 female with a mean age of 63 years) underwent major and minor hepatic resection in which the bipolar vessel sealing device was used without routine inflow occlusion. A crush technique followed by energy application was used to perform the parenchymal transection. No other devices were applied to achieve hemostasis. The bipolar vessel sealing device was effective in 27 cases of hepatic resection. It failed to achieve hemostasis in three patients, all of whom had a cirrhotic liver. Median blood loss was 250 ml (range: 100-1600 ml), and intraoperative blood transfusions were required in five patients (17%). Mean operative time was 200 minutes (range: 140-360 minutes). There was no clinical evidence of postoperative hemorrhage, bile leak, or intraabdominal abscess. The postoperative complication rate was 17%. The bipolar vessel sealing device is a useful tool in standard liver resection in patients with a normal liver parenchyma, but its use should be avoided in cirrhotic livers.

Phase-II randomized study of preoperative IL-2 administration in radically operable gastric cancer patients.

BACKGROUND/AIMS: Surgery has appeared to induce lymphocytopenia and this decrease in host defenses during postoperative period could promote both the proliferation of possible micrometastases and the implantation of surgically disseminated tumor cells. The aim of this study is to evaluate if the preoperative subcutaneous injection of IL-2 (interleukin-2) may be able to abrogate surgery-induced immunosuppression in radically operable gastric cancer and to assess its toxicity. METHODOLOGY: This phase II study included 39 consecutive patients with histologically proven gastric adenocarcinoma (M/F 26/13; mean age 68; range 48-82) who underwent radical surgery from October 1999 to December 2000. Patients were randomized to be treated with surgery alone as controls (20 patients) or surgery plus preoperative treatment with recombinant human IL-2 (19 patients). IL-2 was administered subcutaneously, at a dose of 9,000,000 IU, for three consecutive days, followed by surgery within 36 hours from IL-2 withdrawal. We considered the total lymphocyte count and lymphocyte subset (CD4, CD4/CD8) during the preoperative period, before IL-2 administration, and on the 14th and 50th day. RESULTS: Two groups were well matched for type of surgery and extent of disease. All the patients underwent radical surgery plus D2 lymphadenectomy. At baseline, there were no significant differences in total lymphocyte and lymphocyte subsets between groups. The control group showed a significant decrease of total lymphocytes, CD4 cells, and CD4/CD8 ratio at the 14th postoperative day relative to the baseline value. Among the 22 patients evaluated in the control group 13 had a decreased of CD4 under 500 cells/mm3 (65%). Instead in the IL-2 group a significant increase was observed over the control group values of total lymphocytes and CD4 cells (14th ly total and CD4: IL-2 vs. control p<0.05). Moreover in this group only 3 patients had CD4 under 500 cells/mm3 (15%). This difference in CD4 count, is significant at the 50th postoperative day too (p=0.006). No anesthesiologic or surgical complication was seen in IL-2 treated group, with low grade of toxicity (WHO grade:1): the main effect was fever (14/19) easily manageable, with no cardiovascular complications. Furthermore, IL-2 group showed lower postoperative complications (p<0.05) and higher lymphocyte/eosinophil infiltration into the tumor (p<0.002). CONCLUSIONS: This phase II study would suggest that a preoperative immunotherapy with IL-2 is a well tolerated treatment able to prevent surgery induced lymphocytopenia. IL-2 seems to neutralize the immunosuppression induced by operation and so to stimulate the host reaction against tumor tissue (lymphocytes/eosinophils infiltration). Next randomized clinical trials could investigate the prognostic impact of IL-2 on the clinical course.

Heterotopic mesenteric ossification ("intraabdominal myositis ossificans''): a case report.

Heterotopic ossification has been reported only rarely within the abdominal cavity, specifically in a mesenteric location (heterotopic mesenteric ossification). We describe the case of a 76-year-old man with no history of previous surgery who developed small bowel obstruction associated with multiple foci of heterotopic bone formation within the small bowel mesentery. He underwent small bowel and mesentery resection and is disease-free 9 months later.

Estrogen-induced severe acute pancreatitis in a male.

CONTEXT: Acute pancreatitis is related to drugs in 1.4-2% of cases. Estrogens are an uncommon but well-known risk factor of pancreatitis in women and men with pre-existing hyperlipidemia. CASE REPORT: We report the case of a 37-year-old man with covert hypertriglyceridemia who developed a severe life-threatening pancreatitis strongly associated with estrogen therapy preparatory to sex change surgery, characterized by a massive triglyceride level, pancreatic insufficiency and multiple organ failure at the time of the diagnosis. Other causes of the disease were ruled out. CONCLUSIONS: To our knowledge, this is the first description of severe necrotizing estrogen-induced pancreatitis in a male. Baseline abnormal triglyceride levels should be checked by physicians before starting estrogen therapy in women and men.

Case report of a hepatic angiomyolipoma.

Angiomyolipoma (AML) is a benign mesenchymal tumor that has been frequently reported in the kidney but rarely in the liver. Hepatic AML may be clinically, radiologically and morphologically difficult to distinguish from hepatocellular carcinoma or other hepatic lesions, even though the number of cases has been increasing recently due to improved imaging techniques. Histologically it consists of smooth muscle cells, adipose cells and abnormal blood vessels. It is commonly diagnosed following abdominal pain but may also be asymptomatic, has a predominant female predilection, highly variable size and occurs in subjects with a wide age range. The right lobe is the most common site, and multicentricity has been reported. Here we report a case of the myomatous variant of AML, accidentally discovered in a young woman with no clear features on radiographic examination, which was diagnosed by means of fine needle aspiration biopsy (FNAB) and then surgically removed. Although careful observation with serial radiological follow-up is an option in these cases, we chose the surgical approach because of the risk of rupture due to the large size of the lesion and the risk of malignant behavior or transformation. In case of the myomatous variant composed of irregular cells with epithelioid appearance, hepatocellular carcinoma with fatty changes or the possibility of other malignant tumors must be ruled out by immunohistochemistry (HMB-45), even in biopsy specimens.

The use of LigaSure during pediatric laparoscopic splenectomy: a preliminary report.

BACKGROUND: Laparoscopic splenectomy (LS) is becoming the gold standard for the treatment of hematological disease in children. Intraoperative bleeding is the main complication and main cause of conversion during LS. We present the use of the LigaSure Vessel Sealing System for achieving a safe vascular control, compared with previous techniques. METHODS: LigaSure is an energy-based device which works by applying a precise amount of bipolar energy and pressure to the tissue, thus achieving a permanent seal. We have performed a total of 15 LS in children during 6 years, on 6 males and 9 females with a median age of 11 years (range 5-17). Seven children had hereditary spherocytosis, 4 thrombocytopenic idiopatic purpura (ITP), 3 beta talassemia, and 1 hemolytic anemia. Patients were divided into two groups according to the method of dissection: group 1 ultrasonic coagulation+endostapler (8 pts); group 2 LigaSure (7 pts). We employed a 4 trocars technique with right semilateral position. RESULTS: The groups were well-matched for age, gender, weight, indication and spleen size. Fourteen LS were completed with one conversion (7%) because of hilar bleeding due to accidental injury with endostapler. Median operative time of the series was 140 min (range 90-205), significantly shorter in the group 2 (130 min versus 155 min, P<0.05), as well as median blood loss (group 1, 180 ml versus group 2, 70 ml, P<0.05). There was no mortality, with one postoperative complication (7%) (pulmonary atelectasis). The median postoperative hospital stay was 4 days (range 2-5) without differences between groups. CONCLUSIONS: Each method of dissection seems to be safe and effective. Otherwise LigaSure results in a reduction of operating time and blood loss.

IGF-1 and IGF-1BP3 in gastric adenocarcinoma. Preliminary study.

BACKGROUND/AIMS: Insulin-like growth factor-1 (IGF-1) is a mitogenic and anti-apoptotic factor, mainly produced by the liver, which regulates cell proliferation. Most serum IGF-1s are bound with IGF-1BP3. Plasma IGF-1 values are positively related to cancer risk (breast, colon, and lung cancer) and seem to have a prognostic significance in prostatic cancer. The aim of this study is to investigate the relationship between IGF-1, IGF-1BP3 and gastric cancer. METHODOLOGY: IGF-1 and IGF-1BP3 serum levels were measured in 26 consecutive patients (M/F = 15/11, mean age 65 yrs) with histologically proven gastric adenocarcinoma from January 1999 to December 2000. Blood samples were collected at baseline, before surgery with radical intent (total and subtotal gastrectomies + D2 lymphadenectomy), and then at 14th and 50th postoperative days. These values were compared to a control group of healthy people. RESULTS: At baseline was observed a significant increase of IGF-1 serum levels in cancer patients versus control group (p < 0.001). All gastric cancer patients showed IGF-1 over normal limits. After surgery there was a significant decrease of IGF-1 levels (14th day vs. baseline, p = 0.001) that was still present in late postoperative period (50th day). At baseline IGF-1 values were not related to tumor extension or nodal involvement status. Otherwise in postoperative period IGF-1 significantly decreased in earlier stages (N0; T < or = 2) but not in more advanced ones (N+; T > 2). At baseline, IGF-1BP3 values were increased compared to control group but did not significantly decrease after surgery. CONCLUSIONS: IGF-1 values in gastric cancer patients are increased compared to control group, without stratification for stage and nodal status. Moreover radical surgery, with complete tumor ablation, induces a significant decrease in IGF-1 levels, without reach normal limits. Besides at baseline abnormally higher IGF-1BP3 values were observed, suggesting an alteration in IGF-1 and IGF-1BP3 system.

Surgical treatment of hydatid disease of the liver. An experience from outside the endemic area.

Hydatid disease is quite rare in European countries outside the endemic areas. It occurs most frequently in the liver and lungs. Surgery remains the main treatment modality for hydatid disease of the liver. There is still considerable debate as to whether the best approach is conservative surgery or radical surgery in which the cyst is totally removed including the pericyst by total pericystectomy or partial hepatectomy. We report the results of our 15-year experience with this type of surgery. A series of 35 consecutive patients operated on for hydatid disease of the liver from January 1985 to December 2000 was analysed (18 women and 17 men with a mean age of 47.7 years). The most common complaints were pain (59%), hepatomegaly and intra-abdominal masses (37%). The cysts were single in 23 patients and multiple in 12, and were found in the right lobe in 21 cases (59%), in the left lobe in 9 cases (26%), and in both lobes in 5 (15%). In one patient (2.8%), concomitant extrahepatic (splenic) disease was present. The diameter of the cysts ranged from 3.5 to 20 cm (mean value: 9.5 cm). Patients were subdivided according to the kind of surgery (radical versus conservative) and period of operation (group 1: 1985-1992; group 2: 1993-2000). With the increase in surgical skills and the advent of new techniques, radical surgery (12 cystoperistectomies, 3 left lobectomies and 3 segmentectomies) came to be performed more frequently than conservative surgery in the second period (18/20 in group 2 versus in 7/15 group 1) with low complication rates, a 3.7% mortality rate and similar operative time (175 min versus 145 min) and hospital stay (16.8 days versus 19.2 days) as compared to the conservative approach. The policy of applying radical surgery whenever feasible can be implemented with acceptable morbidity and near zero mortality. Radical surgery, however, needs to be applied judiciously, and there is still an important role for conservative surgery.

Preoperative selective endoscopic retrograde cholangiopancreatography and laparoscopic cholecystectomy without cholangiography.

The aim of this study was to show that laparoscopic cholecystectomy can be performed safely without routine intraoperative cholangiography. We performed a retrospective analysis of 1750 consecutive patients (1170 females and 580 males with a mean age of 51 years) who underwent laparoscopic cholecystectomy between January 1991 and January 2000. In all, 193 patients (11%) were selected to undergo preoperative endoscopic retrograde cholangiopancreatography (ERCP) on the basis of several criteria for risk of stones. No patients underwent intraoperative cholangiography. ERCP allowed us to make a diagnosis of biliary stones in 62.7% (121 cases). Extraction of the stones was successful in 96% of the cases. In 12% of cases ERCP findings were normal; in the remaining 26.3%, useful diagnostic information was obtained. There were three complications (bleeding and pancreatitis) after endoscopy (complication rate: 1.5%). Laparoscopic cholecystectomy was successful in 92.7% of patients, with a postoperative morbidity rate of 3% (0.5% of major complications). There were no deaths in this series. During a mean follow-up of 60 months (range, 12-120), 7 patients (0.43%) were found to have residual biliary stones (5 had not had preoperative ERCP). The study confirms the hypothesis that laparoscopic cholecystectomy can be safely performed without routine intraoperative cholangiography, with selective use of preoperative ERCP.

Splenoportal thrombosis as a complication after laparoscopic splenectomy.

Laparoscopic splenectomy is performed with increasing acceptance for hematologic disorders, with low complication rates reported. Splenoportal thrombosis following splenectomy is a rare complication, anecdotally reported after laparoscopic procedures. We here describe a case of thrombosis of the spleno-mesenteric-portal axis 14 days after a laparoscopic splenectomy using Ligasure. Abdominal ultrasound scans and Doppler examination allowed us to diagnose this event, and an angio-MR scan performed afterward confirmed the diagnosis. Heparin therapy was promptly begun. The patient was then switched to oral anticoagulant therapy, with resolution of the clinical features. The patient was discharged after 1 week of anticoagulant therapy with a stable Doppler ultrasound pattern. Early diagnosis and prompt initiation of anticoagulant therapy associated with careful surgical technique may reduce the risk of this life-threatening complication.