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Biomedical subjects

Fabrizio Romano

Publications and source records attributed to Fabrizio Romano.

At least 19 recordsLinked to original sources

Low-dose interleukin-2 administered pre-operatively to patients with gastric cancer activates peripheral and peritumoral lymphocytes but does not affect prognosis.

BACKGROUND: There is evidence that cancer is immunogenic under certain situations. IL-2 is described to stimulate an effective antitumor immune response in vitro and in vivo. The ability of cancer patients to undergo surgical resection is still the most important prognostic factor for many solid tumors, including gastric adenocarcinoma. The host immune system may be further compromised by surgical procedures leading to a generalized state of immunodepression in the post-operative period. The aim of this randomized case-control study is to evaluate the effects of pre-operative low-dose IL-2 treatment on patients with gastric adenocarcinoma who undergo surgery. METHODS: Sixty-eight patients with gastric adenocarcinoma were enrolled in the study and randomized in two groups: 36 patients were pre-treated with IL-2 and 32 underwent surgery without any treatment. Total peripheral WBC, neutrophils, CD3(+) T, CD4(+) T, CD8(+) T and NK cells were obtained before and after surgery, at different times. Peritumoral infiltration was analyzed on all surgical specimens. Overall survival and relapse-free survival were studied with a median follow-up of 51 months. RESULTS: Low-dose IL-2 treatment resulted in an increase peritumoral lymphocytic and eosinophilic infiltrations and in a minor decrease in CD3(+) T and CD4(+) T cells after surgery (P < 0.05). A stepwise multivariate analysis revealed that overall survival and relapse-free survival were affected only by stage of tumor and age of patients. CONCLUSIONS: According to our data low-doses of IL-2 administered pre-operatively to patients with gastric cancer activate peripheral and peri-tumoral lymphocytes but did not affect prognosis.

Adenocarcinoma↗

Thrombosis of the splenoportal axis after splenectomy.

BACKGROUND AND AIMS: Thrombosis of the portal system is a potentially life-threatening complication after splenectomy. The reported incidence is low (approximately or = 1%), however may be underestimated due to difficult in making the diagnosis. The factors associated with its development and the clinical outcome are poorly characterized. The aim of this study was to assess the incidence, risk factors, treatment, and outcome in series of consecutive cases. MATERIALS AND METHODS: All patients who had undergone a splenectomy (both open and laparoscopic) between January 1997 and December 2004 at the Department of Surgery of University of Milan Bicocca were retrospectively reviewed. Twelve cases of thrombosis (7.6%) among 158 splenectomies were identified. No significant differences were noted in age, gender, and surgical approach between patients who developed thrombosis and those who did not. Indication for splenectomy in patients with thrombosis were myeloproliferative disorders (n=5), hemolytic disease (n=4), and lymphoproliferative disorder (n=3). All patients had splenomegaly (mean 1.380 kg, range 0.400-3.120 kg). RESULTS: Among patients with myeloproliferative disorders, five (33%) developed the complication, compared with 4 of 35 (11.5%) with hemolytic disease. Patients with both splenic weight >2.500 kg and myeloproliferative disorders had 80% incidence of portal thrombosis. Preoperative prophylactic anticoagulant therapy with low molecular weight heparin was administered in each case. All these patients had fever, abdominal pain, or leukocytosis. All diagnoses were made by contrast-enhanced computed tomography (CT) scan and ecocolordoppler ultrasonography, and anticoagulation therapy was initiated immediately. Treatment within 15 days after splenectomy was successful in all patients, while delayed treatment was ineffective. CONCLUSIONS: Portal thrombosis should be suspected in patients with fever or abdominal pain after splenectomy. Patients with myeloproliferative disorders and hemolytic diseases are at higher risk, as well as patients with marked splenomegaly. A high index of suspicion, early diagnosis, and prompt anticoagulation therapy are the keys to a successful outcome.

Abdominal Pain↗

Surgical treatment of metastatic tumors to the pancreas: a single center experience and review of the literature.

BACKGROUND: Unlike primary pancreatic carcinoma, metastases to the pancreas are rare, and their resection may be performed as palliative treatment. The aim of this study was to review our experience with the operative management of pancreatic metastases. MATERIALS AND METHODS: Between January 1994 and December 2004 13 patients (nine women and four men; median age: 59 years; range: 36-79 years) were admitted to our institution with metastatic lesion to the pancreas. The clinical features of the treatment and results were examined. RESULTS: Primary tumors were renal cell carcinoma (n=5), lobular carcinoma of the breast (n=3), endometrioid carcinoma of the ovary (n=1), colonic adenocarcinoma (n=1), jejunal leiomyosarcoma (n=1), melanoma (n=1), and non-small-cell lung cancer (n=1). The median interval between primary tumor and pancreatic metastases was 36 months (range: 5-192 months). Six patients (46%) were asymptomatic, while the other seven patients presented with jaundice, pain, and duodenal obstruction. Two patients with extrapancreatic disease underwent palliative surgery, and the remaining 11 patients underwent operative procedures that included seven pancreaticoduodenectomy and four distal pancreatectomies with splenectomy. Postoperative mortality was nil, and the morbidity rate was 30%. The two patients who underwent palliative surgery died after 7 and 9 months, respectively. The median survival of the resected patients was 26 months (range: 13-95 months). Five patients died of disease, eight are alive at the time of this report. CONCLUSION: A trend towards improved survival, even if not statistically significant, was observed in the renal carcinoma patients reported here. Surgical resection can be performed safely in selected patients with isolated metastases to the pancreas, achieving long-term survival as well as good palliation.

Adult↗

Elective laparoscopic splenectomy and thrombosis of the spleno-portal axis: a prospective study with ecocolordoppler ultrasound.

Thrombosis of the portal system is a potentially life-threatening but otherwise underappreciated complication after splenectomy. Nonspecific and mild onset symptoms are the cause of delay in diagnosis, and the short hospital stay after laparoscopic approach could even contribute to the difficulty of early detection of this condition. The aim of this study was to verify if planned imaging controls are able to discover this complication leading to a prompt treatment. Thirty-eight patients (19 males and 19 females with a mean age of 24 years) who underwent laparoscopic splenectomy at our institution were studied to identify clinical signs of thrombosis of the portal venous system and eventually associated factors. All the patients were enrolled in a protocol of imaging surveillance using a doppler ultrasound method. Postoperative thrombosis of the spleno-portal axis occurred in 7 patients (18.9%) of the series. In 3 cases (8.1%) the thrombus extended from the splenic vein to occlude the portal axis. The complication was symptomatic in 4 cases (10.8%), whereas in 3 cases, the thrombosis was an ultrasonographic surprise in totally asymptomatic patients. Thrombosis occurred even as late as 2 months after splenectomy. Splenomegaly was the only significant factor predictive of thrombosis. Only those patients who had an early detection of portal or splenic vein thrombosis had a recanalization of the veins with anticoagulant therapy. Patients with splenomegaly who underwent laparoscopic splenectomy are at risk of thrombosis of the portal system and should undergo strict imaging surveillance and aggressive anticoagulation therapy.

Adolescent↗

Carcinoma of the neck showing thymic-like elements (CASTLE): report of a case and review of the literature.

Carcinoma showing thymic-like elements (CASTLE) is a rare tumor affecting thyroid and neck soft tissues, which has to be distinguished from squamous cell and anaplastic thyroid carcinoma, because it has a better prognosis. We report a new case of CASTLE which occurred in a patient submitted to total thyroidectomy with central neck dissection. The tumor stained positively for CD5, which seems to be the most useful marker in the differential diagnosis. By the analysis of the 18 cases reported in literature, total thyroidectomy with selective modified neck dissection should be the treatment of choice and radiotherapy should be considered for patients with positive nodal status.

Carcinoma, Squamous Cell↗

Gene expression in mouse spermatogenesis during ontogenesis.

In this study, we evaluated the expression of genes probably involved in spermatogenesis in the mouse. We examined cytosolic chaperonin theta subunit (CCTtheta), Ngg1 interacting factor 3 like 1 binding protein 1 (NIF3L1 BP1) and apolipoprotein H (ApoH) expression during mouse onto-geny using RT-PCR. Testicular tissue was obtained from mice 3, 6, 8, 10, 12, 14, 18, 20 and 40 (adult) days after birth. For each mouse, one testis was used for histological examination, whereas RNA was extracted from the controlateral testis for expression analysis. RT-PCR analysis showed that CCTtheta gene expression was low until day 10, but increased drastically afterwards. At this age, spermatocytes started to be present in the mouse testis. Therefore, CCT protein could be involved in chromatin packaging and remodeling during spermiogenesis, as also suggested by other studies. NIF3L1 BP1 expression increased steadily during ontogenesis reaching maximum levels in the adult mouse when all germ cell stages are present. This finding suggests that NIF3L1 BP1 is a gene not expressed by a specific germ cell type. ApoH expression was very low or absent during prepuberal stages, whereas it was detectable in the adult testis when spermatogenesis was completed. This suggests that ApoH may be involved in clearing apoptotic bodies during spermatogenesis since apoptotic events increase during spermatogenesis. This study contributes to understanding the role played by genes important for spermatogenesis.

Animals↗

A novel mutation of the DHCR7 gene in a sicilian compound heterozygote with Smith-Lemli-Opitz Syndrome.

INTRODUCTION: Smith-Lemli-Opitz syndrome (SLOS) is an autosomal recessive disorder of cholesterol biosynthesis, resulting from deficient 7-dehydrocholesterol reductase (3beta-hydroxysterol Delta7-reductase) activity, the enzyme responsible for conversion of 7-dehydrocholesterol to cholesterol. SLOS is most common among people of European descent, with a reported incidence of 1 per 20,000-60,000 newborns, depending on the diagnostic criteria and the reference population. More than 80 different mutations have been identified in several hundred patients. In Italy, SLOS appears to be a rare condition, probably because of underdiagnosis. METHOD: We analyzed by direct sequencing the 7-dehydrocholesterol reductase gene (DHCR7) in a Sicilian patient with Smith-Lemli-Opitz syndrome and his parents in order to characterize the molecular defect. RESULTS: The molecular analysis of the coding exons and the intron-exon boundaries of the DHCR7 gene demonstrated the presence of two missense mutations: a novel mutation (I251N) and a known mutation (E288K) responsible in a compound heterozygous state for a severe form of SLOS. CONCLUSION: The present study describes a Sicilian patient, a carrier of a novel mutation of the DHCR7 gene (I251N), which is responsible in a compound heterozygous state for a severe form of SLOS.

Heterozygote↗

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.

Adult↗

Bovine seminal ribonuclease is cytotoxic for both malignant and normal telomerase-positive cells.

Bovine seminal-ribonuclease (BS-RNase) is a member of the 'ribonucleases with special biological actions' family since it possesses specific anti-tumour, anti-spermatogenic and embryotoxic activities and exerts an immunosuppressive effect on T lymphocytes. In previous studies it was demonstrated that BS-RNase induced apoptosis in proliferating, malignant and normal cells and that telomerase activity loss also caused apoptotic death in neoplastic cells. Since an obvious relationship between cell proliferation and telomerase activity exists, the aim of this work was to study if the pro-apoptotic cytotoxic action exerted by BS-RNase on proliferating malignant cells (HT29) and proliferating normal cells (PHA-stimulated lymphocytes) could be linked to a possible BS-RNase effect on telomerase activity. In BS-RNase-treated HT29 cells (Na-butyrate-differentiated or not) and human lymphocytes (proliferating or not), we investigated cell vitality (MTT method) and morphology (SEM), BS-RNase localization (immunofluorescence), telomerase activity (TRAP-ELISA method), hTR mRNA expression (RT-PCR), and hTERT levels (western blot). While no BS-RNase effect was detectable on not proliferating cells, a clear relationship was noticed between the diminished number of vital elements of both proliferating cell populations after treatment (48 h and 72 h for HT29 and PHA-stimulated lymphocytes, respectively) with 50 microg/ml BS-RNase and the decrease of their telomerase activity. At the same time, we found that hTR levels, the RNA subunit of telomerase, in proliferation-inhibited BS-RNase-treated cells were diminished. Moreover, by immunofluorescence technique, we detected BS-RNase in the HT29 cell nucleolus after 3-h treatment. Therefore, as hTR has been recently proven to co-fractionate with nucleoli, we hypothesize that a BS-RNase direct action on the telomerase hTR subunit could be a possible mechanism of action by which BS-RNase exerts its pro-apoptotic effects only on proliferating cells.

Animals↗

Biological, histological, and clinical impact of preoperative IL-2 administration in radically operable gastric cancer patients.

BACKGROUND AND OBJECTIVES: Surgery induces lymphocytopenia and this decrease of host defenses, related to interleukin-2 (IL-2) endogenous imbalance during postoperative period could promote the proliferation of possible micrometastases and the implantation of surgically disseminated tumor cells. Moreover, tumor infiltrating lymphocytes (TILs), activated by endogenous IL-2 release, are linked to prognosis in cancer patients. The aim of this randomized study is to assess the biological (peripheral blood cells count, related to the grade of immunosuppression), histological (TILs), and clinical (overall and disease-free survival) impact of preoperative low doses administration of IL-2 in patients with radically operable gastric cancer. METHODS: This prospective study enrolled 69 consecutive patients with histologically proven gastric adenocarcinoma who underwent radical surgery from October 1999 to December 2002 (M/F 39/30; mean age 66; range 42-82) who underwent radical surgery from October 1999 to December 2000. Patients were randomized to be treated with surgery alone as controls (35 patients) or surgery plus preoperative treatment with recombinant human IL-2 (34 patients). 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, peritumoral stromal (fibrosis) reaction, neutrophils, lymphocytes, and eosinophils infiltration in tumor histology, and morbidity disease free and overall survival were evaluated. 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. In the control group 65% of patients had a decrease of CD4 under 500 cells/mmc. Instead it has been observed in IL-2 group a significant increase over the control group values of total lymphocytes and CD4 cells (14th total lymphocytes and CD4: IL-2 vs. control P < 0.05). Moreover in this group only 15% patients had CD4 under 500 cells/mmc. This difference, in CD4 count, is significant even at the 50th postoperative day (P = 0.006). IL-2 group showed lower postoperative complications (2/34 vs. 11/35; P < 0.05), and higher lymphocyte/eosinophil infiltration into the tumor (P < 0.0002). Median follow-up was 26 months (range 10-48) and median overall and disease-free survivals were longer, even if not significantly, in the IL-2 group than in the control arm (P = 0.07 and P = 0.06 respectively). CONCLUSIONS: This randomized 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). Furthermore IL-2 seems to have an impact on clinical course reducing morbidity of surgery and ameliorating overall and disease-free survival.

Adenocarcinoma↗

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.

Acute Disease↗

Melanoma metastatic to the gallbladder and small bowel: report of a case and review of the literature.

From post-mortem case records, the small bowel is the most frequent site of metastatic melanoma in the gastrointestinal (GI) tract, with gallbladder involvement occurring in 15% of cases. However, few cases have been documented in living patients and, when found, are associated with a poor prognosis. We report a case of a Caucasian man with metastatic gallbladder and small bowel melanoma from an unknown primary. He presented with diffuse abdominal pain, vomiting and progressive asthenia; subsequently, intestinal obstruction occurred. He had no past history of malignant melanoma and the primary lesion was not found. The multiple lesions, together with the absence of mucosal involvement in both the gallbladder and small bowel, led us to believe that the lesions were metastatic deposits from a probably regressed primary melanoma. It should be emphasized that surgical resection for melanoma metastatic to the GI tract is recommended for palliative reasons and can be performed safely. The clinical presentation, diagnosis, treatment and prognosis of previously reported cases of melanoma metastatic to the gallbladder and small bowel are reviewed. The differences between primary and secondary GI tract melanomas are also discussed.

Gallbladder Neoplasms↗

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.

Aged↗

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.

Adolescent↗

Safety of subcutaneous clodronate and efficacy in hypercalcemia of malignancy: a novel route of administration.

Bisphosphonates have become standard treatment in management of malignancy-induced hypercalcemia and malignant bone pain. One obstacle to the routine use of bisphosphonates in palliative patients is that oral bisphosphonates have low bioavailability and a degree of gastrointestinal toxicity that may explain poor compliance. Intravenous administration can be cumbersome in patients admitted to long-term care settings or at home. We have developed and tested a new way of administering clodronate via subcutaneous infusion. This retrospective cohort study evaluated 150 patients admitted to a tertiary palliative care unit from May 1996 to May 2000 who received 254 subcutaneous infusions of clodronate for hypercalcemia or bony complications. Data were collected by chart review and specifically evaluated site toxicity and biochemistry. There was minimal local toxicity and only 2 infusions needed to be discontinued because of pain at the subcutaneous site. Clodronate showed efficacy in normalizing the serum calcium within 5 days post-infusion in 32 of 43 infusions given for hypercalcemia. This study shows that subcutaneous clodronate is safe and can lower serum calcium levels in malignant hypercalcemia.

Analgesics, Non-Narcotic↗

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.

Adult↗

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.

Adolescent↗