Antonio Macrì

Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy as upfront therapy for advanced epithelial ovarian cancer: Multi-institutional phase-II trial

OBJECTIVE The primary end-point of this multi-institutional phase-II trial was to assess results in terms of overall survival after cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) in treatment-naive epithelial ovarian cancer (EOC) with advanced peritoneal involvement. Secondary end-points were treatment morbi-mortality and outcome effects of time to subsequent adjuvant systemic chemotherapy (TTC). METHODS Twenty-six women with stage III-IV EOC were prospectively enrolled in 4 Italian centers to undergo CRS and closed-abdomen HIPEC with cisplatin and doxorubicin. Then they received systemic chemotherapy with carboplatin (AUC 6) and paclitaxel (175 mg/m(2)) for 6 cycles. RESULTS Macroscopically complete cytoreduction was achieved in 15 patients; only minimal residual disease (≤2.5 mm) remained in 11. Major complications occurred in four patients and postoperative death in one. After a median follow-up of 25 months, 5-year overall survival was 60.7% and 5-year progression-free survival 15.2% (median 30 months). Excluding operative death, all the patients underwent systemic chemotherapy at a median of 46 days from combined treatment (range: 29-75). The median number of cycles per patient was 6 (range: 1-8). The time to chemotherapy did not affect the OS or PFS. CONCLUSIONS In selected patients with advanced stage EOC, upfront CRS and HIPEC provided promising results in terms of outcome. Morbidity was comparable to aggressive cytoreduction without HIPEC. Postoperative recovery delayed the initiation of adjuvant systemic chemotherapy but not sufficiently to impact negatively on survival. These data warrant further evaluation in a randomized clinical trial.

Attenuated Cerulein-Induced Pancreatitis in Nuclear Factor–κB–Deficient Mice

Nuclear factor (NF)-κB plays a central role in acute pancreatitis. We studied cerulein (CER)-induced pancreatitis in NF-κB knockout (KO) mice. NF-κB KO mice and normal control littermate wild-type (WT) mice were given four hyperstimulating doses of cerulein every hour to elicit secreatagogue-induced pancreatitis. Malonildialdehyde activity, glutathione levels, myeloperoxidase activity, TNF-α, and NF-κB binding activity and its inhibitory protein IκBα were studied in the pancreas. Furthermore, we measured plasma lipase and amylase and the histological damage. KO mice had reduced malonildialdehyde levels (WT + CER = 4.083 ± 0.95 μmol/g; KO + CER = 1.513 ± 0.63 μmol/g), decreased myeloperoxidase activity (WT + CER = 19.3 ± 2.39 mU/g; KO + CER = 10.21 ± 2.05 mU/g), increased glutathione levels (WT + CER 6.22 ± 2.46 μmol/g; KO + CER = 15. 516 ± 2.92 μmol/g), and reduced serum levels of amylase (WT + CER = 2519 ± 656.9 U/L; KO + CER = 916 ± 280.4 U/L) and lipase (WT + CER = 1420 ± 170 U/L; KO + CER = 861 ± 172. 3 U/L). KO mice showed reduced pancreatic NF-κB activation, decreased TNF-α tissue content, and reduced histologic alterations. Our data suggest that KO mice have an attenuated cerulein-induced pancreatitis and help to define the possible interaction between NF-κB activation and oxidative stress in this deleterious event.

Secondary cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for recurrent epithelial ovarian cancer: a multi-institutional study.

Please cite this paper as: Deraco M, Virzì S, Raspagliesi F, Iusco D, Puccio F, Macrì A, Famulari C, Solazzo M, Bonomi S, Grassi A, Baratti D, Kusamura S. Secondary cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for recurrent epithelial ovarian cancer: a multi‐institutional study. BJOG 2012;119:800–809.

Acute gallstone cholecystitis in the elderly: treatment with emergency ultrasonographic percutaneous cholecystostomy and interval laparoscopic cholecystectomy.

BackgroundThe treatment of acute cholecystitis in the elderly is still a subject of debate, particularly with reference to the timing of surgery and the role of laparoscopy.PatientsFrom January 1994 to June 2002 we observed 27 patients aged over 70 years with acute calcolous cholecystitis. The patients were submitted to ultrasonographic percutaneous cholecystostomy within 12 h of the acute attack. For two patients (7.4%) at high operative risk, we chose a conservative treatment. Twenty-five patients (92.6%) were submitted, in 15 cases (60%) within 5 days and in 10 patients (40%) within 8 days, to a laparoscopic cholecystectomy. Statistical significance was accepted when the value of p was less than 0.05.ResultsUltrasonographic percutaneous cholecystostomy was performed successfully in all patients, without major morbidity or mortality, and complete resolution of clinical symptoms was obtained within 48 h. The conversion rate of laparoscopy was 20% (13.3% in patients submitted to surgery within 5 days and 30% in the group submitted within 8 days — p > 0.05). The postoperative morbidity rate was 24%; it was higher (40% versus 15%) in patients converted to laparotomy (p > 0.05); mortality was 4%. The period of hospitalization was 11 days in patients operated laparoscopically and 21 days in those converted to open cholecystectomy (p < 0.001).ConclusionsThe more rational treatment of acute calcolous cholecystitis in elderly patients is represented by ultrasonographic percutaneous cholecystostomy followed, within 5 days, by laparoscopic cholecystectomy using an abdominal insufflation maximum to 12 mmHg and a limited 10–15° head-up tilt.

Serum levels of interleukin 1β, interleukin 8 and tumour necrosis factor α as markers of gastric cancer

Abstract Despite the efforts made, a serum marker reliable for the screening and follow-up of patients with gastric cancer has not yet been identified. The aim of this preliminary study was to test the role of pro-inflammatory cytokines interleukin 1β, interleukin 8 and tumour necrosis factor α in patients with gastric cancer and in control groups. The statistical analysis of cytokines serum levels in the group with gastric cancer versus control groups has shown considerable differences (p<0.001) in their mean rates. The results indicate that the cytokines interleukin 1β, interleukin 8 and tumour necrosis factor α might perhaps act as diagnostic markers in patients with gastric cancer. Therefore, it is hypothesized that after more extended trials, their use in the screening and prognostic assessment of these patients could be a possibility.

Lipid peroxidation inhibition reduces NF-κB activation and attenuates cerulein-induced pancreatitis

Increased lipid peroxidation, enhanced nuclear factor kappa-B (NF- s B) activation and augmented tumor necrosis factor- f (TNF- f ) production have been implicated in cerulein-induced pancreatitis. We investigated whether lipid peroxidation inhibition might reduce NF- s B activation and the inflammatory response in cerulein-induced pancreatitis. Male Sprague-Dawley rats of 230-250 g body weight received administration of cerulein (80 w g/kg s.c. for each of four injections at hourly intervals). A control group received four s.c. injections of 0.9% saline at hourly intervals. Animals were randomized to receive either raxofelast, an inhibitor of lipid peroxidation (20 mg/kg i.p. administered with the first cerulein injection) or its vehicle (1 ml/kg of a 10% DMSO/NaCl solution). All these rats were sacrificed 2 h after the last injection of either cerulein or its vehicle. Raxofelast administration (20 mg/kg i.p. with the first cerulein) significantly reduced malondialdehyde (MDA) levels, an index of lipid peroxidation (CER+DMSO=3.075 - 0.54 w mol/g; CER+raxofelast= 0.693 - 0.18 w mol/g; p <0.001 ), decreased myeloperoxidase (MPO) activity ( CER+DMSO=22.2 - 3.54 mU/g; CER+raxofelast=9.07 - 2.05 mU/g; p <0.01 ), increased glutathione levels (GSH) (CER+DMSO= 5.21 - 1.79 w mol/g; CER+raxofelast=15.71 - 2.14 w mol/g; p <0.001 ), and reduced acinar cell damage evaluated by means of histology and serum levels of both amylase ( CER+DMSO=4063 - 707.9 U/l; CER+raxofelast=1198 - 214.4 U/l; p <0.001 ), and lipase (CER+DMSO=1654 - 330 U/l; CER+raxofelast= 386 - 118.2 U/l; p <0.001 ), Furthermore, raxofelast reduced pancreatic NF- s B activation and the TNF- f mRNA levels and tissue content of mature protein in the pancreas. Indeed, lipid peroxidation inhibition might be considered a potential therapeutic approach to prevent the severe damage in acute pancreatitis.

Rare localizations of echinococcosis: personal experience

Background:  The rare localizations of hydatidosis represent an interesting topic, especially with reference to epidemiological and diagnostic problems. Hydatid disease, common in Mediterranean countries, still remains endemic in some regions of Italy.

Melanocortin 4 receptor stimulation decreases pancreatitis severity in rats by activation of the cholinergic anti-inflammatory pathway

Objective:Acute pancreatitis is an inflammatory condition that may lead to multisystemic organ failure. Melanocortin peptides have been successfully used in experimental models of organ failure and shock, and their protective effect occurs through the activation of a vagus nerve-mediated cholinergic anti-inflammatory pathway by acting at brain melanocortin 4 receptors. In the light of these observations, we studied the effects of the selective melanocortin 4 receptor agonist RO27-3225 in an experimental model of cerulein-induced pancreatitis. Design:Randomized experiment. Setting:Research laboratory at a university hospital. Subject:Experimental pancreatitis in rats. Interventions:Acute pancreatitis was induced in male Sprague-Dawley rats by intraperitoneal injections of cerulein (80 &mgr;g/kg, four injections at hourly intervals). Before pancreatitis induction, groups of animals were subjected to bilateral cervical vagotomy, pretreated with the nicotinic acetylcholine receptor antagonist chlorisondamine or the selective melanocortin 4 receptor antagonist HS024, or not pretreated. Thirty minutes after the first cerulein injection, rats were intraperitoneally treated with a nanomolar dose of RO27-3225 or vehicle. Some experimental groups were prepared for neural efferent activity recording along the vagus nerve starting 30 mins after treatment with RO27-3225 or vehicle, and for a 30-min period. Measurements and Main Results:Serum lipase and amylase activity, tumor necrosis factor-&agr; and interleukin-6 expression, pancreatic myeloperoxidase activity, and histologic damage were evaluated; neural efferent activity of vagal fibers was also assessed. RO27-3225 reduced cerulein-induced serum lipase and amylase activity, blunted the expression of tumor necrosis factor-&agr; and interleukin-6, abated the increase in pancreatic myeloperoxidase activity, and protected against histologic damage. Furthermore, RO27-3225 markedly increased neural efferent activity along the vagus nerve. Vagotomy, chlorisondamine, and HS024 abated these protective effects of RO27-3225. Conclusions:Our data show that melanocortin 4 receptor agonists reduce pancreatitis severity through the activation of the cholinergic anti-inflammatory pathway. These findings could be of particular interest in the clinical setting.

Ischemic Colitis Following Colonoscopy in a Systemic Lupus Erythematosus Patient: Report of a Case

BACKGROUNDIschemic colitis is an uncommon complication in patients with systemic lupus erythematosus but may be precipitated by colonoscopy.CASE REPORTA 43-year-old female with systemic lupus erythematosus under treatment with immunosuppressive drugs and prednisone was submitted to colonoscopy because of a change in bowel habit. Apart from the presence of a small metaplastic polyp, colonoscopy showed only a few erythematosus areas in the sigma and left colon. Four hours after colonoscopy, the patient developed lower colic abdominal pain and mucous diarrhea followed by rectal bleeding from ischemic colitis. The patient was successfully treated with fluids, spasmolytic drugs, sodic heparin, antibiotics and enteral feeding.CONCLUSIONSAwareness of the risk of this potential complication, secondary to colonoscopy, in patients with connective tissue disorders may lead to a prompt diagnosis and effective treatment, with a successful outcome.

Role of osteopontin in breast cancer patients

Aim and background In breast cancer, as in almost all neoplastic diseases, the prognosis is strictly related to the invasive capacity, local and distant, that characterizes the growth of all tumors. Since the mechanisms that regulate replication of the neoplastic cells, with consequent capacity to metastasize, are not completely known, identification of new markers represents the gold standard of research in the stratification of patients with such a pathology. Osteopontin, a specific phosphoglycoprotein isolated from extracellular bone matrix and actively involved in mechanisms of bone reabsorption, appears to play a key role in osteoclastogenesis at the level of the skeleton in some pathologic situations. It has been found that patients with metastatic bone lesions from breast or prostate cancer present, with respect to subjects without repetitive bone lesions, elevated serum levels of the protein, indicating that osteopontin could play an important role in the development and progression of the neoplastic disease at the bone level. Methods and study design The authors studied 26 patients with breast cancer, evaluating as a marker also serum osteopontin levels. Results and conclusions The results, although obtained on a small number of patients, showed that osteopontin evaluation in breast cancer patients can be a particularly interesting method of research in staging of the disease as well as in the prognosis, thereby attributing a role of a biotumoral marker also in the follow-up of the therapy.