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ABSTRACT: The evolution of loco-regional treatments has occurred in the last two decades and has deeply changed the natural history of primitive and secondary peritoneal surface malignancies. Several phase II-III studies have proved the effectiveness of the combination of cytoreductive surgery with peritoneal chemohyperthermia. Cytoreductive surgery allows the reduction of the neoplastic mass and increases tumoral chemosensitivity. The development of chemohyperthermia finds its origins in the necessity to exceed the limits of intraperitoneal chemotherapy performed in normothermia. It permits a continuous high concentration gradient of chemotherapeutic drugs between the peritoneal cavity and the plasma compartment to and a more uniform distribution throughout the abdominal cavity compared to systemic administration.
World journal of gastrointestinal oncology. 12/2011; 3(12):169-74.
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ABSTRACT: 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).
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.
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.
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.
Gynecologic Oncology 06/2011; 122(2):215-20. · 3.89 Impact Factor
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ABSTRACT: Favorable oncological outcomes have been reported in several trials with the introduction of Cytoreductive Surgery (CRS) and Hyperthermic Intraperitoneal Chemotherapy (HIPEC) in the treatment of Advanced Epithelial Ovarian Cancer (EOC). However most of the studies testing the combined approach are observational and have been conducted in inhomogeneous series so that the evidence supporting the performance of this combined treatment is still poor. Median Overall and Disease Free Survivals of up to 64 months and 57 months, respectively have been reported. Although a rate of morbidity of up to 40% has been observed in some series the CRS + HIPEC continues to gain an increased popularity. Several prospective randomized trials are ongoing using the procedure in various time points of the disease. In this review several issues such as the impact of cytoreduction and residual disease (RD) on outcomes as well as the role of HIPEC will be updated from the literature evidence. Some controversial points HIPEC related will also be discussed. Recent experiences regarding the introduction of a more aggressive surgical approach to upper abdomen to resect peritoneal carcinomatosis (PC) allowed increased rates of optimal cytoreduction and has demonstrated an apparent better outcome. This evidence associated with the positive results phase III trial testing normothermic intraperitoneal as first-line chemotherapy is guiding some investigators to propose the CRS + HIPEC in the primary setting. Several prospective phase II and III trials have recently been launched to validate the role of the combined treatment in various time points of disease natural evolution.
European journal of surgical oncology: the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology 01/2011; 37(1):4-9. · 2.56 Impact Factor
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Letteria Minutoli,
Francesco Squadrito,
Piero Antonio Nicotina,
Daniela Giuliani,
Alessandra Ottani,
Francesca Polito,
Alessandra Bitto,
Natasha Irrera,
Giuseppe Guzzo,
Luca Spaccapelo,
Carmine Fazzari, Antonio Macrì,
Herbert Marini,
Salvatore Guarini,
Domenica Altavilla
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ABSTRACT: 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.
Randomized experiment.
Research laboratory at a university hospital.
Experimental pancreatitis in rats.
Acute pancreatitis was induced in male Sprague-Dawley rats by intraperitoneal injections of cerulein (80 μg/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.
Serum lipase and amylase activity, tumor necrosis factor-α 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-α 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.
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.
Critical care medicine 01/2011; 39(5):1089-96. · 6.37 Impact Factor
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ABSTRACT: Peritoneal carcinomatosis is, after liver metastases, the second most frequent cause of death in colorectal cancer patients and at the present time, is commonly inserted and treated as a stage IV tumour. Because there is no published data that outlines the impact of new therapeutic regimens on survival of patients with peritoneal surface diffusion, the story of carcinomatosis can be rewritten in light of a new aggressive approach based on the combination of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy. Also if these treatment perhaps allow to obtain better results than standard therapies, we suggest, that a large prospective randomised control trial is needed to compare long-term and progression-free survival under the best available systemic therapy with or without cytoreductive surgery and hyperthermic intraperitoneal chemotherapy.
World journal of gastrointestinal oncology. 02/2010; 2(2):98-101.
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Antonio Macrì
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ABSTRACT: Peritoneal surface malignancies (PSM) are a clinical entity with an unfavourable prognosis. They comprise peritoneal carcinomatosis, pseudomyxoma peritonei, and primitive tumors of the peritoneum. Because the treatment of PSM presents unique and challenging problems to the cancer clinician, many new approaches have been attempted in recent years. In the current and next issues of World Journal of Gastrointestinal Oncology, some international groups of researchers discuss the most important and innovative aspects of PSM treatment, with particular accuracy for cytoreductive surgery and hyperthermic intraperitoneal chemotherapy. In conclusion, because this new approach to PSM has a reputation for being based more on common sense than on experimental data, I hope that highlighting this topic can make a contribution to the treatment of this group of diseases.
World journal of gastrointestinal oncology. 01/2010; 2(1):9-11.
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Acta Obstetricia Et Gynecologica Scandinavica 06/2008; 80(10):967 - 969. · 1.77 Impact Factor
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ABSTRACT: 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.
In the period April 1983-October 2003 73 patients with hydatid disease were observed.
Seven patients (9.5%) presented a primary rare localization (thyroid, kidney, sacrospinal muscle, peritoneum and spleen). The main peculiarity of primary rare hydatidosis localizations concerns diffusion of the infecting embryo; the most reliable hypothesis is that liver and lung can be bypassed through precapillary anastomosis between pre- and post-parenchymal circulation. The new imaging techniques allow a correct topographic evaluation and so a radical surgical treatment. The chemotherapy, complementary to surgery, produced degenerative modifications of parasite in 75.8% of the present cases and reduction of recurrence from 23.3% to 6.7%. At follow up of 1-5 years no patients had recurrence.
It is important to be aware, especially in countries where echinococcosis is endemic, that it is possible to find an echinococcosis cyst in a rare localization.
ANZ Journal of Surgery 12/2005; 75(11):986-91. · 1.25 Impact Factor
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ABSTRACT: We report a case of post-surgical temporary functional stenosis of the sphincter of Oddi and biliary leak in a patient with a previous Billroth II reconstruction who had undergone cholecystectomy, surgical choledochotomy and sphincterotomy for biliary calculi. The patient was treated by creation of an internal/external biliary drainage using the T-tube access with an unreported technique.
European Radiology 11/2005; 15(10):2200-2. · 3.22 Impact Factor
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ABSTRACT: Ischemic colitis is an uncommon complication in patients with systemic lupus erythematosus but may be precipitated by colonoscopy.
A 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.
Awareness 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.
Diseases of the Colon & Rectum 05/2005; 48(4):866-9. · 3.13 Impact Factor
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Letteria Minutoli,
Domenica Altavilla,
Herbert Marini,
Maria Passaniti,
Alessandra Bitto,
Paolo Seminara,
Francesco S Venuti,
Ciro Famulari, Antonio Macrì,
Antonino Versaci,
Francesco Squadrito
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ABSTRACT: Extracellular regulated kinases (ERK1/2) and c-Jun N-terminal Kinases (JNK), are generally considered to play a key role in signal transduction pathways activated by a wide range of stimuli. We studied the effects of SP600125, a novel inhibitor of both JNK and ERK1/2, in male C57/BL6 mice given with an hyper-stimulating dose of cerulein (50 microg/kg for each of four injections at hourly intervals) to elicit secretagogue-induced pancreatitis. A control group received four intra-peritoneal injections of 0.9% saline at hourly intervals. Animals were randomized to receive either SP600125 (15 mg/kg i.p. administered 2 h before and 30 min after the first injection of cerulein) or its vehicle (1 ml/kg of a 10% DMSO/NaCl solution). A group of animals was killed 30 minutes after the last cerulein injection to evaluate pancreatic JNK and ERK1/2 activation by Western Blot analysis. Another group was sacrificed 2 hours after the last cerulein injection to evaluate serum lipase and amylase levels, pancreas oedema, pancreatic content of Tumor Necrosis Factor-alpha (TNF-alpha) and Intercellular adhesion molecule-1 (ICAM-1) and the histological alterations. SP600125 inhibited almost totally JNK activation (90%) and partially ERK1/2 activation (45%), reduced the serum lipase and amylase levels and the degree of oedema, blunted the increased pancreatic content of TNF-alpha and ICAM-1 and protected against the histological damage. Our data confirm that both JNK and ERK1/2 activation plays a key role in acute pancreatitis and that SP600125 may represent a potential therapeutic approach to the treatment of patients at high risk of developing this life-threatening condition.
Life Sciences 11/2004; 75(24):2853-66. · 2.53 Impact Factor
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Domenica Altavilla,
Ciro Famulari,
Maria Passaniti,
Mariarosaria Galeano, Antonio Macrì,
Paolo Seminara,
Letteria Minutoli,
Herbert Marini,
Margherita Calò,
Francesco S Venuti,
Maria Esposito,
Francesco Squadrito
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ABSTRACT: Nuclear factor (NF)-kappaB plays a central role in acute pancreatitis. We studied cerulein (CER)-induced pancreatitis in NF-kappaB knockout (KO) mice. NF-kappaB 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-alpha, and NF-kappaB binding activity and its inhibitory protein IkappaBalpha 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 micromol/g; KO + CER = 1.513 +/- 0.63 microol/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 micromol/g; KO + CER = 15. 516 +/- 2.92 micromol/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-kappaB activation, decreased TNF-alpha 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-kappaB activation and oxidative stress in this deleterious event.
Laboratory Investigation 01/2004; 83(12):1723-32. · 3.64 Impact Factor
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Domenica Altavilla,
Ciro Famulari,
Maria Passaniti,
Giuseppe M Campo, Antonio Macrì,
Paolo Seminara,
Herbert Marini,
Margherita Calò,
Letterio B Santamaria,
Daniela Bono,
Francesco S Venuti,
Chiara Mioni,
Sheila Leone,
Salvatore Guarini,
Francesco Squadrito
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ABSTRACT: Increased lipid peroxidation, enhanced nuclear factor kappa-B (NF-kappaB) activation and augmented tumor necrosis factor-alpha (TNF-alpha) production have been implicated in cerulein-induced pancreatitis. We investigated whether lipid peroxidation inhibition might reduce NF-kappaB activation and the inflammatory response in cerulein-induced pancreatitis. Male Sprague-Dawley rats of 230-250g body weight received administration of cerulein (80 microg/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 micromol/g; CER + raxofelast = 0.693 +/- 0.18 micromol/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 micromol/g; CER + raxofelast = 15.71 +/- 2.14 micronol/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-kappaB activation and the TNF-alpha 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.
Free Radical Research 05/2003; 37(4):425-35. · 2.88 Impact Factor
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International Journal of Colorectal Disease 02/2002; 17(1):61-2. · 2.38 Impact Factor
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ABSTRACT: The spillage of gallstones into the peritoneal cavity from iatrogenic perforation of the gallbladder that occurs during laparoscopic cholecystectomy can result in late and serious complications. We report a case of vesical granuloma with symptoms of dysuria, pollakiuria, and vesical tenesmus that occurred 23 months after a laparoscopic cholecystectomy. Preoperative diagnostic evaluation showed a 3-cm vesical neoformation. A partial cystectomy was performed; macroscopic and histologic examination documented a central nidus of fragmented gallstones and a picture of chronic granulomatous inflammation. Although complications related to unretrieved gallstones that spill into the peritoneal cavity during laparoscopic cholecystectomy are rare, they are being reported with increasing frequency. Therefore, it is important to use tools and techniques that prevent lacerations of the gallbladder and involve retrieval of spilled gallstones.
Surgical laparoscopy, endoscopy & percutaneous techniques 11/2001; 11(6):368-371. · 1.23 Impact Factor
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ABSTRACT: The case of a giant sigmoid diverticulum complicated by a volvulus of the bowel is reported. After an exhaustive literature review, the Authors analyse the aetiopathogenetic, physiopathological and clinical aspects of this rare condition, considering its diagnostic and therapeutic implications. The Authors describe surgical problems and therapeutic management, pointing out that without an accurate study by radiological imaging, it is very difficult to diagnose the condition, particularly when no specific symptoms have been observed.
Chirurgia italiana 60(3):487-91.
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ABSTRACT: 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.
The authors studied 26 patients with breast cancer, evaluating as a marker also serum osteopontin levels.
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.
Tumori 95(1):48-52. · 0.86 Impact Factor
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ABSTRACT: Gastrointestinal stromal tumours (GISTs) are the most common mesenchymal neoplasms of the gastrointestinal tract. These tumours originate in Cajal interstitial cells and the majority are located in the stomach and small intestine. They frequently develop in males aged 50-60 years. The symptoms of GIST are non-specific and depend on the size and location of the lesion. Imaging difficulties impede an early diagnosis; sometimes these tumours represent an unexpected intraoperative finding or an emergency abdominal picture. GISTs are classified as tumours with low- and high-risk of malignancy, depending on tumour size and mitotic count. Tumour site and acute onset are also significant parameters for prognostic purposes. Fifteen patients with GIST - gastric in 7 cases, ileal in 6, jejunal in 1 and colonic in 1 - were treated surgically and, in 9 cases, with adjuvant therapy (chemotherapy in 4 patients and imatinib mesylate in 5). The mean follow-up was 38 months. No postoperative mortality was recorded, and the morbidity was 13.3%. Histological examinations documented 6 benign tumours and 9 malignancies. Two patients, one with gastric and one with colonic GIST, were lost to follow-up. One patient, with two synchronous gastric neoplasms (GIST + adenocarcinoma) died after 16 months, while the other 5 patients with gastric GIST are still alive; two patients with ileal GIST, treated with chemotherapy, died after 15 and 18 months, respectively. The mean survival of patients treated with imatinib mesylate was 36 months. Surgical management and the use of imatinib constitute the therapeutic gold standard for GIST. The use of imatinib mesylate is recommended today in the treatment of advanced GIST, especially in cases with liver and peritoneal metastases.
Chirurgia italiana 61(2):161-9.
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ABSTRACT: The authors report on a case of voluminous perforated gastrointestinal stromal tumor (GIST) of small intestine and make a review to the light of most recent clinicopathologic advancements. The first clinical manifestation as acute abdomen due to their perforation extremely rare. Gastrointestinal stromal tumor (GIST) represent a rare group of multiform tumors with various biological behaviour. Were identified in the past as leiomyomas, leiomyosarcomas or leiomyoblastomas, has been reclassified on immunochemical features, with a positive expression of Kit (CD117 antigen). Traditionally the prognostic factors of these tumour are: mitotic rate, tumor size and anatomic site. The complete surgical resection and use of imatinib mesylate (Gleevec) are the best available approach.
Annali italiani di chirurgia 80(1):69-73. · 0.23 Impact Factor
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ABSTRACT: To evaluate the role of the hepatic perfusion in the assessment of the colorectal cancer.
For this research 18 patients affected by colorectal cancer were enrolled. All the patients were submitted to the evaluation of the Doppler Perfusion Index (DPI) which represents the ratio of hepatic arterial to total liver blood flow.
The correlation between the evaluation of the Doppler Perfusion Index and the occurrence of the liver metastases did not show false negative but has highlighted 6 false positive, achieved a good sensitivity and very low specificity.
A review of the literature and the results obtained in our study suggest that DPI may be helpful in detection of hepatic metastases.
Hepato-gastroenterology 59(115):731-3. · 0.66 Impact Factor
