Cytoreductive surgery plus bicavitary chemohyperthermia as treatment of pseudomixoma peritonei with pleural extension. A case report and review of the literature.

AIM: Intrathoracic extension in patients with pseudomixoma peritonei is a rare event, but spread of the tumour beyond the abdomen in to pleuropulmonary cavity has been reported. MATERIALS AND METHODS: We report a case of a 50-years-old woman with synchronous pleural manifestation of pseudomixoma peritonei by a mucinous ovarian cancer. During the abdominal cytoreductive surgery an extensive disease under the right hemidiaphragm was noted, requiring partial diaphragmatic resection. Once the pleural space was entered,mucinous neoplastic implants on the pleural surface was observed. The diaphragmatic defect was left open during the hyperthermic chemoperfusion to treat both the pleural and peritoneal surfaces. After a postoperative course uneventful she died after 6 months for a myocardial infarction, in presence of a left side pleural effusion with a positive cytology for high-grade malignant cells with a smear background contained wispy mucin. DISCUSSION: Despite the aggressive spread of the pseudomixoma peritonei within the peritoneal cavity, lymphatic and hematogenous metastasis are rare. However, extension of disease into pleuropolmonary cavity has been well described as pleural effusion or pleuropulmonary metastases. This is the first report in literature, to our knowledge, in which the thoracic extension is due to a mucinous ovarian cancer, and is the second case in which a simultaneous bicavitary hyperthermic chemoperfusion was done as a management option for thoracic extension of pseudomixoma peritonei. CONCLUSION: Due to the rarity of the thoracic involvement by pseudomixoma peritonei, its correct treatment is still unclear. Simultaneous cytoreductive surgery associated to intraoperative intraperitoneal and intrathoracic chemohyperthermia can be a potential therapeutic option for these patients.

Doppler perfusion index and colorectal hepatic metastases: personal experience and review of the literature.

BACKGROUND/AIMS: To evaluate the role of the hepatic perfusion in the assessment of the colorectal cancer. METHODOLOGY: 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. RESULTS: 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. CONCLUSIONS: A review of the literature and the results obtained in our study suggest that DPI may be helpful in detection of hepatic metastases.

Cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy in elderly patients.

BACKGROUND: The treatment of peritoneal malignancies in elderly patients with cytoreductive surgery (CRS) plus hyperthermic intraperitoneal chemotherapy (HIPEC) is an ongoing question due to the high associated surgical risk. PATIENTS AND METHODS: Thirty patients, 11 (36.7%) older than 65 years, were submitted to CRS plus HIPEC. Criteria of patient eligibility were: peritoneal carcinomatosis of different origin, T3-4 gastric cancer, ECOG performance status ≤2, no extra-abdominal extension and no evidence of bowel obstruction. The median follow-up was 21.5 months (range: 1-63). The purpose of this retrospective study, was to evaluate the feasibility of this approach in elderly patients, with special reference to postoperative morbidity, mortality and survival. RESULTS: We have recorded, in elderly patients, higher grade 3 and 4 morbidity and mortality, similar mean duration of cytoreductive surgery, of postoperative hospital stay, of median survival and of overall survival rates. CONCLUSION: Since there no statistical differences, in terms of morbidity and mortality, CRS with HIPEC may also be suitable for elderly patients.

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.

Peritoneal carcinomatosis of colorectal origin.

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.

[Gastrointestinal stromal tumour: our experience]. / I tumori stromali gastrointestinali (GIST): nostra esperienza.

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.

[Acute abdomen for perforated gastrointestinal stromal tumor (GIST). A case report]. / Addome acuto da GIST perforato del digiuno. Contributo clinico.

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.

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.

Volvulus due to a giant sigmoid diverticulum: a rare cause of intestinal occlusion.

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.

Acute acalculous cholecystitis during the course of primary Epstein-Barr virus infection: a new case and a review of the literature.

OBJECTIVE: The aim of this study was to describe a case of acute acalculous cholecystitis occurring in the course of primary Epstein-Barr virus (EBV) infection. METHODS: The clinical features of the case were analyzed and compared to those of three other similar cases reported in the international literature. RESULTS: All cases occurred in European females with cholestatic hepatitis, presented with gallbladder wall thickening, and recovered uneventfully without the need for surgical intervention. CONCLUSIONS: Acute acalculous cholecystitis may occur during the course of acute EBV infection, especially in patients with cholestatic hepatitis. Clinicians should be aware of the possible involvement of the gallbladder during EBV infection to avoid unnecessary invasive procedures or the overuse of antibiotics.

[Skin neuroendocrine carcinoma metastasis: a case report]. / Metastasi da carcinoma neuroendocrino della cute. Caso clinico.

BACKGROUND: Merkel cell carcinoma (MCC) is a rare and aggressive skin tumour with a highly malignant nature whose appropriate treatment is still debated. The Authors report a case of cutaneous metastasis from neuroendocrine carcinoma and analyse new diagnostic and therapeutic options of neoplasms that occurs in sun-exposed areas. METHODS: The authors present the clinical, immunocytochemical characteristic of primary and secondary skin localization of a neuroendocrine tumor that affected a woman. RESULTS: Histological and immunocytochemical analysis demonstrated that the secondary cutaneous localization appeared to be compared to the primary tumour. CONCLUSIONS: The case confirm the high incidence of regional metastasis; a wide surgical excision of tumor and regional lymphadenectomy is therefore recommended for primary treatment of MCC; the radiation treatment minimized the local recidives with long time survival.

Novel use of a T-tube access to perform an internal/external biliary drainage.

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.

Ischemic colitis following colonoscopy in a systemic lupus erythematosus patient: report of a case.

BACKGROUND: Ischemic colitis is an uncommon complication in patients with systemic lupus erythematosus but may be precipitated by colonoscopy. CASE REPORT: 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. CONCLUSIONS: 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.

Complex anal fistula surgery: personal experience.

Personal experience with the treatment cryptogenic complex anal fistulas over the 10-year period from 1993 to 2002 is reported. Such fistulas accounted for 54 out of 255 fistulas observed (21.1%). Accurate anatomo-pathological classification, based on the connections between the fistulas and the sphincter and the musculature of the pelvic floor, is mandatory, as is thorough preoperative evaluation of ano-rectal function and of the risk of faecal incontinence. The surgical strategies used, in relation to the different kinds of complex fistulas treated, are schematically reported. A mixed technique consisting in fistulectomy-fistulotomy with setons was particularly preferred, because of the risk related to immediate dissection of the sphincter, especially when concurrent risk factors are present. As regards the results obtained, the surgical outcome consisted in healing in 49/54 cases (90.7%) as against recurrence or persistence of the fistula in 5/54 (9.3%). Minor complications occurred in 6/54 (11.1%); no major complications were observed and no cases of permanent faecal incontinence were reported. In conclusion, the surgical choice in cases of complex fistulas must lead to definitive, radical treatment of the lesion, at the same time avoiding irreversible anal incontinence due to severe lesions to the sphincter.

Protective effects of SP600125 a new inhibitor of c-jun N-terminal kinase (JNK) and extracellular-regulated kinase (ERK1/2) in an experimental model of cerulein-induced pancreatitis.

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.

Attenuated cerulein-induced pancreatitis in nuclear factor-kappaB-deficient mice.

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.

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

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.