Prognostic value of specific KRAS mutations in patients with colorectal peritoneal metastases.

BACKGROUND: There is little evidence on KRAS mutational profiles in colorectal cancer (CRC) peritoneal metastases (PM). This study aims to determine the prevalence of specific KRAS mutations and their prognostic value in a homogeneous cohort of patients with isolated CRC PM treated with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy. MATERIALS AND METHODS: Data were collected from 13 Italian centers, gathered in a collaborative group of the Italian Society of Surgical Oncology. KRAS mutation subtypes have been correlated with clinical and pathological characteristics and survival [overall survival (OS), local (peritoneal) disease-free survival (LDFS) and disease-free survival (DFS)]. RESULTS: KRAS mutations occurred in 172 patients (47.5%) out of the 362 analyzed. Two different prognostic groups of KRAS mutation subtypes were identified: KRASMUT1 (G12R, G13A, G13C, G13V, Q61H, K117N, A146V), median OS > 120 months and KRASMUT2 (G12A, G12C, G12D, G12S, G12V, G13D, A59E, A59V, A146T), OS: 31.2 months. KRASMUT2 mutations mainly occurred in the P-loop region (P < 0.001) with decreased guanosine triphosphate (GTP) hydrolysis activity (P < 0.001) and were more frequently related to size (P < 0.001) and polarity change (P < 0.001) of the substituted amino acid (AA). When KRASMUT1 and KRASMUT2 were combined with other known prognostic factors (peritoneal cancer index, completeness of cytoreduction score, grading, signet ring cell, N status) in multivariate analysis, KRASMUT1 showed a similar survival rate to KRASWT patients, whereas KRASMUT2 was independently associated with poorer prognosis (hazard ratios: OS 2.1, P < 0.001; DFS 1.9, P < 0.001; LDFS 2.5, P < 0.0001). CONCLUSIONS: In patients with CRC PM, different KRAS mutation subgroups can be determined according to specific codon substitution, with some mutations (KRASMUT1) that could have a similar prognosis to wild-type patients. These findings should be further investigated in larger series.

In Vivo Confocal Microscopy Characterization of Candida parapsilosis Keratitis.

ABSTRACT: The present clinical case concerns two patients with mycotic keratitis because of Candida parapsilosis in which corneal confocal microscopy presented a characteristic feature of this pathogen. Both described patients used a therapeutic contact lens and administered a therapy with steroid eye drops which are well known predisposing factors for the onset of corneal mycoses. This report can be useful for correctly identifying the pathologic condition and quickly directing the therapy.

The role of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in the treatment of ovarian cancer relapse.

Nowadays the standard clinical management for advanced epithelial ovarian cancer is constituted by primary cytoreductive surgery associated to adjuvant systemic chemotherapy. Even if this first-line chemotherapy shows a high rate of complete responses, the disease recurrences occur especially in stage-III patients. Actually an option for this subset of patients is represented by secondary cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy that represents a promising therapy, having shown positive results in terms of median overall survival, progression free survival and overall survival. However, a much more research is still required especially by prospective randomised trials to improve outcomes in recurrent ovarian cancer.

Local repair of a trans-stomal ileocecal prolapse by stapler device.

The creation of a stoma, although considered a simple surgical procedure, is burdened by various complications, one of the most common being prolapse. Usually prolapse increases gradually, involving generally limited functional disorders and it can be well managed with non-operative measures. Occasionally it requires major surgery, for severe skin excoriation, bleeding or incarceration of the bowel. However, for critical clinical conditions of patients, often is not possible to use classical techniques, as bowel-pexy fixation or resection of the prolapse. Maeda has described a simple method for the correction of prolapse of the transverse colon using a stapler device that can be applied in this type of patients. In this report, we describe the first application of this technique to treat the prolapse of the ileocecal loop in an 81-year old woman, suffering from Parkinson's disease. A definitive ciecum stoma was performed the previous year for an Olgivie syndrome. At 6 months, follow-up showed no recurrence of prolapse with a functional stoma and without any skin irritation. In conclusion, this approach is recommended especially for high-risk patients who cannot be submitted to a much more invasive treatment. In fact, the main advantages consist of a minimally invasive technique, with minimal blood loss and with a rapid recovery of a normal quality of life.

Apoptotic-induced cleavage shifts HuR from being a promoter of survival to an activator of caspase-mediated apoptosis.

Little is known about the cellular mechanisms modulating the shift in balance from a state of survival to cell death by caspase-mediated apoptosis in response to a lethal stress. Here we show that the RNA-binding protein HuR has an important function in mediating this switch. During caspase-mediated apoptosis, HuR is cleaved to generate two cleavage products (CPs). Our data demonstrate that the cleavage of HuR switches its function from being a prosurvival factor under normal conditions to becoming a promoter of apoptosis in response to a lethal stress. In the absence of an apoptotic stimuli, HuR associates with and promotes the expression of caspase-9 and prothymosin α (ProT) mRNAs, and pro- and antiapoptotic factors, respectively, both of which have been characterized as important players in determining cell fate. During the early steps of caspase-mediated apoptosis, however, the level of caspase-9 protein increases, while ProT remains unchanged. Under these conditions, the two HuR-CPs selectively bind to and stabilize caspase-9 mRNA, but do not bind to ProT. Hence, taken together, our data show that by maintaining a threshold of expression of proapoptotic factors such as caspase-9 in response to a lethal stress, the HuR-CPs help a cell to switch from resisting death to undergoing apoptosis.

Whole lung lavage for pulmonary alveolar proteinosis after surgery for spontaneous pneumothorax.

INTRODUCTION: Pulmonary alveolar proteinosis (PAP) is a relatively rare lung disorder, probably under diagnosed, characterized by the accumulation of lipoproteinaceosus material in the lung alveoli. The primary (acquired or idiopathic) form occurs in more than 90% of all cases. Whole lung lavage is considered the golden standard of treatment. In this report, we describe a rare case of pulmonary alveolar proteinosis with severe and incapacitating respiratory, in which whole lung lavage followed the thoracotomy for spontaneous pneumothorax. CASE PRESENTATION: A 34-year-old white male patient presented at the respiratory intensive care with severe respiratory failure, aggravated in the last two months, cough, night sweats and important weight loss and left spontaneous pneumothorax. The initial diagnosis of diffuse interstitial pneumopathy was revised to Pulmonary Alveolar Proteinosis after bronchoalveolar lavage. Active pleural drainage of the pneumothorax was unsuccessful and after two months, surgical suture of the lung was performed under general anaesthesia. One month later a whole left lung lavage was performed. The same procedure was also performed on the right lung. Eight months later the patient had a good exercise tolerance, normal arterial blood gas (ABG) values, and persistent ground-glass opacities in some of the pulmonary segments on CT scan. CONCLUSIONS: The most severe forms of pulmonary alveolar proteinosis, in which hypoxemia and cyanosis occur, have a high mortality risk during anaesthesia and whole lung lavage. When a rare complication like spontaneous pneumothorax occurs, the suturing of the pulmonary apical blebs seems to be the only viable solution, despite the high risk of dehiscence of the sutures due to the poor pulmonary tissue integrity at the time of the whole lung lavage and during postoperative care.

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

OBJECTIVE: To assess the efficacy and morbidity and mortality of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) in recurrent epithelial ovarian cancer (EOC). DESIGN: A retrospective study conducted using information extracted from a multi-institutional prospective database on peritoneal surface malignancies (PSMs). Setting Four Italian centres specializing in locoregional treatment of PSM. POPULATION: Patients with recurrent EOC. METHODS: Fifty-six patients underwent 57 combined procedures. CRS was performed using peritonectomy procedures and HIPEC using the closed-abdomen technique with cisplatin and doxorubicin or cisplatin and mitomycin-C. MAIN OUTCOME MEASURES: Overall survival (OS), progression-free survival (PFS), morbidity and mortality rates. RESULTS: The median age of the patients was 55.2 years (range 30-75 years). The median peritoneal cancer index was 15.2 (range 4-30). Forty-seven patients had microscopic residual disease (completeness of cytoreduction, CC-0), seven had residual disease ≤2.5 mm (CC-1) and one had residual disease >2.5 mm (CC>2). Major complications occurred in 15 patients (26.3%), and procedure-related mortality occurred in three patients (5.3%). The median follow-up time was 23.1 months. The median OS and PFS were 25.7 (95% CI 20.3-31.0) and 10.8 (95% CI 5.4-16.2) months, respectively. The 5-year OS and PFS were 23% and 7%, respectively. Independent prognostic factors affecting OS according to the multivariate analysis were Eastern Cooperative Oncology Group performance status, preoperative serum albumin, and completeness of cytoreduction. CONCLUSIONS: Patients with recurrent EOC treated with CRS and HIPEC showed promising results in terms of outcome. The combined treatment strategy could benefit subsets of patients wider than that defined for conventional secondary debulking surgery without HIPEC. These data warrant further evaluation in randomised clinical trials.

[Intestinal perforation by ingested foreign bodies in the digestive tract: an insidious pathology always of interest. Our experience]. / La complicanza perforativa da ingestione di corpi estranei alimentari: una patologia insidiosa sempre attuale. Nostra esperienza.

The authors want to present five cases (from May 1999 to May 2009) of acute abdomen from perforation of the foreign body introduced with food. They highlight how the accidental ingestion is very common but the perforation is rare. The preoperative diagnosis, in these cases, is always very difficult and the radiological examinations are not always able to resolve the diagnostic doubt with other acute intestinal diseases that are responsible of perforation. Then, the surgery procedure is, necessarily, the only possible diagnostic and therapeutic means. The mortality and the morbidity remain still high first of all for the delay in the diagnosis and the advanced age of patients.

Detection of Mycobacterium tuberculosis resistance mutations to rifampin and isoniazid by real-time PCR.

OBJECTIVE: The objective of our study was to evaluate the use of a real-time polymerase chain reaction (PCR)-based technique for the prediction of phenotypic resistance of Mycobacterium tuberculosis. MATERIALS AND METHODS: We tested 67 M tuberculosis strains (26 drug resistant and 41 drug susceptible) using a method recommended for the LightCycler platform. The susceptibility testing was performed by the absolute concentration method. For rifampin resistance, two regions of the rpoB gene were targeted, while for identification of isoniazid resistance, we searched for mutations in katG and inhA genes. RESULTS: The sensitivity and specificity of this method for rapid detection of mutations for isoniazid resistance were 96% (95% CI: 88% to 100%) and 95% (95% CI: 89% to 100%), respectively. For detection of rifampin resistance, the sensitivity and specificity were 92% (95% CI: 81% to 100%) and 74% (95% CI: 61% to 87%), respectively. The main isoniazid resistance mechanism identified in our isolates is related to changes in the katG gene that encodes catalase. We found that for rifampin resistance the concordance between the predicted and observed phenotype was less than satisfactory. CONCLUSIONS: Using this method, the best accuracy for genotyping compared with phenotypic resistance testing was obtained for detecting isoniazid resistance mutations. Although real-time PCR assay may be a valuable diagnostic tool, it is not yet completely satisfactory for detection of drug resistance mutations in M tuberculosis.

Massive bleeding from a Dieulafoy's lesion of the duodenum successfully treated with "adjuvant" transarterial embolization and endoscopic laser coagulation.

Dieulafoy's lesions, very rare in the duodenum, are considered uncommon causes of gastrointestinal bleeding and occur from pinpoint non-ulcerated arterial lesions. We report a case of Dieulafoy's lesion of the duodenum, in which a first diagnostic approach by using endoscopy and angiography was not successful; then, due to a high operative risk, we performed an "adjuvant" embolization of the gastroduodenal artery with the aim of reduce the flow through the artery, allowing the endoscopic localization of the site of bleeding and subsequent effective treatment. To our knowledge, this is the first case reported in the literature, in which, without aetiological diagnosis, an "adjuvant" embolization of the gastroduodenal artery was performed with the aim of reduce the blood flow in the duodenal wall, permitting an easier endoscopic diagnosis of Dieulafoy's duodenal lesion and successful treatment with laser coagulation.

Quintuple primitive malignant neoplasms. A case report.

The authors describe the case of a patient who developed during 31 months, five malignant tumours, three synchronous and two metachronous. The primitive origin and the long interval of time between the occurrence of each tumour, allow to set them in the group of Multiple Primitive Malignant Neoplasm. The authors, reviewing the classifications and the pathogenesis of these tumours, underline the importance of the follow-up in oncology patients and emphasize the role of nosographic setting in order to plan the most suitable therapeutic approach.

CD81 expression on CD19+ peripheral blood lymphocytes is associated with chronic HCV disease and increased risk for HCV infection: a putative role for inflammatory cytokines.

The level of CD81 cell surface expression, a cellular co-receptor for hepatitis C virus (HCV), is critical for productive HCV infection of host cells. In addition, the cross-linking of HCV-E2 protein to CD81 can alter the function of T and B lymphocytes as well as that of NK cells by interfering with the activation signalling pathway. The down-regulation of CD81 expression on peripheral blood lymphocytes (PBL) has been associated to effective therapy of HCV infection. The aim of the present study is to quantitatively assess the levels of CD81 expression in PBL from HCV-infected patients compared to subjects at high risk for HCV infection such as HIV-infected individuals or patients with Porphyria Cutanea Tarda (PCT). The expression of CD81 was quantified by flow-cytometry using Phycoerythrin-labelled standard beads. Determination of CD81 was performed on CD3+ and CD19+ lymphocytes from 34 healthy controls, 51 patients with HCV infection and different clinical outcomes [these included HCV-RNA-negative subjects (8), patients with chronic active hepatitis (16), recipients of liver transplantation under immunosuppressive therapy (12), a subgroup with concomitant HIV infection (9) or concomitant PCT (6)]. In addition, 60 HIV-infected subjects and 4 patients with PCT were studied. The putative role of inflammatory cytokines in modulating CD81 was explored in vitro by assessing the effect of IL-6 or IFN-gamma on cultured human hepatocytes. A significant increase of the CD81 expression was found on CD19+ lymphocytes in association with either HIV or HCV infection, as compared to the control group. Immunosuppressive therapy with FK506, subsequent to liver transplantation, restored CD81 expression at normal levels. Data gathered in vitro using the WRL 68 hepatocytic cell line confirmed that inflammatory cytokines can up-regulate CD81 expression in liver cell inclusion. Our data suggest that CD81 up-regulation can increase the risk of HCV infection, particularly in HIV-infected subjects. In addition, the results strongly suggest that the cytokines released by activated lymphocytes at sites of inflammation may play a part in up-regulating CD81 expression.

Association between porphyria cutanea tarda and beta-thalassemia major.

The paper describes the first two cases of porphyria cutanea tarda associated with beta-thalassemia major. The clinical course of two female patients affected by beta-thalassemia major was complicated by the onset of porphyria cutanea tarda. Both patients were also suffering from hepatitis C virus infection, iron overload and anemia. We discuss about the role performed by some of these conditions in triggering overt porphyria cutanea tarda. An improvement of the clinical and biochemical picture of porphyria cutanea tarda in both patients was obtained with chloroquine therapy given that their chronic anemia did not permit phlebotomy.

Evaluation of quality of life of patients submitted to cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for peritoneal carcinosis of gastrointestinal and ovarian origin and identification of factors influencing outcome.

BACKGROUND: The prognosis of patients with peritoneal tumors has been improved by the association of cytoreductive surgery with hyperthermic intraperitoneal chemotherapy, though still with an unclear impact on patients' quality of life. The purpose of our study was to evaluate the quality of life in 18 cases submitted to cytoreductive surgery and hyperthermic intraperitoneal chemotherapy and particularly to identify the factors that influence it. PATIENTS AND METHODS: Quality of life was evaluated using the functional assessment of cancer therapy; the results were correlated with 25 parameters. RESULTS: The study demonstrated that the patients'quality of life was not modified by treatment with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy; the dose of mitomycin C, the site of the primary tumor, gastrointestinal, renal and neurological toxicity, adjuvant chemotherapy, the patients' age and leukopenia were factors that influenced the quality of life. CONCLUSION: Cytoreductive surgery with hyperthermic intraperitoneal chemotherapy allows conservation of preoperative quality of life.

Four novel mutations of the coproporphyrinogen III oxidase gene.

Here we report the characterization of four novel mutations and a previously described one of the coproporphyrinogen III oxidase (CPO) gene in five Italian patients affected by Hereditary Coproporphyria (HCP). Three of the novel genetic variants are missense mutations (p.Gly242Cys; p.Leu398Pro; p.Ser245Phe) and one is a frameshift mutation (p.Gly188TrpfsX45).

Excretion profile of boldenone and its metabolites after oral administration to veal calves.

The residue profiles of boldenone (17beta-Bol), its epimer (17alpha-Bol) and the related compound androsta-1,4-diene-3,17-dione (ADD), were investigated by liquid chromatography-tandem mass spectrometry (LC-MS/MS) in urine of male calves orally treated with boldenone, boldenone esters, and/or ADD. In all the experiments with the administered steroids residues of 17alpha-Bol decreased rapidly after end of treatment; detectable amounts of 17alpha-Bol were however noticed along the withdrawal observation period after end of treatment. Differently, residues of 17beta-Bol were detectable only shortly after administration. This in vivo research concerning oral treatments of cattle with boldenone related substances proves ADD to be a very active boldenone precursor in bovine animals.

[Multiple primitive lipoma of the transverse mesocolon: a rare disease]. / Lipoma primitivo multiplo del mesocolon: una patologia rara.

The Authors describe a case of multiple lipomatosis of the mesocolon and, after a careful review of the literature, they examine particular findings and discuss diagnostic difficulties, anatomopathological features and treatment. Intraabdominal lipoma is very rare and presents difficulties in diagnosis, both for aspecific symptoms and for the unusual site which does not allow early identification. As it is a tumor which arises from primitive and totipotent mesenchymal cells, radical surgery is the only therapeutic option. The correct diagnosis depends on histological testing which can differentiate the lesion from other mesenchymal tumors.