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.

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.

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.

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.

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.

[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.

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.

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).

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.

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

BACKGROUND: The 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. PATIENTS: From 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. RESULTS: Ultrasonographic 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). CONCLUSIONS: The 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 degrees head-up tilt.

[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.

Hemorrhage from primitive rectal varices in patient with idiophatic thrombosis of portal vein: case report.

INTRODUCTION: Rectal varices, primitive or secondary to hypertensive or thrombotic disorders of mesenteric-portal circle, represent an uncommon cause of lower digestive bleeding. The presence of rectal varices associated to idiopathic venous portal thrombosis represents a distinct nosologic entity, with important clinical and therapeutic problems related to it. CASE REPORT: Patient of young age, with positive anamnesis for primitive rectal varices, admitted to our department for a serious recttorragy. The laboratory underlined moderate anaemia and the endoscopy documented the presence of multiple rectal varices, without evident signs of bleeding; the endoscopy documented the presence of two esophageal small varicose cords F1. The hepatobiliary sonography and the portography showed the massive thrombosis of the portal vein. The new serious episode of rectal bleeding induced us to subject the patient to a surgical operation of Hartmann recto-sigmoid resection. CONCLUSION: Because of the slight number of reported cases of primitive rectal varices and because of the scattering of many dates it is difficult to draw an univocal diagnostic and therapeutic algorithm. Clinical framing and subsequent therapeutic approach rise often up from personal experience rather than well defined guidelines. The treatment is controversial, time by time many therapeutic options are reported either conservative or interventionist. The failure of conservative therapy and the recurrent episodes of bleeding give indication to surgical treatment, that is represented by Hartmann colonic resection and/or the porto-systemic shunts in the cases of portal hypertension; in our case we made colonic resection sec. because of lapsed performing status of the patient.

[Endoscopic prosthetic treatment of the esophagojejunal leaks after total gastrectomy: clinical experience]. / Il trattamento endoscopico protesico delle fistole anastomotiche esofago-digiunali dopo gastrectomia totale per cancro dello stomaco: esperienza clinica.

The Authors, on the basis of their experience on the use of self-expanding prostheses in abdominal surgery, report on the use of these prostheses in two patients who, having undergone a gastrectomy for cancer, developed a fistula of the esophago-jejunal anastomosis. Given recent data from literature, using a prosthesis for an anastomotic fistula may be a valid alternative to a second operation, which, apart from obvious difficulties, has a high mortality rate in patients in weakened general health conditions. In these cases, after the application of a stent, excellent results can be obtained and, after some days, the patients can begin a semi-liquid diet, then proceeding to a semi-solid diet, improving quality of life; in addition, within a reasonable time span, after the healing of the fistula, the prosthesis can easily be removed by endoscopy.

Inhibition of amylases from different origins by albumins from the wheat kernel.

The amylase activity of water extracts from 18 insect species, from 23 marine species and from 17 different species of birds and mammals was determined quantitatively. The inhibition of amylase in these extracts by three albumin fractions from the mature wheat kernel, which had been separated according to their molecular weights (60 000, 24 000 and 12 500 D), was determined as well. The inhibition activity of the three albumin fractions toward amylases extracted from a number of cereal species or from immature and germinating wheat kernel was also tested. The extracts from insects that are destructive of wheat grain and stored wheat products showed much higher amylase activities as compared to the other insect species that do not attack wheat and wheat products. On the basis of the effectiveness with which the three albumin fractions inhibit their activities, the amylase preparations tested were divided into susceptible, partially susceptible and resistent. Susceptible amylases, inhibited by any of the three albumin fractions, were found mainly in insects that attack wheat and in marine species. Partially susceptible amylases, inhibited by only one or two of the three albumin fractions, were present in a few avain and mammalian species including man. Resistent amylases were largely distributed in cereal, avian and mammalian species as well as in insect species that do not usually attack wheat grain or wheat flour products. At no stage of development, wheat alpha-amylase was inhibited by the albumin fractions from the mature kernel. The 12 500 dalton albumin fraction was the most effective in inhibiting insect amylases, but it was inactive toward avian and mammalian amylases. The 24 000 dalton albumin fraction was the most effective in inhibiting amylases from marine avian and mammalian species and inhibited as much as 33 amylases over 66 different amylases tested. It is suggested that protein inhibitors of amylase contributed to natural selection of polyploid wheats by giving some insect resistence to such wheats, even though some insect species were able to overcome this biochemical defense toa large degree by producing higher amylase activities.

[Caroli's disease: literature review and characteristics of a clinical case]. / La malattia di Caroli: revisione della letteratura e particolarità di un caso clinico.

The Author's report the case of the simple form of Caroli's disease, a rare malformation, and review literature pointing out the difficulty of an early diagnosis, because disease can be silent for a long time too and it is identified for complication. Today, imaging, endoscopy and interventionist radiology are the most valid tools for a correct diagnosis and treatment, above all in a case of emergency, when other therapeutic solutions are not possible.

[Diagnostic and therapeutic implications in two cases of pancreatic cystic tumours: mucinous and serous]. / Implicazioni diagnostiche e terapeutiche in due casi di tumori cistici del pancreas: mucinoso e sieroso.

Cystic tumours of the pancreas include a pathologically heterogeneous and rare group of tumours, which however have many common clinical features. They represent about 10% of pancreatic cystic lesions and 1% of all forms of neoplasms, thus having a certain relevance in organ surgery. So far two distinct categories of cystic tumours have been identified, the basically benign serous form and the potentially malign mucinous form, which may sometimes show malignant features as early as the diagnostic stage. As neoplasms are very difficult to interpret before operation, it is essential that diagnosis is as accurate as possible in order to streamline surgery, which will have to be carried out after histological tests have been performed on an adequate number of tumour sections. Basing on these two cases of cystic tumours of the pancreas and on current literature, the Authors discuss the effectiveness of imaging techniques, such as contrast echography, dosage of specific tumour markers and histological tests backed up by immunohistochemistry in identifying these neoplasms, in order to study this rare but interesting pathology more accurately.

[The capillary hemangioma of the stomach: an unusual cause of haemorrhage. Case report]. / L'emangioma capillare dello stomaco: una rara fonte di sanguinamento. Caso clinico.

Gastric haemorrhages are common clinical emergencies which often directly involve the surgeon in diagnosis and treatment; among these, rare vascular neoplasms deserve particular attention. The Authors report a rare case of benign vascular tumour of the stomach, a capillary angioma. After a literature review they highlight the importance of specific exams to reveal these small neoformations which, generally, show up clinically with acute bleeding, which may be severe, and which may not be discovered if the clinical evaluation is not very detailed. The surgical excision supported by a frozen sections is the most effective treatment.

Molecular analysis of the hydroxymethylbilane synthase (HMBS) gene in Italian patients with acute intermittent porphyria: report of four novel mutations.

Acute intermittent porphyria (AIP) is an autosomal disorder caused by molecular abnormalities in the hydroxymethylbilane synthase (HMBS) gene coding for the third enzyme in the heme biosynthetic pathway. So far, more than 160 different mutations responsible for AIP have been identified in this gene. We have now identified seven mutations in eight unrelated Italian patients with AIP: two splicing defects (IVS7+2T-->C, 612G-->T), three small deletions (308-309delTG, 730-731delCT, 182delA) and two missense mutations (134C-->A, 541C-->T). The splicing defects were responsible for activation of splicing cryptic sites respectively within intron 7 (15 bp insertion) and exon 10 (9 bp deletion). The small deletions resulted in frameshifts leading to the formation of premature stop codons. The 134C-->A and 541C-->T mutations caused the formation of stop codons likely to be responsible for drastic disruption of the HMBS structure (Ser45Ter, Gln181Ter). This is the first molecular study in AIP patients of Italian origin leading to the identification of four new mutations and three molecular defects that have already been described.