BoBafit : A copy number clustering tool designed to refit and recalibrate the baseline region of tumors' profiles.

Human cancer arises from a population of cells that have acquired a wide range of genetic alterations, most of which are targets of therapeutic treatments or are used as prognostic factors for patient's risk stratification. Among these, copy number alterations (CNAs) are quite frequent. Currently, several molecular biology technologies, such as microarrays, NGS and single-cell approaches are used to define the genomic profile of tumor samples. Output data need to be analyzed with bioinformatic approaches and particularly by employing computational algorithms. Molecular biology tools estimate the baseline region by comparing either the mean probe signals, or the number of reads to the reference genome. However, when tumors display complex karyotypes, this type of approach could fail the baseline region estimation and consequently cause errors in the CNAs call. To overcome this issue, we designed an R-package, BoBafit , able to check and, eventually, to adjust the baseline region, according to both the tumor-specific alterations' context and the sample-specific clustered genomic lesions. Several databases have been chosen to set up and validate the designed package, thus demonstrating the potential of BoBafit to adjust copy number (CN) data from different tumors and analysis techniques. Relevantly, the analysis highlighted that up to 25% of samples need a baseline region adjustment and a redefinition of CNAs calls, thus causing a change in the prognostic risk classification of the patients. We support the implementation of BoBafit within CN analysis bioinformatics pipelines to ensure a correct patient's stratification in risk categories, regardless of the tumor type.

Clonal and subclonal TP53 molecular impairment is associated with prognosis and progression in multiple myeloma.

Aberrations on TP53, either as deletions of chromosome 17p (del17p) or mutations, are associated with poor outcome in multiple myeloma (MM), but conventional detection methods currently in use underestimate their incidence, hindering an optimal risk assessment and prognostication of MM patients. We have investigated the altered status of TP53 gene by SNPs array and sequencing techniques in a homogenous cohort of 143 newly diagnosed MM patients, evaluated both at diagnosis and at first relapse: single-hit on TP53 gene, either deletion or mutation, detected both at clonal and sub-clonal level, had a minor effect on outcomes. Conversely, the coexistence of both TP53 deletion and mutation, which defined the so-called double-hit patients, was associated with the worst clinical outcome (PFS: HR 3.34 [95% CI: 1.37-8.12] p = 0.008; OS: HR 3.47 [95% CI: 1.18-10.24] p = 0.02). Moreover, the analysis of longitudinal samples pointed out that TP53 allelic status might increase during the disease course. Notably, the acquisition of TP53 alterations at relapse dramatically worsened the clinical course of patients. Overall, our analyses showed these techniques to be highly sensitive to identify TP53 aberrations at sub-clonal level, emphasizing the poor prognosis associated with double-hit MM patients.

Opposite activation of the Hedgehog pathway in CD138+ plasma cells and CD138-CD19+ B cells identifies two subgroups of patients with multiple myeloma and different prognosis.

Hyperactivation of the Hedgehog (Hh) pathway, which controls refueling of multiple myeloma (MM) clones, might be critical to disease recurrence. Although several studies suggest the Hh pathway is activated in CD138- immature cells, differentiated CD138+ plasma cells might also be able to self-renew by producing themselves the Hh ligands. We studied the gene expression profiles of 126 newly diagnosed MM patients analyzed in both the CD138+ plasma cell fraction and CD138-CD19+ B-cell compartment. Results demonstrated that an Hh-gene signature was able to cluster patients in two subgroups characterized by the opposite Hh pathway expression in mature plasma cells and their precursors. Strikingly, patients characterized by Hh hyperactivation in plasma cells, but not in their B cells, displayed high genomic instability and an unfavorable outcome in terms of shorter progression-free survival (hazard ratio: 1.92; 95% confidence interval: 1.19-3.07) and overall survival (hazard ratio: 2.61; 95% confidence interval: 1.26-5.38). These results suggest that the mechanisms triggered by the Hh pathway ultimately led to identify a more indolent vs a more aggressive biological and clinical subtype of MM. Therefore, patient stratification according to their molecular background might help the fine-tuning of future clinical and therapeutic studies.

[Duodenal angiodysplasia and Turner's syndrome. Case report]. / Angiodisplasia duodenale e sindrome di Tuner.

UNLABELLED: The Turner's syndrome is the most common chromosomic disease in the women and touches 1:2,500 women born live. The most important anomaly is the presence of short stature and ovarian failure. Others disorders are increasing in case reports: osteoporosis, hypothyroidism, renal diseases and gastroenteric diseases. The Authors, after careful review of the literature, that proves rarity of the disease, report a case of duodenal vascular anomaly associated with Turner's syndrome and describe surgical therapy, peculiar to this atypical localization. CASE REPORT: A 31 years old woman, genotypic XO and female phenotypic, with diabetes mellitus type I, arterial hypertension and hypertransaminasemia. Since three days the patient reports epigastric pain discontinuous, not widespread, not nocturnal, with wretch, bowel open only to gas. The patient underwent Rx abdomen, Rx with gastrografin, TC abdomen. Diagnosed as a high digestive occlusion, the patient underwent explorative laparotomy. As laparotomy she had a necrotic-hemorrhagic lesion in duodenum D3-D4 and first jejunal loop, with stenosis of the jejunal lumen, perforation of serosa and blood in peritoneal cavity. Resection of necrotic loop and reconstruction with Y loop performing manual duodenum jejunal L-L anastomosis, mechanical gastroenterostomy and enteric-enteric L-L mechanical anastomosis. After operation hemorrhage from anastomosis was observed, treated with omeprazole therapy and total parenteral nutrition. The patient was discharged in 14th p. o. day. After two years she is in good health without gastrointestinal symptoms. In patients with Turner's syndrome gastrointestinal vascular anomalies have to be considered as diagnostic hypothesis in cause of abdominal pain.

[Hepatic haemorrhage in pregnancy: a case report]. / Emorragia epatica in gravidanza: caso clinico.

Spontaneous hepatic haemorrhage in pregnancy (SHHP) is a rare event (1 woman out of 15,000). It is generally considered as an advanced state of the microangiopathic hemolytic anemia (HELLP, Hemolysis, Elevated Liver enzyme levels, Low Platelet count). Furthermore, the HELLP is considered as a different form of preeclampsia. The patient, a 33-year-old-woman at 30 weeks' gestation, was admitted to hospital for preeclampsia, underwent an emergency Stark caesarean section with the extraction of an alive foetus and evidence of massive intraperitonal haemorrhage from a large hepatic haematoma. A haemostasis with gauzes of Surgicel was performed, with consequent arrest of the haemorrhage. After approximately 6 hours, a recurrence of the intraperitonal haemorrhage led to a new surgical intervention with hepatic packing with gauzes. After 4 days the patient died. The etiopathogenesis of disease is uncertain, both foetal and maternal mortality are high, and the slight number of reported cases (27) of SPPH from HELLP in international literature offer elements for debate. The following points have been put forward: 1. the monitoring of the counts of the platelets represent the only valid predictive test of HELLP. These concerned women in the third trimester of pregnancy, especially those with a history of preeclampsia; 2. the treatment must be immediate, intensive and multidisciplinary, the plasmapheresis has remarkably improved the prognosis; 3. surgical treatment performed in order to control the SPPH makes use of packing, embolization and/or fastening of the common hepatic artery and, in extreme cases, total hepatectomy with transplantation. The Authors believe it is useful to suggest a national epidemiological research in order to estimate the real incidence of the syndrome in Italy and to establish the guidelines for the medico-surgical treatment.

[Surgical complications for gastric and small bowel metastases due to primary lung carcinoma]. / Complicanze chirurgiche per metastasi gastriche e digiuno-ileali da carcinoma primitivo polmonare.

Lung carcinoma is the first cause of death for tumors; in Italy there are from 35,000 to 40,000 new cases a year, with a global survival to 5 years from the diagnosis in 13% of cases. The gastric and small bowel metastases are rare, respectively 0.4% and 1.1% and the cases reported in the literature are rare. There is often a poor symptomatology and diagnosis is usually based on post-mortem examination. Yet, sometimes, the first and only demonstration of the secondary illness is a surgical complication, whether it be a haemorrhage, a perforation or an occlusion. The authors report their experience, from April 1999 to March 2003, of 3 cases of small bowel metastases, presented in 1 case with a perforation and in 2 cases with an occlusion and of 1 case of gastric metastasis, which presented with a haemorrhage. These patients were treated by emergency surgery, with 1 case only of postoperative mortality. The 1st patient died 6 months after surgery, and the 2nd patient 6 days after, the 3rd patient 4 months after the 1st operation and the 4th patient is still in follow-up after 6 months. The authors present a review of the literature and some considerations of diagnosis and surgical treatment.

[Extrauterine endometriosis: three new cases]. / L'endometriosi extrauterina: tre nuovi casi.

Extragonadal endometriosis is rarely diagnosed preoperatively due the variety of its localizations. Presentation to general surgeons may be atypical and pose diagnostic difficulties. The Authors report three cases surgically treated between 2000-2003. The Authors stress the peculiarity of one of these cases with endometrial tissue involvement of the intestinal mucosa. They also discuss about various aetiological hypothesis, symptomatology, differential diagnosis and need for multidisciplinary treatment.

[The meshes of polypropylene in emergency surgery for strangulated hernias and incisional hernias]. / La protesi di polipropilene in chirurgia d'urgenza per laparoceli ed ernie strozzate.

INTRODUCTION: The Authors present their experience on the use of meshes of polypropylene in septic surgery of the abdominal wall defects. MATERIALS AND METHODS: From April 1999 to October 2003, 23 patients underwent intestinal resection (20 small intestine, 3 large intestine) for ischemic necrosis strangulation caused by defects in the abdominal wall (inguinal hernia 8, crural hernia 4, umbilical hernia 3, post-incisional hernia under umbilicus 3, post-incisional hernia epigastric 3, giant post-incisional hernia 2). RESULTS: No patient died and the removal of the mesh was never required in cases of infection of the surgical wound; 2 surgical wounds festered, with the reopening of the cutaneous wound and showing of the prosthesis, 5 hygromas were all treated in a conservative way. DISCUSSION: The macroporous structure of the meshes of polypropylene, with pores of diameter larger than 70 microns, allows contact among the bacteria, which measure one micron in diameter, and the cells of the immune system, granulocytes and macrophages, with a diameter of 15-20 microns, allowing the recovery from infections, and determining an high resistance rate to infections. CONCLUSIONS: Polypropylene prostheses, thanks to their macroporous structure, are sufficiently resistant to infections and therefore may be safely used in the surgery of the defects of the abdominal wall, when, following ischemic necrosis, an intestinal resection is necessary.

[Emergency surgery for neoplastic left colon obstruction: resection and primary anastomosis (RPA) versus Hartmann resection (HR)]. / Chirurgia d'urgenza per occlusione neoplastica del colon sinistro: resezione ed anastomosi primaria (RPA) versus resezione secondo Hartmann (HR).

UNLABELLED: This retrospective study compares: hospitalization time, morbidity and mortality (patients operated for neoplastic occlusion of the left colon in emergency, without perforation), considering hanestesiologic risk and surgical technique (RPA versus RH). MATERIALS AND METHODS: From April 1999 to February 2003 the Emergency Surgery of AORN of Caserta has operated, in urgency, 60 neoplastic patients with left colon occlusion realizing: 46 (76.5%) RPA [36 ASA < or = III, low hanestesiologic risk (LAR), 10 ASA = or > IV high hanestesiologic risk (HAR)], 12 (20%) RH (2 LAR and 10 HAR) 2 (3.5%) palliative colostomics. RESULTS: 36 LAR patients with RPA had 5% of specific complications and 5% of medical complications. 2 LAR patients with R-H: no complication. 10 HAR patient with RPA brought 10% of specific complications and 10% of medical complications. 10 HAR patients with RH had 20% of specific complications and 10% of general complications. The middle hospitalization of LAR patients with RPA was 11 days versus 9 days of RH pz. (equal hanestesiologic risk ). The HAR pz., treated with RPA, had as middle hospitalization 15 ggs in comparison to the 9 ggs of the HRA pz. treated with RH. MORTALITY: 1/36 for LAR pz. with RPA (3%), and 0/0 for LAR pz. with RH; 1/10 for HAR pz, with RPA (10%) and 1/10 for HAR pz. with RH (10%). CONCLUSIONS: Resection and primary anastomosis, (correct indications and expert surgeon), gives prevalence of complications and mortality similar to the repeated surgical procedure, a better life quality, but an higher number of post-operating hospitalisation days.

[Nosocomial fungal infections in surgical patients. Older age as factor of risk and early presumptive and systemic therapy versus prophylactic therapy]. / Le micosi nosocomiali nel paziente chirurgico. Età geriatrica come fattore di rischio e terapia sistemica e presuntiva precoce versus terapia profilattica.

Objective of our study has been to verify if the age is a factor of additional risk for the opportunistic fungal infections and if prophylactic therapy cause real advantages in terms of reduction of morbidity, mortality and times of hospitalization. To such we report the experience of the Operational Unity of Emergency Surgery of the Hospital of Relief National and High Specialization of Caserta relatively to the patients submitted to intervention of great abdominal surgery. In the year 2000 antifungal therapy has been administered to 20 patient (of which 18 over 65 years) on the escort of an laboratory diagnosis; in the year 2001 we have administered prophylactic therapy to 53 high-risk patient (of which 48 over 65). In the group of patients essays with preventive therapy the middle hospitalization has been slightly inferior with a reduction of around 2 days of refuge for the elderly patients and of around 1.5 days in the youngest patients. Mortality in the elderly patients has been reduced from 38% of the year 2000 at 23% of the year 2001. Our data confirm that the age is an important factor of risk for the fungal infections in the surgical departments and we believe to a prophylactic therapy can be of benefit in well selected patient, although an ordinary application of antifunfal therapy can not have recommended without an laboratory diagnosis because to emerge of new resistances to the medicines.

[Intraperitoneal hemorrhage from rupture of an aneurysm of splenic artery: case report and literature review]. / Emoperitoneo da fissurazione di aneurisma dell'arteria splenica: case report e revisione della letteratura.

Splenic artery aneurysm presented with rupture is an unusual and potentially deadly reason of intraperitoneal hemorrhage. There are a lot of pathogenetic hypothesis; timing according to disease severity and surgical choices aren't definitely codified authors present one patient with hemoperitoneum for ruptured splenic artery aneurysm affected by chronic lymphatic leukaemia too and review international literature; they underline pathogenesis, symptoms, preoperative investigations and therapy. Degeneration of the media, atherosclerotic changes and high blood flow due to pregnancy and portal hypertension could be the main pathogenetic factors. Ultrasonography is the first investigation we have to practice if we suspect hemoperitoneum. We can practice computed tomography and angiography too if cardiovascular condition are good. Rupture showing acute abdominal pain and cardiovascular collapse suggest strongly urgent operation. The choice of operation is determined by location of the aneurysm. When located in the distal third of the splenic artery, the aneurysm is resected with spleen; alternatively, when it is located in prossimal third we can perform conservative operation.

[Pica: a clinical case and therapeutic problems]. / Il picacismo: caso clinico e problematiche terapeutiche.

Pica is a psychotic disorder characterized by compulsive ingestion of nonfood substances; the primary treatment is the prevention with antipsychotic therapy. When the patient ingests foreign body, endoscopical removal is recommended. Surgical treatment is necessary when an acute abdomen is present, with intestinal occlusion and/or bowel perforation. The Authors report a peculiar case of pica, and analyse the problems of organization and assistance, besides surgical approach, also on the base of international literature.