Armando Calogero

Lactic dehydrogenase and cancer: an overview.

Despite the intense scientific efforts made, there are still many tumors that are difficult to treat and the percentage of patient survival in the long-term is still too low. Thus, new approaches to the treatment of cancer are needed. Cancer is a highly heterogeneous and complex disease, whose development requires a reorganization of cell metabolism. Most tumor cells downregulate mitochondrial oxidative phosphorylation and increase the rate of glucose consumption and lactate release, independently of oxygen availability (Warburg effect). This metabolic rewiring is largely believed to favour tumor growth and survival, although the underlying molecular mechanisms are not completely understood. Importantly, the correlation between the aerobic glycolysis and cancer is widely regarded as a useful biochemical basis for the development of novel anticancer strategies. Among the enzymes involved in glycolysis, lactate dehydrogenase (LDH) is emerging as a very attractive target for possible pharmacological approaches in cancer therapy. This review addresses the state of the art and the perspectives concerning LDH both as a useful diagnostic marker and a relevant molecular target in cancer therapy and management.

Total colectomy for cancer: analysis of factors linked to patients' age.

Total colectomy (TC) is a valid option for cancer treatment in selected cases. Emergency presentation, association to familial adenomatous polyposis (FAP) or intestinal bowel disease (IBD), hereditary non-polyposis cancer (HNPCC), and synchronous tumors are the common indications to TC for cancer. Despite potential high morbidity and mortality rates for worse general health conditions of the advanced age it has even suggested for elderly patients. We reviewed our experience to analyze the current role of TC comparing different results between young and elderly patients. During the period 1990-2012, 76 patients were operated on TC for cancer. Patients were divided in two groups according to the age [<65 - group A (young) and >65 years old - group B (elderly)] and were compared their systemic and surgical complication, considering the presence of comorbidities, ASA score, lifestyle habits, elective or emergency presentation. Morbidity rate was 7.7% and 38.8% in young and elderly patients respectively. 21 systemic complications (3 in group A and 18 in group B) occurred in 17 patients (22.36%) (with the coexistence of two complications in 4 patients belonging to the group B. There were 6 surgical complications (7.9%) (3 in group A and 3 in group B): anastomotic leakage 3, major wound infections 2, postoperative bleeding 1; no intra-abdominal abscess were observed. In 2 cases (2.6%) (1 anastomotic leak and 1 intra-abdominal postoperative hemorrhage) was needed a reoperation. We observed only 2 deaths in the elderly. High ASA score and emergency were associated with worst results. Systemic complications were more frequent in elderly patients cause of significant comorbidities, while the incidence of surgical complications was similar and according to literature. Besides the classic indications, it is a viable surgical option also in cancer associated with complicated diverticulitis. Our data show that TC is a safe and effective procedure providing good results even in elderly patients, when combined with a careful preoperative evaluation and age is not an absolute controindication to this procedure.

Intraperitoneal dedifferentiated liposarcoma showing MDM2 amplification: case report

BackgroundLiposarcoma is the most common type of soft tissue sarcoma (STS). It is divided into five groups according to histological pattern: well-differentiated, myxoid, round cell, pleomorphic, and dedifferentiated. Dedifferentiated liposarcoma most commonly occurs in the retroperitoneum, while an intraperitoneal location is extremely rare. Only seven cases have been reported in literature. Many pathologists recognize that a large number of intra-abdominal poorly differentiated sarcomas are dedifferentiated liposarcomas. We report a case initially diagnosed as undifferentiated sarcoma that was reclassified as intraperitoneal dedifferentiated liposarcoma showing an amplification of the MDM2 gene.Case presentationA 59-year-old woman with abdominal pain and constipation was referred to the Department of Advanced Biomedical Sciences, University of Naples Federico II, Naples, Italy, in November 2012. On physical examination, a very large firm mass was palpable in the meso-hypogastrium. Computed tomography (CT) scan showed a heterogeneous density mass (measuring 10 × 19 cm) that was contiguous with the mesentery and compressed the third part of the duodenum and jejunum.At laparotomy, a large mass occupying the entire abdomen was found, adhering to the first jejunal loop and involving the mesentery. Surgical removal of the tumor along with a jejunal resection was performed because the first jejunal loop was firmly attached to the tumor.Macroscopic examination showed a solid, whitish, cerebroid, and myxoid mass, with variable hemorrhage and cystic degeneration, measuring 26 × 19 × 5 cm. Microscopic examination revealed two main different morphologic patterns: areas with spindle cells in a myxoid matrix and areas with pleomorphic cells. The case was initially diagnosed as undifferentiated pleomorphic sarcoma. Histological review showed areas of well-differentiated liposarcoma. Fluorescence in situ hybridization (FISH) analysis was performed and demonstrated an amplification of the MDM2 gene. Definitive diagnosis was intraperitoneal dedifferentiated liposarcoma.No adjuvant therapy was given, but 5 months after laparotomy, the patient presented with a locoregional recurrence and chemotherapy with high-dose ifosfamide was started.ConclusionsNo guidelines are available for the management of intraperitoneal dedifferentiated liposarcoma. We report this case to permit the collection of a larger number of cases to improve understanding and management of this tumor. Moreover, this study strongly suggests that poorly differentiated sarcomas should prompt extensive sampling to demonstrate a well-differentiated liposarcoma component and, if possible, FISH analysis.

What indication, morbidity and mortality for central pancreatectomy in oncological surgery? A systematic review.

Conventional pancreatic resections for pancreatic neck and body diseases include pancreaticoduodenectomy, distal pancreatectomy with or without splenectomy, and total pancreatectomy. Recent studies have reported encouraging results of non-traditional pancreatic resections, including central pancreatectomy (CP), for central pancreatic disease. This surgical approach offers the potentials of low postoperative morbidity and preservation of metabolic functions. This study performs a systematic review on CP. A comprehensive literature search was conducted, for the period 1992-2015, on three worldwide databases: PubMed, Scopus, ISI-Web of Knowledge. We focused on indications, morbidity and mortality of this surgical procedure. The review shows that CP is particularly suitable for small-medium size diseases localized into the pancreatic body. This procedure is associated with an increased postoperative morbidity but an excellent postoperative pancreatic function. CP is a safe and effective procedure when performed following the right indications.

Rare multiple primary malignancies among surgical patients—a single surgical unit experience

Background A remarkable number of patients presents with multiple primary malignancies (MPM) over their lifetimes. In most cases inherited syndromes, iatrogenic, or viral factors are implicated, while in some cases it is not possible to ascertain a clear aetiopathogenesis. Methods Starting from a series of 315 patients with MPM, we focused our attention on those with extremely infrequent combinations of tumours. We retrospectively analysed patients’ characteristics, type of first and second tumour and the interval between the two tumours. We made a comparison between our own data and data from surveillance, epidemiology, and end results cancer registries, the largest global series on this topic. Results Six patients presented with unusual associations, namely, central nervous system (CNS)/colon, testis/stomach, colon/CNS, CNS/kidney, uterus/soft tissue, and bone/breast. The median age was 50.5 years at the diagnosis of second neoplasm and the male:female ratio was 1:1. All six patients underwent surgery for both tumours. The median interval between the first and the second tumour was 11.3 years (range 1–36 years). Five patients were given chemotherapy as adjuvant systemic treatment, and two of them with CNS tumours also received radiotherapy. Discussion We analysed the behaviour of these rare tumours as first and second neoplasms. More frequent combinations and possible aetiological factors were evaluated. Conclusions Follow-up for patients recovering from a first tumour must be strict, as there is the risk of developing MPM, even after a long time period. Advancement in biomolecular knowledge and cooperation among different specialists are strongly needed to reduce mortality related to MPM and to foresee their occurrence.

Lactoferrin Adsorbed onto Biomimetic Hydroxyapatite Nanocrystals Controlling - In Vivo - the Helicobacter pylori Infection

Background The resistance of Helicobacter pylori to the antibiotic therapy poses the problem to discover new therapeutic approaches. Recently it has been stated that antibacterial, immunomodulatory, and antioxidant properties of lactoferrin are increased when this protein is surface-linked to biomimetic hydroxyapatite nanocrystals. Objective Based on these knowledge, the aim of the study was to investigate the efficacy of lactoferrin delivered by biomimetic hydroxyapatite nanoparticles with cell free supernatant from probiotic Lactobacillus paracasei as an alternative therapy against Helicobacter pylori infection. Methods Antibacterial and antinflammatory properties, humoral antibody induction, histopathological analysis and absence of side effects were evaluated in both in vitro and in vivo studies. Results The tests carried out have been demonstrated better performance of lactoferrin delivered by biomimetic hydroxyapatite nanoparticles combined with cell free supernatant from probiotic Lactobacillus paracasei compared to both lactoferrin and probiotic alone or pooled. Conclusion These findings indicate the effectiveness and safety of our proposed therapy as alternative treatment for Helicobacter pylori infection.

Immunosuppression and Multiple Primary Malignancies in Kidney-Transplanted Patients: A Single-Institute Study

Immunodeficiency is associated with higher cancer incidence. However, it is unknown whether there is a link between immunodeficiency and development of multiple primary malignancies. In the present study we analyse this link focusing on kidney-transplanted patients, as they are at higher risk of developing cancer due to the chronic assumption of immunosuppressants. We followed up 1200 patients who underwent kidney transplantation between 1980 and 2012. A total of 77/1200 kidney-transplanted patients developed cancer and 24 of them developed multiple cancers. Most multiple cancers were synchronous with a nonsignificant association between cancer and rejection episodes. In the general cancer population, one-ninth of patients are at higher risk of developing a second tumor over a lifetime; hence it would be reasonable to conclude that, from a merely theoretical and statistical viewpoint, long-term transplanted patients potentially have a higher risk of developing MPMs. However, data did not confirm this assumption, probably because these patients die before a second primary malignancy appears. Despite many observations on the increased incidence of different tumor types in immunodeficient patients and despite immunosuppression certainly being a predisposing factor for the multicancer syndrome, data so far are not robust enough to justify a correlation between immunodeficiency and multiple primary malignancies in transplanted patients.

Prevention of Fluid Effusion in Kidney Transplantation With the Use of Hemostatic Biomaterials

BACKGROUND Fluid effusion (blood, lymph, or urine) in kidney transplantation may give rise to several complications, directly, such as hematoma, seroma, lymphocele, and/or urinoma, or consequently, such as increased infection risk, longer hospital stay, graft compression--with or without functional impairment--and necessity of further hospitalizations. The aim of this study was to evaluate effectiveness of hemostatic biomaterials in prevention of fluid effusions, especially lymphocele in kidney transplant patients. METHODS We selected 40 patients who underwent kidney transplantation from 2009 to 2012 in which we used hemostatic biomaterials, and compared their results with those of other transplant patients from our center in which we did not used these biomaterials. Evaluated parameters were: fluid effusion, graft function, quality and quantity of drainage, blood count, and operative time. RESULTS There was no difference in operative time. The incidence of complications on which biomaterials can have a role decreased; particularly, we observed a reduction from 24.21% to 7.5% of fluid effusions (lymphocele). There was no evidence of complications due to biomaterials. CONCLUSIONS Hemostasis is important in surgery, and in kidney transplantations lymphostasis also has a significant role. In addition to the traditional hemostatic methods, recently some biomaterials, with the purpose of providing atraumatic hemostasis, were added. In our experience they are easy to use, and their use has proved to be effective for both hemostasis and lymphostasis with consequent reduction of fluid effusions.

Current Tissue Molecular Markers in Colorectal Cancer: A Literature Review

Background Colorectal cancer (CRC) is one of the most spread neoplasia types all around the world, especially in western areas. It evolves from precancerous lesions and adenomatous polyps, through successive genetic and epigenetic mutations. Numerous risk factors intervene in its development and they are either environmental or genetic. Aim of the Review Alongside common screening techniques, such as fecal screening tests, endoscopic evaluation, and CT-colonography, we have identified the most important and useful biomarkers and we have analyzed their role in the diagnosis, prevention, and prognosis of CRC. Conclusion Biomarkers can become an important tool in the diagnostic and therapeutic process for CRC. But further studies are needed to identify a noninvasive, cost-effective, and highly sensible and specific screening test for their detection and to standardize their use in clinical practice.

Multiple splenic hamartomas and familial adenomatous polyposis: a case report and review of the literature

IntroductionSplenoma or splenic hamartoma is a rare primary splenic tumor most often discovered radiologically and incidentally. Splenic hamartomas have a strong association with solid and hematological malignancies and, in rare cases, with tuberous sclerosis, but to the best of our knowledge no reports of splenic hamartomas associated with familial adenomatous polyposis have been documented, although it is recognized that familial adenomatous polyposis presents a variety of extracolonic manifestations.Case presentationWe report on a very rare case of multiple splenic hamartomas in a 46-year-old white woman who had previously undergone surgery for restorative proctocolectomy for familial adenomatous polyposis. A computed tomography scan of her spleen revealed multiple small lesions which measured less than 1cm in diameter. A splenectomy was performed and a histologic examination of the splenectomy specimen revealed the presence of multiple hamartomas.ConclusionIncidence, differential diagnosis, diagnostic procedures, pathologic findings and treatment of splenic hamartomas are discussed here and hamartomas are considered in a differential diagnosis of splenic tumors. A splenectomy is indicated in cases where malignancy cannot be excluded and in cases of associated hematologic disorders. To the best of our knowledge our patient is the first reported case to have splenic hamartomas identified in a familial adenomatous polyposis-affected patient with mutation in exon 15 of the APC gene. At this time it is not possible to correlate with certainty our multiple splenic hamartomas and familial adenomatous polyposis case as a clinical manifestation of the mutation of APC gene; however, we believe that this case report could be important for further observation of similar cases in the future.