Monitoring COVID-19 contagion growth.

We present a statistical model that can be employed to monitor the time evolution of the COVID-19 contagion curve and the associated reproduction rate. The model is a Poisson autoregression of the daily new observed cases and dynamically adapt its estimates to explain the evolution of contagion in terms of a short-term and long-term dependence of case counts, allowing for a comparative evaluation of health policy measures. We have applied the model to 2020 data from the countries most hit by the virus. Our empirical findings show that the proposed model describes the evolution of contagion dynamics and determines whether contagion growth can be affected by health policies. Based on our findings, we can draw two health policy conclusions that can be useful for all countries in the world. First, policy measures aimed at reducing contagion are very useful when contagion is at its peak to reduce the reproduction rate. Second, the contagion curve should be accurately monitored over time to apply policy measures that are cost-effective.

The EU Industrial Strategy: Towards a Post-Growth Agenda?

Along with the Green Deal, the von der Leyen Commission immediately started to look at how to adopt an industrial strategy that would promote EU competitiveness and support the Commission's self-assigned "geopolitical" role by boosting strategic autonomy.

TWIST1 silencing enhances in vitro and in vivo osteogenic differentiation of human adipose-derived stem cells by triggering activation of BMP-ERK/FGF signaling and TAZ upregulation.

Mesenchymal stem cells (MSCs) show promise for cellular therapy and regenerative medicine. Human adipose tissue-derived stem cells (hASCs) represent an attractive source of seed cells in bone regeneration. How to effectively improve osteogenic differentiation of hASCs in the bone tissue engineering has become a very important question with profound translational implications. Numerous regulatory pathways dominate osteogenic differentiation of hASCs involving transcriptional factors and signaling molecules. However, how these factors combine with each other to regulate hASCs osteogenic differentiation still remains to be illustrated. The highly conserved developmental proteins TWIST play key roles for transcriptional regulation in mesenchymal cell lineages. This study investigates TWIST1 function in hASCs osteogenesis. Our results show that TWIST1 shRNA silencing increased the osteogenic potential of hASCs in vitro and their skeletal regenerative ability when applied in vivo. We demonstrate that the increased osteogenic capacity observed with TWIST1 knockdown in hASCs is mediated through endogenous activation of BMP and ERK/FGF signaling leading, in turn, to upregulation of TAZ, a transcriptional modulator of MSCs differentiation along the osteoblast lineage. Inhibition either of BMP or ERK/FGF signaling suppressed TAZ upregulation and the enhanced osteogenesis in shTWIST1 hASCs. Cosilencing of both TWIST1 and TAZ abrogated the effect elicited by TWIST1 knockdown thus, identifying TAZ as a downstream mediator through which TWIST1 knockdown enhanced osteogenic differentiation in hASCs. Our functional study contributes to a better knowledge of molecular mechanisms governing the osteogenic ability of hASCs, and highlights TWIST1 as a potential target to facilitate in vivo bone healing.

An Overview of Direct Somatic Reprogramming: The Ins and Outs of iPSCs.

Stem cells are classified into embryonic stem cells and adult stem cells. An evolving alternative to conventional stem cell therapies is induced pluripotent stem cells (iPSCs), which have a multi-lineage potential comparable to conventionally acquired embryonic stem cells with the additional benefits of being less immunoreactive and avoiding many of the ethical concerns raised with the use of embryonic material. The ability to generate iPSCs from somatic cells provides tremendous promise for regenerative medicine. The breakthrough of iPSCs has raised the possibility that patient-specific iPSCs can provide autologous cells for cell therapy without the concern for immune rejection. iPSCs are also relevant tools for modeling human diseases and drugs screening. However, there are still several hurdles to overcome before iPSCs can be used for translational purposes. Here, we review the recent advances in somatic reprogramming and the challenges that must be overcome to move this strategy closer to clinical application.

Initial experience of robotic versus laparoscopic colectomy for transverse colon cancer: a matched case-control study.

BACKGROUND: Robotic surgery for transverse colon cancer has rarely been described. This study reports our initial experience in robotic resection for transverse colon cancer, by comparing robotic transverse colectomy (RC) to laparoscopic transverse colectomy (LC) in terms of safety, feasibility, short-term outcomes, and the surgeon's psychological stress and physical pain. METHODS: The study population included the first 22 consecutive patients who underwent RC between March 2013 and December 2014 for histologically confirmed transverse colon adenocarcinoma. These patients were compared with 22 matched patients undergoing LC between December 2010 and February 2013. Patients were matched based on age, gender, body mass index (BMI), American Society of Anesthesiology (ASA) score, American Joint Committee on Cancer (AJCC) tumor stage, and tumor location (ratio 1:1). Mortality, morbidity, operative, and short-term oncologic outcomes were compared between groups. The operating surgeon's stress and pain were assessed before and after surgery on a 0-100-mm visual analog scale. RESULTS: The demographic and preoperative characteristics were comparable between RC and LC patients. No group difference was observed for intraoperative complications, blood loss, postoperative pain, time to flatus, time to regular diet, and hospital stay. RC was associated with longer operative time than LC (260 min vs. 225 min; p = 0.014), but the overall operative and robotic time in the RC group decreased over time reflecting the increasing experience in performing this procedure. No conversion to laparotomy was observed in the RC group, while two LC patients were converted due to uncontrolled bleeding and technically difficult middle colic pedicle dissection. Postoperative complications (Dindo-Clavien grade I or II) occurred in 11.3 % of patients with no group difference. Mortality was nil. All resections were R0, with >12 lymph nodes harvested in 90.9 % of RC and 95.5 % of LC patients. The surgeon's stress was not different between RC and LC, whereas the surgeon's hand and neck/shoulder pain were significantly lower after RC. CONCLUSIONS: RC for transverse colon cancer appears to be safe and feasible with short-term outcomes comparable to LC.

Can only histological evaluation determine the allocation of ECD kidneys?

INTRODUCTION: There is a recent debate on the "transplantability" of ECD (Expanded Criteria Donors) kidneys and the selection criteria used to allocate them to single or double transplantation. Remuzzi et al. have defined a protocol incorporating pre-transplant donor biopsy to guide the use of older donor organs. They allocated organs as single or double transplants on the basis of histological findings. We aim to show the pros and cons of the only histological evaluation in the allocation of ECD kidneys, to compare the different experiences in United States and Europe and thus to discuss whether this tool should be used alone or included in a comprehensive clinical and histopathological evaluation. DISCUSSION: In the United States many Authors stated that the biopsy actually increases the percentage of kidney discarded and they raised questions about the importance of the biopsy in evaluating ECD kidneys for transplantation. On the other hand, the experiences of the majority of european transplant centers showed that allocating kidneys as single or dual transplant based on biopsy findings may achieve good graft and patient outcomes. Moreover, the experience of some centers as ours showed that kidneys allocated as DKT (Dual Kidney Transplant) on the basis of Remuzzi's score could have been suitable for single transplantation suggesting the need of an adjustment of the Remuzzi Score System. Many Authors, who are in favor of histological evaluation, actually believe that a comprehensive clinical and histopathological assessment before transplantation remains necessary. We lack precise national- or international-based selection criteria to guide clinicians. An adjustment of the Remuzzi Score System could be taken into consideration such as narrowing the indication for DKT from those ECD kidneys with higher scores and including the histological evaluation in a multifactor score.

Adipose-derived stem cells: a review of signaling networks governing cell fate and regenerative potential in the context of craniofacial and long bone skeletal repair.

Improvements in medical care, nutrition and social care are resulting in a commendable change in world population demographics with an ever increasing skew towards an aging population. As the proportion of the world's population that is considered elderly increases, so does the incidence of osteodegenerative disease and the resultant burden on healthcare. The increasing demand coupled with the limitations of contemporary approaches, have provided the impetus to develop novel tissue regeneration therapies. The use of stem cells, with their potential for self-renewal and differentiation, is one potential solution. Adipose-derived stem cells (ASCs), which are relatively easy to harvest and readily available have emerged as an ideal candidate. In this review, we explore the potential for ASCs to provide tangible therapies for craniofacial and long bone skeletal defects, outline key signaling pathways that direct these cells and describe how the developmental signaling program may provide clues on how to guide these cells in vivo. This review also provides an overview of the importance of establishing an osteogenic microniche using appropriately customized scaffolds and delineates some of the key challenges that still need to be overcome for adult stem cell skeletal regenerative therapy to become a clinical reality.

Exogenous activation of BMP-2 signaling overcomes TGFß-mediated inhibition of osteogenesis in Marfan embryonic stem cells and Marfan patient-specific induced pluripotent stem cells.

Marfan syndrome (MFS) is a hereditary disease caused by mutations in the gene encoding Fibrillin-1 (FBN1) and characterized by a number of skeletal abnormalities, aortic root dilatation, and sometimes ectopia lentis. Although the molecular pathogenesis of MFS was attributed initially to a structural weakness of the fibrillin-rich microfibrils within the extracellular matrix, more recent results have documented that many of the pathogenic abnormalities in MFS are the result of alterations in TGFß signaling. Mutations in FBN1 are therefore associated with increased activity and bioavailability of TGF-ß1, which is suspected to be the basis for phenotypical similarities of FBN1 mutations in MFS and mutations in the receptors for TGFß in Marfan syndrome-related diseases. We have previously demonstrated that unique skeletal phenotypes observed in human embryonic stem cells carrying the monogenic FBN1 mutation (MFS cells) are faithfully phenocopied by cells differentiated from induced pluripotent-stem cells (MFSiPS) derived independently from MFS patient fibroblasts. In this study, we aimed to determine further the biochemical features of transducing signaling(s) in MFS stem cells and MFSiPS cells highlighting a crosstalk between TGFß and BMP signaling. Our results revealed that enhanced activation of TGFß signaling observed in MFS cells decreased their endogenous BMP signaling. Moreover, exogenous BMP antagonized the enhanced TGFß signaling in both MFS stem cells and MFSiPS cells therefore, rescuing their ability to undergo osteogenic differentiation. This study advances our understanding of molecular mechanisms underlying the pathogenesis of bone loss/abnormal skeletogenesis in human diseases caused by mutations in FBN1.

Intraperitoneal dedifferentiated liposarcoma showing MDM2 amplification: case report.

BACKGROUND: Liposarcoma 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 PRESENTATION: A 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. CONCLUSIONS: No 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.

Adrenocortical carcinoma: effect of hospital volume on patient outcome.

PURPOSE: Optimal management of adrenocortical carcinoma (ACC) involves a detailed diagnostic workup, radical surgery, and appropriate adjuvant therapy. However, due to the rarity of this disease, adequate expertise is necessary to ensure optimal patient care. We evaluated if the experience of a treating center influences the outcome of ACC. METHODS: Two hundred sixty-three patients who underwent adrenalectomy for ACC were included in a multi-institutional surgical survey and divided into 2 groups: "high-volume center" (HVC) (≥10 adrenalectomies for ACC) and "low-volume center" (LVC) (<10 adrenalectomies for ACC). A comparative analysis was performed. RESULTS: One hundred seventy-two patients underwent adrenalectomy at HVC and 91 at LVC. The two groups were homogeneous for age, sex, clinical presentation, and stage. The mean lesions size of ACC was higher in HVC than in LVC (104.1 ± 54.6 vs 82.8 ± 41.3 mm; P < 0.001). A significantly higher rate of lymph node dissection (P < 0.01) and of multiorgan resection (P < 0.01) was accomplished in HVC. The number of patients who underwent adjuvant therapy was significantly higher in HVC (P < 0.001). Local recurrence rate was lower in patients treated at HVC (6% vs 18.5%; P = NS). Mean time to recurrence was significantly longer in HVC than in LVC (25.2 ± 28.1 vs 10.1 ± 7.5; P < 0.01). CONCLUSION: The expertise of dedicated centers had a positive impact on the outcome of patients with ACC, resulting in a lower recurrence rate and improved mean time to recurrence. The improved patient outcome could be related not only to the appropriateness of the surgical procedure, but also to a more adequate multidisciplinary approach.

[Perioperative strategies: taking care of the elderly patient with severe advanced comorbidities needing acute surgery.] / Strategie perioperatorie: presa in carico dell'anziano con gravi comorbilità e fase avanzata di malattia con patologia chirurgica acuta.

In the common clinical practice the perioperative risk assessment of an acute surgical patient with advanced chronic comorbidities is carried out independently by surgeon and anesthesiologist, usually in two different steps. While the surgeon evaluates the risk mainly in relation to the surgical outcome, the perioperative risk assessment regarding the weight of the coexisting medical condition on the quality of recovery in the short- mid- and long-term is all about the anesthesiologist evaluation. When frailty and/or comorbidities are so serious that will make surgery seem futile, the patient's assessment on one hand, and the decisions regarding the further clinical waypoint on the other, have to be discussed firstly between surgeons and anesthesiologists before being shared with the patients and their relatives. This is mostly true in the event of an emergency surgical procedure. In regard, a consensus conference attended by a panel of experts respectively from the Italian Society of Anesthesia Analgesia Resuscitation and Intensive Care (SIAARTI) and the Italian Society of Surgery (SIC) was called for developing a shared clinical pathway aimed to select the best care option - operative vs palliative - in the best interest of the surgical patient with advanced chronic comorbidities, in emergency or elective condition. After two years, the panel of experts developed a position paper recommending, in case of potentially futile surgery, to assess the patient verifying two coexisting conditions ("Two Steps method"): Palliative Performance Scale <50%, and at least one of the following general clinical criteria: 1) more than one hospital admission within the last 12 months; 2) hospital admission from or awaiting admission to long-term care facilities, home care service, hospice; 3) chronic renal failure requiring weekly dialysis sessions; 4) home oxygen use and/or non-invasive ventilation. Under these conditions, the surgeon together with the anesthesiologist can share with the patient and/or his relatives the decision between palliative surgery or palliative care taking into account his wishes and preferences.

Twist1-Haploinsufficiency Selectively Enhances the Osteoskeletal Capacity of Mesoderm-Derived Parietal Bone Through Downregulation of Fgf23.

Craniofacial development is a program exquisitely orchestrated by tissue contributions and regulation of genes expression. The basic helix-loop-helix (bHLH) transcription factor Twist1 expressed in the skeletal mesenchyme is a key regulator of craniofacial development playing an important role during osteoskeletogenesis. This study investigates the postnatal impact of Twist1 haploinsufficiency on the osteoskeletal ability and regeneration on two calvarial bones arising from tissues of different embryonic origin: the neural crest-derived frontal and the mesoderm-derived parietal bones. We show that Twist1 haplonsufficiency as well Twist1-sh-mediated silencing selectively enhanced osteogenic and tissue regeneration ability of mesoderm-derived bones. Transcriptomic profiling, gain-and loss-of-function experiments revealed that Twist1 haplonsufficiency triggers its selective activity on mesoderm-derived bone through a sharp downregulation of the bone-derived hormone Fgf23 that is upregulated exclusively in wild-type parietal bone.

[Prognostic value of splenectomy and lymph-node dissection during gastric cancer resection]. / Il ruolo prognostico di splenectomia e linfoadenectoma nella chirurgia del carcinoma gastrico.

Gastric carcinoma is the second most common cause of digestive tumour-related death in Europe, North America and Asia. Today, the gold standard of treatment is still surgery, but outcomes to date are unsatisfactory. The Japanese Society for Research in Gastric Cancer (JSRGC) recommends the routine execution of splenectomy during gastrectomy. This recommendation is contested by western Authors because of increased morbidity and mortality without any real advantage in terms of survival. Patients treated for gastric cancer in our department between 1993 and 2002 were selected for this study. The 132 patients recruited were divided into two groups: a) those treated for gastric cancer without splenectomy; and b) those in whom splenectomy was performed in conjunction with gastrectomy. We analysed: the extent of lymph node dissection, the execution of the splenectomy, and the prognostic importance of factors relating to the patient, tumour and surgeon. Splenectomy was not associated with any increase in morbidity. Complications, especially of the septic type, and perioperative mortality were similar in both groups, and the same was true of survival at both 3 and 5 years. In our opinion, splenectomy should not be routinely combined with surgery for gastric cancer but could be considered for T3-T4 neoplasms or those localized in the upper two thirds of the stomach.

The role of mutation analysis of the APC gene in the management of FAP patients. A controversial issue.

BACKGROUND: A correlation between the location of mutation in the adenomatous polyposis coli (APC) gene and clinical manifestations of familial adenomatous polyposis (FAP) has repeatedly been reported. Some Authors suggest the use of mutational analysis as a guide to select the best surgical option in FAP patients. However, data coming from studies on large series have raised questions on this issue. The aim of this study is to discuss the role of the genetic tests in the management of FAP. METHODS: A literature review was performed considering only peer-reviewed articles published between 1991-2015. All the studies examined the role of genetic as a guide for surgical management of FAP. RESULTS: Of 363 articles identified, 21 were selected for full-text review. We found different positions with regard the use of genetic tests to determine surgical management of FAP. In particular, while consistent correlations between the APC mutation site and FAP phenotype were observed in large series, 8 studies reported a wide variation of genotypephenotype correlation in patients with the same mutation and they recommended that decisions regarding surgical strategy should be based not only on genotype but also on the clinical factors and the will of the patient who must be fully informed. CONCLUSIONS: The decision on the type and the timing of surgery should be based on the assessment of many factors and genotype assessment should be used in combination with clinical data. KEY WORDS: Disease severity, Familial adenomatous polyposis, Genetic tests, Genotype-phenotype correlations, Surgical management.

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.

The mutation spectrum of the APC gene in FAP patients from southern Italy: detection of known and four novel mutations.

Familial adenomatous polyposis (FAP), an autosomal dominantly inherited condition accounting for about 1% of all colorectal cancers, results from mutations in the adenomatous polyposis coli (APC) tumor suppressor gene. The clinical spectrum and severity of FAP varies greatly with the mutation site, and both between and within families. Using the protein truncation test, single strand conformation polymorphism analysis and DNA sequencing, we identified 30 (75%) mutant alleles in 40 unrelated FAP families, for a total of 22 different APC mutations. Of these, 18 are known and 4 are novel: c.1797C>A (C599X), c.893_894delAC, (c.3225T>A; c.3226C>A) and c.4526_4527insT. Of the 30 APC gene mutations, 5 (approximately 17%) are nonsense mutations, 17 (approximately 57%) are small deletions, 5 (approximately 17%) are small insertions and 3 (approximately 10%) are complete deletions. All mutations occurred in single pedigrees, except those at codons 1061 and 1062, each found in two unrelated families, and the mutation at codon 1309 in exon 15, found in five unrelated families. About 40% of mutations, mostly small deletions and insertions, are located at repeated sequences; they promote misalignment-mediated errors in DNA replication and could represent a hot spot mutation region. This study enlarges the spectrum of APC gene mutations and sheds light on the correlation between the site of APC germline mutations and clinical manifestations of FAP.

[Expression of Lewis carbohydrate antigen in human tumors]. / Espressione dell'antigene carboidratico Lewis nei tumori umani.

In this study we show, by immunoblotting, that Mab B3, a newly isolated monoclonal antibody, reacts with a variety of glycoproteins with different molecular weights expressed in gastric, pancreatic and colorectal cancers. The reactivity pattern differed in cancers arising in different tissues, though no correlation was observed with the histopathological characteristics of the lesions analysed. MAb B3 does not react with liver, brain or kidney cancers and has a limited reactivity with lung cancers but reacts very strongly with metastatic lesions. Because of the limited reactivity of this antibody with normal tissues, MAb B3 genetically fused with toxin in the form of a recombinant immunotoxin may be useful in treating certain kinds of cancer such as metastatic lesions. However, until current trials are completed, we will not know whether this immunotoxin will be helpful in cancer treatment.

Laparoscopic cholecystectomy: technical compromise between French and American approach. Presentation of an original technique.

INTRODUCTION: Laparoscopic cholecystectomy (LC) is a well standardized technique. There are two main approaches, proposed by French and American Schools. They have similar operative times, but different arrangements for site ports insertions and for patients and operators' position at operative bed. Although we can foresee new scenarios for the next future (robotics, SILS, NOTES, minilaparoscopy), it seemed interesting to describe a simple variation to LC introduced in the last years in our experience relative to the positioning of operators and patient during standard American technique. METHODS: In a retrospective analysis of 140 patients operated on for LC in the last two years (70 with French technique and 70 with "American modified" technique) we compared the following parameters: laparotomic conversion, duration of operation, hospital stay, morbidity and mortality rates. RESULTS: Conversion to laparotomy, length of operative time and hospital stay were similar. Morbidity rates were slightly different, but it did not show statistically significant differences between the two groups. Mortality was nil. CONSIDERATIONS: Our variant to LC seems to be almost a compromise between the two main techniques. Our operators' arrangement gave a greater comfort for surgeons during LC and our results were similar to those reported with adoption of French and American approaches. These considerations led us to judge our variation safe and reliable.

Simultaneous quadruple carcinoma of colon Case report and literature review.

INTRODUCTION: Multiple primary malignancies can arise in the large bowel as simultaneous, synchronous and/or metachronous. All tumors must be distant from each other to be considered as primitive, none have to be the result of metastasis from other tumors. CASE REPORT: We present a case of a 71 years old woman who was admitted to our hospital for a 3-year history of not well defined abdominal pain and hematochezia. The patient had no family history of cancer. Colonoscopy revealed 4 simultaneous tumors located at 4 and 20 cm from the ileocecal valve and at 23,2 and 19 cm from the anal verge. At CT scan there were no distant metastases, neither lymphonode node involvement. A quadruple adenocarcinoma of the colon was confirmed by the pathologist. Patient was operated on total colectomy with ileo-rectal anastomosis. DISCUSSION: Two or three synchronous tumors of the colon have been already described in literature in about 1,8-14% of cases, but the presence of four simultaneous cancers, as in our case, is very interesting and unusual without an history of FAP or familiar cancer. CONCLUSION: Comprehensive preoperative study, extensive intraoperative exploration, and radical resection can improve surgical results and survival rate, remaining unquestioned the cause.

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.