Multiregion whole-exome sequencing of matched primary and metastatic tumors revealed genomic heterogeneity and suggested polyclonal seeding in colorectal cancer metastasis.

BACKGROUND: Distant metastasis accounts for 90% of deaths from colorectal cancer (CRC). Genomic heterogeneity has been reported in various solid malignancies, but remains largely under-explored in metastatic CRC tumors, especially in primary to metastatic tumor evolution. PATIENTS AND METHODS: We conducted high-depth whole-exome sequencing in multiple regions of matched primary and metastatic CRC tumors. Using a total of 28 tumor, normal, and lymph node tissues, we analyzed inter- and intra-individual heterogeneity, inferred the tumor subclonal architectures, and depicted the subclonal evolutionary routes from primary to metastatic tumors. RESULTS: CRC has significant inter-individual but relatively limited intra-individual heterogeneity. Genomic landscapes were more similar within primary, metastatic, or lymph node tumors than across these types. Metastatic tumors exhibited less intratumor heterogeneity than primary tumors, indicating that single-region sequencing may be adequate to identify important metastasis mutations to guide treatment. Remarkably, all metastatic tumors inherited multiple genetically distinct subclones from primary tumors, supporting a possible polyclonal seeding mechanism for metastasis. Analysis of one patient with the trio samples of primary, metastatic, and lymph node tumors supported a mechanism of synchronous parallel dissemination from the primary to metastatic tumors that was not mediated through lymph nodes. CONCLUSIONS: In CRC, metastatic tumors have different but less heterogeneous genomic landscapes than primary tumors. It is possible that CRC metastasis is, at least partly, mediated through a polyclonal seeding mechanism. These findings demonstrated the rationale and feasibility for identifying and targeting primary tumor-derived metastasis-potent subclones for the prediction, prevention, and treatment of CRC metastasis.

Assessment of 126,913 inguinal hernia repairs in the Emilia-Romagna region of Italy: analysis of 10 years.

PURPOSE: Inguinal hernioplasty could be used as an indicator of the surgical quality offered in different health institutions and countries, thereby establishing a scientific basis from which the procedure can be critically assessed and ultimately improved. Quality assessment of hernioplasties could be conducted using two different methods: either analyzing dedicated regional/national databases (DD) or reviewing administrative databases (AD). METHODS: A retrospective study of inguinal hernioplasties was carried out in the Emilia-Romagna hospitals between 2000 and 2009. Data were obtained by analyzing Hospital Discharge records regional Databases (HDD). Descriptive and multivariate statistical analysis was performed. RESULTS: 126,913 inguinal hernioplasty procedures were performed. The annual rate was on average 34 per 10,000 inhabitants. An increase of the case mix complexity and relevant changes in procedure technique were recorded. From multivariate analysis, the following independent factors related to a hospitalization longer than 1 day emerged: procedures in urgent setting (OR 3.6, CI 3.4-3.7), Charlson's score ≥2 (OR 3.4, CI 3.1-3.7), laparoscopy (OR 2.1, CI 1.9-2.3), no mesh use (OR 2.1, CI 2-2.3), age >65 years (OR 1.9, CI 1.8-1.9), associated interventions (OR 1.9, CI 1.8-1.9), bilateral hernia (OR 1.7, CI 1.6-1.8), recurrent hernia (OR 1.2, CI 1.1-1.2) and female gender (OR 1.2, CI 1.2-1.3). Factors related to non-prosthetic hernioplasty were: bilateral hernia (OR 2.7, CI 2.5-2.9), female gender (OR 1.8, CI 1.8-2.0), emergency setting (OR 1.6, CI 1.5-1.8), recurrences (OR 1.5, CI 1.4-1.6) and associated interventions (OR 1.5, CI 1.4-1.6). CONCLUSION: Inguinal hernia should be treated as an outpatient procedure in the majority of patients. Precise guidelines are necessary. HDD demonstrated to be a good and trustworthy system to collect clinical data. When precise guidelines are lacking, legal/institutional indications play a pivotal role in shifting the hernia surgery toward a one-day surgery regimen.

Treatment of human cartilage defects by means of Nd:YAG Laser Therapy.

Articular cartilage lesions represent a challenging problem for orthopaedic surgeons. The purpose of this study was to evaluate the effect of a new pulsed Nd:YAG High Intensity Laser Therapy on the regeneration of cartilage tissue in patients with traumatic lesions. Clinical, histological and immunohistochemical evaluations were performed. Ten patients affected by chondral lesions scheduled for ACI procedure, were enrolled into the study. During the chondrocyte expansion for ACI procedure, cartilage from five patients was treated by Nd:YAG High Intensity Laser Therapy (HILT group). No laser treatment was performed in the remaining patients, who were used as controls. Cartilage repair was assessed by clinicians using two different scores: Cartilage Repair Assessment (CRA) and Overall Repair Assessment (ORA). Cartilage biopsy specimens were harvested to perform histological and immunohistochemical analyses at T0 (before laser treatment) and T1 (at the end of the treatment). A significant decrease in cartilage depth was noticed in the HILT group at T1. Histological and immunohistochemical evaluations showed some regenerative processes in cartilaginous tissue in terms of high amount of proteoglycans, integration with adjacent articular cartilage and good cellular arrangement in the HILT group. By contrast, a not well organized cartilaginous tissue with various fibrous features in the control group at T0 and T1 was observed. In conclusion, the use of this new pulsed Nd:YAG HILT resulted promising in the treatment of moderate cartilage lesions markedly in the young patients.

Risk factors and incidence of postoperative delirium in elderly patients after elective and emergency surgery.

BACKGROUND: : This study evaluated the incidence of postoperative delirium (POD) in elderly patients undergoing general surgery, the risk factors associated with POD, and its impact on hospital stay and mortality. METHODS: : Patients aged over 65 years who had emergency or elective operations were eligible for this case-control study. Risk factors significantly associated with POD using univariable analysis were entered into multivariable analysis, to establish those independently associated with POD. RESULTS: : A total of 351 patients (357 admissions) were enrolled in the study. The incidence of POD was 13.2 per cent (17.9 per cent for emergency operations). Independent variables associated with POD were: age above 75 years, co-morbidity, preoperative cognitive impairment, psychopathological symptoms and abnormal glycaemic control. Median length of hospital stay was 21 (range 1-75) days for patients with POD versus 8 (range 1-79) days for control patients (P < 0.001). The hospital mortality rate was 19 and 8.4 per cent respectively (P = 0.021). CONCLUSION: : The incidence of POD is high in elderly patients for both emergency and elective surgery, leading to an increase in hospital stay and perioperative mortality. To minimize POD, associated risk factors of co-morbidity, cognitive impairment, psychopathology and abnormal glycaemic control must be identified and treated.

Impact of regionalisation of cardiac surgery in Emilia-Romagna, Italy.

STUDY OBJECTIVE: Assessment of the impact of the regionalisation of cardiac surgery through the organisational form of a hub&spoke model introduced in the year 2000. DESIGN: Case mix adjusted before (1998-1999)-after (2000-2002) comparison of: (a) in-hospital and 30 days mortality rates; (b) proportion of patients timely (within one day) referred for surgery from spoke to hub centres; (c) patients' waiting times to surgery. SETTING: Emilia-Romagna, an Italian region with four million residents. PATIENTS: 16,512 patients aged > or =18 years and referred to cardiac surgery over the period 1998-2002. MAIN RESULTS: Overall, taking into account differences in case mix across the whole study period, the implementation of the regionalisation policy was associated with a 22% reduction (OR: 0.79, 95%CI: 0.66 to 0.93) in in-hospital mortality rate. The corresponding figure for 30 day mortality was 18% (OR: 0.82: 95%CI: 0.69 to 0.98). The individual centres' volume of cases changed over the study period for all hospitals but two, and the biggest reduction in mortality was seen at the centre with the largest increase in caseload. CONCLUSIONS: This study provides additional evidence on the benefit of regionalisation of cardiac surgery interventions. The system allowed each centre to reach the minimum caseload required to assure good quality of care. These findings suggest that policies aimed at increasing cooperation rather than competition among health service providers have a positive impact on quality of care. Timely referrals for surgery increased by 21% (95%CI: 1.12 to 1.31), and mean waiting times were reduced by 7.5 average days (95%CI: -10.33 to -4.71).

A conventional beagle dog model for acute and chronic infection with Helicobacter pylori.

Helicobacter pylori has been widely recognized as an important human pathogen responsible for chronic gastritis, peptic ulcers, gastric cancer, and mucosa-associated lymphoid tissue (MALT) lymphoma. Little is known about the natural history of this infection since patients are usually recognized as having the infection only after years or decades of chronic disease. Several animal models of H. pylori infection, including those with different species of rodents, nonhuman primates, and germ-free animals, have been developed. Here we describe a new animal model in which the clinical, pathological, microbiological, and immunological aspects of human acute and chronic infection are mimicked and which allows us to monitor these aspects of infection within the same individuals. Conventional Beagle dogs were infected orally with a mouse-adapted strain of H. pylori and monitored for up to 24 weeks. Acute infection caused vomiting and diarrhea. The acute phase was followed by polymorphonuclear cell infiltration, interleukin 8 induction, mononuclear cell recruitment, and the appearance of a specific antibody response against H. pylori. The chronic phase was characterized by gastritis, epithelial alterations, superficial erosions, and the appearance of the typical macroscopic follicles that in humans are considered possible precursors of MALT lymphoma. In conclusion, infection in this model mimics closely human infection and allows us to study those phases that cannot be studied in humans. This new model can be a unique tool for learning more about the disease and for developing strategies for treatment and prevention.