Comparison of perometry-based volumetric arm measurements and bioimpedance spectroscopy for early identification of lymphedema in a prospectively-screened cohort of breast cancer patients.

Breast cancer-related lymphedema (BCRL) affects more than one in five women treated for breast cancer, and women remain at lifelong risk. Screening for BCRL is recommended by several national and international organizations for women at risk of BCRL, and multiple methods of objective screening measurement exist. The goal of this study was to compare the use of perometry and bioimpedance spectroscopy (BIS) for early identification of BCRL in a cohort of 138 prospectivelyscreened patients. At each screening visit, a patient's relative volume change (RVC) from perometer measurements and change in L-Dex from baseline (ΔL-Dex) using BIS was calculated. There was a negligible correlation between RVC and ΔL-Dex (r=0.195). Multiple thresholds of BCRL were examined: RVC ≥5% and ≥10% as well as and ΔL-Dex ≥6.5 and ≥10. While some patients developed an elevated RVC and ΔL-Dex, many demonstrated elevations in only one threshold category. Moreover, the majority of patients with RVC ≥5%, ΔL-Dex ≥6.5, or ΔL-Dex ≥10 regressed to non-elevated measurements without intervention. These findings suggest a role for combining multiple screening methods for early identification of BCRL; furthermore, BCRL diagnosis must incorporate patient symptoms and clinical evaluation with objective measurements obtained from techniques such as perometry and bioimpedance spectroscopy.

Efficacy of transversus abdominis plane (TAP) block in colorectal surgery: a systematic review and meta-analysis.

BACKGROUND: Multimodal opioid-sparing analgesia is a key component of the enhanced recovery after surgery (ERAS) protocol for postoperative pain management. Transversus abdominis plane (TAP) block has contributed to the implementation of this approach in different kinds of surgical procedures. The aim of this study was to evaluate the efficacy of TAP block and its impact on recovery in colorectal surgery. METHODS: A comprehensive literature search of the PubMed, Embase, and Scopus databases was conducted. Studies that compared TAP block to a control group (no TAP block or placebo) after colorectal resections were included. The effects of TAP block in patients undergoing colorectal surgery were assessed, including the technical aspects of the procedure. Two measures were used to evaluate the effectiveness of postoperative pain control: a numeric pain rating score at rest and on coughing or movement at 24 h following surgery and the opioid requirement at 24 h. Clinical aspects of recovery were postoperative ileus, surgical site infection, postoperative nausea and vomiting, and length of hospital stay. RESULTS: Sixteen studies were included in the analysis. Data showed that TAP block is a safe procedure associated with a significant reduction in the pain score at rest [WMD - 0.91 (95% CI - 1.56; - 0.27); p < 0.05] and on coughing or movement [WMD - 0.36 (95% CI - 0.72; - 0.01); p < 0.05] at 24 h after surgery and a significant decrease in morphine consumption in the TAP block group the day after surgery [WMD - 2.07 (95% CI - 2.63; - 1.51); p < 0.001]. CONCLUSIONS: TAP block appears to provide both an effective analgesia and a significant reduction in opioid use on the first postoperative day after colorectal surgery. Its use does not seem to lead to increased postoperative complications.

The daily-practiced post-partum hemorrhage management: an Italian multidisciplinary attended protocol.

Postpartum hemorrhage (PPH) is one of the most frequent causes of mortality and morbidity in the obstetric population globally, causing about a quarter of maternal deaths yearly, and is the leading cause of maternal death worldwide. The management of PPH remains a topic of great debate, even in view of new diagnostic and therapeutic possibilities in recent years, for which, however, the body of evidence available thus far is still scarce, as the standard values are lacking. The protocol hereby presented was developed after a literature review and during several meetings of an Italian multidisciplinary task group of specialists adopting a modified Delphi method, and is the result of the synthesis of therapeutic operational protocols for the treatment of PPH applied by the different specialties within the team. This protocol is intended to represent a practical proposal to support clinicians in the management of a particularly complex event that requires the intervention of a multidisciplinary team and the implementation of dedicated management protocols.

Hepatocellular carcinoma recurrence in patients with curative resection or ablation: impact of HCV eradication does not depend on the use of interferon.

BACKGROUND: In HCV-infected cirrhotic patients with successfully treated early hepatocellular carcinoma (HCC), the time to HCC recurrence and the effects of sustained viral eradication (SVR) by interferon (IFN)-based or IFN-free regimens on HCC recurrence remain unclear. AIM: To perform an indirect comparison of time to recurrence (TTR) in patients with successfully treated early HCC and active HCV infection with those of patients with SVR by IFN-based and by IFN-free regimens. METHODS: We evaluated 443 patients with HCV-related cirrhosis and Barcelona Clinic Liver Cancer Stage A/0 HCC who had a complete radiological response after curative resection or ablation. Active HCV infection was present in 328, selected from the Italian Liver Cancer group cohort; 58 patients had SVR achieved by IFN-free regimens after HCC cure, and 57 patients had SVR achieved by IFN-based regimens after HCC cure. Individual data of patients in the last two groups were extracted from available publications. RESULTS: TTR by Kaplan-Meier curve was significantly lower in patients with active HCV infection compared with those with SVR both by IFN-free (P = 0.02) and by IFN-based (P < 0.001) treatments. TTR was similar in patients with SVR by IFN-free or by IFN-based (P = 0.49) strategies. CONCLUSION: In HCV-infected, successfully treated patients with early HCC, SVR obtained by IFN-based or IFN-free regimens significantly reduce tumour recurrence without differences related to the anti-viral strategy used.

Years of life that could be saved from prevention of hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) causes premature death and loss of life expectancy worldwide. Its primary and secondary prevention can result in a significant number of years of life saved. AIM: To assess how many years of life are lost after HCC diagnosis. METHODS: Data from 5346 patients with first HCC diagnosis were used to estimate lifespan and number of years of life lost after tumour onset, using a semi-parametric extrapolation having as reference an age-, sex- and year-of-onset-matched population derived from national life tables. RESULTS: Between 1986 and 2014, HCC lead to an average of 11.5 years-of-life lost for each patient. The youngest age-quartile group (18-61 years) had the highest number of years-of-life lost, representing approximately 41% of the overall benefit obtainable from prevention. Advancements in HCC management have progressively reduced the number of years-of-life lost from 12.6 years in 1986-1999, to 10.7 in 2000-2006 and 7.4 years in 2007-2014. Currently, an HCC diagnosis when a single tumour <2 cm results in 3.7 years-of-life lost while the diagnosis when a single tumour ≥ 2 cm or 2/3 nodules still within the Milan criteria, results in 5.0 years-of-life lost, representing the loss of only approximately 5.5% and 7.2%, respectively, of the entire lifespan from birth. CONCLUSIONS: Hepatocellular carcinoma occurrence results in the loss of a considerable number of years-of-life, especially for younger patients. In recent years, the increased possibility of effectively treating this tumour has improved life expectancy, thus reducing years-of-life lost.

In vivo assessment of tumour angiogenesis in colorectal cancer: the role of confocal laser endomicroscopy.

AIM: Tumour neoangiogenesis is a key factor in tumour progression and metastatic spread and the possibility to assess tumour angiogenesis might provide prognostic information. The aim of this study was to establish the role of probe-based confocal laser endomicroscopy (p-CLE) in the identification of vascular architecture and specific morphological patterns in normal colorectal mucosa and malignant lesions during routine endoscopy. METHOD: Fourteen consecutive patients with colorectal cancer were included. The following features were identified and then compared between normal and neoplastic mucosa on p-CLE images: vessel shape (straight vs irregular) vessel diameter the 'branching patterns' vessel permeability (fluorescein leakage) and blood flow (normal vs defective flux). Immunohistochemistry was used to confirm the presence and to study the morphology of vascular structures (CD-34 staining) and 'neo-vessels' (WT-1 staining) on tumour and normal mucosal sections. RESULTS: Tumour vessels appeared as irregular, ectatic and with a highly variable calibre and branching patterns on p-CLE images. The mean diameter of tumour vessels was significantly larger than those in normal mucosa (weighted mean difference 3.38, 95% CI 2.65-4.11, P = 0.01). Similarly, 'vessel branching' (OR 2.74, 95% CI 1.23-6.14, P = 0.01), fluorescent dye 'extravasation' (OR 3.46, 95% CI 1.39-8.57, P = 0.01) were significantly more frequent in colorectal cancer than in normal colorectal mucosa. Immunohistochemistry corroborated the p-CLE findings, showing higher vascularity in tumour sections due to neoformed vessels, presenting irregular patterns. CONCLUSION: Probe-based confocal laser endomicroscopy provides a noninvasive characterization of the microvascular architecture of colonic mucosa. Different morphological patterns have been described, discriminating normal and malignant microvascular networks in colorectal mucosa.

Comparison between alcohol- and hepatitis C virus-related hepatocellular carcinoma: clinical presentation, treatment and outcome.

BACKGROUND: Hepatitis C virus (HCV) and alcohol abuse are the main risk factors for hepatocellular carcinoma (HCC) in Western countries. AIM: To investigate the role of alcoholic aetiology on clinical presentation, treatment and outcome of HCC as well as on each Barcelona Clinic Liver Cancer (BCLC) stage, as compared to HCV-related HCCs. METHODS: A total of 1642 HCV and 573 alcoholic patients from the Italian Liver Cancer (ITA.LI.CA) database, diagnosed with HCC between January 2000 and December 2012 were compared for age, gender, type of diagnosis, tumour burden, portal vein thrombosis (PVT), oesophageal varices, liver function tests, alpha-fetoprotein, BCLC, treatment and survival. Aetiology was tested as predictor of survival in multivariate Cox regression models and according to HCC stages. RESULTS: Cirrhosis was present in 96% of cases in both groups. Alcoholic patients were younger, more likely male, with HCC diagnosed outside surveillance, in intermediate/terminal BCLC stage and had worse liver function. After adjustment for the lead-time, median (95% CI) overall survival (OS) was 27.4 months (21.5-33.2) in alcoholic and 33.6 months (30.7-36.5) in HCV patients (P = 0.021). The prognostic role of aetiology disappeared when survival was assessed in each BCLC stage and in the Cox regression multivariate models. CONCLUSIONS: Alcoholic aetiology affects survival of HCC patients through its negative effects on secondary prevention and cancer presentation but not through a greater cancer aggressiveness or worse treatment result. In fact, survival adjusted for confounding factors was similar in alcoholic and HCV patients.

Protein-loosing enteropathy in sclerosing mesenteritis.

Sclerosing mesenteritis (SM) is a rare, idiopathic disorder of unknown aetiology that involves the adipose tissue of the mesentery, being characterized by chronic and non-specific fibrous inflammation. Patients usually present with non-specific clinical manifestations, such as abdominal pain and diarrhoea. The diagnosis of SM is difficult and it can be definitely established only by means of surgical or imaging-guided biopsy. Different therapeutic strategies have been used in case series with different rate of success. The disease is generally self-limiting, and the long-term prognosis is good, even if some cases of severe SM are reported in literature. Here, we report a fatal case of sclerosing mesenteritis associated to protein-losing enteropathy.

Immune parameters identify Italian centenarians with a longer five-year survival independent of their health and functional status.

Centenarians are rare and exceptional individuals characterized by a peculiar phenotype. They are the best example of healthy aging in humans as most of them have escaped or substantially delayed the onset of major age-related diseases. Within this scenario, the purpose of the present work was to understand if immune status is associated with survival and health status in centenarians. To this aim, 116 centenarians were concomitantly characterized for their immunological, health and functional status, and followed-up for five-year survival. On the basis of previous knowledge we focused on a core of fundamental and basic immune parameters (number of leukocytes, monocytes, total lymphocytes, CD3(+) T lymphocytes, CD4(+) helper T lymphocytes, CD8(+) cytotoxic T lymphocytes, CD19(+) B lymphocytes and plasma levels of IgM), and the most important findings can be summarized as follows: i. a hierarchical cluster analysis was able to define Cluster1 (88 centenarians) and Cluster2 (28 centenarians) characterized by low and high values of all these immune parameters, respectively; ii. centenarians of Cluster2 showed a statistically longer five-year survival and more favorable values of other important immune (naïve, activated/memory and effector/memory T cells) and metabolic (glycemia, insulin and HOMA-IR) parameters, in accord with previous observations that centenarians have a peculiar immune profile, a preserved insulin pathway and a lower incidence of type 2 diabetes; and iii. unexpectedly, parameters related to frailty, as well as functional and cognitive status, did not show any significant correlation with the immune clustering, despite being capable per se of predicting survival. In conclusion, high values of basic immunological parameters and important T cell subsets correlate with five-year survival in centenarians, independent of other phenotypic characteristics. This unexpected biological scenario is compatible with the general hypothesis that in centenarians a progressive disconnection and loss of biological coherence among the different functions of the body occur, where survival/mortality result from the failure of any of these domains which apparently follow an independent age-related trajectory.

Madelung disease : report of a case and review of the literature.

Madelung disease is a rare disorder characterized by the presence of multiple, symmetric, nonencapsulated fatty accumulations diffusely involving the cheeks, the neck, the upper trunk, the shoulder girdle area, and the upper extremities. The cause of this syndrome is unknown, but it has been associated with alcoholism in 60% to 90% of -patients. The long-term lipomatous deposits are often large and cosmetically deforming, and the upper aerodigestive tract and great veins may be compressed. We report the case of a man with MD, involving the cervical and upper dorsal -regions, who underwent surgical treatment at our Department.

Biliary duct injuries in the laparoscopic era: our experience.

AIM: The main aim of our study is to evaluate the incidence, the type, the causes and the therapy of biliary duct injuries which occurred after the video laparoscopic cholecystectomies performed in our Department during the period from 1990 to 2012. PATIENTS AND METHODS: A retrospective analysis of 1186 VLC has been made in our Department from March 1990 to June 2012. Before the cholecystectomy all patient were evaluated with trans abdominal echography. Beyond the incidence of BDI was evaluated damaging mechanism, etiology, therapy and time of diagnosis. RESULTS: From 1990 to 2012 a total of 9 BDIs occurred, with an incidence of 0,75%. Out of 9 patients 4 had major lesions and 5 had minor lesions; the most common BDI was Strasberg A (45%), the most common etiology was the presence of anatomical variations. In four cases the diagnosis has been intraoperative, in five cases has been postoperative. CONCLUSIONS: Our clinical experience shows that the main cause of BDI are the surgeon experience and the bile ducts anatomical variation.

Does the longevity of one or both parents influence the health status of their offspring?

According to the findings of some recent studies, the centenarians' offspring appear to represent a promising model for research on longevity and healthy aging. This study compares the health status and the functional status of three groups of subjects: 1. individuals with two long-lived parents (one of whom centenarian), 2. individuals with only one long-lived (centenarian) parent, and 3. individuals with no long-lived parents. The goal is to verify whether the centenarians' offspring display any advantage over the offspring of both non-long-lived parents and to evaluate whether the longevity of the non-centenarian parent provides a further advantage. A total of 374 subjects (mean age approximately 70 years) was examined. A threshold for longevity was established for non-centenarian parents through demographic data available for Italy (males surviving to at least 81 years of age and females to 87 years). The participants were assessed for their health and functional status by means of a standardized questionnaire and tests of physical performance. Data were analyzed using multivariate regression models adjusted for socio-demographic characteristics and risk factors for age-related pathologies. The results of the study show that centenarians' offspring have a better functional status, a reduced risk for several age-related pathologies and reduced drug consumption than the offspring of non-long-lived parents. In addition, the health status of centenarians' offspring does not appear to be influenced by the longevity of the second parent. It therefore seems possible to conclude that at ages around 70 years the genetic contribution to health status deriving from having one centenarian parent is not substantially improved if the other parent is also long-lived.

Metabolic syndrome in the offspring of centenarians: focus on prevalence, components, and adipokines.

With aging, an increased prevalence of a clustering of metabolic abnormalities has been observed. These abnormalities include obesity, dyslipidemia, hypertension, and insulin resistance and are collectively known as metabolic syndrome (MetS), a low-grade, systemic, inflammatory condition associated with an increased risk of cardiovascular disease, diabetes, and other adverse health outcomes. A number of studies have demonstrated that centenarians' offspring have a significant survival advantage and a lower risk of developing the most important age-related diseases. They therefore represent one of the best models with which to study the familiar component of human longevity. The aim of this study was to determine if the offspring of centenarians (n = 265 subjects) showed a different prevalence of MetS in comparison to the offspring of non-long-lived parents (controls, n = 101 subjects). In addition, we assessed whether centenarians' offspring showed particular features of MetS and a distinct regulation of circulating adipokines, cytokines, and metabolic mediators. Although the prevalence of MetS was quite similar both in the offspring of centenarians and the controls, MetS-affected centenarians' offspring seemed healthier, more functionally fit, and had lower resistin levels. MetS prevalence did not change in centenarians' offspring across resistin, IGF-1, and resistin/IGF-1 ratio tertiles. On the other hand, in controls, MetS prevalence strongly increased across resistin tertiles and in the third resistin/IGF-1 ratio tertile, indicating a dramatic increase in MetS prevalence when the ratio between these two factors is unbalanced, with high levels of resistin and low levels of IGF-1.

Prophylactic surgery in Lynch syndrome.

Lynch syndrome (LS) is caused by a germline mutations in DNA mismatch repair genes and is a dominantly inherited syndrome, responsible for 2-5% of all colorectal cancer (CRC) cases. Mutation carriers have a 60-85% risk of developing CRC. With the increasing use of genetic predisposition testing, patients and health care providers must decide on cancer risk-reduction strategies. The cancers observed in families with LS are diagnosed at an unusually early age and may be multiple. The decision about which surgery is suitable should be made on the basis of patient factors and preferences, with special emphasis on age, comorbidity, sphincteric function, and the ability of the patient to cope with intensive surveillance. Colectomy decreases the risk of second CRC significantly. The estimated lifetime risk for endometrial adenocarcinoma is 40-60% in women with LS, and the mean age at diagnosis is around 50 years. This risk equals or exceeds the risk of CRC. The optimal management of the elevated risk for cancer in carriers of mutations for hereditary nonpolyposis colorectal cancer is unclear. Patients who are gene mutation carriers should receive counseling about colectomy, and if women, prophylactic hysterectomy and bilateral oophorectomy.

Perspectives on the formation of an interdisciplinary research team.

As research funding becomes more competitive, it will be imperative for researchers to break the mentality of a single laboratory/single research focus and develop an interdisciplinary research team aimed at addressing real world challenges. Members of this team may be at the same institution, may be found regionally, or may be international. However, all must share the same passion for a topic that is bigger than any individual's research focus. Moreover, special consideration should be given to the professional development issues of junior faculty participating in interdisciplinary research teams. While participation may be "humbling" at times, the sheer volume of research progress that may be achieved through interdisciplinary collaboration, even in light of a short supply of grant dollars, is remarkable.

Neo-adjuvant treatment of rectal cancer with capecitabine and oxaliplatin in combination with radiotherapy: a phase II study.

BACKGROUND: Preoperative chemoradiation is now standard treatment for stages II-III rectal cancer. Capecitabine (CAP) and oxaliplatin (OX) are synergistic with radiotherapy (RT) and active in colorectal neoplasms. PATIENTS AND METHODS: Two cycles of CAP 825 mg/m(2) b.i.d. (days 1-14) and OX 50 mg/m(2) (days 1 and 8) every 3 weeks were given concomitantly with pelvic conformal RT (45 Gy). Patients with a > or =T3 and/or node-positive rectal tumour were eligible. The pathologic tumour response was defined according to the tumour regression grade (TRG) scale. RESULTS: Forty-six patients were enrolled. Gastrointestinal adverse events were mostly G1-G2; only two patients experienced G3 vomiting and diarrhoea and six patients had G1 peripheral neuropathy. Haematological toxicity was rare. G2 proctitis and anal pain occurred in two patients. Pathological complete response (TRG1) was observed in nine patients (20.9%; 95% CI 8.7%-33.1%); TRG2 in 19 patients (44.2%); TRG3 in 12 patients (27.9%); and TRG4 in three patients (7%). Overall, nine patients recurred: five with distant metastases, one with local recurrence, and three with both local recurrence and distant metastases. CONCLUSIONS: CAP-OX-RT as preoperative treatment for rectal cancer induces a remarkable rate of complete or near-complete pathologically documented response and is well tolerated.

Immunosenescence and immunogenetics of human longevity.

At present, individuals can live up to 80-120 years, a time much longer than that of our ancestors, as a consequence of the improvements in life conditions and medical care. Thus, the human immune system has to cope with a lifelong and evolutionarily unpredicted exposure to a variety of antigens, which are at the basis of profound age-related changes globally indicated as immunosenescence, a multifaceted phenomenon that increases morbidity and mortality due to infections and age-related pathologies. The major changes occurring during immunosenescence are the result of the accumulation of cellular, molecular defects and involutive phenomena (such as thymic involution) occurring concomitantly to a hyperstimulation of both innate and adaptive immunity (accumulation of expanded clones of memory and effector T cells, shrinkage of the T cell receptor repertoire, progressive activation of macrophages), and resulting in a low-grade, chronic state of inflammation defined as inflammaging. It is unknown whether inflammaging, which represents a risk factor for most age-related pathologies, is a cause or rather an effect of the aging process. In this complex scenario, the role of genetic background likely represents a fundamental variable to attain successful aging and longevity. Accordingly, centenarians seem to be equipped with gene variants that allow them to optimize the balance between pro- and anti-inflammatory molecules, and thus to minimize the effects of the lifelong exposure to environmental insults and stressors. The remarkable features of the genetics of aging and longevity are reviewed, stressing the unexpected and unusual results obtained regarding such a postreproductive type of genetics.