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.

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.

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.

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.

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.

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.

Decreased fluid volume to reduce organ damage: a new approach to burn shock resuscitation? A preliminary study.

OBJECTIVE: To evaluate the impact of decreased fluid resuscitation on multiple-organ dysfunction after severe burns. This approach was referred to as "permissive hypovolaemia". METHODS: Two cohorts of patients with burns>20% BSA without associated injuries and admitted to ICU within 6 h from the thermal injury were compared. Patients were matched for both age and burn severity. The multiple-organ dysfunction score (MODS) by Marshall was calculated for 10 days after ICU admission. Permissive hypovolaemia was administered by a haemodynamic-oriented approach throughout the first 24-h period. Haemodynamic variables, arterial blood lactates and net fluid balance were obtained throughout the first 48 h. RESULTS: Twenty-four patients were enrolled: twelve of them received the Parkland Formula while twelve were resuscitated according to the permissive hypovolaemic approach. Permissive hypovolaemia allowed for less volume infusion (3.2+/-0.7 ml/kg/% burn versus 4.6+/-0.3 ml/kg/% burn; P<0.001), a reduced positive fluid balance (+7.5+/-5.4 l/day versus +12+/-4.7 l/day; P<0.05) and significantly lesser MODS Score values (P=0.003) than the Parkland Formula. Both haemodynamic variables and arterial blood lactate levels were comparable between the patient cohorts throughout the resuscitation period. CONCLUSIONS: Permissive hypovolaemia seems safe and well tolerated by burn patients. Moreover, it seems effective in reducing multiple-organ dysfunction as induced by oedema fluid accumulation and inadequate O2 tissue utilization.

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.

Age-dependent modifications of Type 1 and Type 2 cytokines within virgin and memory CD4+ T cells in humans.

Several alterations in immune function and a concomitant progressive increase in pro-inflammatory status are the major characteristics of ageing process. Cytokines play a key role during ageing acting both in regulatory communication among cells and in effector activity during an immune response. The impact of age on intracellular Type 1 (IFN-gamma and TNF-alpha) and Type 2 (IL-4) cytokines, after stimulation with PMA/ionomycin, was determined in three CD4+ T subsets, i.e. CD95- CD28+ (virgin), CD95+ CD28+ (activated/memory), and CD95+ CD28- (effector/memory) from 47 subjects aged between 21 and 99 years. The percentage of IFN-gamma positive cells significantly decreased in virgin CD4+ subset both in old and nonagenarian subjects, as well as in activated/memory T cells from old in comparison with young subjects. The percentage of TNF-alpha positive cells significantly decreased in activated/memory CD4+ subset from old people. Regarding Type 2 cytokines, IL-4 positive cells significantly increased in activated/memory CD4+ subset from nonagenarians. On the whole our data indicate that: (1) different Type 1 and Type 2 cytokine-positive CD4+ T subsets are differently affected by ageing process; (2) activated/memory T cells appear to be the most affected subset; (3) a shift towards an increased role of Type 2 cytokines and a diminished role of Type 1 cytokines emerges with ageing.

Cinedefecographic findings in patients with obstructed defecation sindrome. A study in 420 cases.

AIM: Obstructed defecation syndrome (ODS) represents a very common clinical problem. The aim of this study was to analyze the cinedefecographic findings in a group of patients with ODS. METHODS: All patients with ODS were prospectively introduced into a database and underwent cinedefecography (CD). The grade of the syndrome was assessed by a new ODS score. The validated Agachan-Wexner Constipation Score System was also used. Four lateral films were taken during resting, squeeze, pushing and postevacuation phases and puborectalis length (PRL), anorectal angle (ARA) and perineal descent were recorded and analysed. The presence of an increased fixed perineal descent (FPD) and dynamic perineal descent (DPD), mucosal rectal prolapse (MRP), recto-rectal intussusception (RRI), recto-anal intussusception (RAI), rectocele (RE), enterocele (ET) and sigmoidocele (SG) were also evaluated. RESULTS: Between February 2002 and March 2005, 420 patients, 404 (96.1%) females and 16 (3.8%) males with a mean age of 49+/-7.7 (range, 21-77) years, underwent CD. In 362 (86.2%) patients CD showed a combination of different cinedefecographic findings. RE, FPD and DPD in association with RAI or RRI were contemporary observed in 118 (26%) patients. MRP, RRI, FPD, RAI and RE were observed as singular finding in 21 (5%), 19 (4.5%), 12 (2.8%), 3 (0.7%) and 3 (0.7%) patients, respectively. In 6 (1.4%) patients a paradoxical contraction of the puborectalis muscle was observed. CONCLUSIONS: CD shows that ODS is largely caused by multiple patterns of different abnormalities of the rectum and pelvic floor. Any treatment in symptomatic patients could be designed to treat multiple combinations of different abnormalities.

Residual damage in mouse lungs at long intervals after cyclophosphamide treatment.

The purpose of these studies was to quantify the effects of radiation given to mouse lungs at intervals up to 6 months after injection of the maximally tolerated dose of cyclophosphamide. In one set of experiments a single i.p. injection of 300 mg/kg of cyclophosphamide was followed at either 1, 3, or 6 months by a range of single doses of gamma-rays delivered to the whole thorax only. In a second set of experiments mice were given five daily i.p. injections of cyclophosphamide, 100 mg/kg, followed at 1, 3, and 6 months by a range of fractionated doses of X-rays. Breathing rate, histology, and mortality were used to assess lung damage. These data were compared with age-matched animals given either the drug alone or single doses of radiation alone. Dose-response curves of lethality were constructed and fitted by a logit program, and 50% lethal doses with 95% confidence limits were determined at monthly intervals after irradiation. Dose enhancement factors were then calculated at this isoeffect for the mice given the drug and radiation. Deaths from radiation pneumonitis occurred as early as 6 weeks in mice given cyclophosphamide before irradiation; few deaths occurred after 26 weeks. However, in the mice given radiation alone, deaths from pneumonitis did not occur before 12 weeks. Cyclophosphamide given as either single doses or fractionated doses at all three times before irradiation enhanced radiation pneumonitis in mouse lung. Dose enhancement factors of 1.2, 1.4, and 1.3 were obtained when single doses of radiation followed single doses of cyclophosphamide at 1, 3, and 6 months, respectively. The dose enhancement factor for radiation pneumonitis after the fractionated exposures was less, 1.1, and was independent of time between the two treatments. An enhancement factor of 1.2 was observed for the later wave of lung damage in those few studies available for analysis at this time. These data clearly show that prior treatment of the animal with cyclophosphamide significantly reduces the radiation dose that can be given to the lung for as long as 6 months after drug treatment. In addition, lung damage occurred sooner when the drug was given prior to irradiation. These data indicate that the lung will be sensitive to retreatment with radiation when a full tolerance dose of cyclophosphamide precedes radiation.

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.

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.