Massive bone allograft engineered with autologous vessels: A new perspective for the future.

Reconstruction is very important to ensure good function and quality of life after bone tumor resection. For metacarpals and phalanges, amputation and toe transfer are the gold-standard indications; nevertheless, allograft reconstruction must also be taken into account. Unfortunately, because of its inert biological behavior, it undergoes progressive resorption, with frequent fracture. Several attempts have been made to induce new vascularization in massive bone allograft, with poor results. However, neo-angiogenesis was reported with vascular loops, and we therefore hypothesized that heterologous graft integration could be enhanced by creating a vascular loop through the graft. A 50-year-old male with chondrosarcoma of the ring finger of the left hand underwent wide resection. An allogenic middle phalanx of comparable size was then prepared to fill the defect. Two small windows were performed proximally and distally on the radial surface of the allogenic phalanx, and a 4 cm-long vein graft was inserted inside the medullary canal. Metacarpophalangeal joint stability was achieved by collateral ligament reconstruction with micro-anchors. The distal part of the allograft was then stabilized to the middle phalanx with a 1.5 mm-thick micro-plate and screws. The radial proper palmar digital artery was proximally and distally sutured end-to-end to the vein graft, under microscopy. At 12-month follow-up, the allograft was fused, and histology performed at plate removal at 18 months revealed viable spindle cells with osteoblastic differentiation, without evidence of atypia, in a dense fibrous stroma. At 22 months' follow-up, the patient was apparently disease-free, and satisfied with his manual function.

Cytology and direct human papillomavirus testing on fine needle aspirates from cervical lymph node metastases of patients with oropharyngeal squamous cell carcinoma or occult primary.

OBJECTIVE: Cervical lymph node fine needle aspirates (FNAs) may represent the only specimens available for an initial characterisation of patients with lymphadenopathy. Morphology and human papillomavirus (HPV) DNA presence were evaluated in FNAs collected from patients with oropharyngeal squamous cell carcinoma (OPSCC) or cancer of unknown primary (CUP). FNA HPV results were compared with those of the respective formalin-fixed paraffin-embedded (FFPE) primary cancer. METHODS: Liquid-based cytology was performed on FNAs collected in PreservCyt. HPV-DNA was analysed by the INNO-LiPA HPV genotyping Extra II on both cytological and FFPE samples. The CINtec® Histology Kit was used to assess p16 expression in cancer tissues. RESULTS: Forty-seven FNAs were collected from OPSCC and 16 from CUP patients. Cancer cells were found in 35/47 cases (74.5%), while 11 (23.4%) showed only necrosis and one (2.1%) was negative for malignancy. HPV-DNA was detected in 30/47 FNAs (63.8%), mostly harbouring HPV16 (90.0%). An excellent agreement was observed between the FNA and corresponding FFPE HPV status (raw agreement: 97.5%; Cohen κ: 0.94). The HPV test result on the necrotic FNAs completely matched that of the respective primary cancer. FNA HPV testing correctly identified 26/27 HPV-driven OPSCCs (96.3%). HPV was detected in nine of 16 FNAs (56.2%) from CUP patients. CONCLUSIONS: HPV status of metastatic cervical lymph node FNAs reflects that of the corresponding primary OPSCCs even when cell integrity in the FNA is not preserved and only necrotic debris are present. In patients with initial CUP, HPV-positivity on the FNA may guide the diagnostic workup and therapeutic management, since it suggests an oropharyngeal origin.

Limb saving procedure in metastatic leiomyosarcoma of the femoral vein: case report and literature review.

Primary venous leiomyosarcoma is very rare and first description was made by Perl in 1871. Most cases are from venous system and half of them are reported to originate in inferior vena cava. We report the case of a 77-year-old Caucasian man with a leiomyosarcoma of the femoral vein. A leg preservation surgery was decided. Eight months later, the patient died of tumor progression. A PubMed search using the terms "leiomyosarcoma femoral vein" and "leiomyosarcoma vein" was performed. All cases of composite iliac-femoral leiomyosarcoma were excluded, and as far as possible, only well-documented cases were included. Median age was 55 years, seven men and six women, tumor resection was performed by six authors, six others performed a vascular resection, and one preferred for a thigh excision. Prognosis remains poor if metastasis is present, and in these cases, a conservative surgery is recommended to preserve patients' quality of life.

A Bayesian network meta-analysis on the effect of inodilatory agents on mortality.

BACKGROUND: Inodilators are commonly used in critically ill patients, but their effect on survival has not been properly studied to date. The objective of this work was to conduct a network meta-analysis on the effects of inodilators on survival in adult cardiac surgery patients, and to compare and rank drugs that have not been adequately compared in head-to-head trials. METHODS: Relevant studies were independently searched in BioMedCentral, MEDLINE/PubMed, Embase, and the Cochrane Central Register of clinical trials (updated on May 1, 2014). The criteria for inclusion were: random allocation to treatment with at least one group receiving dobutamine, enoximone, levosimendan, or milrinone and at least another group receiving the above inodilators or placebo, performed in cardiac surgical patients. The endpoint was to identify differences in mortality at longest follow-up available. RESULTS: The 46 included trials were published between 1995 and 2014 and randomised 2647 patients. The Bayesian network meta-analysis found that only the use of levosimendan was associated with a decrease in mortality when compared with placebo (posterior mean of OR=0.48, 95% CrI 0.28 to 0.80). The posterior distribution of the probability for each inodilator to be the best and the worst drug showed that levosimendan is the best agent to improve survival after cardiac surgery. The sensitivity analyses performed did not produce different interpretative result. CONCLUSION: Levosimendan seems to be the most efficacious inodilator to improve survival in cardiac surgery.

Volatile compared with total intravenous anaesthesia in patients undergoing high-risk cardiac surgery: a randomized multicentre study.

BACKGROUND: The effect of anaesthesia on postoperative outcome is unclear. Cardioprotective properties of volatile anaesthetics have been demonstrated experimentally and in haemodynamically stable patients undergoing coronary artery bypass grafting. Their effects in patients undergoing high-risk cardiac surgery have not been reported. METHODS: We performed a multicentre, randomized, parallel group, controlled study among patients undergoing high-risk cardiac surgery (combined valvular and coronary surgery) in 2008-2011. One hundred subjects assigned to the treatment group received sevoflurane for anaesthesia maintenance, while 100 subjects assigned to the control group received propofol-based total i.v. anaesthesia. The primary outcome was a composite of death, prolonged intensive care unit (ICU) stay, or both. Thirty day and 1 yr follow-up, focused on mortality, was performed. RESULTS: All 200 subjects completed the follow-up and were included in efficacy analyses, conducted according to the intention-to-treat principle. Death, prolonged ICU stay, or both occurred in 36 out of 100 subjects (36%) in the propofol group and in 41 out of 100 subjects (41%) in the sevoflurane group; relative risk 1.14, 95% confidence interval 0.8-1.62; P=0.5. No difference was identified in postoperative cardiac troponin release [1.1 (0.7-2) compared with 1.2 (0.6-2.4) ng ml(-1), P=0.6], 1 yr all-cause mortality [11/100 (11%) compared with 11/100 (11%), P=0.9], re-hospitalizations [20/89 (22.5%) compared with 11/89 (12.4%), P=0.075], and adverse cardiac events [10/89 (11.2%) compared with 9/89 (10.1%), P=0.8]. CONCLUSIONS: There was no observed beneficial effect of sevoflurane on the composite endpoint of prolonged ICU stay, mortality, or both in patients undergoing high-risk cardiac surgery. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov: identifier NCT00821262. Eudra CT (2008-001752-43).

Expression of TP53 mutation-associated microRNAs predicts clinical outcome in head and neck squamous cell carcinoma patients.

BACKGROUND: TP53 mutation is associated with decreased survival rate in head and neck squamous cell carcinoma (HNSCC) patients. We set out to identify microRNAs (miRNAs) whose expression associates with TP53 mutation and survival in HNSCC. PATIENTS AND METHODS: We analyzed TP53 status by direct sequencing of exons 2 through 11 of a prospective series of 121 HNSCC samples and assessed its association with outcome in 109 followed-up patients. We carried out miRNA expression profiling on 121 HNSCC samples and 66 normal counterparts. miRNA associations with TP53 mutations and outcome were evaluated. RESULTS: A TP53 mutation was present in 58% of the tumors and TP53 mutations were significantly associated with a shorter recurrence-free survival. This association was stronger in the clinical subgroup of patients subjected to adjuvant therapy after surgery. The expression of 49 miRNAs was significantly associated with TP53 status. Among these 49, we identified a group of 12 miRNAs whose expression correlates with recurrence-free survival and a group of 4 miRNAs that correlates with cancer-specific survival. The two groups share three miRNAs. Importantly, miRNAs that correlate with survival are independent prognostic factors either when considered individually or as signatures. CONCLUSIONS: miRNAs expression associates with TP53 status and with reduced survival after surgical treatment of squamous cell carcinoma of the head and neck.

An unusual case of lumbar paravertebral miositis ossificans mimicking muscular skeletal tumor.

Several lesions have clinical and radiological characteristics mimicking muscular skeletal tumor. Myositis ossificans usually presents a typical pattern making biopsy unnecessary; nevertheless, in rare cases, neoplasm must be ruled out. Biopsy is often sufficient to allow a diagnosis and a correct related treatment, but, unfortunately, sometimes it may lead to erroneous treatment. We report an unusual case of a lumbar paravertebral mass that had an MRI aspect similar to a chondrosarcoma, a histology pattern based on biopsy compatible with neurinoma and a definitive diagnosis of myosistis ossificans.

A cyanoacrylate and silastic patch to reduce the risk of opening of the tumor: technical note.

BACKGROUND: Wide surgery is the main factor influencing survival in muscular skeletal tumor. Sometimes the margin can be very thin and the contamination risk can be very high because of manipulation of the mass. MATERIALS AND METHODS: A patch of cyanoacrylate and a silastic mesh are applied on tumor surface. In order to demonstrate the tumor sealing an histologic exam was performed. DISCUSSION: The application of protective patch can decrease the risk of accidental tumor rupture and neoplastic cells spreading.

Transcatheter implantation of an aortic valve: anesthesiological management.

AIM: Transcatheter aortic valve implantation (TAVI) is an emergent alternative technique to surgery in high-risk patients with aortic stenosis. Here, we describe the anesthesiological management of patients undergoing TAVI at our institution over an 18-month period. METHODS: After a proper assessment of surgical risk and comorbidities, 69 patients underwent TAVI with the transfemoral/subclavian approach. Both Edwards-Sapien and Corevalve prostheses were implanted. The anesthetic regimen consisted of general anesthesia or local anesthesia plus sedation. RESULTS: Twenty-seven patients received general anesthesia, and 42 received local anesthesia plus sedation. Procedural complications included prosthesis embolization (2), ascending aorta dissection (1), ventricular fibrillation following rapid ventricular pacing (8), vascular access site complications (17), and the valve-in-valve procedure (1). Three patients had to be converted from local anesthesia to general anesthesia (one patient had refractory ventricular fibrillation, and two patients were restless). All patients were alive at the 30-day follow-up. Mechanical ventilation time was 8.5+/-0.03 h. Mean ICU stay was 20.1+/-2.89 h. Postoperative complications included acute renal dysfunction (11), advanced atrioventricular block (9), and stroke (1). Thirty-six out of 42 (86%) patients were alive at the 6-month follow-up. CONCLUSIONS: TAVI is feasible in high-risk patients who would not be able to undergo surgical valve replacement. Hemodynamic management is the main concern of intraoperative anesthesiological management. General or local anesthesia plus sedation are both valid alternative techniques that can be titrated according to patient characteristics. Close postoperative monitoring in the ICU is required.

Percutaneous aortic valve implantation: the anesthesiologist perspective.

Percutaneous aortic valve implantation is an emergent technique alternative to surgical aortic valve replacement in high risk patients with aortic stenosis. Percutaneous aortic valve implantation techniques are undergoing rapid development and currently represent a dynamic field of research. Perioperative optimal strategies keep on evolving too. At a review of the literature, only three previous papers on Pubmed focused specifically on anesthesiological challenges of percutaneous aortic valve implantation. In one of them our first 6 months experience was reported. In this new paper we describe the anesthesiological management of percutaneous aortic valve implantation at our Centre, reporting the results of our implantation program from November 2007 to February 2009.

Acute renal failure and cardiac surgery.

Acute renal failure (ARF) is s a major complication after cardiac surgery and its prevalence still remains high. Even minor changes in serum creatinine are related to an increase morbidity and mortality. Recently two consensus conferences have suggested new diagnostic criteria to define acute kidney injury and risk scores to better identify patients who will probably develop ARF after cardiac surgery. In fact a prompt recognition of high risk patients could allow a more aggressive therapy at a reversible stage of an incoming ARF. To date prophylactic strategies of renal function preservation during surgery include the avoidance of nephrotoxic insult and the prevention or correction of renal hypoperfusion. Although there are still no pharmacological agents able to prevent the perioperative ARF, several trials are investigating new pharmacological approaches. When prophylactic strategies fail and severe ARF occurs, renal replacement therapy becomes mandatory. The timing and the kind of renal replacement therapy remain an open issue. Further randomized case-control studies with adequate statistical power are needed to have more conclusive data. Aim of this paper is to start from the acute renal injury physiopathology to analyze the most common prophylactic and pharmacological strategies.

Oral cavity and base of the tongue tumors. Correlation between clinical, MRI and pathological staging of primary tumor.

The diagnosis of oral cavity and oropharyngeal tumors can be obtained through clinical examination and biopsy. CT and MRI can then be used to define the extension of the disease. The aim of this study was to define the accuracy of clinical and MRI T staging of oral cavity and base of the tongue tumors and correlate the results with pathological data. Mandibular involvement, in a subgroup of patients, was determined and sensitivity, specificity, accuracy and positive and negative predictive values were evaluated. Fifty-nine patients affected by squamous cell carcinoma and 1 case of adenoido-cystic carcinoma were examined by means of a superconductive MR unit, using SE T1, and fat-suppressed T2 weighted sequences before contrast medium infusion. SE T1 and T1 fat-suppressed sequences after gadolinium-DTPA infusion were used. T stage accuracy of both clinical examination and MRI were found to be respectively 62% (k 0.459) and 82% (k 0.775). The sensitivity, specificity and accuracy of MRI in the detection of mandibular involvement were 94.1%, 60% and 81.5%, while the positive and negative predictive values were 80% and 85.7%, respectively. The sensitivity, specificity and accuracy of clinical examination in the detection of mandibular involvement were 100%, 30% and 74.1%, while the positive and negative predictive values were 70.8% and 100%. In the present study, MRI was seen to be an adequate technique for the assessment of oral cavity malignancies, in the evaluation of depth invasion, presence and extension of mandibular involvement.

[Clinical guidelines for the management of gastrointestinal stromal tumors]. / Raccomandazioni cliniche per la diagnosi, la terapia ed il follow-up dei tumori stromali gastrointestinali.

Treatment of gastrointestinal stromal tumors (GIST) has been revolutioned by the recently discovered molecular mechanism responsible for the oncogenesis of this disease. In addition, due to the rapid progress at molecular and clinical level observed in the last few years, there is a need to review the current state of the art in order to delineate appropriate guidelines for the optimal management of these tumors. A panel of experts from several specialities, including medical oncology, surgery, pathology, molecular biology and imaging, were invited to participate in a meeting to present and discuss a number of pre-selected questions, and to achieve a consensus according to the categories of the National Comprehensive Cancer Network (NCCN) and the Standard Options Recommandations (SOR) of the French Federation of Cancer Centers. Generally, consensus points were from categories 2A of the NCCN and B2 of the SOR. Conventional histologic examination with immunohistochemistry for CD117, CD34, SMA, S-100 and desmin is considered standard. Molecular analysis for the identification of KIT and PDGFRA mutation may be indicated in CD117-negative GIST. Complete tumor resection with negative margins is the optimal surgical treatment. Adjuvant imatinib should be considered an experimental approach. Neoadjuvant imatinib is also experimental, although its use may be justified in unresectable or marginally resectable GIST. Imatinib should be started in metastatic or recurrent disease, and should be continued until progressive disease or drug intolerance. In these cases, sunitinib can be used. The optimal criteria for the assessment and monitoring of GIST undergoing imatinib therapy are not well known, but they should include reduction in tumor size and disease stabilization, as well as reduction of tumor density on CT scan and metabolic activity on PET scan.

[Benign metastasizing pulmonary leiomyoma: description of a case and review of the literature]. / Leiomioma metastatizzante benigno nel polmone: descrizione di un caso e revisione della letteratura.

We report the case of a 48-year-old woman with multiple benign metastasizing leiomyomas in both lungs and a single retroperitoneal leiomyoma. The patient underwent surgical resection of the lesions 15 years after total hysterectomy for uterine myomas. Immunohistochemical studies performed on the retroperitoneal and pulmonary neoplasms showed them to be of mesenchymal derivation with smooth muscle differentiation; the samples were negative for HMB-45. Some histogenetic hypotheses for the multiple leiomyomas are presented.

Uterine diffuse adenomatoid tumor. Does it represent a different biological entity?

Adenomatoid tumor represents a type of mesothelioma apparently confined to the genital tract and characterized by its benign behavior. Its morphological aspects are well known and, until now, it has been described as a nodular mass except for a case diffusely infiltrating the entire myometrium in an immunosuppressed patient. We report a case of benign mesothelial tumor characterized by histological, immunophenotypical and ultrastructural features of an otherwise typical adenomatoid tumor but diffusely growing below uterine serosal surface into the myometrium without discernible borders. The existence of a diffuse type of adenomatoid tumor might reflect a different nature of this neoplasm leading to the hypothesis that this variant of benign mesothelioma represents a distinct biological entity.