Role of the Cadaver Lab in Lymphatic Microsurgery Education: Validation of a New Training Model.

BACKGROUND: Microsurgical transplantation of vascularized lymph nodes (VLNT) or lymphatic vessels (VLVT) alongside derivative lymphaticovenous procedures are promising approaches for treatment of lymphedema. However, clinically relevant training models for mastering these techniques are still lacking. Here we describe a new training model in human cadaver and validate its use as training tool for microsurgical lymphatic reconstruction. METHODS: 10 surgeons with previous exposure to microsurgery were trained in a controlled environment. Lymphatic vessel mapping and dissection in 4 relevant body regions, harvesting of five different VLNTs and one VLVT were performed in 5 fresh-frozen cadavers. The number of lymphatic vessels and lymph nodes for each VLNT were recorded. Finally, the efficacy of this model as training tool was validated using the Dundee Ready Education Environment Measure (DREEM). RESULTS: The average cumulative DREEM score over each category was 30,75 (max = 40) while individual scoring for each relevant category revealed highly positive ratings from the perspective of teaching (39,3), training 40,5 (max = 48) and self perception of the training 30,5 (max = 32) from all participants. The groin revealed the highest number of lymphatic vessels (3.2 ± 0.29) as all other regions on the upper extremity, while the gastroepiploic VLNT had the highest number of lymph nodes (4.2 ± 0.37). CONCLUSIONS: This human cadaver model represents a new, reproducible "all-in-one" tool for effective training in lymphatic microsurgery. Its unique diligence in accurately reproducing human lymphatic anatomy, should make this model worth considering for each microsurgeon willing to approach lymphatic reconstruction.

Creation and application of virtual patient cohorts of heart models.

Patient-specific cardiac models are now being used to guide therapies. The increased use of patient-specific cardiac simulations in clinical care will give rise to the development of virtual cohorts of cardiac models. These cohorts will allow cardiac simulations to capture and quantify inter-patient variability. However, the development of virtual cohorts of cardiac models will require the transformation of cardiac modelling from small numbers of bespoke models to robust and rapid workflows that can create large numbers of models. In this review, we describe the state of the art in virtual cohorts of cardiac models, the process of creating virtual cohorts of cardiac models, and how to generate the individual cohort member models, followed by a discussion of the potential and future applications of virtual cohorts of cardiac models. This article is part of the theme issue 'Uncertainty quantification in cardiac and cardiovascular modelling and simulation'.

Collagen (NeuraGen®) nerve conduits and stem cells for peripheral nerve gap repair.

Collagen nerve guides are used clinically for peripheral nerve defects, but their use is generally limited to lesions up to 3 cm. In this study we combined collagen conduits with cells as an alternative strategy to support nerve regeneration over longer gaps. In vitro cell adherence to collagen conduits (NeuraGen(®) nerve guides) was assessed by scanning electron microscopy. For in vivo experiments, conduits were seeded with either Schwann cells (SC), SC-like differentiated bone marrow-derived mesenchymal stem cells (dMSC), SC-like differentiated adipose-derived stem cells (dASC) or left empty (control group), conduits were used to bridge a 1cm gap in the rat sciatic nerve and after 2-weeks immunohistochemical analysis was performed to assess axonal regeneration and SC infiltration. The regenerative cells showed good adherence to the collagen walls. Primary SC showed significant improvement in distal stump sprouting. No significant differences in proximal regeneration distances were noticed among experimental groups. dMSC and dASC-loaded conduits showed a diffuse sprouting pattern, while SC-loaded showed an enhanced cone pattern and a typical sprouting along the conduits walls, suggesting an increased affinity for the collagen type I fibrillar structure. NeuraGen(®) guides showed high affinity of regenerative cells and could be used as efficient vehicle for cell delivery. However, surface modifications (e.g. with extracellular matrix molecule peptides) of NeuraGen(®) guides could be used in future tissue-engineering applications to better exploit the cell potential.

Lymphatic microsurgical preventing healing approach (LYMPHA) for primary surgical prevention of breast cancer-related lymphedema: over 4 years follow-up.

Breast cancer-related lymphedema (LE) represents an important morbidity that jeopardizes breast cancer patients' quality of life. Different attempts to prevent LE brought about improvements in the incidence of the pathology but LE still represents a frequent occurrence in breast cancer survivors. Over 4 years ago, Lymphatic Microsurgical Preventing Healing Approach (LYMPHA) was proposed and long-term results are reported in this study. From July 2008 to December 2012, 74 patients underwent axillary nodal dissection for breast cancer treatment together with LYMPHA procedure. Volumetry was performed preoperatively in all patients and after 1, 3, 6, 12 months, and once a year. Lymphoscintigraphy was performed in 45 patients preoperatively and in 30 also postoperatively after at least over 1 year. Seventy one patients had no sign of LE, and volumetry was coincident to preoperative condition. In three patients, LE occurred after 8-12 months postoperatively. Lymphoscintigraphy showed the patency of lymphatic-venous anastomoses at 1-4 years after operation. LYMPHA technique represents a successful surgical procedure for primary prevention of arm LE in breast cancer patients.

Evolution of chylous fistula management after neck dissection.

PURPOSE OF REVIEW: The present review is focused on the management of lymphatic, chylous, and thoracic duct lesions following head and neck surgery, with particular attention to these complications after neck dissection. Postoperative scenarios may include chylous fistula, chylothorax, chylomediastinum, chylopericardium, lymphocele, persistent lymphorrhea, and secondary lymphedema. RECENT FINDINGS: There is a paucity of literature on the treatment of lymphatic, chylous, and thoracic duct injuries following head and neck surgery; however, this review suggests that the most appropriate treatment should include both conservative and surgical approaches. Nonsurgical options consist of low-fat diet with medium-chain triglycerides, total parenteral nutrition, careful monitoring of fluid and electrolytes, drainage of the leakage, somatostatin analogs such as octreotide, and negative-pressure wound therapy. On the other hand, surgical management includes therapeutic percutaneous lymphography-guided thoracic duct cannulation and embolization, thoracic duct ligation, excision and imbrication of leaking lymphatics, chylous fistula surgical/microsurgical repair, fistula closure by locoregional flaps, video-assisted thoracoscopic surgery, thoracotomy, pleurodesis and decortication, pericardial 'window', and pleura-venous/pleura-peritoneal shunts. In addition, single or, preferably, multiple lymphovenous anastomoses may be taken into account. SUMMARY: The various possible clinical presentations of such challenging lymphatic, chylous, and thoracic duct injuries require an appropriate multidisciplinary approach by experienced teams. Primary prevention of these complications can be achieved through adequate surgical planning to minimize lesions, including structured and thorough patient assessment, and centralization of resources and teams.

Core elements of physiotherapy in cerebral palsy children: proposal for a trial checklist.

BACKGROUND: Currently international literature describes physiotherapy in cerebral palsy (CP) children only in generic terms (traditional / standard / background / routine). AIM: The aim of this study is to create a checklist capable of describing the different modalities employed in physiotherapeutic treatment by means of a non-bias, common, universal, standardised language. DESIGN: A preliminary checklist was outlined by a group of physiotherapists specialised in child rehabilitation. SETTING: For its experimentation, several physiotherapists from various paediatric units from all over Italy with different methodological approaches and backgrounds, were involved. METHODS: Using the interpretative model, proposed by Ferrari et al., and through collective analysis and discussion of clinical videos, the core elements were progressively selected and codified. A reliability study was then carried out by eight expert physiotherapists using an inter-rate agreement model. RESULTS: The checklist analyses therapeutic proposals of CP rehabilitation through the description of settings, exercises and facilitations and consists of items and variables which codify all possible physiotherapeutic interventions. It is accompanied by written explanations, demonstrative videos, caregiver interviews and descriptions of applied environmental adaptations. All checklist items obtained a high level of agreement (according to Cohen's kappa coefficient), revealing that the checklist is clearly and easily interpretable. CONCLUSION: The checklist should facilitate interaction and communication between specialists and families, and lead to comparable research studies and scientific advances. CLINICAL REHABILITATION IMPACT: The main value is to be able to correlate therapeutic results with core elements of adopted physiotherapy.

Hydrogen breath test--diet and basal H2 excretion: a technical note.

BACKGROUND: Hydrogen breath tests are widely used in clinical practice. For a correct evaluation of data, low basal H2 excretion is required, thus, 12-hour fasting is usually prescribed. An additional reduction in the intake of complex carbohydrates in the preceding 24 h is suggested in some centers. The issue, however, has never been directly investigated. AIM: The aim of the present study was to analyze the effect of the pretest diet on the basal H2 excretion and the number of subjects excluded from the test due to high basal H2 excretion. METHODS: Two cohorts of 500 consecutive patients undergoing a lactose tolerance test in the years 1997-1998 (when 12-hour fasting was required) and in 2007-2008 (when a low-carbohydrate diet in the preceding 24 h was also prescribed) were retrospectively reviewed. RESULTS: The mean basal H2 excretion was significantly lower (p < 0.0001) in the low-carbohydrate diet group (2.46 +/- 6.8 vs. 4.73 +/- 3.3 ppm). In 1997-1998, 46/500 patients (9.2%) were excluded from the test due to basal H2 values as compared to 7/500 (1.4%) in the period 2007-2008. DISCUSSION: To the best of our knowledge, ours is the first study to provide objective data on the advantage offered by reducing the intake of complex carbohydrates before H2 breath tests.

Meningitis linfomatosa como sitio de recaída en la enfermedad de Hodgkin / Limphomatous meningitis as recurrence site in Hodgkin's disease

Intracraneal manifestations of Hodgkin's Disease (HD) are extremely rare, with an estimated incidence rate of approximately 0.5%. They can be classified as: 1) treatment-related leucoencephalopathy, 2) central nervous system infections, 3) paraneoplasic syndromes and 4) intracraneal lymphomas, which could be sub-classified into intraparenchymal or intradural masses. We describe a case of a 40 year-old male with mixed cellularity type HD who developed neurological manifestations as relapsed disease. Magnetic resonance imaging suggested leptomeningeal metastases and atypical cells were found in cerebrospinal fluid. The patient died from progressive disease refractory to third line chemotherapy. There are less than 50 similar cases reported in the literature. We review the clinical features and differential diagnosis of leptomeningeal metastases in Hodgkin's disease.

Identification and phenotypic characterization of a subpopulation of T84 human colon cancer cells, after selection on activated endothelial cells.

The extravasation of metastatic cells is regulated by molecular events involving the initial adhesion of tumor cells to the endothelium and subsequently the migration of the cells in the host connective tissue. The differences in metastatic ability could be attributed to properties intrinsic of the various primary tumor types. Thus, the clonal selection of neoplastic cells during cancer progression results in cells better equipped for survival and formation of colonies in secondary sites. A cell line (T84SF) exhibiting an altered phenotypic appearance was selected from a colon cancer cell line (T84) by repetitive plating on TNFalpha-activated human endothelial cells and subsequent selection for adherent cells. Cell growth, motility, chemoinvasive abilities, tyrosine phosphorylation signaling, and the metastasis formation in nude mice of the two cell lines was compared. T84SF cells displayed in vitro an higher proliferation rate and a more invasive behavior compared to the parental cells while formed in vivo a greater number of metastatic colonies in nude mice. As concerns the signaling underlying the phenotypes of the selected cells, we examined the general tyrosine phosphorylation levels in both cell lines. Our results indicate that T84SF have an increased basal tyrosine phosphorylation of several proteins among which src kinase was identified. Treatment of cells with a specific inhibitor of src activity caused a greater in vitro inhibition of proliferation and invasive properties of T84 parental cells with respect to T84SF cells and diminished metastasis formation in vivo. Altogether, these data provide evidences that this new cell line may be valuable for identifying molecular mechanisms involved in the metastatic progression of colon cancer.

Valor pronóstico de la resonancia magnética en pacientes con mieloma múltiple: un estudio prospectivo / MRI prognostic value in multiple myeloma

Propósito: correlacionar los patrones de infiltración de la médula ósea (MO) por RM en pacientes con MM no tratados y valorar los resultados en conjunto con otros factores pronósticos utilizados (clínica, laboratorio, radiología). Material y métodos: evaluamos 21 pacientes con MM no tratados por RM y osteograma corporal para valorar lesiones óseas, plasmocitomas u osteoporosis. Resultados: están descriptos 3 patrones de infiltración de la MO por RM en éstos pacientes: focal (PF), difuso (PD) y variegado (PV). A diferencia de otras series, observamos estudios por RM con 2 o más patrones descriptos: 13 pacientes. Tentativamente proponemos denominar a ésta variedad de presentación, patrón mixto (PM). Conclusión: la RM es más sensible que la radiología convencional en la detección de lesiones óseas. Los patrones de infiltración de la MO por RM, combinados con el resto de factores convencionales usados, constituyen una herramienta muy útil en la determinación del pronóstico de la enfermedad. En nuestra serie, el PD, ya sea aislado o combinado con otros patrones (PM), correlacionó con factores pronósticos más severos

[Eight years of experience in a single institution in hematopoietic stem cell autologous transplantation in malignant hematological diseases and in solid tumors]. / Ocho años de experiencia en una sola institucion en trasplante autólogo de células progenitoras hematopoyéticas en enfermedades hematológicas malignas y en tumores solidos.

Between August 1991 and December 1998, 400 patients (lymphomas: 197; acute leukemia: 86; multiple myeloma: 70 and solid tumors: 47) were admitted for autologous transplantation. All patients were mobilized with chemotherapy plus G-CSF. The hematological recovery was similar in all disease groups. Patients with acute leukemias and multiple myeloma had a slower platelet recovery. Treatment-related death was 4.5%. The status of the disease at diagnosis was the most significant prognostic factor. With a median follow-up of 23 months the probability of event-free survival at 60 months was 46% for low grade lymphoma, 44% for intermediate and high grade lymphoma, 58% for Hodgkin's disease, 45% for acute myeloblastic leukemia, 38% for solid tumors and 15% for multiple myeloma. The probability of survival at 60 months was 67% for low grade lymphoma, 47% for intermediate and high grade lymphoma, 75% for Hodgkin's disease, 52% for acute myeloblastic leukemia, 54% for solid tumors and 25% for multiple myeloma. It can be concluded that autologous progenitor cell transplantation induces a complete and faster hematological recovery in all groups of patients without any late graft failure. Results are similar to those published in the literature. The treatment-related death was low and acceptable.

Autologous peripheral blood progenitor cell transplantation mobilized with high-dose cytarabine in acute myeloid leukemia in first complete remission.

BACKGROUND: The aim of this study was to increase disease-free survival (DFS) in AML in CR1 using a high-dose cytarabine consolidation plus G-CSF as in vivo purging and mobilization of CD34+ cells before ablative therapy and peripheral blood autograft. PATIENTS AND METHODS: Fifty-six consecutive AML patients (pts) (including 11 children < 15 years), with a median age of 32 years, were analyzed. After achievement of CR with cytarabine-mitoxantrone (7 + 3) in adults and a BFM-like protocol in children, pts were intensified with cytarabine 2 g/m2 x six doses plus mitoxantrone for adults, or, 3 g/m2 x six doses plus etoposide for children, followed by G-CSF 5 micrograms/kg SC daily. The ablative regimens used were busulfan and cyclophosphamide (Bu/Cy) in standard-risk pts plus etoposide (2400 mg/m2) for high-risk pts. RESULTS: For the 54 pts who underwent autologous transplant, the median time to reach > 1.0 x 10(9)/l neutrophils was 13 days (8-48), and to reach platelets > 25 x 10(9)/l 32 days (8-364), and the median numbers of red blood cell and platelet units transfused were 3 and 5, respectively. Six pts had treatment-related deaths (11%). The disease-free survival and overall survival at 30 months (mos) for the 56 eligible pts were 61% and 62%, respectively. Only two relapses were observed after 21 mos, while there were 12 relapses within 12 mos. CONCLUSIONS: The above treatment results in a similar DFS rate as does rescue with bone marrow cells, with faster neutrophil and platelet recovery.

Randomized trial of CVPP for three versus six cycles in favorable-prognosis and CVPP versus AOPE plus radiotherapy in intermediate-prognosis untreated Hodgkin's disease.

PURPOSE: To evaluate in a randomized trial the impact of three versus six cycles of cyclophosphamide, vinblastine, procarbazine, and prednisone (CVPP) chemotherapy in favorable-prognosis and CVPP versus doxorubicin, vincristine, prednisone, and etoposide (AOPE) plus involved-field radiotherapy (RT) in intermediate-prognosis previously untreated Hodgkin's disease. PATIENTS AND METHODS: Of 256 patients evaluated, 80 with a favorable prognosis according to a prognostic index designed by the Grupo Argentina de Tratamiento de Leucemia Aguda (GATLA) were randomized to three versus six cycles of CVPP without RT and 176 with intermediate risk to CVPP versus AOPE, both for six cycles with RT between the third and fourth cycles of 30 Gy to the involved areas at diagnosis. CVPP consisted of intravenous (I.V.) cyclophosphamide and vinblastine on days 1 and 8, and oral procarbazine and prednisone on days 1 to 14, every 28 days. AOPE consisted of I.V. doxorubicin and vincristine on day 1, oral prednisone on days 1 to 5, and I.V. etoposide on days 1 and 3, every 28 days. RESULTS: Complete remission was obtained in 39 of 41 (95%) patients treated with three cycles of CVPP and 36 of 39 (92%) treated with six cycles in the favorable-risk group (difference not significant [NS]). In the intermediate-risk group, 89 of 92 (97%) treated with CVPP plus RT versus 75 of 84 (89%) treated with AOPE plus RT achieved a complete remission (P = .05). At 60 months, the event-free survival (EFS) and overall survival rates in the favorable-risk group were 80% and 91% for CVPP x 3 and 84% and 97% for CVPP x 6, respectively (P = NS). In the intermediate-risk group, 60-month EFS rate for CVPP plus RT was 85%, compared with 66% for AOPE plus RT (P = .009). The overall survival rate was 95% versus 87% respectively (P = .157). CONCLUSION: Three cycles of CVPP without RT are equally effective as six cycles in the favorable-risk group. However, in the intermediate-group, CVPP plus RT is superior to AOPE plus RT, with significantly fewer events before and after induction (P = .009), without a difference in overall survival.

Multivariate analyses of prognostic factors associated with hematopoietic recovery in autograft patients with different sources of progenitor cells. A GATMO experience. Argintine Group of Bone Marrow Transplant.

OBJECTIVE: To evaluate in a multivariate analysis the prognostic factors associated with hematopoietic recovery and the supportive care requirements after autotransplant of progenitor cells (PC) from various sources: bone marrow (BMPC), BMPC & peripheral blood (PBPC), and PBPC alone. PATIENTS AND METHODS: A total of 570 patients with hematological malignancies and solid tumors underwent high-dose therapy followed by autotransplant. PBPC were obtained after mobilization with chemotherapy and/or cytokines. One-hundred five patients received BMPC, 217 received BMPC & PBPC and 248 PBPC alone; all of the patients received G-CSF or GM-CSF after infusion. RESULTS: In a multivariate analysis the recovery of neutrophils was adversely associated with low numbers of nucleated cells infused (P < 0.13), bone marrow progenitor cell source, and diagnosis of multiple myeloma and acute leukemia (P < 0.001). The factors that adversely affected platelet recovery were low number of nucleated cells and diagnosis of multiple myeloma and acute leukemia (P < 0.001). CONCLUSIONS: We conclude that BMPC adversely affect neutrophil recovery while low numbers of nucleated cells and diagnosis of multiple myeloma and acute leukemia adversely affect both neutrophil and platelet recovery.

Acute lymphocytic leukemia (ALL) in elderly patients.

OBJECTIVE: To compare the clinical and biologic characteristics, response to therapy and outcome of adult patients with ALL above and below the age of 55. DESIGN: Retrospective review of clinical and laboratory data. SETTING: University affiliated Cancer Center and Veteran's Hospital. PATIENTS: Thirty-three newly diagnosed, consecutive, adults with ALL seen over a nine-year period. RESULTS: while no differences were demonstrated in the distribution of recognized prognostic indicators (such as cytogenetic abnormalities or immunophenotype), individuals over the age of 55 had significantly lower remission rates and shorter survivals. CONCLUSIONS: The outcome of elderly patients with ALL is very poor. This is primarily related to an increase in the number of early deaths during induction, as well as a higher prevalence of disease refractory to standard chemotherapy programmes. There is a need for new treatment protocols designed for the elderly ALL patient, as well as a better understanding of the unique biological characteristics of the disease in this age group.