Favorable outcome with sentinel lymph node biopsy alone after neoadjuvant chemotherapy in clinically node positive breast cancer at diagnosis: Turkish Multicentric NEOSENTI-TURK MF-18-02-study.

PURPOSE: Factors affecting local outcome were evaluated in patients with clinically node-positive (cN+) breast cancer at diagnosis, who underwent sentinel lymph node biopsy (SLNB) alone after neoadjuvant chemotherapy (NAC). METHODS: Between 2004 and 2018, 303 cytopathology-proven cN (+) patients in a multicentric registry, who received NAC and underwent SLNB alone were analysed. All patients had regional nodal irradiation. RESULTS: Median age was 46 (23-70). Of those, 211 patients had ypN0 disease (69.6%), whereas 92 patients had ypN (+) disease including 19 (20.6%) isolated tumor cells (ITC), 33 micrometastases (35.9%) and 40 macrometastases (43.5%). At a median follow-up of 36 months (24-172), one patient (0.3%) with macrometastatic SLN was found to have locoregional recurrence as chest wall and supraclavicular LN metastases at the 60th month. Five-year disease-free survival (DFS) and disease specific survival (DSS) rates were 87% and 95%, respectively. Patients with cT3/4 (HR = 2.41, 95% CI; 1.14-5.07), non-luminal molecular pathology (HR = 2.60, 95% CI, 1.16-5.82), and non-pCR in the breast (HR = 2.11, 95% CI, 0.89-5.01) were found to have an increased HR compared to others in 5-year DFS. However, no difference could be found between ypN0 and ypN ITC and micrometastasis (HR = 1.23, 95% CI, 0.44-3.47), whereas there was a slight increase in HR of patients with ypN macrometastasis versus ypN0 (HR = 1.91, 95% CI, 0.63-5.79). CONCLUSION: ALND could be avoided in meticulously selected cN (+) patients who underwent SLNB after NAC having breast and/or nodal pCR, cT1-2, or low volume residual nodal disease with luminal pathology, as long as axillary radiotherapy is provided.

Trasplante autólogo de progenitores hematopoyéticos en el Linfoma de Hodgkin / Autologous hematopoietic stem cell transplantation in Hodgkin's Lymphoma

Introducción: El trasplante autólogo de progenitores hematopoyéticos es una terapéutica aplicable en determinadas situaciones a pacientes con Linfoma de Hodgkin. Objetivo: Evaluar la respuesta al trasplante autólogo de progenitores hematopoyéticos en los pacientes con Linfoma de Hodgkin. Métodos: Se realizó un estudio de 60 pacientes con Linfoma de Hodgkin trasplantados en el Hospital Clínico Quirúrgico Hermanos Ameijeiras, entre 1991 y 2018. Se estimó el porcentaje de respuesta a los tres meses, la supervivencia global y la supervivencia libre de enfermedad a los cinco años. Resultados: La tasa de respuesta a los tres meses fue de 82,7 por ciento. La supervivencia global y libre de enfermedad a los cinco años fue de 94,7 por ciento y 51,7 por ciento, respectivamente. La mortalidad temprana relacionada con el trasplante fue de 5 por ciento. Conclusiones: La aplicación del trasplante autólogo de progenitores hematopoyéticos constituyó una alternativa terapéutica válida. La baja mortalidad temprana evidenció una realización del procedimiento con un perfil de seguridad satisfactorio(AU)

Introduction: Autologous hematopoietic stem cell transplantation is an applicable therapy in certain situations to patients with Hodgkin's Lymphoma. Objective: To evaluate the response to autologous hematopoietic stem cell transplantation in patients with Hodgkin's Lymphoma. Methods: A study of 60 patients with Hodgkin lymphoma transplanted at Hermanos Ameijeiras Clinical and Surgical Hospital was carried out from 1991 to 2018. The percentage of response at three months, overall survival and disease-free survival period were estimated at five years. Results: The response rate at three months was 82.7 percent. Overall and disease-free survival at five years was 94.7 percent and 51.7 percent, respectively. Early transplant-related mortality was 5 percent. Conclusions: The use of autologous hematopoietic stem cell transplantation was a valid therapeutic alternative. The low early mortality evidenced that the procedure was performed with a satisfactory safety profile(AU)

Trasplante de progenitores hematopoyéticos autólogo en gammapatías monoclonales: primeros resultados del Hospital "Hermanos Ameijeiras" / Autologous stem cell transplantation in monoclonal gammopathies: first results from the "Hermanos Ameijeiras" Hospital

Introducción: Los avances en el manejo del mieloma múltiple (MM) durante los últimos años incluyen la incorporación del trasplante de progenitores hematopoyéticos autólogo (TPHa) a la estrategia de tratamiento de estos pacientes. Objetivo: Dar a conocer los primeros resultados en el hospital Hermanos Ameijeiras (HHA) con la aplicación del TPHa en pacientes con gammapatías monoclonales (GM), empleando las altas dosis de melfalán (AD-Mel) como tratamiento acondicionante (TA) y su impacto en la sobrevida global (SG). Métodos: Se hizo un estudio retrospectivo de todos los pacientes con GM sometidos a TPHa en el Servicio de Hematología del HHA en el período comprendido entre 2009 y 2018. La muestra final comprendió 14 casos. Resultados: La edad promedio fue de 53,5 años; la mayoría tenía como diagnóstico MM (85,7 por ciento) y todos ellos debutaron en estadio III de Durie-Salmon; como TA el 64,2 por ciento recibió AD-mel, en dosis de 200 mg/m2. La recuperación de las cifras de neutrófilos y plaquetas ocurrieron como promedio a los 11,4 y 12 días, respectivamente. La mortalidad relacionada con el trasplante (MRT) al día +30 fue del 7,1 por ciento. La probabilidad de SG a los 2 años fue superior al 90 por ciento y a los 5 años del 68 por ciento. Conclusiones: Se comprobó que la realización del TPHa con el empleo de AD-Mel como TA en pacientes con GM es un proceder realizable en nuestro país con una MRT relativamente baja. Se logró demostrar que la inclusión del TPH en el tratamiento mejora considerablemente las expectativas de sobrevida de estos pacientes(AU)

Introduction: The recent advances in the management of multiple myeloma (MM) during the last years have included the autologous hematopoietic stem cell transplantation (auto-HSCT) to the treatment strategy of these patients. Objective: To present the first results in the Hermanos Ameijeiras hospital (HAH) with the application of auto-HSCT in patients with monoclonal gammopathies (MG) using high doses of melphalan (HD-Mel) as conditioning regimen (CR) and its impacton overall survival (OS). Methods: A retrospective study of all patients with MG who underwent auto-HSCT in the Hematology Service of the HAH in the period between 2009 and 2018 wasmade. The final sample comprised 14 cases. Results: The average age was 53.5 years; the majority had diagnosis of MM (85.7percent) and all of them were diagnosed in stage III of Durie-Salmon; as CR 64.2 percent received HD-mel, at 200 mg/m2. The recovery of neutrophil and platelet counts occurred on average at 11.4 and 12 days respectively. Transplant related mortality (TRM) at day +30 was 7.1 percent. The probability of OS at 2 years was higher than 90 percent and at 5 years of 68 percent. Conclusions: It was verified that the performance of auto-HSCT with the use of HD-Mel as CR in patients with MG is a feasible procedure in our country with a relatively low TRM. It was possible to demonstrate that the inclusion of auto-HSCT in the treatment considerably improves the survival expectations of these patients(AU)

Bone Marrow Transplantation in Patients With Acute Leukemia In Cuba: Results From the Last 30 Years and New Opportunities Through International Collaboration.

Blood and marrow transplantation (BMT) has been performed in Cuba for over 30 years with limited resources and without international relationships. Researchers from University of Illinois at Chicago and Hermanos Ameijeiras Hospital (HAH) in Havana collaborated on retrospectively analyzing 101 consecutive patients with adult acute leukemia who received BMT at HAH from June 1986 to January 2016. Of these, 82 had acute myeloid leukemia (AML) and 19 had acute lymphoblastic leukemia (ALL). BMT eligibility criteria included prior morphologic complete remission, no severe comorbidities, and age between 16 and 60 years. Patients with an HLA-matched donor received an allogeneic BMT, whereas the others received an autologous BMT. All patients received fresh stem cells from marrow (80%) or mobilized peripheral blood (19%). Of 82 patients with AML, 35 received an allogeneic (AML-allo) and 47 an autologous (AML-auto) BMT. Both groups had comparable median age (37 years) and follow-up of survivors. Overall survival (OS) was 34% in AML-allo and 38% in AML-auto. The transplant-related mortality rate was 40% in AML-allo and 17% in AML-auto, whereas the relapse-related mortality rates were 25% and 40%, respectively. Of the 19 patients with ALL, six received an allogeneic transplant. Of these, transplant-related mortality occurred in one patient and three died after disease relapse (OS, 33%). Of 13 patients who received autologous transplants, transplant-related mortality occurred in three and six died after disease relapse (OS, 31%). To our knowledge, this is the first scientific report on BMT performed in patients with acute leukemia in Cuba. The collaboration between University of Illinois at Chicago and HAH will further develop capacity building in research and implementation of new diagnostic and therapeutic strategies in Cuba.

Características clínico microbiológicas de la infección por Acinetobacter baumannii en pacientes con afecciones hematológicas / Clinical microbiological characteristics of Acinetobacter baumannii infection in patients with hematological disorders

Introducción: Las complicaciones infecciosas se han convertido en la causa de mortalidad más frecuente en los pacientes con afecciones hematológicas sometidos a regímenes terapéuticos agresivos. Objetivo: Caracterizar la infección por Acinetobacter baumannii en pacientes con afecciones hematológicas. Métodos: Se realizó un estudio ambispectivo y descriptivo en el servicio de hematología del Hospital Clínico Quirúrgico Hermanos Ameijeiras, entre enero de 2010 y diciembre de 2016. La muestra se conformó con 29 pacientes que cumplieron los criterios de inclusión establecidos. Resultados: La edad promedio fue de 48,3±14,8 años, con predominio del sexo masculino (65,5 por ciento). Resultaron más frecuentes los casos con linfomas (48,3 por ciento). En cuanto al estado de la enfermedad se apreció que prevalecieron por igual (34,5 por ciento) los grupos de pacientes con enfermedad en su inicio y en remisión completa. La neutropenia febril (48,3 por ciento) y la sepsis respiratoria (31,1 por ciento) fueron las manifestaciones clínicas más detectadas. Los enfermos con algún grado de neutropenia resultaron los más frecuentes (55,1 por ciento), principalmente aquellos con neutropenia severa y muy severa. La resistencia a los carbapenémicos entre los infectados fue de 58,6 por ciento. 24,1 por ciento de los casos fallecieron y la resistencia a los carbapenémicos se asoció significativamente (p<0,05) a esta mortalidad. De los procederes invasivos empleados en estos pacientes, predominó la colocación de catéter centro-venoso (58,6 por ciento). Conclusiones: La infección por A. baumannii es más frecuente en pacientes con afecciones hematológicas malignas y que recibieron tratamiento mielodepresor así como en aquellos que presentaron neutropenia severa/muy severa, manifestándose clínicamente de forma mayoritaria como una neutropenia febril; es muy importante señalar que la mortalidad por este agente biológico resultó elevada, principalmente si existe resistencia a los carbapenémicos(AU)

Introduction: Infectious complications have become the most frequent cause of mortality in patients with hematological conditions subjected to aggressive therapeutic regimens. Objective: To characterize Acinetobacter baumannii infection in patients with hematological disorders. Methods: An ambispective and descriptive study was carried out in the hematology department at Hermanos Ameijeiras Clinical Surgical Hospital from January 2010 to December 2016. Twenty nine patients, who met the established inclusion criteria, formed the sample. Results: The average age was 48.3 ± 14.8 years, males were majority (65.5 percent). The lymphomas cases were more frequent (48.3 percent). Regarding the state of the disease, it was observed that the groups of patients with disease in its initial stage and in complete remission prevailed equally (34.5 percent). Febrile neutropenia (48.3 percent) and respiratory sepsis (31.1 percent) were the most detected clinical manifestations. Patients with some degree of neutropenia were the most frequent (55.1 percent), mainly those with severe and very severe neutropenia. The resistance to carbapenems among the infected subjects was 58.6 percent. The deceased cases represented 24.1 percent and resistance to carbapenems was significantly associated (p <0.05) with this mortality. Out of the invasive procedures used in these patients, central venous catheter placement was predominant (58.6 percent). Conclusions: A. baumannii infection is more frequent in patients with malignant haematological conditions and who received myeloablative treatment as well as in those who presented severe or very severe neutropenia, mainly exhibiting as a febrile neutropenia. It is very important to point out that mortality due to this biological agent was high, mainly if there is resistance to carbapenems(AU)

GEF-H1 over-expression in hepatocellular carcinoma promotes cell motility via activation of RhoA signalling.

The interstitial chromosome (chr.) 1q21-q22 region is frequently amplified in human cancers, where it has been reported to carry prognostic significance for patients. We attempted to delineate chr. 1q21-q22 for affected gene(s) in hepatocellular carcinoma (HCC) by array-CGH and detected copy number gains of ρ-guanine nucleotide exchange factor-H1 (GEF-H1) as most significant event. Gene expression evaluation in the HCC cohort indicated common up-regulations of GEF-H1 in 64% tumours compared to adjacent non-tumoural liver (64/100; paired t-test p < 0.0001). Moreover, GEF-H1 over-expressions correlated with microvascular invasion and advanced-stage tumours (p < 0.05). High GEF-H1 levels also predict shorter disease-free and overall survival of HCC patients (p < 0.03). Functional knock-down of GEF-H1 by RNAi indicated marked reduction in cell invasion through matrigel and an inhibition of cell migration (p < 0.035), but an effect on cell viability was not apparent. More interestingly, a mesenchymal-epithelial transition (MET) was readily observed in GEF-H1 knock-down cells, where a concomitant re-expression of epithelial markers (E-cadherin and cytokeratin 18) and cell adhesion proteins (α-catenin and γ-catenin) was found but down-regulation of mesenchymal features (N-cadherin, vimentin and fibronectin). This phenotype was accompanied by reduced filamentous actin polymerizations and diminution of the stress fibre formation. In addition, reduced active form of GTP-RhoA, together with its downstream effectors, including cleaved ROCK1 and phosphorylated MLC2, were also detected in GEF-H1-depleted cells. Taken together, our findings underscore a potent oncogenic role for GEF-H1 in promoting the metastatic potentials of HCC, possibly through activation of RhoA signalling and the EMT phenomenon.

Can radiation-induced chronic oxidative stress in kidney and liver be prevented by dimethylsulfoxide? Biochemical determination by serum and tissue markers.

PURPOSE: To investigate the protective effects of dimethylsulfoxide (DMSO) on chronic oxidative stress in the liver, kidney and serum with biochemical parameters such as malondialdehyde (MDA), advanced oxidation protein product (AOPP), catalase, glutathione (GSH), and free-thiols (F-SH). METHODS: Thirty Wistar albino female rats were randomly divided into 3 groups: group I (control, n=10), group II (irradiation-alone group, n=10) and group III (DMSO and irradiation group, n=10). Rats in groups II and III were irradiated with a single dose of 6 Gy to the entire liver and right kidney. Group III received DMSO 4.5 g/kg by intraperitoneal injection 30 min before irradiation. At the end of the 24th week, the rats were sacrificed and their trunk blood, kidney and liver tissues were collected. RESULTS: Group II rats showed increased levels of lipid peroxidation and protein oxidation, with decreased GSH, FSH and catalase levels in all specimens when compared with group I. Serum and kidney MDA and AOPP levels were significantly lower in group III when compared with group II. However, serum and kidney GSH and F-SH levels were significantly higher in group III when compared with group II. The additive effect on catalase was seen only in the serum. CONCLUSION: DMSO is a protective agent on chronic oxidative stress in the serum and kidney tissue. No oxidant or antioxidant effect of DMSO in the liver was seen.

Block of proliferation 1 (BOP1) plays an oncogenic role in hepatocellular carcinoma by promoting epithelial-to-mesenchymal transition.

UNLABELLED: Genomic amplification of regional chromosome 8q24 is a common event in human cancers. In hepatocellular carcinoma (HCC), a highly aggressive malignancy that is rapidly fatal, recurrent 8q24 gains can be detected in >50% of cases. In this study, attempts to resolve the 8q24 region by way of array comparative genomic hybridization for affected genes in HCC revealed distinctive gains of block of proliferation 1 (BOP1). Gene expression evaluation in an independent cohort of primary HCC (n = 65) revealed frequent BOP1 up-regulation in tumors compared with adjacent nontumoral liver (84.6%; P < 0.0001). Significant associations could also be drawn between increased expressions of BOP1 and advance HCC staging (P = 0.004), microvascular invasion (P = 0.006), and shorter disease-free survival of patients (P = 0.02). Examination of expression of C-MYC, a well-known oncogene located in proximity to BOP1, in the same series of primary HCC cases did not suggest strong clinicopathologic associations. Functional investigations by small interfering RNA-mediated suppression of BOP1 in HCC cell lines indicated significant inhibition on cell invasion (P < 0.005) and migration (P < 0.05). Overexpression of BOP1 in the immortalized hepatocyte cell line L02 showed increase cellular invasiveness and cell migratory rate (P < 0.0001). In both gene knockdown and ectopic expression assays, BOP1 did not exert an effect on cell viability and proliferation. Evident regression of the epithelial-mesenchymal transition (EMT) phenotype was readily identified in BOP1 knockdown cells, whereas up-regulation of epithelial markers (E-cadherin, cytokeratin 18, and γ-catenin) and down-regulation of mesenchymal markers (fibronectin and vimentin) were seen. A corresponding augmentation of EMT was indicated from the ectopic expression of BOP1 in L02. In addition, BOP1 could stimulate actin stress fiber assembly and RhoA activation. CONCLUSION: Our findings underline an important role for BOP1 in HCC invasiveness and metastasis potentials through inducing EMT and promoting actin cytoskeleton remodeling.

Reduced CRYL1 expression in hepatocellular carcinoma confers cell growth advantages and correlates with adverse patient prognosis.

Homozygous deletion screening has been widely utilized to define tumour suppressor genes (TSGs) in cancers. Although these biallelic deletions are infrequent, their identification has facilitated the discovery of many important TSGs. We have systematically examined the genome of hepatocellular carcinoma (HCC), a highly malignant tumour that is rapidly fatal, for the presence of homozygous deletions. Array-CGH analysis on early passage of HCC cultures and cell lines led us to identify six homozygous deleted (HD) regions. A high concordance between array-CGH and expression of HD genes was demonstrated, where crystallin Lambda1 (CRYL1; located on chromosome 13q12.11) displayed the most frequent down-regulation. We found that reduced mRNA expression of CRYL1 was common in HCC tumours when compared with their adjacent non-tumoural liver (p = 0.0097). Significant associations could also be drawn between repressed CRYL1 and advanced tumour staging, increased tumour size, and shorter disease-free survival of patients (p < 0.037). Moreover, homozygous deletions on CRYL1 could be detected in 36% of HCC cases, where recurrent HDs were identified on exons 1, 5, and 8. Examination of other causal events suggested histone deacetylation and promoter hypermethylation to be likely inactivating mechanisms as well. Re-expression of CRYL1 in the SK-Hep1 cell line, where biallelic loss of CRYL1 was found, induced profound inhibition of cellular proliferation and cell growth (p < 0.0015). By Annexin V staining, CRYL1 restoration readily increased pro-apoptotic cells with an induction of PARP cleavage. Flow cytometry further revealed that CRYL1 could prolong the G(2)-M phase, possibly through interruption of the Cdc2/cyclin B pathway. Given that regional chromosome 13q12-q14 loss is a causal genomic event in HCC tumourigenesis, our finding may have implications for identifying a novel TSG CRYL1 within this important locus.

Prognostic factors for renal cell carcinoma: Trakya University experience from Turkey.

The purpose of the present study is to evaluate the prognostic factors of patients with renal cell carcinoma. The treatment results such as distant metastasis-free survival and overall survival of 59 previously untreated patients were retrospectively analysed. Median follow-up was 17.5 months (3.8-88.5 months). Overall survival was 22.4 months (3-87 months). Distant metastasis developed in 35 (59%) patients. The Eastern Cooperative Oncology Group (ECOG) performance status (P=0.022), tumour size (P=0.025) and lymphatic invasion (P<0.0001) were significantly effective prognostic factors for distant metastasis-free survival on multivariate analysis. Related to overall survival, gender (P=0.025), ECOG performance status (P=0.027), nuclear grade (P=0.002), tumour size (P=0.029), T stage (P=0.044), nodal involvement (P=0.003), surgical margin (P=0.046), renal sinus invasion (P<0.0001), perineural growth (P=0.001) and lymphatic invasion (P<0.0001) were significant prognostic factors on univariate analysis. Gender (P=0.008), ECOG performance status (P=0.027), tumour size (P=0.025) and lymphatic invasion (P<0.0001) retained their significance on multivariate analysis. We concluded that the most important prognostic factors for patients with renal cell carcinomas are ECOG performance status, tumour size and lymphatic invasion.

Peutz-Jeghers syndrome combined with breast cancer, cervical carcinoma and ovarian gonadoblastoma: a case report.

Peutz-Jeghers syndrome (PJS) is a rare autosomal dominant condition characterized by gastrointestinal polyps, mucocutaneous pigmentation and an increased risk for cancer. In this report, a 34-year-old woman with PJS associated with a rare ovarian tumor (gonadoblastoma) and synchronous breast and cervical carcinoma is discussed and the relevant literature is reviewed.