Up-regulation of GINS1 highlighted a good diagnostic and prognostic potential of survival in three different subtypes of human cancer

Abstract Cancer is a fatal malignancy and its increasing worldwide prevalence demands the discovery of more sensitive and reliable molecular biomarkers. To investigate the GINS1 expression level and its prognostic value in distinct human cancers using a series of multi-layered in silico approach may help to establish it as a potential shared diagnostic and prognostic biomarker of different cancer subtypes. The GINS1 mRNA, protein expression, and promoter methylation were analyzed using UALCAN and Human Protein Atlas (HPA), while mRNA expression was further validated via GENT2. The potential prognostic values of GINS1 were evaluated through KM plotter. Then, cBioPortal was utilized to examine the GINS1-related genetic mutations and copy number variations (CNVs), while pathway enrichment analysis was performed using DAVID. Moreover, a correlational analysis between GINS1 expression and CD8+ T immune cells and a the construction of gene-drug interaction network was performed using TIMER, CDT, and Cytoscape. The GINS1 was found down-regulated in a single subtypes of human cancer while commonly up-regulated in 23 different other subtypes. The up-regulation of GINS1 was significantly correlated with the poor overall survival (OS) of Liver Hepatocellular Carcinoma (LIHC), Lung Adenocarcinoma (LUAD), and Kidney renal clear cell carcinoma (KIRC). The GINS1 was also found up-regulated in LIHC, LUAD, and KIRC patients of different clinicopathological features. Pathways enrichment analysis revealed the involvement of GINS1 in two diverse pathways, while few interesting correlations were also documented between GINS1 expression and its promoter methylation level, CD8+ T immune cells level, and CNVs. Moreover, we also predicted few drugs that could be used in the treatment of LIHC, LUAD, and KIRC by regulating the GINS1 expression. The expression profiling of GINS1 in the current study has suggested it a novel shared diagnostic and prognostic biomarker of LIHC, LUAD, and KIRC.

Resumo O câncer é uma doença maligna fatal e sua crescente prevalência mundial exige a descoberta de biomarcadores moleculares mais sensíveis e confiáveis. Investigar o nível de expressão de GINS1 e seu valor prognóstico em cânceres humanos distintos, usando uma série de abordagens in silico em várias camadas, pode ajudar a estabelecê-lo como um potencial biomarcador de diagnóstico e prognóstico compartilhado de diferentes subtipos de câncer. O mRNA de GINS1, a expressão da proteína e a metilação do promotor foram analisados usando UALCAN e Human Protein Atlas (HPA), enquanto a expressão de mRNA foi posteriormente validada via GENT2. Os valores prognósticos potenciais de GINS1 foram avaliados por meio do plotter KM. Em seguida, o cBioPortal foi utilizado para examinar as mutações genéticas relacionadas ao GINS1 e as variações do número de cópias (CNVs), enquanto a análise de enriquecimento da via foi realizada usando DAVID. Além disso, uma análise correlacional entre a expressão de GINS1 e células imunes T CD8 + e a construção de uma rede de interação gene-droga foi realizada usando TIMER, CDT e Cytoscape. O GINS1 foi encontrado regulado negativamente em um único subtipo de câncer humano, enquanto comumente regulado positivamente em 23 outros subtipos diferentes. A regulação positiva de GINS1 foi significativamente correlacionada com a sobrevida global pobre (OS) de Carcinoma Hepatocelular de Fígado (LIHC), Adenocarcinoma de Pulmão (LUAD) e Carcinoma de Células Claras Renais de Rim (KIRC). O GINS1 também foi encontrado regulado positivamente em pacientes LIHC, LUAD e KIRC de diferentes características clínico-patológicas. A análise de enriquecimento de vias revelou o envolvimento de GINS1 em duas vias diversas, enquanto poucas correlações interessantes também foram documentadas entre a expressão de GINS1 e seu nível de metilação do promotor, nível de células imunes T CD8 + e CNVs. Além disso, também previmos poucos medicamentos que poderiam ser usados no tratamento de LIHC, LUAD e KIRC, regulando a expressão de GINS1. O perfil de expressão de GINS1 no estudo atual sugeriu que é um novo biomarcador de diagnóstico e prognóstico compartilhado de LIHC, LUAD e KIRC.

Up-regulation of GINS1 highlighted a good diagnostic and prognostic potential of survival in three different subtypes of human cancer / A regulação positiva de GINS1 destacou um bom potencial diagnóstico e prognóstico de sobrevivência em três subtipos diferentes de câncer humano

Abstract Cancer is a fatal malignancy and its increasing worldwide prevalence demands the discovery of more sensitive and reliable molecular biomarkers. To investigate the GINS1 expression level and its prognostic value in distinct human cancers using a series of multi-layered in silico approach may help to establish it as a potential shared diagnostic and prognostic biomarker of different cancer subtypes. The GINS1 mRNA, protein expression, and promoter methylation were analyzed using UALCAN and Human Protein Atlas (HPA), while mRNA expression was further validated via GENT2. The potential prognostic values of GINS1 were evaluated through KM plotter. Then, cBioPortal was utilized to examine the GINS1-related genetic mutations and copy number variations (CNVs), while pathway enrichment analysis was performed using DAVID. Moreover, a correlational analysis between GINS1 expression and CD8+ T immune cells and a the construction of gene-drug interaction network was performed using TIMER, CDT, and Cytoscape. The GINS1 was found down-regulated in a single subtypes of human cancer while commonly up-regulated in 23 different other subtypes. The up-regulation of GINS1 was significantly correlated with the poor overall survival (OS) of Liver Hepatocellular Carcinoma (LIHC), Lung Adenocarcinoma (LUAD), and Kidney renal clear cell carcinoma (KIRC). The GINS1 was also found up-regulated in LIHC, LUAD, and KIRC patients of different clinicopathological features. Pathways enrichment analysis revealed the involvement of GINS1 in two diverse pathways, while few interesting correlations were also documented between GINS1 expression and its promoter methylation level, CD8+ T immune cells level, and CNVs. Moreover, we also predicted few drugs that could be used in the treatment of LIHC, LUAD, and KIRC by regulating the GINS1 expression. The expression profiling of GINS1 in the current study has suggested it a novel shared diagnostic and prognostic biomarker of LIHC, LUAD, and KIRC.

Resumo O câncer é uma doença maligna fatal e sua crescente prevalência mundial exige a descoberta de biomarcadores moleculares mais sensíveis e confiáveis. Investigar o nível de expressão de GINS1 e seu valor prognóstico em cânceres humanos distintos, usando uma série de abordagens in silico em várias camadas, pode ajudar a estabelecê-lo como um potencial biomarcador de diagnóstico e prognóstico compartilhado de diferentes subtipos de câncer. O mRNA de GINS1, a expressão da proteína e a metilação do promotor foram analisados ​​usando UALCAN e Human Protein Atlas (HPA), enquanto a expressão de mRNA foi posteriormente validada via GENT2. Os valores prognósticos potenciais de GINS1 foram avaliados por meio do plotter KM. Em seguida, o cBioPortal foi utilizado para examinar as mutações genéticas relacionadas ao GINS1 e as variações do número de cópias (CNVs), enquanto a análise de enriquecimento da via foi realizada usando DAVID. Além disso, uma análise correlacional entre a expressão de GINS1 e células imunes T CD8 + e a construção de uma rede de interação gene-droga foi realizada usando TIMER, CDT e Cytoscape. O GINS1 foi encontrado regulado negativamente em um único subtipo de câncer humano, enquanto comumente regulado positivamente em 23 outros subtipos diferentes. A regulação positiva de GINS1 foi significativamente correlacionada com a sobrevida global pobre (OS) de Carcinoma Hepatocelular de Fígado (LIHC), Adenocarcinoma de Pulmão (LUAD) e Carcinoma de Células Claras Renais de Rim (KIRC). O GINS1 também foi encontrado regulado positivamente em pacientes LIHC, LUAD e KIRC de diferentes características clínico-patológicas. A análise de enriquecimento de vias revelou o envolvimento de GINS1 em duas vias diversas, enquanto poucas correlações interessantes também foram documentadas entre a expressão de GINS1 e seu nível de metilação do promotor, nível de células imunes T CD8 + e CNVs. Além disso, também previmos poucos medicamentos que poderiam ser usados ​​no tratamento de LIHC, LUAD e KIRC, regulando a expressão de GINS1. O perfil de expressão de GINS1 no estudo atual sugeriu que é um novo biomarcador de diagnóstico e prognóstico compartilhado de LIHC, LUAD e KIRC.

Major threats and habitat use status of Demoiselle crane (Anthropoides virgo), in district Bannu, Pakistan / Principais ameaças e estado de uso de habitat de Demoiselle crane (Anthropoides virgo), no distrito de Bannu, Paquistão

Cranes are the large and attractive Creatures of nature with long necks, legs, and life-span. Adults of both sexes are the same with similar color patterns. Demoiselle cranes spend most of their lifespan on dry grasses. They are also found around the stream, rivers, shallow lakes, natural wetlands, and depressions. To evaluate the current status of habitat use and major threats a study was conducted in tehsil Domel district Bannu. Line transect method and water quality tests (temperature, PH, contamination of E-coli bacteria) were used. To determine the major threats questionnaire method was used. The whole data was analyzed by using SPSS 21 version. Based on the distribution four study sites were selected and four water samples from each study site were taken. Most sites were moderate to highly degraded except Kashoo and kurram river mixing point which was low degraded with livestock grazing and human activities. Water quality tests showed PH ranges from 7-9, temperature 6.5-8.5, and contamination of E-coli in all samples. The social survey revealed that hunting, habitat degradation, and pollution as major threats. Effective long-term conservation and management in the study area are needed to focus on the protection of disturbance-free habitat.

Guindastes são a grande e atraente criatura da natureza com um pescoço longo, pernas e vida útil. Adultos de ambos os sexos são os mesmos com padrões de cores semelhantes. Guindastes Demoiselle passam a maior parte da vida em gramíneas secas. Também se encontram ao redor do córrego, rios, lagos rasos, pântanos naturais e depressões. Para avaliar o estado atual do uso do hábitat e as principais ameaças, um estudo foi realizado no distrito de Tehsil Domel, em Bannu. Foram utilizados o método transect e testes de qualidade da água (temperatura, pH, contaminação da bactéria E. coli). Para determinar as principais ameaças foi utilizado o método de questionário. Todos os dados foram analisados por meio da versão SPSS 21. Com base na distribuição, foram selecionados quatro locais de estudo e quatro amostras de água de cada local de estudo. A maioria dos locais estava moderada a altamente degradada, exceto no ponto de encontro dos rios Kashoo e Kurram, que teve baixa degradação com pastagem de gado e atividades humanas. Os testes de qualidade da água mostraram variação de pH de 7-9, temperatura 6,5-8,5 e contaminação de E. coli em todas as amostras. A pesquisa do questionário revelou que a caça, a degradação do hábitat e a poluição são as principais ameaças. Efetiva conservação e gestão a longo prazo na área de estudo são necessárias para se concentrar na proteção de um hábitat livre de distúrbios.

Major threats and habitat use status of Demoiselle crane (Anthropoides virgo), in district Bannu, Pakistan

Abstract Cranes are the large and attractive Creatures of nature with long necks, legs, and life-span. Adults of both sexes are the same with similar color patterns. Demoiselle cranes spend most of their lifespan on dry grasses. They are also found around the stream, rivers, shallow lakes, natural wetlands, and depressions. To evaluate the current status of habitat use and major threats a study was conducted in tehsil Domel district Bannu. Line transect method and water quality tests (temperature, PH, contamination of E-coli bacteria) were used. To determine the major threats questionnaire method was used. The whole data was analyzed by using SPSS 21 version. Based on the distribution four study sites were selected and four water samples from each study site were taken. Most sites were moderate to highly degraded except Kashoo and kurram river mixing point which was low degraded with livestock grazing and human activities. Water quality tests showed PH ranges from 7-9, temperature 6.5-8.5, and contamination of E-coli in all samples. The social survey revealed that hunting, habitat degradation, and pollution as major threats. Effective long-term conservation and management in the study area are needed to focus on the protection of disturbance-free habitat.

Resumo Guindastes são a grande e atraente criatura da natureza com um pescoço longo, pernas e vida útil. Adultos de ambos os sexos são os mesmos com padrões de cores semelhantes. Guindastes Demoiselle passam a maior parte da vida em gramíneas secas. Também se encontram ao redor do córrego, rios, lagos rasos, pântanos naturais e depressões. Para avaliar o estado atual do uso do hábitat e as principais ameaças, um estudo foi realizado no distrito de Tehsil Domel, em Bannu. Foram utilizados o método transect e testes de qualidade da água (temperatura, pH, contaminação da bactéria E. coli). Para determinar as principais ameaçasfoi utilizado o método de questionário. Todos os dados foram analisados por meio da versão SPSS 21. Com base na distribuição, foram selecionados quatro locais de estudo e quatro amostras de água de cada local de estudo. A maioria dos locais estava moderada a altamente degradada, exceto no ponto de encontro dos rios Kashoo e Kurram, que teve baixa degradação com pastagem de gado e atividades humanas. Os testes de qualidade da água mostraram variação de pH de 7-9, temperatura 6,5-8,5 e contaminação de E. coli em todas as amostras. A pesquisa do questionário revelou que a caça, a degradação do hábitat e a poluição são as principais ameaças. Efetiva conservação e gestão a longo prazo na área de estudo são necessárias para se concentrar na proteção de um hábitat livre de distúrbios.

Major threats and habitat use status of Demoiselle crane (Anthropoides virgo), in district Bannu, Pakistan / Principais ameaças e estado de uso de habitat de Demoiselle crane (Anthropoides virgo), no distrito de Bannu, Paquistão

Cranes are the large and attractive Creatures of nature with long necks, legs, and life-span. Adults of both sexes are the same with similar color patterns. Demoiselle cranes spend most of their lifespan on dry grasses. They are also found around the stream, rivers, shallow lakes, natural wetlands, and depressions. To evaluate the current status of habitat use and major threats a study was conducted in tehsil Domel district Bannu. Line transect method and water quality tests (temperature, PH, contamination of E-coli bacteria) were used. To determine the major threats questionnaire method was used. The whole data was analyzed by using SPSS 21 version. Based on the distribution four study sites were selected and four water samples from each study site were taken. Most sites were moderate to highly degraded except Kashoo and kurram river mixing point which was low degraded with livestock grazing and human activities. Water quality tests showed PH ranges from 7-9, temperature 6.5-8.5, and contamination of E-coli in all samples. The social survey revealed that hunting, habitat degradation, and pollution as major threats. Effective long-term conservation and management in the study area are needed to focus on the protection of disturbance-free habitat.

Guindastes são a grande e atraente criatura da natureza com um pescoço longo, pernas e vida útil. Adultos de ambos os sexos são os mesmos com padrões de cores semelhantes. Guindastes Demoiselle passam a maior parte da vida em gramíneas secas. Também se encontram ao redor do córrego, rios, lagos rasos, pântanos naturais e depressões. Para avaliar o estado atual do uso do hábitat e as principais ameaças, um estudo foi realizado no distrito de Tehsil Domel, em Bannu. Foram utilizados o método transect e testes de qualidade da água (temperatura, pH, contaminação da bactéria E. coli). Para determinar as principais ameaçasfoi utilizado o método de questionário. Todos os dados foram analisados por meio da versão SPSS 21. Com base na distribuição, foram selecionados quatro locais de estudo e quatro amostras de água de cada local de estudo. A maioria dos locais estava moderada a altamente degradada, exceto no ponto de encontro dos rios Kashoo e Kurram, que teve baixa degradação com pastagem de gado e atividades humanas. Os testes de qualidade da água mostraram variação de pH de 7-9, temperatura 6,5-8,5 e contaminação de E. coli em todas as amostras. A pesquisa do questionário revelou que a caça, a degradação do hábitat e a poluição são as principais ameaças. Efetiva conservação e gestão a longo prazo na área de estudo são necessárias para se concentrar na proteção de um hábitat livre de distúrbios.

Up-regulation of GINS1 highlighted a good diagnostic and prognostic potential of survival in three different subtypes of human cancer.

Cancer is a fatal malignancy and its increasing worldwide prevalence demands the discovery of more sensitive and reliable molecular biomarkers. To investigate the GINS1 expression level and its prognostic value in distinct human cancers using a series of multi-layered in silico approach may help to establish it as a potential shared diagnostic and prognostic biomarker of different cancer subtypes. The GINS1 mRNA, protein expression, and promoter methylation were analyzed using UALCAN and Human Protein Atlas (HPA), while mRNA expression was further validated via GENT2. The potential prognostic values of GINS1 were evaluated through KM plotter. Then, cBioPortal was utilized to examine the GINS1-related genetic mutations and copy number variations (CNVs), while pathway enrichment analysis was performed using DAVID. Moreover, a correlational analysis between GINS1 expression and CD8+ T immune cells and a the construction of gene-drug interaction network was performed using TIMER, CDT, and Cytoscape. The GINS1 was found down-regulated in a single subtypes of human cancer while commonly up-regulated in 23 different other subtypes. The up-regulation of GINS1 was significantly correlated with the poor overall survival (OS) of Liver Hepatocellular Carcinoma (LIHC), Lung Adenocarcinoma (LUAD), and Kidney renal clear cell carcinoma (KIRC). The GINS1 was also found up-regulated in LIHC, LUAD, and KIRC patients of different clinicopathological features. Pathways enrichment analysis revealed the involvement of GINS1 in two diverse pathways, while few interesting correlations were also documented between GINS1 expression and its promoter methylation level, CD8+ T immune cells level, and CNVs. Moreover, we also predicted few drugs that could be used in the treatment of LIHC, LUAD, and KIRC by regulating the GINS1 expression. The expression profiling of GINS1 in the current study has suggested it a novel shared diagnostic and prognostic biomarker of LIHC, LUAD, and KIRC.

Major threats and habitat use status of Demoiselle crane (Anthropoides virgo), in district Bannu, Pakistan.

Cranes are the large and attractive Creatures of nature with long necks, legs, and life-span. Adults of both sexes are the same with similar color patterns. Demoiselle cranes spend most of their lifespan on dry grasses. They are also found around the stream, rivers, shallow lakes, natural wetlands, and depressions. To evaluate the current status of habitat use and major threats a study was conducted in tehsil Domel district Bannu. Line transect method and water quality tests (temperature, PH, contamination of E-coli bacteria) were used. To determine the major threats questionnaire method was used. The whole data was analyzed by using SPSS 21 version. Based on the distribution four study sites were selected and four water samples from each study site were taken. Most sites were moderate to highly degraded except Kashoo and kurram river mixing point which was low degraded with livestock grazing and human activities. Water quality tests showed PH ranges from 7-9, temperature 6.5-8.5, and contamination of E-coli in all samples. The social survey revealed that hunting, habitat degradation, and pollution as major threats. Effective long-term conservation and management in the study area are needed to focus on the protection of disturbance-free habitat.

Trends and publication rates of abstracts presented at the British Association of Head and Neck Oncologists' (BAHNO) annual meetings: 2009 - 2015.

The British Association of Head and Neck Oncologists (BAHNO) hosts an annual meeting at which research from all specialties involved in the management of head and neck oncology is presented. We have analysed the rate of publication of the abstracts presented, and reviewed the finalised programmes from the meetings between 2009 and 2015. The 2014 meeting was excluded as it was a combined international meeting. Key terms were searched in PubMed and Google Scholar to identify publications in peer-reviewed journals. If none was identified, these platforms were searched for the authors' names. Published abstracts were excluded. Study and journal demographic data were extracted. A total of 363 abstracts were presented, including 75 oral, 271 poster, and 17 of unclear presentation method. The total publication rate was 31.1%, representing 46.7% of oral abstracts and 27.3% of poster presentations. The mean time to publication was 16.5 months. Research was published in 45 individual journals with a mean (range) impact factor of 2.559 (0.886-36.418). There was a trend towards an increasing number of presentations over time with a decreasing publication rate. However, there was no trend in mean impact factor by year. The publication rate of abstracts presented at the BAHNO annual meetings is comparable with that of other large otolaryngology and head and neck conferences. The mean impact factor has not previously been utilised within this field, but may prove a useful metric that enables monitoring of the quality of presented research and comparison of the impact of the conferences.

Correction to: Laparoscopic-assisted transversus abdominis plane block as an effective analgesic in total extraperitoneal inguinal hernia repair: a double-blind, randomized controlled trial.

In the original publication, one of the co-author 'M. Riaz' details were missed to include in the author group. The complete author group should read as A. Mughal, A. Khan, J. Rehman, H. Naseem, M. Riaz, R. Waldron, M. Duggan, W. Khan, K. Barry, I. Z. Khan.

Laparoscopic-assisted transversus abdominis plane block as an effective analgesic in total extraperitoneal inguinal hernia repair: a double-blind, randomized controlled trial.

PURPOSE: Laparoscopic inguinal hernia repair has facilitated early mobilization. Management of post-operative pain is paramount in these day case procedures. The aim of this study was to compare laparoscopic-assisted transversus abdominis plane (TAP) block with periportal local anaesthetic infiltration in managing post-operative pain. METHODS: A double-blind, randomized controlled trial was conducted with patients undergoing elective laparoscopic inguinal hernia repair (January 2016-October 2017). The intervention group received laparoscopic-assisted TAP block with 30 ml 0.25% Bupivacaine. The control group received 15ml of 0.5% Bupivacaine at the periportal sites. Primary outcome measure was assessment of post-operative pain scores using numerical rating on visual analogue scale (VAS) at rest and on coughing at 3 h. Efficacy of TAP block was assessed as reduction in mean pain scores in the order of 2 points using the VAS. RESULTS: 60 (57 males and 3 females) were enrolled; 30 patients were randomized to each group. Patient demographics, anaesthetic and surgical times were similar in both groups. Mean pain scores were significantly reduced in the intervention group at 3 (3.1 vs 1.1 p < 0.001) and 6 h (4.1 vs 1.7 p < 0.001) at rest and on coughing at 3 (4.8 vs 2.1 p < 0.001) and 6 h (5.4 vs 3.0 p < 0.001). Patient satisfaction was higher (8.0 vs 6.8 p < 0.001) and rescue analgesic requirements (169.4vs 71.3 p < 0.001) lower in the intervention group. CONCLUSIONS: This analysis has demonstrated the therapeutic benefit of laparoscopic-assisted TAP block in initial post-operative pain management for patients undergoing elective laparoscopic inguinal hernia repair.

Regional inequality in radiology research output in the UK: a 5-year bibliometric study.

The objective of this study was to describe the patterns of peer-reviewed general radiology publication rates with reference to deaneries in the UK. This was a retrospective bibliometric analysis of publications in the six highest cited general radiology journals. Publications were identified using a manual search in PubMed between 2005 and 2009. Publications originating from UK radiology departments were identified and subcategorised into primary institution of origin, deanery and publication type. The total number of radiology trainees in each deanery was obtained from the General Medical Council. 913 publications were included in the study. Original papers constituted 48.7% (n=445), review articles 30.3% (n=277) and case reports 17.4% (n=159). The median number of publications in each deanery was 27 [interquartile range (IQR) 11-60], and the median number of publications per trainee was 0.49 (IQR 0.31-0.88). The largest proportion of publications came from the London deanery (n=354, 38.8%), followed by Eastern 86 (9.4%), Oxford and Yorkshire 70 (7.7% each). Relative to the number of trainees within each deanery, Oxford had the highest number of publications per trainee (1.78), followed by East Midlands (1.5), London (1.25) and Eastern (0.99). There was a significantly higher publication rate for those deaneries with academic radiologists (p<0.0001). There is a marked difference in the volume of published work in the general radiology literature among UK deaneries, even accounting for differences in the number of trainees. This probably means that opportunities for training in research are similarly non-uniform.

Hematopoietic stem cell transplantation in Oman.

Hematopoietic SCT (HSCT) is an integral part of the management of patients with hematologic disorders. The Sultanate of Oman, with a population of 2.3 million, has an HSCT program based in the Sultan Qaboos University (SQU) hospital. Initiated in 1995, this two-bed unit continues to be the only program in the country. Between June 1995 and August 2006, a total of 128 patients underwent HSCT in this center, averaging about 10-12 transplants per year. The median age of these patients was 11 years (2 months to 45 years). Hematologic malignancies (49%) and inherited disorders (42%) constituted the major transplant indications, whereas BM failure accounted for the remaining. The majority of transplants carried out so far have been HLA-matched sibling-donor allogeneic HSCTs. Among the inherited disorders, homozygous beta-thalassemia and primary immunodeficiency are important transplant indications in this center. The approximate cost of an uncomplicated transplant in this center is US$50,000. The success of this program has now led to the initiation of a new and larger HSCT complex to provide the opportunity for more patients to benefit from this treatment modality within the country.

Dual-organ ablative surgery using a hand-assisted laparoscopic technique. A report of four cases.

In clinical situations where more than one procedure is required, a properly positioned hand-assist device can be used to obviate the need for two large incisions. We present four cases of hand-assisted laparoscopic nephrectomy combined with a simultaneous second organ extraction. Each of the four primary procedures, as well as one of the four secondary procedures, was performed using a hand-assisted laparoscopic technique. In two cases, the secondary procedure was performed with an open surgical technique through the hand-assist incision. For the remaining secondary procedure, we used a laparoscopically assisted technique.

Laparoscopic repair of diaphragmatic defect by total intracorporeal suturing: clinical and technical considerations.

OBJECTIVE: The use of laparoscopy in urology is increasing. Tumor of the kidney or adrenal gland and, in some cases, metastatic disease can involve the diaphragm. We describe the application of laparoscopic suturing techniques in the case of diaphragmatic involvement with a renal tumor. METHODS: After resection of the tumor and a small area of the diaphragm, a chest tube was placed under laparoscopic guidance. The tube was kept clamped until the end of the procedure. Decreasing intraabdominal pneumoperitoneum pressure made suturing easier with less tension on the edges of the diaphragmatic incision. Nonabsorbable interrupted horizontal mattress sutures were placed to close the diaphragmatic defect. RESULTS: The repair was uneventful; no intraoperative complications occurred. Extubation was done at the end of the procedure in the operating room. The chest tube was removed on postoperative day 2, and the patient was discharged on postoperative day 3. CONCLUSIONS: Laparoscopic repair of the diaphragm should be commensurate with traditional open surgical principles. In this regard, it is essential that surgeons interested in performing "advanced" laparoscopic oncologic surgery become facile in laparoscopic suturing.

Laparoscopic bilateral hand assisted nephrectomy for autosomal dominant polycystic kidney disease: initial experience.

PURPOSE: The laparoscopic technique for bilateral nephrectomy in patients with autosomal dominant polycystic kidney disease is technically difficult. The procedure may be more acceptable if alterations to the technique made it safer and easier to perform. We describe our initial experience with, and the feasibility and potential benefits of hand assisted laparoscopic nephrectomy for approaching these large kidneys in patients with autosomal dominant polycystic kidney disease. MATERIALS AND METHODS: This approach was successfully applied in 3 patients with end stage renal disease due to autosomal dominant polycystic kidney disease. After obtaining transumbilical pneumoperitoneum ports were placed in the umbilicus (12 mm.), sub-xiphoid in the midline (12 mm.) and subcostal in the midclavicular line on each side (12 mm.). The table was tilted 40 degrees away from the planned side of initial nephrectomy with the patient in the half lateral position. A 7 cm. midline incision was made that incorporated the umbilical port and a commercially available hand assistance device was positioned. One surgeon hand was inserted into the abdomen to serve as a retractor/blunt dissector, while the other operated the electrosurgical instruments. The right hand was inserted for left nephrectomy and the left hand was inserted for right nephrectomy. The laparoscope was passed via the sub-xiphoid port and the instruments were placed through the ipsilateral subcostal laparoscopic port. Nephrectomy was completed and the specimen was removed through the hand port incision by draining the cysts as they were exposed to view via the midline incision. When dissection was difficult, an additional port was placed in the anterior axillary line at the umbilical level. Some cysts were ruptured or aspirated to decrease overall kidney size and make extraction possible via the 6 to 7 cm. midline incision. RESULTS: All procedures were successfully completed. Mean operative time for bilateral hand assisted laparoscopic nephrectomy was 5.5 hours (range 4.5 to 6.6). Estimated blood loss was 200 cc or less. Patients resumed oral intake on postoperative day 1. The mean amount of parenteral analgesics required postoperatively was decreased. Mean hospital stay was 4.3 days but it was 3 days when considering nephrectomy only. Patients returned to normal activity after an average of 2 weeks. There was sustained resolution of preoperative discomfort based on pain analog scales. At 1 month or less all patients recorded absent pain. They uniformly noticed improved preoperative pulmonary and gastrointestinal symptoms CONCLUSIONS: Hand assisted laparoscopic nephrectomy in patients with autosomal dominant polycystic kidney disease makes bilateral nephrectomy a reasonable option. The bilateral procedure may be performed as rapidly as laparoscopic only, unilateral nephrectomy in these cases. The advantages of the hand assisted approach include using tactile sensation to facilitate dissection, rapid blunt finger dissection, hand retraction and the application of immediate tamponade when needed. This procedure provides the benefits of minimal intraoperative blood loss, minimal postoperative pain, brief hospital stay and rapid convalescence in this group of patients at high risk.

Missed anterior crossing vessels during open retroperitoneal pyeloplasty: laparoscopic transperitoneal discovery and repair.

PURPOSE: Extrinsic ureteropelvic junction obstruction due to anterior crossing segmental renal vessels is present in more than 50% of patients in adulthood. In this situation the ureter must usually be dismembered and transposed anterior to the crossing vascular structures, where it is anastomosed to the renal pelvis. Via the open retroperitoneal approach there may be a limited view of the anterior surface of the ureteropelvic junction and, hence, anterior crossing vessels may possibly be missed. We describe 2 patients with ureteropelvic junction obstruction in whom anterior vessels were missed during open retroperitoneal repair. Laparoscopic transperitoneal secondary pyeloplasty with posterior displacement of the crossing renal vessel was performed in each case. MATERIALS AND METHODS: Two patients presented with symptomatic congenital ureteropelvic junction obstruction after failed endopyelotomy in 1 and failed open retroperitoneal procedures in both. Preoperatively spiral computerized tomography angiography with a ureteropelvic junction protocol revealed crossing vessels in the 2 cases. This finding was confirmed at transperitoneal laparoscopic pyeloplasty. The ureter and renal pelvis were transposed anterior to the crossing vessels and 2 rows of running sutures were placed to complete the anastomosis. RESULTS: The 2 laparoscopic procedures were completed successfully. The anterior crossing vessels were preserved in each case. Currently the patients are asymptomatic and furosemide washout renal scan was normal. CONCLUSIONS: Spiral CT angiography reliably delineates the renal vascular anatomy in patients with ureteropelvic junction obstruction. This study may be valuable before planned open retroperitoneal ureteropelvic junction obstruction repair. Laparoscopic pyeloplasty may successfully manage anterior crossing vessels associated with secondary ureteropelvic junction obstruction.

Significant physiological roles of ancillary penile nerves on increase in intracavernous pressure in rats: experiments using electrical stimulation of the medial preoptic area.

The objectives of this work were to evaluate the contributions of the ancillary penile nerves to penile erection in male rats in vivo. We investigated the effects of unilateral and bilateral transection of the cavernous nerve (main penile nerve) on the increase in intracavernous pressure (ICP) following electrical stimulation of the medial preoptic area (MPOA) in male rats in vivo. After unilateral or bilateral transection of the cavernous nerve (main penile nerve), the ICP responses showed decreases of 28% and 55%, respectively compared to those ICP responses before transection. In other words, even after bilateral transection of the cavernous nerve, significant increases in the ICP response following central stimulation were observed. In contrast to these findings, the ICP response was completely eliminated following bilateral pelvic nerve transection. These data suggested that the ancillary penile nerves, which originate from the major pelvic ganglia, have a complementary role to the cavernous nerves in the autonomic motor innervation of the penis.

Experimental hyperprolactinemia in a rat model: alteration in centrally mediated neuroerectile mechanisms.

INTRODUCTION: The purpose of this study was to induce hyperprolactinemia in adult male rats and determine its effect on the central and peripheral mediated neurogenic as well as myogenic mechanisms of erectile function/dysfunction in a rat model. The use of penile reflexes in awake animals was used to test the effect of both central and peripheral mechanisms. Electrical stimulation of the cavernous nervous was used to test peripheral neural function and intracorporal injection of papaverine was used to test the intactness of the corporal smooth muscles. These mechanisms were further explored by administration of testosterone. METHODS: Eighteen Fisher-344 200-250 g rats aged 10 weeks were used in this study. Group 1 (n = 6) hyperprolactinemia was induced with subcutaneous (SQ) injection of 5 mg rat prolactin (NIDDK-r-PRL-B-7, biopotency 25 IU/mg) in two divided doses daily for 1 week. Testosterone propionate 100 mg/kg dissolved in sesame oil was given intramuscularly on day 1 (weekly dose). Group 2 (n = 6) control animals received SQ injection of vehicle twice daily and sesame oil I/M on day 1. Group 3 (n = 6) received testosterone propionate. Penile reflexes (erections, cups, flips and clusters) were assessed prior to induction (x 3) of and following one-week state of hyperprolactinemia (day 5, 6 and 7). All animals were trained three times before recording the penile reflexes. The penile reflexes being averaged to give a single composite score for each animal. All animals underwent dissections that isolated the cavernosal bodies and cavernosal nerves. Cavernous nerves were activated and intracorporal pressures were recorded at increasing current magnitude (range 0.5-10 mA). Following that corporal smooth muscle reactivity was determined by increasing injection of papaverine (100-3000 microg). Concentration response curves (CRCs) were then generated by plotting percent change (fractional change to make standardized comparison) to increasing neurostimulation or papaverine concentrations at half-log increments. Serum prolactin was determined by rPRL radioimmunoassay Kit-Amersham while serum testosterone was determined Testosterone ELISA Kit-Neogen. RESULTS: Penile reflexes were normal in all groups at the start of experiment but after 1 week of hyperprolactinemia, reflexes were totally abolished in hyperprolactinemia rats (Group 1) and unchanged in Groups 2 and 3. Response to cavernous nerve activation and resulting rise in intracorporal pressure to increasing current (range 0.5-10 mA) were statistically non-significant in any groups. Similarly the intracorporal pressure response to pharmacologic erection induced by papaverine (100-3000 microg) were also non-statistically significant in any groups. Serum prolactin level in all rats receiving prolactin were > 500 ng/ml and the rat group receiving testosterone, serum level were > 20 x higher than the control rat. CONCLUSIONS: This approach allowed more clear separation of central and peripheral mechanism of erection. This study shows a central neurological effect of hyperprolactinemia on erectile function. Hypogonadism does not seem to contribute to the impaired penile reflexes as documented by replacement of testosterone did not recover the centrally mediated penile reflexes. Lowered serum testosterone is secondary phenomenon. These observations may have important implications for the understanding, the mechanism and treatment of men with hyperprolactinemia as well as future research in this field.

A case of a Spigelian hernia at an unusually high anatomical location.

Most Spigelian hernias occur below the level of the umbilicus close to the level of the arcuate line. We report a case diagnosed by computed tomography in an unusually high anatomical location due to a previous drain site incision.

Leukocyte adhesion molecule expression and T cell naïve/memory status following isoproterenol infusion.

This study examined adhesion molecules on peripheral leukocytes following a 30-min infusion of the beta-adrenergic agonist isoproterenol in 23 healthy subjects. In response to isoproterenol, the number of CD8 +CD62L- T cells and both CD62L+ and CD62L-natural killer (NK) (CD3 CD16+ 56+) cells increased markedly in circulation (p < 0.001). In addition, the surface density of CD62L was significantly lower on both CD8+ and CD4+ T cells (p < 0.001). Plasma levels of soluble CD62L remained unchanged, arguing against an isoproterenol-induced shedding of L-selectin. In contrast to CD62L, the surface density of the beta2 integrin LFA-1 (CD11a) was higher on circulating lymphocytes (p < 0.001) (but not monocytes or lymphocytes) post-infusion. Isoproterenol also led to a mobilization of memory/activated CD8+CD29high T cells (p < 0.01), but had no significant effect on the number of circulating CD8+ CD45RA+ CD62L+ naïve T cells. beta blockade with the non-specific antagonist propranolol eliminated these isoproterenol-induced effects.