BACKGROUND Pancreaticoduodenectomy(PD)is a technically complex operation,with a re-latively high risk for complications.The ability to rescue patients from post-PD complications is as a recognized quality measure.Tail...BACKGROUND Pancreaticoduodenectomy(PD)is a technically complex operation,with a re-latively high risk for complications.The ability to rescue patients from post-PD complications is as a recognized quality measure.Tailored protocols were instituted at our low volume facility in the year 2013.AIM To document the rate of rescue from post-PD complications with tailored protocols in place as a measure of quality.METHODS A retrospective audit was performed to collect data from patients who experienced major post-PD complications at a low volume pancreatic surgery unit in Trinidad and Tobago between January 1,2013 and June 30,2023.Stan-dardized definitions from the International Study Group of Pancreatic Surgery were used to define post-PD complications,and the modified Clavien-Dindo classification was used to classify post-PD complications.RESULTS Over the study period,113 patients at a mean age of 57.5 years(standard deviation[SD]±9.23;range:30-90;median:56)underwent PDs at this facility.Major complications were recorded in 33(29.2%)patients at a mean age of 53.8 years(SD:±7.9).Twenty-nine(87.9%)patients who experienced major morbidity were salvaged after aggre-ssive treatment of their complication.Four(3.5%)died from bleeding pseudoaneurysm(1),septic shock secondary to a bile leak(1),anastomotic leak(1),and myocardial infarction(1).There was a significantly greater salvage rate in patients with American Society of Anesthesiologists scores≤2(93.3%vs 25%;P=0.0024).CONCLUSION This paper adds to the growing body of evidence that volume alone should not be used as a marker of quality for patients requiring PD.Despite low volumes at our facility,we demonstrated that 87.9%of patients were rescued from major complications.We attributed this to several factors including development of rescue protocols,the competence of the pancreatic surgery teams and continuous,and adaptive learning by the entire institution,cul-minating in the development of tailored peri-pancreatectomy protocols.展开更多
Pancreatic resection is the treatment of choice for pancreatic malignancy and certain benign pancreatic disorders. However, pancreatic resection is technically a demanding procedure and whereas mortality after a pancr...Pancreatic resection is the treatment of choice for pancreatic malignancy and certain benign pancreatic disorders. However, pancreatic resection is technically a demanding procedure and whereas mortality after a pancreaticoduodenectomy is currently < 3%-5% in experienced high-volume centers, post-operative morbidity is considerable, about 30%-50%. At present, the single most significant cause of morbidity and mortality after pancreatectomy is the development of pancreatic leakage and fistula (PF). The occurrence of a PF increases the length of hospital stay and the cost of treatment, requires additional investigations and procedures, and can result in life-threatening complications. There is no universally accepted definition of PF that would allow standardized reporting and proper comparison of outcomes between different centers. However, early recognition of a PF and prompt institution of appropriate treatment is critical to the prevention of potentially devastating consequences. The present article, reviews the evolution of post resection pancreatic fistula as a concept, and discusses evolving definitions, the current preventive strategies and the management of this problem.展开更多
Laparoscopic colorectal surgery(LCS) is an evolving subject.Recent studies show that LCS can not only offer safe surgery but evidence is growing that this new technique can be superior to classical open procedures.Few...Laparoscopic colorectal surgery(LCS) is an evolving subject.Recent studies show that LCS can not only offer safe surgery but evidence is growing that this new technique can be superior to classical open procedures.Fewer perioperative complications and faster postoperative recovery are regularly mentioned when studies of LCS are presented.Even though the learning curve of LCS is frequently debated when limitations of laparoscopic surgeries are reviewed,studies show that in experienced hands LCS can be a safe procedure for colorectal cancer treatment.The learning curve however,is associated with high conversion rates and economical aspects such as higher costs and prolonged hospital stay.Nevertheless,laparoscopic colorectal cancer surgery(LCCR) offers several advantages such as less co-morbidity and less postoperative pain in comparison with open procedures.Furthermore,the good exposure of the pelvic cavity by laparoscopy and the magnification of anatomical structures seem to facilitate pelvic dissection laparoscopically.Moreover,recent studies describe no difference in safety and oncological radicalness in LCCR compared to the open total mesorectal excision(TME).The oncological adequacy of LCCR still remains unproven today,because long-term results do not yet exist.To date,only a few studies have described the results of laparoscopic TME combined with preoperative adjuvant treatment for colorectal cancer.The aim of this review is to examine the various areas of development and controversy of LCCR in comparison to the conventional open approach.展开更多
Surgery remains the mainstay of treatment for pancreatic ductal adenocarcinoma and complete removal of the cancer confers a definite survival advantage,especially in early disease.However,the majority of patients do n...Surgery remains the mainstay of treatment for pancreatic ductal adenocarcinoma and complete removal of the cancer confers a definite survival advantage,especially in early disease.However,the majority of patients do not present with early disease,thus precluding the chance of a cure by standard pancreatoduodenectomy(PD),distal pancreatectomy or total pancreatectomy.For this reason,pancreatic surgeons have attempted to push the limits of resection over the last three decades.The aim of these resections has been to determine whether obtaining a complete resection by extending the limits of conventional resection in patients with advanced disease will yield the results seen with PD alone in early disease.This article revisits the data from such studies in an attempt to determine if the available literature supports the performance of extended resections for pancreatic cancer in terms of improvement of survival.展开更多
The outcomes for gallbladder cancer remain largely dismal to this day.Overall,the low incidence of gallbladder cancer around the world coupled with an even lower number of patients amenable to surgery at the time of p...The outcomes for gallbladder cancer remain largely dismal to this day.Overall,the low incidence of gallbladder cancer around the world coupled with an even lower number of patients amenable to surgery at the time of presentation,has precluded the generation of evidence-based guidelines for the management of this cancer.However,while the incidence of the cancer may be decreasing in some parts of the world,in other countries such as India,Japan and Chile,gallbladder cancer continues to affect a sizeable population of patients.As such,there is a growing need to define what constitutes an adequate surgery for each stage of this cancer,based on sound evidence.This editorial provides a broad overview of the existing problems in the management of gallbladder cancer and appeals for multi-institutional studies aimed at answering some of the pertinent questions on the surgical management of gallbladder cancer.展开更多
Artificial intelligence(AI)demonstrated by machines is based on reinforcement learning and revolves around the usage of algorithms.The purpose of this review was to summarize concepts,the scope,applications,and limita...Artificial intelligence(AI)demonstrated by machines is based on reinforcement learning and revolves around the usage of algorithms.The purpose of this review was to summarize concepts,the scope,applications,and limitations in major gastrointestinal surgery.This is a narrative review of the available literature on the key capabilities of AI to help anesthesiologists,surgeons,and other physicians to understand and critically evaluate ongoing and new AI applications in perioperative management.AI uses available databases called“big data”to formulate an algorithm.Analysis of other data based on these algorithms can help in early diagnosis,accurate risk assessment,intraoperative management,automated drug delivery,predicting anesthesia and surgical complications and postoperative outcomes and can thus lead to effective perioperative management as well as to reduce the cost of treatment.Perioperative physicians,anesthesiologists,and surgeons are well-positioned to help integrate AI into modern surgical practice.We all need to partner and collaborate with data scientists to collect and analyze data across all phases of perioperative care to provide clinical scenarios and context.Careful implementation and use of AI along with real-time human interpretation will revolutionize perioperative care,and is the way forward in future perioperative management of major surgery.展开更多
Minimally invasive pancreatoduodenectomy is currently a feasible option in selected patients at high volume centers with available expertise. Although the procedure hasbeen described two decades ago, laparoscopic surg...Minimally invasive pancreatoduodenectomy is currently a feasible option in selected patients at high volume centers with available expertise. Although the procedure hasbeen described two decades ago, laparoscopic surgeons have been reluctant to perform it since it is technically demanding. Currently there is no standardized training process for minimally invasive pancreatoduodenectomy and this is required to ensure the safety of the procedure. Even the open pancreatoduodenectomy can be a challenging procedure where the outcome depends much upon the patient volume and surgeon's experience. In the minimally invasive setting, all the current evidence comes from retrospective data with inherent selection bias. Although the proposed benefits have been reported in many series, a randomized trial comparing with the open approach is highly unlikely to happen, given the complexity of pancreatic cancer and patient selection for complex surgery. Rather, in a disease for which cure is an utopian statement, perhaps the ultimate aim of minimally invasive pancreatoduodenectomy can be the improvement in the quality of life. Also further studies are needed to assess the immunologic role affecting the oncologic outcomes in patients undergoing minimally invasive pancreatoduodenectomy. The robotic platforms have got easily accepted since they can overcome some of the limitations of the laparoscopic platforms such as limited range of motion, two dimensional visualization and poor ergonomics. The main limitations of robotic procedures are related to the high costs associated with the system and disposable equipment. Currently evidence is lacking regarding the cost effectiveness of the procedure and also the push from the industry is on rise. All these minimally invasive techniques have a long learning curve and prior extensive experience in hepatopancreatobiliary surgery is mandatory for surgeons embarking on these endeavours.展开更多
BACKGROUND The prognosis of gastric cancer continues to remain poor,and epigenetic drugs like histone deacetylase inhibitors(HDACi)have been envisaged as potential therapeutic agents.Nevertheless,clinical trials are f...BACKGROUND The prognosis of gastric cancer continues to remain poor,and epigenetic drugs like histone deacetylase inhibitors(HDACi)have been envisaged as potential therapeutic agents.Nevertheless,clinical trials are facing issues with toxicity and efficacy against solid tumors,which may be partly due to the lack of patient stratification for effective treatments.To study the need of patient stratification before HDACi treatment,and the efficacy of pre-treatment of HDACi as a chemotherapeutic drug sensitizer.METHODS The expression activity of class 1 HDACs and histone acetylation was examined in human gastric cancer cells and tissues.The potential combinatorial regime of HDACi and chemotherapy drugs was defined on the basis of observed drug binding assays,chromatin remodeling and cell death.RESULTS In the present study,the data suggest that the differential increase in HDAC activity and the expression of class 1 HDACs are associated with hypoacetylation of histone proteins in tumors compared to normal adjacent mucosa tissue samples of gastric cancer.The data highlights for the first time that pretreatment of HDACi results in an increased amount of DNA-bound drugs associated with enhanced histone acetylation,chromatin relaxation and cell cycle arrest.Fraction-affected plots and combination index-based analysis show that pre-HDACi chemo drug combinatorial regimes,including valproic acid with cisplatin or oxaliplatin and trichostatin A with epirubicin,exhibit synergism with maximum cytotoxic potential due to higher cell death at low combined doses in gastric cancer cell lines.CONCLUSION Expression or activity of class 1 HDACs among gastric cancer patients present an effective approach for patient stratification.Furthermore,HDACi therapy in pretreatment regimes is more effective with chemotherapy drugs,and may aid in predicting individual patient prognosis.展开更多
AIM:To investigate cell type specific distribution ofβ-actin expression in gastric adenocarcinoma and its correlation with clinicopathological parameters.METHODS:β-actin is a housekeeping gene,frequently used as loa...AIM:To investigate cell type specific distribution ofβ-actin expression in gastric adenocarcinoma and its correlation with clinicopathological parameters.METHODS:β-actin is a housekeeping gene,frequently used as loading control,but,differentially expresses in cancer.In gastric cancer,an overall increased expression ofβ-actin has been reported using tissue disruptive techniques.At present,no histological data is available to indicate its cell type-specific expression and distribution pattern.In the present study,we analyzedβ-actin expression and distribution in paired normal and tumor tissue samples of gastric adenocarcinoma patients using immunohistochemistry(IHC),a tissue non-disruptive technique as well as tissue disruptive techniques like reverse transcriptase-polymerase chain reaction(RT-PCR)and western blotting.Correlation ofβ-actin level with clinicopathological parameters was done using univariate analysis.RESULTS:The results of this study showed significant overexpression,at both mRNA and protein level in tumor tissues as confirmed by RT-PCR(1.47±0.13 vs2.36±0.16;P<0.001)and western blotting(1.92±0.26 vs 2.88±0.32;P<0.01).IHC revealed thatβ-actin expression is majorly distributed between epithelial and inflammatory cells of the tissues.Inflammatory cells showed a significantly higher expression compared to epithelial cells in normal(2.46±0.13 vs 5.92±0.23,P<0.001),as well as,in tumor tissues(2.79±0.24 vs6.71±0.14,P<0.001).Further,comparison of immunostaining between normal and tumor tissues revealed that both epithelial and inflammatory cells overexpressβ-actin in tumor tissues,however,significant difference was observed only in inflammatory cells(5.92±0.23vs 6.71±0.14,P<0.01).Moreover,combined expression in epithelial and inflammatory cells also showed significant increase(4.19±0.15 vs 4.75±0.14,P<0.05)in tumor tissues.In addition,univariate analysis showed a positive correlation ofβ-actin level of inflammatory cells with tumor grade(P<0.05)while epithelial cells exhibited negative correlation(P>0.05).CONCLUSION:In gastric cancer,β-actin showed an overall higher expression predominantly contributed by inflammatory or tumor infiltrating immune cells of the tissue microenvironment and correlates with tumor grade.展开更多
Natural orifice transluminal endoscopic surgery (NOTES) is a surgical technique that has received considerable interest in recent years. Although minimal access surgery has increasingly replaced traditional open abdom...Natural orifice transluminal endoscopic surgery (NOTES) is a surgical technique that has received considerable interest in recent years. Although minimal access surgery has increasingly replaced traditional open abdominal surgical approaches for a wide spectrum of indications, in pancreatic diseases its widespread use is limited to few indications because of the challenging and demanding nature of major pancreatic operations. Nonetheless, there have been attempts in animal models as well as in the clinical setting to perform diag- nostic and resectional NOTES for pancreatic diseases. Here, we review and comment upon the available data regarding currently analyzed and performed pancreatic NOTES procedures. Potential indications for NOTES include peritoneoscopy, cyst drainage, and necrosectomy, palliative procedures such as gastroenterostomy, as well as resections such as distal pancreatectomy or enucleation. These procedures have already been shown to be technically feasible in several studies in animal models and a few clinical trials. In conclusion, NOTES is a rapidly developing concept/technique that could potentially become an integral part of the armamentarium dealing with surgical approaches to pancreatic diseases.展开更多
BACKGROUND:The ideal treatment of patients with 'borderline resectable pancreatic tumors (BRTs)' needs to be established.Current protocols advise neoadjuvant chemo(radio)therapy,although some patients may appe...BACKGROUND:The ideal treatment of patients with 'borderline resectable pancreatic tumors (BRTs)' needs to be established.Current protocols advise neoadjuvant chemo(radio)therapy,although some patients may appear to have BRT on preoperative imaging and a complete resection may be achieved without the need for vascular resection.The aim of the present study was to identify specific findings on preoperative imaging that could help predict in which patients with BRT a complete resection,with or without vascular resection (VR),could be achieved.METHODS:Twelve patients with BRTs were identified.Tumor location,maximum degree of circumferential contact (CC),length of contact of the tumor with major vessels (LC),and luminal narrowing of vessels at the point of contact with the tumor (venous deformity,VD) were graded on preoperatively acquired multidetector computed tomography (MDCT) images and then compared with the intraoperative findings and need for VR.RESULTS:A complete resection (R0) was achieved in 10 patients with 2 having microscopic positive margins (R1) on histopathology at the uncinate margin.Four of the 10 patients required VR (40%).In 3 of the 4 patients whose tumors required VRs,CC was ≥grade III and VD was grade 2.LC did not influence the need for VR.CONCLUSIONS:It is possible to achieve a complete resection at the first instance in patients found to have BRTs on preoperative imaging.Preoperative MDCT-based grading systems and our proposed criteria may help identify such patients,thus avoiding any delay in curative resections in such patients.展开更多
基金This study was approved by the Campus Research Ethics Committee,St.Augustine.
文摘BACKGROUND Pancreaticoduodenectomy(PD)is a technically complex operation,with a re-latively high risk for complications.The ability to rescue patients from post-PD complications is as a recognized quality measure.Tailored protocols were instituted at our low volume facility in the year 2013.AIM To document the rate of rescue from post-PD complications with tailored protocols in place as a measure of quality.METHODS A retrospective audit was performed to collect data from patients who experienced major post-PD complications at a low volume pancreatic surgery unit in Trinidad and Tobago between January 1,2013 and June 30,2023.Stan-dardized definitions from the International Study Group of Pancreatic Surgery were used to define post-PD complications,and the modified Clavien-Dindo classification was used to classify post-PD complications.RESULTS Over the study period,113 patients at a mean age of 57.5 years(standard deviation[SD]±9.23;range:30-90;median:56)underwent PDs at this facility.Major complications were recorded in 33(29.2%)patients at a mean age of 53.8 years(SD:±7.9).Twenty-nine(87.9%)patients who experienced major morbidity were salvaged after aggre-ssive treatment of their complication.Four(3.5%)died from bleeding pseudoaneurysm(1),septic shock secondary to a bile leak(1),anastomotic leak(1),and myocardial infarction(1).There was a significantly greater salvage rate in patients with American Society of Anesthesiologists scores≤2(93.3%vs 25%;P=0.0024).CONCLUSION This paper adds to the growing body of evidence that volume alone should not be used as a marker of quality for patients requiring PD.Despite low volumes at our facility,we demonstrated that 87.9%of patients were rescued from major complications.We attributed this to several factors including development of rescue protocols,the competence of the pancreatic surgery teams and continuous,and adaptive learning by the entire institution,cul-minating in the development of tailored peri-pancreatectomy protocols.
文摘Pancreatic resection is the treatment of choice for pancreatic malignancy and certain benign pancreatic disorders. However, pancreatic resection is technically a demanding procedure and whereas mortality after a pancreaticoduodenectomy is currently < 3%-5% in experienced high-volume centers, post-operative morbidity is considerable, about 30%-50%. At present, the single most significant cause of morbidity and mortality after pancreatectomy is the development of pancreatic leakage and fistula (PF). The occurrence of a PF increases the length of hospital stay and the cost of treatment, requires additional investigations and procedures, and can result in life-threatening complications. There is no universally accepted definition of PF that would allow standardized reporting and proper comparison of outcomes between different centers. However, early recognition of a PF and prompt institution of appropriate treatment is critical to the prevention of potentially devastating consequences. The present article, reviews the evolution of post resection pancreatic fistula as a concept, and discusses evolving definitions, the current preventive strategies and the management of this problem.
文摘Laparoscopic colorectal surgery(LCS) is an evolving subject.Recent studies show that LCS can not only offer safe surgery but evidence is growing that this new technique can be superior to classical open procedures.Fewer perioperative complications and faster postoperative recovery are regularly mentioned when studies of LCS are presented.Even though the learning curve of LCS is frequently debated when limitations of laparoscopic surgeries are reviewed,studies show that in experienced hands LCS can be a safe procedure for colorectal cancer treatment.The learning curve however,is associated with high conversion rates and economical aspects such as higher costs and prolonged hospital stay.Nevertheless,laparoscopic colorectal cancer surgery(LCCR) offers several advantages such as less co-morbidity and less postoperative pain in comparison with open procedures.Furthermore,the good exposure of the pelvic cavity by laparoscopy and the magnification of anatomical structures seem to facilitate pelvic dissection laparoscopically.Moreover,recent studies describe no difference in safety and oncological radicalness in LCCR compared to the open total mesorectal excision(TME).The oncological adequacy of LCCR still remains unproven today,because long-term results do not yet exist.To date,only a few studies have described the results of laparoscopic TME combined with preoperative adjuvant treatment for colorectal cancer.The aim of this review is to examine the various areas of development and controversy of LCCR in comparison to the conventional open approach.
文摘Surgery remains the mainstay of treatment for pancreatic ductal adenocarcinoma and complete removal of the cancer confers a definite survival advantage,especially in early disease.However,the majority of patients do not present with early disease,thus precluding the chance of a cure by standard pancreatoduodenectomy(PD),distal pancreatectomy or total pancreatectomy.For this reason,pancreatic surgeons have attempted to push the limits of resection over the last three decades.The aim of these resections has been to determine whether obtaining a complete resection by extending the limits of conventional resection in patients with advanced disease will yield the results seen with PD alone in early disease.This article revisits the data from such studies in an attempt to determine if the available literature supports the performance of extended resections for pancreatic cancer in terms of improvement of survival.
文摘The outcomes for gallbladder cancer remain largely dismal to this day.Overall,the low incidence of gallbladder cancer around the world coupled with an even lower number of patients amenable to surgery at the time of presentation,has precluded the generation of evidence-based guidelines for the management of this cancer.However,while the incidence of the cancer may be decreasing in some parts of the world,in other countries such as India,Japan and Chile,gallbladder cancer continues to affect a sizeable population of patients.As such,there is a growing need to define what constitutes an adequate surgery for each stage of this cancer,based on sound evidence.This editorial provides a broad overview of the existing problems in the management of gallbladder cancer and appeals for multi-institutional studies aimed at answering some of the pertinent questions on the surgical management of gallbladder cancer.
文摘Artificial intelligence(AI)demonstrated by machines is based on reinforcement learning and revolves around the usage of algorithms.The purpose of this review was to summarize concepts,the scope,applications,and limitations in major gastrointestinal surgery.This is a narrative review of the available literature on the key capabilities of AI to help anesthesiologists,surgeons,and other physicians to understand and critically evaluate ongoing and new AI applications in perioperative management.AI uses available databases called“big data”to formulate an algorithm.Analysis of other data based on these algorithms can help in early diagnosis,accurate risk assessment,intraoperative management,automated drug delivery,predicting anesthesia and surgical complications and postoperative outcomes and can thus lead to effective perioperative management as well as to reduce the cost of treatment.Perioperative physicians,anesthesiologists,and surgeons are well-positioned to help integrate AI into modern surgical practice.We all need to partner and collaborate with data scientists to collect and analyze data across all phases of perioperative care to provide clinical scenarios and context.Careful implementation and use of AI along with real-time human interpretation will revolutionize perioperative care,and is the way forward in future perioperative management of major surgery.
文摘Minimally invasive pancreatoduodenectomy is currently a feasible option in selected patients at high volume centers with available expertise. Although the procedure hasbeen described two decades ago, laparoscopic surgeons have been reluctant to perform it since it is technically demanding. Currently there is no standardized training process for minimally invasive pancreatoduodenectomy and this is required to ensure the safety of the procedure. Even the open pancreatoduodenectomy can be a challenging procedure where the outcome depends much upon the patient volume and surgeon's experience. In the minimally invasive setting, all the current evidence comes from retrospective data with inherent selection bias. Although the proposed benefits have been reported in many series, a randomized trial comparing with the open approach is highly unlikely to happen, given the complexity of pancreatic cancer and patient selection for complex surgery. Rather, in a disease for which cure is an utopian statement, perhaps the ultimate aim of minimally invasive pancreatoduodenectomy can be the improvement in the quality of life. Also further studies are needed to assess the immunologic role affecting the oncologic outcomes in patients undergoing minimally invasive pancreatoduodenectomy. The robotic platforms have got easily accepted since they can overcome some of the limitations of the laparoscopic platforms such as limited range of motion, two dimensional visualization and poor ergonomics. The main limitations of robotic procedures are related to the high costs associated with the system and disposable equipment. Currently evidence is lacking regarding the cost effectiveness of the procedure and also the push from the industry is on rise. All these minimally invasive techniques have a long learning curve and prior extensive experience in hepatopancreatobiliary surgery is mandatory for surgeons embarking on these endeavours.
基金Supported by TMH-IRG(account number-466/2012 and 164/2016)LTMT grant for project funding+1 种基金ACTREC-TMC for funding to Gupta labsupported by ACTREC fellowships
文摘BACKGROUND The prognosis of gastric cancer continues to remain poor,and epigenetic drugs like histone deacetylase inhibitors(HDACi)have been envisaged as potential therapeutic agents.Nevertheless,clinical trials are facing issues with toxicity and efficacy against solid tumors,which may be partly due to the lack of patient stratification for effective treatments.To study the need of patient stratification before HDACi treatment,and the efficacy of pre-treatment of HDACi as a chemotherapeutic drug sensitizer.METHODS The expression activity of class 1 HDACs and histone acetylation was examined in human gastric cancer cells and tissues.The potential combinatorial regime of HDACi and chemotherapy drugs was defined on the basis of observed drug binding assays,chromatin remodeling and cell death.RESULTS In the present study,the data suggest that the differential increase in HDAC activity and the expression of class 1 HDACs are associated with hypoacetylation of histone proteins in tumors compared to normal adjacent mucosa tissue samples of gastric cancer.The data highlights for the first time that pretreatment of HDACi results in an increased amount of DNA-bound drugs associated with enhanced histone acetylation,chromatin relaxation and cell cycle arrest.Fraction-affected plots and combination index-based analysis show that pre-HDACi chemo drug combinatorial regimes,including valproic acid with cisplatin or oxaliplatin and trichostatin A with epirubicin,exhibit synergism with maximum cytotoxic potential due to higher cell death at low combined doses in gastric cancer cell lines.CONCLUSION Expression or activity of class 1 HDACs among gastric cancer patients present an effective approach for patient stratification.Furthermore,HDACi therapy in pretreatment regimes is more effective with chemotherapy drugs,and may aid in predicting individual patient prognosis.
基金Supported by TMH-IRG for project funding(account number-466),Advanced Center for Treatment Research and Education in Cancer,India for funding to Gupta lab
文摘AIM:To investigate cell type specific distribution ofβ-actin expression in gastric adenocarcinoma and its correlation with clinicopathological parameters.METHODS:β-actin is a housekeeping gene,frequently used as loading control,but,differentially expresses in cancer.In gastric cancer,an overall increased expression ofβ-actin has been reported using tissue disruptive techniques.At present,no histological data is available to indicate its cell type-specific expression and distribution pattern.In the present study,we analyzedβ-actin expression and distribution in paired normal and tumor tissue samples of gastric adenocarcinoma patients using immunohistochemistry(IHC),a tissue non-disruptive technique as well as tissue disruptive techniques like reverse transcriptase-polymerase chain reaction(RT-PCR)and western blotting.Correlation ofβ-actin level with clinicopathological parameters was done using univariate analysis.RESULTS:The results of this study showed significant overexpression,at both mRNA and protein level in tumor tissues as confirmed by RT-PCR(1.47±0.13 vs2.36±0.16;P<0.001)and western blotting(1.92±0.26 vs 2.88±0.32;P<0.01).IHC revealed thatβ-actin expression is majorly distributed between epithelial and inflammatory cells of the tissues.Inflammatory cells showed a significantly higher expression compared to epithelial cells in normal(2.46±0.13 vs 5.92±0.23,P<0.001),as well as,in tumor tissues(2.79±0.24 vs6.71±0.14,P<0.001).Further,comparison of immunostaining between normal and tumor tissues revealed that both epithelial and inflammatory cells overexpressβ-actin in tumor tissues,however,significant difference was observed only in inflammatory cells(5.92±0.23vs 6.71±0.14,P<0.01).Moreover,combined expression in epithelial and inflammatory cells also showed significant increase(4.19±0.15 vs 4.75±0.14,P<0.05)in tumor tissues.In addition,univariate analysis showed a positive correlation ofβ-actin level of inflammatory cells with tumor grade(P<0.05)while epithelial cells exhibited negative correlation(P>0.05).CONCLUSION:In gastric cancer,β-actin showed an overall higher expression predominantly contributed by inflammatory or tumor infiltrating immune cells of the tissue microenvironment and correlates with tumor grade.
文摘Natural orifice transluminal endoscopic surgery (NOTES) is a surgical technique that has received considerable interest in recent years. Although minimal access surgery has increasingly replaced traditional open abdominal surgical approaches for a wide spectrum of indications, in pancreatic diseases its widespread use is limited to few indications because of the challenging and demanding nature of major pancreatic operations. Nonetheless, there have been attempts in animal models as well as in the clinical setting to perform diag- nostic and resectional NOTES for pancreatic diseases. Here, we review and comment upon the available data regarding currently analyzed and performed pancreatic NOTES procedures. Potential indications for NOTES include peritoneoscopy, cyst drainage, and necrosectomy, palliative procedures such as gastroenterostomy, as well as resections such as distal pancreatectomy or enucleation. These procedures have already been shown to be technically feasible in several studies in animal models and a few clinical trials. In conclusion, NOTES is a rapidly developing concept/technique that could potentially become an integral part of the armamentarium dealing with surgical approaches to pancreatic diseases.
文摘BACKGROUND:The ideal treatment of patients with 'borderline resectable pancreatic tumors (BRTs)' needs to be established.Current protocols advise neoadjuvant chemo(radio)therapy,although some patients may appear to have BRT on preoperative imaging and a complete resection may be achieved without the need for vascular resection.The aim of the present study was to identify specific findings on preoperative imaging that could help predict in which patients with BRT a complete resection,with or without vascular resection (VR),could be achieved.METHODS:Twelve patients with BRTs were identified.Tumor location,maximum degree of circumferential contact (CC),length of contact of the tumor with major vessels (LC),and luminal narrowing of vessels at the point of contact with the tumor (venous deformity,VD) were graded on preoperatively acquired multidetector computed tomography (MDCT) images and then compared with the intraoperative findings and need for VR.RESULTS:A complete resection (R0) was achieved in 10 patients with 2 having microscopic positive margins (R1) on histopathology at the uncinate margin.Four of the 10 patients required VR (40%).In 3 of the 4 patients whose tumors required VRs,CC was ≥grade III and VD was grade 2.LC did not influence the need for VR.CONCLUSIONS:It is possible to achieve a complete resection at the first instance in patients found to have BRTs on preoperative imaging.Preoperative MDCT-based grading systems and our proposed criteria may help identify such patients,thus avoiding any delay in curative resections in such patients.