Charles Yeo - Academia.edu (original) (raw)
Papers by Charles Yeo
Annals of Surgery, 1995
The aims of this analysis were to determine prospectively the effects of surgical resection and r... more The aims of this analysis were to determine prospectively the effects of surgical resection and radiation therapy on the length and quality of survival as well as late toxicity in patients with perihilar cholangiocarcinoma.
Surgery, 2005
Postoperative pancreatic fistula (POPF) is still regarded as a major complication. The incidence ... more Postoperative pancreatic fistula (POPF) is still regarded as a major complication. The incidence of POPF varies greatly in different reports, depending on the definition applied at each surgical center. Our aim was to agree upon an objective and internationally accepted definition to allow comparison of different surgical experiences. An international panel of pancreatic surgeons, working in well-known, high-volume centers, reviewed the literature on the topic and worked together to develop a simple, objective, reliable, and easy-to-apply definition of POPF, graded primarily on clinical impact. A POPF represents a failure of healing/sealing of a pancreatic-enteric anastomosis or a parenchymal leak not directly related to an anastomosis. An all-inclusive definition is a drain output of any measurable volume of fluid on or after postoperative day 3 with an amylase content greater than 3 times the serum amylase activity. Three different grades of POPF (grades A, B, C) are defined according to the clinical impact on the patient's hospital course. The present definition and clinical grading of POPF should allow realistic comparisons of surgical experiences in the future when new techniques, new operations, or new pharmacologic agents that may impact surgical treatment of pancreatic disorders are addressed.
Annals of Surgery, 2004
To assess the authors' experience with intraductal papillary mucinous neoplasms of the pa... more To assess the authors' experience with intraductal papillary mucinous neoplasms of the pancreas (IPMNs). Intraductal papillary mucinous neoplasms of the pancreas are being recognized with increasing frequency. All patients who underwent pancreatic resection for an IPMN at the Johns Hopkins Hospital between January 1987 and December 2000 were studied. The data were compared with those of 702 concurrent patients with infiltrating ductal adenocarcinoma of the pancreas not associated with an IPMN resected by pancreaticoduodenectomy. In the 13-year time period, 60 patients underwent pancreatic resection for IPMNs, with 40 patients undergoing resection in the past 3 years. Mean age at presentation was 67.4 +/- 1.4 years. The most common presenting symptom in patients with IPMNs was abdominal pain (59%). Most IPMNs were in the head of the pancreas or diffusely involved the gland, with 70% being resected via pancreaticoduodenectomy, 22% via total pancreatectomy, and 8% via distal pancreatectomy. Twenty-two patients (37%) had IPMNs with an associated infiltrating adenocarcinoma. In a subset of IPMNs immunohistochemically stained for the Dpc4 protein (n = 50), all of the intraductal or noninvasive components strongly expressed Dpc4, whereas 84% of associated infiltrating cancers expressed Dpc4. The 5-year survival rate for all patients with IPMNs (n = 60) was 57%. Intraductal papillary mucinous neoplasms represent a distinct clinicopathologic entity being recognized with increasing frequency. IPMNs are clinically, histologically, and genetically disparate from pancreatic ductal adenocarcinomas. The distinct clinical features, the presumably long in situ or noninvasive phase, and the good long-term survival of patients with IPMNs offer a unique opportunity for early diagnosis, curative resection, and further studies of the molecular genetics and natural history of these unusual neoplasms.
To examine trends in outcomes of patients undergoing resection at a single tertiary care referral... more To examine trends in outcomes of patients undergoing resection at a single tertiary care referral center over a 16-year period.
American Journal of Pathology, 1999
macules of the lips , buccal mucosa , and digits. Less appreciated is the fact that PJS also pred... more macules of the lips , buccal mucosa , and digits. Less appreciated is the fact that PJS also predisposes patients to an increased risk of gastrointestinal cancer, and pancreatic cancer has been reported in many PJS patients. It was recently shown that germline mutations of the STK11/LKB1 gene are responsible for PJS. We investigated the role of STK11/LKB1 in the development of pancreatic and biliary cancer in patients with and without the PJS. In a PJS patient having a germline splice site mutation in the STK11/LKB1 gene , sequencing analysis of an intestinal polyp and pancreatic cancer from this patient revealed loss of the wild-type allele of the STK11/LKB1 gene in the cancer. Inactivation of STK11/LKB1, by homozygous deletions or somatic sequence mutations coupled with loss of heterozygosity , was also demonstrated in 4 -6% of 127 sporadic pancreatic and biliary adenocarcinomas. Our results demonstrate that germline and somatic genetic alterations of the STK11/LKB1 gene may play a causal role in carcinogenesis and that the same gene contributes to the development of both sporadic and familial forms
Knowledge of the pafterns of allele loss has been useful in identifying the spectrum of the tumor... more Knowledge of the pafterns of allele loss has been useful in identifying the spectrum of the tumor suppressor genes involved in various tumor types. Such analyses in pancreatic carcinoma have been difficult due to the characteristic host desmoplastlc reaction to the neoplasm. We have as sembled the first allelotype of pancreatic adeaocarcinoma, a survey for allelic loss among each chromosomal arm, using seven cryostat-dissected aeoplasms. The fractional allele loss In these seven aeoplasms was 0.18, a value similar to that seen previously in colorectal carcinomaS Alleles of chromosome 18q (lost in five of six Informative tumors) and of chromo some lip (lost in foui@ of five informative tumors) were commoaly af faded. NeltherAPC mutations (33 aeoplasms), allele shifts of dinucleotide repeats (26 neoplasms), nor immunohlstochemlcal evidence of retinoblas toma protein uaderexpression (7 neoplasms) were found. Further evalu atioa of allelic loss in pancreatic cancer would benefit from improved methods for the analysis of lost genetic material which overcome the problems posed by the high admixture of nonneoplastic stromal and inflammatory cells in these tumors.
Annals of Surgery, 1992
Abstract The initial 22-month experience with laparoscopic cholecystectomy in 400 patients employ... more Abstract The initial 22-month experience with laparoscopic cholecystectomy in 400 patients employing an algorithm of selective cholangiographic evaluation is reported. Preoperative or postoperative endoscopic retrograde cholangiography was performed whenever ...
Annals of Surgery, 1993
A review of mortality and morbidity for pancreaticoduodenectomy was performed for 145 consecutive... more A review of mortality and morbidity for pancreaticoduodenectomy was performed for 145 consecutive patients who underwent the operative procedure between 1988 and 1991.
Journal of Gastrointestinal Surgery, 2000
This large-volume, single-institution review examines factors influencing long-term survival afte... more This large-volume, single-institution review examines factors influencing long-term survival after resection in patients with adenocarcinoma of the head, neck, uncinate process, body, or tail of the pancreas. Between January 1984 and July 1999 inclusive, 616 patients with adenocarcinoma of the pancreas underwent surgical resection. A retrospective analysis of a prospectively collected database was performed. Both univariate and multivariate models were used to determine the factors influencing survival. Of the 616 patients, 526 (85%) underwent pancreaticoduodenectomy for adenocarcinoma of the head, neck, or uncinate process of the pancreas, 52 (9%) underwent distal pancreatectomy for adenocarcinoma of the body or tail, and 38 (6%) underwent total pancreatectomy for adenocarcinoma extensively involving the gland. The mean age of the patients was 64.3 years, with 54% being male and 91% being white. The overall perioperative mortality rate was 2.3%, whereas the incidence of postoperative complications was 30%. The median postoperative length of stay was 11 days. The mean tumor diameter was 3.2 cm, with 72 % of patients having positive lymph nodes, 30% having positive resection margins, and 36% having poorly differentiated tumors. Patients undergoing distal pancreatectomy for left-sided lesions had larger tumors (4.7 vs. 3.1 cm, P <0.0001), but fewer node-positive resections (59% vs. 73%, P = 0.03) and fewer poorly differentiated tumors (29% vs. 36%, P<0.001), as compared to those undergoing pancreaticoduodenectomy for right-sided lesions. The overall survival of the entire cohort was 63% at 1 year and 17% at 5 years, with a median survival of 17 months. For right-sided lesions the 1- and 5-year survival rates were 64% and 17%, respectively, compared to 50% and 15% for left-sided lesions. Factors shown to have favorable independent prognostic significance by multivariate analysis were negative resection margins (hazard ratio [HR] = 0.64, confidence interval [CI] = 0.50 to 0.82, P = 0.0004), tumor diameter less than 3 cm (HR = 0.72, CI = 0.57 to 0.90, P = 0.004), estimated blood loss less than 750 ml (HR = 0.75, CI = 0.58 to 0.96, P = 0.02), well/moderate tumor differentiation (HR = 0.71, CI = 0.56 to 0.90, P = 0.005), and postoperative chemoradiation (HR = 0.50, CI = 0.39 to 0.64, P } < 0.0001). Tumor location in head, neck, or uncinate process approached significance in the final multivariate model (HR = 0.60, CI = 0.35 to 1.0, P = 0.06). Pancreatic resection remains the only hope for long-term survival in patients with adenocarcinoma of the pancreas. Completeness of resection and tumor characteristics including tumor size and degree of differentiation are important independent prognostic indicators. Adjuvant chemoradiation is a strong predictor of outcome and likely decreases the independent significance of tumor location and nodal status.
Annals of Surgery, 1995
The aims of this analysis were to determine prospectively the effects of surgical resection and r... more The aims of this analysis were to determine prospectively the effects of surgical resection and radiation therapy on the length and quality of survival as well as late toxicity in patients with perihilar cholangiocarcinoma.
Surgery, 2005
Postoperative pancreatic fistula (POPF) is still regarded as a major complication. The incidence ... more Postoperative pancreatic fistula (POPF) is still regarded as a major complication. The incidence of POPF varies greatly in different reports, depending on the definition applied at each surgical center. Our aim was to agree upon an objective and internationally accepted definition to allow comparison of different surgical experiences. An international panel of pancreatic surgeons, working in well-known, high-volume centers, reviewed the literature on the topic and worked together to develop a simple, objective, reliable, and easy-to-apply definition of POPF, graded primarily on clinical impact. A POPF represents a failure of healing/sealing of a pancreatic-enteric anastomosis or a parenchymal leak not directly related to an anastomosis. An all-inclusive definition is a drain output of any measurable volume of fluid on or after postoperative day 3 with an amylase content greater than 3 times the serum amylase activity. Three different grades of POPF (grades A, B, C) are defined according to the clinical impact on the patient&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s hospital course. The present definition and clinical grading of POPF should allow realistic comparisons of surgical experiences in the future when new techniques, new operations, or new pharmacologic agents that may impact surgical treatment of pancreatic disorders are addressed.
Annals of Surgery, 2004
To assess the authors' experience with intraductal papillary mucinous neoplasms of the pa... more To assess the authors' experience with intraductal papillary mucinous neoplasms of the pancreas (IPMNs). Intraductal papillary mucinous neoplasms of the pancreas are being recognized with increasing frequency. All patients who underwent pancreatic resection for an IPMN at the Johns Hopkins Hospital between January 1987 and December 2000 were studied. The data were compared with those of 702 concurrent patients with infiltrating ductal adenocarcinoma of the pancreas not associated with an IPMN resected by pancreaticoduodenectomy. In the 13-year time period, 60 patients underwent pancreatic resection for IPMNs, with 40 patients undergoing resection in the past 3 years. Mean age at presentation was 67.4 +/- 1.4 years. The most common presenting symptom in patients with IPMNs was abdominal pain (59%). Most IPMNs were in the head of the pancreas or diffusely involved the gland, with 70% being resected via pancreaticoduodenectomy, 22% via total pancreatectomy, and 8% via distal pancreatectomy. Twenty-two patients (37%) had IPMNs with an associated infiltrating adenocarcinoma. In a subset of IPMNs immunohistochemically stained for the Dpc4 protein (n = 50), all of the intraductal or noninvasive components strongly expressed Dpc4, whereas 84% of associated infiltrating cancers expressed Dpc4. The 5-year survival rate for all patients with IPMNs (n = 60) was 57%. Intraductal papillary mucinous neoplasms represent a distinct clinicopathologic entity being recognized with increasing frequency. IPMNs are clinically, histologically, and genetically disparate from pancreatic ductal adenocarcinomas. The distinct clinical features, the presumably long in situ or noninvasive phase, and the good long-term survival of patients with IPMNs offer a unique opportunity for early diagnosis, curative resection, and further studies of the molecular genetics and natural history of these unusual neoplasms.
To examine trends in outcomes of patients undergoing resection at a single tertiary care referral... more To examine trends in outcomes of patients undergoing resection at a single tertiary care referral center over a 16-year period.
American Journal of Pathology, 1999
macules of the lips , buccal mucosa , and digits. Less appreciated is the fact that PJS also pred... more macules of the lips , buccal mucosa , and digits. Less appreciated is the fact that PJS also predisposes patients to an increased risk of gastrointestinal cancer, and pancreatic cancer has been reported in many PJS patients. It was recently shown that germline mutations of the STK11/LKB1 gene are responsible for PJS. We investigated the role of STK11/LKB1 in the development of pancreatic and biliary cancer in patients with and without the PJS. In a PJS patient having a germline splice site mutation in the STK11/LKB1 gene , sequencing analysis of an intestinal polyp and pancreatic cancer from this patient revealed loss of the wild-type allele of the STK11/LKB1 gene in the cancer. Inactivation of STK11/LKB1, by homozygous deletions or somatic sequence mutations coupled with loss of heterozygosity , was also demonstrated in 4 -6% of 127 sporadic pancreatic and biliary adenocarcinomas. Our results demonstrate that germline and somatic genetic alterations of the STK11/LKB1 gene may play a causal role in carcinogenesis and that the same gene contributes to the development of both sporadic and familial forms
Knowledge of the pafterns of allele loss has been useful in identifying the spectrum of the tumor... more Knowledge of the pafterns of allele loss has been useful in identifying the spectrum of the tumor suppressor genes involved in various tumor types. Such analyses in pancreatic carcinoma have been difficult due to the characteristic host desmoplastlc reaction to the neoplasm. We have as sembled the first allelotype of pancreatic adeaocarcinoma, a survey for allelic loss among each chromosomal arm, using seven cryostat-dissected aeoplasms. The fractional allele loss In these seven aeoplasms was 0.18, a value similar to that seen previously in colorectal carcinomaS Alleles of chromosome 18q (lost in five of six Informative tumors) and of chromo some lip (lost in foui@ of five informative tumors) were commoaly af faded. NeltherAPC mutations (33 aeoplasms), allele shifts of dinucleotide repeats (26 neoplasms), nor immunohlstochemlcal evidence of retinoblas toma protein uaderexpression (7 neoplasms) were found. Further evalu atioa of allelic loss in pancreatic cancer would benefit from improved methods for the analysis of lost genetic material which overcome the problems posed by the high admixture of nonneoplastic stromal and inflammatory cells in these tumors.
Annals of Surgery, 1992
Abstract The initial 22-month experience with laparoscopic cholecystectomy in 400 patients employ... more Abstract The initial 22-month experience with laparoscopic cholecystectomy in 400 patients employing an algorithm of selective cholangiographic evaluation is reported. Preoperative or postoperative endoscopic retrograde cholangiography was performed whenever ...
Annals of Surgery, 1993
A review of mortality and morbidity for pancreaticoduodenectomy was performed for 145 consecutive... more A review of mortality and morbidity for pancreaticoduodenectomy was performed for 145 consecutive patients who underwent the operative procedure between 1988 and 1991.
Journal of Gastrointestinal Surgery, 2000
This large-volume, single-institution review examines factors influencing long-term survival afte... more This large-volume, single-institution review examines factors influencing long-term survival after resection in patients with adenocarcinoma of the head, neck, uncinate process, body, or tail of the pancreas. Between January 1984 and July 1999 inclusive, 616 patients with adenocarcinoma of the pancreas underwent surgical resection. A retrospective analysis of a prospectively collected database was performed. Both univariate and multivariate models were used to determine the factors influencing survival. Of the 616 patients, 526 (85%) underwent pancreaticoduodenectomy for adenocarcinoma of the head, neck, or uncinate process of the pancreas, 52 (9%) underwent distal pancreatectomy for adenocarcinoma of the body or tail, and 38 (6%) underwent total pancreatectomy for adenocarcinoma extensively involving the gland. The mean age of the patients was 64.3 years, with 54% being male and 91% being white. The overall perioperative mortality rate was 2.3%, whereas the incidence of postoperative complications was 30%. The median postoperative length of stay was 11 days. The mean tumor diameter was 3.2 cm, with 72 % of patients having positive lymph nodes, 30% having positive resection margins, and 36% having poorly differentiated tumors. Patients undergoing distal pancreatectomy for left-sided lesions had larger tumors (4.7 vs. 3.1 cm, P <0.0001), but fewer node-positive resections (59% vs. 73%, P = 0.03) and fewer poorly differentiated tumors (29% vs. 36%, P<0.001), as compared to those undergoing pancreaticoduodenectomy for right-sided lesions. The overall survival of the entire cohort was 63% at 1 year and 17% at 5 years, with a median survival of 17 months. For right-sided lesions the 1- and 5-year survival rates were 64% and 17%, respectively, compared to 50% and 15% for left-sided lesions. Factors shown to have favorable independent prognostic significance by multivariate analysis were negative resection margins (hazard ratio [HR] = 0.64, confidence interval [CI] = 0.50 to 0.82, P = 0.0004), tumor diameter less than 3 cm (HR = 0.72, CI = 0.57 to 0.90, P = 0.004), estimated blood loss less than 750 ml (HR = 0.75, CI = 0.58 to 0.96, P = 0.02), well/moderate tumor differentiation (HR = 0.71, CI = 0.56 to 0.90, P = 0.005), and postoperative chemoradiation (HR = 0.50, CI = 0.39 to 0.64, P } < 0.0001). Tumor location in head, neck, or uncinate process approached significance in the final multivariate model (HR = 0.60, CI = 0.35 to 1.0, P = 0.06). Pancreatic resection remains the only hope for long-term survival in patients with adenocarcinoma of the pancreas. Completeness of resection and tumor characteristics including tumor size and degree of differentiation are important independent prognostic indicators. Adjuvant chemoradiation is a strong predictor of outcome and likely decreases the independent significance of tumor location and nodal status.