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1.
Oncogene ; 35(15): 1926-42, 2016 Apr 14.
Article in English | MEDLINE | ID: mdl-26119934

ABSTRACT

Cancer cells often gains a growth advantage by taking up glucose at a high rate and undergoing aerobic glycolysis through intrinsic cellular factors that reprogram glucose metabolism. Focal adhesion kinase (FAK), a key transmitter of growth factor and anchorage stimulation, is aberrantly overexpressed or activated in most solid tumors, including pancreatic ductal adenocarcinomas (PDACs). We determined whether FAK can act as an intrinsic driver to promote aerobic glycolysis and tumorigenesis. FAK inhibition decreases and overexpression increases intracellular glucose levels during unfavorable conditions, including growth factor deficiency and cell detachment. Amplex glucose assay, fluorescence and carbon-13 tracing studies demonstrate that FAK promotes glucose consumption and glucose-to-lactate conversion. Extracellular flux analysis indicates that FAK enhances glycolysis and decreases mitochondrial respiration. FAK increases key glycolytic proteins, including enolase, pyruvate kinase M2 (PKM2), lactate dehydrogenase and monocarboxylate transporter. Furthermore, active/tyrosine-phosphorylated FAK directly binds to PKM2 and promotes PKM2-mediated glycolysis. On the other hand, FAK-decreased levels of mitochondrial complex I can result in reduced oxidative phosphorylation (OXPHOS). Attenuation of FAK-enhanced glycolysis re-sensitizes cancer cells to growth factor withdrawal, decreases cell viability and reduces growth of tumor xenografts. These observations, for the first time, establish a vital role of FAK in cancer glucose metabolism through alterations in the OXPHOS-to-glycolysis balance. Broadly targeting the common phenotype of aerobic glycolysis and more specifically FAK-reprogrammed glucose metabolism will disrupt the bioenergetic and biosynthetic supply for uncontrolled growth of tumors, particularly glycolytic PDAC.


Subject(s)
Carcinoma, Pancreatic Ductal/metabolism , Focal Adhesion Kinase 1/physiology , Glycolysis , Mitochondria/physiology , Neoplasm Proteins/physiology , Pancreatic Neoplasms/metabolism , Carcinoma, Pancreatic Ductal/pathology , Cell Adhesion , Cell Line, Tumor , Cells, Cultured , Electron Transport Complex I/metabolism , Epithelial Cells/metabolism , Focal Adhesion Kinase 1/genetics , Gene Expression Regulation, Neoplastic , Glucose/metabolism , Glucose Transporter Type 1/biosynthesis , Glucose Transporter Type 1/genetics , Humans , Lactates/metabolism , Neoplasm Proteins/genetics , Oxidative Phosphorylation , Pancreatic Ducts/cytology , Pancreatic Ducts/metabolism , Pancreatic Neoplasms/pathology , Phosphorylation , Phosphotyrosine/metabolism , Protein Processing, Post-Translational , Protein Structure, Tertiary , RNA Interference , RNA, Small Interfering/genetics , Recombinant Fusion Proteins/metabolism , Transfection
2.
Minerva Chir ; 68(5): 427-33, 2013 Oct.
Article in English | MEDLINE | ID: mdl-24101000

ABSTRACT

Esophagectomy is a surgical operation which requires technical expertise to decrease the morbidity and mortality frequently associated with this advance procedure. Various minimally invasive esophagectomy techniques have been developed to decrease the negative impact of esophageal resection. Recently, robotic assisted esophagectomies have been described with a wide variety in technique and outcome disparity. This article is a summation review of the current literature regarding the various techniques and surgical outcomes of robotic assisted esophagectomies.


Subject(s)
Esophagectomy/methods , Laparoscopy/methods , Robotics/methods , Adenocarcinoma/surgery , Carcinoma, Squamous Cell/surgery , Clinical Trials as Topic/statistics & numerical data , Cost Control , Esophageal Neoplasms/surgery , Esophagectomy/economics , Esophagectomy/instrumentation , Esophagectomy/trends , Esophagoplasty/economics , Esophagoplasty/instrumentation , Esophagoplasty/methods , Follow-Up Studies , Humans , Laparoscopy/economics , Laparoscopy/trends , Lymph Node Excision/methods , Meta-Analysis as Topic , Postoperative Complications/epidemiology , Robotics/economics , Robotics/instrumentation , Robotics/trends , Time Factors , Treatment Outcome
3.
Gastroenterol Res Pract ; 2012: 683213, 2012.
Article in English | MEDLINE | ID: mdl-22919374

ABSTRACT

Esophagectomy is a complex operation with significant morbidity and mortality. Minimally invasive esophagectomy (MIE) was described in the 1990s in an effort to reduce operative morbidity. Since then many institutions have adopted and described their series with this technique. This paper reviews the literature on the variety of MIE techniques, clinical and quality of life outcomes with open versus MIE, and controversies surrounding MIE-such as prone positioning, stapling techniques, size of the gastric conduit, and robotic techniques.

4.
Oncogene ; 31(4): 469-79, 2012 Jan 26.
Article in English | MEDLINE | ID: mdl-21706049

ABSTRACT

LKB1 is a tumor susceptibility gene for the Peutz-Jeghers cancer syndrome and is a target for mutational inactivation in sporadic human malignancies. LKB1 encodes a serine/threonine kinase that has critical roles in cell growth, polarity and metabolism. A novel and important function of LKB1 is its ability to regulate the phosphorylation of CREB-regulated transcription co-activators (CRTCs) whose aberrant activation is linked with oncogenic activities. However, the roles and mechanisms of LKB1 and CRTC in the pathogenesis of esophageal cancer have not been previously investigated. In this study, we observed altered LKB1-CRTC signaling in a subset of human esophageal cancer cell lines and patient samples. LKB1 negatively regulates esophageal cancer cell migration and invasion in vitro. Mechanistically, we determined that CRTC signaling becomes activated because of LKB1 loss, which results in the transcriptional activation of specific downstream targets including LYPD3, a critical mediator for LKB1 loss-of-function. Our data indicate that de-regulated LKB1-CRTC signaling might represent a crucial mechanism for esophageal cancer progression.


Subject(s)
Cell Movement , Cyclic AMP Response Element-Binding Protein/physiology , Esophageal Neoplasms/pathology , Protein Serine-Threonine Kinases/physiology , Signal Transduction/physiology , Transcription Factors/physiology , AMP-Activated Protein Kinase Kinases , Cell Adhesion Molecules/physiology , Cell Line, Tumor , GPI-Linked Proteins/physiology , Humans , Neoplasm Invasiveness , Phosphorylation
5.
Eur J Surg Oncol ; 36(12): 1215-9, 2010 Dec.
Article in English | MEDLINE | ID: mdl-20947288

ABSTRACT

BACKGROUND: Isolated limb infusion (ILI) for recurrent or in-transit melanoma is an accepted technique that allows high-dose chemotherapy to be delivered to an extremity with minimal systemic toxicity. Current infusion systems have relied on manual delivery of drugs and circulation of blood during the treatment. Herein, we document our initial results with an automated circuit for ILI as an alternative to the manual technique. METHODS: Patients undergoing ILI with an automated circuit for recurrent or advanced malignancy were identified. ILI was performed utilizing a Sarns 8000 roller pump attached to a Cobe 4:1 cardioplegia set with heat exchanger with a total priming volume of 80 ml. Melphalan (7.5 mg/L) and Dactinomycin (75 µg/L) doses which were corrected for ideal body weight were delivered via the infusion circuit after limb temperature reached 38 °C. RESULTS: Fourteen lower extremity infusion procedures were performed in 10 patients. Successful infusion procedures were completed in all patients using the automated circuit. Constant flow rates of 50-70 cc/minute were achievable with the automated circuit. Acute toxicity and clinical results were similar to that reported with manual delivery systems. CONCLUSION: ILI for advanced malignancy utilizing an automated circuit is feasible and safe. This automated system offers a safe and reliable alternative to the manual infusion technique.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Chemotherapy, Cancer, Regional Perfusion/methods , Melanoma/drug therapy , Skin Neoplasms/drug therapy , Aged , Aged, 80 and over , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Dactinomycin/administration & dosage , Female , Heart Arrest, Induced , Humans , Lower Extremity , Male , Melphalan/administration & dosage , Middle Aged , Treatment Outcome
7.
Surgery ; 130(2): 363-9, 2001 Aug.
Article in English | MEDLINE | ID: mdl-11490372

ABSTRACT

BACKGROUND: Chemoresistance may involve the anti-apoptotic transcriptional regulator, nuclear factor-kappa B (NF-kappa B). The purpose of this study was to determine whether chemotherapy induces NF-kappa B activation in a human colon cancer cell line (SW48) and whether NF-kappa B is constitutively activated in colorectal cancer. METHODS: SW48 cells were incubated with gemcitabine hydrochloride (Gemzar) in the presence and absence of the 26s proteasome inhibitor, MG132, and NF-kappa B binding (electrophoretic mobility shift assay), DNA synthesis (tritiated thymidine uptake), cell viability (3-[4,5-dimethylthiazol-2-yl]-diphenyl-tetrazolium bromide assay), and apoptosis (caspase-3 activity) were measured at 24 hours. NF-kappa B binding (electrophoretic mobility shift assay) was also assayed in 10 colorectal cancer tumors. RESULTS: SW48 cells demonstrated constitutive NF-kappa B binding that was enhanced by gemcitabine hydrochloride in a dose-dependent manner. MG132 inhibited NF-kappa B binding and enhanced gemcitabine hydrochloride's inhibition of DNA synthesis (gemcitabine hydrochloride = 73% +/- 1.4% vs gemcitabine hydrochloride + MG132 = 6% +/- 0.4%, P <.05), cell killing (gemcitabine hydrochloride = 87% +/- 2.0 vs gemcitabine hydrochloride + MG132 = 25% +/- 1.3%, P <.05), and caspase-3 activity (gemcitabine hydrochloride = 870 +/- 17.4 vs gemcitabine hydrochloride + MG132 = 1075 +/- 20.4, P <.05). NF-kappa B binding was increased in 8 of 10 colorectal cancer tumors compared with adjacent normal mucosa. CONCLUSIONS: Gemcitabine hydrochloride enhances NF-kappa B binding in a colorectal cancer cell line, whereas inhibition of NF-kappa B enhances gemcitabine hydrochloride's antitumor activity. NF-kappa B is also activated in human colorectal cancer. NF-kappa B may identify chemoresistant tumors, whereas inhibition of NF-kappa B may be a novel, biologically based therapy. (Surgery 2001;130:363-9).


Subject(s)
Colorectal Neoplasms/pathology , NF-kappa B/metabolism , Antimetabolites, Antineoplastic/toxicity , Caspase 3 , Caspases/metabolism , Colon/metabolism , Colon/pathology , Colorectal Neoplasms/metabolism , Cysteine Proteinase Inhibitors/pharmacology , DNA/biosynthesis , Deoxycytidine/analogs & derivatives , Deoxycytidine/toxicity , Humans , Intestinal Mucosa/metabolism , Intestinal Mucosa/pathology , Leupeptins/pharmacology , NF-kappa B/antagonists & inhibitors , Protein Binding/drug effects , Protein Binding/physiology , Rectum/metabolism , Rectum/pathology , Tumor Cells, Cultured , Gemcitabine
8.
Ann Surg Oncol ; 8(3): 249-53, 2001 Apr.
Article in English | MEDLINE | ID: mdl-11314942

ABSTRACT

INTRODUCTION: Our objective was to compare the efficacy of CT alone to CT followed by laparoscopy in determining resectability of pancreatic nonfunctioning islet (NFI) cell tumors. METHODS: A retrospective analysis from 1993 to 1999 revealed 48 patients who underwent surgical evaluation for NFI cell tumors. Of these, 34 (71%) patients underwent laparoscopy and CT for either diagnostic purposes or tumor staging. CT and laparoscopic criteria for curative resectability were defined and the sensitivity, specificity, and predictive value of both modalities in determining resectability were calculated. RESULTS: The most frequent tumor location and presenting symptoms were pancreatic head (n = 27, 56%) and abdominal pain (n = 31, 65%), respectively. Median tumor size was 4.0 cm. In the laparoscopy group, curative resection was performed in 20 cases (59%). CT followed by laparoscopy was more sensitive than CT alone in predicting resectability (93% vs. 50%, P = 0.03) with similar specificity (both 100%). The predictive value for tumor resectability was 74% for CT alone and 95% for CT followed by laparoscopy. Reasons for unresectability identified at laparoscopy but not indicated by CT were liver metastases (n = 6) or nodal disease (n = 1). Four of these patients were spared a laparotomy while the other three patients underwent surgical palliation and all are alive with disease (AWD). In those not undergoing laparoscopy (n = 14), curative resection was performed in 64% (n = 9). Four of these patients underwent resection, despite having metastases, and three are AWD. CONCLUSIONS: NFI cell tumors of the pancreas present as large masses with frequent metastases. Despite metastatic disease, prolonged survival is often achieved with or without open surgical treatment. Laparoscopy can be used in diagnosis and accurately identifies metastases not seen on CT, thus sparing laparotomy in some patients.


Subject(s)
Adenoma, Islet Cell/pathology , Laparoscopy , Pancreatic Neoplasms/pathology , Adenoma, Islet Cell/diagnostic imaging , Adenoma, Islet Cell/surgery , Humans , Laparotomy , Middle Aged , Neoplasm Metastasis/diagnosis , Pancreatic Neoplasms/diagnostic imaging , Pancreatic Neoplasms/surgery , Predictive Value of Tests , Retrospective Studies , Sensitivity and Specificity , Tomography, X-Ray Computed
9.
Int J Cancer ; 96 Suppl: 89-96, 2001.
Article in English | MEDLINE | ID: mdl-11992391

ABSTRACT

Sixty-seven patients with early-stage adenocarcinoma of the rectum who had lesions thought to be unsuitable for either local excision alone or endocavitary irradiation were treated with local excision followed by postoperative radiation therapy. The purpose of this study was to evaluate the effectiveness of local excision followed by radiation therapy for treatment of rectal adenocarcinoma. The patients were treated between 1974 and 1999; follow-up time was 6 to 273 months (median, 65 months). All living patients had follow-up for at least 2 years. The indications for postoperative irradiation included equivocal or positive margins, invasion of the muscularis propria, endothelial-lined space invasion, poorly differentiated histology, and perineural invasion. Cox proportional hazards regression analysis was performed using six explanatory variables including tumor size, configuration (exophytic vs. ulcerative), histologic differentiation, pathologic T stage, endothelial-lined space invasion, and margin status. The time interval between treatment and development of recurrent disease was in the range of 11 to 48 months. The 5-year results were as follows: local-regional control, 86%; ultimate local-regional control, 93%; distant metastasis-free survival, 93%; absolute survival, 80%; and cause-specific survival, 90%. When the Cox proportional hazards regression analysis was performed for these endpoints, margin status influenced absolute survival (P = 0.0074), cause-specific survival (P = 0.0405), and ultimate local-regional control (P = 0.0439). Tumor configuration marginally influenced cause-specific survival (P = 0.0577). None of the variables had an influence on the endpoints' local-regional control, ultimate local-regional control with sphincter preservation, or distant metastasis. Five patients (7%) had severe complications; no complication was fatal. Local excision and postoperative radiation therapy results in a high probability of local-regional control and survival for selected patients with relatively early-stage rectal adenocarcinoma. Patients with ulcerative tumors may have a lower likelihood of cause-specific survival.


Subject(s)
Adenocarcinoma/radiotherapy , Adenocarcinoma/surgery , Rectal Neoplasms/radiotherapy , Rectal Neoplasms/surgery , Adenocarcinoma/mortality , Combined Modality Therapy , Disease-Free Survival , Humans , Neoplasm Metastasis , Prognosis , Rectal Neoplasms/mortality , Recurrence , Time Factors
10.
J Gastrointest Surg ; 4(5): 520-5, 2000.
Article in English | MEDLINE | ID: mdl-11077328

ABSTRACT

Gastric cancer patients in the United States have a poor prognosis with a collective 5-year survival rate of less than 15%. We identified a subset of actual 5-year survivors (long-term survivors) and analyzed clinicopathologic variables predictive of recurrence and survival beyond the 5-year mark. A review of our prospective database from July 1985 to February 1993 revealed 154 patients who were long-term survivors and 280 patients who died of disease prior to 5 years (short-term survivors) following curative resection (R0). Tumor (T) stage, nodal (N) status, tumor location, and median number of positive nodes were compared between the two groups. Univariate and multivariate analysis of disease-free and greater than 5-year disease-specific survival was performed within the long-term survivors. Among the long-term survivors, 29% were classified as "early gastric cancers" (T1NX). The median number of positive nodes (0 vs. 5; P <0.001) and percentage of lesions that were T1/T2 (60% vs. 19%; P <0.001), node negative (58% vs. 15%; P <0.001), or proximal (40% vs. 65%; P <0.001) was significantly different in long-term survivors vs. short-term survivors, respectively. Of the 154 five-year survivors, gastric cancer recurred in 23, and 13 patients (8%) died of the disease at a median of 84 months from the original diagnosis. On univariate and multivariate analysis of prognostic factors in the long-term survivors, only the Lauren histologic classification predicted disease-specific and disease-free survival with diffuse histologic types faring significantly less well. T stage and N status are powerful prognostic factors of outcome within the first 5 years after curative resection of gastric carcinoma. However, the Lauren histologic type emerges as the dominant predictor of outcome once a patient with gastric cancer has survived for 5 years or more.


Subject(s)
Stomach Neoplasms/mortality , Survivors , Female , Gastrectomy , Humans , Lymphatic Metastasis , Male , Middle Aged , Multivariate Analysis , Neoplasm Staging , Prognosis , Retrospective Studies , Stomach Neoplasms/surgery , Survival Analysis
11.
HPB Surg ; 11(6): 413-9, 2000 Aug.
Article in English | MEDLINE | ID: mdl-10977121

ABSTRACT

We present a case of giant cavernous hemangioma of the liver with disseminated intravascular coagulopathy (Kasabach-Merritt syndrome) which was cured by enucleation. The 51 year old woman presented with increased abdominal girth and easy bruisability. Workup elsewhere revealed a massive hepatic hemangioma and she was started on radiation therapy to the lesion and offered an orthotopic liver transplant. After careful preoperative preparation, we felt that resection was possible and she underwent a successful enucleation. The operation and postoperative course were complicated by bleeding but she recovered and remains well in followup after 6 months. All coagulation parameters have returned to normal. Enucleation should be considered the treatment of choice for hepatic hemangiomas, including those presenting with Kasabach-Merritt syndrome. The benefits of enucleation as compared to liver transplantation for these lesions are discussed.


Subject(s)
Disseminated Intravascular Coagulation/complications , Hemangioma, Cavernous/surgery , Liver Neoplasms/surgery , Female , Hemangioma, Cavernous/complications , Humans , Liver/surgery , Liver Neoplasms/complications , Liver Transplantation , Middle Aged
13.
Ann Surg Oncol ; 6(7): 664-70, 1999.
Article in English | MEDLINE | ID: mdl-10560852

ABSTRACT

BACKGROUND: Although early gastric cancer (T1, NX) in Japan has been reported to have an excellent prognosis, the experience with this cancer in the United States is limited. The treatment of these tumors in Japan is becoming less aggressive as "good prognostic factors" are increasingly recognized. Our objective was to identify predictors of nodal disease and survival in a large cohort of Western patients with T1 tumors. METHODS: A retrospective review of our prospective data base from July 1985 to March 1998 revealed 165 patients undergoing surgical resection for T1 gastric tumors. Clinicopathological factors analyzed and compared included presence of positive nodes, tumor size (> or =4.5 vs. <4.5 cm), depth (mucosal vs. submucosal), grade (poor vs. moderate and well), and tumor site (proximal vs. distal), presence of venous or perineural invasion, and Lauren's classification. Factors predicting lymph node involvement and disease-specific survival were evaluated by univariate and multivariate analysis. RESULTS: Median follow-up time was 36 months. The actuarial 5-year survival was 88%. Thirteen patients (8%) died of disease. Lymph node involvement was present in 31 tumors (19%), with a 5-year survival of 91% with negative nodes vs. 78% with positive nodes. On univariate and multivariate analysis, the presence of tumor submucosal invasion (P<.05), venous invasion (P = .02), and size of 4.5 cm and larger (P = .02) was significantly associated with an increased risk for nodal positivity. On univariate analysis of survival, node-positive tumors (P = .02) and tumors 4.5 cm and larger (P = .008) were significantly associated with decreased survival. On multivariate analysis, only node-positive tumors were significantly (P = .01) associated with decreased survival. Those tumors that were limited to the mucosa and less than 4.5 cm in size (n = 47) had a 4% rate of positive nodes. In contrast, those tumors that were 4.5 cm and larger and had penetrated into the submucosa (n = 16) had a 56% chance of positive nodes. CONCLUSIONS: Early gastric carcinoma in North America has an excellent prognosis, similar to that in Japan. Tumors that are limited to the mucosa and smaller than 4.5 cm could be considered for limited resection without lymphadenectomy.


Subject(s)
Lymph Node Excision , Stomach Neoplasms/surgery , Adult , Aged , Female , Humans , Lymphatic Metastasis , Male , Middle Aged , Prognosis , Retrospective Studies , Stomach Neoplasms/pathology , Survival Analysis
14.
J Gastrointest Surg ; 3(5): 506-11, 1999.
Article in English | MEDLINE | ID: mdl-10482707

ABSTRACT

Accurate preoperative staging of pancreatic malignancy aids in directing appropriate therapy and avoids unnecessary invasive procedures. We evaluated the accuracy of magnetic resonance imaging (MRI) with magnetic resonance cholangiopancreatography (MRCP) in determining resectability of pancreatic malignancy. Twenty-one patients with suspected pancreatic malignancy underwent dynamic, contrast-enhanced breath-hold MRI with MRCP prior to surgical evaluation. Results of this study were correlated with operative results and pathologic findings. The sensitivity, specificity, and accuracy of MRI with MRCP in detecting a mass, determining the nature of the mass, and predicting lymph node involvement and resectability were determined. MRI with MRCP correctly identified the presence of a pancreatic mass in all 21 of these patients. Following pathologic correlation, it was determined that MRI with MRCP was 81% accurate in determining the benign or malignant nature of the pancreatic mass and 43% accurate in predicting lymph node involvement. In predicting resectability, MRI with MRCP had a sensitivity of 100%, specificity of 83%, positive predictive value of 94%, negative predictive value of 100%, and accuracy of 95%. MRI with MRCP is an accurate, noninvasive technique in the preoperative evaluation of pancreatic malignancy. Information obtained from MRI with MRCP including identification of a mass and predicting tumor resectability may be of value in staging and avoiding unnecessary invasive diagnostic procedures in patients with pancreatic cancer.


Subject(s)
Magnetic Resonance Imaging , Pancreatic Neoplasms/diagnosis , Pancreatic Neoplasms/surgery , Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Predictive Value of Tests , Preoperative Care , Reproducibility of Results , Retrospective Studies , Sensitivity and Specificity
15.
Arch Surg ; 134(3): 261-6, 1999 Mar.
Article in English | MEDLINE | ID: mdl-10088565

ABSTRACT

BACKGROUND: The indications for preoperative biliary stenting in patients with obstructive jaundice are controversial. We evaluated the effect of preoperative biliary stenting on bacterobilia and infectious complications following surgical treatment of proximal cholangiocarcinoma. DESIGN: A retrospective review was performed of all patients undergoing surgical treatment of proximal cholangiocarcinoma. SETTING: A metropolitan cancer surgery service. PATIENTS AND METHODS: Seventy-one patients underwent palliative biliary bypass or curative resection of proximal cholangiocarcinoma from March 1, 1991, to April 1, 1997, and were entered into a prospective database. Forty-one patients underwent preoperative biliary intubation and stent placement. We analyzed patient, nutritional, laboratory, and operating room factors. Statistical evaluation was performed using Student t test and chi2 analysis. MAIN OUTCOME MEASURE: Data were recorded for a history of cholangitis, operative time, amount of blood loss, incidence of intraoperative bacterobilia, proportion of patients with postoperative infectious and noninfectious complications, and length of hospital stay. RESULTS: All patients (n = 14) with a history of preoperative cholangitis had been subjected to previous endoscopic retrograde cholangiopancreatography and/or percutaneous transhepatic biliary drainage. Groups were equivalent for risk for comorbidity, proportion undergoing curative vs palliative procedures, time spent in the operating room, and amount of blood loss. Patients with stents had a significantly lower bilirubin level (P = .005). Patients with stents had a significantly increased risk for bacterobilia (P = .001) and infectious complications (P = .03). Bacterobilia was present in 11 (100%) of 11 patients undergoing endoscopic stenting and in 15 (65%) of 23 patients undergoing percutaneous stenting. There was no increased risk for noninfectious complications, length of hospital stay, or mortality in patients with stents. In 10 (59%) of 17 patients with postoperative infectious complications and positive findings of intraoperative bile culture, the organism was synonymous. CONCLUSIONS: Preoperative biliary stenting in proximal cholangiocarcinoma increases the incidence of contaminated bile and postoperative infectious complications. Endoscopic stents frequently do not relieve jaundice in high biliary obstruction and are rarely indicated, especially in light of their high contamination rate.


Subject(s)
Bacterial Infections/epidemiology , Bacterial Infections/etiology , Bile Duct Neoplasms/surgery , Bile Ducts, Intrahepatic , Bile/microbiology , Cholangiocarcinoma/surgery , Postoperative Complications/epidemiology , Postoperative Complications/etiology , Preoperative Care , Stents/adverse effects , Aged , Female , Humans , Male , Middle Aged , Retrospective Studies
16.
JPEN J Parenter Enteral Nutr ; 23(2): 75-9, 1999.
Article in English | MEDLINE | ID: mdl-10081996

ABSTRACT

BACKGROUND: Increased intestinal permeability may lead to sepsis in resected upper gastrointestinal (GI) cancer patients. This study sought to determine whether these patients demonstrated increased intestinal permeability and if early postoperative enteral nutrition would alter this result. METHODS: Nineteen patients undergoing complete resection of upper GI malignancy were randomized into two groups: the nonfed group received IV crystalloid, and the fed group started enteral nutrition by jejunostomy on postoperative day (POD) 1. Six nonoperative volunteers were controls. The lactulose/mannitol test was performed on PODs 1 and 5. Ten grams of lactulose and 5 g of mannitol were given, and urine was collected for 6 hours. RESULTS: All patients (nonfed, 1.895+/-0.34; fed, 0.893+/-0.24) had elevated lactulose/mannitol ratios on POD 1 vs controls (0.262+/-0.1; p < .008 and p = .05). These elevated levels returned toward control levels in both groups by day 5 (nonfed, 0.533+/-0.1, p = .06; fed, 0.606+/-0.12, p = .08). CONCLUSIONS: Major upper GI surgery for malignancy resulted in a significant increase in intestinal permeability on POD 1. With or without enteral nutrition, this measure of intestinal permeability returned to normal on POD 5 in well-nourished patients.


Subject(s)
Cell Membrane Permeability , Enteral Nutrition , Gastrointestinal Neoplasms/surgery , Intestines/physiopathology , Postoperative Care , Aged , Humans , Jejunostomy , Lactulose/urine , Mannitol/urine , Middle Aged , Time Factors
17.
J Gastrointest Surg ; 2(4): 373-8, 1998.
Article in English | MEDLINE | ID: mdl-9841995

ABSTRACT

Closed suction drains after pancreaticoduodenectomy are theoretically used to drain potential collections and anastomotic leaks. It is unknown whether such drains are effective, harmful, or affect the outcome after this operation. Eighty-nine consecutive patients underwent pancreaticoduodenectomy for presumed periampullary malignancy and were retrospectively reviewed. Thirty-eight had no intra-abdominal drains and 51 had drains placed at the conclusion of the operation. We analyzed patient, nutritional, laboratory, and operating room factors with end points being complications and length of hospital stay. Intra-abdominal complications were defined as intra-abdominal abscess and pancreatic or biliary fistula. Postoperative interventions were defined as CT-guided drainage and reoperation. Analysis was by Student's t test and chi-square test. Two of eight surgeons contributed 92% of the patients without drains. The groups were equivalent with respect to demographic, nutritional, and operative factors. Time under anesthesia was significantly shorter in the group without drains (P = 0.0001). There was no statistical difference in the rate of fistula, abscess, CT drainage, or length of hospital stay. Intra-abdominal drainage did not significantly alter the risk of fistula, abscess, or reoperation or the necessity for CT-guided intervention after pancreaticoduodenectomy. Routine use of drains after pancreaticoduodenectomy may not be necessary and should be subjected to a randomized trial.


Subject(s)
Abdomen/surgery , Pancreaticoduodenectomy , Suction , Abdominal Abscess/etiology , Aged , Anastomosis, Surgical/adverse effects , Anesthesia, General , Biliary Fistula/etiology , Chi-Square Distribution , Common Bile Duct Neoplasms/surgery , Exudates and Transudates , Female , Hospitalization , Humans , Length of Stay , Male , Nutritional Physiological Phenomena , Pancreatic Fistula/etiology , Pancreaticoduodenectomy/adverse effects , Postoperative Complications , Radiography, Interventional , Reoperation , Retrospective Studies , Risk Factors , Suction/adverse effects , Time Factors , Tomography, X-Ray Computed
18.
Ann Surg ; 228(3): 385-94, 1998 Sep.
Article in English | MEDLINE | ID: mdl-9742921

ABSTRACT

OBJECTIVES: To determine the resectability rate for hilar cholangiocarcinoma, to analyze reasons for unresectability, and to devise a presurgical clinical T-staging system. METHODS: Ninety patients with hilar cholangiocarcinomas seen between March 1, 1991, and April 1, 1997, were evaluated. Accurate patterns of disease progression and therapy were evaluable. Disease was staged in 87 patients using extent of ductal tumor involvement, portal vein compromise, and liver atrophy. RESULTS: In 21 patients, disease was deemed unresectable for cure at presentation. In 39 patients, disease was found to be unresectable at laparotomy, 23 secondary to nodal (N2) or distant metastases. Unresectability was the result of metastases in 52% and of locally advanced disease in 28%. Thirty patients (33%) had resection of all gross disease, and 25 of these (83%) had negative histologic margins. Twenty-two patients underwent partial hepatectomy. The 30-day mortality rate was 7%. Projected survival is greater than 60 months in those with a negative histologic margin, with a median follow-up of 26 months. A presurgical T-staging system allows presurgical selection for therapy, predicts partial hepatectomy, and offers an index of prognosis. CONCLUSIONS: In half the patients, unresectability is mainly the result of intraabdominal metastases. Presurgical imaging predicts unresectability based on local extension but is poor for assessing nodal metastases. In one third of patients, disease can be resected for cure with a long median survival. Curative resection depends on negative margins, and hepatic resection is necessary to achieve this. The T-staging system correlates with resectability, the need for hepatectomy, and overall survival.


Subject(s)
Bile Duct Neoplasms/surgery , Bile Ducts, Intrahepatic , Cholangiocarcinoma/surgery , Bile Duct Neoplasms/complications , Bile Duct Neoplasms/mortality , Bile Duct Neoplasms/pathology , Cholangiocarcinoma/complications , Cholangiocarcinoma/mortality , Cholangiocarcinoma/pathology , Cholangiocarcinoma/secondary , Humans , Laparotomy , Neoplasm Staging , Preoperative Care , Survival Rate
19.
Semin Surg Oncol ; 14(4): 276-82, 1998 Jun.
Article in English | MEDLINE | ID: mdl-9588720

ABSTRACT

In the last several years, much debate has centered on the management of the regional lymph nodes in malignant melanoma. The regional lymph nodes are the most common site of melanoma metastases and surgical excision of these involved nodes is the most effective treatment for either cure or local disease control. The issue still in question is the approach to the clinically negative regional lymph node basin. Retrospective studies have yielded conflicting results regarding the value of routine elective lymph node dissection (ELND) when nodes are clinically negative. Four prospective randomized clinical trials have been completed which have indicated that routine ELND is not worthwhile for the majority of melanoma patients. However, ELND may be associated with improved outcome in certain subgroups of patients: those <60 years age with 1 to 2 mm thick melanomas with or without ulceration. In addition, lymphatic mapping with sentinel lymph node biopsy has become increasingly available and has allowed clinicians an alternative to ELND. In the absence of sentinel lymph node biopsy, the role for ELND in these subgroups of patients is one of the remaining unresolved issues.


Subject(s)
Lymph Node Excision , Melanoma/secondary , Melanoma/surgery , Skin Neoplasms/pathology , Humans , Lymphatic Metastasis , Randomized Controlled Trials as Topic , Retrospective Studies
20.
Arch Surg ; 133(2): 149-54, 1998 Feb.
Article in English | MEDLINE | ID: mdl-9484726

ABSTRACT

BACKGROUND: A preoperative biliary stent is commonly used after the initial evaluation of the patient with a periampullary mass. OBJECTIVE: To evaluate the effect of a preoperative biliary stent on operative difficulty, postoperative complications, and length of hospital stay after a pancreatoduodenectomy. DESIGN: A retrospective review of a prospectively collected consecutive series. SETTING: The Memorial Sloan-Kettering Cancer Center's Surgical Service, New York, NY. PATIENTS AND METHODS: Seventy-four patients underwent pancreatoduodenectomy between March 1, 1994, and February 15, 1996. Thirty-five did not receive a biliary stent, and 39 received a biliary stent prior to medical evaluation. We analyzed patient, nutritional, laboratory, and operating room factors. Univariate analysis was by Student t test, chi2 test, and Fisher exact test; multivariate analysis was by logistic regression. Significance was defined at P<.05. MAIN OUTCOME MEASURES: Operative time, amount of blood loss, complications, and length of hospital stay. Wound complications were defined as cellulitis, superficial infections, and deep infections. Intra-abdominal complications were defined as intra-abdominal abscesses and pancreatic or biliary fistula. RESULTS: Groups were equivalent for tumor size, risk of comorbidity, time spent in the operating room, and amount of blood loss. There was 1 perioperative death. Patients with a stent had significantly lower bilirubin (P<.03) and aspartate aminotransferase (P<.04) levels and a significantly increased risk of nodal positivity (P<.05). The patients with a biliary stent had an increased risk of wound or abdominal complications on univariate (P<.003) and multivariate (P<.02) analysis and tended toward a prolonged hospital stay (P<.04, Wilcoxon signed rank test). CONCLUSIONS: A preoperative biliary stent was associated with an increased risk of wound or intra-abdominal complications; a stent may prolong the length of hospital stay. However, length of time under anesthesia, amount of blood loss, and transfusion requirements were not altered. A biliary stent should be used with a high degree of selectivity in the management of patients with resectable periampullary masses.


Subject(s)
Pancreaticoduodenectomy/adverse effects , Postoperative Complications/etiology , Stents/adverse effects , Aged , Blood Loss, Surgical , Female , Humans , Length of Stay , Male , Middle Aged , Prospective Studies , Retrospective Studies , Time Factors
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