AHPBA/SSO/SSAT Consensus Conference on hepatic colorectal metastases: rationale and overview of the conference. January 25, 2006.
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Colorectal Neoplasms↗
Biomedical subjects
Michael A Choti
Publications and source records attributed to Michael A Choti.
Selection of patients for resection of hepatic colorectal metastases: expert consensus statement.
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Biomarkers↗
MKK4 status predicts survival after resection of gastric adenocarcinoma.
HYPOTHESIS: Lack of expression of the tumor-suppressor gene MKK4 is significantly correlated with poor survival after resection of gastric adenocarcinoma. DESIGN: Retrospective review of medical records after construction and immunolabeling of tissue microarrays for clinical correlation. SETTING: The Johns Hopkins Hospital, Baltimore, Md. PATIENTS: Patients operated on because of gastric adenocarcinoma between 1983 and 1995. Main Outcome Measure Long-term survival and MKK4 status. RESULTS: Primary tumors (N = 124) were scored as 0 (no labeling), 1+ (weak labeling), or 2+ (strong labeling) in 9 (7%), 80 (65%), and 35 (28%) patients, and 5-year survival in these patients was 0%, 21%, and 28%, respectively. Given the small size (7%) of the MKK4-negative group (as expected, given the 5%-10% incidence of genetic loss in carcinomas), a Cox proportional hazards analysis was performed, adjusting for age, sex, and tumor stage. This multivariate analysis revealed a 5-fold increased risk of death (P<.001) in patients whose primary tumors were MKK4-negative. Furthermore, the addition of MKK4 status significantly improved the Cox model, changing log likelihood from -1410 to -369, confirming that MKK4 status was truly the effector of the survival difference and not a bystander. CONCLUSIONS: The lack of expression of the tumor-suppressor gene MKK4 in resected gastric adenocarcinoma is robustly associated with poor survival. This finding may provide a useful prognostic tool in patients with gastric adenocarcinoma.
Adenocarcinoma↗
Preoperative positron emission tomography to evaluate potentially resectable hepatic colorectal metastases.
HYPOTHESIS: Positron emission tomography (PET) influences clinical management in the preoperative evaluation of patients with hepatic metastases from colorectal cancer. DESIGN: Prospective cohort study. SETTING: Academic tertiary care center. PATIENTS: From January 1, 2000, through December 31, 2002, 71 consecutive patients referred with potentially resectable hepatic metastases based on conventional imaging findings underwent PET or PET with computed tomography in the subsequent preoperative evaluation. INTERVENTION: Performance of hepatic resection was based on the results of the overall preoperative evaluation. MAIN OUTCOME MEASURES: Concordance with conventional imaging findings, identification of additional findings, and change in clinical management were analyzed. RESULTS: The PET findings confirmed the lesions identified by conventional imaging techniques in 64 (90%) of the patients. Additional lesions were identified on PET in 23 patients (32%). The information obtained by PET resulted in a change in clinical management in 17 cases (24%). False-positive PET findings occurred in 6 patients (8%), whereas false understaging occurred in 11 (15%). In no cases did PET findings have an adverse impact on patient outcome. CONCLUSIONS: Positron emission tomography provides useful information in the selection of patients with hepatic metastases from colorectal cancer being considered for surgical therapy. Such improved selection may serve to reduce the number of unnecessary surgical explorations and result in improved long-term survival in patients undergoing resection. Positron emission tomography should be integrated into the routine preoperative evaluation of patients being considered for hepatic resection of colorectal metastases.
Adult↗
Differences in survival for patients with resectable versus unresectable metastases from pancreatic islet cell cancer.
Well-differentiated islet cell tumors can be associated with aggressive biology, resulting in early metastases to the liver. This study was carried out to determine whether survival for patients with malignant islet cell tumors and synchronous liver metastases is affected by complete surgical resection. Thirty-one patients with synchronous liver metastases from islet cell cancer underwent surgical exploration with the intent for complete tumor resection, and all patients underwent resection of the pancreatic primary. The patients were divided into two groups, those with resectable versus unresectable liver metastases. Twenty-six of 31 (84%) patients underwent complete resection of both the primary tumor and all liver metastases, and 5 (16%) patients underwent only complete resection of the pancreatic primary without liver resection. To extirpate the primary tumor, a pancreaticoduodenectomy was performed in 11 of the 26 (42%) completely resected patients and in 4 of the 5 (80%) incompletely resected patients, P = NS. The remainder of the patients underwent distal pancreatectomy. There were no statistical differences in primary tumor size, lymph node metastases, or adjuvant treatments between patients with resected and unresected liver metastases. The median overall survival for the completely resected group was 78 months, longer than the 17 months for the group with unresectable liver metastases (P = 0.06). Complete tumor resection (or the tumor biology that allows such complete resection) affords a survival advantage to patients with metastatic islet cell tumors of the pancreas. Patterns of liver metastases from islet cell tumors, specifically multiple bilobar metastases that are not amenable to resection and/or ablation, predict a poor outcome despite resection of the primary pancreatic tumor.
Adult↗
Does pancreatic duct stenting decrease the rate of pancreatic fistula following pancreaticoduodenectomy? Results of a prospective randomized trial.
Pancreatic duct stenting remains an attractive strategy to reduce the incidence of pancreatic fistulas following pancreaticoduodenectomy (PD) with encouraging results in both retrospective and prospective studies. We performed a prospective randomized trial to test the hypothesis that internal pancreatic duct stenting reduces the development of pancreatic fistulas following PD. Two hundred thirty-eight patients were randomized to either receive a pancreatic stent (S) or no stent (NS), and stratified according to the texture of the pancreatic remnant (soft/normal versus hard). Four patients were excluded from the study; in three instances due to a pancreatic duct that was too small to cannulate and in the other instance because a total pancreatectomy was performed. Patients who randomized to the S group had a 6-cm-long segment of a plastic pediatric feeding tube used to stent the pancreaticojejunostomy anastomosis. In patients with a soft pancreas, 57 randomized to the S group and 56 randomized to the NS group. In patients with a hard pancreas, 58 randomized to the S group and 63 randomized to the NS group. The S and NS groups for the entire study population, as well as for the subgroup of high-risk patients with soft pancreata, were similar as regard to demographics, past medical history, preoperative symptoms, preoperative procedures, and intraoperative data. The pancreatic fistula rate for the entire study population was 9.4%. The fistula rates in the S and NS subgroups with hard pancreata were similar, at 1.7% and 4.8% (P = 0.4), respectively. The fistula rates in the S and NS subgroups with soft pancreata were also similar, at 21.1% and 10.7% (P = 0.1), respectively. A nonstatistically significant increase in the pancreatic fistula rate in the S group persisted after adjusting for the operating surgeon and technical details of the operation (e.g., anastomotic technique, anastomotic orientation, pancreatic duct size, and number of intra-abdominal drains placed). In patients with soft pancreata, 63% percent of the pancreatic fistulas in stented patients required adjustment to the clinical pathway (including two deaths), compared to 47% of the pancreatic fistulas in patients in the NS group (P = 0.3). Internal pancreatic duct stenting does not decrease the frequency or the severity of postoperative pancreatic fistulas.
Adult↗
1423 pancreaticoduodenectomies for pancreatic cancer: A single-institution experience.
Pancreaticoduodenectomy (PD) with the possible addition of neoadjuvant or adjuvant therapy is the standard of care in the United States for adenocarcinoma originating in the pancreatic head, neck, and uncinate process. We reviewed 1423 patients who underwent a PD for a malignancy originating in the pancreas at our institution between 1970 and 2006. We examined 1175 PDs for ductal adenocarcinomas in greater detail. Eighteen different histological types of pancreatic cancer were identified; the most common diagnoses included ductal adenocarcinoma, neuroendocrine carcinoma, and IPMN with invasive cancer. Patients with ductal adenocarcinoma were analyzed in detail. The median age was 66 years, with patients in the present decade significantly older (68 years), on average, than patients in the three prior decades (e.g., 60 years in 1970, P = 0.02). The median tumor diameter was 3 cm; 42% of the resections had positive margins and 78% had positive lymph nodes. The perioperative morbidity was 38%. The median postoperative stay declined over time, from 16 days in the 1980s to 8 days in the 2000s (P < 0.001). The perioperative mortality declined from 30% in the 1970s to 1% in the 2000s (P < 0.001). The median survival for all patients with ductal adenocarcinoma was 18 months (1-year survival = 65 %, 2-year survival = 37%, 5-year survival = 18%). In a Cox proportional hazards model, pathological factors having a significant impact on survival included tumor diameter, resection margin status, lymph node status, and histologic grade. This is the largest single-institution experience with PD for pancreatic cancer. Patients who have cancers with favorable pathological features have a statistically significant improved long-term survival.
Adult↗
Periampullary and pancreatic incidentaloma: a single institution's experience with an increasingly common diagnosis.
BACKGROUND: While incidental masses in certain organs have received particular attention, periampullary and pancreatic incidentalomas (PIs) remain poorly characterized. METHODS: We reviewed 1944 consecutive pancreaticoduodenectomies (PD) over an 8-year period (April 1997 to October 2005). A total of 118 patients (6% of all PDs) presented with an incidental finding of a periampullary or pancreatic mass. The PI patients were analyzed and compared with the rest of the cohort (NI, nonincidentaloma group, n = 1826). RESULTS: Thirty-one percent of the PI patients (n = 37) had malignant disease (versus 76% of the NI patients, P < 0.001), 47% (n = 55) had premalignant disease, and the remaining 22% (n = 26) had little or no risk for malignant progression. The 3 most common diagnoses in the PI group were IPMN without invasive cancer (30%), cystadenoma (17%), and pancreatic ductal adenocarcinoma (10%). The PI group had a higher overall complication rate (55% versus 43%, P = 0.02), due in part to a significantly increased rate of pancreatic fistulas (18.4% PI versus 8.5% NI, P < 0.001). Patients in the PI group with malignant disease had a superior long-term survival (median, 30 months, P = 0.01) compared with patients in the NI group with malignant disease (median, 21 months). CONCLUSIONS: Incidentally discovered periampullary and pancreatic masses comprise a substantial proportion of patients undergoing PD. Roughly three fourths of these lesions are malignant or premalignant, and amenable to curative resection. Resected malignant PIs have favorable pathologic features as compared with resected malignant NIs, and resection of these early lesions in asymptomatic individuals is associated with improved survival, compared with patients with symptomatic disease.
Adolescent↗
Claudin-4, mitogen-activated protein kinase kinase 4, and stratifin are markers of gastric adenocarcinoma precursor lesions.
Approximately 23,000 new gastric cancer cases and 12,000 associated deaths occur annually in the United States. Intestinal metaplasia and gastric epithelial dysplasia are precursor lesions to gastric adenocarcinoma, but are not readily detectable clinically, radiographically, or endoscopically. A noninvasive method of precursor detection would require the ability to distinguish precursor lesions from adjacent normal mucosa. In search of such markers, tissue microarrays were prepared for 133 patients of resected gastric adenocarcinoma. Tissue microarrays contained primary cancer, normal stomach, intestinal metaplasia, and gastric epithelial dysplasia and were probed with antibodies against nine potential markers that were either identified in a database of genes overexpressed in gastric adenocarcinoma or were already of interest to our laboratory: claudin-4, mitogen-activated protein kinase kinase 4 (MKK4), 14-3-3sigma (stratifin), S100A4, mesothelin, fascin, topoisomerase IIalpha, HER-2/neu, and epithelial growth factor receptor. Three markers discriminated gastric adenocarcinoma precursor lesions from normal gastric mucosa. Claudin-4 expression was present in 36 intestinal metaplasia lesions (100%) and 14 gastric epithelial dysplasia lesions (100%), but in only 16 normal stomach samples (15%). MKK4 expression was present in 24 intestinal metaplasia lesions (89%) and 12 gastric epithelial dysplasia lesions (100%), but in only 6 normal stomach samples (8%). Stratifin expression was present in 29 intestinal metaplasia lesions (97%) and 8 gastric epithelial dysplasia lesions (100%), but in only 2 normal stomach samples (3%). Sensitivity and specificity for detection of the precursor lesion intestinal metaplasia were 100% and 85%, respectively, for claudin-4; 89% and 92%, respectively, for MKK4; and 97% and 97%, respectively, for stratifin. In primary cancers, 123 of 125 (98.4%) were positive for claudin-4, 116 of 126 (94%) for MKK4, and 111 of 120 (92%) for stratifin. In conclusion, claudin-4, MKK4, and stratifin immunolabeling detects precursor lesions of gastric adenocarcinoma that are otherwise clinically, radiographically, and endoscopically inapparent. These findings may prove useful in the diagnosis and therapeutic targeting of gastric adenocarcinoma precursor lesions.
14-3-3 Proteins↗
Bootstrapped ultrasound calibration.
This paper introduces an enhanced (bootstrapped) method for tracked ultrasound probe calibration. Prior to calibration, a position sensor is used to track an ultrasound probe in 3D space, while the US image is used to determine calibration target locations within the image. From this information, an estimate of the transformation matrix of the scan plane with respect to the position sensor is computed. While all prior calibration methods terminate at this phase, we use this initial calibration estimate to bootstrap an additional optimization of the transformation matrix on independent data to yield the minimum reconstruction error on calibration targets. The bootstrapped workflow makes use of a closed-form calibration solver and associated sensitivity analysis, allowing for rapid and robust convergence to an optimal calibration matrix. Bootstrapping demonstrates superior reconstruction accuracy.
Calibration↗
The glycosphingolipid globotriaosylceramide in the metastatic transformation of colon cancer.
The most devastating aspect of cancer is the emergence of metastases. Thus, identification of potentially metastatic cells among a tumor cell population and the underlying molecular changes that switch cells to a metastatic state are among the most important issues in cancer biology. Here we show that, although normal human colonic epithelial cells lack the glycosphingolipid globotriaosylceramide (Gb(3)), this molecule is highly expressed in metastatic colon cancer. In addition, a subpopulation of cells that are greatly enriched in Gb(3) and have an invasive phenotype was identified in human colon cancer cell lines. In epithelial cells in culture, Gb(3) was necessary and sufficient for cell invasiveness. Transfection of Gb(3) synthase, resulting in Gb(3) expression in noncancerous polarized epithelial cells lacking endogenous Gb(3), induced cell invasiveness. Furthermore, Gb(3) knockdown by small inhibitory RNA in colon cancer epithelial cells inhibited cell invasiveness. Gb(3) is the plasma membrane receptor for Shiga toxin 1. The noncatalytic B subunit of Shiga toxin 1 causes apoptosis of human colon cancer cells expressing Gb(3). Injections of the B subunit of Shiga toxin 1 into HT29 human colon cancer cells engrafted into the flanks of nude mice inhibited tumor growth. These data demonstrate the appearance of a subpopulation of Gb(3) containing epithelial cells in the metastatic stage of human colon cancer and suggest their possible role in colon cancer invasiveness.
Animals↗
Inflammatory pseudotumor of the liver.
Inflammatory pseudotumor of the liver (IPL) is a rare benign neoplasm. It often masquerades as a malignancy, either primary or metastatic. We describe the case of a 71-year-old man who presented with fever and malaise. Workup revealed a cecal mass, as well as a lesion in the left lobe of the liver. Pathologic examination showed a cecal neoplasm and a hepatic inflammatory pseudotumor. The patient recovered uneventfully. This case highlights the ability of IPL to masquerade as a malignant hepatic neoplasm, and emphasizes the difficulties in diagnosis.
Aged↗
Hypercalcemia and pancreatic endocrine neoplasia with elevated PTH-rP: report of two new cases and subject review.
Humoral hypercalcemia of malignancy is widely associated with tumor production of parathyroid hormone related protein (PTH-rP). This peptide functions in endocrine, autocrine and paracrine mechanisms in a manner similar to PTH; increasing renal uptake of calcium, decreasing retention of phosphorous, and stimulating adenylate cyclase and phospholipase C. Although PTH-rP production has been well documented in neoplasms of the exocrine pancreas, we present here two cases of endocrine pancreatic neoplasms elaborating PTH-rP. We then review the literature of previous cases and delve into the pathophysiology of this peptide.
Adult↗
Palliative therapy for pancreatic/biliary cancer.
Palliative treatment for unresectable periampullary cancer is directed at three major symptoms: obstructive jaundice, duodenal obstruction, and cancer-related pain. In most cases, the pattern of symptoms at the time of diagnosis in the context of the patient's medical condition and projected survival influence the decision to perform an operative versus a non operative palliative procedure. Despite improvements in preoperative imaging and laparoscopic staging of patients with periampullary cancer and hilar cholangiocarcinoma, surgical exploration is the only modality that can definitively rule out resectability and the potential for curative resection in some patients with nonmetastatic cancer. Furthermore, only surgical management achieves successful palliation of obstructive symptoms and cancer-related pain as a single procedure during exploration. To take advantage of the long-term advantages afforded by surgical palliation,operative procedures must be performed with acceptable morbidity. The average postoperative length of hospital stay for patients who undergo surgical palliation is less than 15 days, even in those who develop minor complications. The average survival of patients who receive surgical palliation alone for nonmetastatic, unresectable pancreatic cancer is approximately 8 months. As with all treatment planning, palliative therapy for pancreatic and biliary cancer should be planned using a multidisciplinary approach, including input from the surgeon, gastroenterologist, radiologist,and medical and radiation oncologist. In this way, quality of life can be optimized in most patients with these diseases.
Bile Duct Neoplasms↗
Controversies in the surgical management of cholangiocarcinoma and gallbladder cancer.
Cholangiocarcinoma and gallbladder cancer are relatively rare malignancies with poor prognoses. Surgery is the primary form of treatment, with few data being available on the use of adjuvant therapies. Even with regard to surgery, there are few definitive data supporting various approaches that nevertheless are widely used and have become recognized as traditional. This review examines available information and controversies in the areas of preoperative evaluation and surgical treatment of cholangiocarcinoma and gallbladder cancer.
Bile Duct Neoplasms↗
Achlorhydria, parietal cell hyperplasia, and multiple gastric carcinoids: a new disorder.
We describe a 54-year-old woman who had multiple gastric carcinoid tumors arising in the setting of marked hypergastrinemia associated with a lack of acid production by hypertrophic parietal cells. The serum gastrin level was 1,400 pg/mL, and investigation revealed no evidence for either of the recognized causes for hypergastrinemia-associated carcinoids, autoimmune gastritis, and Zollinger-Ellision syndrome. Partial gastrectomy was performed. Pathologic examination showed multiple intramucosal and invasive carcinoid tumors of the body and fundus in a background of marked ECL cell hyperplasia. There were no gastric or duodenal ulcerations. One perigastric lymph node was metastatically involved. The oxyntic mucosa showed marked hyperplasia and hypertrophy of the parietal cells. Some of these cells were vacuolated, and many displayed protrusions of apical cytoplasm into dilated oxyntic glands filled with inspissated eosinophilic material. Similar findings have occurred in 1 other patient, strongly indicating that the clinicopathologic alterations in the 2 cases are not random but, on the contrary, represent a very rare disorder of gastric carcinoids associated with an intrinsic acid secretion abnormality of the parietal cells.
Achlorhydria↗
Cost implications of post-surgical morbidity following blood transfusion in cancer patients undergoing elective colorectal resection: an evaluation in the US hospital setting.
OBJECTIVE: To estimate the cost implications of blood transfusions and related surgical site infections (SSIs) in cancer patients undergoing elective colorectal resection in the hospital setting in the United States (US). STUDY DESIGN: A modelling study was performed from the perspective of the hospital sector, based on published clinical outcomes from a study in Taiwan involving 2809 cancer patients who underwent elective colorectal resection using laparotomy and American treatment patterns. METHODS: Data on resource use were retrieved from published literature and from two American hospital centres specialising in colorectal cancer management. Decision analytical modelling was used to estimate the treatment costs and consequences of managing patients undergoing elective colorectal resection with and without blood transfusions. RESULTS: The expected treatment costs of managing patients who required and did not require a blood transfusion were estimated to be US dollars 19,869 (95% CI: 15 797; 23 150) and US dollars 14,586 (95% CI: 14 263; 14 886) per patient respectively. Expected treatment costs for those patients transfused with 1-3 units and > 3 units of blood were estimated to be US dollars 17,449 and US dollars 22,588 per patient respectively. CONCLUSION: This is one of the first studies to specifically address the cost implications of postsurgical morbidity following colorectal resection in cancer patients. The cost of managing cancer patients undergoing elective colorectal resection who require a blood transfusion is expected to be 36% more than that of non-transfused patients, largely resulting from the development of SSIs.
Blood Transfusion↗
Colon cancer clinical practice guidelines in oncology.
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Antineoplastic Combined Chemotherapy Protocols↗