Alternative method for exposure of the retropancreatic mesenteric vasculature during total pancreatectomy.
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Humans↗
Biomedical subjects
S D Leach
Publications and source records attributed to S D Leach.
Laparoscopic staging for gastric cancer.
BACKGROUND: Laparoscopy has become an increasingly important diagnostic tool for the staging of intraabdominal malignancies. Some investigators have suggested laparoscopy to be of questionable value in the preoperative staging of gastric cancer because many patients may require palliative surgery despite laparoscopic findings. However, in other studies laparoscopy was found to be a more accurate staging technique and useful in avoiding unnecessary laparotomy when compared with abdominal sonography, liver scintigraphy, or early generation computed tomography (CT). In recent years marked improvements have been made in CT technology, and laparoscopy has not been compared with current generation CT. Therefore we sought to determine the usefulness of laparoscopy for staging gastric adenocarcinoma in the era of current generation CT scanning. METHODS: Staging laparoscopy was performed in 71 patients with potentially resectable gastric cancer as determined by physical examination and current generation CT. The results of laparoscopy were evaluated in the context of negative or equivocal CT findings. RESULTS: Laparoscopic staging was successful in 69 patients (97%). Laparoscopy identified distant metastatic disease in 16 (23%) patients judged to be eligible for potentially curative resection by current generation CT scanning. Only one of these patients required laparotomy for palliation. Combined CT and laparoscopic staging resulted in a 93% resectability rate for patients operated on with curative intent. CONCLUSIONS: We advocate staging laparoscopy as an important staging procedure for all patients with potentially resectable gastric cancer. The additional cost of laparoscopy should be more than offset by the decreased morbidity and expense of hospitalization for those patients who avoid an unnecessary laparotomy.
Humans↗
Rationale for en bloc vein resection in the treatment of pancreatic adenocarcinoma adherent to the superior mesenteric-portal vein confluence. Pancreatic Tumor Study Group.
OBJECTIVE: Tumor invasion of the superior mesenteric-portal vein (SMPV) confluence is often considered a contraindication to pancreaticoduodenectomy for patients with malignant tumors of the pancreas or periampullary region. The authors sought to determine whether pancreaticoduodenectomy with en bloc resection of the SMPV confluence could be safely performed and whether tumors involving the SMPV confluence were associated with pathologic parameters suggesting poor prognosis. SUMMARY BACKGROUND DATA: Several centers have reported high rates of retroperitoneal margin positivity after pancreaticoduodenectomy for tumors of the pancreatic head and periampullary region. Positive-margin or incomplete resection is associated with early tumor recurrence and no survival benefit compared with palliative therapy. Tumor adherence to the lateral of posterior wall of the SMPV confluence often represents the only barrier to complete tumor resection at the time of pancreaticoduodenectomy. METHODS: Data on all patients undergoing pancreaticoduodenectomy for adenocarcinoma of the pancreas or periampullary region over a 3.5-year period were entered prospectively in a pancreatic tumor database. To be considered for surgery, patients were required to fulfill the following computed tomography criteria for resectability: 1) the absence of extrapancreatic disease, 2) no tumor encasement of the superior mesenteric artery or celiac axis, and 3) a patent SMPV confluence. Tumor adherence to the superior mesenteric vein or SMPV confluence was assessed intraoperatively, and en bloc venous resection was performed when necessary to achieve complete tumor extirpation. Data on operative characteristics, morbidity, mortality, tumor size, nodal metastases, margin positivity, perineural invasion, and tumor DNA content were compared for patients who did and did not receive venous resection. RESULTS: Fifty-nine patients underwent pancreaticoduodenectomy, 36 without venous resection and 23 with en bloc resection of the SMPV confluence. No differences in median hospital stay, morbidity, mortality, tumor size, margin positivity, nodal positivity, or tumor DNA content were observed between groups. CONCLUSIONS: When necessary, segmental resection of the SMPV confluence may be performed safely during pancreaticoduodenectomy for periampullary malignant tumors. Tumors invading the SMPV confluence are not associated with histologic parameters suggesting a poor prognosis. Our data suggest that venous involvement is a function of tumor location rather than an indicator of aggressive tumor biology.
Adenocarcinoma↗
Vascular resection and intraoperative radiation therapy during pancreaticoduodenectomy: rationale and technique.
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Adenocarcinoma↗
bcl-2 and p53 expression in resectable pancreatic adenocarcinomas: association with clinical outcome.
The bcl-2 proto-oncogene and the p53 tumor suppressor gene are important determinants of tumor cell susceptibility to apoptosis. bcl-2 and mutant p53 proteins inhibit apoptosis in vitro and can provide prognostic information in certain tumor types. We analyzed bcl-2 and p53 expression in archival pancreatic (n = 35) and ampullary (n = 6) adenocarcinomas, resected for cure, and their relationship to overall survival. Patients were treated with 5-fluorouracil and irradiation either pre- (n = 21) or postoperatively (n = 15); 5 patients received surgery alone. Using specific monoclonal antibodies, cytoplasmic bcl-2 and nuclear p53 proteins were detected in 22 of 40 (55%) and 20 of 37 (54%) tumors, respectively. No relationship was found between bcl-2 and p53 expression. Neither bcl-2 nor p53 correlated with histological response to preoperative chemoradiation. Lymph node involvement predicted poor overall survival (P = 0.02). A trend toward improved survival was seen in well-differentiated (P = 0.08) tumors and in those with increased bcl-2 expression (P = 0.06). p53 expression was not related to clinical outcome. In a multivariate analysis, nodal status was the single most important predictor of overall survival. Of note, the combined variable of bcl-2 expression and histological grade was a stronger prognostic variable than nodal status alone. Unlike nodal status, these features can potentially be evaluated in preoperative biopsy specimens.
Adenocarcinoma↗
Significance of peritoneal cytology in patients with potentially resectable adenocarcinoma of the pancreatic head.
BACKGROUND: Recurrence in the peritoneum occurs in up to 50% of patients after a potentially curative pancreaticoduodenectomy. Previous authors have implicated preoperative fine-needle aspiration (FNA) as a cause of intraperitoneal tumor dissemination, although prior studies of peritoneal cytology findings have largely involved patients with locally advanced disease. METHODS: A consecutive series of patients referred to our institution between 1991 and 1993 with suspected or biopsy-proven adenocarcinoma of the pancreatic head was studied prospectively. All patients fulfilled criteria for resectability as assessed by computed tomography: no metastatic disease, no encasement of the superior mesenteric or hepatic arteries, and a patent superior mesenteric-portal venous confluence. Peritoneal washings were obtained at the time of staging laparoscopy and/or at subsequent laparotomy. Data regarding peritoneal cytology results, previous FNA, preoperative chemoradiation, eventual resection, pattern of disease recurrence, and survival were collected. RESULTS: A total of 80 peritoneal washings from 60 consecutive patients were prospectively examined. Forty-nine (82%) of 60 patients underwent FNA before peritoneal washings were obtained. A total of four patients (7%) had positive peritoneal cytology findings: three (6%) of 49 who underwent prior FNA and one (9%) of 11 with no prior FNA. Similarly, no differences in eventual peritoneal failure or short-term survival were observed for patients who underwent prior FNA compared with patients who did not. All four patients with positive peritoneal cytology findings had metastatic disease (liver, three; peritoneum, one) at a median of 4.8 months after diagnosis; three of the four died of disease at a median of 8 months. CONCLUSIONS: Positive peritoneal cytology findings are rare in patients with radiologically resectable adenocarcinoma of the pancreas. When found, positive peritoneal washings are an indicator of advanced disease characterized by unresectability, early metastasis, and short survival. Computed tomographic-guided FNA does not appear to increase the risk for positive peritoneal washings and represents a valid approach to the pretreatment diagnosis of patients with suspected pancreatic malignancy.
Adenocarcinoma↗
Adjuvant therapy for resectable gastric adenocarcinoma: preoperative and postoperative chemotherapy trials.
Survival rates for patients undergoing resection of gastric adenocarcinoma remain poor. Even following successful removal of all gross disease, high rates of local-regional and systemic recurrence are observed. During the past twenty-five years, multiple trials have been undertaken to evaluate the possible benefit of either preoperative or postoperative adjuvant chemotherapy in this disease. This report reviews the rationale, design, and outcome of these trials, and further updates the status of preoperative chemotherapy protocols currently employed at the M.D. Anderson Cancer Center.
Adenocarcinoma↗
Laparoscopic local excision of a proximal rectal carcinoid.
Early carcinoids of the distal rectum have been treated effectively by transanal local excision. Unfortunately, small carcinoids of the proximal rectum may be unreachable by transanal approaches, and as a result patients have been subjected to more extensive, transabdominal colorectal resections. The recent introduction of minimally invasive techniques for treatment of colorectal diseases has opened new approaches for the treatment of proximal rectal carcinoids. We describe a patient with a 0.5 cm rectal carcinoid located just above the peritoneal reflection in whom transanal local excision was not feasible. We report the first laparoscopic, full-thickness excision of a proximal rectal carcinoid. Intraoperative colonoscopy was used to localize the lesion. This combined laparoscopic and colonoscopic approach spared the patient from the potential morbidity of a low anterior resection and anastomosis.
Aged↗
Characterization of cAMP-dependent protein kinase activation by CCK in rat pancreas.
This study reports on the use of a new sensitive assay of cAMP-dependent protein kinase activity to examine the effect of cholecystokinin (CCK) on the cAMP second messenger cascade in rat pancreatic acini. Treatment of acini with both low (pM) and high (nM) concentrations of CCK was associated with an increase in cAMP-dependent protein kinase activity. The increases in kinase activity were detected in the absence of phosphodiesterase inhibition, a condition required to detect a measurable increase in cellular cAMP in these cells. Furthermore, the cAMP cascade was dissociated from the secretory effects of CCK, since the CCK analogue, OPE, mediates enzyme secretion but does not increase cellular cAMP levels or kinase activity.
1-Methyl-3-isobutylxanthine↗
Influence of chloroquine on diet-induced pancreatitis.
Recent investigations have suggested that digestive zymogens may become activated within the acinar cell during acute pancreatitis. While the molecular events responsible for intracellular zymogen activation remain unknown, several potential enzymatic pathways require an acidic pH to optimally proceed. We therefore proposed that manipulation of subcellular pH might alter the course of experimental pancreatitis. Chloroquine, a weak base that raises the pH of acidic subcellular compartments, was administered to young female mice in which pancreatitis was induced by a choline-deficient, ethionine-supplemented (CDE) diet. Control animals were maintained on regular laboratory chow. Examination of isolated pancreatic acini using acridine orange cytofluorescence demonstrated expansion of acidic subcellular compartments in animals fed the CDE diet. These compartments were effectively neutralized in animals receiving chloroquine. Animals receiving continuous infusions of high-dose chloroquine demonstrated a significant (p < 0.05) decrease in free pancreatic tryptic activity as well as improved survival. These changes were also associated with decreased trypsinogen content in animals treated with high-dose chloroquine, suggesting an additional potential effect of chloroquine on zymogen synthesis and accumulation. One explanation of these findings is that a low-pH compartment may be important in the pathogenesis of diet-induced pancreatitis.
Acute Disease↗
New perspectives on acute pancreatitis.
The past decade has witnessed considerable changes in the clinical management of acute pancreatitis. Simultaneously, significant advances have been made in understanding the cellular and biochemical events involved in the initiation of this disease. This review summarizes recent clinical and scientific progress regarding acute pancreatitis and suggests areas for future investigation.
Acute Disease↗
Intracellular activation of digestive zymogens in rat pancreatic acini. Stimulation by high doses of cholecystokinin.
The mechanism by which digestive zymogens become activated during acute pancreatitis remains poorly understood. Given the ability for cholecystokinin (CCK) to induce pancreatitis in vivo, the effects of high dose CCK on preparations of isolated pancreatic acini were examined. Using an immunologic technique for the detection of zymogen activation, CCK was found to stimulate the conversion of procarboxypeptidase A1 to a 35-kD form having the same net charge and electrophoretic mobility as purified recombinant carboxypeptidase A1. This enhanced conversion was proportional to the dose of CCK (maximal at 100 nM), and time dependent. CCK also produced changes in the electrophoretic mobility of procarboxypeptidase B and chymotrypsinogen 2 immunoreactivity, consistent with activation of these zymogens. These events were detectable only within acinar cell pellets and not in the incubation medium, suggesting an intracellular site of conversion. The conversion of procarboxypeptidase A1 to its active form was inhibited by pretreatment with the weak base chloroquine (40 microM) and the protonophore monensin (10 microM). This conversion was also inhibited by pretreatment with the serine protease inhibitor benzamidine (10 mM) but not the cysteine protease inhibitor E64 (100 microM). The results suggest that high dose CCK stimulates the intracellular activation of digestive zymogens within isolated pancreatic acini. This event appears to require an acidic subcellular compartment and serine protease activity.
Animals↗
Experimental models of acute pancreatitis.
Acute pancreatitis remains a disease of uncertain pathogenesis and nonspecific therapy. Because of the practical problems plaguing investigation of pancreatitis in man, investigators have developed various experimental animal models of pancreatitis in order to develop rationale concepts regarding pathogenesis and therapy. Despite numerous investigations over the past century, the events involved in the initiation and progression of pancreatitis remain obscure. Indeed, identification of the cellular mechanisms responsible for the initiation of this disease may allow for significant advances in therapy. Previous studies have largely focused on the mechanism of pancreatitis at the organ level. It is now apparent that the early initiating events in acute pancreatitis probably occur at a membrane or intracellular level. The resolution of the cellular events which underlie the development of pancreatitis in combination with the introduction of new therapeutic agents may enable a rational and safe protocol to be developed for the support of patients with pancreatitis. In this review different experimental models of acute pancreatitis are discussed. Emphasis is placed on the relevance of various models to clinical pancreatitis.
Acute Disease↗
Acute pancreatitis at its centenary. The contribution of Reginald Fitz.
1989 represents the 100th anniversary of Reginald Fitz's initial characterization of acute pancreatitis. Our current understanding of this disease has advanced little beyond Fitz's early description. While survival from pancreatitis has improved largely through advancements in critical care techniques, no medical or surgical therapy exists that can limit pancreatic autodigestion and inflammation. Recent investigations have suggested that pancreatitis may result from a disruption of normal stimulus-secretion coupling within the acinar cell. Future research based on these observations may ultimately result in successful therapy for this disease.
Acute Disease↗
Endoscopic sclerotherapy: a risk factor for splanchnic venous thrombosis.
Endoscopic sclerotherapy has been widely advocated as primary therapy for patients surviving hemorrhage from esophageal varices. The potential for endoscopic sclerotherapy to limit subsequent surgical options remains unclear. The following study was undertaken to assess the endoscopic sclerotherapy-related incidence of splanchnic venous thrombosis in patients undergoing surgery for variceal bleeding. We retrospectively identified 27 patients who underwent portosystemic shunting after an episode of variceal hemorrhage documented by endoscopic examination. Eleven patients underwent endoscopic sclerotherapy before portosystemic surgery for shunting. Among the patients undergoing prior endoscopic sclerotherapy, 6/11 had partial splanchnic venous thrombosis at surgery compared with 2/16 in the non-endoscopic sclerotherapy group. This difference was statistically significant. Only one of the eight patients with splenic or portal vein thrombosis detected at surgery showed signs of the condition when an angiograph was performed. Endoscopic sclerotherapy appears to impose a significant risk for splanchnic venous thrombosis. This complication, not reliably detected by angiographic means, may limit the operative options and long-term outcomes of patients in whom endoscopic sclerotherapy fails.
Endoscopy↗
Effect of beta-adrenergic blockade on the growth rate of abdominal aortic aneurysms.
We retrospectively identified 136 patients with abdominal aortic aneurysms (AAAs) who were initially evaluated as outpatients. Twenty-seven of these patients met the following criteria for eligibility in the study: (1) roentgenographic documentation of an AAA larger than 3 cm, (2) at least two serial ultrasound size determinations over a minimum six-month interval, and (3) a documented medication history. Of these 27 patients, 12 received long-term beta-blockade, while 15 received no beta-blockade. The two groups were comparable with respect to age, sex, initial aneurysm size, mean systolic and diastolic blood pressure, and duration of follow-up (mean, 34 months). Among patients with beta-blockade, the mean growth rate was 0.17 cm/y. The rate for the controls was 0.44 cm/y. One patient of 12 (8%) in the beta-blocker group had a rate that exceeded the mean for the overall group compared with eight patients of 15 (53%) in the group with no beta-blockade. This difference was statistically significant. Thus, beta-blockade may be associated with a decreased AAA growth rate in this small, retrospective study.
Adrenergic beta-Antagonists↗
Aberrant hormone production from ovarian neoplasms: strategies for diagnosis and therapy.
Syndromes involving peptide or nonsex steroid hormone secretion due to aberrantly located tumors are rare. We report a collected series of 16 patients with ectopic hormone production from ovarian neoplasms, including 3 patients recently encountered at our institution as well as 13 additional cases identified in the recent literature. These tumors included 2 insulin-producing ovarian carcinoids, 1 ACTH-producing pituitary adenoma within a benign ovarian cystic teratoma, 2 cortisol-producing ovarian neoplasms, 8 gastrin-producing ovarian cystadenomata or cystadenocarcinomata, and 3 thyroxine-producing ovarian strumal carcinoids. All patients presented with syndromes of hormone excess. Only 62% of all tumors were localized preoperatively. Following ovarian resection, 87% of patients remained disease-free with a median follow-up period of 1.5 years. In addition to ovariectomy, 8 additional unnecessary ablative procedures were performed in 7 patients. These included distal pancreatectomy, pancreaticoduodenectomy, adrenalectomy, total gastrectomy, selective vagotomy, and subtotal thyroidectomy. Failure to localize the ovarian neoplasm preoperatively was associated with a significantly higher risk of subsequent unnecessary ablative procedures. Because of the potential for the ovary to act as a source of aberrant hormone secretion, we recommend complete preoperative evaluation of the pelvis in female patients presenting with nonlocalizable endocrine tumors.
Adrenocorticotropic Hormone↗
Nonoperative management of primary colorectal cancer in patients with stage IV disease.
BACKGROUND: Traditional teaching maintains that patients with primary colorectal adenocarcinoma require timely resection to prevent bleeding, perforation, or obstruction. The true benefits of primary tumor resection remain undocumented for patients presenting with metastatic disease, however. We postulated that resection of primary colorectal tumors could be avoided safely in a select population of asymptomatic colorectal cancer patients presenting with incurable stage IV disease. METHODS: A retrospective review of the Vanderbilt University Hospital tumor registry was performed for the years 1985 to 1997. During this period, 955 patients presented for management of primary colorectal cancer. From this group, all patients with stage IV disease at the time of diagnosis were identified. Patients who initially underwent resection of their primary lesion were included in the resection group; those who underwent initial nonoperative primary tumor management were included in the nonresection group. Data were obtained regarding age, extent of disease, nonsurgical therapy, tumor-specific complications, and palliative surgical procedures. Surgery-free survival and overall survival were analyzed using the Kaplan-Meier method. For patients with liver metastases, hepatic tumor burden was defined as either H1 (<25% parenchymal replacement), H2 (25% to 50%), or H3 (>50%) disease. RESULTS: Sixty-six patients were included in the resection group, and 23 patients with intact asymptomatic primary colorectal lesions were included in the nonresection group. Among patients with hepatic metastases, most of the patients in both groups had H1 disease. Ten patients in the resection group and 3 patients in the nonresection group presented with exclusively extrahepatic metastases. In the nonresection group, primary therapy included chemotherapy in 13 patients, external beam radiation therapy in 1 patient, and combination chemoradiation in 9 patients. The median survival in the nonresection group was 16.6 months. The 2-year actuarial survival was 18%, and the surgery-free survival was 91.3%. Only 2 of 23 patients (8.7%) managed without resection eventually developed obstruction at the primary tumor site requiring emergent diversion. There were no episodes of tumor-related hemorrhage or perforation. For the resection group, the operative morbidity was 30.3%, and the perioperative mortality rate was 4.6%. The median survival in the resection group was 14.5 months (P = 0.59, log-rank test vs. nonresection group). CONCLUSIONS: Selected patients with asymptomatic primary colorectal tumors who present with incurable metastatic disease may safely avoid resection of their primary lesions, with an anticipated low rate of hemorrhage, perforation, or obstruction before death from systemic disease. No survival advantage is gained by resection of an asymptomatic primary lesion in the setting of incurable stage IV colorectal cancer.
Adenocarcinoma↗