Sandeep Lahoti

Prospective evaluation of endoscopic ultrasonography, endoscopic retrograde pancreatography, and secretin test in the diagnosis of chronic pancreatitis

BACKGROUND Chronic pancreatitis in its early stages may defy diagnosis despite existing diagnostic modalities. Endoscopic retrograde pancreatography (ERCP), secretin test, and conventional ultrasound are insensitive in detecting the early stages of chronic pancreatitis. The aim of this study was to determine whether endoscopic ultrasonography (EUS) high-resolution imaging allows for the detection of chronic pancreatitis as compared with clinical history, ERCP, and secretin test. METHODS Eighty consecutive patients with recurrent pancreatitis underwent ERCP, EUS, and secretin test. EUS evaluated parenchymal changes: echogenic foci (calcification), prominent interlobular septae (fibrosis), small cystic cavities (edema), lobulated outer gland margin (fibrosis/atrophy), and heterogeneous parenchyma; and ductal changes: dilation, irregularity, echogenic wall (fibrosis), side-branch ectasia, and echogenic foci (stones). EUS criteria for chronic pancreatitis included mild (1 to 2 features), moderate (3 to 5 features), and severe (more than 5 features). RESULTS Abnormal studies were EUS = 63, ERCP = 36, and secretin test = 25. Secretin test had 100% agreement with normal and severe chronic pancreatitis by EUS criteria, but agreement was poor for mild (13%) and moderate (50%) disease. Alternatively, the agreement between ERCP- and EUS-specific criteria was excellent for normal (100%), moderate (92%), and severe (100%) chronic pancreatitis and poor for mild (17%) disease. When the 2-test modality (ERCP and secretin test) was compared with EUS alone, no enhancement in agreement was seen. CONCLUSION Using the above criteria EUS may assist in the diagnosis of chronic pancreatitis not established by ERCP or secretin test. Excellent agreement can be expected between EUS and ERCP in the diagnosis of chronic pancreatitis with the exception of mild changes noted on EUS (kappa statistics = 0.82: 95% CI [0.70, 0.95]). Long-term follow-up of the patients with mild EUS changes will determine the validity of EUS in diagnosing the early stages of chronic pancreatitis.

Effect of Preoperative Biliary Decompression on Pancreaticoduodenectomy-Associated Morbidity in 300 Consecutive Patients

ObjectiveTo examine the relationship between preoperative biliary drainage and the morbidity and mortality associated with pancreaticoduodenectomy. Summary Background DataRecent reports have suggested that preoperative biliary drainage increases the perioperative morbidity and mortality rates of pancreaticoduodenectomy. MethodsPeri-operative morbidity and mortality were evaluated in 300 consecutive patients who underwent pancreaticoduodenectomy. Univariate and multivariate logistic regression analyses were done to evaluate the relationship between preoperative biliary decompression and the following end points: any complication, any major complication, infectious complications, intraabdominal abscess, pancreaticojejunal anastomotic leak, wound infection, and postoperative death. ResultsPreoperative prosthetic biliary drainage was performed in 172 patients (57%) (stent group), 35 patients (12%) underwent surgical biliary bypass performed during prereferral laparotomy, and the remaining 93 patients (31%) (no-stent group) did not undergo any form of preoperative biliary decompression. The overall surgical death rate was 1% (four patients); the number of deaths was too small for multivariate analysis. By multivariate logistic regression, no differences were found between the stent and no-stent groups in the incidence of all complications, major complications, infectious complications, intraabdominal abscess, or pancreaticojejunal anastomotic leak. Wound infections were more common in the stent group than the no-stent group. ConclusionsPreoperative biliary decompression increases the risk for postoperative wound infections after pancreaticoduodenectomy. However, there was no increase in the risk of major postoperative complications or death associated with preoperative stent placement. Patients with extrahepatic biliary obstruction do not necessarily require immediate laparotomy to undergo pancreaticoduodenectomy with acceptable morbidity and mortality rates; such patients can be treated by endoscopic biliary drainage without concern for increased major complications and death associated with subsequent pancreaticoduodenectomy.

Antibiotic Treatment of Gastric Lymphoma of Mucosa-Associated Lymphoid Tissue: An Uncontrolled Trial

Gastric low-grade B-cell lymphoma is related to Helicobacter pylori infection according to histopathologic, epidemiologic, and clinical characteristics. Although normal gastric mucosa does not contain organized lymphoid tissue, lymphoid follicles develop with H. pylori infection (1) and with autoimmune diseases, such as the Sjgren syndrome (2). Low-grade B-cell lymphoma has been postulated to arise within this mucosa-associated lymphoid tissue (MALT) and is often called low-grade MALT lymphoma (3, 4). The incidence of gastric low- and high-grade MALT lymphoma is increased in populations with a high prevalence of H. pylori infection, and H. pylori infection has been reported in up to 90% of patients with low-grade MALT lymphoma (4-6). In addition, investigators have shown that growth of this tumor may depend on antigenic stimulation by H. pylori: They demonstrated that the proliferation of lymphoma B cells in cell culture can be stimulated by H. pylori-specific T cells and related cytokines in the presence of H. pylori (7). On the basis of these findings, trials of antibiotic treatment of gastric low-grade MALT lymphoma have been initiated, and the regression of lymphoma after cure of H. pylori infection has been reported in a high proportion of patients with low tumor burden (8-13). Data on patients with significant tumor infiltration are still forthcoming (13, 14). Because MALT lymphoma has only recently been approached as a distinct clinicopathologic entity (15, 16), its natural history and clinical course are not fully defined. Current data suggest that it is often an indolent tumor with long periods of mild activity and confinement to the stomach. Patients often present with nonspecific upper intestinal discomfort, ulcer-associated symptoms, or gastric bleeding. The endoscopic appearance may suggest benign gastritis, and extensive biopsies may be required for diagnosis. Progression to significant tumor mass, dissemination, or transformation to high-grade, aggressive lymphoma occur in an undefined subset of patients, who may present with early satiety or weight loss. Spontaneous remissions are rare (17-20). Because low-grade MALT lymphoma is an uncommon, often indolent form of cancer with few clinical findings and because the risk for progression to high-grade MALT lymphoma is still unknown (15, 16), definitive data on cure require long-term follow-up of large cohorts from standardized clinical trials. This report presents an interim analysis of an ongoing trial designed to determine the long-term response of low-grade gastric MALT lymphoma to antibiotic treatment and to define criteria for treatment and follow-up. Methods Patients Patients with gastric MALT lymphoma restricted to the stomach and perigastric lymph nodes (modified Ann Arbor stage I and II N1) were eligible for the study. The University of Texas, M.D. Anderson Cancer Center (MDACC), Internal Review Board approved the study, and all patients provided written informed consent. The National Cancer Institute and the institutional review boards of participating institutions approved the multi-institutional protocol. To enable a follow-up period of at least 18 months, only patients treated before May 1997 were included in this analysis. Study Design and Treatment The interim data are derived from an ongoing, prospective, uncontrolled treatment trial with third-party patient registry. Patients were studied at four participating centers. Pathologic diagnosis and resolution of MALT lymphoma were confirmed at MDACC, and all but one patient were examined endoscopically at MDACC. Study design included 1) tumor staging with bilateral bone marrow biopsies and aspirates and computed tomography of the abdomen and pelvis done at baseline and yearly; 2) endoscopy at baseline, at weeks 6 to 8, at 3- to 4-month intervals thereafter until resolution of MALT lymphoma was seen on two consecutive endoscopies, at 6-month intervals thereafter for 2 years, and then yearly thereafter; and 3) endoscopic ultrasonography at baseline and at each endoscopy until resolution of masses or infiltration of the muscularis propria, if present (defined as thickness>2 mm or obliteration of wall architecture), and then at 6- to 12-month intervals. The treatment protocol consisted of two of the following three oral antibiotic regimens1] amoxicillin, 750 mg three times daily, and clarithromycin, 500 mg three times daily; 2) tetracycline, 500 mg four times daily, and clarithromycin, 500 mg three times daily; or 3) tetracycline, 500 mg four times daily, and metronidazole, 500 mg three times dailyadministered sequentially for 21 days at baseline and at 8 weeks along with a proton-pump inhibitor (lansoprazole, 30 mg twice daily [n=29], or omeprazole, 20 mg twice daily [n=5]), and bismuth subsalicylate, two tablets four times daily. Patients who were allergic to penicillin received the tetracycline-based regimens. Tumor Staging Tumors were staged endoscopically to separate superficial gastritis from significant ulcers and infiltration and from mass lesions. A modified Ann Arbor staging system that incorporated changes proposed by Blackledge, Musshoff, and Rohatiner and their coworkers was used initially (21-23). The TNM (tumor, node, metastasis) classification of the American Joint Committee on Cancer and Union Internationale Contre le Cancer (24, 25), which corresponds to the modified Ann Arbor staging, was subsequently adapted and applied (Table 1). The extent of tumor (T) infiltration through the stomach wall and to adjacent organs corresponds to T staging of gastric cancer. Modified Ann Arbor stage I corresponds to stage I T1-4 N0 M0. Modified Ann Arbor stage II1 (22) (involvement of perigastric lymph nodes) corresponds to stage II T1-4 N1 M0. Modified Ann Arbor stage II2 (22) (involvement of distant lymph nodes caudal to the diaphragm, including para-aortic and retroperitoneal lymph nodes) corresponds to stage II T1-4 N2 M0. Ann Arbor stage III (lymph node involvement on both sides of the diaphragm) is designated by stage III T1-4 N3 M0. Ann Arbor stage IV (organ metastasis or involvement of a second extranodal site) is designated by stage IV T1-4 N0-3 M1. Table 1. Staging of Gastric Lymphoma of Mucosa-Associated Lymphoid Tissue Criteria for Response Response to treatment was evaluated at 3- to 4-month intervals beginning with the fifth month after treatment. Treatment was considered to have failed if patients did not meet criteria for improvement; these patients were removed from the study. In stage I T2, I T3, and II N1 tumors, improvement was defined as regression to a lower stage, 30% reduction in abnormal wall thickness, or 30% reduction in the size of the tumor mass (product of the greatest diameters). These patients remained in the study if sequential improvement was evident at each 3-month interval. Patients with persistent mucosal disease (stage I T1) documented by histopathology were formally reviewed at 12-month intervals; a consensus on withdrawal from or continuation in the study was based on clinical considerations, current knowledge, and patient preference. Initially, patients with persistent stage I T1 disease were withdrawn from the study at 12 months (n=2). Subsequently, patients with persistent stage I T1 disease were observed for more than 36 months if improvement was documented at 12-month intervals. Criteria for improvement in stage I T1 disease included reduction in the number of affected gastric sites or affected biopsy specimens or improved histologic score (8), endoscopic appearance of progressive atrophy and scarring, or resolution of abnormal wall thickness on endoscopic ultrasonography. Complete remission was defined as the absence of histopathologic evidence of lymphoma and an endoscopic appearance of gastritis or better. Partial remission was defined as a reduction in endoscopic stage in stage I T2 disease or at least 50% reduction in the size of the mass lesions in stage I T3 or II T3 N1 disease. In stage I T1 disease, partial remission was defined as at least 75% reduction in the number of gastric sites or biopsy specimens showing lymphoma. Treatment was considered to have failed in patients who met criteria for failure or who were withdrawn from the study before complete remission occurred. Endoscopy and Biopsies The gastric mapping protocol included 2 or more maximum-capacity biopsies from each of 7 to 12 areas of the gastric map (26) and at least 6 biopsies from 2 or more of the most abnormal areas. The more extensive mapping was done at baseline and at clinically relevant time points. Studies, done at defined intervals, included routine histopathology, H. pylori testing by Genta stain, rapid urease test (CLO-test, Delta West, Bentley, Australia) or serology, Southern blot or polymerase chain reaction (PCR) for immunoglobulin gene rearrangement analysis, and immunoglobulin light-chain immunocytochemistry. Diagnostic Criteria Low-grade B-cell MALT lymphoma was diagnosed by established histologic criteria [15, 27], including 1) a dense diffuse infiltrate of marginal-zone centrocyte-like B cells with round to slightly irregular nuclear contours, often with abundant pale cytoplasm; 2) presence of lymphoepithelial lesions, characterized by infiltration and disruption of gastric glands or crypts by groups of neoplastic lymphoid cells; and 3) absence of any areas where large cells predominate. Minor criteria supporting but not essential for diagnosis included presence of immunoglobulin light-chain restriction; presence of residual secondary follicle centers with or without intact mantles; and presence of follicular colonization, defined as replacement of follicle centers by neoplastic lymphoid cells. Immunophenotypic expression of pan-B-cell antigens, such as CD20, and lack of expression of CD5 or CD10 supported the diagnosis. Patients with foci of large-cell transformation were excluded from the study. Southern Blot and Polymerase Chain Reaction High-molec

Preoperative Chemoradiation for Patients With Pancreatic Cancer: Toxicity of Endobiliary Stents

PURPOSE A recent multicenter study of preoperative chemoradiation and pancreaticoduodenectomy for localized pancreatic adenocarcinoma suggested that biliary stent-related complications are frequent and severe and may prevent the delivery of all components of multimodality therapy in many patients. The present study was designed to evaluate the rates of hepatic toxicity and biliary stent-related complications and to evaluate the impact of this morbidity on the delivery of preoperative chemoradiation for pancreatic cancer at a tertiary care cancer center. PATIENTS AND METHODS Preoperative chemoradiation was used in 154 patients with resectable pancreatic adenocarcinoma (142 patients, 92%) or other periampullary tumors (12 patients, 8%). Patients were treated with preoperative fluorouracil (115 patients), paclitaxel (37 patients), or gemcitabine (two patients) plus concurrent rapid-fractionation (30 Gy; 123 patients) or standard-fractionation (50.4 Gy; 31 patients) radiation therapy. The incidences of hepatic toxicity and biliary stent-related complications were evaluated during chemoradiation and the immediate 3- to 4-week postchemoradiation preoperative period. RESULTS Nonoperative biliary decompression was performed in 101 (66%) of 154 patients (endobiliary stent placement in 77 patients and percutaneous transhepatic catheter placement in 24 patients). Stent-related complications (occlusion or migration) occurred in 15 patients. Inpatient hospitalization for antibiotics and stent exchange was necessary in seven of 15 patients (median hospital stay, 3 days). No patient experienced uncontrolled biliary sepsis, hepatic abscess, or stent-related death. CONCLUSION Preoperative chemoradiation for pancreatic cancer is associated with low rates of hepatic toxicity and biliary stent-related complications. The need for biliary decompression is not a clinically significant concern in the delivery of preoperative therapy to patients with localized pancreatic cancer.

Obliteration of esophageal varices using EUS-guided sclerotherapy with color Doppler

BACKGROUND The current standard treatment of bleeding esophageal varices is band ligation. Although endoscopic sclerotherapy has largely been supplanted by band ligation, there are still clinical situations in which injection methods are useful. Endoscopic ultrasound (EUS) may allow for a more complete evaluation of esophageal varices and perforating veins and may allow for more effective delivery of sclerosant. Our aim was to evaluate the use of color Doppler EUS-guided sclerotherapy for the obliteration of esophageal varices. METHODS Five patients with esophageal varices (Childs A = 1, B = 2, C = 2) underwent dynamic EUS-guided sclerotherapy with color flow Doppler. EUS sclerotherapy was performed using Varijet (2.5 mm catheter) injector needles and sodium morrhuate directed at the perforating vessels until flow was completely impeded (2 to 4 mL per injection site). Data collected included (1) sessions to obliteration, (2) episodes of recurrent bleeding, (3) complications, and (4) mortality. RESULTS Patients undergoing EUS-sclerotherapy required 2.2 sessions to achieve obliteration of varices. No patient had a recurrence of bleeding and no deaths occurred. One patient developed an esophageal stricture that responded to balloon dilation. CONCLUSIONS Dynamic EUS-guided sclerotherapy with color flow Doppler may be safely and effectively used for the treatment of esophageal varices. It allows for effective delivery of sclerosant with favorable outcomes. Prospective, multicenter, randomized trials are warranted.

Long-term outcome of Phase II trial evaluating chemotherapy, chemoradiotherapy, and surgery for locoregionally advanced esophageal cancer

PURPOSE To evaluate the long-term outcome of chemotherapy, chemoradiotherapy, and surgery for patients with locoregionally advanced esophageal cancer. METHODS AND MATERIALS Thirty-eight patients with locoregionally advanced esophageal cancer were entered into a Phase II study between November 1996 and October 1998 at the University of Texas M. D. Anderson Cancer Center. Patients initially received two cycles of chemotherapy with paclitaxel (200 mg/m(2)), 5-fluorouracil (750 mg/m(2)/d for 5 days), and cisplatin (15 mg/m(2)/d for 5 days), followed by chemoradiotherapy, consisting of radiation (45 Gy during 5 weeks) with 5-fluorouracil (300 mg/m(2)/d during radiation) and cisplatin (15 mg/m(2)/d for 5 days). Surgical resection was performed 4-6 weeks after the completion of the chemoradiotherapy. RESULTS Most patients had adenocarcinoma (n = 32; 84%). Pretreatment endoscopic ultrasonography revealed T3 tumors in 33 patients (87%) and N1 disease in 25 patients (66%). Thirty-seven patients (97%) completed the planned chemotherapy and chemoradiotherapy, and 35 patients (92%) underwent surgery, with a 30-day mortality rate of 6% (2 of 35 patients). A pathologic complete response or microscopic residual carcinoma (<10% viable) was found in 25 (71%) of 35 patients and was associated with a disease-free survival rate of 72% at 3 years and 51% at 5 years. On the basis of an intention-to-treat analysis and a median potential follow-up of 58 months, the 3- and 5-year overall survival rate for all 38 patients was 63% and 39%, respectively. CONCLUSION The long-term results of this study suggest that the strategy of induction chemotherapy followed by chemoradiotherapy and surgery is safe and warrants further evaluation in the treatment of patients with locoregionally advanced esophageal cancer.

Dynamic imaging of the pancreas using real-time endoscopic ultrasonography with secretin stimulation ☆ ☆☆

BACKGROUND Obstructive disorders of the pancreas, including strictures, stones, sphincter of Oddi dysfunction, and pancreas divisum, are diagnostic and therapeutic challenges. Conventional extracorporeal ultrasound with secretin stimulation has been used as a noninvasive study to detect obstruction and predict outcome of therapy. Inconsistent results have been obtained because of the inherent limitations of standard ultrasonography. The aim of this study was to evaluate the behavior of the main pancreatic duct by endoscopic ultrasonography during secretin stimulation and to diagnose obstructive disorders of the pancreas. METHODS Secretin-stimulated endoscopic ultrasound (SSEUS, 1 IU/kg secretin) was performed in 20 control subjects (no pancreatic or biliary disease), 40 patients with symptomatic chronic pancreatitis, 40 patients with symptomatic pancreas divisum, 20 patients with suspected sphincter of Oddi dysfunction, and 20 patients with suspected occlusion of pancreatic duct stents. Ductal diameter was measured by endoscopic ultrasonography at baseline and at 1-minute intervals, after administration of secretin, for 15 minutes. A result was determined to be abnormal when a 1 mm or greater dilation of the pancreatic duct was observed from baseline after secretin administration. RESULTS Of the 40 patients with symptomatic chronic pancreatitis, SSEUS correctly predicted obstructive pathology (stones, strictures) in 12 of 13 patients (92%). Of the 40 patients with symptomatic pancreas divisum, 22 underwent stent therapy (16 of 22 with resolution of symptoms). SSEUS accurately predicted response to stent therapy in 13 patients (81%). Seven of twenty patients with suspected sphincter of Oddi dysfunction had abnormal sphincter manometry. SSEUS accurately predicted sphincter dysfunction in only 4 of 7 patients (57%). Finally, 20 patients with suspected occlusion of pancreatic duct stents were studied. Of the 14 stent occlusions confirmed at ERCP, SSEUS correctly predicted premature occlusion in 12 patients (86%). CONCLUSIONS SSEUS appears to be a useful diagnostic modality in the evaluation of patients with suspected obstructive disorders of the pancreas and it can predict which patients may respond to endoscopic therapy.

Combining Gemcitabine With Radiation in Pancreatic Cancer: Understanding Important Variables Influencing the Therapeutic Index

We compared and evaluated available laboratory and clinical data on the use of concurrent gemcitabine (Gemzar; Eli Lilly and Company, Indianapolis, IN) and radiation in pancreatic cancer to provide guidance for subsequent prospective research initiatives. Preclinical data suggest that the timing of administration of gemcitabine with respect to radiotherapy is important, but this issue has not yet been confirmed by clinical data. Phase I clinical data indicate that the amount of acute toxicity from the combination of gemcitabine and radiotherapy is strongly related to the dose and schedule of administration of gemcitabine, as well as to the radiation field size. There also appears to be an inverse linear relationship between the maximum tolerated gemcitabine dose and radiation dose. Also important, but less clear, is the infusion rate of gemcitabine as it relates to the systemic efficacy of the drug. The combination of additional agents with gemcitabine and radiation appears to be feasible. Finally, the addition of radioprotectors may enable chemotherapy dose escalation, but safe escalation of the radiotherapy dose with newer techniques has not been established. Semin Oncol 28 (suppl 10):25-33.

Endoscopic retrieval of proximally migrated biliary and pancreatic stents: experience of a large referral center

BACKGROUND Proximal migration of a biliary or pancreatic stent is an infrequent event but its management can be technically challenging. METHODS Review of all cases of proximally migrated biliary and pancreatic stents over a 10-year period at a referral pancreatic-biliary center. Data abstracted from patient records included indication for stenting, method of presentation, success of attempt, and method used. Successful methods were determined by reviewing procedure reports. Follow-up was attempted in all patients in whom stent retrieval had failed. RESULTS Thirty-three proximally migrated bile duct stents, and 26 proximally migrated pancreatic duct stents were identified. Most of the patients were without symptoms. Eighty-five percent of common bile duct stents and 80% of pancreatic duct stents were successfully extracted endoscopically. Seventy-one percent (34 of 48) were retrieved with a basket or balloon. Of the stents not retrieved, two patients did not return for repeat ERCP, three patients with malignant common bile duct strictures were managed with placement of a second stent, three patients with pancreatic duct stents have remained without symptoms with no further retrieval attempts, and three patients with proximally migrated pancreatic duct stents required surgery because of pain and failure of multiple endoscopic retrieval attempts. CONCLUSION Over 80% of proximally migrated bile duct and pancreatic duct stents may be extracted endoscopically. Few patients will require surgery.

7009 Endoscopic ultrasound guided fine needle aspiration of solid pancreatic lesions: one year md anderson cancer center experience.

Aim: A prospective evaluation of EUS-FNA of solid pancreatic lesions over a one-year period at a quarternary referral center. Methods: 104 consecutive patients undergoing EUS for suspected pancreatic malignancy at MDACC from 11/1/98 to 10/31/99 were prospectively entered into this study. Procedures were performed using the Pentax FG36-UX echoendoscope, Hitachi EUB-525 processor and Wilson-Cook EUS N-1 22 gauge FNA needle. Passes were made until the endosonographer felt adequate material had been obtained. The aspirate was collected by a cytopathology technician who smeared slides in the room. Examination of the slides was performed by a cytopathologist after the procedure had been completed. Final diagnosis was based on biopsy results, surgical specimen, or clinical follow-up. Data collected included size of mass, number of needle passes, complications of procedure, and final diagnosis. 20 patients with pancreatic cysts on EUS were excluded from further analysis. Results: The average age of patients was 64.6 years. The average size of the mass was 3.2cm (range 1.3 - 7cm). The average number of needle passes was 2.5 (range 1 - 5) per patient. No complications occurred. 79 of 84 patients had malignant pancreatic tumors. EUS-FNA correctly identified 73 while cytology showed atypia in one and suspicious for malignancy in another. In the remaining 4 malignant lesions, FNA was non diagnostic due to poor cellularity. There were no false positives. Of the 5 benign lesions, no mass was seen on EUS. 3 of the 5 benign lesions were shown to have chronic pancreatitis. Of the 4 patients with non - diagnostic FNA specimens later proven to be malignant, one had chronic pancreatitis with no mass seen on EUS while 3 had masses clearly identified by EUS. 2 of these 4 patients were found to have adenocarcinoma while the other 2 had a neuroendocrine tumor. Of the 2 patients with atypia or suspicious lesions, surgical resection specimen showed an islet cell carcinoma in one and adenocarcinoma in the other. Among patients in whom adequate cellularity was obtained (counting atypia and suspicious findings on FNA as signs of malignancy), the sensitivity, specificity, positive predictive value, negative predictive value and accuracy was 100%, 100%, 100%,100%, and 95% respectively. Conclusions: EUS-FNA in the hands of an experienced endosonographer is a remarkably powerful tool with a high sensitivity and specificity at diagnosing pancreatic cancer.