Parupudi V.J. Sriram

Mediastinal lymphadenopathy in patients with or without previous malignancy: EUS-FNA-based differential cytodiagnosis in 153 patients.

OBJECTIVE:Mediastinal lymphadenopathy (ML) is a cause for concern, especially in patients with previous malignancy. The investigation of choice is thoracic CT with a variable sensitivity and specificity requiring tissue diagnosis. We used endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) for cytodiagnosis of ML in patients with and without previous malignancy. The cause, distribution of lesions, and incidence of second cancers were investigated.METHODS:Linear echoendoscopes and 22-gauge needles for cytology were used for EUS-FNA. A cytological diagnosis of malignancy was accepted, and histology or consistent follow-up of at least 9 months confirmed benign results.RESULTS:One hundred fifty-three patients underwent EUS-FNA between November 1997 and November 1999 (mean age, 60 yr; range, 13–82 yr; 105 men). Cytology was adequate in 150 patients. Final diagnosis was malignancy in 84 and benign in 66 patients (sensitivity, specificity, and diagnostic accuracy: 92%, 100%, 95%, respectively). In 101 patients without previous cancer cytology identified 48 malignant (lung, 41; extrathoracic, 7) and 51 benign lesions (inflammation, 35; various, 9; sarcoidosis, 7) (sensitivity, specificity, accuracy: 88%, 100%, 94%). Fifty-two patients had prior malignancy, mostly in extrathoracic sites. Cytology revealed recurrences in 21 patients, second cancer in 9 and benign lesions in 21 patients (inflammatory, 11; sarcoidosis, 8; tuberculosis, 1; abscess, 1) (sensitivity, specificity, accuracy: 97%, 100%, 98%).CONCLUSIONS:In patients without previous cancer malignant ML originates from the lung >80%. In those with previous malignancy recurrence of extrathoracic sites is the major cause. Benign lesions and treatable second cancers occur in a significant frequency, emphasizing the need for tissue diagnosis. EUS-FNA is a safe and minimally invasive alternative for cytodiagnosis in the mediastinum.

Mutations in the pancreatic secretory trypsin inhibitor gene (PSTI/SPINK1) rather than the cationic trypsinogen gene (PRSS1) are significantly associated with tropical calcific pancreatitis

Pancreatitis is a global health care problem with varied aetiologies. Alcoholism is responsible in the majority of patients while other causes, such as heredity, gallstones, hyperlipidaemia, hypercalcaemia, and idiopathic pancreatitis, are relatively rare.1,2 The causal factor in 20-30% of such cases is still not known and they fall into the category of idiopathic chronic pancreatitis (ICP).1,2 Although the exact pathogenesis is not clear, autodigestion secondary to aberrant intraductal activation of zymogens by trypsin is a primary common event. A genetic basis was reported in 1996 by familial linkage analysis3–5 and confirmed by detection of missense mutations, namely R122H and N29I, in the cationic trypsinogen gene ( PRSS1 ) in hereditary pancreatitis (HP) patients.6,7 HP is a relatively rare autosomal dominant disorder where typical acute attacks in childhood and frequent progression to chronic pancreatitis are seen to occur in two or more subjects or generations. Subsequent studies from other parts of the world have also reported the two common mutations8,9 and other mutations in the PRSS1 gene in both HP and ICP patients.8,10,11 However, only about 60% cases of HP and less than 20% with a diagnosis of ICP have a mutated PRSS1 gene, suggesting the presence of other candidate genes. Pancreatic secretory trypsin inhibitor (PSTI/SPINK1) is a potent protease inhibitor and thought to be a major protective mechanism preventing inappropriate activation of pancreatic digestive enzyme cascade by inhibiting up to 20% of potential trypsin activity.12 The human SPINK1 gene on chromosome 5 is approximately 7.5 kb long with four exons and codes for a product of 79 amino acids including a signal peptide of 23 amino acids.13 Since the inhibitor molecule provides the first line of defence against prematurely activated trypsinogen within the pancreas, it has recently …

Prospective evaluation of morphology, function, and quality of life after extracorporeal shockwave lithotripsy and endoscopic treatment of chronic calcific pancreatitis

OBJECTIVE: Therapeutic endoscopy may be effective in selected patients with chronic calcific pancreatitis (CCP). We prospectively evaluated the early outcome of extracorporeal shockwave lithotripsy (ESWL) in combination with interventional endoscopy, using broad inclusion criteria. METHODS: A total of 48 consecutive patients (35 male, 13 female) were recruited for ESWL and endoscopic therapy of symptomatic CCP. Symptoms, quality of life, pancreatic morphology and function were assessed before and after ESWL. RESULTS: Multiple stones (n = 43), strictures (n = 34), and pancreas divisum (n = 11) were found. A median of 13 ESWL sessions (range 2–74) with a median of 22,100 shockwaves (1,700–150,900) were required. Endoscopic pancreatic sphincterotomy (n = 48), stricture dilation (n = 12), and/or stenting (n = 27) were performed. After therapy, drainage of the pancreatic duct system was achieved in 36, complete stone clearance in 21 patients. Follow-up (n = 38) at 7 months (range 5–9) showed a significant decrease in pancreatic duct diameter (p < 0.001) and pain score (p < 0.0001) whereas complete pain relief was observed in 45% of cases. Several quality of life scores improved significantly. Weight gain occurred in 68% of patients. Normalization of fasting blood glucose and HbA1c levels were observed in four patients, without modifying their treatment. Improvement in pain score correlated with weight gain and decrease in pancreatic duct diameter. Nonalcoholic etiology was associated with a better chance for improvement in pain score and decrease in pancreatic duct diameter. The presence of strictures did not deteriorate the clinical outcome. CONCLUSIONS: Besides pain relief, ESWL in combination with interventional endoscopy resulted in pancreatic ductal decompression, weight gain, and improvement in quality of life in a considerable number of patients with advanced CCP.

Intralesional steroids augment the effects of endoscopic dilation in corrosive esophageal strictures

BACKGROUND Intralesional corticosteroid injection has been shown to be effective in refractory esophageal strictures of various etiologies. The present study was conducted to determine the efficacy of intralesional triamcinolone in augmenting results of endoscopic dilation in corrosive esophageal strictures. METHODS Seventeen patients with corrosive esophageal strictures were treated with endoscopic dilation together with injection of triamcinolone acetonide into the stricture. Fourteen patients were already undergoing dilation; 3 patients were newly recruited. The interval between dilations and frequency of dilation were calculated before and after corticosteroid injections, and periodic dilation index was calculated as number of dilations/number of months. RESULTS The mean age of the 17 patients (8 men and 9 women) was 30+/-9.21 (range 13 to 52). Thirteen had strictures due to acid ingestion, four to alkali ingestion. There were 18 strictures in total, involving the upper (n = 2), middle (n = 10), and lower (n = 6) thirds of esophagus. Fourteen patients already on a dilation program had undergone 27.92+/-28.63 (range 6 to 92) dilations over a period of 22.92+/-30.73 months (range 2 to 96) before corticosteroid injections. Nine patients received a single injection of triamcinolone, whereas four each had two and three sessions. The dilation requirement after injections in these 14 patients was reduced to 3.57+/-2.90 (range 0 to 10) dilations over a period of 10.5+/-5.58 (range 4 to 21) months. The median total periodic dilation index irrespective of corticosteroid therapy was 0.33 (range 0.55 to 1.8). In 12 of the 14 patients, periodic dilation index before injections (range 0.91 to 3.0, median 1.67) was higher than the median total periodic dilation index and in all the 14 patients periodic dilation index after corticosteroid therapy (range 0 to 0.83, median 0.32) was less than the median of total periodic dilation index (p < 0.01). In addition three patients received intralesional corticosteroid injections at the time of first dilation. These three patients could be effectively dilated with 5, 3, and 3 dilations. CONCLUSIONS Intralesional triamcinolone injections augment the effects of endoscopic dilation in patients with corrosive esophageal strictures.

Natural History of Late Radiation Proctosigmoiditis Treated with Topical Sucralfate Suspension

Rectal bleeding due to radiationproctosigmoiditis is often difficult to manage. We hadearlier shown the efficacy of short-term therapy withtopical sucralfate in controlling bleeding in theradiation proctosigmoiditis. We now report our long-termresults with this form of therapy. The study comprised26 patients with radiation proctosigmoiditis.Sigmoidoscopically, 9 (34.6% patients had severechanges, 15 (57.69%) had moderate, and 2 (7.69%) hadmild changes. Severity of bleeding was graded as severe(>15 episodes per week), moderate (8-14 episodes perweek), mild (2-7 episodes per week), negligible (1 episode per week), or nil (no bleeding). Tenpatients had moderate rectal bleeding, while 16 hadsevere bleeding. All patients were treated with 20 ml of10% rectal sucralfate suspension enemas twice a day until bleeding per rectum ceased orfailure of therapy was acknowledged. Response to therapywas considered good whenever the severity of bleedingshowed improvement by a change of two grades. Rectally administered sucralfate achieved good responsein 20 (76.9%) patients at 4 weeks, 22 (84.6%) patientsat 8 weeks, and 24 (92.3%) patients at 16 weeks. Thischange was significant by Wilcoxon matched-pairs signed-ranks test. Two patients requiredsurgery due to poor response. Over a median follow-up of45.5 months (range 5-73 months) after cessation ofbleeding, 17 (70.8%) patients had no further bleeding while 7 (22.2%) had recurrence of bleeding. Allrecurrences responded to short-term reinstitution oftherapy. No treatmentrelated complications wereobserved. Ten patients had other associated latetoxicity due to pelvic irradiation in the form ofasymptomatic rectal stricture (N = 3), rectovaginalfistula (N = 1), intestinal stricture (N = 1), vaginalstenosis (N = 1), and hematuria (N = 6). Three patients had progression of the primary disease in theform of pelvic recurrence (N = 2) and hepatic metastases(N = 1). We conclude that topical sucralfate induces alasting remission in a majority of patients with moderate to severe rectal bleeding due toradiation proctosigmoiditis.

Endosonography-guided, fine-needle aspiration cytology extending the indication for organ-preserving pancreatic surgery

Abstract OBJECTIVE: Organ preserving pancreatic resections are considered whenever malignant disease is ruled out. In tumors of low malignant potential such as cystadenomas and neuroendocrine tumors, the diagnosis is rarely established preoperatively. We studied the feasibility of cytodiagnosis using endosonography-guided fine-needle aspiration in determining the operative approach. METHODS: A total of 78 patients (16 female, 62 male; mean age 61.4 yr, range 31–82 yr) with focal pancreatic lesions underwent EUS-FNA. Final diagnosis was confirmed by histology, cytology, or clinical follow up (>9 months). Patients with tumors of low malignant potential were managed by customized pancreatic resections. RESULTS: Final diagnosis was malignant tumors in 36 patients, tumors of low malignant potential in nine (six, neuroendocrine, two, borderline mucinous cystadenomas, one, borderline adenocarcinoma), and benign in 31 (two inadequate smears). No complications occurred. With six false-negative and no false-positive results, the accuracy, sensitivity, specificity, and positive and negative predictive values were 92%, 84%, 100%, 100%, and 86%, respectively. Five patients with low malignant tumors underwent duodenum-preserving pancreatic head resection, three mid segment resection, and one pylorus-preserving pancreatoduodenectomy. CONCLUSIONS: EUS-FNA is useful in the preoperative cytodiagnosis of pancreatic tumors of low malignant potential. It extends the indication for organ-preserving pancreatic resections and avoids the unnecessary sacrifice of adjacent organs.

Endoscopic Ultrasound for Differential Diagnosis of Focal Pancreatic Lesions, Confirmed by Surgery

BACKGROUND Endoscopic ultrasound is increasingly used for evaluation of pancreatic cancer. The potential of sonographic morphology to differentiate histology type and biological behaviour of pancreatic lesions is doubtful. METHODS We prospectively studied 115 patients with focal pancreatic lesions on endoscopic ultrasound. Morphology was assessed using Olympus UM3/20/200 echoendoscopes. Histologic confirmation of diagnosis was obtained in all patients. RESULTS Endoscopic ultrasound correctly diagnosed 18/34 benign and 77/81 malignant lesions. Sensitivity, specificity, accuracy, PPV and NPV for diagnosing malignancy were 95%, 53%, 83%, 83% and 82%, respectively. Endosonographic diagnosis of the lesions (% correct) were: pancreatic cancer, 84 (63.3%); chronic pancreatitis, 14 (71.4%); ampullary cancer, 9 (77.8%); cystadenoma, 5 (80%); ampullary adenoma, 2 (50%); acute pancreatitis, 1 (0). In 13 patients of chronic pancreatitis, diagnosed as cancer, diagnosis was based on absence of sonographic features of chronic pancreatitis (7) or suspected involvement of adjacent structures (6). In 3 patients malignancy was missed owing to features of chronic pancreatitis. Non-suspected neuroendocrine tumours were misjudged in all 10 cases using morphologic criteria as pancreatic cancer (8), cystadenoma and chronic pancreatitis. Accuracy for prediction of metastatic lymph nodes and an advanced pancreatic cancer stage (TxN1 or T3Nx) was 61% and 75%, respectively. On retrospective analysis, a lesion >2 cm, vessel ingrowth, absence of cystic spaces and absence of diffuse pancreatitis were associated with pancreatic cancer. CONCLUSIONS While overall sensitivity was high, specificity of endoscopic ultrasound for diagnosis of malignancy was low, especially in presence of chronic pancreatitis. In addition, endosonography had only a limited potential to predict the histological type of lesions.Background: Endoscopic ultrasound is increasingly used for evaluation of pancreatic cancer. The potential of sonographic morphology to differentiate histology type and biological behaviour of pancreatic lesions is doubtful. Methods: We prospectively studied 115 patients with focal pancreatic lesions on endoscopic ultrasound. Morphology was assessed using Olympus UM3/20/200 echoendoscopes. Histologic confirmation of diagnosis was obtained in all patients. Results: Endoscopic ultrasound correctly diagnosed 18/34 benign and 77/81 malignant lesions. Sensitivity, specificity, accuracy, PPV and NPV for diagnosing malignancy were 95%, 53%, 83%, 83% and 82%, respectively. Endosonographic diagnosis of the lesions (% correct) were: pancreatic cancer, 84 (63.3%); chronic pancreatitis, 14 (71.4%); ampullary cancer, 9 (77.8%); cystadenoma, 5 (80%); ampullary adenoma, 2 (50%); acute pancreatitis, 1 (0). In 13 patients of chronic pancreatitis, diagnosed as cancer, diagnosis was based on absence of sonographic features of chronic pancreatitis (7) or suspected involvement of adjacent structures (6). In 3 patients malignancy was missed owing to features of chronic pancreatitis. Non-suspected neuroendocrine tumours were misjudged in all 10 cases using morphologic criteria as pancreatic cancer (8), cystadenoma and chronic pancreatitis. Accuracy for prediction of metastatic lymph nodes and an advanced pancreatic cancer stage (TxN1 or T3Nx) was 61% and 75%, respectively. On retrospective analysis, a lesion >2 cm, vessel ingrowth, absence of cystic spaces and absence of diffuse pancreatitis were associated with pancreatic cancer. Conclusions: While overall sensitivity was high, specificity of endoscopic ultrasound for diagnosis of malignancy was low, especially in presence of chronic pancreatitis. In addition, endosonography had only a limited potential to predict the histological type of lesions.

Endoscopic treatment of biliary leakage with n-butyl-2 cyanoacrylate

BACKGROUND Biliary leakage is a problematic complication of hepatobiliary surgery. A novel alternative method is described that can obviate the need for reoperation for refractory biliary fistula. METHODS Nine patients with large biliary leaks unresponsive to endoscopic drainage underwent N-butyl-2-cyanoacrylate glue occlusion at ERCP. RESULTS In 7 patients, occlusion was successful with prompt control of the fistula in a single session, averting reoperation. In 1 patient there was a partial response and in another the treatment was unsuccessful. No procedure-related complication occurred over a median follow-up of 35 months (range: 1.6-160 months). CONCLUSION N-butyl-2-cyanoacrylate glue occlusion is a safe and effective endoscopic method for control of refractory bile leaks that eliminates the need for surgical reintervention.

Impact of endoscopic ultrasound for evaluation of submucosal lesions in gastrointestinal tract.

BACKGROUND Endoscopic ultrasound is widely used following endoscopy for evaluation of suspected submucosal lesions and may guide further management of patients. PATIENTS AND METHOD A total of 181 consecutive patients with suspected submucosal lesion in the upper gastrointestinal tract were diagnosed by endoscopic ultrasound between 1990-97. We evaluated: 1) the potential of endoscopic ultrasound criteria to predict histological type of submucosal lesions in 69 patients with available histology, 2) the ability of endoscopic ultrasound alone or with clinical presentation, to predict malignancy in 86 patients with available histology or follow-up of >12 months. RESULTS Sensitivity and specificity for diagnosing 44 gastrointestinal stromal tumours were 95 and 72%, respectively, while 25 miscellaneous lesions were diagnosed correctly in only 56% by endoscopic ultrasound. Diagnosis of malignancy, using any two of three endoscopic ultrasound criteria (heterogeneous echotexture, size >3 cm, irregular margins) showed a sensitivity of 80% and specificity of 77%, giving accurate endoscopic ultrasound diagnosis in 16/20 malignant and 51/66 benign submucosal lesion. Heterogeneous echotexture, size >3 cm, and irregular margins showed a relative risk of 7.2, 5.4 and 4.6, respectively, for presence of malignancy. The presence of symptoms, potentially suggesting malignancy (dysphagia, gastrointestinal bleeding, pain and weight loss), had a relative risk of 4.2, however this did not increase the accuracy of diagnosing malignancy based on endoscopic ultrasound criteria alone. CONCLUSION The accuracy of endoultrasound is high in diagnosing gastrointestinal stromal tumours, which show a significant potential of malignancy. Endoscopic ultrasound morphology appears to be helpful in selection of patients for surgical or conservative treatment. The accuracy of endoscopic ultrasound in differential diagnosis of non-gastrointestinal stromal tumour lesions is limited.

A model of deformable rings for interpretation of wireless capsule endoscopic videos

Wireless Capsule Endoscopy (WCE) provides a means to obtain a detailed video of the small intestine. A single session with WCE may produce nearly 8h of video. Its interpretation is tedious task, which requires considerable expertise and is very stressful. The Model of Deformable Rings (MDR) was developed to preprocess WCE video and aid clinicians with its interpretation. The MDR uses a simplified model of a capsules motion to flexibly match (register) consecutive video frames. Essentially, it computes motion-descriptive characteristics and produces a two-dimensional representation of the gastrointestinal (GI) tracts internal surface - a map. The motion-descriptive characteristics are used to indicate video fragments which exhibit segmentary contractions, peristalsis, refraction phases and areas of capsule retention. Within maps, certain characteristics that indicate areas of bleeding, ulceration and obscuring froth could be recognized. Therefore, the maps allow quick identification of such abnormal areas. The experimental results demonstrate that the number of discovered pathologies and gastrointestinal landmarks increases with the MDR technique.