Effectiveness of Contrast-Enhanced Ultrasonography for the Characterization of Small and Early Stage Pancreatic Adenocarcinoma.

The purpose of this retrospective study is to evaluate the effectiveness of contrast-enhanced ultrasonography for the characterization of small and early stage pancreatic adenocarcinoma. Contrast-enhanced ultrasonography and contrast-enhanced computed tomography (CT) were performed in 200 cases, with pancreatic hypoechoic regions detected with ultrasonography. Assuming that hypo-enhancement was indicative of pancreatic adenocarcinoma, the sensitivity of each imaging modality was calculated. The sensitivities of contrast-enhanced ultrasonography and contrast-enhanced CT to characterize adenocarcinoma were 97.0% and 77.0% (p < 0.0001) for all 100 adenocarcinoma cases, 100% and 76.7% (p = 0.0016) for 43 small (≤20 mm) cancers, 100% and 58.3% (p = 0.0253) for 12 smaller (≤10 mm) cancers and 100% and 72.2% (p = 0.0016) for 36 stage IA cancers, respectively. The sensitivity of contrast-enhanced ultrasonography was sufficiently high and significantly superior to that of contrast-enhanced CT. Contrast-enhanced ultrasonography is a sensitive tool for selecting highly possible pancreatic adenocarcinoma lesions without overlooking early stage tiny adenocarcinomas among a large number of hypoechoic lesions detected with ultrasonography.

A case of stage IA pancreatic ductal adenocarcinoma accompanied with focal pancreatitis demonstrated by contrast-enhanced ultrasonography.

A patient with slight dilatation of the main pancreatic duct was followed-up with ultrasonography every 6 months as a high-risk case of pancreatic cancer. Twelve years later, a faint hypoechoic area 13 mm in diameter was first detected on the body of the pancreas. Contrast-enhanced ultrasonography revealed a well-demarcated hypoenhanced area 8 mm in diameter and a hyperenhanced area with an unclear margin. The former was suspected to be a small pancreatic cancer lesion, and the latter to be focal pancreatitis accompanying cancer. However, contrast-enhanced dynamic CT did not suggest any tumor, diagnosis of adenocarcinoma was confirmed with pancreatic juice cytology through endoscopic retrograde pancreatography. Surgical resection was performed, and the lesion was pathologically diagnosed as invasive ductal carcinoma as follows: pTS1 (1.0 cm), infiltrative type (pT1), stage IA. When comparing the images from contrast-enhanced ultrasonography with the pathological findings, the hypoenhanced area corresponded to ductal adenocarcinoma, and the hyperenhanced area to focal pancreatitis. Contrast-enhanced ultrasonography was able to reveal detailed information on the focal lesion in the pancreas, and it was effective for the early diagnosis of pancreatic cancer.

New approach for local cancer treatment using pulsed high-intensity focused ultrasound and phase-change nanodroplets.

PURPOSE: The aim of this study was to investigate the combination effects of pulsed HIFU (pHIFU) and phase-change nanodroplets (PCND) as a sensitizer on efficient induction of mechanical effects of pHIFU and chemically enhanced tumor growth inhibition for local anti-tumor therapy. METHOD: Changes in growth of colon 26 tumor tissue inoculated onto CDF1 mice were evaluated by the following treatments. (1) pHIFU exposure (1.1 MHz, 3.2 kW/cm(2), 300 cycles, and 50 ms interval) for 60 s, (2) PCND (1 %) injection, (3) adriamycin (4 mg/kg) injection, (4) pHIFU exposure after PCND injection, and (5) pHIFU exposure after PCND + adriamycin injection simultaneously. RESULTS: Significant changes in tumor growth were observed in the group with combination of pHIFU and PCND, although single therapy did not show any significant difference. PCND enhanced mechanical tissue fractionation by pHIFU, which was detectable by Real-time tissue elastography. Moreover, the combination of pHIFU and PCND + Adriamycin suppressed the tumor growth for 2 weeks, and 3 of 4 mice did not show any sign of regrowth during the 30-day observation. CONCLUSION: The combination of pHIFU and PCND exerted a significant anti-tumor effect and may be a new candidate for treatment of locally advanced cancer.

Safety and effectiveness of gemcitabine in 855 patients with pancreatic cancer under Japanese clinical practice based on post-marketing surveillance in Japan.

OBJECTIVE: When gemcitabine was approved as an anti-cancer drug, there were limited data for Japanese patients treated with gemcitabine. Generally, advanced or metastatic pancreatic cancer patients experience poor prognosis and suffer from debilitating disease-related symptoms. Reports and information on gemcitabine use within a large patient pool will be beneficial to aid physicians. Therefore, this post-marketing surveillance was conducted as a non-interventional, observational study on the use of gemcitabine in a clinical practice setting in Japan. METHODS: Patients had no previous treatment with gemcitabine and were diagnosed with pancreatic cancer by an attending physician. Patients were registered between May 2001 and December 2003 in Japan. The patients were treated with gemcitabine. Data such as patient background, treatment details, adverse events, tumor response, serum CA19-9 levels and drug-related symptom improvement were assessed. RESULTS: Of the 890 patients registered for the study, 855 were included in the analysis of gemcitabine for safety. Four hundred and forty-three (51.9%) patients reported drug-related adverse events, with 97 patients (11.4%) experiencing serious adverse events. The incidence of interstitial lung disease was 0.7% (six patients). Six hundred patients were evaluated for tumor response. The overall response rate was 6.0% and the disease control rate was 54.0%. CA19-9 decreased in 63.6% of the 335 evaluable patients, with a ≥75% decrease seen in 19.4% of the total group. Drug-related symptom improvement was observed in 27.0% of the 686 evaluable patients. CONCLUSIONS: This large-scale surveillance could confirm the safety of gemcitabine for Japanese pancreatic cancer patients as well as elucidate the efficacy profile, measured by drug-related symptom improvement, for Japanese pancreatic cancer patients.

Diagnostic clues and subsequent examinations that detected small pancreatic cancer.

BACKGROUND/AIMS: Our aim was to investigate how 2cm or smaller pancreatic cancers were detected successfully in recent years. METHODOLOGY: Diagnostic clues and subsequent examinations that detected 15 histologically confirmed 2 cm or smaller pancreatic cancers were reviewed. RESULTS: Diagnostic clues were imaging findings in 6 patients, symptoms in 5 and laboratory data in 4. Six of 8 patients who had risk factors of pancreatic cancer such as pancreatic cyst, dilated main pancreatic duct, pancreatitis, or diabetes had been followed-up by imaging and laboratory examinations. Five patients with extrapancreatic disease had been followed-up chiefly by laboratory examinations. The remaining 2 had neither of them. Detectabilities of pancreatic mass in US, CT and EUS were 89%, 67% and 100%, respectively; those of pancreatic mass and/or dilated main pancreatic duct were 100% in all three modalities. Cytological examination revealed adenocarcinoma preoperatively in 14 patients (93%). CONCLUSIONS: Small pancreatic cancer of 2 cm or smaller were suggested by symptoms, laboratory data, or imaging examinations. They were confirmed by further examinations including cytology.

Diagnostic accuracy of endoscopic ultrasound-guided fine needle aspiration for suspected pancreatic malignancy in relation to the size of lesions.

BACKGROUND AND AIM: Endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) is an accurate method for cytological confirmation of pancreatic malignancy, but it has been unknown whether its diagnostic accuracy for pancreatic lesions was affected by their size, location, or size of needles. Our aim was to investigate the accuracy of EUS-FNA for suspected pancreatic malignancy in relation to these factors, especially to the size of lesions. METHODS: In a tertiary referral center, EUS-FNAs for 120 suspected pancreatic malignancies in 115 patients based on other imaging studies were evaluated retrospectively. RESULTS: Overall accuracy of EUS-FNA was 96% (115/120), with sensitivity of 95% (76/80), specificity of 98% (39/40), positive predictive value of 99% (76/77), and negative predictive value of 91% (39/43). Accuracies for lesions less than 10mm, 11-20mm, 21-30mm, and more than 31mm were 96%, 95%, 96%, and 100%, respectively; those for lesions in the head, the body, and the tail of the pancreas were 96%, 95%, and 95%, respectively. Accuracies for 22-gauge and 25-gauge needle were 93% and 98%, respectively. CONCLUSION: EUS-FNA was accurate in the evaluation of suspected pancreatic malignancy regardless of its size, location, or size of needles. It was useful also in the confirmation of small pancreatic malignancies less than 10mm.

Combined brush cytology and stent placement in a single session for presumed malignant biliary stricture.

BACKGROUND AND AIM: Biliary stricture may be benign or malignant and causes obstructive jaundice. Brush cytology is a simple technique for diagnosing the cause of biliary stricture; however, its sensitivity has been reported to be low. A technique that comprises diagnosing the cause of stricture with a satisfactory sensitivity and relieving jaundice is required. This study was designed to evaluate the diagnostic performance of brush cytology and the feasibility of the subsequent stent placement in a single endoscopic retrograde cholangiopancreatography (ERCP) session performed for presumed malignant biliary strictures. METHODS: Data were collected by reviewing the medical records of 100 consecutive patients with suspected malignant biliary stricture who underwent brush cytology followed by stent placement at our center. Diagnostic performance of brush cytology, completion rate of the whole procedures comprising brush cytology and stent placement, and complications were evaluated. RESULT: Sensitivity, specificity, positive predictive value, negative predictive value and overall accuracy of brush cytology were 83%, 100%, 100%, 33% and 84%, respectively. Biliary stent was successfully inserted for all patients (100%) subsequent to brush cytology in a single ERCP session. Eight patients (8%) had complications. CONCLUSION: Brush cytology was performed with much higher sensitivity of 83% than those of previous reports and the subsequent stent placement was successfully completed in all cases. For presumed malignant biliary stricture, brush cytology should be selected as an initial attempt because this technique is simple and enables subsequent stent placement in a single ERCP session.

Asymptomatic curable pancreatic ductal carcinoma detected during the follow-up of pancreatic cysts distinct from carcinoma.

Recent studies have reported that pancreatic ductal carcinomas are frequently found during the follow-up of pancreatic cysts distinct from carcinoma; however, the majority of them are detected in advanced stages. Therefore, the early detection of metachronous ductal carcinomas is one of the issues in the management of pancreatic cysts. A 25-mm pancreatic cyst in the pancreatic head was found during an annual check-up in a 70-year-old woman. She was followed up every 6 months by abdominal ultrasound (US) and blood tests, and every 12 months by an additional magnetic resonance imaging scan. Twelve months later, abdominal US revealed a suspicious low-echoic area of 17 mm diameter in the pancreatic body. Eighteen months later, her serum carbohydrate antigen 19-9 level rose to 92 U/ml. Endoscopic retrograde pancreatography demonstrated a strictured main pancreatic duct (MPD) of 15 mm in length in the pancreatic body. A cytological examination of the brushed MPD revealed adenocarcinoma. The patient underwent distal pancreatectomy and splenectomy after chemoradiotherapy. An histological examination revealed a ductal carcinoma of 26 mm diameter in the pancreatic body, which was successfully resected. This case might help to establish an optimal surveillance method to detect metachronous ductal carcinomas arising from the pancreas harboring cystic lesions.

Size of mural nodule as an indicator of surgery for branch duct intraductal papillary mucinous neoplasm of the pancreas during follow-up.

BACKGROUND: A mural nodule is a strong predictive factor for malignancy in branch duct intraductal papillary mucinous neoplasm (IPMN) of the pancreas, but the nodule size has hardly been considered. The aim of this study was to investigate whether a mural nodule of 10 mm was appropriate as an indicator of surgery for IPMN during follow-up. METHODS: The follow-up outcomes of 100 patients who had branch duct IPMN without mural nodules or who had branch duct IPMN with mural nodules of less than 9 mm in a tertiary care setting were investigated retrospectively. The patients underwent abdominal ultrasound (US) every 3 months and additional imaging examinations or cytologic examination of pancreatic juice when necessary. Surgery was recommended to them when a mural nodule developed or when a nodule enlarged and reached 10 mm. RESULTS: During an average follow-up period of 97 months, branch duct IPMNs developed mural nodules that reached 10 mm in 5 patients (0.62% per year). In one patient the IPMN was revealed to be non-invasive carcinoma by resection, 1 IPMN was shown to be malignant by further follow-up, and 3 were not resected because of refusal or the patient's age. In 7 patients, mural nodules stayed within 9 mm. The remaining 88 patients lacked mural nodules in their branch duct IPMNs throughout the follow-up. The occurrence of invasive carcinoma around the IPMN was not indicated by imaging examinations in any patient. Univariate analysis showed that the size of the cyst at baseline significantly predicted the development of a mural nodule that reached 10 mm during follow-up (P = 0.05). CONCLUSIONS: A mural nodule of 10 mm is appropriate as an indicator of surgery in the follow-up of branch duct IPMN.

Improved diagnosis of well-differentiated hepatocellular carcinoma with gadolinium ethoxybenzyl diethylene triamine pentaacetic acid-enhanced magnetic resonance imaging and Sonazoid contrast-enhanced ultrasonography.

AIM: Two new imaging modalities have been developed recently that are directed at the focal liver lesions: gadolinium ethoxybenzyl diethylene triamine pentaacetic acid (Gd-EOB-DTPA)-enhanced magnetic resonance imaging (MRI) and Sonazoid contrast-enhanced ultrasonography (CEUS). We investigated the usefulness of these modalities for the diagnosis of small (<2 cm), well-differentiated hepatocellular carcinoma (HCC). METHODS: A total of 15 nodules from 13 patients, which were histologically diagnosed as well-differentiated HCC, were subjected to this study. Lesions that showed hypervascularity in the arterial phase and washout in the portal or late non-hemodynamic phase were regarded as HCC in the dynamic studies of all imaging modalities. RESULTS: By multidetector computed tomography (MDCT), six of 15 (40%) nodules were diagnosed as HCC. Gd-EOB-DTPA-enhanced MRI diagnosed HCC in nine of the 15 (60%) nodules. Of the nine nodules that were not diagnosed by MDCT, four could be diagnosed by Gd-EOB-DTPA-enhanced MRI. In Sonazoid CEUS, 10 of 15 nodules (67%) were diagnosed as HCC. Four of nine nodules that could not be diagnosed as HCC by MDCT, were diagnosed by Sonazoid CEUS. A total of 11 of the 15 (73%) nodules were diagnosed as HCC by Gd-EOB-DTPA-enhanced MRI and Sonazoid CEUS in addition to MDCT. CONCLUSION: Gd-EOB-DTPA-enhanced MRI and Sonazoid CEUS had greater diagnostic value for small, well-differentiated HCC than did conventional MDCT.

Slight dilatation of the main pancreatic duct and presence of pancreatic cysts as predictive signs of pancreatic cancer: a prospective study.

PURPOSE: To prospectively determine whether slight dilatation of the main pancreatic duct and pancreatic cysts detected at ultrasonography (US) are predictive signs of pancreatic cancer. MATERIALS AND METHODS: The research protocol was approved by the institutional review board, and written informed consent was obtained from all participants. One thousand fifty-eight subjects (age range, 36-80 years; mean, 61.8 years) with various kinds of abnormal US findings in the pancreas were enrolled from 1999 to 2002, after exclusion of pancreatic neoplasm and other malignant diseases. The endpoint was the subsequent development of pancreatic cancer, and the outcome was determined at the end of December 2007. To identify independent predictive variables for the subsequent development of pancreatic cancer, various baseline characteristics were examined by using a Cox regression model and a Cox proportional hazards model. The cumulative incidence of pancreatic cancer was estimated by using the Kaplan-Meyer method. RESULTS: During the mean follow-up of 75.5 months (+/- 17.3[standard deviation]), pancreatic cancer subsequently developed in 12 of 1058 subjects. The risk of pancreatic cancer was significantly elevated in subjects with slight dilatation (> or = 2.5 mm) of the main pancreatic duct or presence of cyst (s) (> or = 5 mm). The respective hazard ratios were 6.38 (P = .018) and 6.23 (P = .003). For subjects with both findings, the 5-year cumulative risk of pancreatic cancer was 5.62% (95% confidence interval: .37%, 13.03%), and the age-and sex-adjusted hazard ratio compared with the risk in the absence of these findings was 27.50 (P = .002). CONCLUSION: Main pancreatic duct dilatation (> or = 2.5 mm) and presence of a pancreatic cyst (> or = 5 mm) were both strong independent predictors of the subsequent development of pancreatic cancer. (c) RSNA, 2010.

A natural course of main duct intraductal papillary mucinous neoplasm of the pancreas with lower likelihood of malignancy.

OBJECTIVES: Main duct intraductal papillary mucinous neoplasms (IPMNs) of the pancreas include neoplasms with varying likelihood of progression to malignancy. The aim of this study was to investigate a natural course of main duct IPMNs with a lower likelihood of malignancy. METHODS: Twenty main duct IPMNs with a lower likelihood of malignancy, which was defined as mural nodule of less than 10 mm or no visualized mural nodule, and negative result of cytological examination of pancreatic juice, underwent regular ultrasound every 3 months. Special imaging examinations and additional pancreatic juice cytological examination were performed when necessary. Surgery was considered when a mural nodule enlarged to 10 mm or the cytological examination result indicated malignancy. RESULTS: During a mean of 70 months, 12 IPMNs (60%) did not progress and 6 (30%) progressed within a lower likelihood of malignancy. The remaining 2 IPMNs (10%) progressed to meet the criteria for resection, underwent surgery, and were demonstrated to be carcinomas. CONCLUSIONS: Main duct IPMN with a lower likelihood of malignancy was divided into 2 subgroups: neoplasm that progressed and that which did not progress during its natural course. The former should be resected considering its malignant potential, whereas the latter may be managed nonsurgically as long as it stays unchanged.

Scraping cytology with a guidewire for pancreatic-ductal strictures.

BACKGROUND: Strictures of the pancreatic duct may be caused by a variety of underlying pathologic conditions that imaging examinations often fail to define. Conventional procedures for acquisition of a specimen for cytology during ERCP have been limited in their ability to discriminate pancreatic-ductal strictures. OBJECTIVE: Our aim was to discriminate pancreatic-ductal strictures by a new technique of sampling material for cytodiagnosis: scraping cytology with a guidewire. DESIGN: A retrospective study. SETTING: A single cancer center. PATIENTS AND METHODS: Eighty-six patients with pancreatic-ductal strictures composed of 71 malignant and 15 benign diseases were evaluated. Malignant diseases included 70 pancreatic carcinomas and 1 endocrine tumor; benign diseases included the following: 7 chronic pancreatitis, 3 autoimmune pancreatitis, 3 idiopathic pancreatic-ductal strictures, and 2 pancreatic cysts. During ERCP, pancreatic juice was collected with a cannula in the main duct just below the stricture after scraping it with a 0.025-inch hydrophilic guidewire. Cytodiagnosis of the specimen was performed by the Papanicolaou method. MAIN OUTCOME MEASUREMENTS: Diagnostic sensitivities and specificities of scraping cytology with a guidewire for pancreatic carcinoma. RESULTS: Scraping cytology with a guidewire yielded 93% sensitivity, 100% specificity, 100% positive predictive value, 75% negative predictive value, and 94% accuracy. Sensitivities for pancreatic carcinoma in the head, body, and tail of the pancreas were 91%, 100%, and 91%, respectively. Sensitivities for pancreatic carcinoma with a tumor of <20 mm, 21 to 40 mm, 41 to 60 mm, and >61 mm were 95%, 92%, 100%, and 100%, respectively. Pancreatitis subsequent to the procedure occurred in 4 patients (5%), all of whom were cured by conservative treatment. CONCLUSIONS: Benign or malignant pancreatic-ductal strictures were accurately discriminated by scraping cytology with a guidewire during ERCP. The technique yielded high diagnostic sensitivities in pancreatic carcinoma, regardless of the location or size of the tumor.

Contrast-enhanced multiphase dynamic ultrasonography for the characterization of liver tumors.

PURPOSE: The purpose of the study was to introduce our protocol for contrast-enhanced multiphase dynamic ultrasonography (US) and examine the effectiveness of this method for characterizing liver tumors. METHODS: The subjects were 142 patients with liver tumors. The final diagnoses were 58 hepatocellular carcinomas (HCCs), 4 cholangiocellular carcinomas (CCCs), 14 metastases, 29 hemangiomas, 6 cases of focal nodular hyperplasia (FNH), and 31 other benign lesions. The contrast agent used was Levovist. A wide-band pulse inversion harmonic imaging mode was employed. Multiphase dynamic US was achieved by changing the sound transmission interval automatically from 0.3 s to 15.0 s according to a preset menu. Early arterial-phase images were observed at the short interval, and an equilibrium-phase image was observed at the longest interval. After a series of vascular images, a postvascular liver parenchymal image was obtained. Based on previously published criteria, the most compatible diagnosis was noted. The accuracy of this multiphase dynamic US technique for diagnosing focal liver lesions was examined by comparing our results with the final diagnosis based on a prospective study. RESULTS: The overall accuracy of all 142 cases was 93.7%. The sensitivity, specificity, and positive predictive value were, respectively, 100%, 92.9%, and 90.6% for HCC; 88.9%, 97.6%, and 84.2% for metastasis or CCC; 89.7%, 100%, and 100% for hemangioma; and 83.3%, 100%, and 100% for FNH. CONCLUSION: Contrast-enhanced multiphase dynamic US is a highly accurate, safe diagnostic tool for characterizing liver tumors.

Periodic ultrasonography checkup for the early detection of pancreatic cancer: preliminary report.

OBJECTIVES: To introduce our new ultrasonography (US) system for early detection of pancreatic cancer and report its preliminary results. METHODS: The basis of the system is periodic checkups for high-risk patients. Abnormal US findings, such as main pancreatic duct dilatation or pancreatic cyst(s), were indicated as high risk. Special US focusing on the pancreas and a set of serum tests were performed every 3 or 6 months. When some development was detected, additional examinations, including ERP with pancreatic juice cytology, were performed. There were 1098 subjects admitted through the end of May 1998, and the outcomes of these subjects were followed through the end of March 2002. RESULTS: Three hundred ninety-three patients were registered for the periodic checkups. Pancreatic ductal adenocarcinoma was detected in 44 patients: 41 by the initial examination and 3 by the periodic checkups. Surgical resection was performed in 40.9%, and 50% of the resected patients were in stages 0-III. The cumulative 3-year survival rates of the resected patients were 100% in stages 0 and III, 75% in stage I, and 33% in stage IVa. CONCLUSION: Periodic US checkups for patients with main pancreatic duct dilatation or cyst(s) are considered to be an effective method for the early detection of pancreatic cancer.

Deficiency of KIT-positive cells in the colon of patients with diabetes mellitus.

BACKGROUND: Diabetes mellitus is a well-known cause of gastrointestinal dysmotility. The pathogenesis of diabetic gastroenteropathy is mainly considered to be a neuropathy, but the cause of dysmotility remains unknown. Interstitial cells of Cajal (ICC), which express c-kit receptor tyrosine kinase (KIT), are considered to be pacemaker cells for the gastrointestinal movement. Therefore, we investigated a possible involvement of ICC in the pathogenesis of diabetic gastroenteropathy in humans. METHODS: The KIT-positive cells in the proper muscle layer of the colon were detected by immunohistochemistry in patients with diabetes mellitus and normal control subjects. Mast cells, which are also known to express KIT, were detected by staining with Alcian blue. The numbers of KIT-positive cells and Alcian blue-positive cells in the proper muscle layer were counted under the microscope and the number of KIT-positive cells apart from Alcian blue-positive cells was calculated. RESULTS: In the normal control subjects, KIT-positive cells were located at the myenteric plexus region and in the circular muscle layer of the colon. Their distribution pattern was similar to that of ICC. The average number of KIT-positive cells, apart from mast cells (which reflects the number of ICC), in patients with diabetes mellitus was approximately 40% of that found in normal subjects. CONCLUSIONS: Deficiency of ICC might be related to the pathogenesis of diabetic gastroenteropathy in humans.