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Introduction: The Japan Lung Cancer Society (JLCS) and the Japanese Society of Clinical Cytology (JSCC) have proposed a new four-tiered cytology reporting system for lung carcinoma (JLCS-JSCC system). Prior to the proposal, the Papanicolaou Society of Cytopathology (PSC) had proposed a revised reporting system (PSC system), which comprises the “neoplastic, benign neoplasm, and low-grade carcinoma” category (N-B-LG category), in addition to the 4 categories of the JLCS-JSCC system. This study aimed to evaluate the interobserver agreement of the JLCS-JSCC system with an additional dataset with more benign lesions in comparison with the PSC system. Methods: We analyzed 167 cytological samples, which included 17 benign lesions, obtained from the respiratory system. Seven observers classified these cases into each category by reviewing one Papanicolaou-stained slide per case according to the JLCS-JSCC system and PSC system. Results: The interobserver agreement was moderate in the JLCS-JSCC (k = 0.499) and PSC (k = 0.485) systems. Of the 167 samples, 17 samples were benign lesions: 7 pulmonary hamartomas, 5 sclerosing pneumocytomas, 2 squamous papillomas, one solitary fibrous tumor, one meningioma, and one lymphocytic proliferation. There were diverse sample types as follows: 11 touch smears, 3 brushing smears, 2 aspirations, and one sputum sample. Fourteen samples (82.3%) were categorized into “negative” or “atypical” by more than half of the observers in the JLCS-JSCC system. Conversely, 3 samples were categorized as “suspicious” or “malignant” by more than half of the observers in the JLCS-JSCC system. On the other hand, 11 samples (64.7%) were categorized into the N-B-LG category by more than half of the observers in the PSC system. Conclusions: The concordance rate in the JLCS-JSCC system was slightly higher than that in the PSC system; however, the interobserver agreement was moderate in both the JLCS-JSCC and PSC systems. These results indicate that both the JLCS-JSCC and PSC systems are clinically useful. Therefore, both systems are expected to have clinical applications. It may be important to integrate the 2 systems and construct a universal system that can be used more widely in clinical practice.

Objectives: For patients with multiple small-sized pulmonary cancers, a lobectomy can disrupt future therapeutic options for other lesions. It was recently reported that limited pulmonary resections were not inferior to lobectomy for the management of selected peripheral small-sized pulmonary adenocarcinomas. Patients with adenocarcinoma in situ or minimally invasive adenocarcinoma, as proposed by the International Association for the Study of Cancer classification, have been reported to have 100% survival after 5 years. However, that classification can be applied postoperatively. Since 2005, we have been intentionally performing limited pulmonary resection procedures for small-sized adenocarcinoma cases based on intraoperative imprint cytological diagnosis and our classification (Nakayama-Higashiyama's classification). Materials and Methods: A total of 120 consecutive cases were included in this study. Lung tumors were removed intraoperatively by wedge resection, and stump smear cytology was performed, from which the cases were classified into 5 groups based on our classification. When the tumor was classified as Group I or II, the operation was finished. When diagnosed as a more advanced classification, a lobectomy and lymph node dissection were additionally performed. Results: The 5-year survival rate for Group I and II was 100%, while those for Group III and IV-V were 95.8% and 94.4%, respectively. The 5-year disease-free survival rates for Group I and Group II were 100% and 97.1%, respectively, and for Group III and IV-V they were 100% and 94.1%, respectively. Conclusion: Use of cytological findings along with Nakayama-Higashiyama's classification for determining operation procedure is effective for treatment of patients with small-sized pulmonary adenocarcinoma.

Objectives: Small-size lung lesions suspected of being cancer are now often being identified on computed tomography. Correspondingly, a new lung cancer staging system has been proposed by the International Association for the Study of Lung Cancer (IASLC), in which the T1 factor and adenocarcinoma are re-subclassified. Previously, we proposed an intraoperative cytological diagnosis and its classification of small-size lung adenocarcinoma, which correlated significantly with clinical malignancy, to be used for selecting the surgical strategy. In the current study, the correlation of our intraoperative cytological classification with the new 8th IASLC classification was investigated. Materials and Methods: A total of 139 consecutive small-size lung adenocarcinoma cases were surgically resected from 2000 to 2006 and included in this study. Intraoperative stump imprint cytology using these specimens was performed, and the cases were classified into 5 groups based on our classification. The cytological classification was compared with the IASLC classification and the WHO histopathological grading. Results: According to our classification, 32 patients were in Group I, 38 in Group II, 24 in Group III, 27 in Group IV, and 18 in Group V. Compared with the IASLC classification, most of Group I was pTis or pT1mi, and most of Group II was pT1mi or pT1a (p

Introduction: The classification of lung carcinoma is based on small biopsies and/or cytology in 80% of patients with non-small cell carcinoma. However, there is no widely accepted classification system for respiratory cytology. The Japan Lung Cancer Society (JLCS) and Japanese Society of Clinical Cytology (JSCC) have proposed a new four-tiered cytology reporting system for lung carcinoma with the following categories: (1) “negative for malignancy,” (2) “atypical cells,” (3) “suspicious for malignancy,” and (4) “malignancy.” Objective: The aim of this work was to perform an interobserver reproducibility study to confirm the utility of the four-tiered reporting system on respiratory cytological samples. Methods: We analyzed 90 cytological samples obtained with bronchoscopy. Seven observers classified these cases into each category by reviewing one Papanicolaou-stained slide per case according to the three-, four-, and five-tiered reporting systems. Results: The interobserver agreement was fair in the three- (κ = 0.50), four- (κ = 0.45), and five-tiered (κ = 0.45) reporting systems. However, the four-tiered reporting system provided more precise information than the three-tiered reporting system in patient management. The risk of malignancy in the four-tiered reporting system was also stratified well: 19.3% for “negative for malignancy,” 45.6% for “atypical cells,” 74.7% for “suspicious for malignancy,” and 88.1% for “malignancy.” Conclusions: The reporting system proposed by the JLCS and JSCC was designed to enhance the communication between clinicians and pathologists and among different institutions. It is simple and applicable to cytological diagnosis of any respiratory diseases. We propose establishing an international classification for respiratory cytology, harmonizing the reporting systems proposed by different countries.

O presente trabalho teve como objetivo analisar a qualidade da água das represas de captação do Ribeirão das Anhumas e do Ribeirão das Cruzes, bem como da água tratada da estação de tratamento Fonte Luminosa, no município de Araraquara (SP). Para tanto, foram realizadas análises das características físicas, químicas e biológicas da água, estudo de comunidade fitoplanctônica, e testes de toxidade aguda e crônica com o microcrustáceo Ceriodaphnia silvestrii (Cladocera, Crustacea). O período de estudo foi de dezembro de 2000 a novembro de 2001. Na água da represa da Ribeirão das Anhumas, a concentração de oxigênio dissolvido foi, em geral, inferior ao limite estabelecido pela legislação para águas naturais. Tanto na água da represa do Ribeirão das Cruzes como em Anhumas, alguns metais apresentaram concentrações superiores ao limite estabelecido pela legislação para águas naturais. Na água tratada, alguns metais também apresentaram concentrações superiores ao limite estabelecido pela legislação para água potável. As águas das represas de captação não causaram toxicidade aguda nem crônica ao organismo-teste. A água da entrada (após aplicação de cal) da estação de tratamento causou efeitos crônicos principalmente sobre a fecundidade do organismo-teste. A água tratada causou toxicidade aguda e crônica ao organismo-teste. As diatomáceas (Bacillariophyceae) foram dominantes na represa do Ribeirão das Cruzes e, principalmente, em Anhumas. As algas Chlorophyceae foram as mais abundantes na água tratada em ambos os períodos estudados. The present work analysed the water quality of the reservoirs Ribeirão das Cruzes and Ribeirão das Anhumas, used to store and supply water for the Fonte Luminosa water treatment plant, in Araraquara, SP. For that, physical, chemical and biological analyses of water were performed, as well as a study of phytoplankton community. The work also included acute and chronic toxicity testing of the water before and after treatment with the microcrustacean Ceriodaphnia silvestrii (Cladocera, Crustacea) as a test organism. The period of study was between December/2000 to November/2001. Dissolved oxygen was below the established limit by legislation for natural waters at the Ribeirão das Anhumas reservoir. Some metals in the Ribeirão das Anhumas and Ribeirão das Cruzes reservoirs were over the established limit by legislation for natural waters. Some metaIs in treated water were also over legislation for potable water. Reservoir waters did not cause neither acute nor chronic toxicity on test organism. Water with lime, from water treatment plant, caused chronic effects on the reproduction of the test organism. Treated water cause acute and chronic toxicity on test organism, with harmful effects on survival and reproduction. Diatoms (Bacillariophyceae) dominated in the phytoplankton of Ribeirão das Cruzes and Ribeirão das Anhumas reservoirs. Chlorophyceae were the most abundant algae in treated water.

2.6% of pancreatic cancer patients have the primary manifestation of gastrointestinal bleeding. It is not feasible to stop the duodenal hemorrhage caused by the pancreatic cancer infiltration. A 43-year-old woman who was diagnosed as having pancreatic cancer with multiple hepatic metastases and duodenal infiltration was administered gemcitabine and S-1 combination therapy. During the chemotherapy, initially, bleeding occurred due to duodenal infiltration. However, we continued the chemotherapy and duodenal infiltration was markedly reduced in size and did not rebleed. Aggressive chemotherapy contributed to maintenance of performance status as well as improvement of quality of life for the patient.

High-grade pancreatic intraepithelial neoplasia (PanIN-3) is recognized as a precursor lesion of invasive ductal carcinoma (IDC). However, histological evidence that PanIN-3 invades beyond the basement membrane of pancreatic ductal epithelium, that is, the moment PanIN-3 becomes IDC, has not been captured yet. This may be because PanINs which are microscopic papillary or flat lesion rarely develop clinical symptoms and are not detectable on imaging examination. On the other hand, most IDCs were found in the advanced stage with massive invasion. In this report, PanIN-3 obstructed several branch pancreatic ducts and subsequently caused pancreatitis which developed clinical symptom and was detectable as a pancreatic mass in imaging studies. A 65-year-old woman was referred to our institution for further examination of her repeated pancreatitis. Abdominal ultrasound revealed a low echoic mass of 13 mm in diameter in the pancreatic body without upstream dilatation of the main pancreatic duct (MPD). Endoscopic retrograde pancreatography showed a strictured segment of 2 mm in length in the MPD at the pancreatic body. Cytological examination of pancreatic juice revealed adenocarcinoma and distal pancreatectomy was performed. A resected specimen revealed a whitish mass of 15 mm in diameter in the pancreatic body, which was identified as pancreatitis by histological examination. Papillary growth of PanIN-3 was seen mainly in the branch ducts. Each PanIN-3 was located separately in the branch ducts with normal epithelia in the MPD between them. In three adjacent branch ducts, PanIN-3 was observed to be invading microscopically beyond the basement membrane.

Reliable indicators that can intraoperatively determine the absence of nodal metastasis are in great demand to avoid unnecessary lymphadenectomy. However, little has been reported about the intraoperative diagnostic performance of sentinel node (SN) biopsy. Sentinel node biopsy by subserosal or submucosal injection of indocyanine green (ICG) was performed in 241 patients with American Joint Committee on Cancer tumor, node, metastasis staging system, 7th edition, clinical T1 (n = 190) and T2 (n = 51) gastric cancer by two experienced surgeons. All nodes that stained green (green node, GN), representing SNs, were excised before gastrectomy and were sliced into 2-mm sections for intraoperative histological examinations with hematoxylin and eosin staining. The sliced GNs were also examined simultaneously by imprint cytology. The GNs were detectable in 240 patients (3.8 ± 2.4 nodes per patient; range 1–17 nodes; median 3 nodes), and the success rate of detection was 99.6 % (240 of 241). Of 240 patients with a successful detection, 29 were found to have lymph node (LN) metastases; 16 were diagnosed with LN metastases in both GNs and non-GNs, 12 in GNs alone, and 1 in non-GNs alone. The false-negative rate based on the SN concept was 3.4 % (1 of 29). However, two patients with cT1 gastric cancer were diagnosed as intraoperative GN negative but were later confirmed as GN positive by histological examinations of paraffin sections. As an intraoperative diagnosis, the false-negative rate was 10.3 % (3 of 29). Sentinel node biopsy using ICG could be performed intraoperatively within reasonable limits under certain conditions, such as multiplanes for detection, combination use of imprint cytology, and open surgery by experienced surgeons.

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 10 mm, 11–20 mm, 21–30 mm, and more than 31 mm 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 10 mm.

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.

We present a case of malignant mesothelioma of the peritoneum with massive direct invasion to the liver in a 58-year-old Japanese woman. She had no history of asbestos exposure or other malignancies. Abdominal computed tomography revealed one 8-cm intrahepatic mass adjacent to the abdominal wall with peritoneal thickening, multiple smaller nodules in the peritoneal cavity, and intra-abdominal lymphadenopathy. Liver biopsy showed a small cluster of atypical cells similar to epithelial neoplasm, which formed a tubulopapillary structure. The tumor cells were positive for calretinin with strong nuclear and cytoplasmic expression together with podoplanin (D2-40) and some cytokeratins, but were negative for hepatocyte paraffin 1 and other adenocarcinoma markers. We confirmed a diffuse peritoneal mesothelioma with direct invasion to the liver. Liver masses with other peritoneal nodules are mostly encountered as metastatic diseases. However, the possibility of mesothelioma should be considered, even in women without an apparent history of asbestos exposure.

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.

症例は68歳，女性．2002年9月，同時性多発肝転移を伴う膵体尾部内分泌腫瘍に対してTACEを行い，肝転移巣の良好な局所制御が得られたため，3カ月後，原発巣に対し膵体尾部切除術を施行した．切除後1，8，58カ月に，肝転移巣の再燃に対し，計3回のTACEを施行した．2009年7月，急速に増大する左胸壁腫瘤を指摘．穿刺細胞診にて膵内分泌腫瘍胸壁転移と診断し，第3・4・5肋骨を含む胸壁腫瘍広範切除術を施行した．初回治療後96カ月現在，生存中である．膵内分泌腫瘍は同時性多発肝転移を伴っていても，本例のように積極的治療を行うことで，長期生存が得られる可能性が示唆された．また，非常に稀な転移形式ではあるが，膵内分泌腫瘍は胸壁転移を考慮した長期的経過観察が必要と思われた．

Indocyanine green (ICG) fluorescence imaging is a promising technique for detection of sentinel node (SN) as it avoids unnecessary resection. However, the ICG fluorescence imaging system cannot be used in laparoscopic surgery because of technological difficulties. A prototype laparoscopic detection system comprising an electron multiplier charge-coupled device (EM-CCD) as the detector and a xenon lamp as the light source was developed. The CCD camera head was attached to the end of a specially designed laparoscope that could transmit ICG fluorescence. The system allows visualization of both color and fluorescence images. Laparoscopic surgery in ten patients with gastric cancer included SN biopsy using ICG dye, ICG fluorescence images using our system, and laparoscopy-assisted gastrectomy (LAG) with lymphadenectomy. SNs were sliced into 2-mm sections for histological examination and imprint cytology. Immediately after intraoperative ICG injection by endoscopy, the laparoscopic ICG fluorescence imaging system allowed easy visualization of the lymphatic vessels draining from the primary gastric tumor toward the lymph nodes and traced the moving injected dye, whereas lymph vessels and nodes were hardly recognized by ICG green color through a standard laparoscope. Surgeons could confirm the removed lymph nodes stained with ICG by fluorescent imaging. SNs were successfully detected in all patients. Three patients had suspicious metastases in the SNs; two patients had lymph node metastases only in the SNs. Our newly developed laparoscopic ICG fluorescence imaging system is promising in the detection of SNs in laparoscopic gastric cancer surgery. The preliminary results suggest an easier and shorter learning curve of dye-guided SN biopsy in laparoscopic gastric surgery.

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.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.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.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.

目的 : 貯留胆汁細胞診の正診率の向上を目的に, 多施設共同研究にて細胞判定基準を作成した.方法 : 胆膵病変から得られた貯留胆汁細胞診標本上の任意の 38 の細胞集塊を対象に, 細胞判定時に重視した所見を抽出してその意義を検討し, 癌細胞の判定に寄与しうる所見を精選して判定基準を作成した.成績 : 判定基準を以下のように定めた.A の 3 項目あるいは B の 3 項目を満たした細胞を腺癌細胞と判定することができる. C および D は参考所見として重視される.A. 細胞集塊の判定基準 1. 不規則な重積性 2. 核の配列不整 3. 集塊辺縁の凹凸不整B. 個々の細胞の判定基準 1. 核の腫大 2. 核形不整 3. クロマチンの異常C. その他の重視される所見 1. 壊死背景 2. 多彩な細胞集塊 (単個∼集塊) の出現D. 注意すべき点 1. 1 ヵ所の異常のみを取り上げないこと 2. 核内構造の判定 : 長時間放置などによる細胞形態変化があっても, 核内構造がみえれば判定することは可能 3. 良性細胞集塊の参考所見 : (1)核間距離均等, (2)集塊辺縁の周囲に細胞質がみられる結論 : 本判定基準を貯留胆汁細胞診の判定に利用することで, 正診率の向上が期待された.

Os efeitos de cianobactérias sobre organismos aquáticos planctônicos foram avaliados, visando caracterizar e quantificar as cianotoxinas e determinar a toxicidade de uma linhagem em cultura monoespecífica e de florações naturais de reservatórios do rio Tietê, SP. Assim, cultivou-se uma linhagem (NPLJ-4) de Microcystis aeruginosa, reconhecidamente tóxica, em meio ASM-1 a 25°C e fotoperíodo de 12h luz/12h escuro em câmara incubadora, avaliando-se sua toxicidade em diferentes estágios do crescimento populacional (meio e final da fase exponencial, fase estacionária e fase senescente), por meio de testes ecotoxicológicos com os organismos-teste Ceriodaphnia dubia e C. silvestrii. Esses testes foram realizados de acordo com normas padronizadas pela ABNT, sendo utilizados também para avaliar a toxicidade das florações naturais e a eficiência de diferentes processos de tratamento de água na remoção de células, microcistinas e subprodutos de cianobactérias. Os resultados indicaram aumento na concentração de microcistinas com o crescimento populacional da cianobactéria. Os extratos na fase estacionária tiveram menor toxicidade, enquanto nas demais fases causaram efeito tóxico agudo, resultando em valores de CE50; 48h de: 1,4 - 4,7 × \'10 POT.6\' cel/mL (meio fase exponencial), 1,6 - 8,7 × \'10 POT.6\' cel/mL (final fase exponencial), 7,5 - 14,1 × \'10 POT.6\' cel/mL (fase estacionária) e 1,9 - 4,6 × \'10 POT.6\' cel/mL (fase senescente) para C. dubia; e 1,9 - 5,4 × \'10 POT.6\' cel/mL (meio fase exponencial), 1,6 - 10,9 × \'10 POT.6\' cel/mL (final fase exponencial), 10,2 - 15,4 × \'10 POT.6\' cel/mL (fase estacionária) e 2,0 - 4,2 × \'10 POT.6\' cel/mL (fase senescente) para C. silvestrii. Células livres de Microcystis (M. aeruginosa, M. panniformis e M. protocystis) e Pseudanabaena mucicola foram as cianobactérias dominantes nas florações dos reservatórios de Barra Bonita e células livres de Microcystis (M. aeruginosa e M. panniformis), no de Promissão. A dominância das cianobactérias em ambos os reservatórios pode estar relacionada a períodos de estabilidade da coluna de água, razões N/P de 8 - 13 (Barra Bonita) e 19 - 20 (Promissão) na superfície, temperatura da água de 19 - 30°C (Barra Bonita) e 26 - 28°C (Promissão) e disponibilidade de nutrientes (0,05 - 0,26 mg/L de fósforo total para Barra Bonita e 0,01 - 0,05 mg/L P-total para Promissão), devido ao grau de trofia dos reservatórios. A água de ambos os reservatórios, coletada durante as florações, apresentou toxicidade aos dafinídeos, sendo que a água de Barra Bonita foi mais tóxica do que a de Promissão. Todos os extratos brutos de material oriundo das florações naturais apresentaram microcistinas (239 - 1647 µg/L para Barra Bonita e 192 - 1295 µg/L para Promissão) e causaram toxicidade aguda aos dafinídeos, com valores de CE50; 48h de: 87 - 282 mg/L (Barra Bonita) e 146 - 428 mg/L (Promissão) para C. dubia, e 98 - 546 mg/L (Barra Bonita) e 110 - 391 mg/L (Promissão) para C. silvestrii. Concentrações dos extratos a partir de 80 mg/L (Barra Bonita) e 100 mg/L (Promissão) afetaram adversamente a sobrevivência e a reprodução dos dafinídeos. Os resultados mostram riscos à biota natural e à saúde humana, bem como comprometimento dos usos múltiplos dos reservatórios, exigindo ações remediadoras e, sobretudo, preventivas para conter o processo de eutrofização. The effects of cyanobacteria upon aquatic organisms were evaluated, aiming to characterize and quantify the toxins of both, a monospecific cyanobacterial culture and material from natural blooms occurring in the reservoirs of Tietê river, SP. The already known toxic strain NPLJ-4 of Microcystis aeruginosa was cultured in ASM-1 medium at 25 Celsius degrees and 12h light/12h dark in the incubator, in order to evaluate its toxicity at different stages of the culture growth by ecotoxicological tests using the cladocerans Ceriodaphnia dubia and C. silvestrii as test-organisms. These tests were carried out according to the procedures standardized by ABNT, in order to evaluate also the toxicity of natural blooms and the efficiency of different water treatment processes in removing cells, microcystins and by-products of cyanobacteria. The results obtained indicated an increase in the concentration of microcystins along the cyanobacterial culture growth. Extracts from the stationary phase of the culture were less toxic compared with those from the other phases which had acute toxicity and adversely affected cladoceran survival, resulting in EC50; 48h values of 1,4 - 4,7 × \'10 POT.6\' cells/mL (middle exponential phase), 1,6 - 8,7 × \'10 POT.6\' cells/mL (final exponential phase), 7,5 - 14,1 × \'10 POT.6\' cells/mL (stationary phase) and 1,9 - 4,6 × \'10 POT.6\' cells/mL (senescent phase) for C. dubia; and 1,9 - 5,4 × \'10 POT.6\' cells/mL (middle exponential phase), 1,6 - 10,9 × \'10 POT.6\' cells/mL (final exponential phase), 10,2 - 15,4 × \'10 POT.6\' cells/mL (stationary phase) and 2,0 - 4,2 × \'10 POT.6\' cells/mL (senescent phase) for C. silvestrii. Cells of Microcystis (Microcystis aeruginosa, M. panniformis and M. protocystis) and Pseudanabaena mucicola were cyanobacteria species dominant in the Barra Bonita reservoir and cells of Microcystis (M. aeruginosa and M. panniformis), in the Promissão reservoir. The dominance of cyanobacteria in both studied reservoirs was related to the stability of the water column, N/P ratios of 8 to 13 (Barra Bonita) and 19 to 20 (Promissão), high water temperatures (19 - 30°C for Barra Bonita and 26 - 28°C for Promissão) and high nutrient availability (0,05 - 0,26 mg/L total phosphorus for Barra Bonita, and 0,01 - 0,05 mg/L total P for Promissão) as a consequence of the trophic state of the reservoirs. The water from Barra Bonita reservoir during the cyanobacterial blooms was more toxic to daphnids than that from Promissão reservoir. Crude extracts from all cyanobacteria blooms tested presented microcystins (239 - 1647 µg/L for Barra Bonita and 192 - 1295 µg/L for Promissão) and caused acute toxicity to daphnids, resulting in EC50; 48h values of 87 - 282 mg/L (Barra Bonita) and 146 - 428 mg/L (Promissão) for C. dubia, and 98 - 546 mg/L (Barra Bonita) and 110 - 391 mg/L (Promissão) for C. silvestrii. Crude extracts concentrations above 80 mg/L to Barra Bonita and 100 mg/L to Promissão adversely affected the survival and reproduction of daphnids. The results obtained evidenced the risks to the natural biota and possibly to the human health, and can therefore jeopardize the multiple uses of the reservoirs. They reveal the urgent necessity for remedial action, particularly to slow down and to prevent eutrophication.

During a cyanobacterial bloom in a eutrophic environment, particularly at the end when decomposition occurs, toxic compounds such as the cyanotoxins and the lipopolysaccharides can be released in high concentrations into the water column damaging aquatic organisms. In this work, the effects of this release of toxic compounds during a cyanobacterial bloom were investigated. The acute and chronic toxicity of cyanobacterial crude extracts from two natural blooms in the Barra Bonita and Ibitinga reservoirs (Middle Tietê River, São Paulo State, Brazil) and of a toxic strain cultured in the laboratory were tested. The cladocerans Daphnia similis, Ceriodaphnia dubia and Ceriodaphnia silvestrii were used as test organisms. In the chronic toxicity tests, only a native cladoceran found in Brazilian freshwaters, Ceriodaphnia silvestrii, was used. Microcystins were detected in all cyanobacterial samples. The acute toxicity tests showed that the crude bloom material extract from the Ibitinga Reservoir (48-h EC(50) values between 32.6 and 35.8 microg microcystin g(-1) of freeze-dried material) exhibited higher toxicity to cladoceran than did the crude bloom material extract from Barra Bonita Reservoir (48-h EC(50) values between 46.0 and 80.2 microg microcystin g(-1) of freeze-dried material). The chronic toxicity test data showed that the three extracts reduced the fecundity of C. silvestrii, and the crude extract of Barra Bonita Reservoir bloom material also affected the survival of this cladoceran. Both acute and chronic tests effectively prognosticated possible changes in the cladoceran population, and probably other components of the biota due to cyanobacterial blooms in natural aquatic ecosystems.

Background Fluoroscopy-guided bronchoscopy is a safe and routine method used to obtain a histologic or cytologic specimen of peripheral lung nodules, but it has low sensitivity in diagnosing malignant tumors. Although feedback from rapid cytology tests are expected to improve diagnostic rates, the value of the routine use of rapid cytology tests has not been established. Materials and Methods We prospectively studied 657 patients with suspected peripheral malignant lung lesions on chest computed tomography who underwent fluoroscopy-guided bronchoscopy between January 2002 and December 2004. Rapid on-site cytopathologic examinations (ROSE) were performed during bronchoscopic examinations. The additional approach to the lesions was performed immediately after conventional bronchoscopic examinations when ROSE was not considered diagnostic. Results There were 528 patients diagnosed as having malignant lesions. In 477 of these patients (90.3%), final malignant diagnosis was established by the initial bronchoscopy. Among these, 84 patients (15.9%) were diagnosed only with the additional feedback from ROSE. Of 240 peripheral lesions ≤2 cm, 174 were found to be malignant. Without ROSE, 110 (63.2%) of peripheral malignant lesions were diagnosed by bronchoscopy. The integration of ROSE enabled us to diagnose an additional 40 patients (23.0%) by bronchoscopy. ROSE improved diagnostic yield independent of the site and histology of the lesions and experience of the operators. Conclusion ROSE increased the diagnostic yield of bronchoscopy from 74.4% to 90.3% and therefore is an effective reinforcement in bronchoscopic diagnosis of peripheral pulmonary malignancies. The use of ROSE in routine bronchoscopy should be encouraged.

目的．末梢性肺野病変に対する呼吸器細胞診の意義を明らかにする．方法．医療判断学の立場から，末梢性肺野病変の治療方針決定の流れの中での，画像診断と，術前病理細胞診断の意義を検討した．結果．高分解能CTで，スリガラス状陰影を呈する場合，がんである事前確率は高いため，術前病理細胞診断が陽性に出ても，事後確率はあまり上昇しない．また病巣への命中の確認が非客観的であるため陰性という結果も信頼性が乏しく，臨床医は術前細胞組織診断の正否に関わらず，患者への切除を勧めている．一方高分解能CTで充実性病変を呈する場合は，がんである事前確率が低いため，術前診断での陽性結果は，事後確率を大幅に向上させる．結論．スリガラス状陰影を呈する病変への，術前細胞組織診断の意義は乏しい．臨床医は画像診断や臨床情報を適切に判断しながら診断のステップを選択すべきであり，また内視鏡医は少なくとも細胞診や組織診の適切な標本作製の手技を理解する必要がある．

To date, surgical resection has offered the only chance for complete cure in the treatment of invasive ductal adenocarcinoma of the pancreas. However, the 5-year survival rates after resection of this cancer have been reported to be as low as 10–30%,1,2 and more than half of patients die of cancer relapse within 2 postoperative years. Such a poor result is largely attributed to a high incidence of local recurrence3,4 after curative (R0) resection had been performed without macroscopic or microscopic cancer residual. In accounting for this fact, we can easily speculate that a minute and occult focus of the cancer might have been left behind in the pancreatic bed because pancreatic cancer cells are likely to infiltrate into the surrounding soft tissues. If occult cancer residual could be predicted correctly and quickly, even after resection, we may have a chance to treat it immediately before it can grow, form an obvious tumor mass, and spread beyond the pancreatic bed, by adding some locoregional therapy. For instance, the GITSG5 succeeded in improving the patient’s survival by combining postoperative radiation therapy on the pancreatic bed with an intravenous administration of 5-fluorouracil. Either peritoneal or pleural lavage cytology has been widely performed to strictly select the operative indication for cancer patients.6,7 However, in addition to preoperative pleural lavage cytology, Higashiyama8 performed postoperative cytology after lung cancer resection to confirm the operative curability. He described that the patients’ survival periods were reduced because of a high incidence of local recurrence among the patients whose cytologic results had shifted from negative to positive following resection, suggesting the need for adjuvant locoregional therapy. Additionally, Doki9 performed a similar analysis after resecting squamous cell carcinomas of the esophagus and showed that patients with positive postoperative cytology had a short survival based on a high incidence of distant metastasis. He recommended systemic chemotherapy rather than radiation therapy for positive patients. Such knowledge is essential in selecting the most suitable adjuvant therapies for each postoperative patient. However, there have been no previous reports of postoperative cytology after resecting cancers of the intra-abdominal organs, including pancreatic cancer. Thus, this study is conducted to investigate whether the postoperative cytology of drained fluid from the pancreatic bed can correctly predict both the patient’s prognosis and the site of disease relapse after a macroscopically curative resection of pancreatic cancer.

Endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) is accurate in cytological diagnosis of pancreatic lesions. Our aim was to determine optimal number of needle passes in EUS-FNA for pancreatic lesions without onsite cytopathologist, who is not routinely available to participate in the procedure.Results of all needle passes in EUS-FNAs for 117 pancreatic neoplasms in 115 patients were reviewed retrospectively. Factors that required 2 or more needle passes for correct diagnosis were identified by multivariate logistic regression analysis. In each lesion group defined by the factors that required 2 or more passes and were known at the time of EUS-FNA, number of needle passes was regarded as optimal when an increase in diagnostic sensitivity by an additional needle pass did not reach 10%.Size of 15 mm or less (OR 4.58, 95% CI 1.70-12.3, P 0.01), location of head (OR 5.02, 95% CI 1.82-13.9, P 0.01), and neuroendocrine tumor (NET) (OR 5.04, 95% CI 1.38-18.4, P = 0.01) independently required 2 or more needle passes. Optimal numbers of needle passes for lesions of 15 mm or less in the head, those of more than 15 mm in the head, those of 15 mm or less in the body or tail, and those of more than 15 mm in the body or tail were 3, 2, 2, and 1, respectively. When these numbers of needle passes were performed, 93% of pancreatic lesions were correctly diagnosed.Optimal numbers of needle passes in EUS-FNA for pancreatic lesions without onsite cytopathologist were between 1 and 3.

Background: We detected benign pancreatic cysts in more than half of 12 cases of in situ pancreatic cancer. A few investigators, having detected K-ras mutation in pancreatic juice before the clinical diagnosis of pancreatic cancer, have suggested that this mutation might be an early event in pancreatic oncogenesis. Therefore, in the present study, we evaluated whether benign pancreatic cysts are a precancerous condition as reflected by K-ras mutation in pancreatic juice. Methods: Pancreatic juice was collected through endoscopic cannulation of the pancreatic duct. Analysis of the mutations was performed using the polymerase chain reaction–preferential homoduplex formation assay. Results: The frequencies and types of K-ras point mutations and the rate of multiplicity of K-ras mutations in patients with benign pancreatic cyst were the same as those with pancreatic cancer. Conclusions: Multiple K-ras codon 12 mutations in the pancreatic juice of patients with benign pancreatic cysts are present as frequently as those with pancreatic cancer. These results indicate that patients with benign cysts may be at a high-risk for the development of pancreatic cancer.

OBJECTIVE To establish new criteria for cytodiagnosis of hepatocellular carcinoma by comparing cytologic findings of hepatocellular carcinoma with those of liver cirrhosis. STUDY DESIGN Review of cytologic findings of hepatocellular carcinoma on preoperative aspiration biopsy of 31 lesions from 27 patients who underwent surgical resection and comparison of these findings with those of liver cirrhosis in 17 patients. RESULTS In the 11 lesions of moderately and poorly differentiated hepatocellular carcinoma, significant cytologic findings included monotonous and abundant cytoplasm, thick cytoplasm, increased nuclear/cytoplasmic ratio, irregular nuclear contours, increased chromatin density, intranuclear vacuoles and naked nuclei. In the 20 lesions demonstrating well-differentiated hepatocellular carcinoma, significant cytologic findings included monotonous and scant cytoplasm, well-defined cytoplasmic borders, thick cytoplasm, eccentric nuclei, increased nuclear/cytoplasmic ratio, thick nuclear membranes and increased chromatin density. We established the criteria for moderately and poorly differentiated hepatocellular carcinoma as including three cytologic parameters: increased nuclear/cytoplasmic ratio, irregular nuclear contours and increased chromatin density. We also established the criteria for well-differentiated hepatocellular carcinoma as including six cytologic parameters: monotonous cytoplasm, scant cytoplasm, well-defined cytoplasmic borders, thick cytoplasm, eccentric nuclei and increased nuclear/cytoplasmic ratio. For all 31 hepatocellular carcinoma lesions, including 27 lesions that were < or = 2 cm in diameter, both sensitivity and specificity were 100% by concurrently employing both criteria. CONCLUSION The new criteria for cytodiagnosis we established were useful for differentiating hepatocellular carcinoma from liver cirrhosis. In particular, our criteria ensured appropriate diagnostic accuracy for well-differentiated hepatocellular carcinoma.

目的．末梢性小型肺野病変は，画像診断の進歩により病理細胞学的な診断を得ずに切除されることが多くなってきた．我々は迅速細胞診のテクニックを用い，術前診断能の向上と術中予後情報の提供を行っている．方法と結果．気管支鏡検査の際には，検査場で1分間で染色できる迅速ショール染色変法を行い，陰性であれば極細径気管支鏡下の4回生検を行っている．このことにより2 cm以下肺癌例の診断率は64％から92％に向上した．また2 cm以下腺癌の術中捺印細胞診を5型に分類し，予後との関連性を明らかにした．今後術中に迅速報告することにより，縮小手術の術中適応の補助診断に応用可能か検討中である．結論．呼吸器細胞診は，適切な標本作製さえ行えば，様々な情報を速やかに提供することが可能である．

During pancreatoduodenectomy for adenocarcinoma of the pancreatic head, we frequently encountered cases in which the superior mesenteric-portal venous confluence (SMPVC) was involved with cancer. With regard to the indication of the concomitant SMPVC resection, as suggested by recent papers, a better long-term outcome would be expected if the cancer invasions were limited to the tunica adventitia or media of the SMPVC wall. Since this raised fears whether such a small SMPVC invasion was always detectable by macroscopic inspection alone, we have performed an intraoperative cytology on the touch smear of the exposed SMPVC wall for 23 patients with pancreatic head cancer. All of their SMPVCs were separated from the pancreatic head and appeared to be intact at a macroscopic level. As a result of the cytologic examination, however, 7 patients (30%) were newly diagnosed as having cancer cells on the SMPVC wall, and they received an additional resection of the SMPVC. Postoperative histology indicated that cancer invasion into the SMPVC wall was present in 6 of the 7 patients, and that the cancer invasions were limited in the tunica adventitia in 5 patients and to the tunica media in 1 patient. Thus, in order not to miss the chance of cure by SMPVC resection, our intraoperative cytology on the touch smear of the SMPVC is worth performing more actively on the macroscopically intact-looking SMPVC during resection of pancreatic cancer.

For detection of early cancer of the pancreas, endoscopic aspiration cytology of pancreatic juice without endoscopic retrograde pancreatography was performed in 64 consecutive outpatients who had symptoms or findings that suggested pancreatic disease. Patients with positive or suspicious cytologic results or abnormal US findings were admitted and underwent detailed examinations. Positive and suspicious cytologic results were obtained in 2 and 10 patients, respectively. Of those with positive and suspicious cytologic results, two, and one patient, respectively, were ultimately found to have pancreatic neoplasms. Of these three resected specimens, one was in situ carcinoma and two presented marked atypia. All patients were alive with no evidence of recurrence. No further cases of pancreatic neoplasm were found. Complications from the procedure did not develop in any patient. This technique is useful in the diagnosis of early neoplasms of the pancreas, because it is simple and safe to perform for outpatients.

膵癌, 慢性膵炎, 膵嚢胞症例と正常対照から内視鏡的に採取した膵液を用いてK-ras遺伝子exonlcodon12の点突然変異の検索と膵液細胞診を行い, 両者を対比して膵癌の診断におけるK-燃点突然変異の役割を検討した.K-ras点突然変異の検索はenriched polymerase chain reaction (PCR)-single-strand conformation polymorphism (SSCP) 法によって行い, 次いでdirect sequence法によって塩基配列を決定した.K-ras点突然変異は膵癌症例では15例中13例 (87%) と高頻度に検出されたが, 慢性膵炎13例中7例 (53%), 膵嚢胞12例中8例 (67%) にも認められた.正常対照から採取した膵液にはK-中央病院点突然変異は認められなかった.これらの非癌変異陽性症例の膵液細胞診では核の腫大, 核の極性の乱れ, 細胞重積を示す異型細胞が認められた.以上の結果より膵液K-ras点突然変異は膵癌の診断よりもむしろ膵癌ハイリスク群の設定に有用ではないかと考えられた.

Background. The early diagnosis of pancreatic carcinoma through the use of traditional radiographic or ultrasonographic methods is extremely difficult. Methods. To detect an early and potentially curable cancer of the pancreas, endoscopic retrograde pancreatography (ERP) and aspiration cytology of pure pancreatic juice were performed in 295 consecutive patients who had symptoms or findings that suggested pancreatic disease but in whom there was neither a pancreatic mass nor ductal stenosis. Results. Positive cytologic results were obtained in 12 patients (4%). With the aid of intraoperative cytodiagnosis, all 12 early neoplasms of the pancreas were successfully resected. Of these 12 resected specimens, 4 were adenocarcinoma with minimal invasion, 3 were in situ adenocarcinoma and 5 were marked atypia. All 12 patients were alive with no evidence of recurrence for an average of 32 months after surgery. The 283 patients who had negative ERP-cytology results were observed, but no further cases of pancreatic cancer were found. Conclusions. Because ERP-cytology is simple to perform, safe, and reliable, it is useful in the diagnosis of patients who have early neoplasm of the pancreas.

Our aim was to investigate how 2cm or smaller pancreatic cancers were detected successfully in recent years.Diagnostic clues and subsequent examinations that detected 15 histologically confirmed 2 cm or smaller pancreatic cancers were reviewed.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%).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.

We present the first reported case of intraductal polypoid growth (IPG) variant of pancreatic acinar cell carcinoma (ACC) metastasizing to the intrahepatic bile duct. A 58-year-old Japanese woman had previously presented with obstructive jaundice and a 7.0 cm mass in the pancreatic head. She underwent biliary drainage for 2 months followed by pancreatectomy. Histological examination revealed a carcinoma with acinar pattern, immunohistochemically positive for trypsin, and acinar cell carcinoma was diagnosed. IPGs were prominent in the main pancreatic duct and its tributaries, extending into the intrapancreatic bile duct with tumor casts in the lumen. Imaging examinations 6 years later revealed a growing lesion within the intrahepatic bile duct. Needle biopsy examination suggested metastasis of ACC, and she underwent chemoradiation therapy and partial hepatectomy. Histological examination demonstrated ACC confined to the intrahepatic bile duct. The localization of metastasis and slow growth may indicate indolent biologic behavior of the IPG variant.

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. In a tertiary referral center, EUS-FNAs for 120 suspected pancreatic malignancies in 115 patients based on other imaging studies were evaluated retrospectively. 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. 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.

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. 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. 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. 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.

Intrathoracic goiters account for 3.1%-5.8% of all mediastinal masses. Primary intrathoracic goiters, which receive their blood supply from mediastinal vessels and disconnect at the cervical thyroid, are even rarer. This report presents two cases of surgical resection of benign and malignant primary intrathoracic goiters. Usefulness of a whole-body (18)F-fluorine-2-fluoro-D: -glucose positron emission tomography/computed tomography study and intraoperative fine-needle aspiration cytology in the management of primary intrathoracic goiters is discussed.

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.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.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).A mural nodule of 10 mm is appropriate as an indicator of surgery in the follow-up of branch duct IPMN.

The detection of intraperitoneal free cancer cells in colorectal cancer (CRC) patients is associated with a poorer prognosis. The aim of this study was to investigate the effects of intraperitoneal chemotherapy (IPC) with mitomycin C (MMC) on preventing peritoneal recurrence in CRC patients with positive peritoneal lavage cytology findings.A total of 52 CRC patients who had no clinically confirmed peritoneal dissemination and whose status of peritoneal lavage cytology was positive were investigated. Conventional peritoneal lavage cytology was performed. Overall, 31 of the 52 patients (59.6%) were administered IPC with MMC. Before closure of the abdomen, 4 silicon catheters were inserted into peritoneal cavity. After closure, the perfusate (diluting 20 mg MMC with 500 ml saline) was instilled from the catheter, and all catheters were clumped. All catheters were opened 1 h later.The mean follow-up period was 83.1 months. According to univariate analyses of all 52 patients and the subgroup of 36 patients with stage II or III tumors, patients with IPC had a significantly better peritoneal recurrence-free survival and cancer-specific survival than patients who did not receive IPC (P0.005). In multivariate analysis, IPC remained an independent prognostic factor for peritoneal recurrence-free survival in all patients.It appears that IPC with MMC is an effective treatment to prevent peritoneal recurrence and prolong the cancer-specific survival in CRC patients without peritoneal dissemination, but who have positive peritoneal lavage cytology. It is necessary to verify the effectiveness of IPC with MMC in a prospective trial.

Background. Although cytologic examination of pure pancreatic juice obtained with a duodenofiberscope has been useful for the diagnosis of pancreatic carcinoma, the rate of false-negative results is reported to be high. To eliminate these false-negative results, the authors developed a new technique, endoscopic retrograde intraductal catheter aspiration cytology, especially for an accurate cytologic diagnosis of carcinoma of the body or tail of the pancreas. Methods. The accuracy of conventional cytologic examination of pure pancreatic juice was assessed in 25 patients with pancreatic carcinoma, 29 patients with pancreatitis, and 52 control subjects. Pure pancreatic juice was collected from the pancreatic duct by endoscopic cannulation using a videoimaging duodenoscope after intravenous administration of secretin. The new endoscopic retrograde intraductal catheter aspiration technique was used in four patients with carcinoma of the body or tail of the pancreas and five patients with localized pancreatitis in whom a correct diagnosis was not made by previous cytologic examination of pure pancreatic juice. Results. Positive cytologic findings were obtained in 76% of the patients with pancreatic carcinoma. Positive cytologic results were more frequent in patients with carcinoma of the head of the pancreas than in those with carcinoma of the body or tail. By the new technique, positive cytologic results were obtained in all of the patients with pancreatic carcinoma. This technique caused no severe complications. Conclusions. This procedure of endoscopic retrograde intraductal catheter aspiration cytology seems useful for diagnosis of pancreatic carcinoma.

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 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.

Purpose: The clinical significance of intraoperative pleural lavage cytology (PLC) for lung cancer has been insufficiently elucidated. We therefore reviewed the surgical results of lung cancer patients without carcinomatous pleuritis followed up over the long term to elucidate PLC implications. Patients and methods: PLC was performed immediately after thoracotomy in consecutive lung cancer patients without carcinomatous pleuritis undergoing tumor resection between 1988 and 1997. Postoperative follow-up was generally performed for at least 5 years while checking tumor recurrence and survival. Results: Eighty-nine (13.1%) of 679 patients had positive PLC findings, which were observed more frequently in patients with advanced stage, larger tumor size, higher involvement of the pleura, lymph node, lymphatics and vessels. The overall 5- and 10-year survival rates in PLC-positive patients were 43% and 25%, respectively, while those in PLC-negative patients were 66% and 58%, respectively (p < 0.0001). Among 395 patients with stage I disease, 35 (8.9%) showed PLC-positive findings, and their overall survival rate was significantly poor compared with those with PLC-negative findings (p < 0.0001). In contrast, such differences were not observed among patients with more advanced stage diseases. In regard to histological type, a difference in the postoperative survival rate according to PLC status was statistically found in adenocarcinoma type (p < 0.0001), but not in squamous cell carcinoma type (p = 0.24). According to multivariate analysis, PLC was an independent prognostic factor for all tested patients (p = 0.007, hazard ratio = 0.60) as well as for those with stage I disease (p = 0.0135, hazard ratio = 0.51). When examining postoperative pleural recurrence, the rate for PLC-positive patients was statistically higher than that for PLC-negative patients (p < 0.0001, hazard ratio = 0.08). Interestingly, late pleural recurrence more than 5 years occurred in five (5.6%) of PLC-positive patients, all of whom were included in stage I. Conclusions: Based on the present analysis of long-term follow-up after operation,PLC mayalso be an independent prognostic factor. In particular, the PLC status of patients with stage I disease or adenocarcinoma type has an important impact on survival. PLC-positive findings may be a high risk for postoperative pleural recurrence. For PLC-positive patients with stage I disease, careful serial follow-up for more than 5 years is required while paying attention to late pleural recurrence. # 2008 European Association for Cardio-Thoracic Surgery. Published by Elsevier B.V. All rights reserved.

Synchronous occurrence of intraductal papillary mucinous neoplasm (IPMN) and ductal carcinoma of the pancreas has been reported. Branch duct IPMNs with lower likelihood of malignancy are not submitted to resection but are followed-up, so ductal carcinoma may develop during the follow-up. The development of ductal carcinoma of the pancreas during follow-up of branch duct IPMNs was investigated.60 patients with branch duct IPMN who had an intraductal tumour of10 mm on imaging examinations and a negative result for malignancy on cytological examination of the pancreatic juice were investigated. They were followed-up mainly by ultrasonography (US), and additionally by endoscopic ultrasonography (EUS), CT, magnetic resonance cholangiopancreatography (MRCP) or endoscopic retrograde cholangiopancreatography (ERCP) with cytological examination of the pancreatic juice for an average period of 87 months.Ductal carcinoma of the pancreas distinct from IPMN developed in 5 of 60 (8%) branch duct IPMNs during follow-up. The 5-year rate of development of ductal carcinoma was 6.9% (95% CI 0.4% to 13.4%), the incidence of ductal carcinoma was 1.1% (95% CI 0.1% to 2.2%) per year and the standardised incidence ratio of development of ductal carcinoma was 26 (95% CI 3 to 48). Patients70 years old developed ductal carcinoma significantly more frequently than those under 69. Four of five ductal carcinomas identified during follow-up were resectable. Cancer developed in IPMN in 2 of 60 (3%) branch duct IPMNs during follow-up.During follow-up of branch duct IPMNs, ductal carcinoma of the pancreas not infrequently developed distinct from IPMN. In the follow-up of IPMN, special attention should be paid to the development of ductal carcinoma of the pancreas.

OBJECTIVES Detection of telomerase activity in pancreatic juice samples by telomeric repeat amplification protocol (TRAP) has been shown to be a useful diagnostic test for pancreatic cancer. However, some investigations suggested that the activity was not specific to pancreatic juice from pancreatic cancer. In the present study using an in situ TRAP assay, we investigated the specificity of telomerase activity in pancreatic juice for pancreatic cancer. METHODS Pancreatic juice were obtained endoscopically at endoscopic retrograde cholangiopancreatography from 10 patients with pancreatic cancer, 4 with intraductal papillary neoplasm, and 3 with normal pancreas. In situ telomerase activity in pancreatic juice samples was examined by in situ TRAP assay and was compared with the results of cytological examination. RESULTS Of 10 samples from pancreatic cancer, high telomerase activity in situ was detected in 9 and cancer cells in 7. Of 4 samples from intraductal papillary neoplasm, low telomerase activity in situ and mild atypical cells were detected in 2. Telomerase activity in situ was detected in none of 3 samples from normal pancreas. CONCLUSIONS Detection of in situ telomerase activity in pancreatic juice might help discriminate pancreatic cancer from other pancreatic diseases.

BACKGROUND. Intraductal papillary mucinous neoplasm (IPMN) is a recently discovered pancreatic tumor that has continuous or discontinuous (skip) lesions. Recent reports suggest a higher frequency of cancer recurrence in the remnant pancreas after surgical resection of IPMN. It is therefore important to precisely detect intraductal cancer extension and skip lesions when resecting IPMN. METHODS. Both intraoperative histologic examination of the surgical margin and cytologic examination of the pancreatic juice from each pancreatic segment (head, body, or tail) were performed on 43 IPMN patients. In addition to the preoperatively planned resection, 1 or 2 pancreatic segment(s) were additionally resected if the pancreatic juice tested positive in cytology. When a surgical margin was positive but the cytology in the remaining segment was negative, a subsegment (2-cm slice in width) was additionally resected until a negative margin was confirmed. RESULTS. Twenty-five patients (58%) demonstrated negative results in both histology and cytology obtained from the segment(s) that were not initially intended to be removed. In contrast to the preoperative estimation, 5 patients were found to have a positive surgical margin and negative cytology, 5 patients demonstrated a negative surgical margin and positive cytology, and 8 patients demonstrated a positive surgical margin and positive cytology. Investigations of the resected specimens revealed that 8 patients (19%) had skip lesions in addition to the main lesion. Logistic regression analysis revealed that patients with a dilated main pancreatic duct, or those with cancerous lesions in the main tumors, were at high risk for positive histology and/or cytology. CONCLUSIONS. Using intraoperative frozen-section histology and pancreatic juice cytology, 18 out of 43 patients in the current study (42%) required additional resection of the pancreas. A necessary and sufficient range of resection should be determined by intraoperative examination. Cancer 2006. © 2006 AmericanCancer Society.