Cytology Reporting System for Lung Cancer from the Japan Lung Cancer Society and the Japanese Society of Clinical Cytology: An Extensive Study Containing More Benign Lesions.

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.

Intraoperative Diagnosis and Surgical Procedure with Imprint Cytology for Small Pulmonary Adenocarcinoma.

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.

Novel Imprint Cytological Classification for Small Pulmonary Adenocarcinoma Using Surgical Specimens: Comparison with the 8th Lung Cancer Staging System and Histopathological Classification.

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<0.001). There was also a significant relationship between lymph node metastasis and our cytological classification (p<0.001). The histological patterns according to the WHO classification also had a significant relationship with our classification (p<0.001). Conclusion: Our cytological classification correlated not only with the T classification, but also with the adenocarcinoma subclassification of the 8th IASLC classification.

Cytology Reporting System for Lung Cancer from the Japan Lung Cancer Society and Japanese Society of Clinical Cytology: An Interobserver Reproducibility Study and Risk of Malignancy Evaluation on Cytology Specimens.

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.

Optimal number of needle passes in endoscopic ultrasound-guided fine needle aspiration for pancreatic lesions.

OBJECTIVES: 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. METHODS: 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%. RESULTS: 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. CONCLUSIONS: Optimal numbers of needle passes in EUS-FNA for pancreatic lesions without onsite cytopathologist were between 1 and 3.

Duodenal Hemorrhage from Pancreatic Cancer Infiltration Controlled through Combination Therapy with Gemcitabine and S-1.

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.

Microinvasion of high-grade pancreatic intraepithelial neoplasia.

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.

Intraoperative diagnosis using sentinel node biopsy with indocyanine green dye in gastric cancer surgery: an institutional trial by experienced surgeons.

BACKGROUND: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

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.

Intraductal polypoid growth variant of pancreatic acinar cell carcinoma metastasizing to the intrahepatic bile duct 6 years after surgery: a case report and literature review.

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.

Surgical management of primary intrathoracic goiters.

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.

Malignant mesothelioma of the peritoneum invading the liver and mimicking metastatic carcinoma: a case report.

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.

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.

Effects of intraperitoneal chemotherapy with mitomycin C on the prevention of peritoneal recurrence in colorectal cancer patients with positive peritoneal lavage cytology findings.

BACKGROUND: 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. METHODS: 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. RESULTS: 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 (P < 0.005). In multivariate analysis, IPC remained an independent prognostic factor for peritoneal recurrence-free survival in all patients. CONCLUSIONS: 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.

Laparoscopic detection of sentinel node in gastric cancer surgery by indocyanine green fluorescence imaging.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

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.

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.