Intraoperative rapid immunohistochemistry with noncontact antibody mixing for undiagnosed pulmonary tumors.

Knowledge of the histologic type and primary origin of pulmonary tumors is essential when preparing a surgical strategy. Intraoperative diagnosis of hematoxylin and eosin (H&E)-stained frozen sections is the gold standard, but reliable pathology requires time-consuming immunohistochemistry (IHC) to distinguish among histological types/organ origins and to analyze molecular status. The aim of this study was to evaluate the clinical reliability of a new rapid-IHC technique for intraoperative diagnosis of pulmonary tumors. In total, 169 patients with undiagnosed pulmonary tumors were enrolled in a multicenter prospective observational study. At three institutes, pulmonary tumor samples were collected through core needle biopsy and/or surgery to determine surgical strategies. Using a new device for rapid IHC, we applied a high-voltage, low-frequency alternating current (AC) field, which mixes the available antibody as the voltage is switched on/off. Rapid IHC can provide tumor histologic type/origin diagnoses within 20 min, as opposed to the 3-6 h required for conventional IHC. No false diagnoses of malignancy were rendered in any of the cases when using simple H&E staining. With H&E staining alone, the overall definitive diagnosis rate, the rate of defined tumor origin, and the rate of determined histological type were 76.92%, 85.80%, and 90.53%, respectively. When rapid IHC was added, those rates were significantly improved to 88.76%, 94.67%, and 91.72%, respectively. By providing prompt and accurate intraoperative histological/molecular analysis, rapid IHC driven by AC mixing could serve as an effective clinical tool guiding the surgical strategy for undiagnosed pulmonary tumors.

Financial burden and health-seeking behaviors related to chronic diseases under the National Health Insurance Scheme in Bolikhamxay Province, Lao PDR: a cross-sectional study.

BACKGROUND: Chronic diseases pose a serious threat to health and longevity worldwide. As chronic diseases require long periods of treatment and may become serious conditions, the ensuing financial burden is often worse than that for non-chronic diseases. In 2016, the Lao PDR implemented the National Health Insurance (NHI) system, which covers select provinces. However, data on health service accessibility and the financial burden on households, especially those with chronically ill members covered by the NHI, are scarce. METHODS: This study used a cross-sectional design. Data collection was conducted in Bolikhamxay province (population = 273,691), from January 15 to February 13, 2019. In total, 487 households, selected through stratified random sampling, were surveyed via questionnaire-based interviews. Healthcare service usage and financial burden were examined. RESULTS: A total of 370 households had at least one member with self-reported health issues within the last 3 months prior to the interview, while 170 had at least one member with a chronic condition. More than 75% of the households accessed a health facility when a member experienced health problems. The majority of households (43.2%) spent the maximum value covered by the NHI, but households in the second largest group (21.4%) spent 10 times the maximum value covered by the NHI. The prevalence of catastrophic health expenditure (i.e., health-related expenditure equivalent to > 20% of total income) was 25.9% (20% threshold) and 16.2% (40% threshold). Through logistic regression, we found that the major factors determining financial catastrophes owing to health problems were household members with chronic illness, hospitalization, household poverty status, household size (for both the 20 and 40% thresholds), visiting a private facility (20% threshold), and distance from the province to the referral hospital (40% threshold). CONCLUSIONS: The NHI system has had a positive effect on households' access to health facilities. However, catastrophic health expenditure remains high, especially among chronically ill patients. Facilities under the NHI system should be improved to provide more services, including care for chronic conditions.

Early essential newborn care in national tertiary hospitals in Cambodia and Lao People's Democratic Republic: a cross-sectional study.

BACKGROUND: Ministries of health in collaboration with the World Health Organization Regional Office for the Western Pacific (WPRO) have been scaling up early essential newborn care (EENC). This study was carried out to understand current EENC practices at hospitals in two priority countries: the Kingdom of Cambodia (Cambodia) and Lao People's Democratic Republic (Lao PDR). METHODS: EENC is subdivided into 79 checkpoints, referencing the self-monitoring checklist developed by the WPRO. Each checkpoint is rated using a 0 to 2-point scale, and a percentage was calculated for the rate of practice of each checkpoint by dividing the total scores by the maximum possible scores. RESULTS: In total, 55 and 56 deliveries were observed in Cambodia and Lao PDR, respectively, and 35 and 34 normal deliveries were included in the analysis. The overall rates of the practices within the first 15 minutes after birth were high in both countries. The rates of the practices before birth and 15 minutes after birth were lower than the rates of the practices performed within the first 15 minutes after birth, especially "hand wash before preparation", "preparation for newborn resuscitation", and "monitoring of postpartum mothers and babies". A detailed analysis revealed that the quality of the practices differed between the two countries regarding skin-to-skin contact and breastfeeding support. CONCLUSIONS: The high rates of the practices within the first 15 minutes after birth suggest that the EENC coaching sessions supported by ministries of health and the WPRO have been effective. Differences in the quality of practices performed at a high rate between the two countries appeared to be related to factors such as the timing of the study, the perception of the staff, and the situation at the health facilities. These differences and identified practices with lower rates should be improved according to the situation in each country or health facility. Therefore, determining the quality of the practices in a country or a health facility is important. To further improve the quality of EENC, interventions tailored to the specific situation are necessary.

Bubbly and cystic appearance on chest radiograph of extremely preterm infants with bronchopulmonary dysplasia is associated with wheezing disorder.

AIM: Bubbly/cystic appearance on chest X-ray (CXR) is an important factor in cases of severe bronchopulmonary dysplasia (BPD). We aimed to determine whether CXR -based BPD classifications obtained in extremely preterm infants with oxygen dependency at 28 days after birth (BPD28) is associated with wheezing disorders. METHODS: This was a multicentre retrospective cohort study of population data from infants (body weight, <1500 g) enrolled in the Neonatal Research Network of Japan. Of the 15 480 infants born at <28 weeks of gestation between 2003 and 2012, 8979 met the BPD28 criteria, and 4007 were classified as the no BPD28 group. BPD28 infants were classified according to the bubbly/cystic or no bubbly/cystic appearance on CXR at postnatal ≧28 days. The effects on wheezing disorder at 3 years of age were analysed. RESULTS: Bubbly/cystic BPD28 infants showed higher rates of wheezing disorders compared with no BPD28 infants. Bubbly/cystic BPD28 (odds ratio 1.7; 95% confidence interval, 1.3-2.2) was a significant independent factor for wheezing disorders. CONCLUSION: A bubbly/cystic appearance on CXR with BPD28 was a potential risk factor of wheezing disorders at 3 years of age. This may be a useful early diagnostic tool at ≧28 postnatal days in extremely preterm infants.

Impact of chest radiography-based definition of bronchopulmonary dysplasia.

BACKGROUND: Bubbly/cystic appearance on chest radiograph is an important factor in severe-type bronchopulmonary dysplasia (BPD) in Japan. The aim of this study was to determine the perinatal characteristics and neonatal complications of the bubbly/cystic(+) group in extremely preterm infants with BPD, that is, oxygen dependency at day 28 after birth (BPD28). METHODS: This was a multicenter retrospective cohort study of population data from infants (birthweight, <1,500 g) enrolled in the Neonatal Research Network of Japan. Of the 15 480 infants born at <28 weeks' gestational age (GA) between 2003 and 2012, 8,979 met the BPD28 criteria. The BPD28 infants were classified according to bubbly/cystic appearance on radiograph (±) at >28 postnatal days. RESULTS: The bubbly/cystic(+) group had lower GA and birthweight and required longer mechanical ventilation and oxygen dependency than the bubbly/cystic(-) group. After adjustment for confounding factors, bubbly/cystic appearance was an independent risk factor for home oxygen therapy at discharge. CONCLUSION: Bubbly/cystic appearance on chest radiograph was a predictor of short-term respiratory outcomes in infants with BPD28, which is diagnosed much earlier (≥28 postnatal days), and has a potentially different etiology to BPD36 (oxygen and/or positive pressure respiratory support dependency at 36 weeks' postmenstrual age).

A case of neonatal lupus erythematosus in a very low-birth-weight infant that suffered intraventricular hemorrhage at birth.

This report describes the case of a very low-birth-weight male infant with neonatal lupus erythematosus. His mother had Sjögren's syndrome, and her previous child had suffered a complete heart block. Accordingly, maternal steroid (betamethasone) therapy was administered to prevent a congenital heart block for 15 weeks (from 13 to 27 weeks' gestation). At 28 weeks' gestation, the mother was weaned off the steroid therapy, and an emergency cesarean section was carried out at 29 weeks and 6 days' gestation because of a nonreassuring fetal status (NRFS). At birth, the infant exhibited grade-III intraventricular hemorrhage (IVH). Although it is unclear why the infant developed a NRFS and IVH, the condition of the fetus should be carefully monitored during and after long-term maternal steroid treatment.

The emergence of CD20-/CD19- tumor cells after rituximab therapy for Epstein-Barr virus-associated post-transplant lymphoproliferative disorder complicated with hemophagocytic lymphohistiocytosis.

Post-transplant lymphoproliferative disorder (PTLD) is a well-recognized aggressive disease commonly associated with Epstein-Barr virus (EBV) infection after hematopoietic stem cell transplantation (HSCT). Although rituximab (RTX) is incorporated into the first-line therapy for EBV-PTLD patients, the outcome of the clinically overt disease is still not optimal mainly due to the regrowth of tumor cells. The proliferation of CD20-/CD19+ tumor cells is increasingly reported in RTX-treated EBV-PTLD patients, whereas the emergence of CD20-/CD19- tumor cells is barely recognized. Here, we report a fatal case of an 18-year-old patient who developed EBV-PTLD after allogeneic HSCT for anaplastic large-cell lymphoma. On day 60 after HSCT, the patient developed abdominal pain, watery diarrhea, and low-grade fever. Colon biopsy revealed the proliferation of CD20+/CD19+/EBV-encoded RNA (EBER)+ tumor cells, and an increase of EBV DNA was detected in peripheral blood (PB). He was treated with RTX for EBV-PTLD and was cleared of EBV DNA in PB. However, he manifested high-grade fever, pancytopenia, and elevated soluble interleukin-2 receptor with a prominent hemophagocytosis in bone marrow aspirates and was treated with etoposide for hemophagocytic lymphohistiocytosis (HLH) complication. He then developed EBV DNA positivity in PB and finally died of Bacteroides fragilis sepsis subsequent to bloody stool and ileus on day 163. Autopsy revealed erosion and bleeding in the whole colon with the proliferation of CD20-/CD19-/EBER+ tumor cells. Immunohistochemical analysis uncovered the CD3-/CD56-/CD79a+/CD79b+ B-cell origin of tumor cells. This case clinically demonstrates the removal of both CD20 and CD19 antigens from EBER+ B cells in an RTX-treated EBV-PTLD patient with HLH complication.

[A case of adjuvant surgery for a patient with initially unresectable locally advanced pancreatic cancer (LAPC) with a favorable response to S-1 chemotherapy].

A 67-year-old man was admitted to our hospital with a complaint of epigastric discomfort. A 29-mm hypovascular tumor was detected in the head of the pancreas by abdominal computed tomography imaging. As the superior mesenteric artery (SMA) was also involved, we diagnosed the tumor as unresectable pancreatic cancer. With S-1 chemotherapy, a radiological partial response was seen. After 4 courses of chemotherapy, a subtotal-stomach-preserving-pancreatoduodenectomy with dissection of the nerve plexus surrounding the SMA was performed. Although the tissue surrounding the SMA was hard, invasion of the SMA was not detected. Microscopic investigation revealed a few moderately differentiated adenocarcinoma cells in the fibrous tissue and the nerve fibers of pancreas. No cancer cells were found at the edges of the surgical specimen. The patient underwent R0 resection and a pathological evaluation showed Grade III tumor according to the Evans classification. After surgery, S-1 was interrupted because of diarrhea and local recurrence appeared 4 months postoperatively. For improving the prognosis of patients with pancreatic cancers, surgical intervention is often performed in patients with initially unresectable pancreatic cancers who have "long-term" favorable responses to chemotherapy or chemoradiotherapy. However, because of the possibility of relatively good prognosis with nonsurgical treatment for such patients and also the demerits of surgical stress, it is important to carefully consider the adjuvant surgery option.

Successful treatment of isolated central nervous system recurrence of primary testicular lymphoma by autologous stem cell transplantation using a conditioning regimen of thiotepa and busulfan.

Primary testicular lymphoma (PTL) frequently relapses in the central nervous system (CNS) despite prophylactic intrathecal chemotherapy, and the outcome for CNS recurrence of PTL is very poor. We report a case of isolated CNS recurrence of bilateral PTL. Our patient achieved complete response (CR) after rituximab-combination chemotherapy for PTL. Approximately five years later, isolated CNS recurrence of PTL occurred. Our patient achieved CR again after high-dose methotrexate therapy and autologous stem cell transplantation (ASCT) with a conditioning regimen of thiotepa and busulfan as a consolidation therapy. The secondary failure of platelet recovery, probably caused by busulfan, occurred after the platelet engraftment. Our patient has remained in CR for over three years. The treatment strategy for CNS recurrence of PTL is mainly whole-brain radiotherapy or high-dose methotrexate-based chemotherapy; however, CNS recurrence of PTL may occur again even after achieving CR. ASCT with a conditioning regimen of thiotepa and busulfan is the optimal consolidation therapy for secondary CNS lymphoma. To the best of our knowledge, this is the second reported case of a patient with isolated CNS recurrence of PTL successfully treated by ASCT with a conditioning regimen of thiotepa and busulfan as a consolidation therapy.

Congenital hyperinsulinism in an infant with paternal uniparental disomy on chromosome 11p15: few clinical features suggestive of Beckwith-Wiedemann syndrome.

Beckwith-Wiedemann syndrome (BWS) is the most common congenital overgrowth syndrome involving tumor predisposition. BWS is caused by various epigenetic or genetic alterations that disrupt the imprinted genes on chromosome 11p15.5 and the clinical findings of BWS are highly variable. Hyperinsulinemic hypoglycemia is reported in about half of all babies with BWS. We identified an infant with diazoxide-unresponsive congenital hyperinsulinism (HI) without any apparent clinical features suggestive of BWS, but diagnosed BWS by molecular testing. The patient developed severe hyperinsulinemic hypoglycemia within a few hours after birth, with macrosomia and mild hydronephrosis. We excluded mutations in the K(ATP) channel genes on chromosome 11p15.1, but found a rare homozygous single nucleotide polymorphism (SNP) of ABCC8. Parental SNP pattern suggested paternal uniparetal disomy in this region. By microsatellite marker analysis on chromosome 11p15, we could diagnose BWS due to the mosaic of paternal uniparental disomy. Our case suggests that some HI of unknown genetic etiology could involve undiagnosed BWS with no apparent clinical features, which might be diagnosed only by molecular testing.

Repeating regional acute pancreatitis in the head of the pancreas caused by intraductal papillary mucinous neoplasms in the tail: report of a case.

Intraductal papillary mucinous neoplasm (IPMN) of the pancreas is a distinct entity characterized by papillary proliferations of mucin-producing epithelial cells with excessive mucin production and cystic dilatation of the pancreatic ducts. The clinical presentation often involves recurrent episodes of pancreatitis associated with the temporal obstruction of the main pancreatic duct caused by the hypersecretion of mucin. We herein describe a case in which the patient repeatedly experienced the occurrence of idiopathic acute pancreatitis in the head of the pancreas over a 9-year period, and who was ultimately was cured by distal pancreatectomy for IPMNs in the pancreatic tail. This case illustrates the potential pitfalls in the diagnosis of IPMNs owing to a discrepancy between the site of pancreatitis and that of the IPMN. The possible mechanisms linking acute pancreatitis with the formation of IPMNs are also reviewed.

Global monitoring of public interest in preventive measures against COVID-19 via analysis of Google Trends: an infodemiology and infoveillance study.

OBJECTIVES: The COVID-19 pandemic has influenced people's concerns regarding infectious diseases and their preventive measures. However, the magnitude of the impact and the difference between countries are unclear. This study aimed to assess the magnitude of the impact of COVID-19 on public interest and people's behaviours globally in preventing infectious diseases while comparing international trends and sustainability. DESIGN: An infodemiology and infoveillance study. SETTING: The study employed a web-based data collection to delineate public interest regarding COVID-19 preventive measures using Google Trends. PRIMARY AND SECONDARY OUTCOME MEASURES: A relative search volume was assigned to a keyword, standardising it from 0 to 100, with 100 representing the highest share of the term searches. The search terms "coronavirus", "wash hand", "social distancing", "hand sanitizer" and "mask" were investigated across 196 different countries and regions from July 2018 to October 2021 and weekly reports of the relative search volume were obtained. Persistence of interest was assessed by comparing the first 20 weeks with the last 20 weeks of the study period. RESULTS: Although the relative search volume of "coronavirus" increased and was sustained at a significantly higher level (p<0.05) than before the pandemic declaration, globally, the trends and sustainability of the interest in preventable measures against COVID-19 varied between countries and regions. CONCLUSIONS: Sustained interest in preventive measures differed globally, with regional differences noted among Asia, Europe, Africa and the Americas. The global differences should be considered for implementing effective interventions against COVID-19. The increased interest in preventive behaviours against COVID-19 may be related to overall infectious disease prevention.

Enhancing hospital quality management and patient safety in Vietnam: a technical assistance project utilizing online solutions during COVID-19 pandemic.

Since 2015, the National Center for Global Health and Medicine in Japan has been conducting a technical assistance project for improving patient safety in Vietnamese hospitals. During the COVID-19 pandemic, the project conducted a patient safety training program utilizing online solutions for participants from Vietnam. This resulted in an increase in the number of participants, and ensured access from remote locations. The convenience of easy access from smartphones encouraged further participation. In addition to online training, the utilization of platforms such as Facebook, a common social networking service in Vietnam, contributed to the dissemination of good practices.

Differentiation of malignant and benign pulmonary nodules with quantitative first-pass 320-detector row perfusion CT versus FDG PET/CT.

PURPOSE: To prospectively compare the capability of quantitative first-pass perfusion 320-detector row computed tomography (CT) (ie, area-detector CT) with that of combined positron emission tomography and CT (PET/CT) for differentiation between malignant and benign pulmonary nodules. MATERIALS AND METHODS: This prospective study was approved by the institutional review board, and written informed consent was obtained from 50 consecutive patients with 76 pulmonary nodules. All patients underwent dynamic area-detector CT, PET/CT, and microbacterial and/or histopathologic examinations. All pulmonary nodules were divided into three groups: malignant nodules (n = 43), benign nodules with low biologic activity (n = 6), and benign nodules with high biologic activity (n = 27). For each dynamic area-detector CT data set, the perfusion derived by using the maximum slope model (PF(MS)), extraction fraction derived by using the Patlak plot model (EF(PP)), and blood volume derived by using the Patlak plot model (BV(PP)) were calculated. These parameters were statistically compared among the three nodule groups. Receiver operating characteristic (ROC) analyses were used to compare the diagnostic capability of the CT and PET/CT indexes. Finally, the sensitivity, specificity, and accuracy of each index were compared by using the McNemar test. RESULTS: All indexes in the malignant nodule group were significantly different from those in the low-biologic-activity benign nodule group (P < .05). Areas under the ROC curve for PF(MS) and EF(PP) were significantly larger than those for BV(PP) (P < .05) and maximal standard uptake value (SUV(max)) (P < .05). The specificity and accuracy of PF(MS) and EF(PP) were significantly higher than those of BV(PP) and SUV(max) (P < .05). CONCLUSION: Dynamic first-pass area-detector perfusion CT has the potential to be more specific and accurate than PET/CT for differentiating malignant from benign pulmonary nodules. SUPPLEMENTAL MATERIAL: http://radiology.rsna.org/lookup/suppl/doi:10.1148/radiol.10100245/-/DC1.

Para-aortic lymph node micrometastasis in patients with node-negative biliary cancer.

BACKGROUND/AIMS: The presence of para-aortic lymph node metastasis in biliary cancer negatively impacts prognosis. The present study aims to immunohistochemically identify and evaluate the clinical significance of para-aortic lymph node micrometastases in 66 patients who had undergone curative resection of biliary cancer. METHODS: We used an antibody against cytokeratins 7 and 8 (CAM5.2) to immunostain 529 para-aortic lymph nodes that were negative according to conventional analysis from 66 patients with biliary cancer. RESULTS: We detected CAM5.2-positive occult carcinoma cells in para-aortic lymph nodes from 3 (5%) of the 66 patients and in 3 (0.6%) of the 529 para-aortic lymph nodes. One of the 3 patients also had micrometastasis in the regional lymph nodes. All 3 patients with para-aortic lymph node micrometastasis are alive at 45, 48 and 90 months after surgery despite having locally advanced cancer. CONCLUSIONS: Occult cancer cells were identified in para-aortic lymph nodes from 5% of patients with node-negative biliary cancer, yet these patients have survived over the long term. The presence of para-aortic nodal micrometastasis might not have an influence on survival. However, further studies using a greater number of patients are required to support this notion.

Activation of an oncogenic TBC1D7 (TBC1 domain family, member 7) protein in pulmonary carcinogenesis.

To develop novel biomarkers and therapeutic agents for lung cancers, we screened molecules that were highly expressed in lung cancers by means of cDNA microarray analysis and found an elevated expression of TBC1 domain family, member 7 (TBC1D7) in the majority of lung cancers. Northern-blot analysis using mRNAs from 16 normal tissues detected its expression only in testis. Immunohistochemical staining using tumor tissue microarrays consisting of 261 archived non-small cell lung cancer (NSCLC) specimens suggested an association of TBC1D7 expression with poor prognosis for NSCLC patients (P = 0.0063). Treatment of lung cancer cells using siRNA against TBC1D7, suppressed its expression and resulted in inhibition of the cell growth. Furthermore, the induction of exogenous expression of TBC1D7 conferred growth-promoting activity at in vitro and in vivo conditions. We also identified TBC1D7 to interact with TSC1 protein in lung cancer cells. TSC1 introduction into cells increased the level of TBC1D7 protein, whereas knockdown of TSC1 expression decreased the level of TBC1D7 protein, suggesting that TBC1D7 is stabilized probably through interaction with TSC1. In addition, inhibition of the binding between TBC1D7 and TSC1 by a TBC1D7-derived 20-amino acid cell-permeable peptide (11R-TBC1D7(152-171)), which corresponded to the binding domain to TSC1, effectively suppressed growth of lung cancer cells. Selective suppression of TBC1D7 and/or inhibition of the TBC1D7-TSC1 complex formation could be promising therapeutic strategies for lung cancer therapy.

[A case report of intrahepatic cholangiocarcinoma diagnosed as lung cancer with liver metastasis treated with radiofrequency ablation].

In December 2008, a 43-year-old male who had been pointed out a nodular shadow in the right upper field on a chest radiography was admitted to hospital. A 35 mm mass infiltrating to superior vena cava in the right upper lobe of the lung, and 32 mm mass in the liver at S7 were detected by CT. Pathological diagnosis of the liver tumor was adenocarcinoma. Under the diagnosis of lung carcinoma and liver metastasis, systemic chemotherapy was started from January 2009. Radiofrequency ablation (RFA) therapy was added for liver S7 mass in February, and radiation therapy was performed for lung mass in December. The lung lesion has markedly reduced, but the liver lesion recurred in October 2009, which continued to grow up to 80 mm until August 2010. He presented to our hospital with the diagnosis of liver metastasis of controlled primary lung cancer. In October, we performed right hepatectomy with diaphragma and right lung resection. The pathological diagnosis was intrahepatic cholangiocarcinoma. Multiple recurrences in remnant liver, lung and peritoneal metastasis were detected in January 2011. For intrahepatic cholangiocarcinoma, hepatectomy is the only established treatment, and RFA treatment remains controversial. Clinical diagnosis of multiple cancers should be decided with caution.

Prognostic impact of regional lymph node micrometastasis in patients with node-negative biliary cancer.

OBJECTIVE: To immunohistochemically identify regional lymph node micrometastases in patients with regional node-negative biliary cancer who underwent curative resection, and to evaluate their clinical significance. SUMMARY BACKGROUND DATA: The clinical significance of immunohistochemically detected lymph node micrometastasis has recently been evaluated in various tumors. However, few reports have focused on this issue with regard to biliary cancer. METHODS: A total of 1421 regional lymph nodes from 151 patients with biliary cancer with negative regional nodes (as determined by conventional methods) were immunostained with antibody against cytokeratins 7 and 8 (CAM5.2). Prognostic impact was evaluated among patients with no metastasis, micrometastasis, and obvious metastasis detected by hematoxylin and eosin staining. Immunostained tumor foci were classified as small micrometastasis or large micrometastasis according to size (above or below 0.2 mm). RESULTS: CAM5.2-positive occult carcinoma cells in regional lymph nodes were detected in 33 (22%) of 151 patients and 49 (3%) of 1421 regional lymph nodes. Small micrometastases were detected in 23 patients, whereas large micrometastases were found in 10 patients. Survival for patients with micrometastasis was significantly worse than that for patients without (P = 0.0051), but was significantly better than that for patients with overt metastasis (P = 0.0092). No significant difference in postoperative survival was seen between patients with small and large micrometastases (P = 0.4221). CONCLUSIONS: Occult cancer cells were present in regional lymph nodes of 22% patients with regional node-negative biliary cancer, and were associated with significantly worse survival. Patients with micrometastases should be treated as carefully as node-positive patients.