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Background: This study aimed to investigate the association between the extent of vascular invasion (VI) and the outcome of widely invasive follicular thyroid carcinoma (WI-FTC)., Methods: The records of 107 patients with WI-FTC confirmed by surgical specimens from January 2005 to December 2016 were retrospectively reviewed., Results: Among the 107 patients with WI-FTC, those with a VI of < 4 (n = 62) and ≥ 4 (n = 45) had a 10 year cause-specific survival (CSS) rate of 97.7% and 89.4% (p = 0.008), respectively. Univariate analysis identified M1 (p = 0.001), and the number of VI of ≥ 4 as significant negative prognostic factors for CSS. Multivariate analysis identified M1 (hazard ratio [HR] = 9.366) as independent negative prognostic factor for CSS. Among the 72 patients with M0 WI-FTC, those with a VI of < 2 (n = 33) and ≥ 2 (n = 39) had a 10-year distant metastasis-free survival (DMFS) rate of 96.8% and 56.8% (p = 0.001), respectively. Univariate analysis identified age ≥ 55 years (p = 0.011), presence of VI, the number of VI of ≥ 2, and resection margin status (p < 0.001) as significant negative prognostic factors for DMFS. Multivariate analysis identified the number of VI ≥ 2 (HR = 9.137), and resection margin status (HR = 5.853) as independent negative prognostic factors for DMFS., Conclusions: It may be unnecessary that WI-FTC with curative resection margin status and a VI of < 2, especially in capsular invasion only, routinely undergo completion thyroidectomy and postoperative ablation., (© 2023. The Author(s) under exclusive licence to Société Internationale de Chirurgie.)

Background: Age has been recognized as one of the strong prognostic indicators for thyroid cancer. However, treatment strategies for papillary thyroid cancer (PTC) are usually determined only by the extent of disease progression, without considering the patient's age. The aim of this study was to investigate how the surgical strategy for PTC should take into account patient age., Methods: To exclude the effect of treatment strategy, 837 patients treated with uniform treatment strategies (hemithyroidectomy without radioiodine therapy) between 1986 and 1995 were the subjects of this study. Using a Cox proportional hazard model, clinical risk factors related to disease-specific survival (DSS), disease-free survival (DFS), and distant metastasis-free survival (DMFS) were analyzed. A receiver-operating characteristic (ROC) curve analysis was performed to identify the optimal cutoff points., Results: Significant risk factors related to DSS and DMFS were age, extrathyroidal extension (ETE), and numbers of metastatic lymph nodes (NMLNs), but age was not significantly related to DFS. The 20-year DSS and DMFS rates were fair in patients without ETE regardless of age or NMLNs. However, in patients with ETE, DSS and DMFS rates were significantly worse in elderly patients than in young patients. ROC curve analysis showed that the optimal cutoff age was 48 years for discriminating DSS in patients with ETE., Conclusion: Regardless of age, PTC patients without ETE are candidates for a treatment strategy not using RAI, and more aggressive treatment may be recommended for elderly PTC patients with ETE., (© 2022. The Author(s) under exclusive licence to Société Internationale de Chirurgie.)

Background: The present study investigated the association between local resection and cause of death in anaplastic thyroid carcinoma (ATC) patients with stage IVC disease., Methods: A total of 54 ATC patients with stage IVC disease were included in the study. Information including patient characteristics, laboratory data including complete blood count, treatment, and death were collected for analysis., Results: The median overall survival (OS) for patients with or without resection was 8.4 [95% confidence interval (CI) 5.9-14.4)] and 4.2 (95% CI 2.5-6.2) months, respectively (p < 0.001). No patients survived without resection at 1 year. Univariate analysis revealed that resection (p < 0.001) and radiotherapy (p = 0.018) were significantly associated with OS. Multivariate analysis revealed that resection (hazard ratio 0.257; 95% CI 0.115-0.575; p < 0.001) was the only independent prognostic factor of OS. In ATC patients with known resection status, the median OS for the patients with a resection status of R0/1 (n = 28) and R2 (n = 7) were 13.0 (95% CI 7.5-18.7) and 1.7 (95% CI 0.1-6.2) months, respectively (p < 0.001). The most common specific cause of death was respiratory insufficiency (35%), followed by airway obstruction (25%) and cerebral cardiovascular-related death (5%). The frequency of airway obstruction was significantly lower in patients with resection (p = 0.018)., Conclusions: Resection probably impacts on clinical course in ATC patients despite the presence of distant metastasis. However, R2 resection is likely to be harmful and surgeons should carefully consider the resectability of thyroid tumors., (© 2022. The Author(s) under exclusive licence to Société Internationale de Chirurgie.)

Background: The Turin criteria including solid, trabecular, and/or insular architecture, lack of typical nuclear features of papillary carcinoma, and mitoses, necrosis, or convoluted nuclei were adopted in the recent 4th edition of the World Health Organization classification published in 2017., Materials and Methods: Between 2006 and 2017, 11,001 cases underwent initial surgery for primary malignant thyroid tumor derived from follicular cells. A total of 75 (0.7%) cases were diagnosed with PDTC according to the 2004 WHO classification. Based on the Turin criteria, 30 (40%) cases were re-classified as PDTC-Turin (+) and 45 (60%) cases were PDTC-Turin (-). Clinicopathological features and prognosis were compared between PDTC-Turin (+) and PDTC-Turin (-)., Results: Seventy-five patients (48 females and 27 males) had a median age at the time of surgery of 57 years. Preoperative diagnosis was benign in 16 (21%), follicular tumor in 40 (53%), and malignant in 19 (25%). The 5-year cause-specific survival (CSS) and disease-free survival (DFS) rates were 97% and 44% for PDTC-Turin (+) and 100% and 88% for PDTC-Turin (-). On univariate analysis, CSS and DFS rates were significantly worse in the PDTC-Turin (+) than in the PDTC-Turin (-) (p = 0.0096, and p = 0.0016). Multivariate analysis showed that Turin criteria status, Ki-67 labeling index ≥ 10%, and age 55 ≥ years were the independent prognostic factors for recurrence., Conclusions: The prevalence of PDTC diagnosed with the Turin criteria was low, but it showed more aggressive behavior. The 2017 WHO classification reflects the prognosis more accurately than the 2004 WHO classification.

Background: Surgical resection is the preferred treatment for locoregional recurrence of differentiated thyroid cancer (DTC). However, some recurrences are unresectable because of their aggressive invasion or severe adhesions. On the other hand, stereotactic radiotherapy (SRT) enables high-dose irradiation to target lesions, and its usefulness for various cancers has been reported. The objective of the present study was to investigate the feasibility and efficacy of SRT as salvage treatment for locoregional recurrence of DTC., Methods: Between August 2011 and December 2017, 52 locoregional recurrent lesions in 31 patients with recurrent DTC were treated by SRT using the CyberKnife system. Information on the adverse events associated with SRT was retrospectively collected from the patients' medical records. Of the 52 lesions, 33 could be evaluated for therapeutic effectiveness by follow-up CT, and response was assessed using the RECIST criteria., Results: Twenty-five patients had papillary carcinoma, 5 had follicular carcinoma, and 1 had poorly differentiated cancer. SRT was delivered in one to 20 fractions, and the median dose was 30 Gy (range 15-60 Gy). Adverse events were not frequent, but 1 patient developed bilateral vocal cord palsy that required emergent tracheostomy. The median follow-up period of 33 lesions was 14 months (range 1-54 months). Complete response, partial response, stable disease, and progressive disease were seen in 10, 11, 9, and 3 patients, respectively. The 3-year local control rate was 84.6%., Conclusion: SRT using the CyberKnife system was found to be a feasible and effective treatment to suppress the growth of locoregional recurrence of DTC.

Background: Cribriform-morular variant of papillary thyroid carcinoma (CMV-PTC) is rare; it may occur in cases of familial adenomatous polyposis (FAP) or be sporadic. To clarify the clinicopathological features of CMV-PTC, the medical records of these patients were investigated retrospectively., Materials and Methods: Between 1979 and 2016, a total of 17,062 cases with PTC underwent initial surgery at Ito Hospital. Of these, 30 (0.2%) cases histologically diagnosed with CMV-PTC were reviewed., Result: The patients were all women, with a mean age at the time of surgery of 24 years. Seven (23%) cases were thought to have FAP because they had colonic polyposis or a family history of FAP or APC gene mutation. The remaining 23 (77%) were thought to be sporadic. Multiple tumors were detected in 6 cases, with a solitary tumor in 24. One patient had lung metastasis at diagnosis. Eleven patients underwent total thyroidectomy or subtotal thyroidectomy, and 19 underwent lobectomy. Twenty-six (87%) patients underwent neck lymph node dissection. Three patients had tumor metastasis in central lymph nodes, but these were incidentally detected metastatic classical PTC (cPTC) based on histological examination. In this series, there were no cases of LN metastases of CMV-PTC. During a mean follow-up of 15 years, one patient had new cPTC in the remnant thyroid after initial surgery, and the other patients showed no signs of recurrence., Conclusion: CMV-PTC occurred in young women, their long-term prognosis was excellent. Total thyroidectomy is recommended for FAP-associated CMV-PTC, but modified neck lymph node dissection is not necessary.

Background: Treatment of patients with liver metastasis of differentiated thyroid carcinoma (DTC) has not been sufficiently defined, because liver metastasis of DTC has been described mostly as case reports. Additionally, such patients are considered end-of-treatment responders. A relatively new approach using tyrosine kinase inhibitors (TKIs) may provide opportunities to manage systemic metastasis. This study aims to define the clinical features of DTC patients with liver metastasis and evaluate the benefits of TKIs., Methods: We retrospectively analyzed clinical features of 29 patients (mean age 67.8 years) diagnosed with liver metastasis of DTC at our institution between January 1981 and May 2017., Results: All patients had distant metastasis at other organ sites upon diagnosis of liver metastasis; 41% of them developed new metastasis afterward. Management after diagnosis of liver metastasis comprised palliative care (48%), radioactive iodine therapy (28%), and TKI therapy (24%). The median survival after diagnosis of liver metastasis was only 4.8 months. Survival rates were significantly better in patients with performance statuses between 0 and 2 on the Eastern Cooperative Oncology Group scale at diagnosis of liver metastasis (n = 22, 76%) treated with TKI compared to those who were not (P = 0.017; log-rank test; hazard ratio 0.19). One-year survival rates were 71.4 and 26.7% for patients treated with or without TKI, respectively., Conclusions: Patients with liver metastasis had poor clinical prognosis. When other distant metastases existed at diagnosis of liver metastasis, TKI therapy was considered an effective therapeutic option for patients with liver metastasis of DTC.

Background: In patients with differentiated thyroid carcinoma (DTC), lung and bone metastasis sometimes occur. However, brain metastasis (BM) is extremely rare. Because most previous reports about BM from DTC included a relatively small number of cases, the clinical characteristics and outcomes of BM are still unclear., Patients and Methods: Between 1965 and 2013, among 961 patients who had died because of DTC, 24 patients were diagnosed with BM from DTC. One patient with BM from DTC is still alive. To identify the prognostic factors for longer survival after BM, the medical records of these 25 patients were retrospectively reviewed., Results: The median age at BM diagnosis was 66 years. Typical symptoms associated with BM had appeared in 20 patients (80%). The Karnofsky Performance Status (KPS) was good (≥70) in 10 patients and poor (≤60) in 15 patients. Seven patients had a single intracranial lesion of BM, 6 patients had 2 or 3 lesions, and 9 patients had 4 or more. Eleven patients did not receive any treatment for BM, and 14 patients underwent surgical resection, radiation therapy, or both. One-year and 5-year disease-specific survival rates were 28 and 10.6%, respectively. Good KPS (≥70), small number of intracranial lesions (≤3), and treatment for BM were prognostic factors for long survival on univariate analysis (p < 0.05). On multivariate analysis, only treatment for BM was significant., Conclusion: Treatment of BM from DTC is indicated in patients who have a good KPS and fewer intracranial lesions, and some of them may achieve long survival.

Background: The aim of this study was to analyze the clinical features and clinical outcomes of papillary thyroid carcinoma (PTC) in the pediatric and adolescent population treated in our institution., Methods: The subjects were 227 PTC patients 20 years of age or under treated initially between 1979 and 2012. Their mean age at diagnosis was 18-year old (range 7-20 years). Patient characteristics and outcomes in the period before 1999 and the period after 2000 were compared. Cause-specific survival (CSS) rates and disease-free survival (DFS) rates were calculated by the Kaplan-Meier method., Results: Two patients died of their disease and 45 patients had recurrent disease (36 in lymph node, seven in a remnant thyroid, and 11 in the form of distant metastasis). The 10-, 20-, and 30-CSS rates were 99.3, 99.3, and 96.5%, respectively, and the 10-, 20-, and 30-DFS were 83.6, 70.7, and 64.0%, respectively. Gender and preoperative lymph node metastasis were identified as significant factors related to DFS in the multivariate analysis. After the year 2000, there were significantly more patients with a small primary tumor size, significantly more patients without distant metastasis at presentation and significantly more patients without extrathyroidal invasion., Conclusion: The number of patients with advanced cancer has been declining in recent years. Lobectomy with prophylactic unilateral central neck dissection is considered acceptable for patients without the risk factors for recurrence.

Background: Diffuse sclerosing variant (DSV) of papillary thyroid carcinoma (PTC) is a rare variant more common among younger patients., Materials and Methods: Excluding patients with microcarcinoma, 5848 patients with PTC underwent initial surgery between 1995 and 2011. Twenty-two patients (0.4 %) were histologically diagnosed with DSV, of whom 20 (91 %) were <45 years old. We compared clinicopathologic characteristics and outcomes between patients with DSV and those with classical PTC <45 years old. Univariate analysis by the Kaplan-Meier method in relation to cause-specific survival (CSS) and disease-free survival (DFS) rates was performed with regard to the following variables: sex; anti-thyroglobulin antibody (TgAb) positivity; presence of distant metastasis; pathological lymph node metastasis; extra-thyroidal invasion; and pathological variant (classical vs. DSV)., Results: The 20 patients with DSV <45 years old comprised 18 females and 2 males. Frequencies of TgAb, pN1b, and local recurrence were higher in the DSV group than in the classical PTC group. Ten-year CSS and DFS rates for PTC patients <45 years old were 99.7 and 88.6 % in the classical PTC group and 100 and 60.5 % in the DSV group. CSS rate did not differ between groups, but DFS rate was significantly lower in the DSV group than in the classical PTC group (p < 0.0001, log-rank test). Multivariate analysis identified DSV group and pN1b as prognostic factors for recurrence in young PTC patients., Conclusions: Most DSV patients were young and had a background of chronic thyroiditis. Outcomes for DSV were very good, but recurrence was more common than in classical PTC.

Background and Objective: The effectiveness of antimicrobial prophylaxis (AMP) in the prevention of surgical site infection (SSI) following thyroid and parathyroid surgery remains uncertain. The objective of this prospective randomized controlled trial (Ito-RCT1) was to assess the effectiveness of AMP in clean neck surgery performed to treat thyroid and parathyroid disease., Methods: Participants comprised patients scheduled for clean neck surgery for thyroid and parathyroid disease at Ito Hospital. Patients whose surgery included sternotomy or resection of the trachea, larynx, pharynx, or esophagus were excluded. AMP consisted of 2 g of piperacillin (PIPC) (group A, n = 541) or 1 g of cefazolin (CEZ) (group B, n = 541) administered intravenously immediately after endotracheal intubation. Patients in the control group (Group C, n = 1,082) did not receive AMP., Results: Statistical analysis was performed to compare the AMP group (Group A + Group B) with the control group (Group C). Drug-induced acute reactions correlated to PIPC or CEZ did not occur in the AMP group. No significant differences in the postoperative incidence of liver or renal dysfunction were seen between the AMP and control groups. Postoperative incidence of urinary tract infection was significantly higher in the control group (p = 0.002). The incidence of SSI events was very low, with only 1 event (0.09 %) in the AMP group and 3 events (0.28 %) in the control group, and this difference between groups was not significant (p = 0.371)., Conclusions: AMP is not necessary to prevent SSI after clean thyroid or parathyroid surgery.

Background: Differentiated thyroid cancer (DTC) is the second most common cancer diagnosed in pregnant women, but there is no consensus as to whether surgery should be performed during pregnancy or after delivery., Methods: We retrospectively reviewed the records of 45 patients with DTC operated on during pregnancy or within 1 year after delivery, and we compared the clinicopathological features and outcomes of the patients operated during pregnancy (group A, n = 24) and the patients operated after delivery (group B, n = 21)., Results: All 45 patients were histologically diagnosed with well-differentiated papillary thyroid cancer. Nineteen (79 %) of the 24 patients in group A underwent thyroidectomy during the second trimester. No complications associated with surgery or general anesthesia were reported in either group. There were no significant differences between the two groups in terms of age, tumor size, incidence of lymph node metastasis, or incidence of extrathyroidal extension. No distant metastases were detected in any of the patients. Two small for date infants (8.3 %) and 2 heavy for date infants (8.3 %) were delivered in group A, but only 1 small for date infant (4.7 %) was delivered in group B. There were no miscarriages, and none of the infants in either group had birth defects. Because 3 patients in group A and 1 patient in group B experienced a local recurrence, salvage surgeries were performed., Conclusions: Although thyroid surgery was performed safely in the second trimester, surgery after delivery was also acceptable. Surgery after delivery is recommended for most patients with non-aggressive DTC.

Background: Total thyroidectomy is well accepted as initial surgery for papillary thyroid cancer (PTC), but the extent of the thyroidectomy remains a matter of controversy. This study was designed to investigate the long-term clinical outcome of PTC patients who had undergone thyroid lobectomy and to elucidate the indications of lobectomy as initial surgery., Methods: The cases of 1,088 PTC patients who underwent thyroid lobectomy with curative intent at Ito Hospital between 1986 and 1995 were analyzed retrospectively in this study. None of the patients had received postoperative radioactive iodine (RAI) ablation therapy. The median follow-up period was 17.6 years. All clinical outcomes, including recurrence and death as a result of PTC or other reasons, were evaluated. To establish the indications for lobectomy as initial surgery for PTC, the potential risk factors, such as age, sex, primary tumor size, extrathyroidal invasion, and clinical lymph node metastasis at the time of the initial surgery, were assessed statistically for associations with recurrence and disease-related death., Results: The remnant-thyroid recurrence-free survival (RT-RFS) rate, the regional- lymph-node recurrence-free survival (L-RFS) rate, and the distant-recurrence-free survival (D-RFS) rate as of 25 years after surgery were 93.5, 90.6, and 93.6%, respectively. The cause-specific survival (CSS) rate at 25 years was 95.2%. Univariate and multivariate analyses showed that none of the factors assessed were significantly associated with the RT-RFS rate. Tumor size, clinical lymph node metastasis, and extrathyroidal invasion were significantly associated with the L-RFS rate. The D-RFS and CSS rates were both significantly lower in the group of patients who were aged 45 years old or older, the group whose tumors were larger than 40 mm, and the group with extrathyroidal invasion. Based on the above findings, we classified the patients into four groups according to age <45 or ≥ 45 years, tumor size ≤ 40 or >40 mm, whether clinical lymph node metastasis was present, and whether extrathyroidal invasion was present. None of the patients without any of these four risk factors died of PTC. On the other hand, 22 patients who died of PTC were positive for one or more of these four factors., Conclusions: The long-term clinical outcome of the PTC patients who had been treated by lobectomy without RAI ablation was excellent. Based on the above results, we concluded that lobectomy is a valid alternative to total thyroidectomy for the treatment of PTC patients who are younger than aged 45 years, whose tumor diameter is 40 mm or less, and who do not have clinical lymph node metastasis or extrathyroidal invasion.

Background: We hypothesized that the survival rate of patients undergoing R0 esophagectomy after induction chemotherapy or chemoradiotherapy for unresectable T4 esophageal cancer (URT4) would be similar to that of patients undergoing esophagectomy for immediately resectable esophageal cancer with no unfavorable prognostic factors (RNU)., Methods: Between April 2002 and June 2012, 87 of 283 patients with esophageal cancer who presented at the University Hospital of the Ryukyus were enrolled in this prospective cohort study. Tumors were classified as RNU and URT4 in 44 and 43 of the 87 patients, respectively. Outcomes of treatment for URT4 patients were compared with those of RNU patients., Results: The R0 resection rate (61 %) and in-hospital mortality rate (20 %) of URT4 patients were significantly poorer than those of RNU patients (98 and 2.3 %, respectively), although the morbidity rate was similar in the two groups (63 and 52 %, respectively). The 5-year survival rate (35 %) of URT4 patients was significantly poorer than that of RNU patients (67 %) in the intention-to-treat analysis. However, no significant difference was noted between the two survival curves for cases of R0 resection (5-year survival rate, 60 % vs. 69 %). Multivariate analysis revealed R status as the only significant independent prognostic factor for URT4 patients (P < 0.001; hazard ratio = 8.279)., Conclusions: Satisfactory survival rates can be achieved if R0 resection is performed after induction treatment in patients with T4 esophageal cancer, although secondary radical esophagectomy is associated with a higher risk of in-hospital mortality.

Background: Transient hypocalcemia is one of the postoperative complications of thyroidectomy for Graves' disease, and perioperative parathyroid hormone (PTH) assays are used to predict postoperative hypocalcemia. We evaluated long-term changes in parathyroid function after surgery for Graves' disease., Methods: Serum PTH values were measured in Graves' patients with postoperative hypocalcemia, and those patients were followed postoperatively., Results: Subtotal thyroidectomy was performed in 275 patients with Graves' disease. Their serum calcium levels were measured on postoperative day (POD) 1, and patients with transient postoperative hypocalcemia were treated with calcium and vitamin D supplementation and followed up. The amount of calcium and vitamin D supplementation was adjusted to keep the patient's serum calcium level within the normal range. Measurement of their serum intact PTH value on POD 1 revealed normal value in 18 patients, a below normal level in 22, and an above normal level in the other 2. During the follow-up period, the serum iPTH values remained normal in 12 patients, recovered to the normal level in 21 patients, and rose above the normal range in 9 patients. The serum iPTH values of all patients eventually reached the normal range during the follow-up period. A marked difference in preoperative serum alkaline phosphatase concentration was observed between the high-iPTH patients and the normocalcemic patients., Conclusions: The phenomenon of an elevated serum PTH level after surgery for Graves' disease was observed in 21% of the patients with postoperative hypocalcemia despite the achievement of normal serum calcium levels by calcium and vitamin D supplementation.

Ultrasonography (US) of the thyroid gland has recently proved to be a useful clinical diagnostic method, and the newly developed high-resolution US with a color Doppler flow mapping function can reveal fine details of the thyroid gland and the hemodynamic features of a thyroid neoplasm. US can yield a diagnostic accuracy of more than 90% for thyroid carcinoma, especially papillary carcinoma. However, neither conventional B-mode US imaging nor aspiration biopsy cytology has delivered satisfactory results for follicular carcinoma. The aim of this study was to evaluate the clinical usefulness of color Doppler imaging for the differential diagnosis of thyroid follicular lesions. A color Doppler scan was performed in 310 patients with a solitary cold nodule, and a combination of B-mode US and color Doppler findings, including tumor vascularity and results of a fast Fourier transform (FFT) analysis were used to create the following diagnostic grading system for differential diagnosis of follicular lesions: grade 1, benign follicular lesion [no color flow mapping (CFM) inside the nodule]; grade 2, benign peripheral type [CFM only in peripheral area, pulsatility index (PI) < 1.0]; grade 3, suspected follicular carcinoma (penetrating CFM, vascularity moderate); grade 4, follicular carcinoma (high-velocity penetrating CFM, PI = 1.0). All patients were subjected to surgical resection, and histologic examination was used to confirm the diagnosis. The grades of the 177 adenomatous nodules were as follows: grade 1, 46.9%; grade 2, 48.0%; grade 3, 5.1%; grade 4, 0%. The corresponding percentages for the 89 follicular adenomas were 16.9%, 49.4%, 30.3%, and 3.4%; and for the 44 follicular carcinomas they were 0%, 13.6%, 45.5%, and 40.9%. On the assumption that grade 1 and 2 lesions are benign and grade 3 and 4 lesions are malignant, 38 of the 44 follicular carcinomas and 227 of the 266 benign tumors had been accurately diagnosed, yielding a sensitivity of 88.9%, a specificity of 74.2%, and an accuracy of 81.0% for the grading system. Color Doppler imaging of 310 follicular tumors has revealed that high-velocity pulsatile blood flow penetrating the tumor is a characteristic finding of follicular carcinoma and is a new diagnostic criterion for performing color Doppler imaging. The differential diagnostic grading scores for color Doppler examinations and the results of FFT analysis demonstrate that US with the color Doppler function can play an important role in the differential diagnosis of thyroid tumors.

Fifty-one cases of resected hepatocellular carcinoma (HCC) were retrospectively analyzed to evaluate the clinicopathologic features of HCC in patients with negative virus markers. The data were compared between three groups: hepatitis B surface antigen positive (HB, n = 11), hepatitis C virus antibody positive (HC, n = 21), and non-BC (both HbsAg and HCVAb negative, n = 12). Seven patients were excluded from the study because of operative death (n = 3), a history of alcohol abuse (n = 3), or the presence of dual positive HB and HC virus markers (n = 1). The data were analyzed by either an analysis of variance (ANOVA) or a contingency table. The age of the non-BC patients was higher (63.0 +/- 4.1, +/- SE) than that of HB patients (54.0 +/- 3.2, p < 0.05) but was identical to that of the HC group (62.0 +/- 1.8). Among the preoperative laboratory data, the serum glutamic oxaloacetate and glutamate pyruvate transaminoses (GOT, GPT) levels were statistically lower in the non-BC patients (32.8 +/- 4.8 and 28.0 +/- 4.4 IU/L, respectively) than in the HB and HC patients. The pathologic features of the resected specimens in the non-BC patients showed more invasive growth than in specimens from the HB or HC patients. The clinical stages (defined based on the criteria of the Japanese Association of Hepatocellular Carcinoma) were also more advanced in the non-BC patients than in the other groups. Postoperative survival time showed no significant difference among the groups. In conclusion, the non-BC patients had comparatively greater invasive growth and more advanced clinical stages than the HB and HC patients, despite the absence of liver cirrhosis, and so demonstrated the same poor survival data as observed in the HB and HC patients.