The platelet-to-lymphocyte ratio is a complementary prognostic factor to tumor markers in predicting early recurrence of hepatocellular carcinoma after hepatectomy.

BACKGROUND: The usefulness of inflammation-based prognostic scores for early recurrence (ER) after hepatectomy for hepatocellular carcinoma has rarely been reported. This study aimed to evaluate the potential of inflammation-based prognostic scores as predictors of ER and their relationship with tumor markers. METHODS: We enrolled 338 patients who underwent hepatectomy for hepatocellular carcinoma between January 2007 and December 2021. Clinicopathological factors were compared between patients who developed ER (ER group) and those who did not develop ER (non-ER group). The association between inflammation-based prognostic scores and ER status was evaluated. These scores were compared with those of well-established tumor markers. RESULTS: The platelet-to-lymphocyte ratio (PLR) correlated with ER of hepatocellular carcinoma, with an area under the curve (AUC) value of 0.70, sensitivity of 68.1%, and specificity of 67.7%. In patients with low tumor marker levels, the PLR showed a strong correlation with ER of hepatocellular carcinoma, with an AUC value of 0.851, sensitivity of 100%, and specificity of 76.2%. Multivariate analysis revealed that the PLR was an independent prognostic factor for ER. CONCLUSIONS: The PLR is useful and complementary to tumor markers for predicting ER after hepatectomy for hepatocellular carcinoma.

Usefulness of intratumoral perfusion analysis for assessing biological features of non-functional pancreatic neuroendocrine neoplasm.

PURPOSE: Here, we evaluated the usefulness of intratumoral perfusion analysis using preoperative contrast-enhanced CT (E-CT) to assess biological features of non-functional pancreatic neuroendocrine neoplasms (NF-PanNENs). METHODS: We retrospectively studied 44 patients who underwent curative surgery for NF-PanNENs. We used preoperative E-CT with compartment model analysis to calculate the tumor perfusion parameters K1 (inflow rate constant), 1/k2 (mean transit time), and K1/k2 (distribution volume). We assessed the association between perfusion parameters and biological features of NF-PanNENs, including the WHO classification tumor histopathological grade and prognosis after surgery. RESULTS: Patients in this study had a neuroendocrine tumor (NET) G1 (n = 32) or NET G2 (n = 12). Neither NET G3 or NEC tumors were observed. Among perfusion parameters, K1 was the most accurate predictor of the high-grade tumor (AUC: 0.726). K1-low (< 0.028 s-1) was significantly associated with large tumors (≥ 20 mm) (p = 0.022), high mitotic index (p = 0.017), high Ki-67 index (p = 0.004), and lymphatic invasion (p = 0.025). Synchronous extra-pancreatic metastasis, including lymph node metastasis or liver metastasis, more frequently developed in K1-low patients than in K1-high patients (29% vs 4%, p = 0.025). Disease-free survival of patients with a K1-low tumor was poorer than that of patients with a K1-high tumor (p = 0.005). Furthermore, no patient with a K1-high tumor developed recurrence after initial surgery. CONCLUSION: The perfusion parameters obtained using E-CT were significantly associated with biological features and prognosis of NF-PanNENs.

Increased mitochondria are responsible for the acquisition of gemcitabine resistance in pancreatic cancer cell lines.

Pancreatic ductal adenocarcinoma has a particularly poor prognosis as it is often detected at an advanced stage and acquires resistance to chemotherapy early during its course. Stress adaptations by mitochondria, such as metabolic plasticity and regulation of apoptosis, promote cancer cell survival; however, the relationship between mitochondrial dynamics and chemoresistance in pancreatic ductal adenocarcinoma remains unclear. We here established human pancreatic cancer cell lines resistant to gemcitabine from MIA PaCa-2 and Panc1 cells. We compared the cells before and after the acquisition of gemcitabine resistance to investigate the mitochondrial dynamics and protein expression that contribute to this resistance. The mitochondrial number increased in gemcitabine-resistant cells after resistance acquisition, accompanied by a decrease in mitochondrial fission 1 protein, which induces peripheral mitosis, leading to mitophagy. An increase in the number of mitochondria promoted oxidative phosphorylation and increased anti-apoptotic protein expression. Additionally, enhanced oxidative phosphorylation decreased the AMP/ATP ratio and suppressed AMPK activity, resulting in the activation of the HSF1-heat shock protein pathway, which is required for environmental stress tolerance. Synergistic effects observed with BCL2 family or HSF1 inhibition in combination with gemcitabine suggested that the upregulated expression of apoptosis-related proteins caused by the mitochondrial increase may contribute to gemcitabine resistance. The combination of gemcitabine with BCL2 or HSF1 inhibitors may represent a new therapeutic strategy for the treatment of acquired gemcitabine resistance in pancreatic ductal adenocarcinoma.

Clinical characteristics, prognosis, and surgical outcomes of patients with non-HBV and non-HCV related hepatocellular carcinoma: three-decade observational study.

BACKGROUND: The incidence of non-hepatitis B virus, non-hepatitis C virus hepatocellular carcinoma (non-B non-C-HCC) is increasing worldwide. We assessed the clinical characteristics and surgical outcomes of non-B non-C-HCC, versus hepatitis B (HBV-HCC) and hepatitis C (HCV-HCC). METHODS: Etiologies, fibrosis stages, and survival outcomes were analyzed of 789 consecutive patients who underwent surgery from 1990 to 2020 (HBV-HCC, n = 149; HCV-HCC, n = 424; non-B non-C-HCC, n = 216). RESULTS: The incidence of hypertension and diabetes mellitus was significantly higher in patients with NON-B NON-C-HCC than in those with HBV-HCC and HCV-HCC. Significantly more advanced tumor stages were observed in patients with non-B non-C-HCC; however, better liver function and lower fibrosis stages were observed. Patients with non-B non-C-HCC had significantly worse 5-year overall survival than patients with HBV-HCC; overall survival was comparable between patients with non-B non-C-HCC and HCV-HCC. Patients with HCV-HCC had significantly worse 5-year recurrence-free survival than patients with HBV-HCC and non-B non-C-HCC. In patients with non-B non-C-HCC, overall survival was comparable among three periods (1990-2000, 2001-2010, and 2011-2020) despite significant improvement in patients with HBV-HCC and HCV-HCC. CONCLUSION: The prognosis of non-B non-C-HCC was similar to that of HBV-HCC and HCV-HCC regardless of tumor progression at surgery. Patients with hypertension, diabetes mellitus, and dyslipidemia require careful systematic follow-up and treatment.

Impact of Early Enteral Nutrition on Delayed Gastric Emptying and Nutritional Status After Pancreaticoduodenectomy.

BACKGROUND: Although early enteral nutrition (EEN) is an accepted practice after pancreaticoduodenectomy (PD), the impact of EEN on postoperative complications or nutritional status remains unclear. We aimed to investigate the impact of EEN on delayed gastric emptying (DGE) and nutritional status after PD. METHODS: A total of 143 patients underwent PD between January 2012 and September 2020. We excluded patients who underwent a two-stage pancreatojejunostomy, in whom the enteral tube was accidentally pulled out, or with insufficient information in their medical records. The incidence of postoperative complications was compared between patients who received EEN (EEN group, n = 21) and those who did not (control group, n = 21) after propensity score matching. Univariate and multivariate analyses were performed to identify the risk factors affecting the incidence of these complications. Nutritional status was assessed at postoperative months 1, 3, and 6. RESULTS: The incidence of grade B/C DGE in the EEN group was significantly lower than that in the control group (4.8% vs. 28.6%, p = 0.03). There was no significant difference in overall morbidity, incidence of any other postoperative complications, or all-grade DGE. In multivariate analysis, EEN was associated with a reduction in the incidence of grade B/C DGE (p < 0.01). In the analysis of nutritional status, EEN was significantly associated with better nutritional status at postoperative month 1. CONCLUSION: EEN can lead to a lower clinically relevant DGE rate and better nutritional status in the early postoperative period in patients undergoing PD.

Preoperative Peripheral Blood Lymphocyte-to-Monocyte Ratio Predicts Long-Term Outcome for Patients with Pancreatic Ductal Adenocarcinoma.

BACKGROUND: Although various biomarkers are useful in predicting cancer prognosis, the most effective preoperative systemic biomarkers for pancreatic ductal adenocarcinoma (PDAC) have not been established. This study aimed to evaluate whether the lymphocyte-to-monocyte ratio (LMR) can predict the long-term outcomes for patients who were to undergo surgical resection of PDAC. METHODS: The study involved 170 patients with PDAC who underwent resection. Multivariate analysis was performed to identify the independent prognostic factors for overall survival (OS) and disease-free survival (DFS) among clinicopathologic, surgical, and seven systemic biomarker-related factors including LMR. Subgroup analysis of PDAC located in the body and tail of the pancreas (B/T PDAC) was performed (n = 60) to eliminate the influence of preoperative cholangitis and surgical procedure. Furthermore, OS according to the postoperative course of the LMR value group was investigated. RESULTS: A low LMR (<3.3) was the only independent predictive factor for OS (hazard ratio [HR], 3.52; p < 0.001) and DFS (HR, 3.31; p < 0.001) among the systemic biomarkers. Subgroup analysis of the B/T PDAC also showed that low the LMR was the independent predictive factor for OS (HR, 3.24; p = 0.002) and DFS (HR, 4.42; p = 0.003). The PDAC that maintained a high LMR from before surgery to 1 year after surgery showed good long-term outcomes (median OS, 8.5 years; 5-year survival rate, 61.8 %). CONCLUSIONS: Preoperative LMR was an independent predictor of OS and DFS after surgery for PDAC. Maintaining a high LMR through the pre- and postoperative courses might improve the prognosis for patients with PDAC.

Safety and Oncological Benefit of Hepatopancreatoduodenectomy for Advanced Extrahepatic Cholangiocarcinoma with Horizontal Tumor Spread: Shinshu University Experience.

BACKGROUND: Although hepatopancreatoduodenectomy (HPD) is the only means of achieving R0 resection of widespread extrahepatic cholangiocarcinoma, its safety and oncological benefit remain controversial because of its inherent high risk of mortality and morbidity. OBJECTIVE: The aim of this study was to retrospectively analyze short- and long-term outcomes and evaluate the safety and oncological benefit of this advanced procedure. METHODS: The study cohort comprised 37 consecutive patients who had undergone major HPD. Portal vein embolization was performed before surgery in 20 (54%) patients with future remnant liver volume < 35%. RESULTS: The median operative time and blood loss were 866 min and 1000 mL, respectively. Concomitant vascular resection was performed in five patients (14%). The overall morbidity and mortality rates were 100% and 5.4% (n = 2), respectively. Nineteen patients (51%) had major (Clavien-Dindo grade III or higher) complications, the most common being intra-abdominal infection (49%) and post-hepatectomy liver failure (46%, grade B/C: 32%/5%), followed by postoperative pancreatic fistula (30%, grade B/C). R0 resection was achieved in 31 patients (84%). The 1-, 3-, and 5-year overall survival (OS) rates were 83%, 48%, and 37%, respectively. In patients with R0 resection, 5-year OS was comparable between patients who had undergone major HPD and major hepatectomy alone (41% vs. 40%, p = non-significant). CONCLUSIONS: HPD is a valid treatment option for extensive cholangiocarcinoma, offering long-term survival benefit at the cost of relatively high but acceptable morbidity and mortality rates. HPD is advocated in selected patients provided that it is considered possible to achieve R0 resection.

Survival Outcomes of Gemcitabine Plus S-1 Adjuvant Chemotherapy after Surgical Resection for Advanced Biliary Tract Cancer.

INTRODUCTION: The usefulness of adjuvant chemotherapy in biliary tract cancer (BTC) is poorly reported. This study aimed to evaluate the effectiveness and safety of adjuvant gemcitabine plus S-1 (GS) chemotherapy after curative surgical resection for BTC. METHODS: 225 BTC patients who underwent surgical resection between January 2006 and May 2019 were enrolled in this study. Twenty-seven patients received adjuvant chemotherapy with GS (GS group), whereas 67 patients underwent surgery alone (S group). Twenty-three matching pairs were derived through propensity score (PS) matching analysis. Patients received 12 cycles of adjuvant chemotherapy (70 mg/m2 oral S-1 for 7 consecutive days plus intravenous gemcitabine 1,000 mg/m2 on day 7). The primary end point was recurrence-free survival (RFS). The secondary end points were the 1-, 2-, and 3-year RFS and overall survival (OS) rates, tolerability, and frequency of grade 3/4 toxicity. RESULTS: The completion rate was 81.5%; no treatment-related deaths were observed. Grade 3/4 adverse events were seen in 40.7% of the patients. RFS (3-year RFS rate: 59.3% vs. 39.1%, p = 0.049) and OS (3-year OS rate: 71.7% vs. 53.4%, p = 0.008) were significantly better in the GS group than in the S group among PS-matched pairs. DISCUSSION/CONCLUSION: GS chemotherapy after curative surgery was well tolerated, showed better clinical benefit in the adjuvant setting, and can effectively reduce BTC recurrence.

The survival benefit of surgery for perihilar cholangiocarcinoma in octogenarians: Shinshu University experience.

BACKGROUND AND OBJECTIVES: In today's aging society, surgery is increasingly performed for older patients with perihilar cholangiocarcinoma (PHCC). This study aimed to examine survival and oncological outcomes in octogenarians with PHCC who underwent surgery. METHODS: We retrospectively examined 480 consecutive PHCC patients treated for PHCC between 1991 and 2020. Two hundred forty-seven underwent resection. Patient and clinical characteristics, including postoperative complications, overall survival (OS), and disease-free survival (DFS) were analyzed. RESULTS: The proportion of octogenarians with PHCC undergoing surgery increased from 5.2% in 1991-2000 to 13.4% in 2016-2020. R0 resection and postoperative complication rates were comparable between octogenarians and younger patients. Five-year OS (30.0% vs. 31.7%) and DFS (20.0% vs. 29.5%) did not significantly differ. One-year OS was significantly better in octogenarians who underwent resection than those who did not (95.0% vs. 17.6%; p < .001). Two octogenarians who developed Clavien-Dindo grade III complications had undergone right hemihepatectomy (RH). Posthepatectomy liver failure and biliary leakage (Grade B) were also observed in octogenarians who underwent RH. CONCLUSION: In well-selected octogenarians with PHCC, surgery offers short- and long-term outcomes comparable with those of their younger counterparts. RH may be considered in octogenarians on an individual basis.

Impact of Remnant Carcinoma in Situ at the Ductal Stump on Long-Term Outcomes in Patients with Distal Cholangiocarcinoma.

BACKGROUND: The management of positive ductal margins with carcinoma in situ (R1-CIS) after resection is controversial. The aim of this study was to evaluate the impact of R1-CIS on survival in patients who underwent resection for distal cholangiocarcinoma. METHODS: We enrolled 121 consecutive patients with distal cholangiocarcinoma. Poor prognostic factors were investigated by multivariable analysis, and we performed a stratified analysis to evaluate the impact of R1-CIS on survival in patients with or without prognostic factors. RESULTS: Multivariable analysis identified node-positive status as the prognostic factor (P = 0.003). Stratified by lymph node status, overall survival (OS) in the R0 group was significantly better than that in the R1-CIS group in node-negative patients (57.1% vs 30.0%; P < 0.050). Although OS was comparable between the two groups in node-positive patients (5-year OS: 22.2% vs 20.0%, respectively; P = not significant). Furthermore, OS in patients in whom R0 was achieved by additional resection was significantly better than that in patients with R1-CIS (5-year OS: 66.7% vs 30.0%, respectively; P < 0.050). CONCLUSIONS: Remnant CIS is associated with a poor prognosis in patients with node-negative distal cholangiocarcinoma. Every effort should be made to achieve negative bile duct margins.

Usefulness and limitation of indocyanine green fluorescence for detection of peritoneal recurrence after hepatectomy for hepatocellular carcinoma: a case report.

BACKGROUND: Peritoneal recurrence of hepatocellular carcinoma (HCC) after hepatectomy occurs rarely, accounting for less than 1% of all recurrences. Reported causes of such dissemination include a history of rupture of the original HCC, needle biopsy or puncture treatment, and surgical procedures. There is no consensus on the optimal treatment strategy for peritoneal dissemination. There have been few reports on assisting resection of peritoneal dissemination by using indocyanine green (ICG) fluorescence. CASE PRESENTATION: A 57-year-old man underwent posterior sectionectomy for HCC. Six months later, computed tomography revealed multiple nodules suspected of indicating peritoneal dissemination. Various preoperative imaging studies demonstrated only four nodules, the doubling time of the tumors being rapid at 22 days. The nodules were therefore resected. ICG (0.5 mg/kg) was injected intravenously 2 days before the procedure, enabling identification of the nodules by their brightness in the operative field under near-infrared lighting. A total of eight lesions were detected during the procedure and resected, some of which had not been identified by preoperative imaging studies. We diagnosed peritoneal dissemination of HCC based on the pathological findings and their similarity to those of the original HCC. We concluded that the recurrences were likely attributable to exposure of the tumor to the serosa at the time of the original operation. CONCLUSIONS: Although ICG fluorescence is useful for identifying peritoneal dissemination of HCC, attention should be paid to the difficulty in detecting deep lesions and occurrence of false positives.

[Pancreatic adenocarcinoma:a case containing a cyst enclosing a dilated tubular gland duct].

This case report describes a 73-year-old woman with pancreatic adenocarcinoma who had undergone a colectomy for colorectal cancer in 1995 and a right mastectomy and axillary dissection for breast cancer in 2013. In January 2019, a tumor, approximately 20mm in diameter, was detected in the pancreatic body. It contained a cyst noted to have delayed perfusion towards the center on abdominal computed tomography. On T1-weighted magnetic resonance imaging (MRI), almost the entire tumor exhibited low intensity. On T2-weighted MRI, however, the tumor center displayed high intensity, the tumor wall displayed low intensity, and the outermost layer displayed high intensity. On endoscopic ultrasound, the tumor center displayed low echo density, the tumor wall had a slightly elevated echo density, and the outermost layer had a low echo density. A distal pancreatectomy was performed for a suspected metastatic pancreatic cancer, pancreatic neuroendocrine neoplasm, or invasive ductal carcinoma without tubular adenocarcinoma. Histopathological examination revealed that the tumor cells had formed atypical tubular gland ducts with a fibrous stroma in the background. The lesion differed from the histopathological findings of her previous colorectal and breast cancers, and it was ultimately diagnosed as a pancreatic ductal adenocarcinoma. The lumen of the cyst was covered with tumor cells identical to those of the atypical tubular gland ducts in the tumor parenchyma, suggesting that the cyst was a dilated tubular gland duct.

Preoperative C-reactive protein-to-albumin ratio predicts long-term outcomes in extrahepatic cholangiocarcinoma patients.

BACKGROUND: Systemic inflammation may have prognostic value in some malignancies and association with lymph node metastasis. This study aimed to evaluate the impact of systemic inflammatory biomarkers on long-term and oncological outcomes as well as to assess the association between biomarkers with lymph node metastasis in extrahepatic cholangiocarcinoma patients. METHODS: We enrolled 271 consecutive patients who underwent surgical resection for extrahepatic cholangiocarcinoma. Poor prognostic factors were compared to identify the biomarkers that were most associated with overall survival (OS) and disease-free survival (DFS) using receiver operating characteristic curves and multivariable analysis. Furthermore, we evaluated the relationship between biomarkers and lymph node metastasis. RESULTS: Four and two biomarkers were predictive for OS and DFS, respectively, among which, the C-reactive protein-to-albumin ratio (CAR) had the highest area under the curve values (OS: 0.631, DFS: 0.624). Multivariable analysis showed that a high CAR was an independent prognostic factor for both OS and DFS (P = .002 and P < .001, respectively). Although a high CAR was not significantly correlated with lymph node metastasis (P = .645), carbohydrate antigen 19-9 showed a significant correlation (P < .001). CONCLUSIONS: Preoperative CAR is the most accurate prognostic factor for OS and DFS in extrahepatic cholangiocarcinoma patients and is independent of lymph node metastasis.

Impact of age on groin hernia profiles observed during laparoscopic transabdominal preperitoneal hernia repair.

BACKGROUND: How increasing age affects the characteristics of groin hernia remains uncertain. This study evaluated the association between age and the type of groin hernia, especially with respect to its multiplicity, observed during laparoscopic transabdominal preperitoneal (TAPP) hernia repair. METHODS: We retrospectively evaluated 634 consecutive patients with primary groin hernia who underwent laparoscopic TAPP repair between October 2000 and June 2017. Patients were stratified into 4 age groups: < 60 years, 60-69 years, 70-79 years, and 80 years or older. RESULTS: The incidence of occult contralateral hernia and multiple ipsilateral hernias increased significantly with each increasing age group: 7.3%, 10.4%, 12.7%, and 20.8% for occult contralateral hernia (p = 0.005), and 5.6%, 9.2%, 16.8%, and 21.7% for multiple ipsilateral hernias (p < 0.001), respectively. Univariate analyses showed that an older age (age ≥ 70 years) was the only factor significantly associated with the presence of multiple groin hernias (odds ratio, 2.69; 95% confidence interval, 1.89-3.81; p < 0.001). In patients with multiple ipsilateral hernias, the prevalent form in men was a pantaloons hernia, with an incidence of about 70% across all age groups, whereas in women it was groin hernias, with one component being a femoral hernia, an obturator hernia, or both. CONCLUSIONS: The multiple occurrence of groin hernias, either unilaterally or bilaterally, was a clinical feature in the elderly.

Survival Benefits of Surgical Resection in Patients with Recurrent Biliary Tract Carcinoma.

BACKGROUND: Whether surgical resection for recurrent biliary tract carcinoma (BTC) prolongs survival and the patients who are most likely to benefit from such treatment remain unclear. METHODS: Among 251 patients with recurrences after the initial resection of BTC, a total of 21 patients (8.4%) underwent surgical resection for the recurrence, with a zero mortality rate. The clinicopathological features of these patients were compared with those of patients who did not undergo surgery. RESULTS: The median survival time (MST) after the first recurrence and the 5-year post-recurrent survival (PRS) rate were 19.8 months and 32.8%, respectively, for patients who underwent re-resection. Fourteen patients (66.7%) experienced second recurrences; however, none of these patients underwent further surgical resection. Surgical resection for recurrence was identified as an independent prognostic factor for survival after recurrence (hazard ratio of 0.33, 95% CI of 0.17-0.58, p < 0.001). Patients with less than three liver metastases had a significantly better PRS after surgical resection than after chemotherapy (p = 0.015). Among the patients with an isolated solitary liver metastasis, patients who underwent resection had a significantly longer MST after the first recurrence than patients receiving chemotherapy (22.8 vs. 10.9 months, p = 0.025), whereas the PRS was similar between the two groups among patients with two liver lesions. CONCLUSIONS: Surgical resection for recurrent BTC may prolong survival in highly selected patients. A hepatectomy might offer a survival benefit for patients with a solitary liver metastasis.

Nomogram predicting long-term survival after the diagnosis of intrahepatic recurrence of hepatocellular carcinoma following an initial liver resection.

BACKGROUND: The aim of this study was to construct and validate a nomogram for predicting survival after the intrahepatic recurrence of hepatocellular carcinoma (HCC) following an initial hepatectomy. METHODS: A primary cohort of 268 patients who underwent curative hepatectomy for HCC at Shinshu University Hospital between 1990 and 2010 was retrospectively studied. A nomogram was constructed based on independent prognostic factors for overall survival after recurrence. The predictive performance was evaluated using the concordance index (c-index) and a calibration curve. The nomogram was then externally validated in a cohort of patients from Tokyo University Hospital (n = 296). RESULTS: In multivariate analysis, the following 5 variables were identified as independent predictors of overall survival and incorporated into the nomogram-Japan Integrated Stage score at initial liver resection, platelet count at initial liver resection, time until intrahepatic recurrence, vascular invasion at recurrence, and type of treatment used for intrahepatic recurrence. The nomogram had a c-index of 0.75 (95% confidence interval 0.60-0.85) for the Shinshu cohort and 0.71 (0.57-0.81) for the Tokyo cohort. The predicted 3- and 5-year survival probabilities corresponded well with the actual outcomes. CONCLUSIONS: The established nomogram might be useful for estimating survival after the intrahepatic recurrence of HCC.

Contrast-enhancement ratio on multiphase enhanced computed tomography predicts recurrence of pancreatic neuroendocrine tumor after curative resection.

BACKGROUND/OBJECTIVE: No previous study has quantitatively investigated the degree of enhancement of pancreatic neuroendocrine tumors (pNETs) using a routine preoperative modality. The aim of this study was to evaluate the contrast-enhancement ratio (CER) of pNETs using multiphase enhanced CT and to assess the impact of the CER on disease recurrence after surgery. METHODS: A retrospective study was performed using data from 47 consecutive patients with pNETs who had undergone curative surgery. The CER of the tumor was calculated by dividing the CT attenuation value obtained during the maximum-enhanced phase by that obtained during the pre-enhanced phase. A region of interest was placed in the largest tumor dimension plane so as to cover as much surface of the tumor as possible while avoiding adjacent normal structures, calcification, and necrotic areas of the tumor. RESULTS: During a median follow-up period of 51 months (range, 1-132 months), a total of 4 patients (8.5%) developed disease recurrence. The median CER value was significantly lower for the patients with recurrence than for the patients without recurrence (2.9 vs. 4.3, P = 0.013). Univariate analyses showed that a CER ≤3.2 was significantly associated with disease recurrence (P < 0.001). All the patients with disease recurrence had tumors that were both large (>20 mm) and weakly enhanced (CER ≤ 3.2), whereas no recurrences were observed even in patients with tumors >20 mm when the CER was greater than 3.2. CONCLUSIONS: CER might be a useful predictor of disease recurrence in patients with pNETs.

Differential requirements for IRF-2 in generation of CD1d-independent T cells bearing NK cell receptors.

NK cell receptors (NKRs) such as NK1.1, NKG2D, and Ly49s are expressed on subsets of CD1d-independent memory phenotype CD8(+) and CD4(-)CD8(-) T cells. However, the mechanism for the generation and functions of these NKR(+) T cells remained elusive. In this study, we found that CD1d-independent Ly49(+) T cells were reduced severely in the spleen, bone marrow, and liver, but not thymus, in mice doubly deficient for IFN regulatory factor-2 (IRF-2) and CD1d, in which the overall memory phenotype T cell population was contrastingly enlarged. Because a large fraction of Ly49(+) T cells coexpressed NK1.1 or NKG2D, the reduction of Ly49(+) T cells resulted indirectly in underrepresentation of NK1.1(+) or NKG2D(+) cells. Ly49(+) T cell deficiency was observed in IRF-2(-/-) mice additionally lacking IFN-α/ßR α-chain (IFNAR1) as severely as in IRF-2(-/-) mice, arguing against the involvement of the accelerated IFN-α/ß signals due to IRF-2 deficiency. Rather, mice lacking IFN-α/ßR alone also exhibited relatively milder Ly49(+) T cell reduction, and IL-2 could expand Ly49(+) T cells from IFNAR1(-/-), but not from IRF-2(-/-), spleen cells in vitro. These results together indicated that IRF-2 acted in Ly49(+) T cell development in a manner distinct from that of IFN-α/ß signals. The influence of IRF-2 deficiency on Ly49(+) memory phenotype T cells observed in this study suggested a unique transcriptional program for this T cell population among other NKR(+) T and memory phenotype T cells.