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We examined the value of preoperative dual time point (DTP) 18F-fluorodeoxyglucose positron emission tomography/computed tomography fusion imaging (FDG PET/CT) as a predictor of early recurrence or the outcomes in patients with pancreatic cancer. Standardized uptake values (SUVs) in DTP FDG PET/CT were performed as preoperative staging. SUVmax1 and SUVmax2 were obtained in 60 min and 120 min, respectively. ΔSUVmax% was defined as (SUVmax2 − SUVmax1)/SUVmax1 × 100. The optimal cut-off values for SUVmax parameters were selected based on tumor relapse within 1 year of surgery. Optimal cut-off values for SUVmax1 and ΔSUVmax% were 7.18 and 24.25, respectively. The combination of SUVmax1 and ΔSUVmax% showed higher specificity and sensitivity, and higher positive and negative predictive values for tumor relapse within 1 year than SUVmax1 alone. Relapse-free survival (RFS) was significantly worse in the subgroups of high SUVmax1 and high ΔSUVmax% (median 7.0 months) than in the other subgroups (p < 0.0001). The multivariate Cox analysis of RFS identified high SUVmax1 and high ΔSUVmax% as independent prognostic factors (p = 0.0060). DTP FDG PET/CT may effectively predict relapse in patients with pancreatic cancer. The combination of SUVmax1 and ΔSUVmax% identified early recurrent patient groups more precisely than SUVmax1 alone.

Aberrant right hepatic arteries are sometimes involved in pancreatic head tumors or accidentally damaged during surgical procedures, which could result in postoperative complications. The risk of such injury has been discussed in patients undergoing pancreatoduodenectomy; however, no reports describe the influence of this anomaly in distal pancreatectomy. We report a patient with pancreatic body cancer with an accessory right hepatic artery following a very unique route. A 77-year-old man was referred to our hospital for the treatment of pancreatic cancer. Computed tomography revealed an anomaly in the hepatic artery, with an accessory right hepatic artery encased in the extensive tumor, which also involved the stomach, left gastric artery, and portal vein. Curative resection was achieved by distal pancreatectomy with wedge resection of the stomach and portal vein reconstruction. Both the accessory right hepatic artery and the left gastric artery were sacrificed after confirming intrahepatic arterial flow by intraoperative Doppler ultrasonography. The route of the accessory right hepatic artery in this patient was unique in that it did not run directly into the hepatic hilum but from behind the pancreatic body, where it was incorporated into the tumor. Accurate preoperative assessment and identification of arterial variations is mandatory in any type of pancreatectomy.

Background Tumor-infiltrating lymphocytes (TILs) and tumor-associated macrophages (TAMs) may be useful prognostic indicators in endometrial cancer. However, standardized assessment methods and the prognostic roles of these cells in different stage groups are unclear. Methods Formalin-fixed paraffin-embedded tissue samples of 107 endometrioid-type endometrial carcinomas (EECs) comprising 60 stage IB and 47 stage IIIC or IVB cases were evaluated. CD3+ TILs, CD8+ TILs, CD68+ TAMs, and CD163+ TAMs were detected by immunohistochemistry, and their densities were evaluated by semiquantitative and quantitative methods. TILs within tumor epithelial cell nests (E-TILs) and those within the stroma at the invasive front (S-TILs) were evaluated separately for CD3+ and CD8+ cells. The “TIL score” was defined as the sum of semiquantitative scores of CD3+ E-TILs, CD3+ S-TILs, CD8+ E-TILs, and CD8+ S-TILs. For TAMs, the area of CD68+ and CD163+ cells in the invasive margin were semiquantitatively and quantitatively evaluated. Clinicopathological and prognostic implications of TILs and TAMs in stage IB and IIIC/IVB EECs were examined by Cox univariate and multivariate analyses. Results By Cox univariate analyses, semiquantitatively low CD3+ E-TILs, low CD8+ E-TILs, and low “TIL score” were significantly correlated with worse prognosis in stage IB patients (P = 0.011, 0.040, and 0.039, respectively). Likewise, low CD3+ E-TILs and low CD8+ E-TILs, by both semiquantitative (P = 0.011 and 0.0051) and quantitative evaluations (P P = 0.0015) and low “TIL score” (P = 0.020) were significantly correlated with worse prognosis in stage IIIC/IVB patients. By Cox multivariate analyses, semiquantitatively low CD3+ E-TILs and low CD8+ E-TILs, low “TIL score”, and quantitatively low CD3+ E-TILs and low CD8+ E-TILs were independent worse prognostic factors in stage IIIC/IVB (P = 0.0011, 0.0053, 0.012, + or CD163+ TAMs were not correlated with prognosis in any patients. Conclusions Both semiquantitatively and quantitatively low E-TILs, are correlated with worse prognosis in both early and advanced stage patients with EECs. In particular, CD3+ E-TILs and CD8+ E-TILs are potentially useful prognostic markers in patients with EEC regardless of the stage.

Aquaporins (AQPs) are a family of transmembrane water channel proteins distributed in various human tissues. Recent studies revealed that AQPs play important roles in cancer biology. Few studies have documented the relationship between the prognosis, stage, and histological grade of uterine endometrioid carcinoma, with AQP expression. Hence, the present study aimed to investigate this relationship between uterine endometrioid carcinoma and AQP expression. We retrospectively reviewed records of the patients who underwent surgery for uterine body cancer between 1990 and 2010 at the National Defense Medical College Hospital, Saitama, Japan. In 241 cases of endometrioid carcinoma, we immunohistochemically examined the expression of AQP 1, 2, 3, 4, and 5, and their relationship with clinicopathological parameters and the patients’ prognosis. We investigated the relationship between the clinicopathological parameters and AQP3 expression, and found that as the FIGO stage and histological grade progressed, the percentage of AQP3 expression tends to decrease. Furthermore, we analyzed progression-free survival/overall survival (PFS/OS) using the log-rank test, and found that the AQP3-positive group had a better prognosis than AQP3-negative group (PFS: P

Purpose 18F-Fluorodeoxyglucose positron emission tomography/computed tomography fusion imaging (18F-FDG PET/CT) is an important diagnostic tool in breast cancer. The utility of maximum standardized uptake values (SUVmax) of primary tumors has been evaluated to predict sentinel node (SN) and non-SN metastasis in clinically node-negative (cN0) patients. Patients and Methods 18F-FDG PET/CT was performed on 414 cN0 patients. The following parameters were evaluated: SUVmax at 60 min (SUVmax1), SUVmax at 120 min (SUVmax2), percent change between SUVmax1 and SUVmax2 (ΔSUVmax%), SN metastasis foci maximum size (SN meta size), and ratio of metastatic SNs to total SNs or SN ratio (SNR). It was assessed whether these were risk factors for SN metastasis. The relationship between these parameters and the status of SN and/or non-SN metastasis was retrospectively explored to predict non-SN metastasis. Results All SUV parameters significantly correlated with pathological T factor (pT), nuclear grade, lymphatic invasion (Ly), and Ki-67 labeling index. On multivariate analysis, pT and Ly were independent predictive factors for SN metastasis. In SN meta-positive cases, SN meta size, SNR, and ΔSUVmax% were predictors for non-SN metastasis on univariate analyses, and the former two were independent predictors on multivariate analysis. The combination of SUVmax2 and ΔSUVmax% was an independent predictor of non-SN metastasis (P = 0.0312) and was associated with prediction of non-SN metastasis negative status with high probability (92.3%). Conclusions In patients with cN0 breast cancer, SUV parameters of the primary tumor were correlated with pathological features. The combination of SUVmax2 and ΔSUVmax% may be useful for predicting non-SN metastasis.

Background: The expression of mesothelin correlates with a poor prognosis in patients with breast cancer. Since mesothelin plays a role in cancer metastasis in association with CA125, we herein examined the clinicopathological significance and prognostic implications of the co-expression of mesothelin and CA125 in breast cancer. Methods: The expression of mesothelin and CA125 was immunohistochemically examined in tissue samples collected from 478 breast cancer patients. The expression of these two molecules in more than 1% of tumor cells was defined as positive. The relationships between the co-expression of mesothelin and CA125, clinicopathological parameters, and clinical outcomes were analyzed by the chi-squared test and Cox’s univariate and multivariate proportional hazard model analyses. Results: Among 478 patients, mesothelin and CA125 were co-expressed in 48 (10%), mesothelin only in 75 (16%), CA125 only in 217 (45%), and neither in 234 (49%). A strong correlation was observed between the expression of mesothelin and CA125 (P =0.0004). The co-expression of mesothelin and CA125 correlated with unfavorable patient relapse-free survival (RFS) (P = 0.0001) and was identified as an independent predictor of RFS by Cox’s multivariate analysis. Conclusion: This is the first study to demonstrate the prognostic significance of the co-expression of mesothelin and CA125 in breast cancer. The co-expression of these two molecules may play a significant role in the acquisition of aggressive clinical behavior.

The present study reports a case of metachronous bilateral breast cancer associated with neurofibromatosis type 1 (NF1). A 67-year-old female, who had undergone a radical mastectomy of the left breast 34 years ago due to breast cancer, presented with a tumor of the right breast. The clinical stage of the original breast cancer was T2N0M0 stage IIA and adjuvant chemotherapy had not been not administered. With regard to the right-sided breast tumor, on physical examination, multiple neurofibromas and cafe-au-lait spots were found to be scattered over the skin. A 2-cm tumor was palpable. The preoperative histopathological diagnosis of the right-sided breast tumor was invasive ductal carcinoma, T2N0M0 stage IIA, with negative results for hormone receptors and human epidermal growth factor receptor 2. The patient underwent a modified radical mastectomy and axillary node dissection, and received adjuvant chemotherapy. The bilateral tumors were similar in histology and immunophenotype, each being histological grade 3, triple-negative and with a basal-like subtype. Based on a literature review of 90 breast cancers in 84 patients with NF1 (84 patients, 90 breasts), younger age onset, advanced clinical stage and hormone receptor negativity were characteristic features. Bilateral cancer occurred in 8.3% of patients and was characterized by ER negativity, earlier stage and younger age compared with patients with unilateral cancer.

The expression of mesothelin correlates with a poor prognosis in patients with breast cancer. Since mesothelin plays a role in cancer metastasis in association with CA125, we herein examined the expression of mesothelin and CA125, and the clinicopathological meaning and prognosis of the co-expression of mesothelin and CA125 in breast cancer. Our results showed that among 478 patients, mesothelin and CA125 were co-expressed in 48 (10 %), mesothelin only in 75 (16 %), CA125 only in 217 (45 %), and neither in 234 (49 %). A high correlation was observed between the expression of mesothelin and CA125 (P =0.0004). The co-expression of mesothelin and CA125 correlated with poor patient relapse-free survival (RFS) (P = 0.0001) and was identified as an independent predictor of RFS by Cox’s multivariate analysis. In conclusion, this is the first to report the prognostic significance of the co-expression of mesothelin and CA125 in breast cancer. The co-expression of mesothelin and CA125 may be clinically useful for prognostication after surgical therapy in patients with breast cancer. Supplementary Information The online version contains supplementary material available at 10.1186/s40364-021-00335-3.

Recent studies have suggested that the interaction of mesothelin (MSLN) and cancer antigen 125 (CA125) enhances tumor metastases. The aim of the present study was to clarify the impact of MSLN and CA125 co-expression on the prognosis of patients with extrahepatic bile duct carcinoma (BDC). Tissue samples from patients who underwent surgical resection between 2007 and 2015 for perihilar or distal BDC were immunohistochemically examined. The expression levels of MSLN and CA125 in tumor cells were analyzed. The expression in

Background The 8th edition American Joint Committee on Cancer (AJCC) proposed a prognostic stage (PS), which included not only anatomical factors, but also biological factors. We aimed to investigate the clinicopathological significance of the PS and to compare PS and anatomical stage (AS) that has been established by the Union for International Cancer Control (UICC). Methods Between 2002 and 2017, 800 patients were included in the study. Patients were classified using pathological UICC AS and pathological AJCC PS. The usefulness of PS in comparison with AS was validated using the Akaike information criterion (AIC) and Harrell concordance index (C-index). Results A total of 401 (50.1%) patients had pathological AS I, 324 (40.5%) had AS II, and 75 (9.4%) had AS III. Meanwhile, 535 (66.8%) had pathological PS I, 163 (20.4%) had PS II, and 102 (12.8%) had PS III. The number of AS II cases was 1.99-fold higher than that of PS II cases. For each stage, these survival curves were almost similar between AS and PS classification. Therefore, many patients to be classified into stage I and stage III were included in AS II group, while many patients to be classified into stage II were included in AS I group. To trichotomize the survival groups, PS appeared to be more specific than AS, and AIC and C-index confirmed the speculation. Conclusion For the prognostication of primary breast cancer patients, AJCC PS appeared to be able to stratify the cases more appropriately than UICC AS.

Background To evaluate the clinicopathological and prognostic significance of the percentage change between maximum standardized uptake value (SUVmax) at 60 min (SUVmax1) and SUVmax at 120 min (SUVmax2) (ΔSUVmax%) using dual time point 18F-fluorodeoxyglucose emission tomography/computed tomography (18F-FDG PET/CT) in breast cancer. Methods Four hundred and sixty-four patients with primary breast cancer underwent 18F-FDG PET/CT for preoperative staging. ΔSUVmax% was defined as (SUVmax2 − SUVmax1) / SUVmax1 × 100. We explored the optimal cutoff value of SUVmax parameters (SUVmax1 and ΔSUVmax%) referring to the event of relapse by using receiver operator characteristic curves. The clinicopathological and prognostic significances of the SUVmax1 and ΔSUVmax% were analyzed by Cox’s univariate and multivariate analyses. Results The optimal cutoff values of SUVmax1 and ΔSUVmax% were 3.4 and 12.5, respectively. Relapse-free survival (RFS) curves were significantly different between high and low SUVmax1 groups (P = 0.0003) and also between high and low ΔSUVmax% groups (P = 0.0151). In Cox multivariate analysis for RFS, SUVmax1 was an independent prognostic factor (P = 0.0267) but ΔSUVmax% was not (P = 0.152). There was a weak correlation between SUVmax1 and ΔSUVmax% (P R2 = 0.166). On combining SUVmax1 and ΔSUVmax%, the subgroups of high SUVmax1 and high ΔSUVmax% showed significantly worse prognosis than the other groups in terms of RFS (P = 0.0002). Conclusion Dual time point 18F-FDG PET/CT evaluation can be a useful method for predicting relapse in patients with breast cancer. The combination of SUVmax1 and ΔSUVmax% was able to identify subgroups with worse prognosis more accurately than SUVmax1 alone.

Purpose 18F-Fluorodeoxyglucose positron emission tomography/computed tomography fusion imaging (18F-FDG PET/CT) is an important diagnostic tool in breast cancer. The utility of maximum standardized uptake values (SUVmax) of primary tumors has been evaluated to predict sentinel node (SN) and non-SN metastasis in clinically node-negative (cN0) patients. Patients and Methods 18F-FDG PET/CT was performed on 414 cN0 patients. The following parameters were evaluated: SUVmax at 60 min (SUVmax1), SUVmax at 120 min (SUVmax2), percent change between SUVmax1 and SUVmax2 (ΔSUVmax%), SN metastasis foci maximum size (SN meta size), and ratio of metastatic SNs to total SNs or SN ratio (SNR). It was assessed whether these were risk factors for SN metastasis. The relationship between these parameters and the status of SN and/or non-SN metastasis was retrospectively explored to predict non-SN metastasis. Results All SUV parameters significantly correlated with pathological T factor (pT), nuclear grade, lymphatic invasion (Ly), and Ki-67 labeling index. On multivariate analysis, pT and Ly were independent predictive factors for SN metastasis. In SN meta-positive cases, SN meta size, SNR, and ΔSUVmax% were predictors for non-SN metastasis on univariate analyses, and the former two were independent predictors on multivariate analysis. The combination of SUVmax2 and ΔSUVmax% was an independent predictor of non-SN metastasis (P = 0.0312) and was associated with prediction of non-SN metastasis negative status with high probability (92.3%). Conclusions In patients with cN0 breast cancer, SUV parameters of the primary tumor were correlated with pathological features. The combination of SUVmax2 and ΔSUVmax% may be useful for predicting non-SN metastasis. Electronic supplementary material The online version of this article (10.1245/s10434-020-08269-0) contains supplementary material, which is available to authorized users.

Background To evaluate the clinicopathological and prognostic significance of the percentage change between maximum standardized uptake value (SUVmax) at 60 min (SUVmax1) and SUVmax at 120 min (SUVmax2) (ΔSUVmax%) using dual time point 18F-fluorodeoxyglucose emission tomography/computed tomography (18F-FDG PET/CT) in breast cancer. Methods Four hundred and sixty-four patients with primary breast cancer underwent 18F-FDG PET/CT for preoperative staging. ΔSUVmax% was defined as (SUVmax2 − SUVmax1) / SUVmax1 × 100. We explored the optimal cutoff value of SUVmax parameters (SUVmax1 and ΔSUVmax%) referring to the event of relapse by using receiver operator characteristic curves. The clinicopathological and prognostic significances of the SUVmax1 and ΔSUVmax% were analyzed by Cox’s univariate and multivariate analyses. Results The optimal cutoff values of SUVmax1 and ΔSUVmax% were 3.4 and 12.5, respectively. Relapse-free survival (RFS) curves were significantly different between high and low SUVmax1 groups (P = 0.0003) and also between high and low ΔSUVmax% groups (P = 0.0151). In Cox multivariate analysis for RFS, SUVmax1 was an independent prognostic factor (P = 0.0267) but ΔSUVmax% was not (P = 0.152). There was a weak correlation between SUVmax1 and ΔSUVmax% (P

Mesothelin is expressed in various types of malignant tumors. The present study immunohistochemically investigated mesothelin expression and its clinicopathological significance in each subtype of breast cancer, with special reference to its cellular localization, in particular, membrane mesothelin expression. Using tissue specimens from 482 patients with breast cancer, immunohistochemistry was used to study mesothelin expression and help classify its localization as membrane or cytoplasmic expression. Mesothelin expression was detected in 77 (16.0%) cases and was the highest in triple-negative breast cancer (31/75; 41.3%), followed by human epithelial growth factor receptor type 2 type (6/33, 18.2%) and luminal type (36/374; 9.6%). Among the 482 cases, membrane mesothelin expression was detected in 73 cases and was significantly associated with a negative hormone receptor status, higher Ki-67 labeling index, nuclear grade 3 and a lower relapse-free survival rate. Cytoplasmic mesothelin expression was not significantly associated with a lower relapse-free survival rate (P=0.058). In the 343 cases of luminal type, the membrane mesothelin expression-positive group had significantly worse prognosis than the membrane mesothelin-expression-negative group (P=0.042). There was no significant difference in the relapse-free survival rate according to the membrane mesothelin expression status in the triple-negative type and other types. It was suggested that membrane mesothelin expression in luminal type breast cancer is associated with a lower rate of relapse-free survival.

Deuterium-labelled coenzyme Q10 ([2-CD3-1′-CD2]coenzyme Q10, coenzyme Q10-d5 ) was synthesized by condensation of 2,3-dimethoxy-[5-CD3]methyl-1, 4-hydroquinone with [1-CD2]decaprenol. Five positions were selected for deuteration as replacement at these positions allowed examination of every step of the synthesis. This examination was carried out by a combination of 1H- and 13C-nuclear magnetic spectrometry and mass spectrometry. Further, these positions have been proved to be metabolically stable. This reagent makes simultaneous quantification of the source of coenzyme Q10 (exogenously supplied or endogenously supplied) possible in biological samples by measurements on gas chromatography–mass spectrometry. Copyright © 2002 John Wiley & Sons, Ltd.

Radio-labelled coenzyme Q10, labelled at the 3′-position with 14C, was synthesized starting from natural solanesol and ethyl [3-14C] acetoacetate. The radiochemical yield was 8.0% from ethyl [3-14C] acetoacetate. The specific radioactivity of the product was 44.8 μCi, 1.66 MBq/mg. The specific radioactivity and radiochemical purity are sufficiently high to enable us to use this labelled form of coenzyme Q10 in metabolic studies. Copyright © 2002 John Wiley & Sons, Ltd.

A series of oxazoles (III) is prepared in good yields by a Hantzsch-type reaction of amides (I) with bromides (II) and a subsequent dehydration of intermediate 4,5-dihydro-1,3-oxazol-4-ol derivatives.