Risk stratification for predicting postoperative recurrence of gastric cancer by grade of venous invasion.

BACKGROUND: Venous invasion (VI) in pathological examination of surgically resected gastric cancer (GC) may predict postoperative recurrence, but there are no objective criteria for VI grading. METHODS: 157 GC patients (pathological stages I 82, II 34, and III 41) who underwent surgery with curative intent were analyzed. VI was graded in pathological examination by elastica van Gieson staining based on the number of VIs per glass slide as follows: v0, 0; v1, 1-3; v2, 4-6; and v3, ≥ 7. Filling-type invasion in veins with a minor axis of ≥ 1 mm increased the grade by 1. The association of VI grade with prognosis was statistically analyzed. RESULTS: Recurrence increased with VI grade (v0 1.5%, v1 29.6%, v2 41.7%, v3 78.6%). VI grade as well as pathological (p) tumor, node, metastasis (TNM) stage was a significant recurrence predictor by the multivariate Cox analysis. VI grade was implicated in hematogenous and peritoneal recurrences independent of pTNM stage but not in nodal recurrence. GC was then divided into two tiers, without indication of adjuvant chemotherapy (AC) (pStage I, pT1 and pT3N0) and with AC indication (pStages remaining II/III), based on the ACTS-GC trial, which is common in Japan and East Asia. VI grade was a significant recurrence predictor in both tiers. v2/v3 revealed a significantly worse recurrence-free survival (RFS) than v0/v1 in GC without AC indication. v0/v1 exhibited RFS rate exceeding 95% even after 5 years but that of v2/v3 fell around 70% within one year postoperatively, suggesting that AC may be considered for this tier with v2/v3. GC with AC indication exhibited dismal RFS according to the VI grade. RFS rate fell below 80% within one year postoperatively when VI was positive, while recurrence was not observed in v0, which was, however, rare in this tier (10.9%). Differentiation grade did not significantly affect postoperative prognosis in both tiers. CONCLUSIONS: VI grade was a significant predictor of postoperative GC recurrence irrespective of the AC indication based on the ACTS-GC study and this VI grading system could be applied in future studies of adjuvant therapy in GC presently deemed without AC indication in Japan.

Risk stratification for predicting postoperative recurrence/metastasis of colorectal cancer by grade of venous invasion coupled with histological subtype.

BACKGROUND: Colorectal cancer (CRC) consists of several histological subtypes that greatly affect prognosis. Venous invasion (VI) has been implicated in the postoperative recurrence of CRC, but the relationship between the VI grade and postoperative recurrence in each histological subtype has not been clarified thus far. METHODS: A total of 323 CRCs without distant metastasis at surgery (pathologic stage III or lower), including 152 well-to-moderately differentiated adenocarcinomas (WMDAs), 98 poorly differentiated adenocarcinomas (PDAs), and 64 mucinous adenocarcinomas (MUAs), were analyzed. They were routinely processed pathologically, and VI was graded as follows irrespective of location by elastica van Gieson staining: v0 (none), no venous invasion; v1 (mild), 1-3 invasions per glass slide; v2 (moderate), 4-6 invasions per glass slide; and v3 (severe), ≥ 7 invasions per glass slide. Filling-type invasion in veins with a minor axis of ≥ 1 mm increased the grade by 1. The association of VI grade with prognosis was statistically analyzed. RESULTS: All recurrences occurred as distant metastases. Recurrence increased with VI grade in WMDA (v0 11.8%, v1 15.8%, v2 73.9%, v3 75.0%) and MUA (v0 15.2%, v1 30.8%, v2 40.0%). The recurrence rate was relatively high in PDA even with v0 and increased with VI grade (v0 27.8%, v1 32.7%, v2 33.3%, v3 60.0%). VI grade was a significant predictor of recurrence in WMDA but not in PDA and MUA by multivariate analysis. In node-negative (stage II or lower) CRC, the recurrence-free survival (RFS) rate exceeded 90% in v0 and v1 WMDA until postoperative day (POD) 2100 and v0 MUA until POD 1600 but fell below 80% in the other settings by POD 1000. In node-positive (stage III) CRC, the RFS rate fell below 80% in all histological subtypes by POD 1000. CONCLUSIONS: VI grade v1 had a similar recurrence rate and RFS as grade v0 and may not warrant adjuvant chemotherapy in node-negative (stage II or lower) WMDA. In addition to node-positive (stage III) CRC, adjuvant chemotherapy may be indicated for node-negative (stage II or lower) CRC when it is WMDA with VI grade v2 or v3, MUA with VI, or PDA.

Effect and limitation of neoadjuvant chemotherapy for pancreatic ductal adenocarcinoma: consideration from a new perspective.

BACKGROUND: Effect of neoadjuvant chemotherapy (NAC) for pancreatic ductal adenocarcinoma (PDAC) has remained under investigation. We investigated its effect from a unique perspective and discussed its application. PATIENTS AND METHODS: We retrospecively analyzed consecutive 131 PDAC patients who underwent pancreatoduodenectomy and distal pancreatectomy. Clinicopathologic data at surgery and postoperative prognosis were compared between patients who underwent upfront surgery (UFS) (n = 64) and those who received NAC (n = 67), of which 62 (92.5%) received gemcitabine plus S-1 (GS). The GS regimen resulted in about 15% of partial response and 85% of stable disease in a previous study which analyzed a subset of this study subjects. RESULTS: Tumor size was marginally smaller, degree of nodal metastasis and rate of distant metastasis were significantly lower, and pathologic stage was significantly lower in the NAC group than in the UFS group. In contrast, significant differences were not observed in histopathologic features such as vessel and perineural invasions and differentiation grade. Notably, disease-free and overall survivals were similar between the two groups adjusted for the pathologic stage, suggesting that effects of NAC, including macroscopically undetectable ones such as control of micro-metastasis and devitalizing tumor cells, may not be remarkable in the majority of PDAC, at least with respect to the GS regimen. CONCLUSIONS: NAC may be useful in downstaging and improving prognosis in a small subset of tumors. However, postoperative prognosis may be determined at the pathologic stage of resected specimen with or without NAC. Therefore, NAC may be applicable to borderline resectable and locally advanced PDAC for enabling surgical resection, but UFS would be desirable for primary resectable PDAC.

Clinical impacts of resection margin status and clinicopathologic parameters on pancreatic ductal adenocarcinoma.

BACKGROUND: The clinical relevance of pancreatic intraepithelial neoplasia (PanIN) at the resection margin of pancreatic ductal adenocarcinoma remains unknown. We aimed to investigate its clinical impact at the pancreatic transection margin (PTM) and, based on the result, determine the prognostic values of the resection margin status and other clinicopathologic parameters. PATIENTS AND METHODS: We retrospectively analyzed 122 consecutive patients who underwent pancreatoduodenectomy or distal pancreatectomy between 2006 and 2018. Pathologic slides were reviewed and survival data were retrieved from institutional databases. Associations between two variables were investigated by Fisher's exact test. Survival curves were generated by the Kaplan-Meier method. Prognostic factors were assessed using Cox regression analysis. RESULTS: Tumors were resected without leaving macroscopic remnants. The median follow-up period after surgery was 524.5 days. Cancer-related death (n = 72) was marginally and significantly associated with local recurrence (n = 22) and distant metastasis (n = 79), respectively. Local recurrence and distant metastasis occurred independently. After excluding cases with invasive cancer at any other margin, PanIN-2 or PanIN-3 (n = 21) at the PTM did not adversely affect prognoses compared with normal mucosa or PanIN-1 (n = 57) with statistical significance. R0 resection (n = 78), which is invasive cancer-free at all resection margins, showed somewhat better local recurrence-free and overall survivals as compared with R1 resection (n = 44), which involves invasive cancer at any resection margin, but the differences did not reach statistical significance. In contrast, differentiation grade and nodal metastasis were significant predictors of distant metastasis, and tumor location and differentiation grade were significant predictors of cancer-related death. Although there was no significant difference in differentiation grade between the head cancer and the body or tail cancer, nodal metastasis was significantly more frequent in the former than in the latter. CONCLUSIONS: PanINs at the PTM did not adversely affect prognosis and R0 resection was not found to be a significant prognostic factor. Differentiation grade might be an indicator of occult metastasis and affect patients' overall survival through distant metastasis. In addition to successful surgical procedures, tumor biology may be even more important as a predictor of postoperative prognosis.

Impact of Tumor Location on Postoperative Outcome of Intraductal Papillary Neoplasm of the Bile Duct.

BACKGROUND: The concept of intraductal papillary neoplasm of the bile duct (IPNB) has been proposed to be the biliary equivalent of intraductal papillary mucinous neoplasm (IPMN) of the pancreas. While the classification of IPMNs is based on their location of duct involvement, such classification has not been fully evaluated for IPNBs. The aim of this study is to investigate the value of IPNB classification based on its location. METHODS: A total of 306 consecutive patients who underwent surgical resection with a diagnosis of bile duct tumor were enrolled. Among these patients, 21 were diagnosed as having IPNB. The IPNBs were classified into two groups as follows: extrahepatic IPNB, which located in the distal or perihilar bile duct, and intrahepatic IPNB, which located more peripherally than the hilar bile duct. The clinicopathological features of the two groups were then compared. RESULTS: Extrahepatic IPNB tended to show more invasive characteristics than intrahepatic IPNB (presence of invasive component: 40.0 vs. 9.1%, p = 0.084). Moreover, patients with extrahepatic IPNB showed significantly poorer relapse-free survival (RFS) than those with intrahepatic IPNB [5-year RFS rate (%): 81.8 vs. 16.2, p = 0.014]. CONCLUSION: Patients with intrahepatic IPNB show more favorable pathological characteristics and postoperative survival outcomes than those with extrahepatic IPNB.

Uterine cervical adenocarcinoma metastasizing concurrently to eutopic and ectopic ovaries: A case report.

Ectopic ovary, a designation that includes supernumerary ovaries and accessory ovaries, is a rare gonadal anomaly. We encountered a patient with a metastasis to such an anomaly and herein provide a review of the published work. A 43-year-old woman was diagnosed with stage IIb cervical adenocarcinoma with suspicion for a right ovarian malignancy. She underwent laparotomy after completing three cycles of neoadjuvant chemotherapy. Intraoperative inspection revealed two normal ovaries, but an ovary-like structure was identified attached to the fimbriae of the left fallopian tube. A cystic tumor, 12 cm in diameter, developed from this structure, which was not connected to the infundibulopelvic ligament. The mass was pulled and elevated into the right pelvis by omental adhesions. Pathological examination revealed uterine cervical endometrioid adenocarcinoma with deep stromal invasion, vaginal invasion, and pelvic lymph-node metastases. Both the left eutopic ovary and the ovary-like structure contained endometrioid adenocarcinoma metastases. The ovary-like structure contained spindle-shaped theca cells, which were positive for inhibin α; therefore, this structure was defined as ovarian tissue. The final diagnosis was well-differentiated uterine cervical endometrioid adenocarcinoma with metastases to the pelvic lymph nodes and to the left eutopic and ectopic ovaries (pT2a2N1M0). To the best of our knowledge, there have been no previous descriptions in the English-language published work of uterine cervical adenocarcinoma metastasizing concurrently to unilateral eutopic and ectopic ovaries. © 2016 Japan Society of Obstetrics and Gynecology.

Aberrant keratin 7 and 20 expression in triple-negative carcinoma of the breast.

Early studies characterizing the keratin (K) profile of various epithelial tissues indicated that breast carcinoma is K7 positive and K20 negative, but not all breast carcinomas show this profile. Triple-negative carcinoma (TNC) has been characterized by negativity for estrogen receptor (ER), progesterone receptor (PgR), and Her2/neu protein. TNC is more likely to metastasize to the viscera and present as a metastatic poorly different carcinoma. In our study, on the basis of immunohistochemical staining of ER, PgR, and Her2/neu, 75 of the 290 patients with invasive breast carcinoma were judged to have TNC. K20 expression was detected in 6 of 75 patients with TNC, and non-TNC was negative in all 215 cases (P = .0003). K7 expression was also detected in 72 of 75 TNC cases. However, non-TNC was negative in 26 of 215 cases, which was significant (P = .0457). An aberrant profile of K was observed in the TNC group, indicating that caution is needed in determining the site of primary tumors using immunohistochemical algorithms. It should be kept in mind that patients with TNC show highly variable K profiles in practical diagnosis.

Poorly differentiated adenocarcinoma of the colon: subsite location and clinicopathologic features.

PURPOSE: Colorectal cancers of the proximal colon are characterized by good prognosis, microsatellite instability (MSI), and poor differentiation. MSI is associated with a favorable prognosis, but poorly differentiated adenocarcinomas (PDAs) have a poor prognosis. In this study, we aimed to investigate this inconsistency by analyzing the heterogeneity of PDAs. METHODS: A total of 156 surgically resected PDAs were analyzed according to tumor subsite by morphological and immunohistochemical analyses. RESULTS: Proximal PDAs (n = 86) were significantly associated with females, older age, cytokeratin (CK) 20 downregulation, aberrant MUC5AC expression, and MSI compared with distal PDAs (n = 70). Proximal PDAs tended to show a better overall survival rate than distal PDAs. PDAs with microsatellite stability (MSS) were suggested to progress from well- and moderately differentiated adenocarcinomas (WMDAs), but MSI PDAs typically not. MSI PDAs demonstrated a prognosis marginally better than MSS PDAs, but significantly worse than WMDAs (n = 170). Proximal MSS PDAs had a similar unfavorable prognosis but were significantly associated with females and aberrant MUC5AC expression compared with distal MSS PDAs. MSI may be predictive of prognosis only in proximal PDAs, because nearly all distal PDAs were MSS. In contrast, CK20 downregulation was significantly associated with better prognosis in both subsites. CONCLUSIONS: Proximal PDAs had a better prognosis than distal PDAs due to a higher incidence of MSI PDAs, whose prognosis was significantly worse than WMDAs. Female and MUC5AC expression were characteristic of proximal PDAs independent of MSI. Subsite-specific features of PDAs may serve for subclassification and predicting prognosis.

Prognostic relevance of the most predominant and least differentiated grades of gastric adenocarcinoma after curative gastrectomy.

BACKGROUND: Prognostic relevance of differentiation grade has remained controversial in gastric adenocarcinoma (GAC) after curative resection. METHODS: GAC patients who underwent curative gastrectomy were analyzed. Differentiation grade was evaluated according to either the most predominant or least differentiated component. Impacts of clinicopathologic parameters on postoperative recurrence and nodal metastasis were analyzed by the multivariate Cox regression analysis in pT1/2/3/4a and pT1b/2/3 GAC and by the logistic regression analysis in pT1b GAC, respectively. RESULTS: 154 patients with GAC, consisting of 34 pT1a (recurrence rate 0%), 45 pT1b (4.4%), 18 pT2 (22.2%), 40 pT3 (35.0%), and 17 pT4a (76.5%), were included. In pT1/2/3/4a GAC, recurrence was significantly associated with only depth of invasion (pT) and grade of venous invasion (VI), although either mode of differentiation grade was significantly associated with pT by the Spearman's rank correlation test. Next, given no recurrence in pT1a and high-grade histopathology in nearly all pT4a, pT1b/2/3 GAC was analyzed, revealing that recurrence was significantly associated with only VI grade and nodal metastasis. Finally, nodal metastasis was not found in any pT1a GAC, of which 44.1% was predominantly high-grade. In pT1b GAC, nodal metastasis was irrelevant to either mode of differentiation grade, tumor size, and ulceration status but was only associated with lymphatic invasion, suggesting that endoscopic resection of pT1 GAC with negative margin can be curative even with high-grade histopathology. CONCLUSION: Either mode of differentiation grade revealed limited prognostic relevance after curative gastrectomy. Our results may warrant a controversy over current curability evaluation of endoscopic GAC resection.

Stage IV and recurrent colorectal cancer cured following multimodal therapy: A case series.

The treatment strategies for colorectal cancer (CRC) with distant metastasis or metastatic recurrence after resection of the primary tumor are controversial. In the present study, four cases of patients with advanced CRC with distant metastasis who achieved disease-free survival (DFS) for >5 years and were deemed potentially cured were reported. Case 1 was that of a 53-year-old male patient with rectal cancer and liver metastases (pT3N2bM1, pStage IV), and case 2 was that of a 58-year-old female patient with descending colon cancer (pT3N1M1, pStage IV) who had lung metastases at surgery and postoperatively. Both patients achieved DFS for >5 years after simultaneous or staged partial hepatectomy or pneumonectomy followed by chemotherapy. Case 3 was that of a 75-year-old male patient with transverse colon cancer (pT3N1M0, pStage IIIB) and case 4 was that of a 73-year-old male patient with sigmoid colon cancer (pT3N0M0, pStage IIA). These cases developed liver metastases after resection of the primary tumour and were subsequently treated with chemotherapy before or after partial hepatectomy. DFS for >5 years was achieved. All four patients were considered cured. The data revealed that even patients with CRC and distant metastases can potentially be cured following multidisciplinary treatment. In the present case report, the factors that enabled these patients to be considered cured were discussed and the aim was to improve the treatment strategy to cure CRC with distant metastasis or recurrence.

Efficacy of Touch Imprint Cytology in Intraoperative Diagnosis of Invasive Mucinous Adenocarcinoma of the Lung: A Case Report and Literature Review.

A preoperative diagnosis of the peripheral small lung nodule is often difficult, and an intraoperative frozen section diagnosis (FSD) is performed to guide treatment strategy. However, invasive mucinous adenocarcinoma (IMA) is prone to be overlooked because of the low sample quality and weak atypia. We herein report a case of IMA, in which touch imprint cytology (TIC) revealed diagnostic efficacy. A 74-year-old male with a small, subsolid nodule in the right upper lobe underwent a thoracoscopic wedge resection. A grayish brown, 10 × 7 mm-sized nodule was observed on the cut surface. Intraoperative FSD revealed lung tissue with mild alveolar septal thickening and stromal fibrosis but without overt atypia. Meanwhile, TIC revealed mucus and a few epithelial cells with intranuclear inclusions, which pathologists evaluated as reactive. Finally, focal organizing pneumonia was tentatively diagnosed, and surgery was finished without any additional resection. However, permanent section diagnosis revealed a microinvasive mucinous adenocarcinoma. Nuclear inclusions were confirmed in tumor cells. In the intraoperative setting, TIC may be more advantageous than FSD in observing nuclear inclusions and mucus. Mucinous background and nuclear inclusion on TIC may suggest IMA even if FSD does not suggest malignancy in an intraoperative diagnosis of the peripheral small lung nodule.

Aberrant cytokeratin expression as a possible prognostic predictor in poorly differentiated colorectal carcinoma.

BACKGROUND AND AIM: The cytokeratin (CK)7(-) /CK20(+) immunoprofile is characteristic of colorectal carcinoma (CRC), although CK7(+) or CK20(-) phenotypes are occasionally encountered, particularly in histologically variant CRCs. We analyzed CK7/CK20 profiles in variant CRCs in association with clinicopathologic parameters and prognosis. METHODS: CK expression in well- and moderately differentiated adenocarcinoma (WMDA) (n = 63), poorly differentiated adenocarcinoma (PDA) (n = 91), mucinous adenocarcinoma (MUA) (n = 81), signet-ring cell carcinoma (SRCC) (n = 15), undifferentiated carcinoma (UDC) (n = 12), and adenosquamous carcinoma (n = 2) was analyzed using immunohistochemistry. Cut-off scores were set at 1% for CK7 and 25% for CK20 using the receiver operating characteristic curve analysis of PDA. Association between CK20(-) and better prognosis in PDA was validated in the second cohort (n = 66). RESULTS: CK7/CK20 immunoprofiling revealed a predominant CK7(-) /CK20(+) profile in WMDA, MUA, and SRCC, while the majority of UDC was characterized by a CK7(-) /CK20(-) profile. The CK7/CK20 profile in PDA was variable. Contingency table analysis revealed that CK expression was not significantly associated with any clinicopathologic parameters in WMDA, PDA, and MUA. However, survival analysis demonstrated that CK20(-) was significantly associated with better prognosis in PDA. Although CK20(-) was significantly associated with mismatch repair deficiency in PDA, it was an independent prognostic factor in multivariate analysis. Finally, we confirmed that CK20 status, determined using a 25% cut-off score, was a significant prognostic parameter in the second PDA cohort. CONCLUSIONS: CK20 status may be used as a prognostic predictor of PDA.

The Impact of Venous Invasion on the Postoperative Recurrence of pT1-3N0cM0 Gastric Cancer.

The impact of venous invasion (VI) on postoperative recurrence in pathological (p)T1-3N0 clinical (c)M0 gastric cancer (GC) remains unclear. We investigated the association of VI grade with prognosis in 94 (78 stage I and 16 stage IIA) patients. VI was graded during pathological examinations based on the number of VIs per glass slide as follows: v0, 0; v1, 1-3; v2, 4-6; and v3, ≥7. Filling-type invasion in veins with a minor axis of ≥1 mm increased VI grade by 1. Four (4.3%) patients experienced recurrence. Recurrence increased with pT (pT1, 0.0%; pT2, 11.1%; pT3, 18.8%) and VI grade (v0, 0.0%; v1, 3.7%, v2, 14.3%; and v3, 40.0%). Recurrence was significantly more frequent in pT3 than pT1 and in v2 + v3 than v0 (p = 0.006 and 0.005, respectively). Kaplan-Meier curve analyses demonstrated a significant decrease in recurrence-free survival according to pT (p = 0.0021) and VI grade (p < 0.0001). Multivariate Cox analysis revealed a significant association of VI grade with recurrence (p = 0.049). These results suggest that VI grade is a potential recurrence predictor for pT1-3N0cM0 GC. No recurrence can be expected in cases with pT1 or VI grade v0. Adjuvant therapy might be considered for pT3 or VI grade v2 + v3.

An unusual cytological presentation of solid pseudopapillary neoplasm of the pancreas mimicking adenoid cystic carcinoma: a case report and literature review.

Endoscopic ultrasound-guided fine-needle aspiration has become the common procedure for the diagnosis of pancreatic mass, and cytological examination is usually the first approach. Solid pseudopapillary neoplasm (SPN) cytologically represents papillary structures of branching capillaries surrounded by discohesive neoplastic cells. However, it may present various degrees of tissue degeneration, causing diagnostic challenges. Here, we report a 21-year-old female who had a 2-cm-sized mass in the pancreas head. Cytological examination revealed clumps of small round/oval cells that represented microcystic configurations with mucus, mimicking adenoid cystic carcinoma or mucinous adenocarcinoma. Cercariform cells, nuclear grooves/folding, and cytoplasmic vacuoles were not observed. Histopathological examination revealed confluent small glandular structures containing acidic mucus. The tumor cells were positively stained for ß-catenin, CD10, and CD56, and negative for chromogranin A and E-cadherin, suggesting SPN, micropseudocystic variant. This variant has been scarcely described, but we should recognize it for accurate cytological triage of pancreatic tumors.

Apparent diffusion coefficient by magnetic resonance cholangiopancreatography is useful for grading cholecystitis and surgery planning.

INTRODUCTION: Laparoscopic cholecystectomy is a standard procedure for treating cholescytitis, but severe inflammation may cause complications. Our previous study showed that the apparent diffusion coefficient (ADC) values could predict difficult surgery. In the present study, relevance of ADC values in grading the severity of cholecystitis was pathologically investigated. METHODS: We retrospectively analyzed a total of 50 patients who underwent laparoscopic cholecystectomy or laparotomic cholecystectomy/choledocholithotomy. The degree of inflammation in the neck of the gall bladder was pathologically graded into three tiers (grade 1, mild; grade 2, moderate; grade 3, severe), and ulceration, lymphoid follicle formation, and wall thickness of the gallbladder neck were recorded. All factors were statistically compared with the measured ADC values. RESULTS: The ADC value was significantly lower in the severe inflammation group ( grade 3) than in the weak inflammation group (grades 1 and 2) (1.93 ± 0.22 vs 2.38 ± 0.67, respectively; P = .02). Ulceration and wall thickness in the gallbladder neck were significantly correlated with ADC values (P = .04 and .006, respectively), and lymphoid follicle formation was marginally correlated with ADC values (P = .06). The diagnostic utility of the ADC values decreased as the interval between imaging and cholecystectomy increased. [Correction added on 19 October 2022, after first online publication: [On the first sentence of the Results section, (grades 2 and 3) for weak inflammation group has been changed to (grades 1 and 2).] CONCLUSION: ADC values were inversely associated with the pathologic intensity of cholecystitis. We recommend that the ADC value be measured before surgery, so that the procedure can be accordingly planned.

[Validity of the NAFLD fibrosis score in a Japanese population].

Scoring systems for the diagnosis of fibrosis in non-alcoholic fatty liver disease (NAFLD) have been devised all over the world. However, the usefulness of these scoring systems for Japanese populations has not been established. We examined the diagnostic ability of several scoring systems for the diagnosis of advanced fibrosis in NAFLD patients. A total of 52 patients with NAFLD who had undergone liver biopsy were included in this study. The area under the receiver operating characteristic (AUROC) of the scoring system for the advanced fibrosis was greatest for NAFLD fibrosis score (NFS) (0.913). At a cutoff point of -0.876 modified from the original low cutoff point (-1.455), the sensitivity, specificity, and positive and negative predictive values for advanced fibrosis were 100%, 82.5%, 63.2%, and 100%, respectively. Based on these results, we conclude that low cutoff point of NFS should be modified to -0.876 for a Japanese population with a lower BMI than Western populations.

Reclassification of atypical immature metaplasia of the uterine cervix by combination of nuclear features on hematoxylin and eosin-stained sections without auxiliary immunohistochemistry.

Reclassification of endocervical atypical immature metaplasia (AIM) into reactive changes and neoplastic lesion is often challenging. We aimed to accurately reclassify AIM on hematoxylin and eosin (HE)-stained sections without auxiliary immunohistochemistry (IHC). A total of 133 AIM diagnosed by punch biopsy were reclassified by IHC for p16 and Ki-67 into high-grade squamous intraepithelial lesion (HSIL) or negative for intraepithelial lesion or malignancy or low-grade squamous intraepithelial lesion (NILM/LSIL) as a reference. Nuclear features significantly associated with HSIL on HE-stained sections were extracted by multivariate logistic regression analysis. Propensity score (PS) of HSIL was calculated in each case and cut-off was determined by receiver operation characteristic (ROC) curve analysis. As a result, AIM was reclassified into 104 NILM/LSIL and 29 HSIL by IHC. Compared with reference diagnosis, accuracy of pathologists' subjective diagnosis was 54.9% (kappa coefficient, 0.208). Three nuclear features on HE-stained sections, ie, nuclear enlargement with anisokaryosis, nuclear hyperchromasia, and mitosis, were significantly associated with HSIL. The ROC curve analyses revealed that PS and number of nuclear features were significant predictors of HSIL. Diagnostic accuracy of PS-based diagnosis was 76.7% (kappa, 0.447). When AIM with 2 or more of the 3 nuclear features was diagnosed with HSIL, diagnostic accuracy was 77.4% (kappa, 0.448). Nuclear feature-based diagnosis significantly improved diagnostic accuracy on HE-stained sections compared with subjective diagnosis and may be useful when IHC is not available. However, a considerable proportion of AIM would still remain misdiagnosed and IHC for p16 and Ki-67 should be mandatory for accurate reclassification.

Pulsed magnetic stimulation with a high-frequency continuous magnetic stimulator (SMN-X) does not exert an adverse effect on genital organs and the estrous cycle in female Iar:Wistar-Imamichi rats.

AIMS: To histopathologically verify whether high-frequency continuous stimulation exerts adverse effects on genital organs (uterus and ovaries) and the estrous cycle in rats through comparison of 3 groups. METHODS: The device studied was a high-frequency continuous magnetic stimulator (SMN-X, Nihon Kohden, Tokyo). Thirteen female Iar:Wistar-Imamichi rats (SPF) were randomly divided into 3 groups: active treatment (MS) group (n = 7), sham treatment group, where rats were placed on a table 1 m away from the stimulator so that they could hear the sounds of the stimulator (n = 3) and control (no treatment) group (n = 3). The MS group underwent thirty-six 25-minute sessions of pulsed magnetic stimulation at the maximum output level (560 mT peak) (once/day, 5 days/week). At the end of the study period, the uterus and ovaries were removed for histological examinations. Estradiol and progesterone levels were assayed and the estrous cycle, bodyweight gain and daily behaviors were recorded. RESULTS: From results of histopathology and endocrinology, assays of the estrous cycle, and recordings of bodyweight gain and organ weight, no adverse effects of long-term pulsed magnetic stimulation were noted. There were no significant intergroup differences with regard to any item evaluated. CONCLUSION: In the study setting, SMN-X did not exert any adverse effect on the uterus, ovaries, estrous cycle and hormone levels as well as blood cell counts, bodyweight gain and daily behavior in female SPF rats. The present results may be a step forward in the discussion of the safety of SMN-X for clinical use in humans.

Histopathological Analysis of Decellularized Porcine Small Intestinal Submucosa after Treatment of Skin Ulcer.

BACKGROUND: Decellularized porcine small intestinal submucosa (SIS), commercialized as an extracellular matrix rich in cell-inducing substrates and factors, has been clinically applied to treat intractable skin ulcers and has shown therapeutic effects. The SIS reportedly induces cell infiltration and integrates with the ulcer bed after 3-7 days of application. The attached SIS degenerates over time, and the remaining mass appears as slough, below which is granulation tissue that is essential for healing. This study aimed to determine whether the slough should be removed in clinical settings. METHODS: Five patients with intractable skin ulcers were included in this case series. Seven days after applying a two-layer fenestrated-type SIS to the ulcer, the removed slough was histopathologically examined. RESULTS: The collagen fibers of the SIS somewhat degenerated, and inflammatory cell infiltration was observed from the ulcer side to the surface side of the SIS. Neovascularization was similarly observed on the ulcer side. The degree of inflammatory cell infiltration decreased from the ulcer side to the surface side, whereas pus (ie, aggregates of neutrophils) was observed on the surface and ulcer edges. Additionally, the removed slough contained regenerative epithelium on the ulcer side of the remaining collagen fibers. CONCLUSIONS: After treating intractable skin ulcers using SIS, we recommend removal of the upper surface and ulcer edge of the degenerated SIS or slough to prevent infection and preservation of the lower side of the degenerated SIS to maintain the granulation tissue and regenerative epithelium.

Immunohistochemical detection of fibroblast growth factor receptor 3 in human breast cancer: correlation with clinicopathological/molecular parameters and prognosis.

OBJECTIVE: Reportedly, fibroblast growth factor receptor 3 (FGFR3) that regulates embryonic growth and development may function as an oncoprotein in certain malignancies. We aimed to investigate the biological significance of FGFR3 expression in invasive breast cancer. METHODS: FGFR3 expression was investigated in 50 invasive breast cancer specimens by immunohistochemistry. The association between FGFR3 expression and clinicopathological/molecular parameters or prognosis was evaluated. RESULTS: Weak FGFR3 expression was observed in myoepithelial cells, but not in duct epithelial cells, of the normal mammary ducts and lobules. FGFR3 expression in breast cancer cells was observed in 19 of 50 (38.0%) cases (9 weak positive and 10 strong positive). Besides the cytoplasm and cell membrane, nuclear staining was observed in 3 of 10 strong-positive cases. FGFR3 was further detected in non-neoplastic duct epithelial cells or duct papillomatosis in 5 strong-positive cases. No significant correlation was observed between FGFR3 expression and specific clinicopathological/molecular parameters. In contrast, FGFR3 expression was found to be significantly associated with overall survival in our cohort. CONCLUSIONS: FGFR3 expression in invasive breast cancer was not found to be significantly associated with specific clinicopathological/molecular parameters, but might be used as a candidate marker for a poor prognosis.