Deep Learning-Based Nuclear Morphometry Reveals an Independent Prognostic Factor in Mantle Cell Lymphoma.

Blastoid/pleomorphic morphology is associated with short survival in mantle cell lymphoma (MCL), but its prognostic value is overridden by Ki-67 in multivariate analysis. Herein, a nuclear segmentation model was developed using deep learning, and nuclei of tumor cells in 103 MCL cases were automatically delineated. Eight nuclear morphometric attributes were extracted from each nucleus. The mean, variance, skewness, and kurtosis of each attribute were calculated for each case, resulting in 32 morphometric parameters. Compared with those in classic MCL, 17 morphometric parameters were significantly different in blastoid/pleomorphic MCL. Using univariate analysis, 16 morphometric parameters (including 14 significantly different between classic and blastoid/pleomorphic MCL) emerged as significant prognostic factors. Using multivariate analysis, Biologic MCL International Prognostic Index (bMIPI) risk group (P = 0.025), low skewness of nuclear irregularity (P = 0.020), and high mean of nuclear irregularity (P = 0.047) emerged as independent adverse prognostic factors. Additionally, a morphometric score calculated from the skewness and mean of nuclear irregularity (P = 0.0038) was an independent prognostic factor in addition to bMIPI risk group (P = 0.025), and a summed morphometric bMIPI score was useful for risk stratification of patients with MCL (P = 0.000001). These results demonstrate, for the first time, that a nuclear morphometric score is an independent prognostic factor in MCL. It is more robust than blastoid/pleomorphic morphology and can be objectively measured.

Identification of nodal micrometastasis in colorectal cancer using deep learning on annotation-free whole-slide images.

Detection of nodal micrometastasis (tumor size: 0.2-2.0 mm) is challenging for pathologists due to the small size of metastatic foci. Since lymph nodes with micrometastasis are counted as positive nodes, detecting micrometastasis is crucial for accurate pathologic staging of colorectal cancer. Previously, deep learning algorithms developed with manually annotated images performed well in identifying micrometastasis of breast cancer in sentinel lymph nodes. However, the process of manual annotation is labor intensive and time consuming. Multiple instance learning was later used to identify metastatic breast cancer without manual annotation, but its performance appears worse in detecting micrometastasis. Here, we developed a deep learning model using whole-slide images of regional lymph nodes of colorectal cancer with only a slide-level label (either a positive or negative slide). The training, validation, and testing sets included 1963, 219, and 1000 slides, respectively. A supercomputer TAIWANIA 2 was used to train a deep learning model to identify metastasis. At slide level, our algorithm performed well in identifying both macrometastasis (tumor size > 2.0 mm) and micrometastasis with an area under the receiver operating characteristics curve (AUC) of 0.9993 and 0.9956, respectively. Since most of our slides had more than one lymph node, we then tested the performance of our algorithm on 538 single-lymph node images randomly cropped from the testing set. At single-lymph node level, our algorithm maintained good performance in identifying macrometastasis and micrometastasis with an AUC of 0.9944 and 0.9476, respectively. Visualization using class activation mapping confirmed that our model identified nodal metastasis based on areas of tumor cells. Our results demonstrate for the first time that micrometastasis could be detected by deep learning on whole-slide images without manual annotation.

Hydroxygenkwanin Increases the Sensitivity of Liver Cancer Cells to Chemotherapy by Inhibiting DNA Damage Response in Mouse Xenograft Models.

Molecules involved in DNA damage response (DDR) are often overexpressed in cancer cells, resulting in poor responses to chemotherapy and radiotherapy. Although treatment efficacy can be improved with the concomitant use of DNA repair inhibitors, the accompanying side effects can compromise the quality of life of patients. Therefore, in this study, we identified a natural compound that could inhibit DDR, using the single-strand annealing yeast-cell analysis system, and explored its mechanisms of action and potential as a chemotherapy adjuvant in hepatocellular carcinoma (HCC) cell lines using comet assay, flow cytometry, Western blotting, immunofluorescence staining, and functional analyses. We developed a mouse model to verify the in vitro findings. We found that hydroxygenkwanin (HGK) inhibited the expression of RAD51 and progression of homologous recombination, thereby suppressing the ability of the HCC cell lines to repair DNA damage and enhancing their sensitivity to doxorubicin. HGK inhibited the phosphorylation of DNA damage checkpoint proteins, leading to apoptosis in the HCC cell lines. In the mouse xenograft model, HGK enhanced the sensitivity of liver cancer cells to doxorubicin without any physiological toxicity. Thus, HGK can inhibit DDR in liver cancer cells and mouse models, making it suitable for use as a chemotherapy adjuvant.

The association between immune-related adverse events and survival outcomes in Asian patients with advanced melanoma receiving anti-PD-1 antibodies.

BACKGROUND: The association between immune-related adverse events (irAEs) and survival outcomes in patients with advanced melanoma receiving therapy with immune checkpoint inhibitors (ICIs) has not been well established, particularly in Asian melanoma. METHODS: We retrospectively reviewed 49 melanoma patients undergoing therapy with ICIs (anti-PD-1 monotherapy), and analyzed the correlation between irAEs and clinical outcomes including progression-free survival (PFS) and overall survival (OS). RESULTS: Overall, the patients who experienced grade 1-2 irAEs had longer PFS (median PFS, 4.6 vs. 2.5 months; HR, 0.52; 95% CI: 0.27-0.98; p = 0.042) and OS (median OS, 15.2 vs. 5.7 months; HR, 0.50; 95% CI: 0.24-1.02; p = 0.058) than the patients who did not experience irAEs. Regarding the type of irAE, the patients with either skin/vitiligo or endocrine irAEs showed better PFS (median PFS, 6.1 vs. 2.7 months; HR, 0.40, 95% CI: 0.21-0.74; p = 0.003) and OS (median OS, 18.7 vs. 4.5 months; HR, 0.34, 95% CI: 0.17-0.69, p = 0.003) than patients without any of these irAEs. CONCLUSIONS: Melanoma patients undergoing anti-PD-1 monotherapy and experiencing mild-to-moderate irAEs (grade 1-2), particularly skin (vitiligo)/endocrine irAEs had favorable survival outcomes. Therefore, the association between irAEs and the clinical outcomes in melanoma patients undergoing anti-PD-1 ICIs may be severity and type dependent.

Pleomorphic mantle cell lymphoma morphologically mimicking diffuse large B cell lymphoma: common cyclin D1 negativity and a simple immunohistochemical algorithm to avoid the diagnostic pitfall.

AIMS: To characterize the clinicopathological and genetic features of pleomorphic mantle cell lymphoma (PMCL), which morphologically mimics diffuse large B cell lymphoma (DLBCL). METHODS AND RESULTS: We screened systematically 500 B cell lymphomas morphologically compatible with DLBCL using an immunohistochemical algorithm of three markers (CD5, cyclin D1 and SOX11). Ten cases of PMCL were identified for further study and, surprisingly, four (40%) of them were cyclin D1-negative. These 10 patients were mainly elderly males with advanced disease, and their median survival was only 11 months. All cyclin D1-positive PMCLs tested showed an IGH-CCND1 translocation, whereas one of the four cyclin D1-negative PMCLs had a translocation involving CCND2 and a high CCND2 mRNA level (P < 0.000001). The genomewide copy number profiles of both cyclin D1-positive and cyclin D1-negative PMCLs were similar to those of classical mantle cell lymphoma (MCL) reported previously, confirming the diagnosis. Secondary genetic alterations involved in oncogenic pathways of MCL were observed more frequently in these PMCLs, possibly decreasing the dependence on the driving CCND1 translocation and accounting for the common cyclin D1 negativity. Copy number gains of PIK3CA and CCDC50 were detected in all cyclin D1-negative PMCLs but in only 40% of the cyclin D1-positive PMCLs. These additional oncogenic signals may compensate for the common absence of CCND2 translocation in cyclin D1-negative PMCL. CONCLUSION: We demonstrate for the first time that cyclin D1 negativity is surprisingly common in PMCL morphologically mimicking DLBCL, and the use of a simple immunohistochemical algorithm can prevent misclassification and inappropriate treatment.

Comparison of the diagnostic accuracy of contrast-enhanced MRI and diffusion-weighted MRI in the differentiation between uterine leiomyosarcoma / smooth muscle tumor with uncertain malignant potential and benign leiomyoma.

PURPOSE: To compare the diagnostic accuracy of contrast-enhanced (CE) magnetic resonance imaging (MRI) and diffusion-weighted MRI (DWI) in the differentiation between uterine leiomyosarcoma (LMS) / smooth muscle tumor with uncertain malignant potential (STUMP) and benign leiomyoma. MATERIALS AND METHODS: A consecutive cohort of 8 LMS/STUMP and 25 benign leiomyomas underwent pelvic MRI exam at 3T. Two radiologists independently evaluated images based on CE-MRI (central nonenhancement at equilibrial phase) and DWI (hyperintensity on b = 1000 s/mm2 and hypointensity on apparent diffusion coefficients [ADC] map). The ADC values were calculated from b = 0 and 1000 s/mm2 . RESULTS: CE-MRI yielded a significantly superior diagnostic accuracy (0.94 vs. 0.52) and a significantly higher specificity (0.96 vs. 0.36) than DWI (P < 0.05 for both), and remained a comparably high sensitivity as DWI (0.88 vs. 1.00). A combination of DWI and ADC value <1.08 × 10(-3) mm2 /s (determined by receiver operating characteristic analysis) improved diagnostic accuracy, sensitivity, and specificity of DWI to 0.88, 0.88, and 0.88, respectively, by post-hoc analysis based on the same study cohort. CONCLUSION: For prospective differentiation between uterine LMS/STUMP and benign leiomyoma, CE-MRI can provide accurate information and is preferable to DWI. Combination of DWI and ADC values can achieve a comparable diagnostic accuracy to CE-MRI.

Clinical utility of dual-energy contrast-enhanced spectral mammography for breast microcalcifications without associated mass: a preliminary analysis.

OBJECTIVE: To assess the utility of dual-energy contrast-enhanced spectral mammography (DE-CESM) for evaluation of suspicious malignant microcalcifications. METHODS: Two hundred and fifty-six DE-CESMs were reviewed from 2012-2013, 59 cases fulfilled the following criteria and were enrolled for analysis: (1) suspicious malignant microcalcifications (BI-RADS 4) on mammogram, (2) no related mass, (3) with pathological diagnoses. The microcalcification morphology and associated enhancement were reviewed to analyse the accuracy of the diagnosis and cancer size measurements versus the results of pathology. RESULTS: Of the 59 microcalcifications, 22 were diagnosed as cancers, 19 were atypical lesions and 18 were benign lesions. Twenty (76.9 %) cancers, three (11.55 %) atypia and three (11.55 %) benign lesions revealed enhancement. The true-positive rate of intermediate- and high-concern microcalcifications was significantly higher than that of low-concern lesions (93.75 % vs. 50 %). Overall, the diagnostic sensitivity of enhancement was 90.9 %, with 83.78 % specificity, 76.92 % positive predictive value, 93.94 % negative predictive value and 86.4 % accuracy. Performance was good (AUC = 0.87) according to a ROC curve and cancer size correlation with a mean difference of 0.05 cm on a Bland-Altman plot. CONCLUSIONS: DE-CESM provides additional enhancement information for diagnosing breast microcalcifications and measuring cancer sizes with high correlation to surgicohistology. KEY POINTS: • DE-CESM provides additional enhancement information for diagnosing suspicious breast microcalcifications. • The enhanced cancer size closely correlates to microscopy by Bland-Altman plot. • DE-CESM could be considered for evaluation of suspicious malignant microcalcifications.

Molecular characteristics of endometrial cancer coexisting with peritoneal malignant mesothelioma in Li-Fraumeni-like syndrome.

BACKGROUND: Endometrial cancer that occurs concurrently with peritoneal malignant mesothelioma (PMM) is difficult to diagnose preoperatively. CASE PRESENTATION: A postmenopausal woman had endometrial cancer extending to the cervix, vagina and pelvic lymph nodes, and PMM in bilateral ovaries, cul-de-sac, and multiple peritoneal sites. Adjuvant therapies included chemotherapy and radiotherapy. Targeted, massively parallel DNA sequencing and molecular inversion probe microarray analysis revealed a germline TP53 mutation compatible with Li-Fraumeni-like syndrome, somatic mutations of PIK3CA in the endometrial cancer, and a somatic mutation of GNA11 and JAK3 in the PMM. Large-scale genomic amplifications and some deletions were found in the endometrial cancer. The patient has been stable for 24 months after therapy. One of her four children was also found to carry the germline TP53 mutation. CONCLUSIONS: Molecular characterization of the coexistent tumors not only helps us make the definite diagnosis, but also provides information to select targeted therapies if needed in the future. Identification of germline TP53 mutation further urged us to monitor future development of malignancies in this patient and encourage cancer screening in her family.

Predictors of underestimation of malignancy after image-guided core needle biopsy diagnosis of flat epithelial atypia or atypical ductal hyperplasia.

Flat epithelial atypia (FEA) and atypical ductal hyperplasia (ADH) are precursors of breast malignancy. Management of FEA or ADH after image-guided core needle biopsy (CNB) remains controversial. The aim of this study was to evaluate malignancy underestimation rates after FEA or ADH diagnosis using image-guided CNB and to identify clinical characteristics and imaging features associated with malignancy as well as identify cases with low underestimation rates that may be treatable by observation only. We retrospectively reviewed 2,875 consecutive image-guided CNBs recorded in an electronic data base from January 2010 to December 2011 and identified 128 (4.5%) FEA and 83 (2.9%) ADH diagnoses (211 total cases). Of these, 64 (30.3%) were echo-guided CNB procedures and 147 (69.7%) mammography-guided CNBs. Twenty patients (9.5%) were upgraded to malignancy. Multivariate analysis indicated that age (OR = 1.123, p = 0.002, increase of 1 year), mass-type lesion with calcifications (OR = 8.213, p = 0.006), and ADH in CNB specimens (OR = 8.071, p = 0.003) were independent predictors of underestimation. In univariate analysis of echo-guided CNB (n = 64), mass with calcifications had the highest underestimation rate (p < 0.001). Multivariate analysis of 147 mammography-guided CNBs revealed that age (OR = 1.122, p = 0.040, increase of 1 year) and calcification distribution were significant independent predictors of underestimation. No FEA case in which, complete calcification retrieval was recorded after CNB was upgraded to malignancy. Older age at diagnosis on image-guided CNB was a predictor of malignancy underestimation. Mass with calcifications was more likely to be associated with malignancy, and in cases presenting as calcifications only, segmental distribution or linear shapes were significantly associated with upgrading. Excision after FEA or ADH diagnosis by image-guided CNB is warranted except for FEA diagnosed using mammography-guided CNB with complete calcification retrieval.

Diagnostic performance of dual-energy contrast-enhanced subtracted mammography in dense breasts compared to mammography alone: interobserver blind-reading analysis.

PURPOSE: To analyse the accuracy of dual-energy contrast-enhanced spectral mammography in dense breasts in comparison with contrast-enhanced subtracted mammography (CESM) and conventional mammography (Mx). MATERIALS AND METHODS: CESM cases of dense breasts with histological proof were evaluated in the present study. Four radiologists with varying experience in mammography interpretation blindly read Mx first, followed by CESM. The diagnostic profiles, consistency and learning curve were analysed statistically. RESULTS: One hundred lesions (28 benign and 72 breast malignancies) in 89 females were analysed. Use of CESM improved the cancer diagnosis by 21.2 % in sensitivity (71.5 % to 92.7 %), by 16.1 % in specificity (51.8 % to 67.9 %) and by 19.8 % in accuracy (65.9 % to 85.8 %) compared with Mx. The interobserver diagnostic consistency was markedly higher using CESM than using Mx alone (0.6235 vs. 0.3869 using the kappa ratio). The probability of a correct prediction was elevated from 80 % to 90 % after 75 consecutive case readings. CONCLUSION: CESM provided additional information with consistent improvement of the cancer diagnosis in dense breasts compared to Mx alone. The prediction of the diagnosis could be improved by the interpretation of a significant number of cases in the presence of 6 % benign contrast enhancement in this study. KEY POINTS: • DE-CESM improves the cancer diagnosis in dense breasts compared with mammography. • DE-CESM shows greater consistency than mammography alone by interobserver blind reading. • Diagnostic improvement of DE-CESM is independent of the mammographic reading experience.

Integration of the cancer cell secretome and transcriptome reveals potential noninvasive diagnostic markers for bladder cancer.

PURPOSE: Bladder cancer (BLCA) is a major cancer of the genitourinary system. Although cystoscopy is the standard protocol for diagnosing BLCA clinically, this procedure is invasive and expensive. Several urine-based markers for BLCA have been identified and investigated, but none has shown sufficient sensitivity and specificity. These observations underscore the importance of discovering novel BLCA biomarkers and developing a noninvasive method for detection of BLCA. Exploring the cancer secretome is a good starting point for the development of noninvasive biomarkers for cancer diagnosis. EXPERIMENTAL DESIGN: In this study, we established a comprehensive secretome dataset of five representative BLCA cell lines, BFTC905, TSGH8301, 5637, MGH-U1, and MGH-U4, by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Expression of BLCA-specific secreted proteins at the transcription level was evaluated using the Oncomine cancer microarray database. RESULTS: The expressions of four candidates-COMT, EWSR1, FUSIP1, and TNPO2-were further validated in clinical human specimens. Immunohistochemical analyses confirmed that transportin-2 was highly expressed in tumor cells relative to adjacent noncancerous cells in clinical tissue specimens from BLCA patients, and was significantly elevated in BLCA urine compared with that in urine samples from aged-matched hernia patients (controls). CONCLUSIONS: Collectively, our findings suggest TNPO2 as a potential noninvasive tumor-stage or grade discriminator for BLCA management.

Identification of CD5/SOX11 double-negative pleomorphic mantle cell lymphoma.

Cyclin D1 protein-positive diffuse large B cell lymphoma (DLBCL) has an immunophenotype of CD5(-) cyclin D1(+) SOX11(-), and most cases lack a CCND1 rearrangement and have a gene expression profile of DLBCL. Rarely, cyclin D1 protein-positive DLBCL harbors a CCND1 rearrangement, and some genetic copy number features typical of mantle cell lymphoma (MCL) have been detected. Since gene expression studies have not been performed, whether such CCND1-rearranged cases represent cyclin D1 protein-positive DLBCL or CD5/SOX11 double-negative pleomorphic MCL remains unclear. To date, no cases of CD5/SOX11 double-negative MCL have been reported. In this study, we collected eight cases initially diagnosed as cyclin D1 protein-positive DLBCL, including four with a CCND1 rearrangement and four without. Immunohistochemically, all four CCND1-rearranged cases had >50% of tumor cells positive for cyclin D1 protein, whereas only one (25%) non-rearranged case had >50% positive tumor cells. Analysis of genome-wide copy number, mutational, and gene expression profiles revealed that CCND1-rearranged cases were similar to MCL, whereas CCND1-non-rearranged cases resembled DLBCL. Despite the SOX11 negativity by immunohistochemistry, CCND1-rearranged cases had a notable trend (P = 0.064) of higher SOX11 mRNA levels compared to non-rearranged cases. Here, we show for the first time that CCND1 rearrangement could be useful for identifying CD5/SOX11 double-negative pleomorphic MCL in cases diagnosed as cyclin D1 protein-positive DLBCL. Cases with >50% cyclin D1 protein-positive tumor cells immunohistochemically and higher SOX11 mRNA levels are more likely to have a CCND1 rearrangement, and fluorescence in situ hybridization can be used to detect the rearrangement.

Prognostic significance of pituitary tumour-transforming gene-binding factor (PBF) expression in papillary thyroid carcinoma.

BACKGROUND: Pituitary tumour-transforming gene (PTTG)-binding factor (PBF), originally known as PTTG1 interacting protein (PTTG1IP), has been found to be significantly increased in well-differentiated thyroid cancer and independently associated with early tumour recurrence. OBJECTIVE: To assess the prognostic significance of PBF expression in a large cohort of papillary thyroid carcinoma (PTC) patients with a long-term follow-up. DESIGN AND PATIENTS: Retrospective analysis of PBF expression in PTC cases at different stages and correlate it with various clinicopathological parameters and patient survival. Subjects included 153 patients who received a thyroid operation for PTC at Chang Gung Memorial Hospital between 1991 and 2000. All patients had a complete follow-up till the end of 2010. MEASUREMENTS: Immunohistochemical study for PBF expression on tissue sections from tumour specimens. Bond automated machine (Leica Microsystems, Germany) with a polyclonal rabbit anti-PBF antibody (LifeSpan BioSciences, LS-C118942, Seattle, WA, USA) was used. SPSS 13.0 for Windows (SPSS Inc, Chicago, IL, USA) was used for all statistical analyses. RESULTS: High PBF expression was significantly correlated with age (P = 0·0298), distant metastases at diagnosis (P = 0·0139), tumour multicentricity (P = 0·0035), TNM stage (P = 0·0103), locoregional recurrence (P = 0·0410) and disease-specific mortality (P = 0·0064). The expression level of PBF was significantly correlated with disease-specific survival (P = 0·0065). Cox regression analysis showed that age, tumour size and PBF expression were independent prognostic indicators (P = 0·0097, P = 0·0021 and P = 0·0179). CONCLUSION: PBF expression may be a promising biomarker for prognostic and therapeutic purpose. More large-scale studies are needed to clarify its potential usefulness.

Favorable outcome of secondary axillary dissection in breast cancer patients with axillary nodal relapse.

PURPOSE: Little evidence can be found about the long-term outcome of breast cancer patients after axillary lymph node recurrence (ALNR) and its survival benefit after different kinds of management. The present study intends to evaluate the risk factors associated with axillary recurrence after definite surgery for primary breast cancer. The prognosis after ALNR and particularly outcome of different management methods also were studied. METHODS: We retrospectively reviewed data from 4,473 patients who were diagnosed with primary breast cancer and received surgical intervention in a single institute from January 1990 to December 2002. Medical files were reviewed and data on survival were updated annually. Risk factors and prognosis of patients with axillary recurrence were analyzed. Breast-cancer-specific survival of patients with ALNR and outcomes after different management methods also were studied. RESULTS: After a median follow-up of 70.2 months, axillary recurrence developed in 0.8% of patients. Factors associated with ALNR included: age younger than 40 years, medial tumor location, no initial standard level I & II axillary dissection, and not receiving hormonal therapy. The 5-year breast-cancer-specific survival after ALNR was 57.9%. For patients who received further axillary dissection, the 5-year survival rate was 82.5% compared with 44.9% for patients who did not receive further dissection. CONCLUSIONS: ALNR is a rare event in treating breast cancer. Young age at diagnosis and medially located tumor are associated with higher risk, but standardized initial axillary dissection to level II and adjuvant hormonal therapy is protective against ALNR. In patients with ALNR, the outcome is not dismal and survival may be improved if further axillary dissection is given.

Transvaginal natural-orifice transluminal endoscopic surgery (NOTES) in adnexal procedures.

From August 2010 to June 2011, 10 consecutive patients underwent transvaginal NOTES of the adnexa, including tubal sterilization in 3, salpingectomy because of ectopic pregnancy in 3, and ovarian tumor enucleation in 4. The mean (SD; 95% CI) age of the patients was 34.8 (9.7; 27.9-41.8) years, and their body mass index was 21.6 (2.8; 19.4-23.8). In 9 of the 10 patients, the procedure was completed. The 3 tubal sterilization procedures were completed in 18 to 30 minutes, with negligible blood loss. Operative time for the 3 salpingectomies because of ectopic pregnancy was 62 to 116 minutes. One of these procedures included management of 2000 mL hemoperitoneum. Three of the 4 attempts at ovarian enucleation were successfully completed within 64 to 162 minutes, with estimated blood loss ≤ 50 mL. One NOTES procedure failed because of a misdiagnosed peritoneal mucinous tumor located anterior to the uterus and inaccessible, leading to subsequent conversion to transabdominal laparoscopy. Our preliminary results show that purely transvaginal NOTES is feasible and safe for use in performing uterine adnexal procedures in selected patients. However, the procedure cannot be used in patients with cul-de-sac disease, and could have limited use in treating lesions located anterior to the uterus.

Unusual trocar site metastasis in a uterine leiomyosarcoma after laparoscopic hysterectomy.

With widespread use of laparoscopy in patients with gynecologic malignancy, occasionally port-site metastasis is an item of concern. Herein we report a case of leiomyosarcoma of the uterus that metastasized to an accessory port after laparoscopic-assisted vaginal hysterectomy. A 46-year-old woman with a preoperative diagnosis of leiomyoma underwent laparoscopic-assisted vaginal hysterectomy. Final histopathologic findings revealed leiomyosarcoma. A postoperative abdominopelvic computed tomography scan demonstrated no evidence of metastatic tumor. The patient received 6 courses of combined chemotherapy consisting of cisplatin and ifosfamide. Follow-up computed tomography was performed because of pelvic pain at 4 months after treatment and revealed a recurrent pelvic tumor and a metastatic mass at previous right trocar site. At debulking surgery, a pelvic mass measuring 10 cm was observed, and a subcutaneous nodule measuring 4 cm was noted at the site of the right accessory port, with intact underlying peritoneum. After complete removal of both tumors, concurrent chemoradiation consisting of external radiotherapy and cisplatin was administered. Six months after the second surgery, a pelvic mass measuring 15 cm was observed. A second debulking surgical procedure was performed. However, the patient died of the disease 6 months after the second recurrence.

Treatment of fallopian tube metastasis in cervical cancer after laparoscopic ovarian transposition.

A 40-year-old woman, gravida 2, para 2, with squamous cell carcinoma of the cervix, stage IIB, underwent ovarian transposition. Bilateral salpingectomy was performed as part of the operative technique. Histopathologic analysis revealed mucosal spread of the tumor to one of the fallopian tubes. The patient underwent radiation of the ovaries in their new location in addition to standard chemoradiotherapy to the pelvis. There has been no evidence of disease for more than 5 years. Inasmuch as performance of bilateral salpingectomy in ovarian transposition is not standard practice, the finding of fallopian tube metastasis presented a dilemma to the clinician. It remains to be proved whether the finding of metastasis to the fallopian tubes can be evidence for ovarian metastasis in grossly normal-appearing ovaries to validate this practice. Literature review demonstrates that fallopian tube metastasis is usually associated with endometrial involvement.

Clinicodemographic aspect of resectable pancreatic cancer and prognostic factors for resectable cancer.

BACKGROUND: Pancreatic adenocarcinoma (PCA) is one of the most lethal human malignancies, and radical surgery remains the cornerstone of treatment. After resection, the overall 5-year survival rate is only 10% to 29%. At the time of presentation, however, about 40% of patients generally have distant metastases and another 40% are usually diagnosed with locally advanced cancers. The remaining 20% of patients are indicated for surgery on the basis of the results of preoperative imaging studies; however, about half of these patients are found to be unsuitable for resection during surgical exploration. In the current study, we aimed to determine the clinicopathological characteristics that predict the resectability of PCA and to conduct a prognostic analysis of PCA after resection to identify favorable survival factors. METHODS: We retrospectively reviewed the medical files of 688 patients (422 men and 266 women) who had undergone surgery for histopathologically proven PCA in the Department of Surgery at Chang Gung Memorial Hospital in Taiwan from 1981 to 2006. We compared the clinical characteristics of patients who underwent resection and patients who did not undergo resection in order to identify the predictive factors for successful resectability of PCA, and we conducted prognostic analysis for PCA after resection. RESULTS: A carbohydrate antigen 19-9 (CA 19-9) level of 37 U/ml or greater and a tumor size of 3 cm or more independently predicted resectability of PCA. In terms of survival after resection, PCA patients with better nutritional status (measured as having an albumin level greater than 3.5 g/dl), radical resection, early tumor stage and better-differentiated tumors were associated with favorable survival. CONCLUSIONS: Besides traditional imaging studies, preoperative CA 19-9 levels and tumor size can also be used to determine the resectability of PCA. Better nutritional status, curative resection, early tumor stage and well-differentiated tumors predict the favorable prognosis of PCA patients after resection.

Predictors of acquired perforating dermatosis in uremic patients on hemodialysis: a case-control study.

OBJECTIVES: The purpose of this study was to identify the predictors of acquired perforating dermatosis (APD) in patients on maintenance hemodialysis (HD). METHODS: A case-control study was performed at our outpatient HD center between January 1, 2000 and March 31, 2011. Patients on HD with APD were matched (1 : 2) for gender and age with controls on HD. Conditional logistic regression was used to identify factors associated with APD. RESULTS: A total of 19 patients with APD and 38 age and gender matched patients were enrolled in the study. Univariate logistic regression showed that APD was significantly associated with diabetes mellitus (DM), reduced levels of intact parathyroid hormone (iPTH) and albumin (Alb), reduced dialysis adequacy (Kt/V) and urea reduction rate (URR), and elevated levels of high-sensitivity C-reactive protein (hsCRP). Multivariate logistic regression identified reduced iPTH (hazard ratio (HR): 0.983; P = 0.026) and Alb (HR: 0.099; P = 0.047) and elevated hsCRP (HR: 1.210, P = 0.024) as risk factors for APD. CONCLUSIONS: iPTH, hsCRP, and Alb are predictors for APD in HD patients.

Nodular mass-A case of auricular schwannoma.

Schwannomas are benign tumors derived from the sheath of Schwann cells. Though it is common to see schwannomas in the head and neck region, auricular schwannomas are rare and only few cases have been reported. There are no distinguishing clinical findings or images; therefore, the histopathological diagnosis is mandatory. We describe a case of auricular schwannoma with clinical pictures and discuss the differential diagnoses according to histopathologic findings.