Clinicopathologic analysis of surgically proven intraductal papillary mucinous neoplasms of the pancreas in SNUH: a 15-year experience at a single academic institution

Purpose  

The clinical importance of intraductal papillary mucinous neoplasm of the pancreas (IPMN) has been increasing with a large number of newly diagnosed IPMN. This study was designed to explore the characteristics of resected IPMN and to determine the predictive factors for malignant and invasive IPMN.     

Patterns of recurrence after sentinel lymph node biopsy for cutaneous melanoma

BACKGROUND: Previous sentinel lymph node (SLN) studies for cutaneous melanoma have shown that the SLN accurately reflects the nodal status of the corresponding nodal basin. However, there are few long-term studies that describe recurrence site patterns, predictors for recurrence, and overall survival and disease-free survival after SLN biopsy. METHODS: A retrospective review of patients over a 6-year period was performed to determine patient outcomes and the patterns of recurrence. In all cases, Tc-99 sulfur colloid along with isosulfan blue dye was injected at the primary melanoma site. After resection, the SLN was serially sectioned and evaluated by hematoxylin and eosin staining and immunohistochemistry. RESULTS: One hundred ninety-eight patients were identified who underwent SLN biopsy for cutaneous melanoma including T1 (n = 21), T2 (n = 88), T3 (n = 75), and T4 (n = 14) primary tumors. Of these patients, 38 had a positive SLN. Of the 38 patients with a positive SLN (mean follow-up 38 months), recurrent disease was identified in 10 (26.3%) at a mean interval of 14.2 months. The site of first recurrence was distant (n = 4) and local (n = 6). Regional lymphatic basin recurrence was not identified. Of the 160 patients with a negative SLN (mean follow-up 50 months), recurrent disease was identified in 16 (10.0%) at a mean interval of 31.3 months. The site of first recurrence was systemic (n = 11), local (n = 4), and nodal (n = 1). Overall survival and disease-free survival for patients with a positive SLN at 55 months was 53.3% and 47.7% respectively, while overall survival and disease-free survival for patients with a negative SLN at 53 months was 92.2% and 87.7% respectively (P <0.01). Univariate and multivariate analysis of the entire cohort (n = 198) identified primary tumor depth and positive SLN status as significant predictors of recurrence. CONCLUSIONS: The incidence of nodal basin recurrence after SLN biopsy was found to be 0.6%. Primary tumor depth and pathological status of the SLN are significant predictors of local and systemic recurrence. Long-term follow-up indicates that patients with a positive SLN clearly recur sooner and have decreased overall survival than those with a negative SLN.     

Comparison of 1.0 M gadobutrol and 0.5 M gadopentate dimeglumine-enhanced MRI in 471 patients with known or suspected renal lesions: results of a multicenter, single-blind, interindividual, randomized clinical phase III trial

The purpose of this phase III clinical trial was to compare two different extracellular contrast agents, 1.0 M gadobutrol and 0.5 M gadopentate dimeglumine, for magnetic resonance imaging (MRI) in patients with known or suspected focal renal lesions. Using a multicenter, single-blind, interindividual, randomized study design, both contrast agents were compared in a total of 471 patients regarding their diagnostic accuracy, sensitivity, and specificity to correctly classify focal lesions of the kidney. To test for noninferiority the diagnostic accuracy rates for both contrast agents were compared with CT results based on a blinded reading. The average diagnostic accuracy across the three blinded readers (‘average reader’) was 83.7% for gadobutrol and 87.3% for gadopentate dimeglumine. The increase in accuracy from precontrast to combined precontrast and postcontrast MRI was 8.0% for gadobutrol and 6.9% for gadopentate dimeglumine. Sensitivity of the average reader was 85.2% for gadobutrol and 88.7% for gadopentate dimeglumine. Specificity of the average reader was 82.1% for gadobutrol and 86.1% for gadopentate dimeglumine. In conclusion, this study documents evidence for the noninferiority of a single i.v. bolus injection of 1.0 M gadobutrol compared with 0.5 M gadopentate dimeglumine in the diagnostic assessment of renal lesions with CE-MRI.

The utility of capsule endoscopy and its role for diagnosing pathology in the gastrointestinal tract

BACKGROUND: Capsule endoscopy (CE) is a new device that enables visualization of areas of the small bowel that were previously inaccessible through other noninvasive procedures. The purpose of this study is to evaluate this new diagnostic tool and its efficacy in finding occult GI tract pathology. METHODS: A single-institution retrospective review was completed on patients undergoing CE from January 2002 to September 2004. Data evaluated included indications for CE, results of previous studies, CE findings, and complications of the CE study. RESULTS: A total of 702 CE studies in 652 patients were performed during the study period. Suspicious GI bleeding presenting as anemia, guaiac positive stools, or history of gross bleeding were the most common reasons to perform CE (75.8%). Other indications included abdominal pain (11.5%), diarrhea (3.1%), or others (9.5%). In studies performed for GI bleeding (N = 532), a source was found in 49.3% of CE studies. Arteriovenous malformation (AVM) was the most common reported finding (43.9%), followed by ulcer (24.1%), colon or gastric pathology (14.1%), mass/tumor (9.1%), and stricture (6.9%). Patients with abdominal pain (n = 81) had findings 46.9% of the time including edema/ulcer (47.4%), stricture (10.5%), mass/tumor (26.3%), gastric pathology (10.5%), AVM (2.6%), or sprue (2.6%). Patients with diarrhea (n = 22) had findings 45.5% of the time including edema/ulcer (75%), mass/tumor (12.5%), or sprue (12.5%). A total of 66 patients underwent operative exploration after a CE study at this institution either because of the observed findings or for other reasons. There were 12 (1.7%) CE studies in which the capsule was retained and required surgical removal. Pathology at the retention site included benign strictures or adhesions (n = 9, 75%), Crohn's stricture (n = 1, 8.3%) carcinoid tumor (n = 1, 8.3%), and villous adenoma (n = 1, 8.3%). CONCLUSIONS: CE is an accurate study to locate abnormalities in the GI tract that may have either been missed by previous diagnostic studies or cannot be observed through other non-invasive means. When used for diagnostic challenges such as GI bleeding with no apparent source, CE can be helpful in guiding surgical decisions in patients and thus should be integrated as part of the diagnostic workup.     

Comparative Diagnostic Utility of Low‐Dose Breast‐Specific Gamma Imaging to Current Clinical Standard

To retrospectively compare low‐dose (7–10 mCi) to high‐dose (15–30 mCi) breast‐specific gamma imaging (BSGI) in the detection of breast cancer. A retrospective review of 223 consecutive women who underwent BSGI exam between February 2011 and August 2013 with subsequent pathologic analysis was performed. Women were divided into low‐dose and high‐dose groups. The results of BSGI and pathology were compared, and the sensitivity, positive predictive value (PPV), and negative predictive value (NPV) were determined. A subgroup analysis was performed to evaluate specificity using benign follow‐up imaging to establish true‐negative results. There were 223 women who met inclusion criteria with 109 patients with 153 lesions in the low‐dose group and 114 patients with 145 lesions in the high‐dose group. Pathologic correlation demonstrates sensitivities of 97.6% (95% CI = 90.9–99.6%) and 94.6% (95% CI = 84.2–98.6%; p = 0.093), PPVs of 62.1% (95% CI = 53.2–70.3%) and 50.5% (95% CI = 40.6–60.3%, p = 0.089), and NPVs of 90.5% (95% CI = 68.2–98.3%) and 92.5% (95% CI = 78.5–98.0%, p = 0.781) in the low‐dose and high‐dose groups, respectively. Subgroup analysis included 72 patients with 98 lesions in the low‐dose group and 116 patients with 132 lesions in the high‐dose group, with a specificity of 53.7% (95% CI = 39.7–67.1%) and 66.3% (95% CI = 56.2–75.2%%, p = 0.143), respectively. Low‐dose BSGI demonstrated high sensitivity and NPV in the detection of breast cancer comparable to the current standard dose BSGI, with moderate specificity and PPV in a limited subgroup analysis, which was associated with a substantial number of false‐positives.     

Gender differences in trabecular bone architecture of the distal radius assessed with magnetic resonance imaging and implications for mechanical competence

High-resolution magnetic resonance imaging (hrMRI) has recently made it possible to evaluate trabecular bone structure in vivo. Despite obvious gender differences in fracture incidence at the distal radius, little is known about gender differences in trabecular bone microarchitecture and its relationship to the structural strength of the forearm. The aim of this study was to determine trabecular bone structure in the distal radius of elderly women and men and its correlation with failure loads of the distal radius as determined in a fall configuration. Specifically, we tested the hypotheses that structural indices differ between women and men and that they offer information that is independent from BMD for predicting structural strength. Intact right arms were obtained from 73 formalin-fixed cadavers (age 80±11 years, 43 women, 30 men). Trabecular structural indices (apparent bone volume fraction [app. BV/TV], trabecular number [app. Tb.N], trabecular separation [app. Tb.Sp], trabecular thickness [app. Tb.Th] and fractal dimension [Frac.Dim]) were assessed in the distal metaphysis, using hrMRI with 156 µm in-plane resolution and proprietary digital image analysis, while BMD was measured with dual X-ray absorptiometry (DXA). Women displayed significantly lower BMD (–29.8%, p <0.001), app. BV/TV (–8.2%, p <0.05) and app. Tb.Th (–10.2%, p <0.001) than men, whereas app. Tb.N, app. Tb.Sp. and fractal dimension did not differ significantly. Structural parameters differed between normal and osteopenic women (BV/TV: –11%, p <0.01; Tb.Th: –8%, p <0.001) and between normal and osteoporotic women BV/TV: –21%, p <0.001; Tb.Th: –16%, p <0.001). App. BV/TV, app. Tb.Th and fractal dimension provided information independent from BMD in the prediction of radial failure loads in multiple regression models. These findings imply that it should be of clinical interest to monitor both bone mass and trabecular microstructure for predicting osteoporotic fracture risk.     

Actual long-term outcome of extrahepatic bile duct cancer after surgical resection

OBJECTIVES: The objectives of this study were to analyze the actual long-term outcome after the surgical resection of extrahepatic bile duct cancer and to identify the characteristics shared by long-term survivors (5 years or longer). SUMMARY BACKGROUND DATA: Although reported 5-year survival rates of extrahepatic bile duct cancer lie between 20% and 30%, these data are not reflecting the actual cure rate. Some patients survive longer than 5 years with recurrent disease. In some patients, recurrence is detected after 5 years. Accordingly, true cure rate is probably substantially lower than the 5-year survival rate. METHODS: One hundred fifty-one patients from a total of 282 patients with extrahepatic bile duct cancer (excluding ampulla of Vater cancer) underwent surgical resection between 1986 and 1997. We analyzed the actual survival outcome and postresection prognostic factors after resection, which included hepatobiliary resection (HBR; extended either right or left hepatectomy, caudate lobectomy, and hilar bile duct resection, n = 23), bile duct resection (BDR; n = 25), and pancreatoduodenectomy (PD; n = 103). We also compared the clinicopathologic characteristics of actual long-term survivors (n = 49) with those who survived longer than 5 years and with short-term (<5 years) survivors. RESULTS: Forty-nine of the 151 resection cases (32.5%) survived 5 years or longer; there was no 5-year survivor in the nonresected cases. The actual 5-year survival rate was 47.8% after HBR (11 of 23), 28.0% after BDR (7 of 25), and 30.1% after PD (31 of 103) (P = 0.083). Tumor histology and lymph node metastasis were identified as independent prognostic factors by multivariate analysis. Some long-term survivors had poor postoperative prognostic factors such as T3, lymph node metastasis, or microscopic margin involvement, but none with a poorly differentiated tumor. Seven long-term survivors had recurrent disease at 5 years, and recurrence was detected after 5 years in 8 more patients. Therefore, the actual cure rate (<19.2%) was substantially less than the 5-year survival rate. CONCLUSIONS: In cases of extrahepatic bile duct cancer, resection should be considered and efforts should be made to obtain a tumor-free margin. An aggressive surgical approach will give some survival benefit to the patients with even advanced disease. Long-term follow up is needed before declaring "a cure," because late recurrence after 5 years is detected not infrequently. Adjuvant therapy, local and systemic, needs to be further developed.     

Improved Performance of Hip DXA Using a Novel Region of Interest in the Upper Part of the Femoral Neck: In Vitro Study Using Bone Strength as a Standard of Reference

We tested the hypothesis that bone mineral density (BMD) and bone mineral content (BMC) in proximal human femur specimens in the upper neck region of interest (ROI) and femoral neck axis length (FNAL) provide a significantly better prediction of femoral bone strength than standard ROIs in vitro. BMD and BMC were measured in 110 proximal femur specimens using a standard dual-energy X-ray absorptiometry (DXA) scanner. The analysis included a new ROI in the upper neck as well as the standard ROIs. FNAL was obtained from the scan images. The specimens' failure-load was measured in a mechanical loading device, simulating a fall on the greater trochanter. For the standard ROIs, correlations between failure-load and BMD ranged from R2 = 0.64 (shaft ROI) to R2 = 0.70, p < 0.001 (femoral neck). Prediction of strength by BMD did not significantly differ from those of BMC (R2 ranging from 0.65 to 0.75, p < 0.001). In the upper neck ROI, for both BMD and BMC correlations with failure-load were higher (R2 = 0.76 and 0.81, respectively; p < 0.001). A lower, yet still significant, correlation was found between FNAL and bone strength (R2 = 0.23, p < 0.001). Normalization of failure-load with respect to FNAL did not significantly increase the correlations with densitometric measures. This study provides in vitro evidence indicating that among the ROIs of the proximal femur the newly defined upper neck ROI provides the best prediction of bone strength. Only a weak association was observed between failure load and FNAL.     

Outcome of hepatic resection for metastatic gastric cancer

The role of hepatic resection for metastatic gastric cancer is less well defined due to the tendency of gastric cancer to widely metastasize. The purpose of this study is to examine the beneficial effect of hepatic resection in patients with metastatic gastric cancer. The clinicopathologic features and long-term results of 11 patients who underwent hepatic resection for metastatic gastric cancer from January 1988 to December 1996 at Seoul National University Hospital were analyzed retrospectively. All resected hepatic metastases were solitary lesions. Among eight patients with synchronous hepatic metastases, one patient with early gastric cancer and lymph node metastases (T1N2M1) remained alive for 8 years 6 months after hepatic resection without recurrence. Among three patients with metachronous hepatic metastases, two patients with advanced gastric cancer and lymph node metastases (T3N2MO, T2N1MO at the initial operation, respectively) survived 8 years 6 months and 3 years after hepatic resection, respectively. Median survival times of synchronous and metachronous hepatic metastases were 13.0 and 74.3 months, respectively. In solitary hepatic metastatic lesions from gastric cancer, surgical resection should be considered as one of the treatment options.     

Characterization of the inflammatory infiltrate and expression of endothelial cell adhesion molecules in lupus erythematosus tumidus

Lupus erythematosus tumidus (LET) is a disease with characteristic clinical and histopathologic features that has not always been considered a subset of cutaneous lupus erythematosus (CLE). Although LET was first mentioned in the literature in 1930, it has rarely been documented, and immunohistochemical studies have never been performed. The aim of the present study was to characterize the inflammatory infiltrate and to analyze the expression of endothelial cell adhesion molecules in skin specimens from patients with LET and to compare the results with those from patients with other variants of CLE, such as discoid lupus erythematosus (DLE) and subacute cutaneous lupus erythematosus (SCLE). Cryostat sections of lesional skin specimens from ten patients with LET demonstrated an infiltrate composed of more than 75% CD4+, CD8+, and HLA-DR+ cells. Interestingly, CD45RO+ cells, in contrast to CD45RA+ cells, were the prevailing inflammatory cell population. Compared with skin specimens from patients with DLE and SCLE, the mean expression of CD4+ and CD8+ cells was higher (but not significantly so) in LET, and no differences were observed with the other three antibodies. Furthermore, in contrast to controls, intercellular adhesion molecule-1, vascular adhesion molecule-1, E-selectin, and P-selectin showed the same expression pattern in skin specimens from patients with DLE, SCLE, and LET. In conclusion, the inflammatory infiltrate of LET primarily consists of CD4+/CD8+ lymphocytes. Furthermore, expression of endothelial cell adhesion molecules was equally upregulated in LET compared with the expression in DLE and SCLE, suggesting a similar immunopathomechanism of these subtypes of CLE.