Greatest Tumor Dimension Research Articles

S3725 A Rare Hybrid gNET: The Neoplastic Jack of All "Grades"

Introduction: Gastric neuroendocrine tumors (gNETs) are rare malignancies which arise from enterochromaffin-like cell (ECL) precursors within the gastric mucosa. There are 4 classifications of gNETs primarily based on size, number of lesions, serum gastrin level, tissue invasion, proliferation index and immunohistochemistry. Applying a combination of factors, gNETs are typically classified into one of these four categories with relative ease. The following case highlights an exceedingly rare hybrid presentation of gNET containing features of all four classification subtypes. Case Description/Methods: A 78-year-old female with a past medical history of hypertension, diabetes mellitus, chronic kidney disease and gastroesophageal reflux disease (GERD) initially presented with worsening symptoms of GERD. The patient denied any alarm symptoms but did endorse persistence of reflux symptoms despite proton pump inhibitor use. Screening EGD with EUS showed polyps which were removed with mucosal resection. Initial pathology illustrated well differentiated gNET. She underwent a DOTA-TATE PET/CT scan which showed heterogenous uptake involving the gastric body reflecting focal gNET without evidence of metastatic disease. The patient underwent total gastrectomy and esophagojejunostomy with upper GI series revealing no evidence of anastomotic leak. On subsequent pathology, at least 46 semi pedunculated gastric polyps were identified of which the greatest tumor dimension was 0.6 cm with a mitotic rate less than 2 mitoses/2mm2. Pathology and immunohistochemistry revealed well differentiated gNET, grade 1 and 2, staining positivity for Chromogranin A (CgA), synaptophysin, CD56, and CAM 5.2 with a Ki67 proliferation index > 6%. Patient’s serum gastrin was within normal limits at 51pg/ml and 24-hour urine 5-HIAA revealed a normal level of 5.7 mg/24hr. She was referred to a geneticist for massive parallel sequencing also known as next generation sequencing (NGS). (Figure) Discussion: This case displays a rare, hybrid presentation of gNET with features of all four classification subtypes. The positive synaptophysin, normal serum gastrin and increased Ki67 index are characteristic of gNET Type 3 and 4 which carry a poor prognosis. Type 3 and 4 however, are typically large ( >2cm), single tumors. This patient had many, smaller tumors with positive CgA staining commonly seen in Type 1 and 2. Hybrid gNETs are extremely uncommon neoplasms which create both a diagnostic and therapeutic challenge requiring a truly multidisciplinary effort.Figure 1.: Ga-68 Dotatate PET-CT showing diffuse heterogenous uptake in the gastric body.

B-PO02-147 IMPACT OF ORAL ANTICOAGULATION THERAPY ON COLORECTAL CANCER DIAGNOSIS

Oral anticoagulation therapy (AC) is associated with an increased risk of gastrointestinal (GI) bleeding which is frequently the presenting symptom of colorectal cancer (CRC). There is currently no evidence that AC is associated with an earlier diagnosis of CRC. We sought to investigate if GI bleeding on AC leads to earlier diagnosis of CRC. We retrospectively reviewed pathology findings from 417 patients with CRC undergoing tumor resection. Data was analyzed by tumor greatest dimension, histopathology grade and TNM system. Data was then compared by AC and anti-platelet therapy (AP) use at the time of tumor resection. At time of diagnosis, 27 patients were on AC (6.5%, DOAC n=20, Warfarin n=7) and 390 patients were not. Patients on AC had smaller tumor size (3.3 ± 1.3 cm) vs. those not on AC (4.3 ± 2.7cm, p= 0.02). Of 27 patients on AC, only 2 (8%) were diagnosed ≥ tumor stage 4 compared to 72/374 patients not on AC (19%, p= 0.125). Distant metastasis was found in 5/27 patients (19%) on AC vs. 122/388 patients not on AC (31%, p=0.4). AP therapy was not associated with a decrease in tumor size or stage at diagnosis. AC use was associated with smaller tumor size at the time of diagnosis with a trend toward less advanced tumor stage. Earlier diagnosis of CRC may lead to earlier treatment and improved mortality. Further studies are needed to determine whether AC use is associated with lower mortality in this patient population.

MON-434 Encapsulated Follicular-Variant of Micropapillary Carcinoma Presenting with Distant Bony Metastasis

INTRODUCTION The incidence of thyroid cancer has risen steadily over the last decades, in part due to increasing diagnosis of apparently low-risk well-differentiated cancers. The outcomes of well-differentiated thyroid cancers, including follicular variant papillary thyroid carcinoma (PTC), are believed to be quite favorable, with a largely indolent benign course. We examine an encapsulated follicular-variant of micropapillary carcinoma presenting with distant bony metastasis. CASE 55-year-old lady presented to clinic after biopsy of iliac crest (IC) mass revealed thyroid tissue. One year prior she started having dull pain at right hip, attributed to increased physical activity. She noticed a tender “lump” on her right hip. CT revealed destructive right iliac 8 cm mass with extraosseous soft tissue component, central necrosis, and eccentric calcifications; and right ovarian cyst. Right IC biopsy was consistent with thyroid tissue with positive Thyroglobulin and TTF-1 immunostains. Physical exam was normal, except for mild tachycardia, hypertension, right flank large rounded mass fixed to IC, tender to palpation without erythema or warmth on overlying skin. Thyroid ultrasound showed normal thyroid gland except 5.58 x 6.22 x 7.76 mm left lobe nodule without increased vascularity but with coarse peripheral calcification. FNA was unsatisfactory. Thyroid function tests revealed undetectable TSH, elevated FT4, FT3, and markedly elevated thyroglobulin and TSI. PET/CT scan showed focal area of mild FDG avidity, corresponding to the right iliac crest mass, without additional areas of FDG avidity suggestive of metastatic disease or primary neoplastic process. Three weeks after presentation, patient began having symptoms of hyperthyroidism. As FT4 and FT3 continued to rise, she was started on propranolol and methimazole. Due to inadequate response, methimazole was switched to high dose propylthiouracil with mild improvement. Thyroid uptake and scan and SPECT-CT revealed increased thyroid uptake and thyromegaly consistent with Graves’ disease and redemonstrated large right IC lesion with increased uptake in the periphery and central photopenia, suggesting metastatic thyroid malignancy. Pathology from total thyroidectomy reported encapsulated follicular variant of PTC, confined to the left lobe of the thyroid, without extrathyroidal extension, greatest tumor dimension 0.6cm. As metastasis to the IC were unlikely to have originated from this small encapsulated thyroid cancer, it was recommended to proceed with right oophorectomy for suspected malignant struma ovarii and IC lesion debulking. Surgical pathology revealed right ovary and fallopian tube without pathologic changes or features of teratoma and tissue from right iliac mass consistent with PTC. Patient is off all antithyroid medications and remains biochemically euthyroid, awaiting radioactive iodine therapy.

Outcome of Chinese children with craniopharyngioma: a 20-year population-based study by the Hong Kong Pediatric Hematology/Oncology Study Group.

Craniopharyngioma is a rare low-grade neoplasm in children. Tumor progression occurs frequently, and survivors are at risk of long-term disease and treatment-related morbidities. We reviewed the population-based experience of managing pediatric craniopharyngioma in Hong Kong. The Hong Kong Pediatric Hematology/Oncology Study Group database was interrogated for patients with craniopharyngioma younger than 18years between 1999 and 2018. Patient demographics, clinical characteristics, outcomes, and long-term morbidities were summarized. Twenty-eight patients with craniopharyngioma were included (approximate incidence of 1.1 per 1,000,000 individuals). The treatment approaches were heterogeneous and included surgery only, surgery with adjuvant radiation, and surgery with intracystic interferon. With a median follow-up of 6.1years, 12 (43%) patients experienced disease progression, and 3 patients died of progression, postoperative complication, and gastrointestinal bleeding. The 5-year progression-free survival (PFS) and overall survival (OS) rates were 56.8% (± 10.0%) and 92.0% (± 5.4%), respectively. The 10-year PFS and OS rates were 37.3% (± 11.4) and 92.0% (± 5.4%), respectively. Patients receiving treatment in a high-volume center had significantly better outcomes than did those treated at other centers (PFS, p = 0.007; OS, p = 0.029). Period of diagnosis, sex, age at diagnosis, greatest tumor dimension, extent of resection, and radiotherapy use did not significantly affect patient survival. Long-term visual impairment (60%) and endocrinopathies (92%) were common. Prognosis of pediatric craniopharyngioma in Hong Kong compares unfavorably with published reports. Centralization and standardization of treatment may prove valuable in mitigating patient outcomes.

Low-risk uterine endometrioid carcinoma: The necessity of intraoperative histopathological assessment and lymphadenectomy

Objective: Current practice of surgical management of low-risk uterine endometrioid carcinoma (EEC) and based on Mayo criteria FIGO grade 1 or 2, greatest tumor dimension (GTD) ≤2 cm, and myometrial invasion ≤50%) is hysterectomy without lymphadenectomy. Lymphadenectomy is considered for patients whose tumor does satisfy all 3 criteria and requires intraoperative histopathological assessment. The use of frozen section diagnosis can significantly prolong the surgery and is not always available in all health care facilities. This study investigates the use of preoperative histologic grade with intraoperative greatest tumor dimension measurement, bypassing the intraoperative assessment of myometrial invasion, to determine the indication of lymphadenectomy.

Abstract OT2-03-03: Delivery of a single fraction lumpectomy cavity boost using a novel immobilization device and treatment delivery system

Abstract Background: The lumpectomy cavity (LPC) boost has been shown in 2 randomized studies to improve local control in breast cancer. Hypofraction is now being used for delivery of the LPC boost in some early-stage patients. This trial delivers the LPC boost in a single fraction using a novel breast immobilization device/treatment delivery system. Trial design: Patients are enrolled in this trial after standard resection with lumpectomy/sentinel lymph node biopsy (as appropriate) and chemotherapy (as indicated per standard of care). At the time of CT simulation for whole-breast radiation therapy (RT), the radiation oncologist evaluates breast size and LPC position. If consented for treatment, the patient receives a single fraction “boost” treatment of 8 Gy in 1 fraction followed by standard whole-breast RT to start within 7 days of completion of the boost. Whole-breast radiation is delivered in the supine or prone position with the following fractionation schemes: 4005 cGy in 15 fractions or 5000 cGy in 25 fractions. On the day of the boost treatment, the patient is fitted with the breast immobilization device, with a plastic inner cup that is fitted so that the breast fills all or most of the cup. A rigid outer cup with a built-in stereotactic fiducial system is attached. Moderate negative pressure is applied to immobilize the breast within the cup system. Patients then undergo CT simulation in the prone position. Clip placement and LPC cavity location must meet eligibility criteria before proceeding with treatment planning and delivery. Eligibility criteria: Eligibility criteria: age >60 yo; female only; dx of invasive ductal or lobular carcinoma or ductal carcinoma in situ; estrogen receptor positive; successful completion of lumpectomy ± sentinel lymph node biopsy with negative margins for invasive or noninvasive cancer; greatest tumor dimension <4 cm before surgery; weight <330 lb; height <76 inches; nonlactating and nonpregnant. Various additional dosimetric factors must be met prior to treatment. If these are unable to be met, the patient will become ineligible for treatment. Specific aims: The aim of this study is to demonstrate the feasibility and safety of delivering the LPC boost RT using a single fraction with a novel immobilization device/treatment delivery system while ensuring coverage of the target volume with appropriate dose homogeneity and conformity. Secondary aims are evaluation of patient comfort, acute toxicity (1 month), and late toxicity (1 year). Statistical methods: A Simon 2-stage design is utilized for this trial. After evaluating the device and treatment on 8 patients in the first stage, the trial was designed to be terminated and device rejected if the dose distribution was acceptable for ≤5 patients. The first stage was completed in spring 2017 and progressed to the second stage, designed to include a total of 17 patients. Accrual and target accrual: Target accrual for this study is 14 patients successfully treated while meeting all protocol constraints. As of 6/2017, 16 patients have been enrolled, of whom 13 have been successfully treated while meeting all protocol constraints. Citation Format: Nichols EM, Becker S, Hong J, Cohen RJ, Mishra MV, Citron W, Cheston SB, Niu Y, Mutaf Y, Yu CX, Feigenberg SJ. Delivery of a single fraction lumpectomy cavity boost using a novel immobilization device and treatment delivery system [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr OT2-03-03.

The Relationship Between Serum Interleukin-6 and the Recurrence of Hepatitis B Virus Related Hepatocellular Carcinoma after Curative Resection.

The aim of this study is to assess whether preoperative serum interleukin-6 (IL-6) can predict recurrence of hepatitis B virus (HBV)-associated hepatocellular carcinoma (HCC).The association between preoperative IL-6 levels and HCC recurrence following curative hepatectomy in 146 patients with chronic HBV infection was determined. Patients were divided into groups based on the presence or absence of HCC recurrence. Serum IL-6 levels were compared between groups, and the association between serum IL-6 level and greatest tumor dimension was also analyzed. Receiver operating characteristics (ROC) curve was used to define the optimal cutoff value for predicting recurrence-free survival (RFS) and overall survival (OS) rates. The OS and RFS rates were calculated using the Kaplan-Meier method.Out of 146 patients, 80 (54.8%) patients were documented as having HCC recurrence during the follow-up period. After adjusting for potential confounders, serum IL-6 levels were significantly associated with HCC recurrence, and a saturation effect existed with serum IL-6 levels up to 3.7 pg/mL. In addition, patients with preoperative serum IL-6 levels over 3.1 pg/mL had lower RFS and OS rates (P < 0.01). There was no significant correlation between preoperative serum IL-6 levels and maximal tumor dimension (r = 0.0003, P = 0.84).Elevated serum levels of IL-6 were significantly associated with an increased risk of HBV-associated HCC recurrence suggesting that preoperative IL-6 serum level is potential biomarker for early prediction of HBV-associated HCC recurrence.

Novel Hat–Spherical partial nephrectomy for localized kidney cancer treatment

Objective To present a novel Model for partial nephrectomy and evaluate its oncological, functional outcomes and complication risks in the application for localized kidney cancer treatment. Methods Two hundred and ten patients with localized kidney cancer underwent open or laparoscopic Hat–Spherical partial nephrectomy from Mar. 2011 to Dec. 2013, and were included for this retrospective analysis. Of the 210 patients, 145 were males and 65 were females. The age ranged from 25 to 78 (56±12) years. The tumor greatest dimension was ≤4.0 cm in 143 cases (68.1%), 4.1–7.0 cm in 49 cases (23.3%) and >7.0 cm in 18 patients (8.6%). According to PADUA (Preoperative Aspects and Dimensions Used for an Anatomical) classification, 90, 86 and 34 patients were respectively stratified as low– (42.9%), intermediate– (40.9%) and high–risk (16.1%) groups. In contrast to traditional technique, the key points of Hat–Spherical partial nephrectomy were as follows: after clamping, the renal capsule was incised sharply 3–5 mm away from the tumor edge, and the incision plane was wedge–shaped and towards the tumor pseudocapsule. The transition between pseudocapsule and normal renal parenchyma was the ideal surgical plane. When reached, the tumor was bluntly separated from the surrounding parenchyma following the natural plane. When close the bottom or approaching the renal sinus, the tumor was enucleated along the pseudocapsule. The positive surgical margin rate, warm ischemic time, complication rate and the postoperative eGFR decline were evaluated. The criteria, in which the 3 key outcomes of negative cancer margin, minimal renal functional decrease and no urological complications, were applied to evaluate the Hat–Spherical partial nephrectomy technique. Results Ninety–two patients underwent open Hat–Spherical partial nephrectomy. The mean operation time was 120±45 min, the mean warm ischemic time was 15±5 min. The estimated blood loss was 246±188 ml. Twenty–two patients (23.9%) needed renal calyceal repairing. One hundred and eighteen patients underwent laparoscopic Hat–Spherical partial nephrectomy. The mean operation time and warm ischemic time were 145±50 min and 23±7 min, respectively. The mean estimated blood loss was 185±120 ml and 30 patients (25.4%) needed renal calyceal repairing. The rate of positive surgical margin was 0.95% (2/210). A total of 42 patients (20.0%) experienced complications during 30 days postoperatively, including 36 ClavienⅠ–Ⅱ minor complications and 6 cases of Clavien Ⅲ–Ⅳ major complications. There were 6 postoperative bleeding events (2.9%) and 4 urine leakages (1.9%). There was no perioperative death. The median (range) follow–up was 18 (10–38) mon. The mean decrease in postoperative eGFR was 9.8±20.4 ml/(min· 1.73 m2), and 62 patients had a greater than 10% reduction in the actual vs volume predicted postoperative eGFR. Until the last follow–up, there was no local recurrence and distant metastasis. Trifecta outcome was achieved in 85 patients (40.5%). Conclusions The Hat–Spherical partial nephrectomy has three main technical advantages, including safely keeping negative surgical margin, maximal preservation of renal parenchyma and reducing the risk of vessel and renal calyceal injury. The superiority of Hat–Spherical technique over traditional partial nephrectomy needs further validation by prospective comparative clinical trials. Key words: Kidney cancer; Hat–Spherical partial nephrectomy; Transition zone

Argyrophilic nucleolar organizer region in MIB-1 positive cells in non-small cell lung cancer: clinicopathological significance and survival.

ObjectiveTo evaluate the relation between argyrophilic nucleolar organizer region (AgNOR)-associated proteins and clinicopathological parameters and survival in non-small-cell lung cancer (NSCLC).MethodsA total of 207 surgical specimens diagnosed as NSCLC were included in this study. Double-staining procedures were performed using antigen Ki-67 (clone MIB-1) and silver nitrate by immunohistochemical and AgNOR-staining methods.ResultsThe AgNOR area in MIB-1-positive cells of NSCLC is related to clinicopathological parameters under the TNM (tumor, node, and metastasis) system. The survival of patients with small AgNOR area in MIB-1-positive cells is better than that of patients with large AgNOR area. Molecular, biological (AgNOR area in MIB-1-positive cells), and clinicopathological (greatest tumor dimension, metastases to regional lymph nodes, histology, and differentiation) parameters are independent prognostic factors of NSCLC.ConclusionThe AgNOR area in MIB-1-positive cells is related to clinicopathological parameters and survival in NSCLC.

Association between Argyrophilic Proteins of Nucleolar Organizer Regions, Clinicomorphological Parameters, and Survival in Non-Small-Cell Lung Cancer.

We studied argyrophilic proteins associated with nucleolar organizer regions (AgNOR) in non-small-cell cancer. We determined the area index (AI) and coefficient of variation (CV) of AgNOR. AI is associated with the key clinicomorphological parameters within the TNM system: T and N values, greatest tumor dimension up to 3 cm and more, disease stage, histogenesis, and tumor differentiation. CV is associated with T value, greatest tumor dimension up to 3 cm and more, histogenesis, and tumor differentiation. Survival of patients is longer in low AI or CV values versus high AI or CV values, longer in low AI and CV values (−AI/−CV type), shorter in high AI and CV values (+AI/+CV type), and intermediate in opposite AI and CV values (−AI/+CV and +AI/−CV types). Independent predictors in non-small-cell lung cancer include N value, greatest tumor dimension, histogenesis, and CV. Assessment of quantitative values and heterogeneity of AgNOR is important for differential diagnosis and prognosis of non-small-cell lung cancer.

Abstract P2-02-09: Accuracy of MRI for estimating residual tumor size after neoadjuvant endocrine therapy in early stage breast cancer with ER positive and HER2 negative

Abstract Back ground Neoadjuvant endocrine therapy (NET) is increasingly being used in the management of breast cancer patients with ER positive and HER2 negative. A major clinical benefit is that patients with large operable tumors may be offered breast-conserving surgery (BCS). Therefore, success of BCS following NAT depends on accurate assessment of the residual tumor extent after NAT. The correlation between the extent of the tumor at pathology and preoperative assessments of the size obtained by physical examination and conventional imaging is impaired by hormonal therapy-induced necrosis and fibrosis. However, the most superior method to assess the extent of residual disease after NAT was unknown. The aim of this study was to evaluate the relative accuracies of mammography(MMG), ultrasound(US), specimen mammography(SMMG) and MRI in predicting residual tumor size and pathological response after neoadjuvant endocrine therapy (NET) in patients with ER positive and HER2 negative. Each prediction method (EPM) was compared with the gold standard of surgical pathology. Patients and methods From April 2010 to December 2012, 50 post menopausal patients with breast cancer at clinical stages T1c-T2N0 were prospectively enrolled in this study on NET. Fifty patients (age range, 52-75 years; mean age, 64.1 years) who received NET with 24 weeks of letrozole were evaluated with EPM before and after NET. We compared the predicted residual tumor size and the predicted response on imaging with residual tumor size and response on the pathologically determined size. We defined the tumor sizes measured by EPM and pathology as in agreement when the greatest tumor dimension measured by EPM was within 70_120% of the measurement determined by microscopic pathology. The EPM assessment was categorized as an underestimation when the longest diameter on imaging was &amp;lt;70% that at pathology and as an overestimation when the longest diameter on imaging was&amp;gt;120% that at pathology. Statistical analysis was performed using logistic regression analysis. Results The correlation coefficient between the residual tumor sizes determined by pathology and the predicted tumor size was 0.721(p = 0.651) for MMG, -0.111(p = 0.642) for US, 0.723(P = 0.001) for SMMG and 0.714 (p&amp;lt;0.000001) for MRI. The rate of agreement between the final response predictions and the responses measured by pathology were 50% for MMG, 40% for US, 35% for SMMG and 78% for MRI. The MMG,US, SMMG and MRI measurement disagreed with the pathologically determined size in 50%,60%,65%,22%, overestimating the size in 0%,12%, 11%,2% and underestimating the size in 50%, 48%,53%,20% respectively. Conclusions Predictions of response and residual tumor size made on MRI were best correlated with the assessments of response and residual tumor size made on pathology than were predictions made on the basis of clinical examination, mammography or ultrasound. MRI is one of the most accurate methods for predicting the extent of residual tumor after NET. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P2-02-09.

Impact of Schwartz Enhanced Visualization Solution on Staging Colorectal Cancer and Clinicopathological Features Associated With Lymph Node Count

Stage-specific survival for colon cancer improves when more lymph nodes are reported in the surgical specimen. This has led to a minimum standard of identifying 12 lymph nodes as a quality indicator. The aim of this study was to determine whether the addition of Schwartz solution increases node yield and impacts pathologic staging. This is a prospective cohort study. The study was conducted in an academic medical center. Included were 104 consecutive patients with colorectal cancer. Lymph node counts before and after specimen treatment with Schwartz solution and incidence of upstaging were measured. An additional 20 minutes (interquartile range, 15-40 minutes) was spent searching for lymph nodes, increasing the median number of nodes from 22.5 to 29.0 nodes. However, only 1 patient was upstaged. Schwartz solution decreased the number of specimens with less than 12 lymph nodes from 15 to 6. The following factors were associated with Schwartz solution leading to the detection of additional nodes: number of nodes detected initially with formalin only (p < 0.000), mesenteric fat volume (p < 0.000), mesenteric fat weight (p < 0.000), length of specimen (p < 0.016), tumor greatest dimension (p < 0.016), patient body surface area (p < 0.034), and patient age (p < 0.003). Clinical data for this study were obtained retrospectively and were not available for all of the patients. Although Schwartz solution increased the number of nodes detected in 95% of patients and improved compliance with the 12-node standard for colon resection, there was minimal impact on cancer staging. Upstaging is unlikely to explain the increase in overall survival in patients with higher lymph node counts, casting doubt on the validity of this process measure as a meaningful quality indicator. Rather, the lymph node count may be a reflection of inherent tumor biology or host-related factors.

Stereotactic body radiation therapy for inoperable hepatocellular carcinoma as a local salvage treatment after incomplete transarterial chemoembolization

The objective of this study was to evaluate the efficacy and safety of stereotactic body radiation therapy (SBRT) as a local salvage treatment after incomplete transarterial chemoembolization (TACE) for inoperable hepatocellular carcinoma (HCC). The main eligibility criteria were a greatest tumor dimension (LD sum) <10 cm, inoperable HCC, and incomplete response after TACE. Prescribed SBRT doses were up to 60 gray (Gy) in 3 fractions, but doses were reduced until normal tissue constraints were allowed. Between May 2008 and February 2011, 50 patients were enrolled in this phase 2 trial, of which 47 patients were evaluable. Forty-one patients had Child-Pugh class A disease (A5/A6 were 32/9), 6 patients had class B7 disease, and 5 patients had portal vein tumor thrombosis. All patients underwent TACE 1 to 5 times before SBRT. SBRT doses ranged from 42 to 60 Gy in 3 fractions (median dose, 57 Gy), and the median LD sum was 29 mm (range, 13-78 mm). Eighteen patients (38.3%) achieved complete remission within 6 months of completing of SBRT, and 18 patients (38.3%) had a partial response. The 2-year local control rate was 94.6%, the overall survival rate was 68.7%, and the progression-free survival rate was 33.8%. Three patients (6.4%) experienced grade 3 gastrointestinal toxicity, and 2 patients (4.3%) experienced grade 4 gastric ulcer perforation. This trial demonstrated that SBRT after incomplete TACE for inoperable HCC achieves promising rates of response and local control. On the basis of these study results, a modified, multi-institutional, phase 2 trial to reduce gastrointestinal toxicity is recommended.

Chronic Schistosomiasis Japonica is an Independent Adverse Prognostic Factor for Survival in Hepatocellular Carcinoma Patients Who Have Undergone Hepatic Resection: Clinicopathological and Prognostic Analysis of 198 Consecutive Patients

The present study was carried out to clarify the clinicopathological features of hepatocellular carcinoma (HCC) patients with chronic schistosomiasis japonica (SJ) who underwent hepatic resection. Furthermore, we also analyzed the impact of chronic SJ on survival after hepatic resection. During the last 10 years in our department, 198 patients have undergone hepatic resection for HCC. Forty-four patients were diagnosed as having chronic SJ by histological examination. Clinicopathological features and survival were retrospectively analyzed. Age in the SJ group was significantly higher than in the non-SJ group. In the SJ group, positivity to HBsAg (hepatitis B surface antigen) was significantly lower than in the non-SJ group, and patients more often developed intrahepatic cholangiocellular carcinoma (or cholangiolocellular carcinoma) than in the non-SJ group. Greatest tumor dimension in the SJ group was significantly larger than in the non-SJ group. Univariate analysis revealed that chronic SJ, prothrombin time 80% or less and Child-Pugh B, des-gamma-carboxyprothrombin (DCP) level >40 milli-arbitrary units (mAU)/ml, tumor diameter of more than 5.0 cm, multiple tumors, vascular invasion, intrahepatic metastasis, advanced T stage (T2-4), and non-curative resection were associated with significantly worse overall survival. By multivariate analysis, chronic SJ, Child-Pugh B, advanced T stage, and non-curative resection were independent predictors of the adverse overall survival of HCC patients after hepatic resection. Patients with chronic SJ were older, had larger HCC, and were more often complicated by cholangiocellular carcinoma (or cholangiolocellular carcinoma) than non-SJ patients. Chronic SJ was an independent adverse prognostic factor for survival after hepatic resection in HCC patients.

Fluorodeoxyglucose positron emission tomography and tumor marker expression in non–small cell lung cancer

The best current noninvasive surrogate for tumor biology is fluorodeoxyglucose positron emission tomography (FDG-PET). Both FDG-PET maximal standardized uptake values and selected tumor markers have been shown to correlate with stage, nodal disease, and survival in non-small cell lung cancer (NSCLC). However, there are limited data correlating FDG-PET with tumor markers. The purpose of this study was to determine the correlation of tumor marker expression with FDG-PET maximal standardized uptake values in NSCLC. FDG-PET maximal standardized uptake values were calculated in patients with NSCLC (n = 149). No patient had induction chemoradiotherapy. Intraoperative NSCLC tissue was obtained and tissue microarrays were created. Immunohistochemical analysis was performed for 5 known NSCLC tumor markers (glucose transporter 1, p53, cyclin D1, epidermal growth factor receptor, and vascular endothelial growth factor). Each tumor marker was assessed independently by two pathologists using common grading criteria. Subgroup analysis based on histologic characteristics and regional nodal status was performed. FDG-PET correlated with T classification (P < .0001), N stage (P = .002), and greatest tumor dimension (P < .0001). In addition, increasing maximal standardized uptake values correlated with increased expression of glucose transporter 1 (P < .0001) and p53 (P = .04) in adenocarcinoma. Epidermal growth factor receptor expression correlated with maximal standardized uptake values without predilection for histologic subtype (P = .004). FDG-PET maximal standardized uptake values correlate with an increased expression of glucose transporter 1 and p53 in lung adenocarcinoma, but not squamous cell cancer. Future studies attempting to correlate FDG-PET with tumor biology will need to consider the effect of different tumor histologic types.

The expression of HSP27 is associated with poor clinical outcome in intrahepatic cholangiocarcinoma

BackgroundThe heat shock proteins (HSPs) 27-kDa (HSP27) and 72-kDa (HSP72), are ubiquitous chaperone molecules inducible in cells exposed to different stress conditions. Increased level of HSPs are reported in several human cancers, and found to be associated with the resistance to some anticancer treatments and poor prognosis. However, there is no study of the relationship between HSPs expression and patient's prognosis in intrahepatic cholangiocarcinoma (IHCCA). In this exploratory retrospective study, we investigated the expressions of HSP27 and HSP72 as potential prognostic factors in IHCCA.MethodsThirty-one paraffin-embedded samples were analyzed by immunohistochemical methods using HSP27 and HSP72 monoclonal antibodies. Proliferation rate was assessed in the same specimens by using monoclonal antibody against phosphorylated histone H3 (pHH3). Fisher's exact test was used to assess the hypothesis of independence between categorical variables in 2 × 2 tables. The ANOVA procedure was used to evaluate the association between ordinal and categorical variables. Estimates of the survival probability were calculated using the Kaplan-Meier method, and the log rank test was employed to test the null hypothesis of equality in overall survival among groups. The hazard ratio associated with HSP27 and HSP72 expression was estimated by Cox hazard-proportional regression.ResultsThe expression of HSP27 was related to mitotic index, tumor greatest dimension, capsular and vascular invasion while the expression of HSP72 was only related to the presence of necrosis and the lymphoid infiltration. Kaplan-Maier analysis suggested that the expression of HSP27 significantly worsened the patients' median overall survival (11 ± 3.18 vs 55 ± 4.1 months, P-value = 0.0003). Moreover HSP27-positive patients exhibited the worst mean survival (7.0 ± 3.2 months) in the absence of concomitant HSP72 expression.ConclusionThe expression of HSP27, likely increasing cell proliferation, tumor mass, vascular and capsular invasion, might promote aggressive tumor behaviour in IHCCA and decrease patients' survival. Immunohistochemical detection of HSP27 on routine sections may provide a reliable prognostic marker for IHCCA able to influence the therapeutic strategies for this cancer.

Accuracy of contrast-enhanced breast ultrasound for pre-operative tumor size assessment in patients diagnosed with invasive ductal carcinoma of the breast

Our aim was to assess the feasibility and accuracy of contrast-enhanced ultrasound (CEUS) of the breast with SonoVue microbubbles for pre-operative size measurement of invasive breast carcinomas. Seven patients diagnosed with nine invasive breast carcinomas prospectively underwent gray-scale ultrasound and CEUS of the breast according to a standardized protocol. CEUS of the breast was performed by a Philips iU22 scanner equipped with a 4–8 MHz linear array transducer. We used a single dose of 2.4 ml SonoVue as contrast agent. Breast lesion morphology was scored according to the sonographic BI-RADS lexicon criteria and classified accordingly. The greatest tumor dimensions on gray-scale ultrasound and CEUS of the breast were finally compared with the greatest histopathologic tumor sizes. Gray-scale ultrasound underestimated the histopathologic tumor size in 6/9 cases (67%), whereas CEUS of the breast underestimated tumor size in only 3/9 (33%) cases. CEUS of the breast was significantly more accurate for tumor size assessment. Greatest tumor dimension as measured with gray-scale ultrasound of the breast was within 2 mm of the pathologic tumor size in only 2/9 cases (22%), whereas CEUS of the breast accurately assessed tumor size within 2 mm of pathologic tumor size in 6/9 (67%) of the cases (P<0.05). CEUS of the breast proved to be a feasible and safe procedure. It is more accurate than gray-scale ultrasound of the breast for pre-operative size assessment of invasive ductal breast carcinomas.

Simple Enucleation for the Treatment of PT1a Renal Cell Carcinoma: Our 20-Year Experience

ObjectivesTo evaluate the safety and efficacy of simple enucleation as a conservative treatment for pT1a RCC, and to report on the incidence of major complications, local recurrence, and progression-free and disease-specific survival rates. MethodsWe retrospectively reviewed the data of 232 patients who had nephron-sparing surgery (NSS) by simple enucleation between 1986 and 2004 for sporadic, unilateral, pathologically confirmed pT1a RCC. The patients’ status was evaluated last in September 2005. The mean (median, range) follow-up was 76 (61, 12–225) months. ResultsThe mean (SD, median, range) tumor greatest dimension was 2.8 (0.78, 2.85, 0.6–4) cm. The histopathologic review according to the International Union Against Cancer and American Joint Commission for Cancer (1997) classification revealed 198 clear cell (85.3%), 18 papillary (7.8%), 15 chromophobe (6.5%) and one (0.4%) collecting duct RCCs. There were no major complications, such as prolonged acute tubular necrosis/chronic renal insufficiency and bleeding requiring open reoperation. One patient developed postoperative late retroperitoneal fluid collection consistent with urinoma, which required aspiration, drainage position and JJ stenting for 3 weeks. The 5- and 10-year cancer-specific survival were 96.7% and 94.7%, respectively. The 5- and 10-year progression-free survival were 96% and 94%, respectively. Overall, 13 (6.4%) patients had disease progression, three of whom had local recurrences alone (1.5%) elsewhere in the kidney; none had local recurrence at the level of the enucleation bed. ConclusionsSimple tumor enucleation is a safe and acceptable nephron-sparing treatment that provides excellent long-term local control and cancer-specific survival rates.

PROGRESSION AND LONG-TERM SURVIVAL AFTER SIMPLE ENUCLEATION FOR THE ELECTIVE TREATMENT OF RENAL CELL CARCINOMA: EXPERIENCE IN 107 PATIENTS

We present our findings in a series of T1a renal cell carcinoma treated with elective simple enucleation, specifically reporting the incidence of local recurrence, and progression-free and disease specific survival rates. A total of 107 patients who underwent elective nephron sparing surgery performed with simple enucleation from January 1989 to December 2000 were studied retrospectively. None of the patients had preoperative or intraoperative suspicion of positive nodes. All patients were free from distant metastases before surgery (M0). Patient status was last evaluated in July 2004. Mean (median, range) followup was 88.3 (84, 44 to 175) months. Pathological review according to the 2002 TNM classification showed that 95% (102 of 107) of tumors were pT1a, 4% (4 of 107) pT1b and 1% (1 of 107) pT3a. Mean (SD, median, range) tumor greatest dimension was 2.7 (0.93, 2.5, 0.6 to 5) cm. None of the patients died in the immediate postoperative period (within the first 30 days). There were no major complications such as bleeding and urinary leakage/urinoma requiring reoperation. The 5 and 10-year cancer specific survival was 99% and 97.8%, respectively. The 5 and 10-year progression-free survival was 98.1% and 94.7%, respectively. Overall 3 patients had disease progression (2.8%) of whom 2 (1.9%) were local recurrence, 1 alone and 1 associated with distant metastases diagnosed 12 months earlier. Simple tumor enucleation is a safe and acceptable approach for elective nephron sparing surgery. It provides excellent long-term progression-free and cancer specific survival rates, and is not associated with an increased risk of local recurrence compared with partial nephrectomy.

Invasive cutaneous malignant melanoma in Sweden, 1990-1999. A prospective, population-based study of survival and prognostic factors.

The objective of the current study was to compile prospective, population-based data on cutaneous invasive melanomas in Sweden during the period from 1990 to 1999, to describe and analyze survival data and prognostic factors, and to make comparisons with previously published Swedish and international data. Twelve thousand five hundred thirty-three patients, which included 97% of all registered melanomas in Sweden, were included and described. Among these, 9515 patients with clinical Stage I and II melanoma were included in an analysis of survival and in a univariate analysis, and 6191 patients were included in a multivariate analysis of prognostic factors. There was no significant change in melanoma incidence during 1990-1999. Favorable prognostic factors were found, especially in younger and female patients, resulting in a relative 5-year survival rate of 91.5%. In the multivariate analysis, significant factors that had a negative effect on survival were Clark level of invasion, Breslow thickness, ulceration, older patient age, trunk location, greatest tumor dimension, nodular histogenetic type, and male gender. During the period from 1990 to 1999, the 5-year survival of patients with malignant melanoma in Sweden was better compared with the previously reported rates in published, population-based studies from Sweden, probably as a result of better secondary prevention due to better knowledge and awareness by both patients and the medical profession. The more favorable prognostic factors and the change in melanoma location found in younger patients, compared with earlier reports, may reflect changes in clothing as well as tanning habits; however, a decrease also was found in Clark Level II and thin melanomas for the same patient group. The authors concluded that further improvements can be achieved with better access to health care and with the use of early melanoma detection campaigns.