Presence Of Capsular Invasion Research Articles

Risk factors for central lymph node metastasis in patients with papillary thyroid carcinoma: a retrospective study.

Thyroid cancer is the most prevalent endocrine malignancy, with its global incidence increasing annually in recent years. Papillary carcinoma is the most common subtype, frequently accompanied by cervical lymph node metastasis early on. Central lymph node metastasis (CLNM) is particularly the common metastasis form in this subtype, and the presence of lymph node metastasis correlates strongly with tumor recurrence. However, effective preoperative assessment methods for CLNM in patients with papillary thyroid carcinoma (PTC) remain lacking. Data from 400 patients diagnosed with PTC between January 1, 2018, and January 1, 2022, at the Shandong Provincial Hospital were retrospectively analyzed. This data included clinicopathological information of the patients, such as thyroid function, BRAF V600E mutation, whether complicated with Hashimoto's thyroiditis, and the presence of capsular invasion. Univariate and multivariate logistic regression analyses were performed to assess the risk factors associated with cervical CLNM in patients with PTC. Subsequently, a clinical prediction model was constructed, and prognostic risk factors were identified based on univariate and multivariate Cox regression analyses. Univariate and multivariate analyses identified that age >45 years (P=0.014), body mass index ≥25 (P=0.008), tumor size ≥1 cm (P=0.001), capsular invasion (P=0.001), and the presence of BRAF V600E mutation (P<0.001) were significantly associated with an increased risk of CLNM. Integrating these factors into the nomogram revealed an area-under-the-curve of 0.791 (95% confidence interval 0.735-0.846) and 0.765 (95% confidence interval: 0.677-0.852) for the training and validation sets, respectively, indicating strong discriminative abilities. Subgroup analysis further confirmed that patients with papillary thyroid microcarcinoma and BRAF V600E mutations who underwent therapeutic central compartment neck dissection had significantly better 3-year disease-free survival than those who had prophylactic central compartment neck dissection (P<0.001). The study revealed that age >45 years, body mass index ≥25, tumor size ≥1 cm, BRAF V600E mutation, and capsular invasion are the related risk factors for CLNM in patients with PTC. For patients with clinically nodal-negative (cN0) papillary thyroid microcarcinoma, accurately identifying the BRAF V600E mutation is essential for guiding the central lymph node dissection approach and subsequent treatments.

Risk factors associated with high-risk nodal disease in patients considered for active surveillance of papillary thyroid microcarcinoma without extrathyroidal extension.

Active surveillance (AS) has become an alternative treatment approach for papillary thyroid microcarcinoma (PTMC). The purpose of this study is to uncover the clinicopathological factors associated with high-risk nodal disease in order to select proper candidates for AS of PTMC. We retrospectively reviewed 5,329 patients with PTMC without extrathyroidal extension (ETE) who underwent thyroidectomy with central compartment neck dissection (CCND) between 2007 and 2021 at Seoul St. Mary's Hospital. Patients with more than five metastatic lymph nodes (MLNs) (higher-risk N1 disease) and/or lateral neck node metastases (N1b disease) were defined as having high-risk nodal disease. The clinicopathological factors associated with high-risk nodal disease were analyzed. A total of 415 (7.8%) patients had higher-risk N1 disease. These patients were younger on average, included a higher proportion of males, and had a larger tumor size and more frequent capsular invasion and multifocality compared with other patients. For the tumor size, a cutoff value of 0.65 cm was the best predictor of nodal risk groups. In a multivariate analysis, the independent risk factors associated with higher-risk N1 disease were younger age, male sex, tumor size >0.65 cm, and the presence of capsular invasion and/or multifocality. A total of 246 (4.6%) patients had N1b disease at initial diagnosis. In a multivariate analysis, the independent risk factors associated with N1b disease were younger age, male sex, tumor size >0.65 cm, and the presence of capsular invasion and/or multifocality. Young age, male sex, tumor size >0.65 cm, and presence of capsular invasion and/or multifocality can be considered risk factors for high-risk nodal disease in PTMC. Therefore, cautious observation is necessary for AS of patients with these characteristics.

An immediate postoperative response to therapy assessment can help avoid unnecessary RAI therapy.

BackgroundRadioiodine (RAI) therapy plays a vital role in the postoperative treatment of differentiated thyroid cancer (DTC) patients underwent total thyroidectomy (TT). However, even in the presence of capsular invasion and lymph node metastasis prognosis can be excellent and a postoperative RAI treatment might not be necessary for all patients. Therefore, this study explored the criteria for avoiding unnecessary RAI therapy in these patients.MethodWe applied response to therapy assessment immediately after surgery and prospectively recruited 179 excellent or indeterminate response DTC patients with capsular invasion and/or LNM who underwent TT without RAI therapy. During the follow-up, thyroglobulin (Tg), thyroglobulin antibody (TgAb) levels, and cervical ultrasonography were collected and analyzed. Disease-free survival (DFS) was calculated using the Kaplan-Meier method. In addition, response to therapy assessments was performed on patients during each follow-up.ResultsThe mean follow-up period was 29.85 ± 17.44 months, and the 3- and 5-year DFS for all the patients was 99.3% in each. At the last follow-up, 165 (92.2%) patients had excellent responses, while 12 (6.7%) had an indeterminate response, and one (0.6%) each had biochemical and incomplete responses. No significant difference was observed in response to therapy between the subgroups of LNM and tumor invasion (P>0.05). For patients with capsular invasion and a number of metastatic lymph nodes ≤5 and >5, the proportions of recorded excellent responses were 95.9%, 91.0%, and 85.7%, respectively. Better responses were observed in females (excellent response: 95.5%, P=0.023), patients with stimulated Tg (s-Tg) ≤1ng/ml (excellent response: 100%, P<0.001), s-Tg ≤ 2ng/ml (excellent response: 98.4%, P<0.001), and excellent response for the immediate postoperative assessment (excellent response: 98.5%, P=0.004).ConclusionsThe current study suggested that the response to therapy assessment immediately applied postoperatively could help avoid unnecessary RAI therapy among DTC patients with capsular invasion and/or LNM. Moreover, excellent response patients and patients with indeterminate response and s-Tg ≤ 2ng/ml could be managed without RAI therapy.

Spatially resolved immune microenvironmental profiling for follicular thyroid carcinoma with minimal capsular invasion

AbstractSpatial profiles of the tumor-immune microenvironment are associated with disease progression and clinicopathological factors in various cancers. Follicular thyroid carcinoma (FTC) is the second most common thyroid cancer, where the presence of capsular invasion or angioinvasion determines the pathological diagnosis; however, little is known about the immune microenvironment profiles associated with the acquisition of invasive potential of FTC. In this study, we focused on FTC with minimal capsular invasion, and the spatially resolved immune microenvironment of FTC was studied in the discovery (n = 13) and validation cohorts (n = 40). CD8+ T cells, helper T cells, regulatory T cells, B cells, natural killer cells, tumor-associated macrophages, CD66+ granulocytes, mature dendritic cells, and mast cells were quantitatively evaluated in single tissue sections, via a 12-marker multiplex immunohistochemistry and image cytometry. Cell densities and compositions of immune cells were spatially stratified by six tissue regions including tumor center, subcapsular region, capsular invasion, adjacent stroma of capsular invasion, peritumoral stroma, and adjacent normal. Lymphoid cell lineages in the tumor center and subcapsular regions were significantly lower than those in adjacent normal and peritumoral stroma, potentially related to the lymphoid lineage exclusion from the intratumoral regions of FTC. Interestingly, immune cell composition profiles in the capsular invasive front were distinct from those of intratumoral region. The ratios of T cells to CD66b+ granulocytes with capsular invasion were significantly higher than those without capsular invasion, suggesting the presence of a unique immune microenvironment at the invasive front between tumor foci and stroma. In addition, tumor cells at the capsular invasive front showed significantly higher expression of tumor programmed cell death ligand 1 (PD-L1) than those at the tumor center. This study revealed spatial immune profiles associated with capsular invasion of FTC, providing new insights into the mechanisms underlying its development and initial invasion.

Sarcopenia is Associated with Reduced Survival following Surgery for Adrenocortical Carcinoma

ABSTRACT Aim Adrenocortical cancer (ACC) is an aggressive malignancy and robust prognostic factors remain unclear. The presence of sarcopenia has been shown to negatively impact survival for other malignancies, but has not been extensively analyzed in ACC. Methods Patients who underwent resection of their ACC between 2010 and 2020 were identified; therapeutic, operative, and outcome data were analyzed. Sarcopenia was assessed by calculation of the skeletal muscle index (SMI) and was defined as an SMI <52.4cm2/m2 for males and <38.5cm2/m2 for females. Results Data on 35 patients (18 F: 17 M; median age 54 [range: 18–86]) who had primary surgical treatment were analyzed. Median tumor size was 10 cm [range:3–15]. In eleven patients (31%), the tumor was hormonally active (cortisol = 8;23%). Seventeen patients (49%) were classified as having sarcopenia on their pre-operative CT scan. The Intraclass Correlation Coefficient (ICC) for intra- and inter-observer variability showed very good agreement (0.99 and 0.98). There was no difference in incidence of sarcopenia stratifying for sex, BMI, or tumor-size, but incidence was higher with increasing age (p < .05). Overall median survival was 36 months, with 1- and 3-year survival rates of 77% and 52%. The presence of sarcopenia was strongly associated with a shorter overall survival (HR = 3.21; [95%CI: 1.06–9.69];p = .03) on unadjusted analyses. Moreover, age, higher T-stage, and presence of capsular invasion were also associated with poorer survival on univariable analyses. Conclusion The presence of sarcopenia in patients undergoing surgery for ACC could be a predictor of reduced overall survival, although replications of these analyses should be performed in similar, larger cohorts. Specifically, the influence of a patient’s hormonal status on the manifestation of sarcopenia should be further defined.

Detection and assessment of capsular invasion, vascular invasion and lymph node metastasis volume in thyroid carcinoma using microCT scanning of paraffin tissue blocks (3D whole block imaging): a proof of concept

In the modern era, detailed pathologic characteristics of a thyroid tumor are crucial to achieve accurate diagnosis and guide treatment. The presence of capsular invasion (CI) is diagnostic for carcinoma, whereas vascular invasion (VI) and nodal metastasis (NM) are included in risk stratification. However, the very definition of CI and VI is surrounded by controversies and an accurate assessment of NM is lacking. Whole Block Imaging (WBI) by microCT is a new imaging modality to create 3D reconstruction of whole tissue block with microscopic level resolution without the need for tissue sectioning. In this study, we aimed to define CI, VI, and NM volume using WBI by microCT. Twenty-eight paraffin blocks (PBs) from 26 thyroid tumors were scanned. Ten PBs contained CI, whereas 7 had VI. 3D microCT images were compared with whole slide images (WSI) of corresponding H&E slides. In 2 cases with VI and/or CI, WSI of serial H&E slides were obtained and underwent 3D-reconstruction to be compared with the WBI. Satellite tumor nodules beyond tumor capsule were shown to be CI by demonstrating the point of penetration using microCT and 3D reconstruction. Additional foci of CI were detected using microCT. VI was seen using microCT. Fibrin associated with tumor thrombus was not always present on serially sectioned H&E slides. WBI by microCT scanner was able to assess the volume of NM. In conclusion, WBI is able to detect CI, VI, and assess the volume of NM in thyroid carcinoma without tissue sectioning. It is the ultimate method for the complete sampling of the tumor capsule. It has the potential to increase the detection rate of CI, better define criteria for CI and VI, and provide an accurate assessment of the volume of nodal disease. This technology may impact the future practice of surgical pathology.

Massive Relief: Papillary Adenoma of the Lung in Asymptomatic Former Smoker Patient.

Benign epithelial tumors of the lung are uncommon and can represent a diagnostic challenge. Herein, we describe one such emblematic case. A 59-year-old former smoker male was admitted to the hospital complaining of cough for a long time. A radiological examination showed a centrally excavated mass strictly connected to the visceral pleura. The patient underwent tumorectomy. At gross examination, the tumor was composed of solid and cystic areas containing clear liquid. Histological examination highlighted a sub-pleural encapsulated tumor, with foci of capsular invasion, characterized by a single layer of columnar and cuboidal epithelial cells lining moderately cellular fibro-vascular cores. A wide spectrum of immunohistochemical markers was performed. The final diagnosis was suggestive of a peripheral pulmonary papillary tumor of undetermined malignant potential. At the last follow-up, six years after surgery, no recurrence or metastases were described. Reporting this case, we would like to point out the existence of these rare entities that should be taken into account in the diagnostic process, thus avoiding potential misdiagnosis. Moreover, the presence of capsular invasion should be better investigated in order to reconsider the exact terminology of the tumor and the classification of its malignant potential.

Evaluation of clinical risk factors for predicting insidious right central and posterior right recurrent laryngeal nerve lymph node metastasis in papillary thyroid microcarcinoma patients (cN0): experience of a single center.

Papillary thyroid microcarcinoma (PTMC), one specific subtype of papillary thyroid carcinoma (PTC) which measures less than 10 mm in maximum dimension, presents with a high risk of insidious lymph node metastasis escaping from preoperative examinations (cN0). Given the complications of lymph node dissection (LND) and metastasis risk, proper stratification of PTMC for performing prophylactic LND bears great importance. From June 2015 to December 2017, 338 PTMC patients undergoing thyroidectomy were included in the present study. Potential risk factors, including age, gender, maximal tumor size, etc. were collected and analyzed for association with thyroid lymph node metastasis. Among the 338 patients, 87 patients (25.7%) presented with right central lymph node metastasis (CLNM) and 28 patients (8.3%) had posterior right recurrent laryngeal nerve lymph node metastasis (PRRLN-LNM). The maximal tumor was prone to occur at the middle part of the lower pole (35.3%) in patients with right CLNM, while the proportion of tumors located in the middle part of the upper pole (17.2%) was highest in PRRLN-LNM patients. Ages younger than 45 years old, male gender, and a tumor size of more than 0.5 cm were correlated independently with right CLNM and PRRLN-LNM. Presence of capsular invasion also had a significant association with the occurrence of PRRLN-LNM. Ages younger than 45, male gender, and a maximal tumor size larger than 0.5 cm, in addition to capsular invasion, were independent risk factors for stratification of PTMC patients. PTMC patients with these clinical characteristics were suggested to receive prophylactic LND in their initial thyroid surgeries.

Significance of stromal-1 and stromal-2 signatures and biologic prognostic model in diffuse large B-cell lymphoma.

Objective: Diffuse Large B Cell Lymphoma (DLBCL) is a heterogeneous group of tumors with different biological and clinical characteristics that have diverse clinical outcomes and response to therapy. Stromal-1 signature of tumor microenvironment of DLBCL represents extracellular matrix deposition and histiocytic infiltrate, whereas stromal-2 represents angiogenesis that could affect tumor progression.Methods: The aim of the present study is to assess the significance of stromal-1 signature using SPARC-1 and stromal-2 signature using CD31 expression and then finally to construct biologic prognostic model (BPM) in 60 cases of DLBCL via immunohistochemistry.Results: Microvessel density (P<0.05) and SPARC percentage of expression (P<0.001) were higher in DLBCL, including germinal and nongerminal cases, compared with reactive follicular hyperplasia. High microvessel density was significantly associated with splenic involvement (P=0.008), high mitotic count (P=0.045), and presence of capsular invasion (P=0.035). Percentage of SPARC expression was significantly associated with splenic involvement (P=0.03). Constructing BPM showed that 42 cases (70%) were of low biologic score (0–1) and 18 cases (30%) were of high biologic score (2–3). Low BPM cases showed less probability for splenic involvement (P=0.04) and a higher rate of complete response to therapy compared with high score cases (P=0.08). Conclusions: The DLBCL microenvironment could modulate tumor progression behavior since angiogenesis and SPARC positive stromal cells promote dissemination by association with spleen involvement and capsular invasion. Biologic prognostic models, including modified BPM, which considered cell origin of DLBCL and stromal signature pathways, could determine DLBCL progression and response to therapy.

Pattern and Distribution of Lymph Node Metastases in Papillary Thyroid Cancer

Background: The indications and extent of lymph node dissection in the treatment of papillary thyroid carcinoma remains controversial, and benefit from therapy is debatable. This study was designed to identify the pattern and distribution of lymph node metastases and to establish an optimal strategy for neck dissection for those patients. Methods: A total of 44 patients diagnosed with papillary thyroid cancer were treated from 2006 to 2013. All patients underwent total thyroidectomy, central neck dissection, and ipsilateral selective neck dissection removing lymphatic structures in levels II through V. The frequency of cervical lymph node metastases in each level, and the presence of capsular invasion were analysed. In addition, we investigated postoperative complications after total thyroidectomy and central lymph node dissection. Results: Lymph node metastases were found in 18 patients (40.9%); all of them had ipsilateral level VI nodal involvement. 7 patients had level V involvement, 2 patients had level II affection, 3 patients had level III & IV affection and 2 patients had contralateral level VI lymph node affection. We also found extracapsular invasion in 6 (13.6%) patients and grade I, II, III in 2, 40, 2 patients respectively. The frequency of temporary hypocalcaemia, permanent hypocalcaemia and temporary vocal cord paralysis were 6.8%, 2.3% and 4.5%, respectively. Conclusion: We recommend total thyroidectomy and central compartment lymph node dissection. If ipsilateral central lymph nodes are positive for metastases in frozen section, we proceed to ipsilateral selective neck dissection removing lymphatic structures in levels II through V even in the absence of clinically evident lymph node metastasis irrespective of tumor size. The technique had a low rate of complications; namely laryngeal nerve injury and hypoparathyroidism.

BRAF mutation in papillary thyroid microcarcinoma – additional marker of risk stratification

Background Papillary thyroid microcarcinoma (PTMC) is heterogeneous group of tumor less than 1 cm in the diameter. The volume of surgical treatment stay unstable because unclear biological potential of PTMC. Aim The aim of our study was to assess the utility of BRAF gene mutation as preoperative additional marker of risk stratification. Materials and methods We include 44 patient who were operated in general surgery department Pavlov State Medical University from 2001 to 2013. In all 44 cases BRAF gene mutation was detected and compared with clinic-morphological features (multifocality, invasive growth, lymph node metastasis, recurrence) retrospectively Results In our study the frequency of BRAF gene mutation was 68.2%. On multivariate regression analysis the presence of bilateral tumoural foci, lymph node metastasis and the presence of capsular invasion were significantly related to BRAF positive gene status. Conclusions Thus, appropriate volume for the BRAF positive PTMC is thyroidectomy with central compartment lymph node dissection.

Evaluation of MMP2 and Caspase-3 expression in 107 cases of papillary thyroid carcinoma and its association with prognostic factors

Papillary thyroid carcinoma (PTC), including its variants and widely varying behavior, constitutes about 80% of all thyroid malignancies. Increased knowledge regarding molecular alterations has led to attempts to identify diagnostic or prognostic factors for a reliable preoperative approach to the classification of patients according to risk of recurrence. In this study, 107 cases of PTC with known histological properties, including vascular or capsular invasion, were assessed for expression of MMP2 and Caspase-3 using immunohistochemistry. Considering 10% as a cutoff to discriminate cases with invasive behavior from the non-invasive group, there was no relationship between expression of MMP2 or Caspase-3 in tumor cells and the presence of capsular invasion (p=0.45 and 0.64, respectively), as well as for the expression of Caspase-3 and vascular invasion (p=0.43). In case of MMP2, a borderline correlation was found between the positive reaction of tumor cells with the presence of vascular invasion (p=0.05). So the evaluation of MMP2 in thyroid PTC appears to be of some benefit to the prediction of tumor behavior while Caspase-3 as a marker of prediction seems to be of no use.

IGFBP-3 nuclear localization predicts human prostate cancer recurrence.

Insulin-like growth factor binding protein-3 (IGFBP-3) is a pro-apoptotic, anti-metastasic, and anti-angiogenic protein. Low serum IGFBP-3 has been associated with risk of more aggressive prostate cancer (PCa). We investigated the impact of nuclear and cytoplasmic IGFBP-3 protein expression levels in PCa by examining their in situ expression across a wide spectrum of primary tumors by immunohistochemical analysis of tissue microarrays. Immunohistochemistry was performed on PCa microarrays constructed from 226 hormone naïve patients who underwent radical prostatectomy. Both cytoplasmic and nuclear IGFBP-3 expressions were scored in a semi-quantitative fashion using an integrated measure of intensity and positivity. The distribution of IGFBP-3 protein expression was examined across the spectrum of epithelial tissues, and its association with standard clinicopathological covariates and tumor recurrence was examined. There was a broad range of IGFBP-3 staining across all histologies examined. Tumor had higher IGFBP-3 cytoplasmic and nuclear staining than benign histologies. For IGFBP-3 nuclear staining, PCa was significantly different than benign prostatic hyperplasia, normal prostate, and prostate intraepithelial neoplasia. As both a continuous and dichotomized variable, higher nuclear IGFBP-3 expression had statistically significant associations with PCa recurrence. The cytoplasmic staining had no significance in any patient subgroup. In patients with low-grade cancer, IGFBP-3 nuclear positivity was a better predictor of recurrence than baseline PSA, tumor margin status, TNM tumor stage, or presence of capsular invasion. High nuclear IGFBP-3 is amongst the strongest predictors of cancer recurrence in patients with low-grade prostate cancers and may therefore play an important role in risk stratification.

Rate of renal cell carcinoma subtypes in different races.

We sought to identify racial differences among histological subtypes of renal cell carcinoma (RCC) between black and non-black patients in an equal-access health care system. We established a multi-institutional, prospective database of patients undergoing partial or radical nephrectomy between January 1, 2000 and Sept 31, 2009. For the purposes of this study, data captured included age at diagnosis, race, tumor size, presence of lymphovascular invasion, presence of capsular invasion, margin status, and tumor histology. 204 kidney tumors were identified (Table-1). Of these, 117 (57.4%) were in black patients and 87 (42.6%) were in non-black patients. Age at surgery ranged from 37 to 87 with a median of 62. Tumor size ranged from 1.0 to 22.0 cm with a median of 5.0 cm. Overall, tumors were composed of clear cell RCC in 97 cases (47.5%), papillary RCC in 65 cases (31.9%), chromophobe RCC in 13 cases (6.4%), collecting duct/medullary RCC in 2 cases (1.0%), RCC with multiple histological subtypes in 8 cases (3.9%), malignant tumors of other origin in 6 cases (2.9%), and benign histology in 13 cases (6.4%). Among black patients, papillary RCC was seen in 56 cases (47.9%), compared to 9 cases (10.3%) among non-black patients (p < 0.001) (Table-2). Clear cell RCC was present in 38 (32.5%) of black patients and in 59 (67.8%) of non-blacks (p < 0.001). In our study, papillary RCC had a much higher occurrence among black patients compared to non-black patients. This is the first study to document such a great racial disparity among RCC subtypes.

Treatment and prognostic factors of papillary thyroid microcarcinoma

To discuss the prognostic factors and outcomes of treatment in patients diagnosed with papillary thyroid microcarcinoma. Retrospective observational case review. Department of Otorhinolaryngology of the tertiary referral teaching hospital of Parma. Ninety-seven patients diagnosed with PTMC and surgically treated between January 1998 and December 2007. Clinical and histopathological characteristics of the study group were identified and statistically analysed. No cancer-related deaths were registered. Incidence of recurrent disease was 9% after a 43 month mean follow-up (range 12-120). Univariate analysis detected that metastases in neck lymph nodes at diagnosis (p = 0.025), a tumour >5 mm in size (p = 0.011), the presence of bilateral tumoural foci (p = 0.007), the presence of capsular invasion (p = 0.001), and the presence of vascular invasion (p = 0.004) were related to recurrent disease. On multivariate analysis, the presence of bilateral tumoural foci (p = 0.030), and the presence of capsular invasion (p = 0.005) were significantly related to tumour recurrence. The prognosis for patients with papillary thyroid microcarcinoma in this series was excellent, with a 100% survival rate and minimal surgical-related morbidity. Nevertheless, approximately 10% of patients developed recurrent disease; aggressive treatment may be justified depending on the presence or absence of prognostic risk factors.

Factors Affecting Adrenal Gland Involvement in Patients Who Underwent Radical Nephrectomy for Renal Cell Carcinoma

Aim: We investigated pathological characteristics of adrenal involvement in patients who underwent radical nephrectomy (RN) for renal cell carcinoma (RCC). Materials and Methods: 49 patients (34 male, 15 female) who underwent RN and simultaneous ipsilateral adrenalectomy due to RCC were included. Patient and tumor characteristics, histopathologic features, disease stage, and radiologic computerized tomography (CT) features were studied in order to see if any of them are associated with pathological evidence of adrenal involvement. Results: Presence of adrenal irregularity (P = 0.002), venous thrombosis (P = 0.010), tumor necrosis (P = 0.031), and lymph node (LN) involvement (P = 0.013) on CT, increased Fuhrman grade (P = 0.037), and presence of capsular invasion (P = 0.027) and perirenal fatty tissue invasion by RCC (P = 0.011) were found to be significantly associated with ipsilateral adrenal involvement. There was no statistically significant association with location of the tumor in the upper pole of the kidney (P = 0.077), increased tumor size (P = 0.098), pathologic stage (P = 0.085), presence of vascular invasion (P = 0.067), and metastasis despite higher incidence of them in the group with adrenal involvement. Conclusions: Risk factors for ipsilateral adrenal involvement by RCC appear to be the presence of adrenal gland irregularity, venous thrombosis and necrosis on CT, increased Fuhrman grade, presence of capsular and peripheral fatty tissue invasion, LN involvement, and metastasis. Therefore, we recommend ipsilateral adrenalectomy particularly in this patient group.

Evaluation of malignancy of hepatocellular carcinoma using the ultrasonic B-mode method: clinical significance of extracapsular invasion of hepatocellular carcinoma using ultrasonography.

To determine the influence of capsule formation or presence of capsular invasion on the prognosis of hepatocellular carcinoma (HCC) patients. The patient group consisted of 70 patients with 74 HCC lesions who had been examined by US and undergone surgical tumor resection at our institution. For these patients, we conducted the following comparative studies: (a) comparison between halo findings on US and microscopic capsular results; (b) comparison between halo findings on US and tumor diameter, tumor histological differentiation, and serum value of each tumor marker; and (c) comparison between halo findings on US and tumor recurrence. (a) The corresponding value between sonographic halo and histological capsule was 90.1%, and that between presence of extracapsular invasion on US and that seen by histology was 88.0%. (b) There was no relation between US images and histological differentiation of tumors. (c) Presence of extracapsular invasion on US was a predisposing factor for the development of tumor recurrence. (1) Globally speaking, sonographic halo corresponded to the histological tumor capsule. (2) In patients with extracapsular invasion, tumor recurrence after treatment increased. Thus, a better understanding of sonographic halo findings helps determine diagnostic and therapeutic strategies in HCC patients.

Seminal vesicle involvement after radical prostatectomy: predicting risk factors for progression

Objectives To evaluate and study the factors for progression after radical prostatectomy with seminal vesicle invasion in a cohort of European and American patients. Methods The data of 137 patients with isolated seminal vesicle invasion who underwent radical retropubic prostatectomy between 1988 and 2001 were analyzed. The Gleason score of the specimen, presence of capsular invasion, and surgical margin status were noted. Follow-up data were obtained through routine serum prostate-specific antigen (PSA) assays and digital rectal examinations. A defining criterion for progression was a postoperative serum PSA level greater than 0.2 ng/mL or any postoperative radiotherapy or hormonal treatment. Kaplan-Meier analysis was used to determine the actuarial biochemical recurrence-free likelihood, and the log-rank test was used to compare these results. Differences were considered statistically significant when the P value was less than 0.05. Results After a mean follow-up of 4.9 years (range 0.9 to 13.4), 70 patients (51.9%) had progression. The biochemical 5-year progression-free survival rate was 33.8%. In univariate and multivariate analyses, only preoperative PSA level ( P = 0.001) and Gleason score of the specimen ( P = 0.01) were independent predictors of progression. Neither capsular invasion nor positive surgical margins predicted progression. When an analysis was performed according to the major Gleason grade of the radical prostatectomy specimen, Gleason grade 5 was associated with a worse prognosis compared with Gleason grade 3 and 4 ( P = 0.01). The mean time to progression was 20.5, 17.1, and 10.1 months for Gleason grade 3, 4, and 5, respectively. Conclusions Seminal vesicle invasion after radical prostatectomy has historically been associated with a poor prognosis. However, in the present study, seminal vesicle invasion was associated with a 34% rate of freedom from progression at 5 years after surgery alone. Preoperative PSA and Gleason score of the radical prostatectomy specimen were independent factors for progression in the present study, which described the largest patient group to date. The Gleason grade of the radical prostatectomy specimen distinguished among different times to progression.

Expression, regulation, and function of αV integrins in hepatocellular carcinoma: An in vivo and in vitro study

The expression of αV integrins by neoplastic cells contributes to the promotion of local invasion and metastasis. The most characteristic extracellular ligands of αV integrins are vitronectin and fibronectin. Hepatocytes are the main source of vitronectin, and the capacity to synthesize and secrete vitronectin is usually retained in hepatocellular carcinoma. The aim of this study was to explore the expression, regulation, and functional role of αV integrins in hepatocellular carcinoma. We first analyzed the expression of αV integrins and their ligands fibronectin and vitronectin in 80 cases of hepatocellular carcinoma. αV integrin chain was detected in 44 cases and vitronectin in 50. Twenty-four of the 44 αV-positive tumors contained large amounts of vitronectin. These cases presented more frequently with adverse histoprognostic factors, including infiltrative growth pattern (62.5%), lack of capsule (71%), presence of capsular invasion (57%), and satellite nodules (50%). We then used HepG2 and Hep3B cell lines as in vitro models to study αV integrin regulation and function. HepG2 and Hep3B cells expressed αV integrin chain and used αVβ1 and αVβ5 for adhesion and migration on vitronectin. Tumor necrosis factor (TNF) α and transforming growth factor (TGF) β significantly increased the expression levels of αV integrins and stimulated the adhesion and migration of both HepG2 and Hep3B cell lines on vitronectin. The effects of growth factors on cell adhesion and migration were reproduced by incubation with conditioned medium from rat liver myofibroblasts. In conclusion, our results support the existence of an αV integrin/vitronectin connection in hepatocellular carcinoma and suggest that this connection may be an adverse prognostic factor. (H EPATOLOGY 2002;36:418-426.)

Overexpression of p53 protein and MDM2 in papillary carcinomas of the thyroid: Correlations with clinicopathologic features.

Expression of p53 protein and MDM2 was evaluated in paraffin-embedded tissue from 78 patients with papillary carcinomas of the thyroid (PCT), in order to elucidate the relationship between them and their correlations with some clinicopathologic features implicated in tumor progression. These proteins were expressed in nuclei of tumor cells, but not in non-tumor cells. Staining was defined as positive when 10% or more of tumor cells expressed these proteins. The number of cases positive for p53 protein was 21/78 (27%), and that positive for MDM2 was 26/78 (33%). Co-overexpression of p53 protein and MDM2 was observed in 12/78 cases (15%). A significant positive relationship was found between them (P < 0.01); p53-positive cases tended to be also positive for MDM2 and vice versa. Statistical analysis revealed that overexpression of p53 protein significantly correlated with large tumor size (P = 0.0271) and the presence of capsular invasion (P = 0.04). There were significant positive correlations between tumor size and intrathyroidal invasion and between tumor size and capsular invasion in PCT, suggesting that p53 protein overexpression is associated only with tumor progression (tumor size). However, we could not find any significant correlations between MDM2 expression and clinicopathologic features. Our findings suggest that overexpression of p53 protein and MDM2 in papillary carcinoma of the thyroid is associated with the progression of the tumors, and that p53 may be a marker of the progression of PCT.