Preoperative prediction of gastrointestinal stromal tumors with high Ki-67 proliferation index based on CT features.

BACKGROUND: To determine whether preoperative computed tomography (CT) features can be used for the prediction of gastrointestinal stromal tumors (GISTs) with a high Ki-67 proliferation index (Ki-67 PI). METHODS: A total of 198 patients with surgically and pathologically proven GISTs were retrospectively included. All GISTs were divided into a low Ki-67 PI group (<10%) and a high Ki-67 PI group (≥10%). All imaging features were blindly interpreted by two radiologists. Receiver operating characteristic (ROC) curve analyses were conducted to evaluate the predictive performance of the imaging features. RESULTS: Imaging features were found to be significantly different between the low and the high Ki-67 PI groups (P<0.05). Wall thickness of necrosis showed the highest predictive ability, with an area under the curve (AUC) of 0.838 [95% confidence interval (CI): 0.627-0.957], followed by necrosis, necrosis degree, hyperenhancement of the overlying mucosa (HYOM), and long diameter (LD) (AUC >0.7, P<0.05). HYOM was the strongest predictive feature for the high Ki-67 PI GISTs group, with an odds ratio (OR) value of 30.037 (95% CI: 5.707-158.106). CONCLUSIONS: Imaging features, including the presence of necrosis, high necrosis degree, thick wall of necrosis, and HYOM were significant predictive indicators for the high Ki-67 PI GISTs group.

Prognoses in patients with primary gastrointestinal neuroendocrine neoplasms based on the proposed new classification scheme.

AIM: The aim of this study is to investigate the clinicopathological characteristics, as well as explore the prognostic accuracy of the proposed new classification in gastrointestinal NENs (GI-NENs) patients. METHODS: Patients diagnosed with GI-NENs were retrospectively indentified from existing databases of the pathological institute at our institution from January 2009 to November 2015. RESULTS: We identified 414 patients with GI-NENs, 250 cases were diagnosed as neuroendocrine tumor G1 (NET G1), 25 as neuroendocrine tumor G2 (NET G2), 53 as neuroendocrine tumor G3 (NET G3), 55 as neuroendocrine carcinoma G3 (NEC G3), and 31 as mixed adenoneuroendocrine carcinoma (MANEC); the overall survival (OS) rate at three years were 94.9%, 91.7%, 74.3%, 62.7% and 38.1%, respectively. The difference in progression-free survival (PFS) duration among the patients with NET G1, NET G2, NET G3, NEC G3, and MANEC was statistically significant (P < 0.001). However, the PFS of NEC G3 and MANEC was low and similar (P = 0.090). In multivariate analysis of patients with GI-NENs, surgical margin, comorbidity, proposed new classification and tumor location were useful predictors of OS (P < 0.05). CONCLUSION: Our findings suggest that the proposed new classification can accurately reflect the clinical outcome, together with surgical margin, comorbidity, and tumor location may be meaningful prognostic factors for the OS of GI-NENs.

Bone metastasis from lung cancer identified by genetic profiling.

Cancer metastasis remains responsible for the vast majority of cases of cancer-related morbidity and mortality. Metastasis, by its definition, is the spread of cancer from the primary site to the distant tissues. Advancing the scientific and clinical understanding of cancer metastasis is a high priority. The prerequisite requirement for pathological consistency may be compromised during metastasis. The present study reports the case of a cancer patient with different pathological types. The patient presented with pain in the neck and right hip, as well as weight loss. He underwent whole-body positron emission tomography-computed tomography, which identified a mass in the lung and abnormal metabolism of the bone. Biopsies of the ilium and lung were performed and he was shown to have lung adenocarcinoma and bone squamous carcinoma. The morphology and immunohistochemical patterns were completely different, while each lesion harbored an identical genetic profile. The bone lesion was identified to be a metastasis from the lung cancer. The patient was prescribed an epithelial growth factor receptor inhibitor, which resulted in a partial response in the lung mass and alleviation of the patient's bone pain. Through this case study, we advocate the importance of using genetic testing in addition to pathological assessment.

Negative pathology of ureteral carcinoma significantly delaying the diagnosis of the primary tumor of osteoblastic metastases: A case report and review of the literature.

Ureteral urothelial carcinoma (UC) is a rare malignant tumor. The most common clinical manifestations of ureteral UC are hematuria, increased urinary frequency, dysuria and pain. The diagnosis of ureteral UC is made via radiography, endoscopy and pathology. Although osteoblastic destruction is usually observed in metastasis of prostate cancer, UC can also be a reason for osteoblastic metastasis. The present study reports the case of a 66-year-old man presenting with osteoblastic metastases, in which the primary tumor was finally diagnosed as a ureteral UC. However, the lack of pathological evidence significantly delayed the diagnosis of the primary tumor (>6 months), even though the results of radiographic examination, and the type and mode of bone metastases significantly suggested a ureteral UC. The case reveals that a suitable screening test should be recommended for patients at high risk due to the possibility of a negative pathology result for ureteral UC. Additionally, a more efficient diagnostic method is required. Moreover, the possibility of new diagnostic criterion that do not rely on the pathology of primary foci in ureteral UC should be considered in future.

[Characteristics of Clinicopathology and Genotype in 179 Cases with Gastrointestinal Stromal Tumor].

OBJECTIVE: To analyze the characteristics of the clinicopathology and genotypes in patients with gastrointestinal stromal tumor (GIST). METHODS: The clinicopathological and genotypic data of 179 patients with GIST, who underwent treatment and genetic testing in the Hostital of West China from September 2009 to February 2009 were collected retrospectively. RESULTS: The tumor sites of the cases were located in stomach (88 cases, 49.2%), small intestine (70 cases, 39.1%), colorectum (7 cases, 3.9%) and the other sites (14 cases, 7.8%) respectively. 94.4%, 74.9% and 93.3% of GIST patients were positive for CD117, CD34 and DOG-1 immunophenotypes respectively. C-kit and PDGFRα mutations were found in 151 cases (84.4%) and 8 cases (4.5%) except for the wild types of the rest 20 cases (11.2%). Among all the c-kit mutation, 92.2% mutation types in exon 11 were deletion mutation, point mutation and hybrid mutations, and in exon 9 the mutation types were just involving A502_Y503dup (n = 6) and Y403_F504ins (n = 14), while the mutation type were K642Q in exon 13 (n = 1) and N822K in 17 (n = 2). There were 6 patients with the mutation types of PDGFRα in exon 18, and 3 of them were type of D842V. In the GIST genotyping, DOG-1 positive rate in PDGFRα mutation patients were significantly lower than that in c-kit mutation and wild type patients (P = 0.007). In the various type of c-kit mutations, the positive rate of CD34 in point mutation patients were significantly lower than that in other mutation types (P < 0.001). The rate of high-risk patients in point mutation and insertion mutation patients were lower than that in deletion mutation and deletion + insertion mutation patients (P = 0.006). CONCLUSION: The most common localizaions of GISTs are the stomach and small intestine. The most frequent mutation type of GIST is c-kit exon 11. The individualized treatment is required for GIST patients because its high mutation rate and types.

NLRC5 expression in tumors and its role as a negative prognostic indicator in stage III non-small-cell lung cancer patients.

Major histocompatibility complex (MHC) class I molecules have a crucial role in tumor immune evasion; however, the association of MHC class I molecules with outcomes in cancer patients remains controversial. Nucleotide-binding oligomerization-like receptor family caspase recruitment domain-containing 5 (NLRC5) has been reported to be a MHC class I transactivator. However, the expression and function of NLRC5 in cancer remains to be elucidated. The present study aimed to retrospectively examine NLRC5 expression in human tumor tissues and its association with clinical outcomes of non-small-cell lung cancer (NSCLC) stage III patients. The expression of MHC class I and NLRC5 in NSCLC were detected using immunohistochemistry (IHC). The association between their expression levels was assessed using the Pearson's χ2 test and their association with survival was assessed using Kaplan-Meier analysis and the log-rank test. In addition, the expression of NLRC5 and MHC class I were examined in 323 cases of seven other types of tumors and their correlations were studied. The results revealed that the expression of NLRC5 was correlated with that of MHC class I in NSCLC patients (P=0.008). MHC class I-positive and nuclear NLRC5-positive NSCLC patients were found to have shorter overall survival (OS) rates (log-rank, P=0.032 and P=0.039, respectively). In addition, in the seven different tumor types, there was a significant correlation between MHC class I and NLRC5 nuclear expression (P<0.001) as well as MHC class I and NLRC5 cytoplasmic expression (P=0.003). In conclusion, NLRC5 was demonstrated to be widely expressed in eight tumor tissues and its expression was correlated with that of MHC class I. Of note, nuclear NLRC5-negative and MHC class I-negative stage III NSCLC patients had improved OS rates compared to those with positive expression. Therefore, NLRC5 and MHC class I may be negative prognostic indicators in NSCLC stage III patients.

Clinical characteristics of the mixed form of neuroendocrine tumor in the lung: A retrospective study in 2501 lung cancer cases.

BACKGROUND: A neuroendocrine tumor (NET) is a special kind of epithelial tumor with predominant neuroendocrine differentiation, which arises throughout the body, including the lung. A subpopulation of lung cancer patients suffer from the mixed (combined) form of NET with components of non-neuroendocrine carcinoma. However, the clinical characteristics of the mixed form of NET are not well established. METHODS: We analyzed 2501 consecutive cases of primary lung cancer from 2009 to 2011. The diagnosis, histology, therapy, and outcome were collected. RESULTS: A total of 22 patients were enrolled. The occurrence rate of lung cancer was 0.9%. Neither gender (1.2% and 0.3% for male and female, respectively, P = 0.35) nor age (0.6% and 1.3% for patients aged ≤60 and >60, respectively, P = 0.13) was associated with the onset of this disease; however it has become more frequent in recent years (0.6% and 1.6% at the time ≤ and >2010 respectively, P = 0.03). This cohort of 22 patients had a median survival of 60.0 months (95% confidence interval: 14.3-105.6 months). Patients with metastatic disease (60 months and not reached [NR], P = 0.18) or a small-cell lung cancer component tended to have a shorter survival (35 months and NR, P = 0.16). Patients who underwent surgery had a significantly longer survival period (NR and 17.0 months, P = 0.001). CONCLUSIONS: A mixed form of NET in the lung is a rare disease. While stage and histology might influence prognosis, surgery is the critical factor for long-term survival.

[Prognosis of patients with adrenocortical carcinoma].

OBJECTIVE: To investigate the prognosis and influencing factors of patients with adrenocortical carcinoma. METHODS: Thirty-five patients (20 males and 15 females) with biopsy-diagnosed adrenocortical carcinoma were followed retrospectively. Cox proportional hazards regression analysis was performed to identify factors that influenced the prognosis of the patients. RESULTS: Three patients were classified as stage I, 15 as stage II, 12 as stage III, and 5 as stage IV. Fourteen patients were still alive and 21 died at the end of the follow-up. The patients had a median survival time of 33 months, with a survival rate of 77.1%, 62.5%, and 38.3% for the first year, second year, and fifth year respectively. The univariate analysis found no significant differences in survival rates with gender, tumor location (left or right adrenal), diameter (> or = 10 cm or <10 cm) of tumor, functionality of tumor, smoking, hypertension and hypokalemia (P > 0.05). The multivariate analysis revealed that being male, younger than 50 years, non-smoking and early-stage of tumor were significant protective factors for the survival of patients with adrenocarcinoma. Patients at stage III and stage II had 52 and 3 times higher mortality than those at stage I, respectively. CONCLUSION: Clinical stage and age are the main factors that influence the survival of patients with adrenocortical carcinoma. Patients younger than 50 years and those with an earlier stage of tumor would have a better prognosis.

Features of time-intensity curve parameters of colorectal adenocarcinomas evaluated by double-contrast enhanced ultrasonography: initial observation.

PURPOSE: This study is to investigate the value of double contrast-enhanced ultrasonography (DCEU) in assessing microcirculation of colorectal adenocarcinomas and to describe the perfusion features of the tumours. MATERIAL AND METHODS: DCEUS was performed in 42 patients with adenocarcinoma. The time-intensity curve parameters (arrival time (AT), time-to-peak (TTP), peak intensity (PI) and area under the curve (AUC)) within the tumours were extracted. The parameters were compared among the tumours with different CEUS features and stages. RESULTS: The mean values of AT, TTP, PI and AUC of the colorectal adenocarcinomas were 13.68±13.36s, 32.61±19.56s, 19.82±16.54dB and 271.10±159.19dBs, respectively. In the adenocarcinomas with necrosis, the mean values of AUC was significantly lower than that of the adenocarcinomas without (231.10±219.27dBs, 278.10±123.20dBs, p=0.004). In the adenocarcinomas with necrosis, the AUC and PI of the non-necrotic part were significantly higher than that of the necrotic part (p=0.007, 0.0025, respectively). AUC increased progressively in the subgroups of T2, T3 and T4 and the difference of AUC between T2 and T4 subgroup was significant (p=0.008). CONCLUSIONS: Double contrast-enhanced ultrasonography is a valuable technique for quantifying tumour vascularity of colorectal adenocarcinomas. AUC was significantly different in the subgroups of different T stage. AUC and PI could reflect the different perfusion status of tumours with or without necrosis.

Gastric adenocarcinoma: can perfusion CT help to noninvasively evaluate tumor angiogenesis?

BACKGROUND: Perfusion CT is an attractive technique to assess tumor vascularity, and no studies have addressed the relationship between CT perfusion imaging and gastric tumor angiogenesis with volume-based technique. This study aims to assess the correlation between perfusion CT parameters using a volume-based technique and immunohistochemical markers of angiogenesis in gastric adenocarcinoma. METHODS: 37 patients with gastric adenocarcinoma who completed whole tumor CT perfusion examination with volume-based technique were studied. Post surgical specimens were stained using a polyclonal antibody to VEGF and CD34. Perfusion measurements were correlated with microvessel density (MVD) and VEGF by using Pearson or Spearman rank correlation analysis, in which a P value < 0.05 was considered statistically significant. RESULTS: The mean MVD of all 37 tumors was 108.9 ± 38.2 vessels/0.723 mm². 70.3% (26 of 37) of tumors expressed VEGF positively. MVD of gastric adenocarcinoma was significantly correlated with blood volume (the Pearson correlation coefficient being 0.420, P = 0.001). No correlations were found between VEGF expression and perfusion CT parameters. There were no significant differences in the parameters between the high and low MVD groups, and between the positive and negative VEGF groups. CONCLUSIONS: Blood volume was significantly correlated with MVD. It could reflect the angiogenesis in gastric adenocarcinoma.

Whole tumour quantitative measurement of first-pass perfusion of oesophageal squamous cell carcinoma using 64-row multidetector computed tomography: correlation with microvessel density.

PURPOSE: To assess correlations between whole tumour first-pass perfusion parameters obtained with 64-row multidetector computed tomography (MDCT), and microvessel density (MVD) in oesophageal squamous cell carcinoma. MATERIALS AND METHODS: Thirty-one consecutive patients with surgically confirmed oesophageal squamous cell carcinomas were enrolled into our study. All the patients underwent whole tumour first-pass perfusion scan with 64-row MDCT. Perfusion parameters, including perfusion (PF), peak enhanced density (PED), blood volume (BV), and time to peak (TTP) were measured using Philips perfusion software. Postoperative tumour specimens were assessed for MVD. Pearson correlation coefficient tests were performed to determine correlations between each perfusion parameter and MVD. RESULTS: Mean values for PF, PED, BV and TTP of the whole tumour were 28.85 ± 20.29 ml/min/ml, 23.16 ± 8.09 HU, 12.13 ± 5.21 ml/100g, and 35.05 ± 13.85 s, respectively. Mean MVD in whole tumour at magnification (×200) was 15.75 ± 4.34 microvessel/tumour sample (vessels/0.723 mm(2)). PED and BV were correlated with MVD (r=0.651 and r=0.977, respectively, all p<0.05). However, PF and TTP were not correlated with MVD (r=0.070 and r=0.100, respectively, all p>0.05). CONCLUSION: The BV value of first-pass perfusion CT could reflect MVD in oesophageal squamous cell carcinoma, and can be an indicator for evaluating the tumour angiogenesis.

Reproducibility of the Nottingham modification of the Scarff-Bloom-Richardson histological grading system and the complementary value of Ki-67 to this system.

BACKGROUND: The reproducibility of the Nottingham modification of the Scarff-Bloom-Richardson (NSBR) histological grading system for invasive breast cancer (IBC) adopted by the World Health Organization (WHO) has previously not been studied in Chinese hospitals. The proliferation marker, Ki-67, has been widely applied in detecting IBC. The objective of this study was to assess the reproducibility of the NSBR system among Chinese pathologists and the complementary value that Ki-67 brings to this system. METHODS: Four general pathologists graded 100 IBC cases independently, which had previously been graded by specialists in breast pathology. The interobserver reproducibility among four general pathologists and pairwise reproducibility between each of them and the specialists were assessed. The Ki-67 labeling index (Ki-67LI) was determined by immunohistochemistry, and its correlations with histological grade and survival were determined. RESULTS: With respect to interobserver reproducibility, NSBR grading was fairly reproducible (kappa = 0.34); as for the components of NSBR grading, agreement was best for tubule formation (kappa = 0.46), intermediate for nuclear pleomorphism (kappa = 0.42), and poorest for mitotic count (kappa = 0.28). In terms of pairwise reproducibility, agreement was fair to substantial with NSBR grading (kappa = 0.30 - 0.69) and nuclear pleomorphism (kappa = 0.28 - 0.69), moderate to substantial for tubule formation (kappa = 0.51 - 0.78), and slight to substantial for mitotic count (kappa = 0.19 - 0.71). There were characteristic Ki-67LI ranges for grades 1, 2 and 3 tumors. Univariate analysis showed that Ki-67 was able to divide grade 2 patients into two different prognostic subgroups. Multivariate analysis of grade 2 patients with negative lymph node demonstrated that Ki-67 was an independent prognosticator for overall survival. CONCLUSIONS: The reproducibility of grading by general pathologists could be enhanced. Specialization in breast pathology is essential for accurate grading and treatment for IBC. Ki-67, with proven prognostic significance, adds complementary value to the NSBR system.

Infantile hepatic hemangioendothelioma: a clinicopathologic study in a Chinese population.

AIM: To investigate whether the clinicopathologic features of infantile hemangioendothelioma (IHE) of the liver in a Chinese population are similar to the features observed in other races. METHODS: The clinical data, radiological findings, histopathological changes and outcome of 12 cases of IHE diagnosed by the Department of Pathology, West China Hospital over the last 10 years were analyzed retrospectively. Immunohistochemical studies were carried out using antibodies against CD31, CD34, Factor VIII, cytokeratin 8 and cytokeratin 18. RESULTS: The 12 patients were aged from fetal to 5 years (three males and nine females). The tumor was presented with different clinical manifestations, mainly as an asymptomatic, palpable, upper abdominal mass, except for the two fetuses who were detected antenatally by ultrasound. In one patient, this presentation was accompanied by an initial severe pneumothorax. No symptoms of congestive heart failure were present and neither congenital abnormalities nor vascular tumors in the skin or other organs were found. Laboratory abnormalities included leukocytosis (40%), anemia (60%), thrombocytosis (60%), hyperbilirubinemia (16.7%), abnormal liver function (50%) and increased α-fetoprotein (80%). Based on radiological findings and gross specimens, the tumor presented as a solitary lesion or a multifocal space-occupying lesion. The tumor size ranged from 5.0 cm × 3.5 cm × 2.0 cm to 13.8 cm × 9.0 cm × 7.7 cm, and the 0.2-1.1 cm nodules were diffusely distributed within the multifocal tumor. Seven cases were surgically resected, three cases underwent biopsy and the two fetuses were aborted. Histologically, nine cases were classified as type I and three as type II, presenting aggressive morphologic features, immature vessels, active mitosis and necrosis. An inflammatory component, predominantly eosinophilic granulocytes, sometimes obscured the nature of the tumor. Ten patients are alive after a follow-up of 1-9 years. Based on immunohistochemistry, the endothelial cells in all cases were positive for CD31, CD34 and polyclonal factor VIII antigen, whereas the scattered hyperplasia bile ducts were positive for cytokeratin 8 and cytokeratin 18. CONCLUSION: The clinical manifestations of IHE are non-specific. There is no significant correlation between histological type and prognosis. The clinicopathologic features of IHE in Chinese patients may provide a clue to further evidence-based studies.

[Expression of beta-catenin and estrogen receptor in desmoid-type fibromatosis].

OBJECTIVE: To detect the expression of beta-catenin and Estrogen Receptor in desmoid-type fibromatosis. METHODS: Nuclear beta-catenin expression was detected by immunohistochemistry in 77 lesions with desmoid-type fibromatosis and 171 other spindle cell lesions, including superficial fibromatosis (n = 18), nodular fasciitis (n = 36), keloid (n = 16), scar (n = 10), granulation tissue (n = 9), synovial sarcoma (n = 38), neufibroma (n = 13), solitary fibrous tumor (n =12), gastrointestinal stromal tumor (n = 10), low-grade myxofibrosarcoma (n = 3), low-grade fibromyxoid sarcoma (n = 3), and smooth muscle tumor (n = 10). In addition, the immunohistochemical expressions of ER-alpha, ER-beta and Ki-67 were examined in all of the lesions with desmoid-type fibromatosis. The nuclear immunohistochemical staining for nuclear beta-catenin and ER-beta was graded as high level ( > or = 25% of cells), low level (5%-25%) or none. RESULTS: High-level nuclear beta-catenin staining was detected in a very limited subset of tissue types, which included 70.1% of lesions with desmoid-type fibromatosis (54/77) and 6.3% of lesions with keloid (1/16). No high-level nuclear beta-catenin staining was seen in any of the other lesions. None of the lesions with desmoid-type fibromatosis expressed ER-alpha. However, 62 (80.5%) of the lesions with desmoids-type fibromatosis were positive in ER-beta, which included 52 (67.5%) with high-level expression, and 10 (13%) with low-level expression. The Spearman correlation analysis suggested that the expression of beta-catenin was positively correlated (r = 0.867, P < 0.05) with the expression of ER-beta. The lesions with desmoid-type fibromatosis had very low Ki-67 positive rate. The recurrence of desmoids-type fibromatosis was not correlated independently with beta-catenin, ER-beta or Ki-67. CONCLUSION: High-level nuclear beta-catenin staining serves as a useful diagnostic tool for desmoid-type fibromatosis. The high expression of ER-beta in desmoid-type fibromatosis provides a biological mechanism for the antiestrogenic compounds to treat fibromatosis. There might exists an interaction between beta-catenin and ER-beta. Beta-catenin, ER-beta or Ki-67 can not predict the prognosis of desmoid-type fibromatosis.

Peripheral lung carcinoma: correlation of angiogenesis and first-pass perfusion parameters of 64-detector row CT.

PURPOSE: To investigate the value of 64-detector row CT first-pass perfusion imaging in the evaluation of tumor perfusion in patients with lung carcinoma, and to assess the correlation between the perfusion parameters and tumor angiogenesis. MATERIALS AND METHODS: Forty-six surgically peripheral lung carcinomas were examined with 64-detector row CT. First-pass CT perfusion study comprised of 12 repeated spiral acquisitions over 60s following a 50-ml intravenous bolus of contrast medium at 6-7 ml/s. Tumor specimens were assessed for microvessel density (MVD). Perfusion, peak enhancement intensity (PEI), time to peak (TTP), and blood volume (BV) and MVD of the tumor were compared by means of one-way ANOVA analysis of variance among histological type, size, metastasis and necrosis. Pearson correlation coefficients were conducted to represent the relationships between the perfusion parameters and MVD of the tumor. RESULTS: Mean values for perfusion, PEI, TTP, and BV of the 46 tumors were 70.3+/-39.4 ml/min/ml, 67.0+/-37.6 HU, 36.9+/-11.2s, and 34.9+/-17.9 ml/100g, respectively. No statistically significant differences in perfusion parameters were found among different histological types (p>0.05). Considerable differences with higher perfusion, PEI and BV were noted in tumor < or = 3.0 cm than in tumor>3.0 cm (p<0.05). No statistically significant differences were found between nodule metastasis positive and negative groups (p>0.05). The necrotic tumors showed significantly lower perfusion, PEI and BV compared with non-necrotic tumors (p<0.05). Perfusion, PEI, and BV of the necrotic part manifested significantly lower, but TTP longer, than those of non-necrotic part of the necrotic tumors (p<0.05). Perfusion, PEI and BV were positively correlated with extent of MVD (r=0.715, 0.681, 0.762, respectively, all p<0.001), whereas no significant correlation was found between TTP and MVD (r=-0.154, p>0.05). CONCLUSION: 64-detector row CT first-pass perfusion imaging is a valuable noninvasive method in evaluating tumor perfusion of peripheral lung carcinoma. CT perfusion parameters can be indicators for evaluating tumor necrosis and angiogenesis.

Synergistic myoprotection of L-arginine and adenosine in a canine model of global myocardial ischaemic reperfusion injury.

BACKGROUND: Endogenous nitric oxide and adenosine increase simultaneously to keep the balance of energy demand and supply when the oxygen supply is insufficient, which suggests that nitric oxide and adenosine might exert a synergistic myoprotection during tissue hypoxia. In this study, we tested this hypothesis utilizing a canine model of prolonged global myocardial ischaemic reperfusion injury. METHODS: In this double blind, controlled study, the hearts of 24 anaesthetized mongrel dogs were arrested for 2 hours with aortic cross clamping and blood cardioplegia. The treatment groups were those supplemented with 2 mmol/L L-arginine (ARG), supplemented with 1 mmol/L adenosine (ADO), ARG + ADO supplemented with both, and no supplementation (control) (n = 6 in each group). Haemodynamics, biochemical indices, adenosine triphosphate (ATP) content and myeloperoxidase activities of myocardium were determined to evaluate myocardial injury. Statistical comparison was performed by two way ANOVA. RESULTS: Although the requirements for inotropic supports were higher, the cardiac outputs were lower in control group than in ARG, ADO and the combination groups. Plasma cardiac troponin I levels were higher and the areas of hydropic changes were larger in control group than in ARG and ADO groups. Combination of arginine and adenosine provided further myoprotection with respect to better cardiac performance, lower release of cardiac troponin I, and smaller areas of hydropic changes compared with ARG and ADO groups. ATP content was higher, but myeloperoxidase activities of myocardium were significantly lower in the combination group than in control, ARG and ADO groups (P < 0.05). CONCLUSIONS: Combination of L-arginine and adenosine provides synergistic myoprotection in a canine model of global myocardial ischaemia. Thus, the combination is recommended when the heart is exposed to a prolonged ischaemia during cardiac surgery.

Clinicopathologic features of pleomorphic hyalinizing angiectatic tumor of soft parts.

BACKGROUND: Pleomorphic hyalinizing angiectatic tumor (PHAT) of soft parts is a rare soft tissue tumor, which is generally considered low-grade. To distinguish the tumor from other soft tissue lesions, we analyzed the clinicopathologic and ultrastructural features, immunophenotypes, and flow cytometric DNA ploidy of PHAT in 9 cases. METHODS: PHAT specimens were collected from 9 patients with PHAT from 1990 to 2004. Each specimen was cut into pieces and stained with hematoxylin-eosin, phosphotungstic acid-hematoxylin, Prussian blue, and Masson trichrome, respectively. Immunohistochemical stains for vimentin, S-100 protein, CD34, CD31, CD99, VEGF, desmin, CD117, alpha-SMA, and MIB-1 were performed with the Envision system. Flow cytometry was used in four specimens, two of which were observed by electron microscopy. RESULTS: In the 9 cases, the PHAT occurred at the lower extremity in 2 patients, inguinal in 2, waist in 1, forearm in 1, buttock in 1, foot in 1, and the chest wall in 1. All the lesions presented in the superficial subcutaneous tissues. Follow-up data were available in 7 of the patients, among whom 2 (28.6%) had recurrence after primary therapy. Microscopically, typical PHAT was characterized by sheet-like proliferation of spindle or pleomorphic cells and clusters of thin-walled hyalinized cstatic vessels. In some areas of the tumor, hemosiderin-laden spindle cells, numerous small single vessels, and myxoid extracellular matrix could be identified, indicating an "atypical PHAT". Mitotic figures were rare in all the cases. In 5 of the 9 patients (55.6%), the tumor was typical PHAT; and in the other 4 (44.4%), typical and atypical PHAT coexisted. Immunohistochemically, the neoplastic cells were positive for vimentin, CD34, CD99, and VEGF, but negative for S-100 protein, desmin, SMA, and CD31. In all the cases, the MIB-1 proliferative activity of the neoplastic cells was lower than 2%. Ultrastructural analysis did not reveal any evidence of specific differentiation. Aneuploidy was not detected by flow cytometry. CONCLUSIONS: Histologically, typical PHAT is characterized by spindle and pleomorphic cells associated with an angiectatic vasculature. The neoplastic cells often express vimentin and CD34, and may be positive for CD99 and VEGF. Ultrastructurally, the tumor usually has no specific differentiation. The low MIB-1 index and the absence of aneuploidy in PHAT indicate a non-malignancy. However, we consider the tumor as a borderline neoplasm because of its aggressive behaviour, and suggest wide local resection with tumor-free margin for the treatment of the disease.