Prospective study of differential diagnosis of hepatic tumors by pattern-based classification of contrast-enhanced sonography

AIM: To prospectively evaluate the usefulness of a pattern-based classification of contrast-enhanced sonographic findings for differential diagnosis of hepatic tumors. METHODS: We evaluated the enhancement pattern of the contrast-enhanced sonography images in 586 patients with 586 hepatic lesions, consisting of 383 hepatocellular carcinomas, 89 metastases, and 114 hemangiomas. After injecting a galactose-palmitic acid contrast agent, lesions were scanned by contrast- enhanced harmonic gray-scale sonography in three phases: arterial, portal, and late. The enhancement patterns of the initial 303 lesions were classified retrospectively, and multiple logistic regression analysis was used to identify enhancement patterns that allowed differentiation between hepatic tumors. We then used the pattern-based classification of enhancement we had retrospectively devised to prospectively diagnose 283 liver tumors. RESULTS: Seven enhancement patterns were found to be significant predictors of different hepatic tumors. The presence of homogeneous or heterogeneous enhancement both in the arterial and portal phase was the typical enhancement pattern for hepatocellular carcinoma, while the presence of peritumoral vessels in the arterial phase and ring enhancement or a perfusion defect in the portal phase was the typical enhancement pattern for metastases, and the presence of peripheral nodular enhancement both in the arterial and portal phase was the typical enhancement pattern forhemangioma. The sensitivity, specificity, and accuracy of prospective diagnosis based on the combinations of enhancement patterns, respectively, were 93.2%, 96.2%, and 94.0% for hepatocellular carcinoma, 87.9%, 99.6%, and 98.2% for metastasis, and 95.6%, 94.1%, and 94.3% for hemangioma. CONCLUSION: The pattern-based classification of the contrast-enhanced sonographic findings is useful for differentiating among hepatic tumors.

Intraductal neoplasm of the intrahepatic bile duct: Clinicopathological study of 24 cases

AIM: To investigate the clinicopathological features of intraductal neoplasm of the intrahepatic bile duct (INihB). METHODS: Clinicopathological features of 24 cases of INihB, which were previously diagnosed as biliary papillomatosis or intraductal growth of intrahepatic biliary neoplasm, were reviewed. Mucin immunohistochemistry was performed for mucin (MUC)1, MUC2, MUC5AC and MUC6. Ki-67, P53 and β-catenin immunoreactivity were also examined. We categorized each tumor as adenoma (low grade), borderline (intermediate grade), and malignant (carcinoma in situ , high grade including tumors with microinvasion). RESULTS: Among 24 cases of INihB, we identified 24 tumors. Twenty of 24 tumors (83%) were composed of a papillary structure; the same feature observed in intraductal papillary neoplasm of the bile duct (IPNB). In contrast, the remaining four tumors (17%) showed both tubular and papillary structures. In three of the four tumors (75%), macroscopic mucin secretion was limited but microscopic intracellular mucin was evident. Histologically, 16 tumors (67%) were malignant, three (12%) were borderline, and five (21%) were adenoma. Microinvasion was found in four cases (17%). Immunohistochemical analysis revealed that MUC1 was not expressed in the borderline/adenoma group but was expressed only in malignant lesions (P = 0.0095). Ki-67 labeling index (LI) was significantly higher in the malignant group than in the borderline/adenoma group (22.2 ± 15.5 vs 7.5 ± 6.3, P < 0.01). In the 16 malignant cases, expression of MUC5AC showed borderline significant association with high Ki-67 LI (P = 0.0622). Nuclear expression of β-catenin was observed in two (8%) of the 24 tumors, and these two tumors also showed MUC1 expression. P53 was negative in all tumors. CONCLUSION: Some cases of INihB have a tubular structure, and are subcategorized as IPNB with tubular structure. MUC1 expression in INihB correlates positively with degree of malignancy.

Perimuscular connective tissue contains more and larger lymphatic vessels than the shallower layers in human gallbladders

AIM： To clarify whether perimuscular connective tissue contains more lymphatic vessels than the shallower layers in human gallbladders. METHODS： Lymphatic vessels were stained immunohistochemically with monoclonal antibody D2-40, which is a specific marker of lymphatic endothelium, in representative sections of 12 normal human gallbladders obtained at the time of resection for colorectal carcinoma liver metastases. In individual gallbladder specimens, nine high-power （×200） fields with the highest lymphatic vessel density （LVD）, termed ＂hot spots＂; were identified for each layer （mucosa, muscle layer, and perimuscular connective tissue）. In individual hot spots, the LVD and relative lymphatic vessel area （LVA） were measured microscopically using a computer-aided image analysis system. The mean LVD and LVA values for the nine hot spots in each layer were used for statistical analyses. RESULTS： In the mucosa, muscle layer, and perimuscular connective tissue, the LVD was 16.1 ± 9.2, 35.4 ± 15.7, and 65.5 ± 12.2, respectively, and the LVA was 0.4 ± 0.4, 2.1 ± 1.1, and 9.4 ± 2.6, respectively. Thus, both the LVD and LVA differed significantly （P 〈 0.001 and P 〈 0.001, respectively; KruskaI-Wallis test） among the individual layers of the wall of the gallbladder, with the highest LVD and LVA values in the perimuscular connective tissue. Most （98 of 108） of the hot spots within the perimuscular connective tissue were located within 500 μm of the lower border of the muscle layer. CONCLUSION： The perimuscular connective tissue contains more and larger lymphatic vessels than the shallower layers in the human gallbladder. This observation partly explains why the incidence of lymph node metastasis is high in T2 （tumor invading the perimuscular connective tissue） or more advanced gallbladder carcinoma.

Study on vasculogenic mimicry in malignant esophageal stromal tumors

AIM: To investigate whether malignant esophageal stromal tumors contain PAS-positive patterned matrix-associated vascular channels, which are lined by tumor cells, but not vascular endothelial cells. That is vasculogenic mimicry (VM) independent of tumor angiogenesis. METHODS: Thirty-six tissue samples of malignant esophageal stromal tumors were analyzed. Tissue sections were stained for Vascular endothelial growth factor (VEGF), CD31 and periodic acid Schiff (PAS). The level of VEGF, the microvascular density (MVD) and the vasculogenic mimicry density (VMD) were determined. RESULTS: PAS-positive patterned matrix-associated vascular channels were detected in 33.3% (12/36) of tumor samples. Within these patterned channels, red blood cells were found. The level of VEGF and the MVD in tumors containing patterned channels were significantly higher than those in tumors not containing patterned channels (P < 0.05). At the same time, the malignant degree of tumors was higher, the proportions of tumors containing patterned channels were not only more, but also in the each kind of tumors containing patterned channels. CONCLUSION: In malignant esophageal stromal tumors, a VM mechanism causes some tumor cells to deform themselves and secrete extracellular matrix; thus, PAS-positive patterned matrix-associated vascular channels appear and supplying blood to the tumors to sustain their growth and metastasis.

Expression of caveolin-1 in clear cell renal cell carcinoma and its correlation with microvessel density

Objective:The aim of the study was to investigate the clinicopathologic significance of caveolin-1 expression in clear cell renal cell carcinoma (CCRCC) and its correlation with microvessel density (MVD).Methods:The expression of caveolin-1 was detected by the immunohistochemistry method,while the microvessel density was detected by the immunohistochemistry expression of CD34.Results:In the CCRCCs,the positive rate of caveolin-1 was 67.4%,the over expression of caveolin-1 was not related with sex and age,but related with clinicopathologic parameter,such as tumor sizes,clinical TMN stage,nuclear stage and survival time (P < 0.05).The MVD of positive caveolin-1 cases was significantly higher than that without caveolin-1 expression (P < 0.05).Conclusion:The expression of caveolin-1 is helpful in the prognostic evaluation of CCRCCs and it may be involved in the tumor angiogenesis.

Bile tract adenomyoma:A case report

This paper described a rare case of adenomyoma of common bile duct. The case is a 51-year-old man who was hospitalized for yellow color skin and sclera and itching for 2 mo without abdominal pain. Nothing special was found in physical examination except yellowish skin and sclera. The clinical presentation and Computerized Tomography (CT),Magnetic resonance cholangiopancreatography (MRCP),and ultrasonography suspected a tumor of the distal bile duct. The patient was treated successfully by pancreaticoduodenectomy. Histologically,the lesion consisted of adenoid and myofibrous tissue and moderate atypia. The immunophenotype of the epithelial component was cytokeratin 7+/cytokeratin 20-. The patient has been well without any evidence of recurrence for 12 mo since his operation.

Mediastinal tuberculous lymphadenitis presenting as an esophageal intramural tumor: A very rare but important cause for dysphagia

Dysphagia associated with esophageal mechanical obstruction is usually related to malignant esophageal diseases. Benign lesions are rarely a cause for this type of dysphagia, and usually occur either as an intramural tumor or as an extrinsic compression. Mediastinal tuberculous lymphadenitis is rare in adults, and even more rarely causes dysphagia. We report two cases of dysphagia in adult patients caused by mediastinal tuberculous lymphadenitis, presenting radiologicaUy and endoscopically as an esophageal submucosal tumor. Based on the clinical and imaging diagnosis, the patients underwent a right thoracotomy, and excision of the mass attached to and compressing the esophagus. Pathological examination of the specimens showed a chronic granulomatous inflammation with caseous necrosis, which was consistent with tuberculous lymphadenitis.

Chemoradiotherapy with twice-weekly administration of low-dose gemcitabine for locally advanced pancreatic cancer

AIM:To evaluate the chemoradiotherapy for locally advanced pancreatic cancer utilizing low dose gemcitabine as a radiation sensitizer administered twice weekly. METHODS: We performed a retrospective analysis of chemoradiotherapy utilizing gemcitabine administered twice weekly at a dose of 40 mg/m2. After that, maintenance systemic chemotherapy with gemcitabine, at a dose of 1000 mg/m2, was administered weekly for 3 wk with 1-wk rest until disease progression or unacceptable toxicity developed. RESULTS: Eighteen patients with locally advanced unresectable pancreatic cancer were enrolled. Three of those patients could not continue with the therapy; one patient had interstitial pneumonia during radiation therapy and two other patients showed liver metastasis or peritoneal metastasis during an early stage of the therapy. The median survival was 15.0 mo and the overall 1-year survival rate was 60%, while the median progression-free survival was 8.0 mo. The subgroup which showed the reduction of tumor development, more than 50% showed a tendency for a better prognosis; however, other parameters including age, gender and performance status did not correlate with survival. The median survival of the groups that died of liver metastasis and peritoneal metastasis were 13.0 mo and 27.7 mo, respectively.CONCLUSION: Chemoradiotherapy with low-dose gemcitabine administered twice weekly could be effective to patients with locally advanced pancreatic cancer; however, patients developing liver metastases had a worse prognosis. Another chemoradiotherapy strategy might be needed for those patients, such as administrating one or two cycles of chemotherapy initially, followed by chemoradiotherapy for the cases with no distant metastases.

Littoral-cell angioma of the spleen:A case report

Littoral-cell angioma （LCA） is a primary splenic vascular tumor that arises from the normal littoral cells lining the sinus channels of the splenic red pulp. We report a case of LCA of the spleen, which has been infrequently communicated in the literature. A 76-year-old man with a 2-wk history of weight loss, abdominal pain and changes in bowel habits was admitted to our hospital. Imaging studies （CT and MR1） showed multiple lesions in the spleen. Splenectomy was performed. Lining cells were positive for CD31/CD68 markers. Our case was associated with a serrated colonic adenoma. LCA is a benign vascular tumor of the spleen that needs to be included in the differential diagnosis of multiple splenic nodules.

A study of histogenesis of pulmonary sclerosing hemangioma

Objective： To investigate the histogenesis and differential diagnosis of pulmonary sclerosing hemangioma （PSH）. Methods： Thyroid transcription factor-1 （TTF-1）, surfactant proteins A, B （SP-A, SP-B）, epithelial membrane antigen （EMA）, vimentin, pancytokeratin, cytokeratin7 （CK7）, CK5/6, calretinin, S-100, neurospecific enolase （NSE）, synaptophysin （Syn）, chromogranin A （CgA）, CD34, factor-Ⅷ-related antigen （F-Ⅷ） and smooth muscle actin （SMA）in 55 patients with PSH were examined with immunohistochemistry, while samples from 19 patients were also observed by electron microscope. Follow-up information were reviewed. Results： Pathologically, PSH mainly consisted of both surface lining cuboidal cells and pale polygonal cells. Immunohistochemitry revealed that coexpression of TTF-1, EMA and vimentin in both cuboidal and polygonal cells was 94.5 % （52/55）, 90.5% （50/55） and 58.2% （32/55）, respectively. In cuboidal cells, the expression of SP-A and SP-B was 92.7% （51/55） and 81.8 % （45/55）, respectively. Whereas pancytokeratin and CK7 immunostained the cuboidal cells in all cases. The polygonal cells were difussed immunostained with Syn in 13 PSHs （24%） and NSE in 8 PSHs （15%）, while immunoreactions with S-100 and CgA were separated detected in 7 PSHs （13%）. There was no significant difference of TTF-1 and EMA expression between these two cells （χ^2 value was 1.371 and 3.352, respectively. P 〉 0.05）. In contrast, there was a significant difference of vimentin between them （χ^2 value was 17.720, P 〈 0.001）. Electron microcopy observation showed that ultrastructure may not differ from each other sometime. The follow-up was obtained for 49 cases ranged from 3 months to 14 years. 48 of them had no recurrence or metastasis except one case had recurrence. Conclusion： PSH may origin from the primitive respiratory epithelial. Polygonal and cuboidal cells are all parenchymal neoplasm cells. The concomitant examination of TTF-1, SPA, SP-B, EMA, virnentin and pancytokeratin may favor the diagnosis and differential diagnosis of PSH.

Reflections on the New Classification of Tumors by the WHO and Changes in Esophageal Cancer in a High-risk Area

ABSTRACT In year 2000, a book entitled the Pathology and Genetics of Tumors of the Digestive System was published by the WHO, presenting some new diagnostic criteria and treatment principles. I have analyzed the epidemiologic change of tumors in over 30 years in the high-risk area with esophageal cancer. The following phenomenon was found： accompanied by the sharp decrease in the incidence and mortality of esophageal cancer, there was an increase in the incidence and death rate of stomach cancer involving cardiac cancer. This fact should be considered when analyzing the sharp decrease in esophageal cancer incidence and mortality rate. More attention was given to diagnosis of cardiac cancer; at the same time it is more practical to improve the early screening of cancers. To observe the development of high and low - grade intraepithelial neoplasms will be an urgent task for esophageal cancer research in the high risk area, according to WHO＇s new classification.

Primary Angiosarcoma of the Womb: A Case Report

Case Report A 35-year-old patient was admired to the hospital on March 27th, 2005 because of profuse leukorrhea for 3 months and progressive abdominal pain for half a month. The leukorrhea, which started for no apparent reason, contained streaks of blood and had an odor. One month prior to her hospitalization, her symptoms intensified and she was diagnosed by pathological examination with chronic inflammation of the mucous membranes of the cervix. A half month before being admitted, the patient＇s symptoms became more serious with abdominal distension and pain.

Analysis of Clinicopathologic Features of Esophageal Carcinoma Patients Undergoing Surgery-a Report of 4,329 Cases

OBJECTIVE To investigate the clinicopathological features of esophageal carcinoma （EC） patients, and to analyze epidemiologic characteristics and the current situation of esophageal cancioma in the southern area of Hebei Province. METHODS A total of 4329 patients with esophageal cancinoma, undergoing surgery in the Fourth Hospital of Hebei Medical University during a period from January 1996 to December 2005, were selected. Collection and statistical analysis of the pathologic data were performed using a SAS 6.0 software package. RESULTS Over the past ten years, there has been a tendency for an increase in the mean age of EC onset （P 〈 0.05）, a downtrend in the percentage of squamous cancer （SqCa） （P 〈 0.05） and an uptrend in the frequency of small cell carcinoma （P 〈 0.05）. In clinical stages, there was a drop in the percentage of Stage-Ⅱ squamous EC patients （P 〈 0.05）, and an increase in that of Stage-Ⅳ patients （P 〈 0.05）. There were statistical differences in sex, age, pathologic types, depth of infiltration, ratio of stages and lymph node metastasis, etc. among the superior, middle and inferior segments of the EC diseased region （P 〈 0.05）. CONCLUSION It was relatively late for the EC patients from this area to see a doctor, resulting in a drop in the ratio of SqCa and an ascensus in that of small cell cancer. However, due to a low incidence of adenocarcinoma, no obvious ascending tendency was found in the frequency of this carcinoma over the past ten years.

Progress in pancreatic cancer therapeutics: The potential to exploit molecular targets

Pancreatic ductal adenocarcinoma is an aggressive and devastating disease associated with poor survival outcomes. Even though signifcant advances have been made towards understanding the intricate pathology of this cancer, several important aspects remain unknown. Recently, key genetic mutations within the tumour have been identified, but the exact role they play in tumourigenesis has yet to be determined.For many years, the micro-tumour environment and stroma was thought to aid proliferation but there is now emerging research that suggests the contrary. Several novel targeted agents in pre-clinical and early clinical studies have been promising but it remains to be seen whether they will have a signifcant impact on patient outcomes. In this review we discuss the unique nature of pancreatic cancer biology, current treatment options and summarise the latest results from pre-clinical and clinical research. We also discuss the future strategies that are needed to improve outcomes for this disease.

Epithelioid Hemangioendothelioma of the Liver:Etiology,Natural History and Treatment

Epithelioid hemangioendothelioma （EHE） is an uncommon vascular tumor, which also has been called histiocytoid haemangioma. This low-grade malignant tumor was first described as a distinctive entity in 1982 by Weiss and Enzinger Histopathologically, EHE is characterized by round or spindle-shaped endothelial cells with cytoplasmic vacuolation121. The tumor may occur in numerous organs, including liver, lung, parotid grand, skin, pleura, thyroid, spleen, cardiac valve, radial artery, oral cavity and parapharyngeal space. Many cases have been reported, but its etiology and natural history remain unclear.

Telomerase activity analysis of esophageal carcinoma using microdissection-TRAP assay

OBJECTIVES: To investigate telomerase activity in esophageal squamous cell carcinoma (SCC) and its preneoplasia lesions, and to study the relationships between telomerase activity and cancer differentiation, cancer invasiveness, and lymphatic metastasis. METHODS: Telomerase activity in esophageal SCC tissues, adjacent dysplasia tissues and normal epithelia from the surgical edge were assessed by microdissection-TRAP (telomeric repeat amplification protocol)-silver staining assay. RESULTS: Telomerase activity was detected in 37 (82.2%) of 45 esophageal tumors, 23 (79.3%) of 29 dysplasias, and 2 (5%) of 40 normal epithelia. There was a significant difference in activity between dysplasia and normal epithelium, as well as between tumor and normal epithelium. Twenty-six (92.9%) of 28 tumors with lymphatic metastasis had detectable telomerase activity compared to 11 (64.7%) of 17 non-lymphatic metastasis tumors. These relationships were statistically significant (P

Effect of moxibustion on VEGF and EGF expressions in tumor tissues of rats with gastric tumor

Objective:To explore the inhibitory effect of moxibustion on tumor growth and metastasis, and also its possible mechanism, in gastric tumor-bearing rats by investigating the expressions of vascular endothelial growth factor (VEGF) and epidermal growth factor (EGF). Methods:Fifty healthy Sprague-Dawley (SD) rats (half male and half female) were routinely housed for 1 week. A total of 20 rats were randomly divided into a blank group and a sham operation group, with 10 rats in each group. The remaining 30 rats were used to make gastric cancer models by implantation of ascites-type Walker-256 cancer cells. After successful modeling, rats were randomly divided into a model group, a moxibustion group and an infrared group, with 10 rats in each group. From the day of modeling, the body weight of each group was weighed every 4 days. Warm moxibustion was alternately performed at two-group acupoints [Zhongwan (CV 12), Guanyuan (CV 4) and bilateral Zusanli (ST 36) in one group, and bilateral Pishu (BL 20) and Weishu (BL 21) in another group] in the moxibustion group. The body surface projection area of the stomach was irradiated with short-wave infrared rays in the infrared group, once a day, 20 min per time for 21 d. At the end of the treatment, the gastric tumor was completely dissected, and the tumor volume and tumor growth inhibition rate were calculated. Then the gastric tumor cell metastasis was recorded. The levels of VEGF and EGF in rat gastric tumor tissues were determined by enzyme-linked immunosorbent assay (ELISA). Results:Compared with the blank group, the body weight of the model group decreased significantly after modeling (P<0.05);compared with the model group, the rats in the moxibustion group had increased body weight during the middle and late stages (bothP<0.05). The tumor volumes of rats in the moxibustion group and the infrared group were smaller than the volume in the model group (bothP<0.05). The tumor growth inhibition rate in the moxibustion group was significantly higher than that in the infrared group (P<0.05). The case number of tumor metastasis in the moxibustion group was smaller than that in the model group and the infrared group. The VEGF level in the tumor tissues of the model group was statistically significantly higher than that in the blank group (P<0.05). Compared with the model group, the VEGF levels in the moxibustion group and the infrared group were statistically significantly lower (bothP<0.05). The EGF levels in the tumor tissues of the model group was statistically significantly lower than that in the blank group (P<0.05);compared with the model group, the EGF levels in the moxibustion group and the infrared group were statistically significantly increased (bothP<0.05). Conclusion:Moxibustion can increase the body weight, inhibit the tumor growth, invasion and metastasis in gastric tumor-bearing rats, which may be related to the regulation of VEGF and EGF expressions in tumor tissues.

HIF-1 inhibitors as anti-cancer therapy

Hypoxia is a hallmark of solid tumors.Hypoxia increases the progression of malignancy and metastasis by promoting angiogenesis and triggering the over-expression of various protein products critical for tumor growth.The transcription factor HIF-1 mediates cellular response to hypoxia by promoting processes,such as glycolysis and angiogenesis.Clinical evidence has demonstrated that expression of HIF-1 is strongly associated with poor patient prognosis and activation of HIF-1 contributes to malignant behavior and therapeutic resistance.Therefore,HIF-1 is a viable target for cancer therapy.This review summarizes agents that have been described in the literature as HIF-1 inhibitors.The majority of these compounds are indirect inhibitors of HIF-1.