General management

Hepatocellular carcinoma is one of the most common malignancies worldwide. The general management of hepatocellular carcinoma begins with an accurate diagnosis. With advances in imaging studies, noninvasive diagnosis has become an accepted standard of care for hepatocellular carcinoma, though pathologic examination is still required in selected cases. Following diagnosis, accurate staging is the next most important step in selecting the most appropriate treatment modality. Patients with localised tumor and compensated liver disease should be considered for partial hepatectomy, and patients with poor hepatic function but early tumor stage are candidates for liver transplantation. Patients who do not qualify for either of these curative treatments may be evaluated for palliative therapy, of which transarterial chemoembolisation is most widely used. This review will discuss the role of biopsy, the pros and cons of noninvasive and pathologic tissue diagnosis as well as the general approach to choose the most appropriate treatment for patients with hepatocellular carcinoma.     

Seltene Raumforderung des Nebenhodens

A 51-year-old man with known ethyl toxic chronic pancreatitis presented with a tumor of the left epididymis. Immunhistological examination disclosed it as a metastasis of a pancreatic carcinoma. Paratesticular metastases of a pancreatic carcinoma are very rare. Nevertheless a metastasis of a primary pancreatic carcinoma should be included in the differential diagnosis of a tumor of the paratesticular tissue. The epididymis should be integrated in the diagnostic procedures of pancreatic carcinoma.     

Cancer biology for individualized therapy: correlation of growth fraction index in native-state histoculture with tumor grade and stage.

There is a need for individualization of all aspects of cancer therapy. Because of significant heterogeneity within a tumor class, there is a need to develop an in vitro test to accurately gauge tumor aggressiveness. Such a measurement would greatly aid treatment decision making. Current methodologies such as flow cytometry, which lacks unambiguous interpretation of cell-proliferative data, and determination of the thymidine-labeling index, which measures nucleotide uptake in a nonphysiological state, have not reproducibly attained this goal. We have developed an in vitro native-state three-dimensional gel-supported histoculture system that allows the growth of all human solid tumor types for relatively long time periods. The native-state system was used to identify the percent of cells capable of incorporating [3H]thymidine over a 4-day period, which we term the growth fraction index (GFI). We have compared the ability of cancer tissue to proliferate in native-state culture to the stage and histological grade of four major types of human carcinomas: breast, ovarian, colon, and lung. Eighty percent of tumor explants could be evaluated, even when sent from across the country. We have determined that the GFI correlates with tumor stage and grade for breast and ovarian carcinoma. In colon carcinoma, there is a trend toward higher GFIs in tumors of more advanced stage and grade. In non-small cell lung carcinomas, GFI, stage, and grade do not correlate. These results suggest the applicability of gel-supported three-dimensional native-state histoculture for prognostic purposes in patients with breast and ovarian cancers and demonstrate the clinical relevance of the native-state histoculture system.     

Ovarian carcinoma: Increase in clinical validity by simultaneous determination of SRA and CA 125

Summary Ovarian carcinomas are distinguished by their polyclonality, i.e., heterogeneity and polymorphism of their tissue. There ist no marker available complying with the clinical demands in the case of ovarian carcinoma regarding statisfactory sensitivity and specificity. Therefore, we have simultaneously determined two entirely distinct tumor markers, serum ribonuclease activity (SRA) and cancer antigen 125 (CA 125), recommended in the literature with respect to ovarian carcinoma. After evaluation by logistic regression analysis, we found a specificity of 93% together with a sensitivity of 97% for the simultaneous determination of SRA and CA 125 (37 ovarian carcinomas, 11 cases without pathological findings after treatment, 11 benign tumors of the ovary, 61 controls). The patients are not exposed to increased stress by this simultaneous determination method compared to the determination of a single marker. The increased clinical validity justifies the recommendation of routine simultaneous determinations of SRA and CA 125 for diagnosis and monitoring of patients with ovarian carcinoma.This work was supported in part by a grant from the DFG (WI 748-3-1) awarded to Wolfgang Wiest     

Diagnosis of hepatocellular carcinoma (HCC) in a high-risk patient by using transgastric EUS-guided fine-needle biopsy (EUS-FNA)

Hepatocellular carcinoma (HCC) is the most common primary malignancy arising within the liver and most often affects individuals with chronic hepatitis and/or liver cirrhosis. Patients often present at an advanced stage of disease or with poor liver function, thus limiting treatment options and resulting in a poor prognosis of the disease. Therefore, an early tissue-based diagnosis of HCC is necessary to direct further work-up and treatment. We present the case of a 70-year-old man with alcoholic cirrhosis at stage Child C, in whom a tumor nodule was found incidentally within the left lobe of the liver. Percutaneous biopsy was deemed too dangerous because a deteriorated liver function with coagulopathy was present, and a significant amount of ascites surrounded the small cirrhotic liver. To obtain a conclusive diagnosis, we performed transgastric fine-needle biopsy of the tumor under direct endosonographic guidance (EUS-FNA) without complications. Cytologic examination confirmed the presence of a well differentiated HCC. Based on this finding, super-selective CT-guided angiography and chemoembolization were subsequently performed without complications and the patient remained free of tumor relapse for the 8 months of surveillance. We conclude that EUS-guided fine-needle biopsy and cytologic examination represent a reliable alternative for tissue sampling in HCC, particularly in selected high-risk patients such as those with poor liver function and coagulation disorders; this should be assessed in prospective clinical trials.     

Expression and correlation of CD44v6, vascular endothelial growth factor, matrix metalloproteinase-2, and matrix metalloproteinase-9 in Krukenberg tumor

AIM: To explore the expression and correlation of CD44v6, vascular endothelial growth factor (VEGF), matrix metalloproteinase (MMP)-2 and matrix metalloproteinase (MMP)-9 in Krukenberg and primary epithelial ovarian carcinoma. METHODS: The expressions of CD44v6, VEGF, MMP-2 and MMP-9 were detected by immunohistochemical method in 20 cases of normal ovarian tissues, 38 cases of Krukenberg tumor and 45 cases of primary epithelial ovarian carcinoma. RESULTS: The expression of CD44v6 (primary epithelial ovarian carcinoma tissue vs normal ovarian tissue: x2 = 4.516, P= 0.034; Krukenberg tumor tissue vs normal ovarian tissue: x2 = 19.537, P= 0.001) and VEGF (primary epithelial ovarian carcinoma tissue vs normal ovarian tissue: P = 0.026; Krukenberg tumor tissue vs normal ovarian tissue: x2 = 22.895, P= 0.001) was significantly higher in primary epithelial ovarian carcinoma tissue and Krukenberg tumor tissue than in normal ovarian tissue. The positive expression rate of MMP-2 and MMP-9 was 0% in the normal ovarian tissue. The positive expression rate of CD44v6 (x2 = 10.398, P= 0.001), VEGF (x2 = 13.149, P= 0.001), MMP-2 (x2= 33.668, P= 0.001) and MMP-9 (x2 = 38.839, P = 0.001) was remarkably higher in Krukenberg tumor than in primary epithelial ovarian carcinoma. The correlation of CD44v6, VEGF, MMP-2, and MMP-9 was observed in primary epithelial ovarian carcinoma and Krukenberg tumor. CONCLUSION: CD44v6, VEGF, MMP-2, and MMP-9 are involved in ovarian carcinoma, gastric cancer and Krukenberg tumor. Detection of CD44v6, VEGF, MMP-2 and MMP-9 may contribute to the diagnosis of ovarian carcinoma, gastric cancer, and Krukenberg tumor.     

螺旋CT检查在喉癌诊断中的应用

目的探讨螺旋CT检查在喉癌诊断中的应用价值。方法 29例经手术切除的喉癌患者,术前行螺旋CT检查,与术后病理检查结果作比较。结果 CT诊断喉癌侵犯周围组织的准确性在90%以上;以临床检查和CT检查结合行T分期的准确性为83%,高于单纯临床分期的52%（P〈0.05）。结论螺旋CT检查能比较准确的显示喉癌的侵犯范围;CT检查失误的主要原因包括不能显示喉软骨或周围软组织的微小浸润,对肿瘤引起的周围组织的炎性水肿易产生假阳性。     

Tissue polypeptide antigen in serum and tissue in patients with lung cancer

To evaluate the significance of TPA (tissue polypeptide antigen) as a tumor marker for lung cancer, the present studies were designed to measure serum TPA levels as well as TPA contents in tumor tissues in patients with lung cancer. Average serum TPA levels (203.5 +/- 180.5 U/l, mean +/- SD) in 76 patients with lung cancer (30 squamous cell carcinoma, 38 adenocarcinoma, 8 small cell carcinoma) were significantly higher than those in pneumonia (83.3 +/- 42.7 U/l, n = 13), pulmonary tuberculosis (87.6 +/- 36.3 U/l, n = 16), and normal controls (46.8 +/- 23.7 U/l, n = 28). There was no significant difference in TPA levels according to the histological type of lung cancer. Comparing respective stage cases, statistically significant differences were observed in serum TPA levels between normal controls and stage 1, stage 1 and stage 3, and in stage 3 and stage 4, suggesting a gradual increase in TPA levels accompanying the progress of the lung cancer. In patients with 12 squamous cell carcinoma and 9 adenocarcinoma, the TPA levels in carcinoma tissues and non-tumor invaded lung tissues were 115.2 +/- 187.7 and 148.9 +/- 223.3 U/mg protein, indicating no significant difference in carcinoma and normal tissues. There was definite correlation between serum TPA levels and TPA contents in carcinoma tissues. No significant relationship, however, was observed between serum TPA levels and TPA contents in tissue not invaded by tumor. These results suggest that serum TPA levels reflect the tumor burden in patients with lung cancer. In conclusion, the determination of TPA in blood is useful for the diagnosis of lung cancer.     

Ovarian mucinous cystadenocarcinoma as a cause of Zollinger-Ellison syndrome: report of a case and review of the literature

Gastrin producing ovarian tumor is a rare cause of the Zollinger-Ellison syndrome. We report the case of an ovarian carcinoma showing increased plasma gastrin concentration. A 60-yr-old woman presented with epigastric pain and diarrhea. Physical examination showed a large mass in the lower abdomen. Computed tomography revealed a large multilocular ovarian cyst. Upper gastrointestinal endoscopy examination showed multiple ulcerations of the stomach and duodenum. The plasma gastrin level was 1500 pg/ml. No tumors were found in the pancreas and duodenum, and salpingo-oophorectomy was performed. Histologic examination revealed a mucinous tumor of borderline malignant potential. Immunoperoxidase studies for gastrin showed many gastrin-producing cells within the epithelium of the tumor. There have been 11 cases (including our patient) of gastrin-producing ovarian tumor reported in the literature. We review here the relevant literature. Although ovarian gastrinoma is extremely rare, it should be considered as a possible cause of the Zollinger-Ellison syndrome in women.     

Hormone sensitivity of gynecological tumor cells in tissue culture

Summary Proliferating tumor cells obtained from ovarian, mammary, and endometrial tumors in tissue culture were tested for the influence of proteohormones and steroid hormones on cellular DNA synthesis and cell growth. The gonadotropic hormones stimulated DNA synthesis of ovarian tumor cells by single administration, or in combination with cortisol, up to the 11-fold of the comparable controls. The hormone sensitivity of the cell lines was variable, resulting in individual reaction patterns. There was no correlation to the histological diagnosis of the primary tumors with respect to the grade of differentiation. The results suggest that ovarian tumor cells in tissue culture can maintain sensitivity to organotropic hormones. Compared to the ovarian carcinoma lines, mammary or endometrial tumor cells did not respond to a similar extent. Progesterone decreased DNA synthesis of endometrial carcinoma cells.     

NIH conference. Hepatocellular carcinoma

Hepatocellular carcinoma is the most frequent cancer worldwide, responsible for approximately 1,000,000 deaths annually, most of them in the Far East and in sub-Saharan Africa. It usually presents at an advanced stage and has a poor prognosis. There is evidence of an etiologic role for hepatitis B virus infection in the etiology of hepatocellular carcinoma. Carriers of the virus are 94 times more at risk for hepatocellular carcinoma than noncarriers. In many cases hepatitis B virus DNA is integrated within the cellular genome of the tumor. Programs have been established to detect hepatocellular carcinoma at an early stage; persons at high risk are regularly screened by measurement of serum alpha-fetoprotein levels and ultrasound examination of the liver. Surgical resection offers the only hope of cure at present, as chemotherapy, radiotherapy, and immunotherapy have not shown promise. Ideally, surgery should be done on small asymptomatic tumors.     

女性盆腔结核性包块的诊断及治疗

女性盆腔结核性包块是临床上较常见的妇科疾病,容易与其他盆腔包块和肿瘤相混淆,造成误诊或漏诊。在临床工作中,为提高对女性盆腔结核性包块诊断的准确性,应全面、综合分析患者病史、症状,完善有关的辅助检查,包括结核菌素试验、病原学检查、诊断性刮宫、血清癌抗原125检测、腹腔积液及影像学检查;诊断方法上有结核病免疫学诊断、分子生物学检查,为肺外结核的诊断提供了快速检查技术;对诊断困难者进行腹腔镜或剖腹探查术也是必要的。女性盆腔结核性包块需要与盆腔炎性疾病、卵巢子宫内膜异位囊肿、卵巢良恶性肿瘤,尤其应与卵巢癌进行鉴别;也需要与腹腔其他恶性肿瘤以及其他发热性疾病鉴别。女性盆腔结核性包块治疗上主要是全身化学治疗,对临床高度怀疑生殖器结核患者可行诊断性治疗;必要时辅以手术治疗,术中注意防止损伤发生;对结核中毒症状严重者可考虑加用糖皮质激素治疗。     

Melena： A rare complication of duodenal metastases from primary carcinoma of the lung

Small bowel metastases from primary carcinoma of the lung are very uncommon and occur usually in patients with terminal stage disease. These metastases are usually asymptomatic, but may present as perforation, obstruction, malabsorption, or hemorrhage. Hemorrhage as a first presentation of small bowel metastases is extremely rare and is related to very poor patient survival. We describe a case of a 61- year old patient with primary adenocarcinoma of the lung, presenting with melena as the first manifestation of small bowel metastasis. Both primary tumor and metastatic lesions were diagnosed almost simultaneously. Upper gastrointestinal endoscopy performed with a colonoscope revealed active bleeding from a metastatic tumor involving the duodenum and the proximal jejunum. Histological examination and immunohistochemical staining of the biopsy specimen strongly supported the diagnosis of metastatic lung adenocarcinoma, suggesting that small bowel metastases from primary carcinoma of the lung occur usually in patients with terminal disease and rarely produce symptoms. Gastrointestinal bleeding from metastatic small intestinal lesions should be included in the differential diagnosis of gastrointestinal blood loss in a patient with a known bronchogenic tumor.     

Rapidly Progressing Anaplastic Carcinoma of the Pancreas with Mucoepidermoid Carcinoma: An Autopsy Case Report

A 75-year-old man visited our hospital for the examination of a tumor in the pancreas. Computed tomography showed an 85×85-mm low-density tumor in the pancreas. The tumor was pathologically diagnosed as poorly differentiated carcinoma by endoscopic ultrasound-guided fine-needle aspiration. Although we started chemotherapy, the patient died 84 days after the diagnosis. An autopsy demonstrated a ruptured anaplastic carcinoma with mucoepidermoid carcinoma of the pancreas. Anaplastic carcinoma with mucoepidermoid carcinoma is a very rare histologic subtype of pancreatic carcinoma, so pathological findings are important for predicting the patient''s prognosis. Physicians should be aware of this rare but fatal disease.     

Late pulmonary manifestation of ovarian and breast cancer--which contribution provide immunohistochemical techniques?

The two case studies are describing 2 females with tumor-suspicious lung opacities including pleural effusions. Both patients have had a smoking history of more than 20 packyears and both underwent surgery for a breast respectively an ovarian cancer 10/15 years before. Conventional staining of the biopsies does not allow in most cases the differentiation between a primary lung carcinoma or the metastasis of an extrapulmonary tumor. Immunohistochemical techniques can give clues as to the origin of the primary tumor. The contribution of these methods in finding the correct diagnosis in the two presented cases is discussed. The cooperation between clinician and pathologist should be emphasized. The transfer of all important information is essential.     

A case of intrahepatic cholangiocarcinoma detected after successful interferon therapy for chronic hepatitis C

A 65-year-old man presented at our hospital in 2006 because of a liver tumor. He had been treated for chronic hepatitis C with interferon-α2b for 6 months in 1998. A pathological examination showed that the hepatic tissue before interferon (IFN) therapy was classified as moderately active hepatitis with severe hepatic fibrosis. The IFN therapy induced the disappearance of the hepatitis C virus (HCV) RNA from his serum and normalized alanine aminotransferase activity. In 2005, a tumor (2 cm in diameter) was detected in the right lobe of the liver by ultrasonography and computed tomography, and the tumor was stained with contrast medium during abdominal angiography. A right lobectomy was performed under the diagnosis of hepatocellular carcinoma. The pathological examination revealed that the tumor was an intrahepatic cholangiocarcinoma (ICC). The noncancerous hepatic tissue was classified as having minimal activity with mild fibrosis. It is important to monitor closely for ICC as well as hepatocellular carcinoma even patients in whom the HCV RNA has disappeared after IFN therapy, because the outcome of treatment for small ICC is favorable.     

The prospect of endoscopic submucosal dissection for early anal canal squamous cell carcinoma

Squamous cell carcinoma (SCC) of the anal canal is seldom diagnosed at an early stage. Chemoradiation therapy is a standard in Europe and the United States, though in squamous cell carcinoma there is no evidence-based therapy. In Japan, endoscopic submucosal dissection (ESD) is the standard minimally invasive treatment for early stage cancer of the digestive tract, including the colorectum. Therefore, if the lesion is diagnosed at an early stage, ESD may be selected for anal canal lesions. We experienced two cases of early stage anal canal cancer in which the diagnosis and the extent of the lesions were confirmed using magnifying endoscopy with narrow-band imaging (NBI), as well as performing ESD. Pathological examination showed the resected specimen to be SCC in situ; the horizontal and vertical margins were free of tumor; and in one case there was no lymphovascular invasion. In the other case it showed the tumor was contained within the epithelium; horizontal and vertical margins were free of tumor; The follow-up period is not long enough to assert that ESD for anal canal squamous cell carcinoma may be an option of minimally invasive therapy. However, if there is a possibility of lymphatic invasion as in one of our cases, we need to give serious consideration to ESD for these lesions, and careful follow-up is necessary even if the lesion is in situ.     

Unusual cause of painful shoulder in an elderly woman with rheumatoid arthritis

The painful shoulder is a very common condition encountered in the rheumatology clinic with rotator cuff disorders, glenohumeral disorders, acromioclavicular joint disease and referred neck pain being the most common causes. Other rare causes have to be considered in the presence of “red flag” indicators. We describe a case of a patient with mild rheumatoid arthritis and a past medical history of stage 2C epithelial ovarian carcinoma who presented to the rheumatology clinic with a painful shoulder and who was initially diagnosed with rotator cuff tendinopathy. When seen 3 months later she was found to have a 15 x 10-cm firm, non-tender soft tissue mass over the right scapula and X-rays showed a large lytic mass destroying much of the upper border of the scapula, suggestive of metastasis. Bone metastases in patients with ovarian carcinoma are very rare; they occur in about 2% of cases and are invariably predictors of poor prognosis. To our knowledge, this is the first case of ovarian cancer metastasised to the scapula. We suggest that rheumatologists should be aware of the differential diagnosis of painful shoulder and look for “red flag” indicators in patients with known rheumatic conditions.     

High IL-17-positive tumor immune cell infiltration is indicative for chemosensitivity of ovarian carcinoma

Purpose

Ovarian carcinoma in most instances is diagnosed in an advanced stage which cannot be cured by surgical tumor debulking alone. Standard adjuvant chemotherapy usually follows surgical procedures. Yet, few reliable predictive tissue markers exist for the response of ovarian carcinoma to chemotherapy. In this study, we evaluated the predictive value of IL-17- and FOXP3-positive tumor immune cell infiltration (TICI) for response to chemotherapy in ovarian carcinoma.

Methods

Formalin fixed and paraffin embedded biopsies of mostly high-grade primary serous ovarian carcinomas and their matched recurrences were immunostained with IL-17 and FOXP3 on a tissue microarray. Chemoresistance was defined as tumor recurrence within 6 months of the completion of platinum-based chemotherapy. In 94 and 90 biopsies, conclusive data for IL-17 and FOXP3 were available, respectively.

Results

IL-17, but not FOXP3-positive TICI, displayed a significantly higher density in biopsies of chemosensitive tumors (p = 0.01). No significant difference in the expression of IL-17 and FOXP3 TICI was observed in all paired primary and recurrent biopsies without respect to chemoresponse (p = 0.77 and p = 0.87, respectively). However, significantly more IL-17-positive recurrences were encountered in the group of patients with chemosensitive tumors (p = 0.008).

Conclusions

High IL-17-positive TICI is indicative for response to chemotherapy in ovarian carcinoma. Higher frequency of IL-17-positive TICI might persist in recurrent tumor tissues of chemosensitive biopsies, suggesting repetitive platinum-based chemotherapy as an appropriate therapy for patients with IL-17-positive recurrences.     

不同原发部位胃转移癌12例

目的:探讨不同原发部位胃转移癌的临床特点及诊治.方法:对我院1990-01/2010-01诊断胃癌的病例资料进行检索,其中符合胃转移癌诊断者12例,计算其在胃癌中的构成比,结合国内外相关文献,分析不同原发部位胃转移癌的临床特点、诊治手段及其效果与预后.结果:胃转移癌原发部位以食管癌居多,占胃转移癌的50%(6/12).患者多有原发肿瘤病史,临床表现与原发性胃癌相似,诊断主要依赖于原发癌病史及病理组织学检查,预后较差(生存期9.5 mo),尽早诊断并手术可改善预后.结论:胃转移癌发病率极低,不易与原发性胃癌鉴别,诊断依据是原发癌病史及病理组织学检查,预后差,手术是主要的治疗手段.