CD44 expression in patients with combined hepatocellular cholangiocarcinoma

PURPOSE: Combined hepatocellular cholangiocarcinoma (ChC) is a rare type of primary liver cancer, which is thought to have a poorer prognosis than hepatocellular carcinoma (HCC). Cancer stem cells are associated with tumorigenesis, tumor progression, recurrence, metastasis, and poor prognosis in several malignancies including HCC. The aim of this study was to investigate the expression pattern of cancer stem cell markers in ChC and HCC, and to evaluate whether this pattern correlated to patient prognosis. METHODS: Thirteen patients who underwent curative hepatic resection for ChC and 13 patients who underwent curative hepatic resection for HCC (matched control cases) were included. Immunohistochemical staining for cancer stem cell markers (cytokeratin [CK]7, CK19, C-kit, cluster of differentiation [CD] 44, CD133, and epithelial cell adhesion molecule) was performed and clinical outcomes were analyzed retrospectively. RESULTS: There was no significant difference in cancer stem cell marker expression between ChC and HCC. In ChC, the group that expressed CD44 showed earlier recurrence than the group that did not express CD44 (P = 0.040). CONCLUSION: The expression of cancer stem cell markers in ChC did not show a different pattern compared to that found in HCC. The expression of cancer stem cell marker CD44 was associated with poor prognosis in patients with ChC.

Is Microsatellite Instability Really a Good Prognostic Factor of Colorectal Cancer?

PURPOSE: The aim of this study was to investigate the clinicopathologic features of and the prognosis for colorectal cancers (CRCs) with microsatellite instabilities (MSIs). METHODS: Between 2006 and 2009, genotyping was performed on 245 patients with stage II/III CRCs to establish the MSI status. The clinicopathologic differences and the prognostic value of MSI were analyzed. The median follow-up period was 38 months (range, 7-68 months). RESULTS: Of the total 245 patients, 20 (8.2%) had MSI-high (H) and 225 (91.8%) had MSI-low (L) or stable (S) CRCs. Adjuvant chemotherapies were performed on 101 stage II (87.8%) and 107 stage III patients (82.3%). Patients with MSI-H CRCs more frequently had a family history of colon cancer (10% vs. 2.7%, P = 0.003), more frequently had a cancer located at the proximal colon (90.0% vs. 19.1%, P < 0.0001), and more often showed a mucinous phenotype or poor differentiation (35.0% vs. 7.1%, P = 0.001). Despite less frequent lymph node metastasis (25% vs. 55.6%, P = 0.01), the number of retrieved lymph nodes was higher (26.3 +/- 13.1 vs. 20.7 +/- 1.2, P = 0.04) in the MSI-H group. The overall survival and the disease-free survival (DFS) did not differ with respect to MSI status. However, in the stage II subgroup, the DFS for patients with MSI-H CRCs was significantly worse (72.2% vs. 90.7%, P = 0.03). The multivariate analysis performed on this subgroup revealed that MSI-H was an independent poor prognostic factor (adjusted hazard ratio, 4.0; 95% confidence interval, 1.0-15.6, P = 0.046). CONCLUSION: MSI-H CRCs had distinct clinicopathologic features, and MSI-H was an independent poor prognostic factor in stage II CRCs. Considering the majority of stage II patients were administrated adjuvant chemotherapy, the efficacy of adjuvant chemotherapy for treating MSI CRCs might be different from that for treating MSI-L/S tumors.

Role of Peritoneal Lavage Cytology and Prediction of Prognosis and Peritoneal Recurrence After Curative Surgery for Colorectal Cancer

PURPOSE: In colorectal cancer, the role of detecting free malignant cells from peritoneal lavage is currently unclear. In this study, we investigated the positive rate of free malignant cells in peritoneal lavage fluid and their predictive value for prognosis and peritoneal recurrence after a curative resection. METHODS: From October 2009 to December 2011, in a prospective manner, we performed cytologic examinations of peritoneal lavage fluid obtained just after the abdominal incision from 145 patients who underwent curative surgery for colorectal cancer. We used proportional hazard regression models to analyze the predictive role of positive cytology for peritoneal recurrence and survival. RESULTS: Among total 145 patients, six patients (4.1%) showed positive cytology. During the median follow-up of 32 months (range, 8-49 months), 27 patients (18.6%) developed recurrence. Among them, 5 patients (3.4%) showed peritoneal carcinomatosis. In the multivariate analysis, positive cytology was an independent predictive factor for peritoneal recurrence (hazard ratio [HR], 136.5; 95% confidence interval [CI], 12.2-1,531.9; P < 0.0001) and an independent poor prognostic factor for overall survival (HR, 11.4; 95% CI, 1.8-72.0; P = 0.009) and for disease-free survival (HR, 11.1; 95% CI, 3.4-35.8; P < 0.0001). CONCLUSION: Positive cytology of peritoneal fluid was significantly associated with peritoneal recurrence and worse survival in patients undergoing curative surgery for colorectal cancer. Peritoneal cytology might be a useful tool for selecting patients who need intraperitoneal or systemic chemotherapy.

A Case of Cholangiocarcinoma with Brain and Leptomeningeal Carcinomatosis / 대한내과학회지

Cholangiocarcinoma is a malignant disease originating from the epithelium of the biliary tract, and its prognosis is dismal due to distant metastasis in its early stages. The most common metastatic sites are the intra-abdominal organs, lymph nodes, and lungs. A patient was diagnosed with intrahepatic cholangiocarcinoma and underwent surgical resection. During the follow-up period, metastases were detected at the remnant liver and both lung fields. Eleven months after resection, the patient complained of severe headache. An approximately 5-cm cystic mass was found at the left occipital lobe of the cerebrum, and metastatic malignant cells were present on cerebrospinal fluid cytology. The patient underwent whole-brain radiotherapy. We herein report a rare case of cholangiocarcinoma with cystic brain metastasis together with a review of the relevant literature.

Expression of the Transmembrane Glycoprotein CD44s Is Potentially an Independent Predictor of Recurrence in Hepatocellular Carcinoma

BACKGROUND/AIMS: Cluster differentiation 44 standard isoform (CD44s) is a transmembrane glycoprotein. CD44s is a known prognostic factor in various cancers, due to its involvement in tumor cell growth, invasion and metastasis. Its prognostic role, however, is debated because it can be a positive or negative prognostic factor depending on tumor type and is still an ambiguous prognostic indicator in other cancers, especially hepatocellular carcinoma (HCC). We investigated the relationship between CD44s expression and survival in HCC patients. METHODS: A total of 260 HCC samples were collected to generate a tissue microarray. Staining of the arrays with a primary mouse CD44s monoclonal antibody was followed by evaluation of the relationship between CD44s expression and tumor differentiation. The effect of CD44s expression on patient survival was analyzed. RESULTS: CD44s protein expression correlated with histological grade (most and worst Edmondson grade) of the HCC (p=0.029 and p=0.039, respectively) and adversely affected the disease free survival period based on univariate and multivariate analyses (p=0.038 and p=0.077, respectively). CONCLUSIONS: High CD44s protein expression correlates with shorter disease free survival and poorly differentiated HCC. CD44s-targeted therapy may be efficacious for HCC treatment in the future.

Impact on Prognosis of Lymph Node Micrometastasis and Isolated Tumor Cells in Stage II Colorectal Cancer

PURPOSE: Even though the importance of micrometastases (MMS) and isolated tumor cells (ITC) has been brought up by many physicians, its impact on the prognosis in stage II colorectal cancer is uncertain. In this research, we tried to investigate the clinical features of MMS and ITC and to prove any correlation with prognosis. METHODS: The research pool was 124 colorectal cancer patients who underwent a curative resection from April 2005 to November 2009. A total of 2,379 lymph nodes (LNs) were examined, and all retrieved LNs were evaluated by immunohistochemical staining with anti-cytokeratin antibody panel. Clinicopathologic parameters and survival rates were compared based on the presence of MMS or ITC and on the micrometastatic lymph node ratio (mmLNR), which is defined as the number of micrometastatic LNs divided by the number of retrieved LNs. RESULTS: Out of 124 patients (26.6%) 33 were found to have MMS or ITC. There were no significant differences in clinicopathologic features, such as gender, tumor location and size, depth of invasion, histologic grade, except for age (P = 0.04). The three-year disease-free survival rate for the MMS or ITC positive group was 85.7%, and that for MMS and ITC negative group was 92.8% (P = 0.209). The three-year disease-free survival rate for the mmLNR > 0.25 group was 73.3%, and that for the mmLNR < or = 0.25 group was 92.9% (P = 0.03). CONCLUSION: The presence of MMS or ITC was not closely correlated to the prognosis. However, mmLNR is thought to be a valuable marker of prognosis in cases of stage II colorectal cancer.

Fat Tissue Infiltration into the Pancreas Parenchyme and Its Effect on the Result of Surgery

PURPOSE: In Korea, there are few reports regarding the infiltration of fat tissue in pancreatic parenchyma in surgically resected organs. It is necessary to ascertain the correlation between the presence of fat tissue in the resection margin of the pancreas and the surgery outcome. METHODS: Fifty four patients who underwent pancreatic resection from Jan. 2007 to Nov. 2008 were enrolled in this study. Pathologic examination was performed to determine the presence of fat tissue in resected pancreatic parenchyma. Statistical correlation between the presence of fat tissue with clinical parameters and postoperative complication rates was analyzed. RESULTS: Among the specimens of all fifty four patients, fat tissue was found in 32 specimens of patients (59.3%). Female gender and patients whose body mass index exceeded 24 kg/m2 were statistically correlated with the presence of the fat tissue in pancreatic parenchyma. There was no statistical relationship between infiltration of fat tissue with postoperative complications. CONCLUSION: This study may serve as the base data for study in radiological imaging in detecting pancreatic tissue. A further larger scaled study is needed to validate the result of this study.

Focal-Type Autoimmune Pancreatitis Mimicking Cholangiocarcinoma / 대한내과학회지

Autoimmune pancreatitis (AIP) is a rare pancreatic disorder of autoimmune etiology. It has characteristic clinical features, such as pancreatic parenchymal swelling and irregular narrowing of the main pancreatic duct due to plasma cell infiltration. It occurs mostly in Far East Asia. Although it generally involves whole pancreatic parenchyma, some cases demonstrate focal involvement of the pancreas or adjacent organs, which are often mistaken for cancer. We report a case of AIP that was confused with cholangiocarcinoma of the distal common bile duct (CBD). The patient experienced sudden development of jaundice with vague abdominal discomfort. Abdominal computed tomography revealed a well-enhanced lesion, and positron emission tomography showed high standard uptake value at the distal CBD, indicating malignant disease. However, pathological examination by surgical excision indicated focal-type AIP. This is believed to be the first case of focal-type AIP mimicking cholangiocarcinoma.

Phenotypic Differences of Gastric Cancer according to the Helicobacter pylori Infection in Korean Patients

PURPOSE: Infection with Helicobacter pylori is an important risk factor for gastric cancer in humans. We compared the clinicopathologic features of gastric cancer patients based on H. pylori infection. MATERIALS AND METHODS: We prospectively studied 155 patients who had gastric cancer and underwent gastrectomies in 1 hospital in Korea. We examined H. pylori infections using the rapid urease test (RUT) with gastrectomy specimens and collected clinical and pathologic data. RESULTS: The number of H. pylori infections based on the RUT was 137 (88%). The H. pylori-negative group was significantly associated with AGC and tumor histology. H. pylori infection was significantly correlated with type I/IIa in EGC and type III/IV/V in AGC. AGC was significantly correlated with larger tumor size, lymphatic invasion, perineural invasion, and H. pylori infection based on univariate and multivariate analyses. CONCLUSIONS: We report the prevalence of H. pylori based on the RUT in gastric cancer patients. H. pylori infection influences the tumor histology, progression, and growth type of gastric cancer.

Phenotypic Differences of Gastric Cancer according to the Helicobacter pylori Infection in Korean Patients

PURPOSE: Infection with Helicobacter pylori is an important risk factor for gastric cancer in humans. We compared the clinicopathologic features of gastric cancer patients based on H. pylori infection. MATERIALS AND METHODS: We prospectively studied 155 patients who had gastric cancer and underwent gastrectomies in 1 hospital in Korea. We examined H. pylori infections using the rapid urease test (RUT) with gastrectomy specimens and collected clinical and pathologic data. RESULTS: The number of H. pylori infections based on the RUT was 137 (88%). The H. pylori-negative group was significantly associated with AGC and tumor histology. H. pylori infection was significantly correlated with type I/IIa in EGC and type III/IV/V in AGC. AGC was significantly correlated with larger tumor size, lymphatic invasion, perineural invasion, and H. pylori infection based on univariate and multivariate analyses. CONCLUSIONS: We report the prevalence of H. pylori based on the RUT in gastric cancer patients. H. pylori infection influences the tumor histology, progression, and growth type of gastric cancer.

The Clinical Significance and Detection of Intraperitoneal Micrometastases by ThinPrep(R) Cytology with Peritoneal Lavage Fluid in Patients with Advanced Gastric Cancer

PURPOSE: Peritoneal lavage cytology is regarded as a useful diagnostic test for detecting intraperitoneal micrometastsis. However, there are currently no reports about cytological examination with ThinPrep(R) (CY), a newly introduced fluid-based diagnostic system, in patients with advanced gastric cancer (AGC). This study was performed to analyze the clinical significance of intraoperative peritoneal lavage for CY in AGC patients. MATERIALS AND METHODS: 424 AGC patients were suspected to have serosal exposure macroscopically during surgery and they underwent intraoperative peritoneal lavage for CY between 2001 and 2006 at Korea Cancer Center Hospital. The clinical data, pathological data and CY results were collected and analyzed retrospectively. RESULTS: The percentage of cytology positive results was 31.1%, and this was well correlated with the T-stage, N-stage and P-stage. The 3-year survival rates of CY0 and CY1 were 68.1% and 25.9%, respectively. According to the P-stage and CY, the 3-year survival rates were 71.1% in P0CY0, 38.9% in P0CY1, 38.5% in P1/2/3CY0 and 11.0% in P1/2/3CY1. Interestingly, both the P0CY1 and P1/2/3CY0 survival curves were similar figures, but they were significantly different from those of the other groups. Multivariate analysis indicated that CY was an independent, strong prognostic factor for survival, as well as sex, the T-stage, N-stage, P-stage, other metastasis and the serum CEA. CY1 was revealed as a risk factor for peritoneal recurrence in the curative resection group. CONCLUSION: The results certify indirectly that cytological examination using ThinPrep(R) is a very reliable diagnostic method for detecting intraperitoneal micrometastasis from the fact that it is not only a strong prognostic factor, but it is also a risk factor for peritoneal recurrence in AGC patients. Therefore intraoperative peritoneal lavage should be included in the routine intraoperative staging workup for AGC, and its result will provide a good target for the treatment of peritoneal micrometastasis.

A Case of Uterine Cervical Cancer Presenting with Granulocytosis

Granulocytosis occurs in 40% of patients with lung and gastrointestinal cancers, 20% of patients with breast cancer, 30% of patients with brain tumor and ovarian cancer and 10% of patients with renal cell carcinoma. Granulocytosis occurs because of production of G-CSF, GM-CSF and IL-6. Uterine cervical carcinoma with granulocytosis as a paraneoplastic syndrome, however, has been rarely reported. We recently witnessed a case of invasive squamous cell carcinoma of the uterine cervix with granulocytosis. Leukocytosis developed up to 69, 000/micro L, and then normalized after chemo-radiotherapy. There was no evidence of infection, tumor necrosis, glucocorticoid administration, or myeloproliferative disease by examination of a bone marrow aspirate when granulocytosis appeared. This phenomenon was probably associated with the secretion of hematopoietic growth factors such as G-CSF, GM-CSF and IL-6 by the tumor. We suggest that, like some other solid tumors, cervical cancer can present with granulocytosis as a paraneoplastic syndrome.

The Significances of EGFR Overexpression in Colorectal Cancer

PURPOSE: Epidermal growth factor receptor (EGFR) is a transmembrane cell surface receptor which has tyrosine kinase activity stimulated upon EGF binding. EGFR was found to be up-regulated in various malignancies. Recently, chimeric monoclonal antibody (C225) to EGFR is under investigation as a targeted therapeutic agent for advanced colorectal cancer. Along with this advance, identification of EGFR expression in colorectal cancer became more important. METHODS: To investigate the expression of EGFR in colorectal cancer, we carried out the immunohistochemical staining in surgical specimen of 46 consecutive enrolled colorectal cancer patients of Korea Cancer Center Hospital from August, 1998 to June, 1999. The stained slides were read by pathologist and scored as negative or positive. These results were analyzed according to clinical parameters. RESULTS: Average age was 55 years old (32~73 yr) and sex ratio was 1.56 : 1. The expression rate of EGFR in colorectal cancer was 56.5% (26/46 cases). EGFR expression was not correlated with age, sex, Tie-1, Tie-2 expression, TNM stage, lymphatic invasion, presence of distant metastasis, serum VEGF level. We could not find out staitistical difference of survival according to EGFR expression. CONCLUSIONS: EGFR overexpression was well characterized by immunochemical staining method, which could be applied easily as a basic pathologic step to decide additional therapy after resection for advanced colorectal cancer.

A case of pulmonary cryptococcosis mimicking pulmonary metastasis in a patient with cutaneous squamous cell carcinoma / 대한내과학회지

Multiple pulmonary nodules were found in a 71-year-old Korean female patient with cutaneous squamous cell carcinoma during diagnostic work-up. A presumptive diagnosis of metastases was made and percutaneous fine needle aspiration cytology was undertaken. Finally, pathological examination of the tissue revealed granulomatous inflammation with cryptococcal infection. The patient received 6 months of antifungal treatment with fluconazole and her chest radiographic findings were improved after the treatment. She is now under clinical follow-up. Recognition that pulmonary cryptococcal infection can mimic metastasis is important in reaching the correct diagnosis and in determining the correct treatment.

A Case of Long-Term Survivor after Surgical Resection for Undifferentiated Embryonal Sarcoma of the Liver in Adult / 한국간담췌외과학회지

An undifferentiated (embryonal) sarcoma of the liver (USL) is a rare and highly malignant hepatic neoplasm of mesenchymal origin. This tumor almost exclusively affects pediatric patients, with a poor prognosis. The highest incidence is noted in pediatric patients, usually from 5~10 years of age, but only 43 cases of USL have been reported in adults worldwide since it was first as a clinicopathological entity. With a USL in adults, most patients are known to have died within 1 year of diagnosis. The absence of specific symptoms, rapid tumor growth, normality of common tumor markers and the consequential delay in diagnosis often result in significant enlargement of the tumor, with a poor prognosis. Various therapeutic modalities have been attempted in adult patients, but only a few long-term survivors have been reported. Herein, our experience of a 42-year-old female patient who is still alive, 55 months after the first resection for a USL is reported.

A Case of Symtomatic Inflammatory Myofibroblastic Tumor (IMT) of the Liver in Adult / 한국간담췌외과학회지

An inflammatory myofibroblastic tumor (IMT) is a rare benign hepatic neoplasm that is characterized by a mass of localized proliferations of fibroblasts and infiltrations of mononuclear inflammatory cells. An IMT can occur in a variety of locations, including the lung, orbit, parotid, pleura and stomach. However, they have rarely been encountered in the liver. An IMT of the liver most often presents in young adults. The clinical presentations of a hepatic IMT vary: asymtomatic, fever, abdominal pain, palpable mass, vomiting, obstructive jaundice, anemia and hepatosplenomegaly. Their radiographic appearance and clinical presentation make them extremely difficult to distinguish from a malignant neoplasm, preoperatively. Therefore, surgical management is used when a malignancy can not be excluded preoperatively or when the IMT produces a biliary obstruction. We encountered a 31-year-old male patient who is still alive for 38 months following a resection for symtomatic IMT.

Outcome after Partial Hepatectomy for Hepatocellular Carcinoma Combined with Liver Cirrhosis / 한국간담췌외과학회지

BACKGROUND/AIMS: Partial hepatectomy is considered as best treatment for selected HCC patients combined with liver cirrhosis. We conducted this study to assess the safety and effects of partial hepatectomy for HCC combined with liver cirrhosis and to identify the prognostic factors. METHODS: Retrospective analysis was performed for 115 HCC patients with liver cirrhosis who underwent hepatectomy in Korea Cancer Center Hospital from 1987 September to 2002 July. Median follow-up period was 30 months. RESULTS: In-hospital mortality rate was 0.87% (1/115 cases). 5-years overall and disease free survival rates were 59.3% and 44.75%, respectively. Fifty three patients developed recurrence and most common recurrent site was remnant liver (81.1%) and 3-year survival rate after recurrence was 33.4%. Independent prognostic factors for overall survival rate were TNM stage, multiplicity and venous invasion (p<0.05). CONCLUSION: Hepatectomy plays a significant role for HCC with compensated liver cirrhosis and is regarded as the effective treatment with acceptable mortality. However, recurrence rate is still high, so frequent follow-up study should be needed for early detection of recurrence amenable to effective treatment. For the high risk patients, further study should be followed to reduce the recurrence after hepatectomy, including surgical technique and adjuvant treatment.

Outcome of Hepatic Resection for Hepatocellular Carcinoma Patients

PURPOSE: This study was conducted to evaluate the effects of a partial hepatic resection for a hepatoma, to elucidate the recurrence patterns and to identify the prognostic factors, as the standard treatment option for the selected hepatocellular carcinoma (HCC) patients. METHODS: Retrospective analysis was performed on 201 HCC patients who underwent hepatic resection in Korea Cancer Center Hospital (KCCH) from September 1987 to August 2001. They consisted of 158 men and 43 women whose median age was 51 years (range: 24~73) and median follow-up period was 76.3 months. Statistical analysis was performed using the Kaplan-Meier method, Log-rank test and Cox regression hazard model using SPSS 10.0 for Windows. RESULTS: Three patients died without discharge due to 2 hepatic failures and one multiple organ failure. Therefore, the in-hospital mortality rate was 1.5% (3/201). The 5 year overall survival rate and disease free survival rate were 56.3% and 42.8%, respectively. Eighty patients developed recurrences at various sites, of which remnant liver was the most common site (60.8%) and 3 year survival rate after a recurrence was 24.7%. The independent prognostic factors for overall survival rate were venous invasion, multiplicity, TNM stage, an ICG-R15 and transfusion. CONCLUSION: Partial hepatic resection plays a significant role for selected HCC patients and is regarded as an effective treatment modality with acceptable mortality. However, postoperative recurrence still remains a unresolved crux. A recurrence amenable to retreatment should be detected through a diligent follow-up study. For the high risk patients, further study including adjuvant therapy is needed to reduce the recurrence rate.

Bilateral Mammary Metastasis of Alveolar Soft Part Sarcoma: A Case Report

An alveolar soft part sarcoma(ASPS) is a rare malignant soft tissue tumor, which metastasizes to the lung, bone and brain. Recently, we encountered an unusual case of a metastatic ASPS to the bilateral breasts in a 27-year-old woman. She had undergone surgery for an ASPS in her right thigh two years ago, which metastasized to the breast on three occasions, 15 months, 20 months and two years after surgery.

Fine Needle Aspiration Cytologic Features of Follicular Lymphoma / 대한세포병리학회지

The accuracy of fine needle aspiration cytology(FNAC) for the diagnosis of follicular lymphoma was investigated by a review of 13 FNAC specimens from 10 patients. All patients included in this study were confirmed by surgical biopsy preceded by FNAC. Three aspirates were unsatisfactory because of scanty cellularity. Among the remaining 10 cases, 5(50%) were diagnosed as lymphoma, 3(30%) as reactive hyperplasia, one(10%) as metastatic small cell carcinoma, and one(10%) as granulomatous inflammation. Cytologic distinction between follicular lymphoma and reactive hyperplasia is very difficult with cytomorphology alone. Compared to reactive hyperplasia, the characteristic cytologic features such as relatively homogeneous cellular constituent, paucity of tingible body macrophages and lymphohistiocytic aggregates, and less mitotic activity in follicular lymphoma are important findings to prevent false negative diagnosis. In addition, lymphoglandular bodies are useful in distinguishing malignant epithelial tumor from lymphoid lesion.