Cancer Research and Treatment

Clinico-pathologic Parameters for Prediction of Microsatellite Instability in Colorectal Cancer: Sang-Bong Jung, Han-IL Lee, Hoon-Kyu Oh, Im-Hee Shin, Chang-Ho Jeon; Cancer Res Treat. 2012;44(3):179-186. Published online September 30, 2012; DOI: https://doi.org/10.4143/crt.2012.44.3.179

PURPOSE
Although the incidence of microsatellite instability (MSI) accounts for 10-15% of cases of colorectal cancer, its clinical application for all colorectal cancers has widened. We attempted to identify clinical and pathological parameters that may be helpful in selection of patients with MSI-high (MSI-H).
MATERIALS AND METHODS
A total of 120 resected colorectal cancers were enrolled retrospectively for this MSI study. Polymerase chain reaction (PCR) and denaturing high performance liquid chromatography and/or real time PCR methods with five markers and immunohistochemistry (IHC) for MLH1 and MSH2 were performed for analysis of cancer and blood specimens. Clinico-pathologic parameters, including IHC, were investigated in order to determine their usefulness as predictive factors of MSI.
RESULTS
Among 120 cases of colorectal cancer, MSI was observed in 15 cases (12.5%), including 11 cases of MSI-H and four cases of MSI-low. Patients with MSI were younger, less than 50 years old, had a family history of cancer, Rt. sided colon cancer and/or synchronous multiple colorectal cancer, mucinous histologic type, and serum carcinoembryonic antigen group in the normal range. Results of multivariate analysis showed Bethesda guidelines, Rt. sided and/or synchronous multiple colorectal cancer, and negative expression of IHC for MLH1, which was consistently associated with MSI-H. MSI-H colorectal tumors have met at least one of these three parameters and their sensitivity and specificity were 100% and 72.5%, respectively.
CONCLUSION
Bethesda guidelines, tumor location, and negative expression of MLH1 protein are important parameters for selection of patients with colorectal cancers for MSI testing. MSI testing is recommended for patients showing any of these three parameters.

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Effects of Some Korean Food Extracts on In Vitro Benzo(a)pyrean Metabolism by Rat Liver Microsomal Preparation and its DNA Pamaging Effect: Sun Whe Kim, Jin Pok Kim, Sang Chul Park; J Korean Cancer Assoc. 1989;21(1):18-35.

Abstract PDF: N umerous epidemiologic and experimental studies have proven that there is a close cause and effect relationship between diet and cancer. Several Korean traditional foods (ginseng, red pepper, maejoo, onion, natural salt, garlic) were chosen in order to find if there is any effect of those food materials on the chemical carcinogenesis. To evaluate effects of food extracts on the metabolism of chemical carcinogen, metabolite patterns of benzola)pyrene (B(a)p), especially of 3-hydroxy benzo(a)pyrene (3-OH) as major metabolite, 7, 8-dihydrodiol (7,8-diol), precursor of ultimate carcinogen 7,8-diol-9,10-epoxide, praduced by in vitro metabolism by rat liver Sg were analysed and compared with those in the presence of acetone soluble fractions of food materials, using high performance liquid chromatography (HPLC). And to find the biologic significance of these results, DNA damaging effect of B(a)p was measured and compared with that in the presence of food extracts using SOS chromotest. As a result of analysis using HPLC, 7,8-diol production rate was increased in the presence of the extracts of ginseng, onion and natural salt, while decreased in the presence of the extracts of maejoo, red pepper and garlic. 7,8-diol/3-OH ratio was markedly increased in the presence of red pepper and decreased in the presence of onion. In SOS chromotest, ginseng, red pepper and natural salt had enhancing effect in contrast that maejoo, onion and garlic had inhibitory effect of the SOS inducing act.ivity of B(a)p in the presence of S9. Namely, ginseng and natural salt increased both detoxifying and bioactivating metabolism of B(a) p and enhanced the DNA damaging effect, while maejoo and garlic decreased both detoxifying and bioactivating metabolism and DNA damaging effect. And by red pepper, the detoxifying metabolism was markedly decreased and bioactivation was relatively increased as well as DNA damaging effect. While the detoxifying metabolism was markedly increased by onion, bioactivation was relatively decreased as well as DNA damaging effect. Therefore, it is evident that various food extracts could have some effects on the metabolism of chemical carcinogen, specifically on the production of procarcinogen and the DNA damaging effect of chemical carcinogen.

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In Vitro Activation and expansion of Human Tumor - Infiltrating Lymphocytes ( TIL ) with Intreleukin 2 ( IL 2 ) and Their Antitumor - Cytotoxic Properties Against Autotogous Tumor Cells: Kyu Chul Choeh, Sang Yun Nam, Jai Kyung Park, Youn Mun Ha, Yong Mook Choi, Chang Il Ahn; J Korean Cancer Assoc. 1989;21(1):35-51.

Abstract PDF: To determine the effect of interleukin 2 (IL 2) on human tumor-infiltrating lymphocytes (TIL) from surgically excised solid tumors and to charscterize the antitwhor-cytotoxicity of activated TIL comparing with lymphokine-activated killer (LAK) cells generated from peripheral blood mononu- clear cells, this study wss performed. Single cell suspensions of TIL snd tumor cells were prepared from 20 surgical specimens (12 stomach canrers, 4 breast cancers, 1 lung cancer, 1 colon cancer, 1 ovarian cancer, and 1 cervix cancer) by mechanical and enzymatic means. And freshly isolated TIL were separated from tumor cells by fishing method. The amount of TIL obtained by the above means was 7.1x10+-6.7 (SD) cells/cm(3) of tumor mass with range of 0.8~27.5 x 10(5). The TIL prepatrations contaminated partially with tumor cells (10~20%) were cultured in IL 2 containing media. Cell numbers were reduced from the initial seeding density until about 7 days of culture. After 10 days of culture with IL 2, TIL increased in number with a concomitant disappearance of tumor cells, whereas there were slow decreases of lymphocytes and increases of tumor cells in control cultures. TIL were expanded between 0.5 and 118,000 fold increases for 10 to 34 days (2~9 subcultures). Partially purified natural IL 2-induced expansions of TIL were more rapid than highly purified recombinant IL 2-induced expansions, and showed 10 times high for 18 days of culture. The majority of TIL were T lymphocytes with range of 56~68.8% of Leu4+, 25.0~40. 8%of Leu2a+, and 0~51. 5% of Leu3a+cells. With continued in vitro expansion for 14-20 days, there was a concomitant increase in T lymphocytes (Leu4+) to 71~76.8% but the changes af phenotypes of Leu2a+ and Leu3a+ were variable. TIL were tested for cytotaxicity against fresh autologous and alfogenic tumor cells, and Raji and K562 targets in a 4-hr Cr release assay. IL 2-activated TIL showed more potent cytotoxicity against autologous tumor targets than allogenic (P<0.05). And cytotoxic activity of activated TIL in killing autologous tumor targets was higher level than that of LAK celis, but the defference was not statistically significant (0.05

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A pathologic Study on N - Nitrosoheptamethyleneimine - induced Squamous Cell Carcinoma of Lung in Rats: Eun Sil Yu, Eui Keun Ham, Won Keun Chung; J Korean Cancer Assoc. 1989;21(1):51-67.

Abstract PDF: Squamous cell carcinomas of the lung were induced in female Sprague Dawley rats by oral administration of N-Nitrosoheptamethyleneimine (NHMI) for 14 weeks, and their ultrastructure and immunohistochemical nature were investigated in special reference to their histogenesis and cellular origin. 1) The major pathologic changes during the administration of NHMI were bronchial basal cell hyperplasia, subsequent development of squamous metaplasia and bronchioloalveolar hyperplasia. 2) The pulmonary tumors at eight weeks after tapering NHMI were exclusively squamous cell carcinoma. 3) Ultrastructure of the peripheral squamous cell carcinomas presented characteristice of bronchiolar epithelium such as electron dense or lucent granules, many degenerated mitochondria and well developed Golgi apparatus. Presence of thin filaments or bundles of intracytoplasmic keratin and transformation of microvilli to interdigitating cytoplasmic processes with desmosomes represented a squamous metaplastic process through the carcinogenesis of NHMI-induced squamous cell carcinoma. 4) Bidirectional differentiation to squamous and mucus secreting cells within the keratinizing squamous cell carcinomas was identified with ultrastructural examination, which was assumed an expression of phenotypic heterageneity of lung tumors and suggested the importance of electron microscopic evaluation in lung tumor classification. 5) Pulmonary epithelial cells in rats were all negative on immunohistochemical staining for three types of cytokeratin. However, metaplastic bronchial or bronchiolar epithelial cells were positive for polycfonal cytokeratin (56-64 kd). All squamous cell carcinomas showed strong stainability for polyclonal cytokeratin, and weak and focal positivity for high molecular weight cytokeratin (68 kd). The above pathologic findings suggest that NHMI-induced pulmanary squamous cell carcinomas be assumed to develop through a squamous metaplasia of bronchial and/or bronchioloalveolar epithelial cells. A similarity in histogenesis and histopathologic characteristics between this animal model and human squamous cell careinoma supports this model being expected to be suitable for the study of biological nature of squamous cell carcinoma.

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Effect of Cisplatin on Glomerular Filtration Rate and Effective Renal Plasma Flow: Yong Hyun Kim, Weon Seon Hong, Sang Moo Lim, Jae Kwan Song, Young Whan Kim, Seong Woon Hong, Jhin Oh Lee; J Korean Cancer Assoc. 1989;21(1):67-74.

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The Effect of Splenectomy on the Prognosis of Gastric Cancer: Seong Chul Kim, Sun Whe Kim, Sung Han Bae, Jae Gahb Park, Jin Pok Kim; J Korean Cancer Assoc. 1989;21(1):74-82.

Abstract PDF: 1n the surgery of gastric cancer, combined splenectomy has been advocated in order to enhance the radical nature of the operation. In some cases, splenectomy is done due to incidental injury of the spleen during the operation. There may be micrometastasis of gastric cancer to the lymph node of the splenic hilum or the splenic artery. When gastrectomy with combined splenectomy be performed for gastric cancer, though it can remove the micrometastasis to ihe lymph node of the splenic hilum or splenic artery, postsplenectomy change will affect the body. In order to examine the effect of splenectomy-incidental or as a part of curative resection-on the postoperative course of the gastric cancer patients, we studied the cases of gastrectomy with splenectomy for stage II and stage III gastric cancer, and compared with those of gastrectomy without splenectomy for the same stage. The results were as follows; from 1970 to 1986, the number of cases of gastrectomy with splenectomy for stage II and stage III gastric cancer was 90, among which retrospective study was possible in 74 cases; stage II 25cases, stage III 49 cases. 1) The cumulative survival rates of gastrectomy with splenectomy group in stage II gastric cancer were 1 year 96.0%, 2 year 84.0%, 3 year 79.8%, 4 year 74.8%, and 5 year 69.0%-100%, 85.7%, 85.7%, 76.1%, 76.1% in radical subtotal gastrectomy with splenectomy group and 90.1%, 81.8%, 72.7%, 72.7 %, 62.3% in total gastrectomy with splenectomy group, respectively. In stage III gsstric cancer, gastrectomy with splenectomy showed that 1, 2, 3, 4 and 5 year survival rates were 89.8%, 46.9%, 23.5%, 17.1%, and 17.1%, respectively -88.0%, 36,0%, 20.0%, 16.09o, and 16. 0% in radical subtotal gastrectorny with splenectomy group and 91.7%, 58.3%, 26.9%, 17.9 %, and 17. 9% in total gastrectomy with splenectomy group. 2) The splenectomy had the negative effect on the stage III gastric cancer (p < 0.001, Log-rank test). The negative effect on the subtotal gastrectomy for stage Ill gastric cancer was statistically significant (p < 0.010) but not on the total gastrectomy for stage III gastric cancer. 3) The portion of lymphocytes to the white blood cells and the number of platelets per cubic millimeter increased postoperatively in the group surviving more than 3 years, which is consistent with the postsplenectomy change, but not in the patients who could not survive 3 years after operation. 4) The postoperative complications developed in 8 cases-pfeural effusion in 4 cases, LUQ abscess in 2 cases, fever, unknown origin in 1 case, and meningitis in 1 case.

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Combination Chemotherapy with Cisplatin , Etoposide , and Vinblastine ( PEV ) in the Advanced Non - Small Cell Lung Cancer: Keun Chil Park, Yoon Koo Kang, Dong Bok Shin, Si Young Kim, Yung Jue Bang, Sung Koo Han, Young Soo Shim, Noe Kyeong Kim, Keun Youl Kim, Keun Youl Kim; J Korean Cancer Assoc. 1989;21(1):82-93.

Abstract PDF: Fifty patients with the advanced non-small cell lung cancer, who had no previous treatment, were treated with a combination chemotherapy regimen consisting of cisplatin (20mg/m i.v. day 1-5), etoposide (100 mg/m i.v. day 2-4), and vinblastine (6 mg/m(2) i.v, day 1) every 3 weeks. Among the 50 patients entered into this study 45 patients were evaluable for response. Objective responses were achieved in 49 % (22/45) of patients (2 CRs, 20 PRs). In 23 patients with limited disease, the response rate was 61% (14/23) with no complete response, higher than that, but not statistically significant, in the extensive disease patients (36% with 2 CRs). The overall median survival of the patients was 42.6 weeks and the responding patients survived longer than non-responders (median survival; 51.5 weeks vs. 37.4 weeks, p<0.05). Toxicity with this regimen was acceptable; myelosup- pression was the major toxic effect and was severe in only 11% of the patients with one treatment- related death from sepsis associated with granulocytopenia. The gastrointestinal side effects and alopecia were rather universal and the peripheral neuropathy (20%) and azotemia (9%) were not uncommon, but manageable in general.

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Clinical Evaluation of Total Gastrectomy and Extended Total Gastrectomy for Gastric Cacner: Ma Hae Cho, Jae Gahb Park, Jin Pok Kim; J Korean Cancer Assoc. 1989;21(1):93-101.

Abstract PDF: During 16 years from Jan. 1970 to Dec. 1986, total gastrectomy and extended total gastrectomy were performed in 566 patients. The results are as follows: 1) Gastrectomy was performe4 in 2891 out of 3791 patients (76%) who underwent operation. 2) Total gastrectomy and extended total gastrectomy were performed in 566 patients (19%) of them. 3) The most frequent site of primary gastric cancer was the body (40. 5%), followed by the cardia and fundus (24.4%), diffuse infiltration of gastric wall (18.1%) and antrum (17.0%). 4) In the cases of advanced carcinoma, the most common Borrmann type was Type III (55.8%), followed by Type IV (18.1%), Type II (17.0%) and Type I (3.4%). 5) Early gastric cancer was 26 cases (5.7%). 6) In the pathologic findings, the most common type was adenocarcinoma (68.9%), followed by mucinous cell (9.7%), signet ring cell (8.6%) and undifferentiated carcinoma (5.7%). 7) In the staging of cancer according to TNM postsurgical-pathologic stage group, stage I was 4. 4%, stage Il 17.4%, stage III 78.2%. 8) In the extended total gastrectomy, partial hepatectomy was performed in 10 cases (8.4%) and transverse colectomy was performed in 10 cases (8.4%) in addition to pancreaticosplenectomy. 9) Overall operative mortality was 3.8% and no significant difference of operative mortality was found between total and extended total gastrectomy. 10) The expected 5 YSR, according to Cohort life table, was 45% in total gastrectomy and 24% in extended total gastrectomy. In the total gastrectomy patients, 5 YSR of stage I, II, Ul were 100%, 68% and 36%, respectively. In the extended total gastrectomy patients, 5 YSR of stage II and III were 48% and 16%, respectively.

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Wilms Tumor - Clinicopathologic Variation and Prognosis: Choal Hee Park, Kwang Sae Kim, Sung Choon Lee, Kun Young Kwon; J Korean Cancer Assoc. 1989;21(1):101-112.

Abstract PDF: A histologic classification based on tumor differentiation, degree of tubular formation and favorable histology versus unfavorable histology was applied in a retrospective study of 21 patients with Wilms tumor to determine if it might provide an index to prognosis from 1977 through 1987. A comparison of the histologic findings with survival through statistical analysis was undertaken and it was found that the histologic classification was significantly correlated with survival. The results were as follows: 1. Low grade tumors(grade I) with predominance of differentiated tubules & glomeruli were associated with better survival rate than high grade tumorrade III) composed mainly of undiffer- entiated spindle elements: 2-year survival rate was 100% for grade I with 11% for grade III (p< 0.01). 2. Survival rate was lower for the low degree of tubular formation than for the high degree of tubular formation: 2-year survival rate were 14%, 50%, 75%, 100% for group 0, +, ++, and +++ respectively(p < 0.05). 3. 11 patients with the focal or diffuse anaplasia and sarcomatous stroma (unfavorable histology) had poor prognosis, giving 36% of 2-year survival rate but 10 patients with favorable histology had 70% of 2-year survival rate (p<0.05).

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Clinical Analysis of Krukenberg Tumor - A review of 25 cases -: Jong Kwon Park, Jae Gahb Park, Jin Pok Kim; J Korean Cancer Assoc. 1989;21(1):112-117.

Abstract PDF: We analyzed 25 cases of Krukenberg tumor who had been treated at the Department of Surgery, Seoul National University Hospital from January 1980 to December 1988. We obtained the following results. 1) The primary sites of tese tumores were stomach in 23 cases (92%), ascending colon in 1 cases (4 %) and unknown in 1 case (4%). Among the 23 cases of gastric cancer, 12 cases were stage IU and 11 cases were stage IV. 2) Among the 948 female patients with gastric cancer admitted during these period, 23 cases (2.4%) had Krukenberg tumor. 3) The most prevalent age group was the 4th decade (11 cases) and followed by the 5th decade (9 cases), and the mean age was 44 years. 4) The most common symptom was abdominal mass (80%) and followed by abdominal distension (72%), and abdominal pain (72%). 5) Eighteen cases (72%) showed bilateral ovarian involvement and 5 cases (20%) showed left and 2 cases (8%) showed right involvement. 6) Both the primary lesion and Krukenberg tumor were found simultaneously in 13 cases at initial explolation, among them 3cases had radical subtotal gastrectomy and bilateral oophorectomy. But 10 cases had ovarian biopsy. In the 12 cases, Krukenberg tumor developed 26 months later (mean duration) after the primary operation. 7) We could follow the 21 patients out of 25 patients and their median survival was 19 months, the median survival of the patients who had both radical subtotal gastrectomy and bilateral oophorectomy was 19 months and that of the patients who discovered Krukenberg tumor later was 13 months and the median survival of those patients who had only ovarian biopsy was 7.5 moths.

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Combined Hyperthermia and Radiation Therapy on Primary Hepatocellular Carcinoma: Jin Sil Seong, Yun Ku Lee, Chang Ok Suh, John Juhn Kyu Loh, Hyung Sik Yoo, Jae Kyung Roh, Byung Soo Kim, Kwang Hyub Hahn, Sang In Lee, Heung Jae Choi; J Korean Cancer Assoc. 1989;21(1):117-129.

Abstract PDF: Thirty patients with unresectable hepatocellular carcinoma due to either locally advanced lesion or association with liver cirrhosis, treated with combined hyperthermia and radiotherapy between April 1988 and July 1988, at Dept. of Radiation Oncology, Yonsei University College of Medicine, were prospectively ananlysed. External radiotherapy of a total dose of 3060 cGy/3.5 wks was given. Hyperthermia was given twice a week with a total of 6 treatment sessions using 8 MHz radiofrequency capacitive type heating device, i.e., Thermotron RF-8 and Cancermia. In all cases hyperthermia was given within 30 minutes after radiotherapy. Temperature was measured by inserting thermocouple into the tumor mass under the ultrasonographic guidance in all patients except for those who had bleeding tendency. As a result, PR was achieved in 12 patients (40%) and symptomatic improvement was observed in 22 patients (78. 6%) among 2S patients who had suffered from abdominal pain. The most significant factor affecting tumor responae rate was the type of tumor (single massive; 10/14, 71.4%, diffuse infiltrative; 2/10, 20%, multinodular; 0/6, 0%, P< 0.005>. There were not any significant side effects relating to combined treatment. Hepatic failure was the leading cause of death (5/11, 45.5%) and distant metastases were observed in 5 patients (one to brain, four to lung). In conclusion, combined hyperthermia and radiotherapy can be considered as an effective treatment modality in management of primary hepatocellular carcinoma.

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Urinary and Sexual Dysfunction after Abdominaoperineal Resection for Rectal Cancer: Hae Wan Lee, Jae Gahb Park, Sung Kuk Hong; J Korean Cancer Assoc. 1989;21(1):129-135.

Abstract PDF: It is well known that sexual dysfunction and bladder dysfunction, although sometimes transient, accompanies abdominoperineal resection of the rectum for carcinoma. Fifty-three patients has been evaluated with regard to sexual function and bladder function following abdominoperineal resection for rectal cancer in period 1980 to 1986. The results were as follows, 1) The overall incidence of urinary dysfunction was 58.5 percent (67.9 percent in men and 48.0% in women). 2) The most common urinary discomfort was increased frequency. 3) The extent of the disease is the most important factor related to urinary dysfunction. 4) The sex, circumferential position of tumor, distance of tumor from anal verge, and tumor size were found to be of no value as a prognostic index of postoperative bladder function. 5) The overall incidence of sexual dysfunction was 64.3 percent. 6) The extent of the disease is the most important factor related to sexual dysfunction. 7) The age, circumferential position of tumor, distance of tumor from anal verge, and tumor size were found to be of no value as a prognostic index of postoperative sexual function. 8) Correlation was found between postoperative sexual dysfunction and urologic problem.

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Two Cases of Primary Mediastinal Endodermal Sinus Tumor: Kee Chun Jean, Myeong Soo Lee, Doo Il Kim, Chang Hak Sohn, In Sook Lim; J Korean Cancer Assoc. 1989;21(1):135-141.

Abstract PDF: Primary mediastinal endodermal sinus tumor (or yolk sac tumor) is very rare and malignant tumor and has been reported by only several authors. Mediastinal endodermal sinus tumor located in anterior section is histologically compatible with endodermal sinus tumor located in genital tract. This tumor responds relatively well to chemotherapy and the pure form has the worst prognosis. We experienced 2 cases of primary mediastinal endodermal sinus tumor which affected 19yrs and 18yrs old males. The first patient has been treated with four cycles of BEP combination chemotherapy (cisplatinum, vp-16, Bleomycin) and followed by other treatment for brain metastasis, The 2nd patient received the 1st cycle of BEP chemtherapy and followed up.

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A Report of Two Cases of Leptomeningeal Carcinomatosis on Stomach Cancer: Dong Lip Kim, Jae Kyung Roh, Jin Hyuk Choi, Hyun Cheol Chung, Yong Jun Park, Won Ho Kim, Seung Min Kim, Jin Sik Min, Kwang Hwa Park, Chang Ok Suh, Jun Kyu Loh, Byung Soo Kim; J Korean Cancer Assoc. 1989;21(1):141-150.

Abstract PDF: Meningeal carcinomatosis is an important neurologic complication. It is increasingly being recog- nized as a cause of neurologic disability in life. But stomach cancer has rarely been reported to be a cause of meningeal carcinomatosis. We reported two cases of 46-year-old male and 56-year-oldfemale who were diagnosed gastric cancer by biopsy under fiberoptic gastroscopy. These two cases of stomach cancer with meningeal invasion revealed malignant cells in their cerebrospinal fluid by repeated lumbar puncture. After diagnosis, they were treated radiation therapy in whole brain field. And, now, we have the plan of intrathecal chemotherapy.

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Five Years Report for Cancer Register Programme in the Republic of Korea July 1 , 1982 - June 30 , 1987: Ministry of Health and Social Affairs; J Korean Cancer Assoc. 1989;21(1):151-217.

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