Abstract: BACKGROUND: Neoadjuvant chemotherapy has recently become common therapy for breast cancer. This work studied whether or not the effects of neoadjuvant chemotherapy can be predicted from morphological features of breast cancer in initial diagnostic imaging. MATERIALS AND METHODS: A total of 186 cases who underwent neoadjuvant chemotherapy at this hospital in 2006 were studied. Morphological features were classified into four categories. One is a type of invasive carcinoma that tends to grow along the mammary ducts (type A1), another is a type of expansively growing invasive carcinoma that is relatively well-defined (type A2), a third is a type of irregularly shaped mass that retracts surrounding tissue (type A3), and the fourth is a mixed type. Thus, the effects of neoadjuvant chemotherapy on carcinomas of the four types were compared on the basis of image and pathological findings. Effects of neoadjuvant chemotherapy were classified into three categories of enlarged mass, pCR, and other, with the latter indicating no change or shrinkage. RESULTS: Of the 186 total cases, 72 were classified as type A1, 31 as type A2, 52 as type A3, and 31 as a mixed type. Seven of 31 cases of type A2 (22.6%) were cases of an enlarged mass, revealing a high percentage of such cases. Dividing cases into type A2 and other types and looking at the proportion of cases of an enlarged mass thus indicated a significantly higher tendency. pCR was achieved in 6 of 31 cases with type A2 (19.4%). Here, also, the proportion of type A2 cases was significantly higher. CONCLUSION: Morphological features prior to neoadjuvant chemotherapy can contribute to determining the effects of the therapy. Expansively growing well-defined masses contain lesions at both extremes, tending to enlarge in some instances or instead allowing pCR, so the course of therapy must be carefully followed when performing neoadjuvant chemotherapy.

Abstract: BACKGROUND: Since microcalcifications classified as category 3 on mammography include not only malignant lesions but also benign lesions, it is difficult to decide whether stereotactic vacuum-assisted breast biopsy (Mammotome(R), MMT) should be performed or the patient should merely be follows. The purpose of this study is to adequately diagnose microcalcifications classified as category 3 and to formulate a correct clinical policy. In addition, we examined the characteristics of the calcifications. METHODS: This study included 51 patients who underwent MMT from July 2003 to October 2004. All the cases were evaluated as category 3, and no abnormal findings were detected on ultrasonography. We classified the pattern of calcifications based on three aspects: 1. density and size, 2. pleomorphic appearance 3. number of calcifications per square centimeter. RESULTS: Of the 51 patients, 14 were histologically diagnosed with ductal carcinoma in situ (DCIS). Heterogeneity in the density and size were observed in 9 of 14 patients (64.3%). The calcifications had a pleomorphic appearance in 6 of 14 patients (42.9%). A large number of calcifications (20/cm(2)) were observed in 8 of 14 patients (57.1%). Better examination characteristics were obtained with heterogeneity in density and size (AUC=0.72 95%C.I: 0.56-0.89) compared with pleomorphic appearance and the number of calcifications per square centimeter. The potential for malignancy was an average of 6 times higher for calcifications with heterogeneity in density and size compared to that for calcifications which were homogeneous in these aspects. CONCLUSION: Attention should be paid to prevent unnecessary mammotome procedures. Heterogeneity in the density and size of calcifications is a reliable criterion for clinical decision-making.

Abstract: PURPOSE: Detection of sentinel lymph node (SLN) metastasis in breast cancer patients has conventionally been determined by intraoperative histopathologic examination of frozen sections followed by definitive postoperative examination of permanent sections. The purpose of this study is to develop a more efficient method for intraoperative detection of lymph node metastasis. EXPERIMENTAL DESIGN: Cutoff values to distinguish macrometastasis, micrometastasis, and nonmetastasis were determined by measuring cytokeratin 19 (CK19) mRNA in histopathologically positive and negative lymph nodes using one-step nucleic acid amplification (OSNA). In an intraoperative clinical study involving six facilities, 325 lymph nodes (101 patients), including 81 SLNs, were divided into four blocks. Alternate blocks were used for the OSNA assay with CK19 mRNA, and the remaining blocks were used for H&E and CK19 immunohistochemistry-based three-level histopathologic examination. The results from the two methods were then compared. RESULTS: We established CK19 mRNA cutoff values of 2.5 x 10(2) and 5 x 10(3) copies/muL. In the clinical study, an overall concordance rate between the OSNA assay and the three-level histopathology was 98.2%. Similar results were obtained with 81 SLNs. The OSNA assay discriminated macrometastasis from micrometastasis. No false positive was observed in the OSNA assay of 144 histopathologically negative lymph nodes from pN0 patients, indicating an extremely low false positive for the OSNA assay. CONCLUSION: The OSNA assay of half of a lymph node provided results similar to those of three-level histopathology. Clinical results indicate that the OSNA assay provides a useful intraoperative detection method of lymph node metastasis in breast cancer patients.

Abstract: We report on the clinical significance of sentinel lymph node (SLN) biopsy in the 3 major visceral cancers for which these biopsies are performed. In cases of gastric cancer, the SLN concept was established from the viewpoint that QOL was clearly improved by a reduction in lymph node dissections or the extent of gastric resection. In such cases, it would be of great clinical significance if it was possible to determine the appropriateness of lymph node dissection. For colon cancer, SLNs are expected to become an indicator for lateral lymph node dissection in cases of rectal cancer, and to contribute to a more efficient diagnosis of micrometastasis. In cases of breast cancer, where SLN biopsies are already being used to determine axillary nodal status to obviate axillary lymph node dissection, SLNs also help to more accurately classify the stage of the disease. This helps in determining appropriate multidisciplinary treatment. Thus, SLNs help to promote the streamlining of cancer treatments, albeit the significance varies depending on the affected viscera. We therefore believe SLN research to be very important.

Abstract: We performed combined therapy with trastuzumab-vinorelbine for 6 HER2 positive metastatic breast cancer patients from which informed consent was obtained. As the initial dosage, we administered 4 mg/kg of trastuzumab, followed by a dosage of 2 mg/kg every week thereafter. At the same time, 25 mg/m2 of vinorelbine was administered for 2 weeks, followed by a week of rest. Total administration frequency of trastuzumab was 13-34 times (median: 27 times) and vinorelbine was 8-22 times (median: 17 times). A partial response was seen in 4 patients and no change in 2, for a response rate of 66%. A fixed period effect was recognized in each case, and the TTP was 112-274 days (median: 205 days). The side effects recognized were leukopenia of grade 3 in 1 patient, but she recovered during a withdrawal period. After that, continuous administration was possible. Trastuzumab-vinorelbine combined therapy expanded treatment alternatives for HER2 positive metastatic breast cancer patients and might prolong life.

Abstract: We have established a highly sensitive and quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) method to detect axillary lymph node metastases of breast cancer. Amplifying cytokeratin 19 (CK19) mRNA transcripts using real-time TaqMan PCR made it possible to quantify axillary metastatic burden. Metastases in 358 axillary lymph nodes obtained from 23 breast cancers of 22 patients were investigated by conventional haematoxylin and eosin (H&E) staining, immunohistochemical staining and quantitative RT-PCR assay. The detection rates of axillary lymph node metastasis using H&E staining, immunohistochemistry and RT-PCR assay were 4.5, 5.9 and 13.1%, respectively. RT-PCR assay was the most sensitive of these three methods for detecting lymph node metastases. Cytokeratin 19 mRNA expression values of both histologically and immunohistochemically positive lymph nodes were significantly higher than the values for lymph nodes judged to be negative by both histological and immunohistochemical methods (P<0.0001), and those of histologically negative, but immunohistochemically positive lymph nodes were significantly higher than the values for lymph nodes judged to be negative by both histological and immunohistochemical methods (P<0.0001). Furthermore, metastatic rates of sentinel nodes were higher than the rates of nonsentinel lymph nodes as measured by all three methods. These results indicate that quantitative RT-PCR assay is a sensitive and reliable method for detecting lymph node metastasis. Furthermore, quantification of metastases in sentinel lymph nodes by quantitative RT-PCR assay may be useful to assess the entire axillary burden of breast cancer patients.

Abstract: The patient was a 52-year-old woman who underwent left partial mastectomy on April 30, 1999. The stage was T0N1bM1 (bone). After operation, adjuvant therapy consisting of 6 cycles of CMF therapy and radiation was performed. On September 2000, the tumor marker (NCC-ST 439) was at a high level. On January 2001, chest CT examination revealed multiple lung metastases of the right lobe. Oral combination chemotherapy of 5'-deoxy-5-fluorouridine (5'-DFUR, 1,200 mg/day) and cyclophosphamide (CPA, 100 mg/day) was thus performed, and definite improvement resulted in the lung. No adverse reactions occurred except for anemia and thrombocytopenia of grade 1. It is suggested that this oral combination chemotherapy may be useful for advanced recurrent breast cancer patients and applicable in ambulatory chemotherapy administered with consideration for the patient's quality of life.

Abstract: BACKGROUND: It has become common to divide ductal carcinoma in situ (DCIS) of the breast into two main groups, comedo or noncomedo by tumor morphology. But noncomedo DCIS can be further stratified into several morphological patterns that exhibit several different growth patterns and most DCIS lesions have more than one pattern. In this study, DCIS elements were classified by morphological pattern and the association between predominant or recessive elements of DCIS lesions and clinicopathological findings was evaluated. METHODS: DCIS lesions from 46 patients were studied regarding the histological architectural patterns: comedo, cribriform, papillary, solid and micropapillary. The predominant architectural pattern which comprised more than 50% of the cells of the cancerous lesion was defined as the major element of the tumor and minor elements consisted of less than 50% but more than 25% of cells comprising the tumor. RESULTS: Of 24 tumors containing a comedo pattern as the major or minor element, 9 (38%) had microscopic intraductal spread over 2 cm and 11 (46%) had involvement of lobules, which was significantly higher than that observed in other types. Of 20 tumors containing a cribriform pattern as the major or minor element, 8 (40%) had microscopic intraductal spread over 2 cm and 9 (45%) had involvement of lobules, which was significantly higher than that seen in other types. Of 10 tumors containing a papillary type as the major or minor element, 5 (50%) had discrete multicentric lesions in the ipsilateral or contralateral breast, which was significantly higher than that seen in other types. CONCLUSIONS: DCIS lesions containing a comedo or cribriform element are more likely to have microscopic spread and involvement of lobules and DCIS lesions containing a papillary element are likely to be multicentric, whether the pattern are predominant in the tumor or not.

Abstract: We examined the feasibility of sentinel lymph node biopsy for thyroid cancer. Thirty-eight patients with papillary thyroid carcinoma underwent intraoperative lymphatic mapping and sentinel lymph node biopsy. At surgery, we exposed the thyroid gland and used a tuberculin syringe to inject 0.2 ml of 1% patent blue dye directly into the thyroid mass. The lymphatics and the lymph node dyed with blue dyes, was excised as a sentinel lymph node. Modified radical neck dissection was performed following sentinel lymph node biopsy and the diagnostic ability of sentinel lymph node biopsy was examined. A sentinel lymph node was identified successfully in 27 (71%) of 38 patients. Sentinel lymph node biopsy removed one to three lymph nodes (median, two nodes). Eighteen patients had paratracheal sentinel lymph nodes, five patients had jugular sentinel lymph nodes, and four patients had both. Histological nodal metastasis was recognized in 16 of 27 cases. The positive rate of cancer metastases in sentinel lymph nodes was 58%, which was significantly higher than 11% in non-sentinel lymph nodes. Diagnostic ability of sentinel lymph node biopsy showed that accuracy was 89%, sensitivity was 84%, and specificity was 100%. Our preliminary study indicated that sentinel lymph node biopsy was available on detection of non-palpable nodal metastasis in the patients with thyroid cancer; however, further experience and refinement are needed.

Abstract: BACKGROUND: Sentinel lymph node (SLN) biopsy is a promising method for the diagnosis of the axillary nodal status. We examined the availability of the SLN biopsy using two mapping procedures: the dye- and gamma probe-guided method, and preoperative lymphoscintigraphy by gamma camera imaging. METHODS: We enrolled 48 patients with breast cancer. Technetium-99m-labeled human serum albumin was injected into the subdermal tissue above the primary tumor or biopsy cavity, and preoperative gamma camera imaging was performed. After induction of general anesthesia, patent blue dye was injected into the peritumoral area prior to the surgical procedure. A handheld gamma-detection probe was used to assist in SLN detection. Careful dissection was performed to identify blue-stained afferent lymphatic vessels and nodes. An SLN was defined as any blue and/or radioactive node, and was excised. After SLN biopsy, axillary lymph node dissection of level I, II, and III was completed, in order to confirm the diagnostic ability of the SLN biopsy. RESULTS: Intraoperative SLN identification of axillary lesions was successful in 43 of 48 patients (90%). The dye- and gamma probe-guided method was successful in 25 patients (52%), the dye-guided method alone succeeded in 11 patients (23%), and the gamma probe-guided method alone succeeded in 7 patients (15%). Preoperative lymphoscintigraphy revealed axillary focal accumulations in 29 of 48 patients (60%). All patients who underwent successful preoperative SLN identification by lymphoscintigraphy had successful intraoperative SLN identification. A diagnostic accuracy of 95%, a sensitivity of 89%, and a specificity of 100% were achieved in the diagnosis of axillary metastasis. Internal mammary SLNs were identified in four patients intraoperatively, but we could not detect cancer metastasis in the internal mammary SLNs. CONCLUSIONS: The dye-guided and gamma probe-guided methods were complementary. Preoperative lymphoscintigraphy was useful to predict intraoperative SLN identification. Further study is necessary to assess the role of SLN biopsy of the internal mammary lymph nodes.

Abstract: BACKGROUND AND OBJECTIVES: Sentinel lymph node (SLN) biopsy is not usually performed with respect to the internal mammary lymph node chain. However, the SLN may be located in the internal mammary chain, particularly with medial lesions. We carried out this study to investigate whether lymphatic mapping and SLN biopsy can detect internal mammary involvement in patients with breast cancer. METHODS: A dye- and gamma probe-guided SLN biopsy was performed in a consecutive series of 41 patients with tumor in situ or clinical stage I or II breast cancer. After the biopsy, these patients underwent either a modified radical mastectomy or breast-conserving surgery including axillary lymph node dissection. Biopsy of internal mammary lymph nodes was performed in 19 of these patients. RESULTS: No involvement of internal mammary lymph nodes was found histologically in 5 patients in whom lymphatic flow or a "hot nodule" in the internal mammary chain was found using lymphoscintigraphy. Nodal involvement was demonstrated histologically in only 1 of 5 cases where lymphatic vessels showed dye staining or faintly stained nodes. Internal mammary lymph node biopsy also was performed in 14 of 36 patients with neither stained lymphatic vessels or nodes, nor with lymphatic flow or a hot nodule by lymphoscintigraphy. Nodal involvement was found histologically in 1 of these patients. CONCLUSION: SLN biopsy guided by lymphatic mapping is unreliable for identifying metastases to internal mammary lymph nodes.

Abstract: Several pilot studies have indicated that SLN biopsy can be used to identify axillary lymph node metastases in patients with breast cancer. To confirm this finding, a multicenter study in a variety of practice settings was performed. A total of 674 patients with breast cancer at five institutions were enrolled. The techniques of SLN identification included the vital dye-guided and the vital dye- and gamma probe-guided methods. The SLN was removed, and complete axillary lymph node dissection (ALND) was performed. SLN and ALND specimens were examined separately. The SLN was successfully identified in 214 (94%) of 227 patients using the combined dye- and gamma probe-guided methods. The SLN was identified in 332 (74%) of 447 patients using vital dye-guided method alone. Patient age of at least 21 years, medially located primary tumor, and clinically positive nodes were correlated with failure to identify the SLN. The accuracy of SLN biopsy for the detection of metastatic disease was 96% (522 of 546), and the sensitivity was 90% (203 of 226). Accuracy of 100% was achieved in the patients with tumors less than 1.6 cm in diameter. All 23 false negative results occurred with larger primary tumors. SLN biopsy can accurately predict the presence or absence of axillary lymph node metastases, particularly in patients with small (< or = 1.5 cm) breast cancers.

Abstract: Sentinel lymph node (SLN) biopsy is a useful way of assessing axillary status and obviating axillary dissection in patients with node-negative breast cancer. A combination of dye- and gamma probe-guided methods can identify SLN more accurately and easily than either of these techniques alone. On the other hand, SLN biopsy is highly accurate and sensitive in patients with small tumors, and no false-negative SLN biopsy has been reported for a breast cancer < 1.0-1.5 cm. Moreover, extensive intraoperative examination of SLNs using frozen sections can attain a sensitivity comparable to that obtained by histologic examination on the permanent sections. In practice, therefore, axillary dissection can be avoided in patients with small tumors in whom the SLNs are negative.

Abstract: The authors examined the survival rates of 60 patients with breast cancer who underwent parasternal lymph node biopsy during surgery with axillary lymph node dissection and had histologically confirmed axillary node metastasis followed by adjuvant doxorubicin- or mitoxantrone-containing combination chemotherapy to ascertain whether administration of anthracycline or its analogue improved the prognosis of both axillary and parasternal node-positive patients. The overall survival rate (OS) for the parasternal node-positive patients (n=13, 21.7%) was 30.6%, and relapse-free survival rate (RFS) fell to 0% at the 104-month follow-up. Although the survival rate for all axillary node-positive patients was similar to those in previous reports, the OS and RFS for both axillary and parasternal node-positive patients were significantly worse than that for axillary node-positive and parasternal node-negative patients, despite treatment with adjuvant doxorubicin- or mitoxantrone-containing combination chemotherapy. Other intensive adjuvant treatment strategies are needed to reduce distant metastases for high-risk breast cancer patients having both axillary and parasternal nodes positive.

Abstract: BACKGROUND: The purpose of this study was to determine the feasibility of sentinel lymph node (SLN) biopsy using blue dye with or without isotope localization to predict the presence of axillary and internal mammary lymph node (IMN) metastases in patients with breast cancer. We also investigated whether multiple sectioning of the SLN could improve the accuracy of frozen section examination. METHOD:One-hundred twenty-six patients underwent dye-guided or dye- and gamma probe-guided SLN biopsy followed by complete axillary lymph node dissection (ALND). No ALND was performed in the 14 patients with small tumors and a negative SLN. In addition, 69 patients underwent IMN biopsy. RESULTS: The axillary SLN was identified in 123 of 140 (88%) patients. An accuracy rate of 90% was obtained by frozen section examination of the SLN, which increased to 100% in patients examined with a greater number of sections. Lymphatic flow to the IMN and/or a radioactive hot spot in the IMN was found in 9 of 102 (9%) patients, while a hot node was detected using a gamma probe in only 2 of these patients. No involvement of the IMNs was found histologically in these 9 patients. IMN involvement was found in 7 of 61 (11%) patients without lymphatic flow to the IMNs or a hot spot by lymphoscintigraphy or who did not undergo lymphoscintigraphy. CONCLUSION: ALND can be avoided in patients with small breast cancers and a negative SLN. SLN biopsy guided by lymphatic mapping is unreliable for identifying metastases to IMNs.

Abstract: BACKGROUND: Breast conserving treatment (BCT) is accepted as an appropriate therapy for most patients with stage I and stage II breast cancer. However, BCT is associated with a relatively high incidence of local recurrence, and aesthetically unacceptable results occur in some patients. A novel method of immediate volume replacement using autogenous tissue has been developed to strike a balance between adequate excision and cosmesis. We determined the oncological outcome inpatients with breast cancer treated with wide excision, immediate volume replacement with autogenous tissue, and axillary dissection followed by radiotherapy. METHODS: One hundred fifty-three patients with TIS, stage I, II, or III breast cancer underwent wide excision and axillary dissection. The surgical margin ofexcised breast tissue was examined histologically during surgery. If involved, the breast tissue adjacent to the primary site was excised. When the margin of re-excision was positive, patients underwent modified radical mastectomy with or without breast reconstruction. After wide excision, immediate volume replacementwith autogenous tissue was perform-ed, unless the deformity was corrected by undermining and conization of the residual breast tissue. Postoperatively, all patients received breast irradiation. RESULTS: Eighteen patients underwent modified radical mastectomy. The surgical margin was negative in 132 of the 135 patients who underwent BCT. The crude local recurrence rate was 0.7% (1/135). Estimated overall and disease-free 5-year survival rates were 96% and 94%, respectively. CONCLUSION: Wide excision with tumor-free margins and axillary dissection followed by breast irradiation provides adequate local control in many patients with breast cancer. Immediate breast volume replacement with autogenous tissue mayavoid some unpleasant cosmetic results associated with extensive local resection. Our technique eliminates the need for mastectomy in selected patients.

Abstract: Sentinel lymphadenectomy is a useful way of assessing axillary status and obviating axillary dissection in patients with node-negative breast cancer. However, controversies remain concerning the optimal method to identify the sentinel lymph node (SLN) and detect micrometastases in this lymph node. We reviewed the literature concerning sentinel lymphadenectomy in breast cancer and reached the following conclusions: (a) A combination of preoperative lymphoscintigraphy with intraoperative dye-guided and gamma probe-guided methods achieves a higher rate of identification of SLN than any of these techniques alone. (b) Immediate and reliable intraoperative assessment of sentinel node status is vital to the technique's success. However, the reliability of sentinel node diagnosis using frozen sections is questionable, because micrometastatic foci cannot always be identified. (c) Hematoxylin and eosin (H&E) staining and/or immunohistochemistry on permanent sections are useful for the detection of micrometastases in the sentinel node. Although a reverse transcriptase-polymerase chain reaction (RT-PCR) method is more sensitive than H&E staining and immunohistochemistry, it would not distinguish benign from malignant epithelial cells in the SLN. Therefore, further study is required before sentinel lymphadenectomy gains general acceptance for patients with primary breast cancer.

Abstract: Seventy-two patients underwent dye-guided or dye- and gamma probe-guided sentinel lymphadenectomy (SLND) followed by complete axillary lymph node dissection (ALND). The results of imprint cytology, frozen sections, and permanent sections of the sentinel lymph node (SLN) were compared to each other and to the histologic findings in the nonsentinel nodes. The SLN was identified in 62 (88%) of 72 patients. Evaluation of the SLN on the permanent sections yielded a diagnostic accuracy of 95%, a sensitivity of 89%, and a specificity of 100%, although the reliability of SLN diagnosis using frozen sections or imprint cytology is limited. Therefore, it may be concluded that SLND with multiple sectioning and histopathologic examination of the SLNs can predict the presence or absence of axillary-node metastases in patients with breast cancer. However, further studies will be needed to investigate the value of SLND in respect to the long-term regional control and any possible detriment or benefit to survival, before it can replace routine ALND as the preferred staging operation for operable breast cancer.

Abstract: A phase II pilot study was carried out on 30 patients to ascertain the toxicity and efficacy of combination chemotherapy with mitoxantrone, methotrexate, 5-fluorouracil (NMF) in the adjuvant setting for axillary lymph node-positive breast cancer. The NMF regimen was mitoxantrone 10 mg/m2, methotrexate 40 mg/m2, and 5-fluorouracil 600 mg/m2 administered i.v. on day 1, repeated every 3-4 weeks for 6 cycles. The median nadir WBC count was 2,000/microl; grade 4 leukocytopenia occurred only in 1 patient. Nausea and vomiting appeared as grade 0 and 1 severity in 26/30 patients. Alopecia was extremely mild, appeared as grade 0 and 1 in 29/30 patients. The overall and relapse-free survival rates were 67.8% and 68.4% at the 82-month follow-up, respectively. The overall survival rate in premenopausal patients was significantly better than that in postmenopausal patients (P<0.05). NMF is a well-tolerated combination regimen, suitable as adjuvant chemotherapy for node-positive breast cancer.

Abstract: We examined amplification of the c-met, c-erbB-2, and epidermal growth factor receptor (EGFR) gene in the patients with primary gastric cancer, and compared the data with clinical features in order to clarify the relationship between oncogenic abnormality and clinical features. Oncogene amplifications were examined by slot blot hybridization using DNAs extracted from formalin-fixed and paraffin-embedded tissues of primary gastric cancers. Seven of the seventy cancers (10.0%) had c-met gene amplification, nine (12.9%) had c-erbB-2 gene amplification, and six (8.6%) had EGFR gene amplification, respectively. Eighteen cases (25.7%) exhibited one or multiple oncogene amplification, and two cases (2.9%) exhibited simultaneous amplification of the three genes. The cases with c-met gene amplification tend to show invasive character and were related to peritoneal dissemination. The cases with c-erbB-2 gene amplification were related to lymph node metastasis. The cases with EGFR gene amplification had large tumors and were in highly advanced stage. The survival rate in patients with oncogene amplification was significantly lower than that in patients without amplification. Our data indicated that these genes were related to growth and metastasis of gastric cancer. Furthermore, this study about the three genes suggested that the type of activated gene might decide on the type of metastasis and clinical features.

Abstract: Prognostic significance of c-erbB-2 gene abnormalities is unclear in the poorly differentiated type of gastric carcinoma, because the abnormalities of this gene have been reported to be restricted to the differentiated type of gastric carcinoma. In this study, correlation of c-erbB-2 gene amplification/overexpression of mRNA and protein were studied in the poorly differentiated type of gastric carcinoma. c-erbB-2 gene amplification determined by the slot-blot hybridization was observed in 11 (13%) of 82 gastric cancer, and 8 of 11 tumors were poorly differentiated. In addition, c-erbB-2 mRNA expression was studied by the reverse transcriptase-polymerase chain reaction. Four (17%) of 24 tumors showed overexpression of c-erbB-2 mRNA, and all these four exhibited morphologically a poorly differentiated type. Among 157 poorly differentiated gastric cancers, 20 (13%) tumors showed immunohistochemically c-erbB-2 protein expression. These tumors had significantly higher incidences of larger tumor, serosal invasion-positive tumors, node-positive tumor, or peritoneal dissemination-positive tumor than those without c-erbB-2 expression. Furthermore, patients with c-erbB-2 protein overexpression ran poorer prognoses than those without c-erbB-2 expression. From these results, we conclude that expression c-erbB-2 tissue status may be a good prognostic indicator in poorly differentiated gastric carcinoma.

Abstract: We reviewed the literature concerning sentinel lymphadenectomy in breast cancer and reached the following conclusions: (a) A combination of lymphoscintigraphy and dye-guided and/or gamma probe-guided techniques are superior to either technique alone for identifying the sentinel lymph node. (b) lmmediate and reliable intraoperative information on the sentinel node is vital for the technique's success. However, the reliability of sentinel node diagnosis using frozen sections is questionable, because micrometastatic foci cannot be identified. (c) A reverse transcriptase-polymerase chain reaction(RT-PCR)method is more sensitive than immunohistochemistry for the detection of micrometastasis in the sentinel node. (d) Until there are new tumor markers or new imaging techniques to identify axillary metastasis without operative intervention, sentinel lymphadenectomy is a highly accurate, minimally invasive way to assess disease extent. Before sentinel lymphadenectomy gains general acceptance for patients with primary breast cancer, however, a large clinical trial will be essential to verify the value of this technology.

Abstract: Preventing local recurrence and preserving cosmetic appearance are often in conflict in breast-conserving therapy. Immediate volume replacement with autogenous tissue has been developed to allow a wider excision without compromising the aesthetic results. A review of the literature regarding immediate volume replacement in breast-conserving therapy has led to the following conclusions. When excision of the skin overlying the tumor is unnecessary, a transverse or lateral incision should be used which allows wide excision and immediate volume replacement with autogenous tissue while minimizing scar morbidity. The options for immediate volume replacement include the latissimus dorsi flap with adipose tissue, the latissimus dorsi myocutaneous flap, and the lateral thoracic adipose tissue flap. The choice of technique depends on the amount and position of the skin, subcutaneous tissue, and breast tissue which must be excised. These procedures can be used to extend the indications for breast-conserving therapy, eliminating the need for mastectomy in selected patients. Future developments in the endoscopic harvesting of flaps may further expand the role of volume replacement.

Abstract: BACKGROUND: Sentinel lymphadenectomy has been used to assess the axillary nodal status in patients with breast cancer in an attempt to avoid unnecessary axillary dissection. Most studies have examined the utility of this procedure in clinically node-negative patients. However, the clinical evaluation of axillary nodes is often inaccurate for both clinically node-negative and clinically node-positive patients. METHODS: We performed dye-guided sentinel lymphadenectomy in both clinically node-negative and clinically node-positive patients with breast cancer. All patients also underwent a formal axillary dissection. The results of imprint cytology, frozen sections, and permanent sections of the sentinel lymph node (SLN) werecompared with each other and with histologic findings of the nonsentinel nodes. RESULTS: The SLN was identified in 30 (79%) of 38 patients with clinically negative nodes, and in 11 (92%) of 12 patients with clinically positive nodes. Forclinically node-negative patients, SLN evaluation yielded a diagnostic accuracyof 90%, a sensitivitiy of 72%, and a specificity of 100%. For clinically node-positive patients, these values were 100%, 100% and 100%, respectively. These values were not significantly different for the two groups of patients. CONCLUSION: Sentinel lymphadenectomy may be useful in assessing the axillarynodal status of both clinically node-positive and clinically node-negative breast cancer patients.

Abstract: We reviewed the literature regarding internal mammary lymph node metastasis in the management of breast cancer. Internal mammary dissection or radiotherapy provides no survival advantage in breast cancer patients. However, internal mammary nodal metastasis is an important independent prognostic factor. Patients with such metastases are candidates for systemic adjuvant hormonal therapy and/or chemotherapy. Moreover, in patients with histologically confirmed internal mammary metastases, irradiation of the nodes is appropriate for local control. Noninvasive techniques, such as internal mammary lymphoscintigraphy, parasternal sonography, computed tomography, and magnetic resonance imaging, are not satisfactory for the practical diagnosis of internal mammary metastasis. At present, biopsy of the internal mammary nodes in the first and second intercostal spaces is indicated for assessing nodal status and planning treatment.

Abstract: BACKGROUND: The most common cause of noncurative resection and recurrence is gastric cancer is peritoneal seeding. However, the results of treatment of peritoneal dissemination with chemotherapy have been poor with 5-year survival rates of 0%. METHODS: A new in vitro thermochemosensitivity test was performed on gastric cancer cells obtained from 19 surgically resected specimens by using tetrazolium-based colorimetric assay (MTT assay). A novel treatment of the intraoperative chemohyperthermia was undertaken in 83 patients with gastric cancer with peritoneal dissemination. After aggressive resection of primary tumor, lymph nodes, and peritoneal metastases, warmed saline solution containing mitomycin C 30 mg, etoposide 150 mg, and cisplatin 300 mg was introduced into the peritoneal cavity via a closed circuit continuous hyperthermic peritoneal perfusion (CHPP) for 60 minutes to keep the abdominal temperature at 42 degree to 43 degrees C by means of a heat exchange mechanism. RESULTS: The in vitro thermochemosensitivity test that 43 degrees C enhanced the cytotoxin effects on gastric cancer cells under clinically achievable drug concentrations. During CHPP, drug concentrations of cisplatin, mitomycin C, and etoposide in the perfusate remained statistically higher than in the peripheral venous circulation. Among 43 evaluable patients with residual peritoneal seeding, eight (19%) and nine (21%) exhibited complete response and partial response, respectively. The overall 1- and 5-year survival rates were 43% and 11%, respectively. Patients who underwent complete resection survived significantly longer than those with residual disease, and those with complete response had a significantly better prognosis than did those with partial response, and nonresponders. One-year survival rates with complete response, partial response or nonresponders were 88%, 27% and 22%, respectively. Five patients survived longer than 5 years. Conclusions: Our triple treatment combining surgery and CHPP is an effective therapy for selected patients with gastric cancer with peritoneal dissemination.

Abstract: In 88 resected patients with esophagus-invading gastric cancer, the factors determining the prognosis of this disease were investigated by multivariate analysis. Neither, age, sex, macroscopic type, thoracotomy, nor histological type proved to be independent prognostic factors. The presence or absence of lymph node metastasis, serosal invasion, tumor size, and the extent of esophageal invasion were found to be significant independent prognostic factors. Among lymph node metastases, involvement of para-aortic lymph nodes was especially important. The prognosis was significantly better in cases in which these nodes were carefully dissected (R4 gastrectomy), than in cases in which selected dissection was performed (R2). However, no patient with mediastinal lymph node metastasis survived for any lengthy period, and thus the mediastinal lymph nodes seemed to be nodes, the dissection of which brought little effect. Postoperative results were very poor in cases in which the extent of the esophageal invasion was 3 cm or more. These patients should be treated with multi-modal therapy such as neoadjuvant chemotherapy.

Abstract: One-hundred and sixty-four patients with gastric carcinomas, who underwent gastrectomy during 1979-1985, were studied. The nuclear DNA contents were measured by cytofluorometry, and immunohistochemical study on the expression of c-erbB-2 protein was performed using a monoclonal antibody against the c-erbB-2 oncogene product. Furthermore immunohistochemical detection of proliferating cell nuclear antigen (PCNA) was performed using a monoclonal antibody against the PCNA. The patients with aneuploid tumor had a significantly worse prognosis than those with diploid tumor. The group with positive staining for c-erbB-2 had a significantly worse prognosis than negative one. The higher group of PCNA indices had a worse prognosis. The patients with tumor showing both aneuploid and positive staining for c-erbB-2 tissue status and PCNA indices. But no correlation was formed between c-erbB-2 tissue status, PCNA indices and DNA contents. From these results, it can be concluded that DNA ploidy, c-erbB-2 protein, and PCNA may reflect the malignant potential of gastric carcinoma.

Abstract: We encountered a case of non-curatively resected gastric cancer (p1, n4) who responded well to sequential MTX/5-FU therapy and PMUE therapy. A 63-year-old man was admitted to our hospital with complaints of nausea and vomiting. Upper gastrointestinal examination and CT scan revealed Borrmann type 3 gastric cancer with pyloric stenosis and multiple paraaortic lymphnodal metastasis. The patient underwent palliative gastrectomy for extensive gastric cancer (H0, P1, N4, T3, Stage IV b). Histological examination of the resected stomach revealed poorly differentiated adenocarcinoma with paraaortic lymphnodes metastasis (n4) and peritoneal dissemination (p1). Chemotherapy with sequential MTX/5-FU was given 13 times. Ten months after the operation, abdominal pain and back pain required analgesic treatment. Abdominal CT scan revealed increased size of paraaortic lymphnodes, suggesting recurrence. Sequential MTX/5-FU therapy was switched by PMUE therapy. Lymphnode size became smaller and habitual analgesics could be discontinued. Since then he was given MTX/5-FU and PMUE therapies alternately on an ambulant basis. The patient resumed his daily activities at 2 years and 8 months after the operation.

Abstract: The correlation between the clinical features in 103 patients with primary gastric carcinoma and amplification of epidermal growth factor receptor (EGFR) gene was analyzed retrospectively. EGFR gene amplification was examined by slot-blot hybridization using DNA extracted from formalin-fixed, paraffin-embedded tissues. EGFR expression was also examined immunohistochemically using the same tissues with a monoclonal antibody that is monospecific for EGFR. In 5 of 103 cases (4.9%), a 2- to 11-fold amplification of EGFR gene was detected. Four of these 5 cases were poorly differentiated adenocarcinomas. All of them had overexpressions of EGFR. The cumulative survival rate of patients with EGFR gene amplification was significantly lower than that of the patients without amplification (p < 0.05) and all of them died within 3 years. Except for tumor size (p < 0.03), there were no significant clinicopathologic differences between the two groups. On the other hand, 41 of 103 cases (39.8%) exhibited expression of EGFR. However, there was no significant correlation between EGFR expression and clinicopathologic factors or prognosis. These results indicate that EGFR gene amplification may occur in advanced stages during the progression and be an important indicator of poor short-term prognosis in gastric carcinoma.

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Abstract: We performed continuous hyperthermic peritoneal perfusion (CHPP) or continuous normothermic peritoneal perfusion (CNPP) combined with cisplatin (CDDP) 300 mg/kg and mitomycin C (MMC) 30 mg/kg in an attempt to prevent peritoneal recurrence after surgery for gastric cancer. Twenty-two patients were treated with perfusion using about 10 liters of saline heated to 41 degrees to 42 degrees C (CNPP group); 18 patients were treated with saline heated to 37 degrees to 38 degrees C (CNPP group); and 18 patients underwent only gastric surgery without perfusion (control group) in a randomized control study. There were two deaths (9%) due to peritoneal recurrence in the CHPP group, four (22%) in the CNPP group, and four (22%) in the control group. The 1-, 2-, and 3-year survival rates were 95%, 89%, and 68%, in the CHPP group; 81%, 75%, and 51%, in the CNPP group; and 43%, 23%, and 23%, in the control group, respectively. There was a significant difference between the three survival curves by the log-rank test (p < 0.01). This difference showed that CNPP and CHPP are both effective procedures for preventing peritoneal recurrence. The maximum concentrations in the perfusate of total and free CDDP with 300 mg administration were 12.2 and 10.1 micrograms/ml, respectively, at the end of the perfusion, and the maximum concentrations of total and free CDDP in plasma were 2.1 and 1.0 micrograms/ml, respectively. The maximum concentrations of MMC in perfusate and plasma with 30 mg administration were 1.00 and 0.05 micrograms/ml, respectively, which are intraperitoneally cytotoxic but systemically safe concentrations.

Abstract: In spite of recent advances in the early diagnosis of gastric cancer by mass screening, gastric stump cancers following gastrectomy are still diagnosed at a highly advanced stage, and the surgical results remain very poor. Involvement of the fourth level lymph node stations, local peritoneal carcinomatosis and tumor growth invading the neighboring organs are frequently observed in advanced stump cancers. With the aim of achieving complete resection of these tumors, left upper abdominal evisceration (LUAE) + R4 gastrectomy was performed in 29 patients (Group B) with stump cancer as a radical surgical procedure. The survival of these patients was compared with that of 74 patients (Group A) who underwent total gastrectomy with or without pancreaticosplenectomy. Duration of surgery blood loss, and incidence of postoperative complications were similar with the two methods. When the survival rates were compared, the 5-year-survival rate in stage IV cases was higher for Group B than for Group A. LUAE + R4 gastrectomy is a rational technique for the surgical treatment of stage IV gastric stump cancer.

Abstract: Because gastric cancers located in the upper third of the stomach are difficult to detect at an early stage, the surgical results remain poor. We performed R4 gastrectomy as a radical procedure for 25 patients, involving complete resection of the latero-aortic and interaorticovenous lymph modes above and below the left renal vein, in combination with the ordinary R2 or R3 gastrectomy (the R4 group). These patients were compared with 156 others who underwent R2 gastrectomy alone (the R2 group). There were no significant differences in operation time, blood loss, or the incidence of complications between the two groups; however, when the survival rates of the patients with tumors invading beyond the subserosa were compared, the 5-year survival rate was found to be significantly higher in the R4 group than in the R2 group. Furthermore, in patients with para-aortic nodal involvement, a significant survival advantage was observed in the R4 group, as compared with the R2 group. These results suggest that the R4 gastrectomy is a rational approach for patients with advanced gastric cancer located in the upper third of the stomach.

Abstract: Cell proliferation of 174 specimens obtained from the primary gastric cancers using endoscopic biopsy was investigated by immunohistochemical analysis with the monoclonal antibody PC10, which recognizes a proliferating cell nuclear antigen (PCNA) in formalin-fixed and paraffin-embedded material. All the examined samples showed nuclear staining for PCNA in cancer cells. The investigation was to test the correlation between PCNA labeling and lymph node metastasis. DNA aneuploidy was often encountered in tumors with nodal involvement and lymphatic invasion. The logistic regression analysis identified PCNA labeling rates (LRs), tumor size, and macroscopic type as independent significant factors for lymph node metastasis. When the PCNA LRs and clinicopathologic parameters were entered into the Cox regression analysis, PCNA LRs and DNA ploidy emerged as independent significant prognostic factors. In addition, combination assay of PCNA LRs and DNA ploidy yielded a powerful prognostic indication for patients with gastric cancer.

Abstract: The incidence of metastases from gastric stump cancer to various regional lymph node stations was studied after meticulous node dissection in 87 patients, who had undergone curative resection. Fifty-five (63%) patients had microscopically involved nodes. The incidence of node metastases varied between 17% and 30% in the perigastric nodes (n 1), with the same incidence in second-station lymph nodes (n 2; nodes along the left gastric, common hepatic and splenic artery, or nodes at the splenic hilus) With respect to third-station lymph nodes (n 3), metastases in nodes in the hepatoduodenal ligament (No 12) and retropancreatic nodes (No 13) were found only in 2% and 8% of the cases, respectively, but there was a high incidence of metastases (14/54, 31%) in the nodes along the mesenteric root. The overall 5-year survival rate was 48% and those for n 1 and n 2 patients were 78%, and 41%, respectively. With regard to the third level lymph node station, no 5-year survivors were seen when there was nodal involvement in node station No. 12 or No. 13. However, involvement of nodes at the root of the mesentery was associated with a 5-year survival rate of 25%. These results suggest that resection of the second level lymph nodes station must be combined with total gastrectomy and distal pancreatectomy, and that the resection of the mesenteric root is very important in patients with a tumor invading the jejunum.

Abstract: One-hundred and sixty-four patients with gastric carcinomas, who underwent gastrectomy during 1979-1985, were studied. Sixty-five of these cases were early gastric carcinomas, and the others were advanced gastric carcinomas, and the others were advanced gastric carcinomas. The nuclear DNA contents were measured by cytofluorometry, and immunohistochemical study on the expression of c-erbB-2 protein was performed using a monoclonal antibody against the c-erbB-2 oncogene product. Furthermore, immunohistochemical detection of proliferating cell nuclear antigen (PCNA) was performed using a monoclonal antibody against the PCNA. The rates of positive invasion beyond submucosal layer, lymphatic invasion, and vascular invasion in aneuploid cases were significantly higher than those in diploid ones, and the patients with aneuploid tumor had a significantly worse prognosis than those with diploid tumor. The rates of positive lymph node metastases and invasion beyond submucosal layer in the group with positive staining of the c-erbB-2 protein was significantly higher than in the negative group, and the group with positive staining for c-erbB-2 had a significantly worse prognosis than the negative one. PCNA indices showed a significant correlation with lymph node metastasis, and the group with higher PCNA indices had a worse prognosis. The patients with tumor showing both aneuploid and positive staining for c-erbB-2 protein, had the worst prognosis. There is a relationship between c-erbB-2 tissue status and PCNA indices, but no correlations were found among c-erbB-2 tissue status, PCNA indices and DNA contents. From these results, it can be concluded that DNA ploidy, c-erbB-2 protein, and PCNA may reflect the malignant potential of gastric carcinoma.

Abstract: We analyzed immunohistochemically the association between p53 tissue status and prognostic parameters of 357 gastric cancer patients, using endoscopically obtained biopsy materials, embedded in paraffin. Using PAb1801, an anti-p53 monoclonal antibody p53 immunoreactivity was detected in the nuclei of cancer cells in 113 cases (32%). The nuclear p53 immunoreaction was closely associated with positive lymph node metastasis, serosal invasion, and liver metastasis. For the estimation of proliferative activity, proliferating cell nuclear antigen (PCNA) labeling rates (LRs) of biopsy specimens were immunohistochemically measured. A significant positive correlation was found between PCNA LRs and p53 tissue status. In addition, a positive nuclear p53 immunoreaction was found to be significantly associated with shorter overall survival. Especially, in the group of patients with stages III and IV, the prognosis of patients with p53-positive tumours was significantly poorer than that of patients with p53-negative tumours. These results indicate that immunohistochemical staining for nuclear p53 in biopsied materials may be useful in deciding the therapeutic schedule of patients with gastric cancer, preoperatively.

Abstract: Distal pancreatectomy combined with total gastrectomy for gastric carcinoma was evaluated in regard to the availability and quality of life for patients. We performed a question-naire survey of their daily life, especially regarding postpancreatectomy diabetes, for 67 patients passed 5 years after total gastrectomy inclusive of five cases without pancreatectomy as control. Eleven cases developed diabetes mellitus which needed insulin injection after distal pancreatectomy excluding three patients with glucose intolerance before operation. These were 19% of cases performed pancreatectomy, while there was no diabetes in cases without pancreatectomy. The incidence of postpancreatectomy diabetes was 60 per cent of the cases which underwent Appleby operation (65% pancreas resection), while it was 50 percent of the cases which underwent total gastrectomy combined with distal pancreatectomy (50% resection). There is significant difference at < 0.05 level. The incidence of postpancreatectomy diabetes was increased as passing of years after operation. These results suggest that distal pancreatectomy combining total gastrectomy improves the prognosis of patients with nodal metastasis. But considering the occurrence of postpancreatectomy diabetes, it should be emphasized the adequate indication is needed for the operation, and close and long-term follow up is essential for keeping QOL.

Abstract: c-erbB-2 gene amplification was examined by slot blot hybridization using DNAs extracted from formalin-fixed and paraffin-embedded tissues of primary gastric carcinomas. Eleven of the 82 carcinomas (13.4%) exhibited amplification. Twenty-eight carcinomas (34.1%) expressed c-erbB-2 protein immunohistochemically. All of the tumors with amplified c-erbB-2 genes had expression of c-erbB-2 protein. The incidence of diploid and aneuploid tumors with c-erbB-2 gene amplification was similar. The survival rate was significantly lower in cases with c-erbB-2 gene amplification. Furthermore, patients with tumors showing a combination of c-erbB-2 gene amplification and DNA aneuploidy had the poorest prognosis. c-erbB-2 gene amplification may be an important prognostic indicator in gastric carcinomas.

Abstract: An in vitro chemosensitivity study of both biopsy specimens and surgically resected tumors of advanced gastric cancer from 12 patients was evaluated using the succinate dehydrogenase inhibition (SDI) test. A decrease in succinate dehydrogenase (SD) activity as an indicator of chemosensitivity was determined using cisplatin (CDDP), etoposide (VP-16), and mitomycin C (MMC). In this study, 29 of a total 36 experiments were evaluable (80.6%) and significant correlations were found in all three of the antitumor drugs (P < 0.03). This finding suggests that the SDI test using biopsy specimens may prove valuable for assessing the preoperative chemosensitivity of advanced gastric cancer.

Abstract: For the prediction of nodal status of early gastric cancer, sections of formalin-fixed, paraffin-embedded tissue from 220 early gastric cancers were analyzed immunohistochemically, using a polyclonal antibody against erbB-2 protein. The data of erbB-2 protein expression have been correlated with pathologic data, and a logistic regression analysis was made for the estimation of the significant factors responsible for lymph node metastasis. A pattern consistent with cell membrane staining was regarded as most specific for the erbB-2 expression. There were 22 (10%) cancers with evidence of erbB-2 protein expression. Positive staining was associated with only lymph node metastasis. The risk of lymph node metastasis was 3-fold greater in tumors having erbB-2 protein expression than in tumors without the expression. When the erbB-2 tissue status and clinicopathological parameters were entered into the logistic regression analysis, erbB-2 protein expression emerged as one of the independent significant factors for lymph node metastasis. These results indicate that early gastric cancer with erbB-2 protein expression may represent a potential risk of lymph node metastasis.

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Abstract: An immunohistochemical study for transforming growth factor-alpha (TGF alpha) and epidermal growth factor receptor (EGFR) was made with 167 primary tumors of advanced gastric cancer to demonstrate the potential existence of autocrine mechanism. TGF alpha stained positively in 87 (52%), and EGFR in 68 (41%) of the tumors. The authors classified the tumors into the following three groups: group 1 with neither TGF alpha nor EGFR staining positively (63 tumors); group 2 with either TGF alpha or EGFR staining positively (53 tumors); group 3 with both TGF alpha and EGFR staining positively (51 tumors). The incidence rates of macroscopically infiltrative tumors and large tumor measuring 6 cm or more in diameter were significantly higher for group 3 than for groups 1 and 2. The patients of group 3 had the poorest prognosis, with a 5-year survival rate of only 12%, while the 5-year survival rates were 45 and 36% for groups 1 and 2. There was a significant difference in survival between the patients of group 1 and those of group 3. Bromodeoxyuridine labeling indices were significantly higher in the tumors belonging to group 3 (median 15.8%) than in those of group 1 (median 10.8%). The results suggest that the autocrine mechanism between TGF alpha and EGFR may play an important role in the progression of gastric cancer, and that when such a mechanism becomes operative, prognosis may be poor.

Abstract: CDDP, MMC, UFT and Etoposide (PMUE)-combined therapy was given to a 62-year-old man with advanced gastric carcinoma. PMUE therapy consists of i.v. injection of CDDP 75 mg/m2 and MMC 10 mg/body on day 1, i.v. injection of Etoposide 50 mg/body on days 3, 4 and 5 and consecutive daily administration of UFT 400 mg/body, with 3 weeks as one course. He was admitted for Borrmann type 3 gastric carcinoma with multiple liver metastasis, lymph node metastases and peritoneal dissemination, the underwent total gastrectomy with R2 lymph node dissection. He was treated four times with this therapy after sensitivity test for carcinostatic agents (SDI test), which resulted in complete remission, as confirmed by CT scan and second-look operation. The patient has currently been free of disease, and we conclude that this PMUE therapy is extremely effective for advanced gastric carcinoma.

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Abstract: Expression of proliferation associated nuclear antigen P-105 was examined with flow cytometry in forty-three patients with advanced gastric cancer. Expression of P-105 was observed abundantly in cancer, about four times than normal mucosa, but little in normal gastric mucosa. We evaluated the expression of P-105 in cancer as P-105 intensity: mean FITC levels of G0G1 of the cancer cells/those of normal cells. The P-105 intensity did not correlate with DNA index or S-phase fraction. Furthermore, it did not correlate with histologic type, stromal type, infiltrating type, and gross appearance. However, P-105 intensity was significantly higher in the patients with hepatic metastasis, and lower in those with peritoneal dissemination than those without metastasis, respectively. From the results, it was supposed that P-105 intensity might be a useful indicator for metastatic type different from those previously reported in human gastric cancers.

Abstract: Anti-p105 monoclonal antibody was used to discriminate between M-phase and G2-phase of gastric cancer cells. p105 is a proliferation-associated nuclear antigen and its expression increases with cell cycle progression, especially in the mitotic phase. As an example of cell cycle analysis, the modes of action of etoposide and podophyllotoxin were examined by multiparameter flow cytometry. We found that etoposide caused G2 block and retarded S phase transit and podophyllotoxin caused potential M phase block in gastric cancer cells. This cell cycle analysis by using anti-p105 monoclonal antibody should be useful for analysis of the actions of anti-tumor agents, especially for M phase analysis, because of its convenience and reliability.

Abstract: Thermochemotherapy was performed on gastric cancer cases of hepato-metastasis. The subjects were 12 gastric cancer cases having hepato-metastatic lesions (10 synchronous, 2 heterochronous). Using 8 or 13.58 MHz-dielectric heating apparatus, thermotherapy was carried out for 40-60 min (twice a week, 5-35 times, averaging 12.8 per case) at an intra-tumoral temperature greater than 42 degrees C. Chemotherapy consisted of hepato-arterial infusion of MMC 10 mg/BW, CDDP 75 mg/m2 once per 3-4 weeks and consecutive daily administration p.o. of UFT 800 mg/BW. Effect greater than PR was noted in 75% (9/12) on the whole and in 100% (5/5) and 57% (4/7) for H1-2 and H3, respectively. Mean and 50% survival periods were 9.3 and 7.2 months, respectively, with a one-year survival rate of 38%. Chemotherapy-induced side effects were nausea and vomiting in 83% and leukopenia and thrombopenia in 67%, while the only thermotherapy-induced side effect was subcutaneous fatty tissue necrosis in 3 cases. The above results suggested the effectiveness of the present thermochemotherapy in the treatment of hepato-metastasis of gastric cancer.