Eradication of microscopic metastases with intratumoral injection of bacillus Calmette-Guerin

The studies reported here were designed to examine the effects of intratumoral preoperative administration of Bacillus Calmette-Guerin (BCG) on the cure rates of C3H mice transplanted with MH134 tumor cells and on the metastatic rates in the regional lymph nodes. Furthermore, the morphological findings occurring in the regional lymph nodes were monitored during tumor growth using H-E stain and non-specific esterase staining. The cure rate of the Group treated with BCG intratumoral injection and surgery was significantly higher than that of the Group treated with surgery alone, and in the BCG + surgery group metastatic rates of regional lymph nodes decreased consistently after operation. Moreover, in this group, extensive sinus histiocytosis and marked swelling of the regional nodes were frequently observed. Quantitative studies of the cell kinds using the esterase staining indicated that intratumoral injection of BCG has an effect on the influx of lymphoid cells into the regional nodes, but does not aid specific cell lineage to flow into the regional nodes. In cytostatic assays, it was shown that the regional lymph node cells and spleen cells in the BCG + surgery group always have a greater per cent of inhibition than those in the surgery alone group.     

Role of lymph node density in predicting survival of patients with lymph node metastases after radical cystectomy: A multi-institutional study

Objectives:   To evaluate the prognostic role of different clinico-pathological parameters in node-positive patients treated by radical cystectomy.
Methods:   A retrospective multi-institutional study of 435 patients who underwent radical cystectomy between 1990 and 2005 was carried out. Of them, pathological lymph node (LN) metastases were found in 83 patients. Sixty of these 83 patients, whose clinical information and follow-up data were available, were included in the analysis. Twenty-five patients had undergone adjuvant chemotherapy, whereas 35 had not. A Cox proportional hazards model was used to determine the impact of the following clinico-pathological parameters on patient survival: number of resected LNs, number of positive LNs, LN density (defined as the ratio of the number of positive LNs divided by the total number of resected LNs) and adjuvant chemotherapy.
Results:   Median follow-up for surviving patients was 41 months (range 4–138) after surgery. The median survival time for all patients was 22 months (95% confidence interval, 15–42 months). At multivariate analysis, LN density of 25% or less, adjuvant chemotherapy and pure urothelial carcinoma were independently significant predictors of survival.
Conclusions:   Lymph node density predicts survival in patients with node-positive bladder cancer.     

The impact of lymph node metastases on the survival of breast cancer patients with ten or more positive lymph nodes

To investigate the impact of the number of involved lymph nodes on survival, we retrospectively reviewed the data for 37 patients with breast cancer and metastases of ten or more lymph nodes who underwent treatment between 1987 and 1995. Based on the number of positive lymph nodes, the patients were allocated to one of three groups. The 5-year disease-free and overall survival rates for all patients were both 53.0%. The 7 patients with 26 or more positive nodes had significantly poorer survival than either the 19 patients with 10–15 nodes, or the 11 with 16–25 nodes, although there were no differences in survival related to the extent of node involvement as defined using the Japanese staging system. Patients with 50%–75% frequency of metastasis, defined as the positive nodes/total resected nodes, had significantly better survival than those with <50% or >75% frequency. These results indicate that the number of involved lymph nodes is related to survival and that 25 positive nodes is a cutoff point in breast cancer patients with ten or more positive lymph nodes.     

Mode of lymph node metastases in esophageal cancer induced in rabbits with Vx2 carcinoma

We carried out experimental studies in which Vx2 carcinoma was inoculated submucosally into the esophagi of 57 rabbits. The purpose was to clarify the mode of tumor growth and lymph node metastasis of esophageal cancer. The inoculation was given into five different segments of the esophagus and the cardia in six different groups of rabbits: the cervical (Ce), the cervicothoracic junction (Ce=Iu), the upper thoracic (Iu), the middle and lower thoracic (ImEi) and the abdominal (Ea) segments and the cardia (C). The lymph node metastatic pattern of the Vx2 carcinoma was then observed. The Ce and Ce=Iu located carcinomas metastasized mainly above the tracheal bifurcation; the ImEi located carcinomas metastasized equally above and below the tracheal bifurcation. In cases of the Ea and C located carcinomas, the lymph node metastasis was restricted to the abdomen when serosal invasion was excluded but it spread widely from the abdomen to the neck when serosal invasion was positive. Thus, in experimentally-induced carcinoma, tracheal lymph node metastasis occurred with a high frequency. As intraoperative assessment is closely related to anatomical factors and operative risk, care should be taken that such assessments are thoroughly carried out.     

Analysis of mucosal bladder leucocyte subpopulations in patients treated with intravesical Bacillus Calmette-Guerin

Summary Immunohistochemical techniques were used to investigate leucocyte subpopulations in the bladders of patients with superficial transitional cell carcinoma treated with BCG Pasteur. Leucocyte subsets were enumerated with a panel of monoclonal antibodies which included CD3, CD4, CD8, TQ1, Leu7, CD15, HLA-DR, CD25, CD22. We demonstrated in the bladders of patients treated with BCG a particular lymphocyte population; the major subset was an inducer (CD4⁺, TQ1^-) which was activated (CD25⁺, HLA-DR⁺) and associated with polymorphonuclear eosinophils. There was neither inducer of suppression nor major cytotoxic/suppressive subsets. CD8⁺ and NK cells could not be the primary mediators of BCG activity. These data supported the hypothesis of a helper T lymphocyte activity associated with lymphokine production and activation of effector killer cells.     

The treatment of squamous cell carcinoma of the tonsil with neck node metastases

BACKGROUND: Patients with tonsillar carcinoma and neck nodes seen at the clinic are not an uncommon occurrence in head and neck practice. Over the years, treatment has ranged from radical jaw neck dissection to radical neck dissection for the nodes and primary radiotherapy to the primary site. Much controversy exists as to which treatment modality yields the best survival. Certainly, surgery to the oropharynx leads to gross morbidity, with problems of swallowing, speech, and cosmesis, although it has been claimed that radiotherapy with neck dissection yields a lower cure rate. METHODS: We investigated a retrospective series of 96 patients all of whom had squamous cell carcinoma of the tonsil and associated lymph node metastases. Of these, 44 primary tumors were treated with surgery and 52 with irradiation. All 44 patients in the surgery group had a radical neck dissection, as did all but 12 in the radiotherapy group. RESULTS: Of the tabulations, patients in good general condition were more likely to receive primary surgery. Overall cause-specific survival for all patients was 69%. Multiple logistic regression revealed no associations; thus, the radiotherapy and surgery groups were well matched. Five-year actuarial survival for those having irradiation was 74%. The five-year survival for the group receiving surgery was 63% (p =.4372). This lack of difference between survival for surgery and radiotherapy was confirmed using Cox's proportional hazards model. CONCLUSION: We conclude that tonsillar carcinoma with lymph nodes can be safely treated by applying appropriate radiotherapy to the tonsillar region and treating the neck with radical surgery, if the disease is more than N1.     

Long-term follow-up results of breast cancer patients with sentinel lymph node biopsy using periareolar injection

Background

Areolar injection for sentinel lymph node biopsy (SLNB) in breast cancer surgery has been adopted by many institutions. However, only one study has reported the follow-up results for patients whose SLNB was performed with this injection method alone.

Methods

Three hundred eighty patients with breast cancer underwent SLNB with periareolar injection of both blue dye and radiotracer. The follow-up consisted of a physical examination every 3 months and annual mammography.

Results

Of 380 patients with SLNB, 261 were found to have negative sentinel lymph nodes so that no ALND was performed. At a median follow-up of 39 months (range 13-74), 2 of the 261 patients developed axillary recurrence for an axillary relapse incidence of .77%. Five-year distant disease-free survival was 96.9%, and overall survival was 99.4%.

Conclusions

The incidence of axillary recurrence for the areolar injection method was low and consistent with that reported in other observational studies using other injection methods.     

The relationship of p53 Protein and lymph node metastases in invasive breast cancer

The p53 expression in invasive breast cancers from 106 patients was correlated with clinicopathological variables to ascertain its usefulness for estimating prognosis. The p53 expression was significantly associated with the number of axillary lymph node metastases and the presence of internal mammary lymph node metastases; however, it was not associated with age, menopausal status, histologic type, or tumor size. Although p53 expression was a significant prognostic factor according to univariate analysis, it did not appear to be an independent prognostic factor according to multivariate analysis. Thus, the prognostic power of p53 expression is likely to be weak and therefore probably of limited clinical value. Nevertheless, the number of patients in our study was small, and we believe that an investigation of a larger series of patients is indicated.     

Androgen receptor status of lymph node metastases from prostate cancer

To date androgen receptor (AR) expression and structure in human prostatic cancer have been studied in primary tumor specimens and in cell lines. Investigation of alterations in the androgen-signalling transduction cascade in prostatic carcinoma metastases is important to improve our understanding of tumor progression towards androgen insensitivity. In the present study we have collected data comparing AR expression in both the primary tumors and the respective pelvic lymph node metastases. Formalin-fixed and paraffin-embedded tissues derived from the primary tumors and positive lymph nodes of 12 patients undergoing radical prostatectomy were immunostained for the AR and prostate-specific antigen (PSA). AR expression was evaluated with the polyclonal antibody PG-21, which is directed against amino acids 1–21 in the N-terminal region of the AR. All primary tumors stained for the AR. In 8 of the 12 lymph nodes examined more than 50% of the tumor cells were AR positive and displayed a uniform staining pattern; in one lymph node metastasis remarkable heterogeneity in AR expression was observed. In two cases less than 10% of the tumor cells stained for the AR. In one case the lymph node metastasis was immunohistochemically negative for the AR, whereas the primary tumor obtained from the same patient displayed intense staining for the AR. PSA was expressed in all metastases and primary tumors. Our data demonstrate that loss of the AR in lymph node metastases from prostatic carcinoma is a rare event. © 1996 Wiley-Liss, Inc.     

Tumour size as a predictor of axillary node metastases in patients with breast cancer

BACKGROUND: The ability to predict the behaviour of breast cancer from its dimensions allows the clinician to inform a woman about the absolute benefits of adjuvant therapies or further surgery to control her disease. Tumour size and grade are independent predictors of nodal disease. This study aims to generate a tool, using Australian data, allowing surgeons to calculate the probability of axillary lymph node involvement in a preoperative setting. METHODS: The histological reports of patients with breast cancer treated in 1995 in New South Wales were examined and tumour size, grade and nodal status recorded. Univariate and multivariate analyses identified predictors of node positivity and, using linear regression analysis, a simple formula to predict nodal involvement was derived. RESULTS: In a 6-month period, 754 women had non-metastatic, unifocal breast cancer treated with surgery and complete axillary dissection and 283 (37.5%) had positive nodes. Tumour size remained an independent predictor of node positivity and the probability (%), y, of nodal involvement may be predicted by the formula y = 1.5 x tumour size (mm) + 7, r = 0.939 and P = 0.001. CONCLUSIONS: This paper shows the need to assess the axilla in every patient because even patients with small tumours (0-5 mm) have the possibility of axillary involvement (7-14.5%). Use of this simple formula allows clinicians and patients to make informed decisions about the possible need for a full axillary dissection to reduce the chance of understaging and potentially undertreating a woman's breast cancer.     

乳腺癌原发灶及淋巴结转移灶中表皮生长因子受体、C-erbB-2的表达及临床意义

目的 探讨乳腺癌原发灶和淋巴结转移灶中表皮生长因子受体（EGFR）、C-erbB-2的表达及其与肿瘤类型、肿瘤分期的关系.方法 选择行手术治疗且术前均未行抗癌治疗,术后病理证实无同侧腋窝淋巴结转移的乳腺癌患者24例,伴有同侧腋窝淋巴结转移的乳腺癌患者36例,用免疫组化S-P法检测原发灶和淋巴结转移灶EGFR、C-erbB-2的表达.结果 有同侧腋窝淋巴结转移的乳腺癌原发灶EGFR、C-erbB-2的表达明显高于无同侧腋窝淋巴结转移的乳腺癌.乳腺癌原发灶EGFR、C-erbB-2的表达呈正相关（P=0.01）.原发灶和淋巴结转移灶之间的EGFR、C-erbB-2的表达无相关性.原发灶EGFR、C-erbB-2的表达在不同的肿瘤分期存在差异.浸润性导管癌和浸润性小叶癌之间EGFR、C-erbB-2的表达无差异.结论 乳腺癌细胞淋巴结转移的过程中由于体内某种机制的作用导致了恶性程度的变化;EGFR、C-erbB-2的表达正相关并共同促进了乳腺癌的淋巴结转移;原发灶EGFR、C-erbB-2的表达与肿瘤的分期呈正相关.     

Intramammary sentinel lymph node in patients with breast cancer: Report of four cases

To analyze breast cancer patients with intramammary sentinel lymph node, we reviewed T1-T2N0 breast cancer patients who underwent sentinel lymph node mapping using radioisotope methods. Intramammary sentinel lymph (ISN) nodes were detected in 4 of 166 patients. Three of four ISNs were present in completely different quadrants of the breast from those of primary lesions. Although two patients had no involved nodes, including ISNs, the remaining two with T2 tumor had metastasis of ISNs alone with resulting upstaging. We should keep in mind the presence of intramammary SN in regions apart from the primary tumor, particularly when performing breast conservative surgery.     

Localization of the sentinel node in breast cancer: identical results with same-day and day-before isotope injection

Background:Although the technique of sentinel lymph node (SLN) biopsy in breast cancer is not fully standardized, an increasing number of centers map the SLN by using radioisotope supplemented by blue dye, and most have injected isotope on the day of surgery. Here we directly compare the results of same-day and day-before isotope injection in a large series of breast cancer patients having SLN biopsy with our mature technique.Methods:Starting with our 961st SLN procedure for breast cancer, 1320 consecutive patients had SLN biopsy after the injection of unfiltered ^99mTc-labeled sulfur colloid given as a single-site, low-volume (0.05 ml) intradermal injection: 933 on the day of surgery (1-day protocol) and 387 on the day before (2-day protocol). All had intraparenchymal injection of blue dye.Results:The two groups were comparable in age, tumor location, histopathologic characteristics, and number of SLNs identified. LSG taken at 2 hours in the 2-day protocol was positive more often than LSG performed at 30 minutes in the 1-day protocol, and nonaxillary sites of lymphatic drainage were seen in <1% of each group. Absolute isotope counts and the ratio of SLN to axillary background counts were similar. Isotope localization of the SLN succeeded in a comparable fraction of patients, as did SLN identification overall.Conclusions:The results of SLN mapping with same-day and day-before injection of radioisotope are virtually identical. The logistical advantages of day-before injection do not compromise the success of the procedure.Presented at the 54th Annual Meeting of the Society of Surgical Oncology, Washington, DC, March 15–18, 2001.     

Retroperitoneal lymph node dissection in patients with interaortocaval lymph node metastases of transitional cell carcinoma of the urinary tract

Three patients suffered from renal pelvic, ureteral and bladder cancers that were treated with both standard surgical treatments and two adjuvant cycles of cisplatin-based combination chemotherapy. Metastases of interaortocaval lymph nodes were detected in all patients between 9 and 33 months from the surgery for primary lesions. All patients received three cycles of cisplatin-based combination chemotherapy and retroperitoneal lymph node dissection (RPLND). The chemotherapy achieved partial response (62-98%). Two patients with viable cancer cells died with hepatic metastases; the first 15 months and the second 25 months from the date of diagnosis of distant lymph node metastasis. The third patient, who had no viable cancer cells, remains alive and disease-free 36 months later. Therefore, RPLND after chemotherapy provides prognostic information that helps to define patients who might benefit from additional systemic chemotherapy.