Uninvolved Nodes Research Articles

Cytoreductive Surgery in Ovarian Cancer: Why, When, and How?

Retrospective evidence supports the value of optimal cytoreductive surgery in the initial therapy of patients with advanced ovarian cancer. Specialized procedures, including radical pelvic surgery, bowel resection, and diaphragm resections, are frequently necessary to accomplish optimal cytoreduction. Cytoreduction and total gross tumor removal are possible more frequently with new surgical instruments such as the Cavitron ultrasonic surgical aspirator and argon beam laser. Pelvic and periaortic lymph node resection is an important aspect of cytoreductive surgery, and systematic removal of grossly uninvolved lymph nodes may improve survival. Secondary cytoreductive surgery appears to benefit a select group of patients.

Long-term follow-up of elderly patients with operable breast cancer treated with surgery without axillary dissection plus adjuvant tamoxifen.

Between 1982 and 1990, 321 elderly patients (range 70-92 years, median age 77) with operable breast cancer (T1 in 219, T2 in 77, T3 in one and T4b in 24 patients) and clinically uninvolved axillary nodes underwent surgery without axillary dissection and received adjuvant tamoxifen. All patients had surgery performed under local anaesthesia. Tamoxifen was given after surgery at the dose of 20 mg daily, indefinitely. With a median follow-up of 67 months (range 42-141), 17 patients developed local relapse, 14 ipsilateral axillary recurrence, five ipsilateral breast cancer, five contralateral breast cancer, 13 second primary and 23 developed distant metastases. The cumulative probability of developing a local, axillary and distant recurrence at 72 months was estimated to be 5.4%, 4.3% and 6.2%, respectively. Out of 244 patients who did not develop any relapse, 83 (25.8%) died from intercurrent disease. The 72 month relapse-free survival rate was 76%. This experience suggests that elderly patients with small tumours without clinical axillary involvement may be satisfactorily treated with conservative surgery and tamoxifen. The importance of axillary dissection is controversial owing to a high response rate to hormonal therapy and an increased death rate due to concomitant diseases.

Where exactly does failure occur after radiation in head and neck cancer?

Loco-regional recurrence in squamous cell carcinoma of the head and neck can occur at the site of the original primary tumour or in the marginal zone at its periphery. While nodal recurrence may occur in previously involved nodes or in uninvolved nodes within or outside the treatment volume. The exact site of failure was determined in 89 patients treated with radical radiotherapy for carcinoma of the head and neck. Of 73 patients who failed at the primary site 71 (97%) did so within the site of the original tumour; only two patients developed a marginal recurrence. Of the 30 (93%) patients with N1–3 disease who later showed failure in the lymph nodes, 28 (93%) did so at their original site of disease. These results support the view that when radiation fails it usually does so in the centre of the tumour. In order to improve our results we need to deal with radioresistance at the site of mass disease. Ways of approaching this include the combination of surgery with radiotherapy, the addition of a sensitiser or an increase in the dose to the tumour mass by boosting a ‘mini’ volume using conformal techniques.

シゾフィランの所属リンパ節への影響

The effects of preoperative Sizofiran (SPG) administration on cellular immunity in regional lymph nodes were studied in patients with head and neck cancer and compared with the effect on circulating lymphocytes in peripheral blood. SPG enhanced im-munological activities in the regional lymph nodes, as shown by increased cytotoxic activities of the effector cells and increased helper T lymphocytes and effector cells in the lymph nodes. The tumor-involved lymph nodes treated with SPG contained significantly fewer cytotoxic effector cells with decreased cytotoxic activities and fewer helper T lymphocytes than did uninvolved lymph nodes treated with SPG. The LAK cells derived from the regional lymph node, especially from the tumor-uninvolved nodes which were previouly treated with SPG were thought to have higher cytotoxic activities than those not treated with SPG.

Diagnostic and prognostic significance of clonal T‐cell receptor beta gene rearrangements in lymph nodes of patients with mycosis fungoides

In this study, 25 involved and uninvolved lymph nodes from 22 patients with mycosis fungoides (MF) and seven dermatopathic lymph nodes from patients with benign skin disorders were studied for the presence of clonal T-cell receptor beta (TCR beta) gene rearrangements by Southern blot analysis. These results were correlated with the histological classification, follow-up data, and survival. The results of the histological classification and Southern blot analysis were concordant in 26 of 32 cases. Clonal TCR beta gene rearrangements were found in all six MF lymph nodes showing (partial) effacement of the normal lymph node architecture, but in none of the eight uninvolved dermatopathic MF lymph nodes and in none of the seven dermatopathic control lymph nodes. In addition, in 5 of 11 dermatopathic MF lymph nodes that were considered to have early involvement by MF at histological examination, clonal TCR beta gene rearrangements were detected. In the group of MF patients with dermatopathic lymphadenopathy, patients with detectable clonal T-cell populations had a significantly shorter survival than patients without such a population (P < 0.01). The results of this study indicate that within the group of dermatopathic MF lymph nodes, prognostically different groups can be distinguished and that TCR beta gene rearrangement analysis may be an important adjunct in the early diagnosis of lymph node involvement by MF.

Pathologic correlates of prognosis in lymph node-positive breast carcinomas

Many pathologic features of breast carcinomas have been proposed as prognostic correlates; their interrelationships and their relative value as prognostic indicators were studied. A series of 399 axillary lymph node-positive infiltrating ductal breast carcinomas was studied histologically and compared with the patient prognosis. Many pathologic findings fit into two groups of closely related features--those related to the extent of local spread and those related to histologic anaplasia and mitotic count. Both groups correlated with the primary tumor size. The best predictors of long-term survival were measures of the extent of axillary metastasis (the number of axillary metastases, the size of the largest metastasis, and lymph node capsular invasion), which are components of the pathologic node stage. The mitotic count, tumor grade, primary tumor stage, smooth tumor border, tumor necrosis, and multifocal primary tumors were weaker but significant survival correlates. The mitotic count and Bloom-Richardson grade best predicted the survival time of patients with node-positive disease who died. Four years after diagnosis, less than 25% of the patients who would die of breast carcinoma in the low mitotic count and Bloom-Richardson Grade 1 (well differentiated) groups already had died; more than 75% of those in the high mitotic count and Bloom-Richardson Grade 3 (poorly differentiated) groups already had died. Among patients with small tumors (< 1.8 cm in diameter), those with one micrometastasis (1-2 mm) had a worse prognosis than those with uninvolved lymph nodes of similar size. The extent of axillary metastasis best predicted the long-term prognosis of patients with infiltrating ductal carcinoma and axillary metastases. The mitotic count and tumor grade best predicted the survival time of those who died.

The importance of interpectoral nodes in breast cancer

In a consecutive series of 73 patients undergoing a level III axillary clearance, interpectoral nodes were sought and, if palpable, excised. 18 interpectoral nodes were identified in 15 patients, 10 (14%) of whom had involved and 5 of whom had uninvolved interpectoral nodes. 7 of the 10 patients with involved interpectoral nodes also had axillary node involvement, but 3 patients had positive interpectoral nodes in the absence of involved axillary nodes. A comparison of patient and tumour characteristics in the groups of patients with and without interpectoral node involvement showed that patients who had involved interpectoral nodes were significantly younger and had significantly larger tumours. Interpectoral node involvement by breast cancer is not uncommon and these nodes can be involved in the absence of axillary nodal involvement. They should be looked for, and if identified, excised during axillary clearance.

Squamous cell carcinoma of the nasal vestibule.

We reviewed 30 patients with squamous cell carcinoma of the nasal vestibule to present our experience of their management and to evaluate the prognostic factors that may influence their outcome. For T1 lesions radiotherapy remains the treatment of choice, because of the superior cosmetic result. Fifteen (68 per cent) out of 22 patients with T2 lesions were treated with primary radiotherapy. Surgery however, was eventually required in 16 (72 per cent) out of 22 patients, either as a primary treatment (seven patients) or as salvage surgery (nine patients). For the larger T3 lesions the treatment of choice is surgery followed by post-operative radiotherapy where appropriate. Regional nodal metastases at the time of presentation were a significant indicator of local and regional recurrence and of prognosis. The cause specific five-year survival for patients with an uninvolved neck (22 patients) was 100 per cent compared with 38 per cent for patients with nodal metastases at presentation (eight patients). Elective treatment for uninvolved regional nodes is not considered necessary.

Variation in mantle technique: implications for establishing priorities for quality assurance in clinical trials

74 European and American radiotherapists responded to a questionnaire investigating the treatment of a patient with stage IIA non-bulky Hodgkin's disease by mantle irradiation. A consensus was present for the dose aims to involved and uninvolved lymph nodes and the acceptable incidence of late normal tissue effects. There was less agreement as to the total dose and dose per fraction required to maintain normal tissue toxicity within the agreed acceptable incidence. Variation was found in the radiation technique employed, the amount of spinal cord shielding used, the prescription point, modifications if irradiation was given after chemotherapy, and the routine recording of dose and dose per fraction to the normal tissue at risk. This descriptive survey confirms the need for well designed quality assurance programmes and indicates the areas of particular uncertainty that currently exist.

Bacterial Translocation in Patients Undergoing Elective Colorectal Surgery

Bacterial translocation from the gastrointestinal tract into the mesenteric lymph nodes was studied in 39 patients operated on for colorectal carcinoma and in eight patients operated on for non-malignant colorectal diseases. Bacterial translocation was more common into lymph nodes with metastatic carcinoma than in uninvolved lymph nodes in patients with colorectal tumours and in lymph nodes from patients with benign colorectal diseases. More aerobic grampositive cocci were isolated from uninvolved lymph nodes than from involved lymph nodes and aerobic gram-negative rods were only recovered from uninvolved lymph nodes. There were more anaerobic strains found in the involved nodes compared to the uninvolved nodes. Postoperative infections related to the surgical procedure occurred in one patient. Measurable concentrations of cefoxitin, cefuroxime and metronidazole were found in the lymph nodes of the patients receiving these antimicrobial agents. Keywords: Bacterial translocation; Colorectal carcinoma; Elective surgery.

Functional and Phenotypic Analysis of Lymphocytes in Head and Neck Cancer

We compared the phenotype and antitumor effector function of lymphocytes obtained from tumor tissues, lymph nodes, and the peripheral blood of patients with head and neck cancer. Freshly isolated tumor-infiltrating lymphocytes were deficient in CD4+ T cells in comparison with lymph node lymphocytes (LNL) and peripheral blood lymphocytes. A significantly higher CD4/CD8 ratio observed in LNL vs tumor-infiltrating lymphocytes and peripheral blood lymphocytes was attributable to both a significant enrichment in CD4+ T cells as well as a decrease in CD8+ T cells. The percentage of natural killer cells (CD3-CD56+) was uniformly low in both tumor-infiltrating lymphocytes and LNL. In patients with cervical metastases, LNL contained an increased proportion of CD16+ cells. Tumor-involved lymph nodes were not enriched in the CD8+C11b+ subset of T "suppressor" lymphocytes compared with uninvolved lymph nodes. Also, tumor-involved lymph nodes had significantly fewer CD4+ T cells than did uninvolved lymph nodes. In comparison with peripheral blood lymphocytes, freshly isolated tumor-infiltrating lymphocytes and LNL were depleted of cytotoxic effector cells, as indicated by low or absent cytotoxic activity against tumor cell targets. The ability to generate lymphokine-activated killer cells was significantly reduced in LNL in comparison with peripheral blood lymphocytes. In patients with head and neck cancer, depressed local and regional antitumor responses are associated with a deficiency of functional cytotoxic effector cells rather than an increase in suppressor T lymphocytes.

EFFECTIVENESS OF CHEMOTHERAPY AND RADIOTHERAPY IN WALDEYER'S RING NON-HODGKIN'S LYMPHOMA

This paper reported the effectiveness of chemotherapy combined with radiotherapy in Walde-yer's ring non-Hodgkin/s lymphoma. 40 Gy to 60 Gy were given to Waldeyer's ring and involved cervical nodes, Uninvolved low cervical nodes received 30 Gy to 40 Gy. The chemotherapy consisted of COP regimen (cyclophosphamide, VCR and prednisone) or COPP regimen (cyclophosphamide, VCR, prednisone and procarbazine) . Complete remission was 78.8% (26/33 cases) . 5-year disease-free survival was 69.0% (20/29cases) . The survival was better in patients with. stage I, II, III (80.0%) than those with stage IV (0) . Owing to the high incidence of distant metastasis, combinaton of chemotherapy and radiotherapy was primarily used in the treatment of Wald-eyer's ring non-Hodgkin's lymphoma in this study. The result was preliminary and further therapeutic study was needed. Key words: Chemotherapy; radiotherapy; Waldeyer's ring non-Hodgkin's lymphoma

C-erbB-2 protein overexpression in breast cancer is a risk factor in patients with involved and uninvolved lymph nodes.

The c-erbB-2 gene is overexpressed in about 20% of human breast cancers. Four hundred and eighty-three cases previously examined by immunohistochemical staining for c-erbB-2 expression were analysed to assess the risk associated with the elevated protein expression. Oncoprotein expression was correlated with increasing tumour grade but not with oestrogen receptor status, nodal involvement, tumour size or age. There was an increased risk of relapse and death associated with c-erbB-2 expression irrespective of nodal involvement. This marker thus appears to be a significant prognostic factor in the early as well as the late stages of breast cancer.

Rhabdomyosarcoma of the larynx in children: A series of five patients treated in the Institut Gustave Roussy (Villejuif, France)

Rhabdomyosarcoma of the larynx is a malignant disease rarely seen in children. We present five cases (3 males, 2 females) observed among 126 patients with rhabdomyosarcoma of the head and neck (excluding the orbit) treated in the Institut Gustave-Roussy between 1955 and 1981. The patients were aged between 5 1/2 years and 13 1/2 years at the time of diagnosis. The presenting symptoms were dysphonia and/or dyspnea; tracheotomy was required in two cases. All five patients received chemotherapy consisting of vincristine, cyclophosphamide, actinomycin D + procarbazine or doxorubicin. Four patients also received radiotherapy (45 Gy during 5 weeks). Laryngectomy was not performed. Treatment sequelae included regional hypoplasia, huskiness, and subclinical thyroid insufficiency; two patients developed a benign thyroid adenoma. One patient presented a bilateral carotid stenosis subsequent to radiotherapy performed on "wide fields" portal designed to provided prophylactic treatment on uninvolved lymph nodes. All the patients are alive and relapse-free with a follow-up of between 13 and 17 years. This small series of RMS of the larynx shows that patients can be cured without laryngectomy, although long-term sequelae associated with radiotherapy are observed.

The absence of lymphoid suppressor cells in tumor-involved lymph nodes of patients with head and neck cancer

Patients with head and neck cancer often have decreased local or regional immunocompetence. Lymphocytes obtained from tumor-involved or -uninvolved lymph nodes (LNL) of these patients showed low or undetectable levels of antitumor cytotoxicity and low proliferative responses in vitro to interleukin 2 (IL2) or mitogens in comparison to peripheral blood lymphocytes (PBL). Lymphokine-activated killer (LAK) cell activity of LNL was lower ( P < 0.05) than that of autologous PBL. Fresh LNL were neither enriched in cells with the CD8 +CD1 1b + “suppressor” phenotype nor did they suppress proliferative or cytotoxic responses of autologous PBL in mixing experiments. LNL did not inhibit LAK cell generation from autologous PBL in the presence of IL2. Also, no evidence for the inhibition of autotumor-restricted responses by IL2-activated LNL was obtained. Spontaneous or in vitro-induced production of IL1β, TNFα, and IFN-τ was low or undetectable in LNL from tumor-involved and -uninvolved lymph nodes in comparison to that in normal or autologous PBL. Mitogen-induced IL2 production was normal in LNL. The depressed ability to produce certain cytokines may be in part responsible for a state of unresponsiveness present in lymph nodes obtained from patients with head and neck cancer. No evidence for the presence of lymphoid suppressor cell in LNL of these patients was obtained.

Preoperative radiation therapy in regionally localized stage III non-small cell lung carcinoma: Long-term results and patterns of failure

Seventy-four patients from January 1975 through December 1982, with clinical Stage III M o non-small cell carcinoma of the lung were treated at our Medical Center with a course of pre-operative radiation therapy to be followed by surgical resection. Radiation therapy consisted of delivering a total dose of 40 Gy with 200 cGy per fraction over a period of 4 weeks to the primary tumor in the lung and the regional lymph nodal areas. Surgical resection was attempted 4 weeks later. Fifty-eight percent of the patients had squamous cell carcinoma whereas the remaining had other histologies like adenocarcinoma, large cell carcinoma, or a combination thereof. All the patients except two were followed up to a minimum of 5 years or until death. Sixty-four patients (82%) had T 3 tumors whereas mediastinal nodal involvement was found in 41 patients (55%). Fifteen patients (20%) did not have the operation because of tumor progression, patient's refusal or death. All but two surgically treated patients had tumor resection. Of these 19% had histologically negative specimens, 9 patients (16%) had microscopic disease only, and 37 patients had gross residual disease at the time of surgery. The actuarial 5-year survival and recurrence-free survival rates for the entire group were 20% and 24%, respectively. Patients with a pathologic response had an actuarial recurrence-free survival rate of 53% at 5 years whereas only 17% of those with gross residual disease at surgery had remained recurrence-free at 5 years. One-half of the patients with clinically uninvolved nodes were living recurrence-free at 5 years whereas only 20% of the patients with N 2 disease did so. The patterns of failure according to the histology and stage of the disease will be presented.

Elective versus therapeutic neck dissection in early carcinoma of the oral tongue

A prospective, randomized trial was carried out to assess the value of elective versus therapeutic neck dissection in early squamous cell carcinoma of the oral tongue. Disease-free survival (median follow-up 20 months) was 52 percent versus 63 percent in patients who underwent hemiglossectomy alone and those who underwent hemiglossectomy and radical neck dissection, respectively (difference not statisti cally significant). Patients with a tumor depth of less than 4 mm did significantly better than those with a tumor depth of greater than 4 mm; they were also more likely to have uninvolved nodes at elective radical neck dissection compared with thost with a tumor depth of greater than 4 mm. However, when the survival rates of patients in the two treatment groups were compared with respect to a tumor depth of 4 mm, there was no significant difference between the hemiglossectomy and the hemiglossectomy and radical neck dissection groups. A policy of interval elective radical neck dissection only in those with a tumor depth of greater than 4 mm may optimize cure rates and avoid neck dissection in those unlikely to develop neck recurrence.

Nonpalpable breast lesions: diagnosis with slightly overpenetrated screen-film mammography and hook wire-directed biopsy in 1,014 cases.

Slightly overpenetrated screen-film mammography and hook wire-directed localization were used in 1,014 breast biopsies performed for nonpalpable, mammographically detected breast abnormalities. One lymphoma and 205 breast cancers (20%) were found; 115 breast cancers (56%) were noninvasive, and 90 (44%) were invasive. Mastectomy was performed in 69 breast cancers (34%); 136 (66%) were treated conservatively, 28 with biopsy only and 108 with lumpectomy, node dissection, and radiation therapy. All patients with noninvasive breast cancers treated with axillary dissection had uninvolved lymph nodes. Of the 90 invasive breast cancers, six (7%) had metastases to axillary nodes, which, to the authors' knowledge, is lower than percentages reported in other studies of wire-directed breast biopsies. The authors believe that the slightly overpenetrated technique is a valuable adjunct to screen-film mammography.

Immunohistochemical analysis of mesocolic lymph node cells in human colorectal cancer.

Localization of lymphocyte subsets and macrophages in the mesocolic lymph node of the colorectal cancer and their distribution among the paracolic, intermediate, and main nodes were studied quantitatively by means of immunohistochemical staining with monoclonal antibodies. In all of the three lymph node groups, in the paracortex, helper/inducer T cells were more numerous than suppressor/cytotoxic T cells. The number of whole T cells in the paracortex diminished with increasing proximity to the primary tumor. In the three lymph node groups, no significant difference was found regarding the ratio of the cell number among suppressor/cytotoxic T cells, natural killer cells, and macrophages. Lymphocytes in the paracortex of lymph node had a positive correlation to lymphocytes in the peritumoral stroma and intratumoral fields. These data neither suggest the presence of a powerful immunological reaction in the mesocolic lymph node nor support the concept of conservation of uninvolved regional lymph nodes in the surgery of the colorectal cancer.

Prognostic significance of mRNA‐encoding estrogen receptor and epithelial growth factor receptor in breast carcinoma progression into lymph nodes: 1. Estrogen receptor encoding mRNA

The main objective of this study was to differentiate between lymph nodes infiltrated by estrogen receptor-positive (ER+) and estrogen receptor-negative (ER-) breast carcinoma. Lymph nodes were obtained from 40 postmenopausal cancer patients, 10 from each disease stage. Six patients from each group had estrogen receptor-positive (BCaER+) and four estrogen receptor-negative (BCaER-) tumors. Both tumor-containing (T) and uninvolved (N) lymph nodes from the same patient were examined by the following parameters: magnitude of lymph node nucleic acid hybridization with cDNA probes from breast cancer MCF-7ER+ and MCF-7ER- cells; and binding capacity of 3H-estradiol, 125I-EGF, and 125I-PDGF binding and protein kinase C activities of the lymph nodes. Concomitant with the appearance of transformed cells, several events occur: Tumor cells induce stimulation of mononuclear cells and macrophages and evoke T- and B-cell proliferation, leading to the synthesis of tumor cell membrane-associated antibodies. In estrogen receptor-positive (ER+) breast carcinoma, estrogens and host hormonal modulatory mechanisms stimulate production and release of epithelial growth (EGF) and platelet-derived growth factors (PDGF). These factors are characterized by protein kinase C activities. There is infiltration of tumor cells into the lymph node and infiltration of leukocytes into the tumor site. In the lymph node, tumor progression depends on tumor cell proliferation rate and metastatic aggressiveness. The experiments described in this study document the changes that occur in lymph nodes, with differences between nodes infiltrated with BCaER+ and BCaER- breast carcinomas. Hybridization of 32P-cDNA from MCF-7ER+ cells with cellular RNA from BCaER+ involved (T) lymph nodes is greater than with cellular RNA from uninvolved (N) lymph nodes. The magnitude of hybridization correlated (P less than 0.005) with the disease stage.