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Adjuvant CMF effect on site of first recurrence, and appropriate follow-up intervals, in operable breast cancer with positive axillary nodes.

From June 1973 to May 1978 a total of 845 patients with operable breast cancer were entered into different adjuvant programs. The medical records of the 278 patients showing relapse were carefully re-evaluated to assess the pattern(s) of first recurrence and the consistency of follow-up modulation. Ninety-one of 179 patients treated with surgery alone, 130 of 414 given 12 cycles of adjuvant CMF and 57 of 252 treated with 6 cycles of CMF showed treatment failure within 5 years from radical mastectomy. The frequency of new disease manifestations was significantly affected by primary treatment, since patients given adjuvant CMF showed a lower tendency to recur in local-regional area(s) and in bone(s). However, in relapsed patients, patterns of new lesions were not substantially altered by type of primary treatment. The most frequently involved sites were soft tissues (37.8%) and bones (37%) followed by viscera (34.2%). Retrospective evaluation of X-rays revealed that in 26.2% of osseous metastases, diagnosis could have been assessed earlier, with a median delay of 4 months (range 1-8). Present analysis also revealed that short-term repeated X-ray examinations yielded findings more controversial than reliable for assessing the exact time of relapse, thus preventing firm conclusions in the presence of suspicious recurrence. A new follow-up schedule after completion of adjuvant chemotherapy is proposed, since on the basis of our experience, in asymptomatic patients frequently repeated examinations are not necessary and some can safely be omitted.

Antineoplastic Combined Chemotherapy Protocols↗

Melanotic neuroectodermal tumor of infancy (MNTI) in the epididymis. A case report with immunohistological studies and special consideration of malignant features.

Melanotic neuroectodermal tumors of infancy (MNTI) are uncommon, usually benign neoplasms, most frequently found in the maxilla. These tumors are extremely rare in the epididymis. Only 18 cases with this site of origin are documented. We report on the third epididymal MNTI with some morphological characteristics of malignancy but favorable clinical outcome. The 2 cm large tumor of a 6-month-old male infant showed large epitheloid cells in the center and small neuroblastoma-like cells at the periphery. Despite invasion of lymphatics there is no evidence of relapse or metastases during 4 years of follow-up. Immunohistochemically, the large tumor cells were distinctly positive for cytokeratin, vimentin, GFAP, the melanoma marker NKI-C3, NSE, and S100. The small tumor cells were only slightly positive for GFAP, NKI-C3, NSE, and S100 but they were negative for cytokeratin and vimentin. Neurofilament and chromogranin could not be proved in the tumor.

Biomarkers, Tumor↗

Trefoil factor 3 overexpression in prostatic carcinoma: prognostic importance using tissue microarrays.

BACKGROUND: Human intestinal trefoil factor 3 (TFF3) is a member of a family of polypeptides encoded by a cluster of genes on chromosome 21. Through gene expression profiling studies TFF3 mRNA has been found to be overexpressed in prostate cancer. METHODS: We used immunochemistry on tissue microarrays and software tools, collectively referred to as TMAJ, for online assessment of staining to analyze samples from 294 primary tumors and 61 metastatic lesions. RESULTS: Applying a cutoff of 20% of cells staining as positive, the frequency of staining was 18.8% in normal (51 of 272) and 47.0% in primary tumors (126 of 268), P < 0.0001, Wilcoxon rank sum). Expression of TFF3 in metastatic prostate cancer was similar to that in primary tumors. TFF3 expression was not associated with time to biochemical recurrence, development of distant metastasis, or death due to prostate cancer. Scoring data derived from visual estimation of expression correlated highly with semi-automated image analysis using the Automated Cellular Imaging System (ACIS) from Chromavision, Inc. CONCLUSIONS: These studies validate that TFF3 is overexpressed at the protein level in a subset of primary and metastatic prostate cancers, show the first use of the TMAJ database, and demonstrate the ability to semi-automatically scan and score immunohistochemically stained tissue microarray slides.

Biomarkers, Tumor↗

[Carcinogenic effect of a heavy catalytic gas oil].

The carcinogenic effect of treatment with heavy catalytic gasoil on the skin of 120 albino noninbred mice was studied. Skin tumors arose in 97 of 115 animals (84.3%) which survived until the appearance of the first papillomas. In 21 mice, tumors were benign while cancer developed in 76 animals. 116 visceral neoplasms were detected in 99 animals (93.4%). They were found in the upper part of digestive tract of 57, the hematopoietic and lymphatic tissues of 57 and in the lungs of two animals. The study established a high carcinogenicity of heavy catalytic gasoil matched by early appearance and multicentric growth of tumors as well as rapid generalization of the process.

Animals↗

Hypercalcemic VX-2 carcinoma in rabbits: a clinicopathologic study.

Rabbits receiving intramuscular injections of VX-2 carcinoma cells in biceps femoris muscles developed rapidly progressive neoplastic growths at 14 to 21 days associated with a significant hypercalcemia. The biologic behavior of the VX-2 carcinoma was characterized by local infiltration and metastases to regional lymph nodes and lungs. No metastases to skeletal tissues were evident. Femora from intramuscularly injected rabbits had varying degrees of osteophytosis and lysis evident roentgenographically. Histopathologic evaluation of femoral sections revealed periosteal new bone growth, cortical osteolysis, endosteal new bone growth, and in a few long term rabbits, pathologic fractures. Bone lesions were evident histologically in the vicinity of neoplastic growth (i.e., femora, tibiae) but not at distant sites (i.e., humeri and vertebrae). Mineral analyses of VX-2 carcinoma tissues and kidneys from VX-2-bearing rabbits revealed concentrations of calcium 83 and 3 times greater, respectively, than those of skeletal muscle and kidneys from controls. These findings correlated well with histochemical evidence of excessive amounts of calcium in sections of kidneys and VX-2 carcinoma tissues. Rabbits receiving intraperitoneal injections of VX-2 carcinoma cells did not develop hypercalcemia despite an extensive, progressive neoplastic burden with metastases to abdominal and thoracic viscera. Roentgenographic, histopathologic, and physiochemical analyses of selected bones from these rabbits revealed no significant alterations. These findings indicate that VX-2 carcinoma cells need to be in close proximity to skeletal tissues in order to induce hypercalcemia. The development of a significant hypercalcemia in intramuscularly injected rabbits precedes the invasion of osseous tissues by VX-2 carcinoma cells. Therefore, it appears that VX-2 carcinoma cells have the ability to alter skeletal morphology and physiochemistry through a dual humoral/cellular mechanism. The clinicopathologic characteristics of the VX-2 carcinoma in the rabbit suggest that the neoplasm is a good experimental model to study osseous-mediated hypercalcemia of malignancy.

Animals↗

[A case of anisosynchronously duplicated tumors consisting of leiomyosarcoma of the rectum and malignant paraganglioma of gluteal soft tissue].

A 62-year-old man received a Miles' operation for the recurrence of low grade rectal leiomyosarcoma which had been enucleated 8 years earlier. The tumor, measuring 11 x 12 cm, was located in the lower rectal area (Rb) and had developed into the pelvic cavity. One year after operation, after the uncovery of a malignant paraganglioma in the right gluteal soft tissue, the patient died from the metastases of the liver and the lung, and from lymph node that covered his body. This case is a rare example of anisosynchronously occurring duplicated carcinomas.

Cytoplasmic Granules↗

[Expression and significance of GST-Pi and HIF-1alpha in bladder carcinoma].

BACKGROUND & OBJECTIVE: Multidrug resistance plays an important role in chemotherapy failure of bladder cancer, but its mechanism is unclear. Hypoxia in tumors is generally associated with chemoresistance. However, the correlation of nuclear transcription factor hypoxia-inducible factor-1 (HIF-1) to multidrug resistance transporter glutathione-S-transferase-Pi (GST-Pi) has not been investigated. This study was to explore the expression and significance of GST-Pi and its correlation to HIF-1alpha in bladder carcinoma by tissue microarray. METHODS: A tissue microarray containing 119 cases of bladder carcinoma and 6 cases of normal bladder tissue was built up. The expression of GST-Pi and HIF-1alpha was detected by SABC immunohistochemistry. RESULTS: In the 119 cases of bladder carcinoma, the positive rate of HIF-1alpha was 57.9%, the positive rate of GST-Pi was 67.2%. The positive rate of HIF-1alpha in G3 grade bladder carcinoma was 64.6%. Their expression was closely related to pathologic grade, clinical stage, and postoperative relapse after adjuvant chemotherapy (P<0.01). HIF-1alpha expression was positively related to GST-Pi expression (P<0.01). CONCLUSIONS: Overexpression of HIF-1alpha may be related to hypoxia. Co-expression of HIF-1alpha and GST-Pi is a object index for judging differentiation and chemoresistance of bladder cancer.

Adult↗

Endocrine differentiation of gastric adenocarcinoma. The prevalence as evaluated by immunoreactive chromogranin A and its biologic significance.

The prevalence of endocrine differentiation of conventional gastric adenocarcinoma was evaluated on the 212 cases (including 62 mucosal carcinomas) of consecutively resected stomach for adenocarcinoma in our hospital using anti-chromogranin A (CGA) antibodies. CGA-positive cells were found in 28 of 150 cases (18.7%) as an integral tumor component. In immunocytochemistry and electron microscopic examinations, we could classify these 28 cases into three groups according to the distribution patterns of CGA-positive cells. The first group consisted of 12 cases in which scattered CGA-positive cells were located in neoplastic glands. The second group consisted of six cases of scirrhous carcinoma in which CGA-positive cells were separated by fibrovascular tissue. The third group consisted of ten cases in which the positive cells were present in clusters. No definite correlation was recognized between the appearance of CGA cells and histologic types of predominance. In the analysis of the hormonal substances coexpressed by CGA-positive cells, immunoreactive serotonin (SER) was found most frequently, and somatostatin (SS), gastrin (GAS), glucagon/glicentin (GLU/GLI), and peptide-tyrosine-tyrosine (PYY) like immunoreactivities were found in a few tumor cells. CGA-positive cells occupied limited parts of the tumors in most cases, and they were noticeably more frequent in advanced stage cases. This might explain why endocrine differentiation reflects the dysexpression of the neoplastic stem cells. Furthermore, absence of mitotic figures in this type of cell and negativity of a single colony composed exclusively of CGA cells in metastatic foci suggested that these cells are in a dormant phase and are probably postmitotic.

Adenocarcinoma↗

Tumor proliferation in squamous cell carcinoma of the vulva.

Tumor proliferation is of important prognostic significance for several neoplasms. The very few previous studies on this parameter in vulvar carcinoma have shown contradictory results. The aim of this study was to determine the prognostic significance of tumor proliferation in vulvar carcinoma. Paraffin-embedded tissue of 74 squamous cell carcinomas of the vulva was immunostained for MIB-1, detecting Ki-67, and analyzed for staining patterns and the percentage of positive cells. There were three general staining patterns: a diffuse distribution (diffuse type), a localized staining at the infiltrating tumor border (infiltrating type), and a localized staining in basal parts of infiltrating tumor cell aggregates (basal type). The percentage of positive cells was not correlated with morphologic or clinical parameters, nor was it correlated with disease-free and overall survival. MIB-1 staining types were correlated with tumor type and grading. Tumors of diffuse and infiltrating type seemed to have more frequent lymph node metastasis (p = 0.053) and shorter disease-free survival (p = 0.076). In these tumors, overall survival time was reduced significantly (p = 0.02). In multivariate analysis, MIB-1 staining types were the most important factor for overall survival with an odds ratio of 4.73. In conclusion, distribution and not the percentage of proliferating cells is of prognostic significance in squamous cell carcinoma of the vulva.

Antigens, Nuclear↗

Soft tissue sarcomas of the extremities and trunk in the adult. Report of 124 cases.

Between 1970 and 1988 surgery was performed on 124 patients with soft tissue sarcomas of the extremities and trunk in the University Clinics of Hamburg. Liposarcoma, malignant fibrous histiocytoma, fibrosarcoma and malignant schwannoma were the most common histological types. High-grade sarcomas (G3) predominated, with 41%, while 26% were graded G2 and 33% G1. Resection with wide margins all round was achieved in only 54% of the patients. The quality of the operation proved to be only therapy-related prognostic factor. In addition, tumour grade, size, regional lymph node and distant metastasis and histological type proved to be relevant to the prognosis. With multivariate analysis, distant metastasis, grade, resectability and histological type retained prognostic significance. The efficacy of adjuvant chemo- and radiotherapy was related to the quality of the preceding tumour resection. In case of gross tumour the rate of either partial or complete response was 28% for chemotherapy and 22% for radiotherapy. The mean survival time was 102 months; the 5- and 10-year survival rates were 48% and 37%, respectively.

Adolescent↗

[Does the use of free transplanted jejunum segments in advanced laryngeal and hypopharyngeal cancer prolong survival? A matched-pair analysis].

The effect of free transplanted jejunum autografts, inserted after resection of extensive squamous cell carcinoma of the larynx and hypopharynx is evaluated in terms of survival and the development of local and regional recurrences. In a matched-pair analysis, 22 patients with jejunum transplants were compared with 44 patients with the same performance status, in whom after laryngopharyngectomy, the pharynx had been closed with local mucosa. The cumulative survival rate was calculated using the Kaplan-Meier method; the statistical comparison of the survival curves of the two groups was made with the Mantel-Haezel test. Patients of the study group had a statistically significant (p less than = 0.01) better survival rate than those of the control group, the 50% survival rate being 36 and 11 months, respectively. Local recurrences occurred in 9.1% of the patients in both the study group and in controls, and regional recurrences in 40.8 and 43.2%, respectively. This militates against the possibility that the surgery in patients in whom reconstruction with jejunum was possible might have been more radical. Further, it may be speculated that the statistically significant better survival rate is due to the jejunum itself, presumably to a tumourprotective effect of the lymphatic tissue of the transplant.

Follow-Up Studies↗

Desmoplastic small round cell tumor of the abdomen: radiologic-histopathologic correlation.

PURPOSE: To characterize the imaging features of desmoplastic small round cell tumor of the abdomen and correlate them with the histopathologic findings. MATERIALS AND METHODS: Eleven of 14 patients with desmoplastic small round cell tumor had primary abdominal involvement. In nine of these patients (mean age, 20 years), results of imaging studies (computed tomography in nine patients, ultrasonography [US] in three) and histopathologic specimens were retrospectively analyzed. RESULTS: The hallmark imaging feature was lobulated peritoneal masses (mean number, 4.4; range, 1-17) with a mean diameter of 5.0 cm (range, 2-12 cm). Omental and paravesical tumors were each present in six patients. Retroperitoneal masses were present in three patients. The tumors were well defined and hypoechoic at US. Heterogeneity due to tumor hemorrhage or necrosis was seen in seven patients. Ascites was present in five patients. Parenchymal and/or serosal hepatic metastases, punctate calcifications, nodular peritoneal thickening, lymphadenopathy, hydronephrosis, and bowel obstruction were less common associated findings. CONCLUSION: Bulky peritoneal soft-tissue masses without an apparent organ-based primary site are characteristic of intraabdominal desmoplastic small round cell tumor. Although the findings are nonspecific, this diagnosis can be considered in adolescents and young adults with characteristic imaging findings.

Abdominal Neoplasms↗

Recurrences in the soft tissues of the neck after surgery or radiotherapy plus surgery on regional lymph nodes in patients bearing carcinomas of the head and neck.

A series of 45 recurrences in the soft tissues of the neck following lymph node dissection in 497 patients bearing carcinoma of the upper aerodigestive passages is reported. Only 22 cases that presented perilymph node metastases and/or in which there were reasons to indicate insufficient surgical radicality had been subjected to radiotherapy after surgical lymph node dissection; the other 23 cases had not been subjected to radiotherapy because the aforementioned premises had been lacking. All the recurrences therefore occurred in patients with clinically and histologically ascertained metastatic lymph nodes. The presence of perilymph node metastases and the judgment of surgical radicality was thus found insufficient criteria to plan future complementary postoperative radiotherapy. However, even in those cases in which postoperative radiotherapy was performed, there was a rather high incidence of recurrences, as high as 64.7% in patients with carcinoma of the tongue. Our data indicate the opportunity of a clinical trial with preoperative radiation therapy in patients with clinically evident lymph node metastases. Thirty-six of these recurrences were situated in the upper parts of the cervical region. The prognosis is very poor in such cases, so much so that only 2 of our series were disease free at 3 years after the treatment.

Carcinoma↗

Cervical node metastases in squamous cell carcinoma of the upper aerodigestive tract: the significance of extracapsular spread and soft tissue deposits.

BACKGROUND: Literature regarding the prognostic significance of extracapsular spread and soft tissue deposits in cervical lymph node metastases of squamous cell carcinoma of the upper aerodigestive tract shows variable results. METHODS: We analyzed 215 prospectively collected neck dissections from 155 patients with upper aerodigestive tract squamous cell carcinoma to assess the prevalence of extracapsular spread and soft tissue deposits and to assess their effect on survival. RESULTS: Both extracapsular spread and soft tissue deposits significantly reduced survival (actuarial and recurrence free) compared with pN0 necks (p <.001) and pN+ve necks without extracapsular spread (p <.0025). There was no statistically significant difference between pN+ve necks without soft tissue deposits or extracapsular spread compared with those with pN0 necks (p =.24). Multivariate analysis revealed comparable results. CONCLUSIONS: Microscopic and macroscopic extracapsular spread and soft tissue deposits are of prognostic significance for survival and recurrence-free survival in patients with upper aerodigestive tract squamous cell carcinoma.

Carcinoma, Squamous Cell↗

Gallbladder cancer invading the perimuscular connective tissue: results of reresection after prior non-curative operation.

BACKGROUND AND OBJECTIVES: Most T2 gallbladder cancers are diagnosed at final pathology after cholecystectomy. Reoperations including liver resection and regional lymph node dissection are needed to achieve better long-term results. The aim of this study is to evaluate long-term results of reresections after prior non-curative surgery for T2 carcinomas. METHODS: Retrospective study from January 1985 to July 2001. Twelve out of 14 pT2 cancers were found postoperatively. All but one underwent reresection: these 11 patients are the basis of our series. RESULTS: The in-hospital mortality rate was 0%. Overall 5-year survival was 63.5% with a median survival of 25 months. Median and 5-year survival of the eight cases without preoperative signs of disease (Group A) were 46.7 months and 100%. These results were significantly better than those obtained in the subset (Group B: three cases) with preoperative signs of disease (P = 0.01): all these patients died of recurrence within 25 months from the reoperation. Mean time between cholecystectomy and reresection was 2.2 and 11.3 months in the Group A and B (P = 0.01), respectively. CONCLUSIONS: T2 cancers discovered incidentally after simple cholecystectomy should be reoperated on as soon as possible, as the appearance, before reoperation, of a recurrence is significantly related to a dismal prognosis.

Adult↗