Basal cell carcinoma of the face: surgery or radiotherapy? Results of a randomized study.

Basal cell carcinomas (BCCs) are very frequent cutaneous cancers, often located on the face. Cure rates with surgery and radiotherapy are high, but these treatments have never been compared prospectively. A randomized trial was initiated in 1982 to compare surgery and radiotherapy in the treatment of primary BCC of the face measuring less than 4 cm. The primary end point was the failure rate (persistent or recurrent disease) after 4 years of follow-up. The secondary end point was the cosmetic results assessed by the patient, the dermatologist and three persons not involved in the trial. In the course of the trial, 347 patients were treated. Of the 174 patients in the surgery group, 71% had local anaesthesia and 91% frozen section examination. Of the 173 patients in the radiotherapy group, 55% were treated with interstitial brachytherapy, 33% with contactherapy and 12% with conventional radiotherapy. The 4-year actuarial failure rate (95% CI) was 0.7% (0.1-3.9%) in the surgery group compared with 7.5% (4.2-13.1%) in the radiotherapy group (log-rank P = 0.003). The cosmetic results assessed by four of the five judges were significantly better after surgery than after radiotherapy. Eighty-seven per cent of the surgery-treated patients and 69% of the radiation-treated patients considered the cosmetic result as good (P < 0.01). Thus, in the treatment of BCC of the face of less than 4 cm in diameter, surgery should be preferred to radiotherapy.

Melanoma in childhood: an EORTC-MCG multicenter study on the clinico-pathological aspects.

Melanoma in children is rare. Nevertheless, it is imperative that clinicians be aware that melanoma does occur in childhood. Yet there is very little information available on the clinico-pathologic variations, and the prognostic parameters of melanoma in children. This report presents the results of a multicenter study of 102 lesions originally diagnosed as cutaneous melanoma, conducted among 5 Western European countries and collected during the period 1961-1994. Criteria for inclusion in the study included: (1) diagnosis of cutaneous melanoma; (2) age up to 16 years at diagnosis; and (3) availability of representative microscopic slides. On the basis of the histologic review only, 60 lesions were confirmed as melanoma, and 42 lesions initially diagnosed as melanoma were reclassified as nevi; 31 of the latter contained a predominance of spindle cells. The only significant parameter associated with the development of metatases or fatal outcome was thickness of more than 2.00 mm. The 5-year survival rate observed in this study was 84%. Based on these findings we conclude that considerable over-diagnosis of melanomas in children occurs. In order, therefore, to give consistent epidemiological data on melanomas in children and to improve proper recognition of their diagnostic features, both by clinicians and by pathologists, we propose to set up a central registry of melanomas in children in Europe, under the auspices of the European Organization for Research and Treatment of Cancer.

Comparison between familial and nonfamilial melanoma in France.

BACKGROUND AND DESIGN: Five percent to 10% of cutaneous malignant melanomas (CMMs) occur in a familial setting. Clinical, epidemiologic, and genetic studies of familial CMM in different regions of the world have led to various results. To assess the characteristics of familial CMM in France, the clinical, histologic, and epidemiologic characteristics of 295 patients with CMM were recorded, and a comprehensive familial investigation was performed for each case. Patients with a family history of CMM were compared with nonfamilial cases. RESULTS: Cutaneous malignant melanoma occurred as a familial cancer in 22 (8%) of 295 patients. Among the multiple variables studied, those significantly associated with the familial occurrence of CMM were red hair, inability to tan, and presence of clinically atypical moles. When these variables were considered together in a multivariate analysis, only the association with red hair (P = .001) and atypical moles (P < .05) remained significant. In addition, the patients with familial melanoma exhibited the following tendencies: a younger age at diagnosis, a higher number of moles, and the development of multiple primary melanomas, but these results did not reach statistical significance. Factors relating to UV light exposure, histologic features of CMM, course of the disease, and occurrence of nonmelanoma cancers showed a similar distribution between familial and nonfamilial cases. CONCLUSION: A familial investigation should be performed for each patient with CMM in France, particularly when he or she exhibits phenotypic risk factors for CMM such as red hair and atypical moles.

Prognostic value of neural invasion in rectal carcinoma: a multivariate analysis on 339 patients with curative resection.

To determine whether neural invasion or other clinico-pathological factors are prognostic, we performed a retrospective study on 339 rectal carcinomas. The overall 5-year survival was 62%. In the multivariate analysis, age over 60 years, a distance from the anal verge of less than 6 cm, the number of positive lymph nodes, neural invasion and tumour penetration were found to be prognostic. A scoring system identified five prognostic groups of patients. Neural invasion is an independent prognostic factor in our scoring system and it is suggested that this parameter should be taken into consideration for postsurgical treatment.

Tumour oxygenation, radiosensitivity, and necrosis before and/or after nicotinamide, carbogen and perflubron emulsion administration.

Hypoxia is one of the factors involved in tumour resistance to radiotherapy. One way to improve tumour oxygenation is to use oxygen carriers such as perflubron emulsion plus carbogen or vasoactive drugs such as nicotinamide. The perflubron emulsion and carbogen act mainly on hypoxia caused by limited diffusion of oxygen; nicotinamide acts mainly on acute hypoxia. The aim was to correlate radiosensitivity and pO2 measurements (computerized pO2 histograph) after nicotinamide, perflubron emulsion and carbogen administration, and to determine the role of necrosis in this correlation. Two human tumour xenografts (HRT18, Na11 +) and one rodent tumour (EMT6) were used. Clonogenic assays and pO2 measurements were performed under similar conditions. The radiosensitization and oxygenation levels increased with all treatments. The maximal effects were found with the combination of nicotinamide (1 g/kg), perflubron emulsion and carbogen. A correlation between the radiosensitization and the pO2 measurements was found for the three cell lines with a cut-off point of 10 mmHg. The presence of necrosis could explain the low pO2 (< 2 mmHg) found even when complete radiosensitization was observed.

Melanoma arising de novo in childhood: experience of the Gustave-Roussy Institute.

Between January 1956 and December 1990, 17 patients younger than 17 years with available pathological screens of de novo cutaneous melanoma, and with no other risk factors (xeroderma pigmentosum, giant congenital naevi, congenital melanoma or a proven family history of dysplastic naevus syndrome) were seen at the Gustave-Roussy Institute. The median age was 9 years and 9 months (range 2 years and 3 months-16 years and 9 months). The primary disease was located in the lower extremities in 10 cases, the trunk in five cases, and the upper extremities or head and neck in one case. The disease was localized for 10 patients at presentation (stage I), six had proven nodal metastasis (stage II) and one patient had nodal and breast metastases. The median thickness of the primary lesion was 2.89 mm (range 0.64-10). Five tumours were at level III on Clark's index, eight at level IV and four at level V. Six cases were classified as superficial spreading, two as unclassified radial growth, three nodular, three with Spitzoid cells, and three were unclassified. Two patients presented local recurrence with an initial unclassified melanoma, with a thickness greater than 2.5 mm. At a median follow-up time of 7 years, two patients had died from recurrent disease, and one patient had died from a second malignancy.

Carcinomas of the colon with multidirectional differentiation. Report of two cases and review of the literature.

Two cases of colonic carcinomas with multidirectional differentiation are presented. Both tumors showed light microscopic and immunohistochemical evidence of areas of adenocarcinomatous, squamous cell carcinomatous, and neuroendocrine differentiation. Only six similar cases have been previously reported. These highly malignant tumors support the recent concept of a multipotential stem cell within the mucosa of the gastrointestinal tract capable of differentiation in several directions.

Borderline and malignant serous tumor arising in pelvic lymph nodes: evidence of origin in benign glandular inclusions.

This report describes two cases of malignant serous cancers with areas of borderline malignancy, which appear to have arisen within benign glandular inclusions of coelomic origin in pelvic or para-aortic lymph nodes. The patients were 44 and 62 years of age. In both cases the nodes contained benign glandular inclusions lined by a single layer of epithelium which resembled that of tubal epithelium. The location of the glandular epithelium varied from within the fat near the node to intracapsular, subcapsular, or interfollicular positions. The number of glands ranged from few to extensive. In both cases the glandular inclusions disclosed epithelial proliferations, ranging from minor degrees of stratification with formation of small papillae of atypical cells (borderline serous tumor) to almost solid tumor typical of serous cancer. In both cases, the borderline and cancerous tumors exhibited areas of transition which appeared to arise from benign glands. Although benign glandular inclusions of coelomic origin are well documented to occur in pelvic or para-aortic lymph nodes of 5-20% of women and have been considered to be of significance only because of the possibility of the misdiagnosis of cancer, it should now be recognized that the glandular inclusion cysts themselves can become neoplastic.

[Classification of ovarian tumors based on embryogenesis]. / Classification des tumeurs de l'ovaire basée sur l'embryogenèse.

This paper studies gonadal differentiation into the ovary from the earliest interaction between germ cells and somatic cells in the developing urogenital ridge up to the formation of primordial follicles. Granulosa cells appear to be derived from the breaking down of the cordlike arrangement of epithelial cells resulting from proliferation of surface coelomic mesothelium. Thecal cells arise from mesenchymal progenitors cells in the ovarian stroma. Based on the findings of embryology and biology, the authors then propose a classification of ovarian tumors by rearranging the WHO classification.

Identification of genes overexpressed in tumors through preferential expression screening in trophoblasts.

Early trophoblastic cells share several features with neoplastic cells. Based on that observation, we attempted to identify genes overexpressed in tumors by analyzing genes preferentially expressed in trophoblasts. A subtracted library enriched in complementary DNA from early cytotrophoblasts was constructed, and the expression level of selected recombinants was analyzed on a large panel of normal and tumor tissues. The library was prepared using a polymerase chain reaction-based complementary DNA subtraction method with 6-week amenorrhea cytotrophoblast endoplasmic reticulum-bound RNA as target, and a mixture of complementary DNA prepared from terminal placenta and activated T-lymphocytes as driver. Two rounds of screening were performed to isolate clones preferentially expressed in early placenta. From a total number of recombinant clones estimated at 32,000 in the subtracted library, 594 inserts were analyzed by Southern blot and 21 sequences were isolated as corresponding to genes highly expressed in early placenta. Eleven encoded known molecules, such as carcinoembryonic antigen, human chorionic gonadotropin, and mitochondrial rRNAs. Ten sequences represented novel genes. Northern blot analysis confirmed that most of these genes were preferentially expressed in early trophoblast in comparison to terminal placenta. Three clones that gave detectable hybridization signals on total RNA were extensively studied and were found to be overexpressed in various tumors. Two of these clones, designated B9 and E4, were later identified as corresponding to genes coding for the putative ribosomal protein S18 and the bifunctional enzyme ADE2H1 involved in purine biosynthesis, respectively. Expression of the third clone, E9, was increased up to 10-fold in breast cancer tissues in comparison with normal counterparts. Present results confirm that many genes expressed in the trophoblast are overexpressed in malignant cells. This approach could provide a general targeted method for the identification of genes overexpressed in various neoplastic cell types.

[Cervical cancer in the young woman]. / Le cancer du col utérin de la femme jeune.

Uterine cervix carcinoma is considered by some authors to carry a poor prognosis in young patients (< 35 years of age). From 10 years, many series have been published with divergent conclusions. However, a group of patients with poor prognosis could be individualized; age < 30 years, locally aggressive tumour, poorly differentiated, nodal involvement, amplification of c-Myc proto-oncogene. New imaging technics and coelioscopy could help to the diagnosis. The role of combined treatment remains to be demonstrated and biological factors (kinetics, oxygenation) will help in the future to more adapted treatments.

A comparison of early effects with two dose rates in brachytherapy of cervix carcinoma in a prospective randomised trial.

This phase III randomised trial examined the early effects of two low dose rates (0.38 and 0.73 Gy/h) in brachytherapy of stage I and IIp cervical cancer patients. A total of 204 patients were included between January 1985 and September 1988. Since the main analysis of this paper concerned surgical difficulties, only the 155 patients (76%) on whom surgery was performed at the Institut Gustave-Roussy were retained in this analysis. Treatment consisted of uterovaginal 137Cs irradiation followed by immediate or deferred surgery. The two groups were similar for pretreatment characteristics except for endocervix involvement. Their brachytherapy parameters were also similar (60 Gy pear dimensions, doses to critical organs, total kerma, etc.). The factors with a poor prognosis were, for surgical difficulties, older age, stage II and a small irradiated pear volume; for difficulties with haemostasis, immediate surgery, stage II and previous surgery; and for difficulties in dissection, lymph node involvement. The dose rate significantly influenced surgical difficulties for the stage IIp patients operated on by deferred surgery. Those treated with the higher dose rate showed a 2-fold increase in surgical difficulties compared to those irradiated at the lower dose rate (P = 0.03). The independent prognostic factors for sterilisation of the surgical specimen were small tumour size and absence of lymph node involvement. An inverse dose rate effect was observed for medium size tumours, with significantly more sterilisations observed in stage IIp patients in the lower dose rate group (P < 0.01).

Experimental study of balloon-expandable metallic vena caval stents in rabbits.

PURPOSE: The reactivity and patency of balloon-expandable Strecker stents were determined in the superior vena cava (SVC) and inferior vena cava (IVC) of rabbits. MATERIALS AND METHODS: One stent was placed in each of 24 rabbits; 15 were placed in the SVC and nine in the IVC. The duration of stent placement varied between 3 days and 15 months. After the animals were killed, the segments in which the stent was placed were sectioned and analyzed under light microscopy for quantification of neointimal hyperplasia with metal struts in situ. RESULTS: Twenty-three stents remained patent throughout. Two SVC stents thrombosed at 1 week; one of these recanalized spontaneously after 4 weeks. Self-limiting neointimal hyperplasia reached a maximum thickness at 1 month and receded over 3-6 months. In five rabbits with long-term SVC stents, there was a radial shift of the stent to the perivascular layer of fat. Despite this shift, these stents remain patent. CONCLUSION: Strecker stents are well adapted to the venous system in terms of both patency and histocompatibility.

[Cutaneous malignant melanoma in New Caledonia (South Pacific) 1973-1991. A study of 97 cases]. / Le mélanome malin cutané en Nouvelle-Calédonie (Pacifique Sud) 1973-1991. Etude de 97 observations.

The Cancer Registries have been operational in the South Pacific since 1958 (Papua New Guinea), Fiji (1965) and New Caledonia (1977) and complete cancer incidence rates are available, based on histologic data. We studied 97 melanomas, histologically confirmed, which were diagnosed in New Caledonia from 1973 to 1991. New Caledonia is located in the same latitude as Queensland in Australia, known for having the highest incidence of melanoma in the world. Standardised incidence rates (world population) were 9.82 and 7.65/100,000/year for European males and females, compared to 1.65 and 1.05 for Melanesian and Polynesian males and females. The European population is exposed and Melanesians/Polynesians are relatively protected as are black Americans or Africans. The mixed populations are protected, but no study is available as to the exact proportion of mixed people (20%?) in the entire population. For Europeans, among males, the main areas in which melanomas occur are the trunk (45%) the arm (13%) and the leg (13%). Among females, the main areas are the leg (27%), the trunk (20%) and the head (18%). Screening for melanoma has been more effective in the last 6 years, a period in which we diagnosed half the total cases and generally at earlier stages. Prognosis was poor for this period (1973-1991): the five year survival rates were 64% +/- 8%, not as good as in Europe or Australia, but these lesions were diagnosed between 1973 and 1985 and were generally more invasive. A better prognosis will probably be observed in a few years, and another evaluation of melanoma screening should be made in the future as well the study of precursors and early lesions.

[Benign glandular inclusions in inguinal and abdominopelvic lymph nodes in gynecologic pathology]. / Les inclusions glandulaires bénignes dans les ganglions lymphatiques inguinaux et abdominopelviens en pathologie gynécologique.

From 4 cases recently seen at the Institut Gustave-Roussy, this report describes the pathological and evolutive features of benign glandular inclusions in inguinal, pelvic or abdominal lymph nodes. These lesions are defined by the presence of tubular formations in lymph nodes, lined by a single layer of epithelium which is cuboidal or columnar and resembled that of tubal epithelium with ciliated, secretory and intercalary cells. In most cases, benign glandular inclusions in lymph nodes still quiescent. In rare instances, they may proliferate and become papillary. The association of proliferating glandular inclusions in lymph nodes with borderline tumor of the ovary raises the problem of their primary or metastatic origin. However, their pathological features argues for a primary origin in lymph nodes. Thus, we think that a metastatic potential of borderline tumors of the ovary is not supported by any convincing argument.

Relationship between the melanin content of a human melanoma cell line and its radiosensitivity and uptake of pimonidazole.

The intra-cellular uptake of the weakly basic radiosensitiser pimonidazole (PIMO) was determined as a function of the pigmentation of Na11+ human melanotic melanoma cells in vitro. Two experimental conditions were considered: exponentially growing cells (Exp.) and plateau-phase cells (PI.). The melanin content of Na11+ cells ranged from 500 micrograms/g cell weight in exponentially growing cells to 6000 micrograms/g in heavily pigmented plateau-phase cells. Cells were exposed to PIMO (medium dose, 0.2 mmol/dm3; 58.2 micrograms/ml). The intra-cellular concentration ranged from 163 micrograms/g in Exp. to 900 micrograms/g in pigmented Pl.; the latter being equivalent to an intra- to extracellular concentration ratio (Ci/Ce) of 17. However, this increase in the cellular uptake of PIMO was not accompanied by an increase in radiosensitising efficiency. In comparison, the Ci/Ce for etanidazole (ETA), a radiosensitiser that is uncharged at physiological pH, remained approximately constant at 1 for all values of melanin contents. Treatment of Na11+ tumours in vivo with [3H]-PIMO resulted in a tumour:blood ratio of about 3 at 30-60 min after administration. However, at 24 h a grain count of label derived from [3H]-PIMO showed that picnotic areas of tumours contained levels that were some 40 times greater than the background value. This high level of label was coincident with areas of highest apparent melanin content. In conclusion, PIMO accumulates in very heavily pigmented melanoma cells present in necrotic zones with picnosis. As these cells are probably non-clonogenic, PIMO is not suitable for use in melanoma radiotherapy.