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The clinical staging of rectal cancer in patients treated by preoperative radiotherapy.

We describe the results of clinical and (or) surgical staging used by the same surgeon to select a group of 41 patients with advanced rectal cancer for preoperative radiotherapy. Fifteen patients with resectable but advanced rectal cancer were subjected to a short course of radiotherapy (30 Gy in 10 days), immediately followed by resection. High dose preoperative radiotherapy (50-56 Gy in 5 weeks) was administered to 26 patients with borderline resectable or fixed cancer. Adequate resection of the tumour was possible in 21 of these 26 patients 4 weeks after the end of the radiotherapy. A total of 36 patients thus underwent resection after preoperative radiotherapy. No radiotherapy related acute or late morbidity was seen. On 31 December 1992 the results were investigated retrospectively. The median time since entering into the study was 87 months (range 27-141). During the follow-up, pelvic recurrence was detected in six patients; one patient had concomitant distant metastases. The local recurrence free survival at 5 years calculated by the Kaplan-Meier method was 72% (95% CI 58-85). Distant metastases without local recurrence developed in 11 patients. The calculated survival at 5 years was 45% (95% CI 30.5-59).

Brain Neoplasms↗

[Local control of the primary tumor. Necessary step in control of cancer].

There is clear evidence for a cancer cure. The hypothesis behind a treatment with curative intent is the ability to eradicate all the cancer cells of a tumour. Out of three cancer deaths, one is related to local failure. In some cancers like breast carcinoma, death is mainly in relation with the development of distant metastases. Even in such a tumour, an improvement in local control can translate as better survival. Radiation therapy, often in association with surgery, is playing a major role in tumour local control. Such a local control is mandatory if cure is at aim. One of the main goals of clinical research is to find a good compromise between local control of the disease and a non mutilating surgical approach.

Antineoplastic Agents↗

Effects of primary chemotherapy in conservative treatment of breast cancer patients with operable tumors larger than 3 cm. Results of a randomized trial in a single centre.

272 women with operable breast adenocarcinomas larger than 3 cm were included in a randomized trial. The patients in group A (n = 138) with histological nodal involvement (N+) or a lack of estrogen and progesterone receptors (EPR-) were treated by initial mastectomy and axillary node dissection + adjuvant chemotherapy. Those in group B (n = 134) were treated by initial chemotherapy (the same as in group A) followed by loco-regional treatment, adjusted according to their response to chemotherapy. Prognostic factors were identical in the two groups. In group A, 32 patients received no adjuvant treatment (N- and EPR+), while 104 were given adjuvant chemotherapy (N+ and/or EPR-). Two patients were lost to follow-up. In group B, all patients received initial chemotherapy; 44 were in complete clinical remission and were treated with radiotherapy only; 40 with residual tumor (less than 20 mm) were treated with tumorectomy + axillary node dissection + radiotherapy; 49 with residual tumors (greater than 20 mm) had mastectomies. Conservative treatment was administered to 84 patients in group B (62.6%). EPR-tumors responded better to chemotherapy than did EPR+ ones (p = .003). After a median follow-up of 34 months, isolated local recurrences were more frequent in the group with initial chemotherapy, which, however, experienced a better overall survival (p = 0.04).

Adenocarcinoma↗

Nodular melanoma in 62 Japanese patients: influence of initial surgical treatment on local recurrence and prognosis.

The incidence of malignant melanoma is much lower in Japanese than in Caucasians, and the commonest type of melanoma in Japanese is acral lentiginous melanoma (ALM). In contrast to the improved prognosis noted in ALM, it is now of increasing concern that there is a rise in both the frequency and mortality of nodular melanoma. During the 25 years from 1970 to 1994, we observed 190 patients with melanoma, including 62 nodular melanomas and 96 ALM, at the Department of Dermatology, Tohoku University Hospital, Sendai, Japan. We retrospectively reviewed the recurrence and survival rates of nodular melanoma observed. The proportion of nodular melanoma, once comprising only 24% of all melanomas, showed a sharp increase to 40% after 1982. The anatomical sites of the primary tumor were the hands and feet (29%), extremities excluding hands and feet (27%), head and neck (23%), and trunk (21%). Comparison of the stages of nodular melanoma when diagnosed showed that the proportion of stage III remained highest throughout the whole period, but that of stage II melanomas increased after 1982. After treatment, local recurrence occurred far more frequently in nodular melanoma (19%) than in ALM (1%). The prognosis of nodular melanoma was also less favorable than that of ALM, although it slightly improved after 1982; the 5-year survival rates before and after 1982 were 34 and 50%, respectively. Twenty-eight patients with nodular melanoma had underwent simple excision or incisional biopsy of the primary tumor at another institution and were later referred to us for further intensive care or for the treatment of local recurrence and/or metastases.(ABSTRACT TRUNCATED AT 250 WORDS)

Combined Modality Therapy↗

Melanoma of the ear: prognostic factors and surgical strategies.

BACKGROUND: The ear's specific anatomical and lymphatic characteristics impose special requirements on the treatment of melanoma of the ear. OBJECTIVES: The aim of this prospective study was to define prognostic factors for melanoma of the ear and to evaluate surgical strategies for excision margins, histological evaluation and sentinel lymph node biopsy (SLNB) in order to achieve better cosmetic and functional results. PATIENTS AND METHODS: One-hundred and sixty-one patients with stage I/II melanoma of the external ear were treated in the Department of Dermatology, University of Tuebingen, from March 1976 to March 2004 (median follow-up 62 months). Malignant melanoma of the external ear represented 3% of the stage I/II cutaneous melanomas and 20% of the stage I/II head and neck melanomas recorded in the Melanoma Registry of the Department of Dermatology at the University of Tuebingen. Twenty of 42 lentigo maligna melanomas (LMM) underwent conventional histological evaluation, 22 underwent complete three-dimensional histology of excision margins (3D histology) in a paraffin-technique, i.e. micrographic surgery. SLNB was performed in 28 patients with melanomas thicker than 1.0 mm. Clinical, histological and surgical risk factors were evaluated by univariate and multivariate analysis. RESULTS: The median thickness of the tumours in the present study was 1.08 mm (mean 1.51 mm; range 0.18-8.50 mm), and the median excision margins were 11.0 mm (mean 12.61 mm; range 2.0-31.0 mm). The 3-year disease-specific survival rate was 98%, and the 3-year recurrence-free survival rate was 83%. Tumour thickness and invasion level were the only risk factors significant for disease-specific survival. Tumour thickness, location of the tumour and extent of excision margins were independently significant risk factors for recurrence-free survival. LMMs removed surgically with accompanying 3D histology were thicker than those examined by conventional histology (median 0.93 mm vs. 0.83 mm). The use of surgery with 3D histology, i.e. micrographic surgery, made it possible to reduce the excision margins (median 5 mm vs. 10 mm) without an increased risk of recurrence. Two of 29 SLNBs were positive (6.9%). There were six preregional recurrences after negative SLNB and one after positive SLNB. None of the patients who underwent SLNB died of melanoma-related causes during the observation period. CONCLUSIONS: This is the largest series of ear melanomas reported so far. The overall survival depended only on the tumour thickness and Clark level of invasion. Local recurrence was more frequent with smaller excision margins, but this did not influence the overall survival. Smaller excision margins under 3D-histological control did not carry an increased risk of local recurrence. Our results do not permit conclusions regarding the prognostic impact of SLNB for patients with melanoma of the ear.

Adult↗

Ploidy status and the response of T1 glottic carcinoma to radiotherapy.

Flow cytometric DNA ploidy measurements were performed on formalin fixed paraffin embedded tumour specimens from patients with a T1 glottic laryngeal carcinoma in order to evaluate the role of DNA content in relation to local control. From 1980 to 1987, a consecutive series of 90 patients with a T1 glottic laryngeal carcinoma were treated by radiotherapy with curative intent. Biopsies from 44 of these patients were readily available for DNA flow cytometry. In this group aneuploidy was associated with a significantly higher risk (P = 0.018) of local recurrence within 2 years after completion of radiotherapy (38% vs. 9% in the diploid group).

Aged↗

Laryngeal carcinoma. IV. Analysis of treatment results using the Cohen model.

Long term results, obtained in the treatment of 308 patients with laryngeal carcinoma are analysed with respect to local recurrence and complications. In this analysis the Cell Population Kinetic model, proposed by COHEN (1971) is used. The model for squamous cell carcinoma is found to be useful and in close agreement with observations of local recurrence, although a slight modification may be justified from the present data. No special model exists for late edema, but the model for late effects in the vascular stroma seems to be useful in this respect. Based on the model, a working hypothesis has been proposed, by which it is possible to predict the frequency of local recurrence and late edema. An optimum treatment schedule is calculated and converted to a split-course technique.

Carcinoma, Squamous Cell↗

[Selection criteria for breast conservation in patients with early breast carcinoma].

During the past two decades, breast-conserving therapy (excision of the tumor and axillary lymphadenectomy followed by irradiation) for early stage breast carcinoma has become firmly established as an equivalent treatment approach to mastectomy. The purpose of this review as to examine the risk factors for local recurrence after breast-conserving therapy. Better mammographic evaluation, better margin assessment, recognition of an extensive intraductal component and the use of adjuvant systemic therapy has improved the logo-regional control.

Breast Neoplasms↗

[Postoperative complications and local recurrence of mid-lower rectal carcinoma treated with neoadjuvant chemoradiotherapy and surgery. Preliminary results].

In our study we evaluate postoperative complications and local recurrence in local advanced rectal cancer after preoperative chemoradiation plus surgery. We treated 24 patients, 15 males and 9 females; in all cases the cancer was at stage II or III. Down-staging was observed in 14 patients (58.3%), 2 patients (8.3%) had no residual disease. We performed 2 APR, 20 low anterior resections (10 of which laparoscopic) and 2 transanal local excisions. In postoperative period we observed 8 complications, 4 minor and 4 major ones, with an over-all morbidity of 33.3% and of 16.6% if considering major complications. At present no local recurrence was registered.

Adult↗

Major amputation for advanced malignant melanoma.

The Memorial Sloan-Kettering Cancer Center experience with major amputation for advanced malignant melanoma from 1965 to 1984 is reported. This is a retrospective review of 58 patients who underwent hemipelvectomy, disarticulation of the hip and above knee or forequarter amputation for advanced or recurrent malignant melanoma. Major amputation with curative intent was performed upon 43 patients. There were three deaths that occurred 30 days postoperatively (7 per cent). Intransit metastasis was one of the indications for amputation in 33 patients, and local control of disease was achieved in 30 of 43 patients. The median time to recurrence in those patients who did have a recurrence was 12 months (a range of 18 days to 16 years). Fifteen of 40 patients who survived the operation had no evidence of disease five years after undergoing a major amputation. Age, sex, primary site, stage of disease at diagnosis and amputation, disease-free interval and positive node status at any time during the course of the disease were not predictive of the outcome. Neurovascular involvement with melanoma and positive margins of resection predicted early failure. A palliative amputation for impending major vascular disruption or extensive, fungating disease was performed upon 15 patients. There was one death 30 days after the operation, and generally, hospitalization did not exceed 30 days. Median survival time was five months. All of the patients died of local or distant disease within 33 months of treatment. Local recurrence preceded death in nine of 15 patients.

Adolescent↗

Breast cancer.

This year, manuscripts addressed numerous pertinent breast cancer issues. Notable conclusions from each of the discussed sections suggest that: (a) oral contraceptives do not increase a woman's risk for breast cancer; (b) the vast majority of women with resected premalignant breast lesions do well for prolonged periods after diagnosis regardless of therapy; (c) satisfactory cosmetic results can occur with either lumpectomy, axillary nodal dissection, and radiotherapy or with mastectomy and breast reconstruction; (d) the primary tumor thymidine labeling index can give prognostic information; (e) immunohistochemical methods can accurately measure tumor estrogen receptors; (f) there are multiple hormonal therapies of similar efficacy; (g) two new single agent chemotherapy drugs deserving further investigation are idarubicin and lonidamine; (h) none of several combination chemotherapy regimens is clearly superior to any of the other 'standard' regimens; (i) there is a lack of consensus among the conclusions of recent adjuvant breast cancer consensus conferences held in the United States and London; (j) inflammatory breast cancer patients treated with initial combination chemotherapy consistently appear to have improved relapse-free and overall survivals when compared to historical controls; and (k) the prognosis in locally recurrent breast cancer patients is better in those previously treated with lumpectomy and irradiation when compared to those previously treated with mastectomy.

Antineoplastic Agents↗

High-dose radiotherapy for localized prostatic cancer. An analysis of treatment results and early complications.

Between 1970 and 1983, 477 consecutive patients with clinically localized prostatic adenocarcinoma were treated with primary external-beam radiotherapy. With a minimum follow-up period of 60 months, the five- and 10-year survival rates were 59% and 33%, respectively. The five-year survival rate was 89% for patients with stage-A disease, 59% for stage-B disease and 25% for stage-C disease; it was 79% for patients with well-differentiated carcinomas, but only 37% for patients with high-grade tumours. The over-all local in-field control rate was 88%. Local failure occurred in 6% of patients with stage-A disease, 11% with stage-B disease, and 18% with stage-C disease. All patients experienced some radiation-induced reactions, but these were significant in only 14.2% of cases. The role of local- versus extended-field radiotherapy for curative treatment of prostatic cancer is discussed in some detail. Our unexpectedly low over-all survival figures emphasize the need to exclude the presence of distant metastases as fully as possible before commencing radical radiotherapy. High-dose radiotherapy to localized prostatic cancer offers significant advantages over radical surgery and is associated with an excellent local control rate, which can be achieved with an acceptable degree of early morbidity.

Adenocarcinoma↗

[Preoperative staging and follow-up in rectal cancer using endorectal sonography].

32 patients suffering from rectal carcinoma were examined by endorectal sonography. The preoperative staging by sonography was compared with digital palpation, colon enema and computertomography of the pelvis. In 90% of the cases the sonographic determination of the grade of invasion was identical to the histopathological examination. The efficiency of local destruction methods of rectal carcinoma (cryotherapy) can be controlled by this method.

Biopsy↗

Analysis of tumor spillage during radical prostatectomy using RT-PCR of prostate specific antigen.

Recent reports have suggested the shedding of cancer cells during radical extirpation of tumors. Prostate cells can be expressed from the prostate ex vivo and found in the expressed prostatic secretions. We conducted an in vivo study to determine if prostate epithelial cells can be found in the operative site as determined by RT-PCR targeted at prostate specific antigen (PSA) and to correlate this with pathologic stage and outcome. We analyzed 14 consecutive radical retropubic prostatectomy procedures with a minimum 1-year follow-up. Intraoperatively, 5-10 ml of fluid (representing blood, urine, and irrigant) was aspirated from the operative field at three time points: after transaction of the dorsal vein complex, urethra, and bladder neck. Ficoll gradient fractionation was carried out on the specimens, and RNA was extracted from the cell pellet. Quality of RNA and presence of the PSA mRNA was determined by RT-PCR targeted at actin and PSA, respectively, using previously published primers. The medical records were reviewed for pathologic stage. There were nine patients with extraprostatic disease and five patients with organ confined disease. Five of 14 (36%) patients tested positive for prostate epithelial cells in the operative field at one or more points during radical prostatectomy. All five positive RT-PCR PSA assays were in patients with locally advanced disease, whereas all of the patients with organ-confined disease were negative for RT-PCR. This preliminary in vivo study suggests that locally advanced prostate cancer may be associated with PSA expressing cells in the operative field during radical prostatectomy. The clinical significance of this is unclear, but this finding suggests that shedding of cells in the operative field is more likely with locally advanced disease.

Combined Modality Therapy↗

Intestinal-type adenocarcinoma of the nasal cavity and paranasal sinuses.

Intestinal-type adenocarcinoma (ITAC) of the nasal cavity and paranasal sinuses may occur sporadically or as an occupational-related hazard, especially in cases of wood dust exposure. The clinical and pathologic features of 17 cases of sporadic-type ITAC are presented and compared to those among woodworkers. Both groups are analyzed collectively to define further the biological spectrum of this rare neoplasm. Histologically, five variants of ITAC were recognized: papillary, colonic, solid, mucinous, and mixed. The nine men and eight women in this series ranged from 31 to 80 years of age. Eight tumors originated in the maxillary sinus, seven in the nasal cavity, and two in the ethmoid sinus. Unilateral nasal obstruction and epistaxis, averaging 6.8 months in duration, were the most common symptoms. At least four of the patients are known to have died of their disease. In contrast, ITAC in woodworkers occurs primarily in men, originates almost exclusively in the nasal cavity or ethmoid sinus, and has a better prognosis. Data pooled from 213 cases of ITAC indicate that 53% of patients have experienced local recurrences following therapy, 8% (range 0-22%) have developed cervical lymph node and 13% (range 0-29%) distant metastases, and 60% have died of their disease. Of those dying, 80% did so within 3 years of diagnosis (range 1 month to 9.1 years).

Adenocarcinoma↗

Patterns of failure in anorectal melanoma. A guide to surgical therapy.

Anorectal melanoma is an aggressive tumor with a reported 5-year survival rate of 6%. Recommendations for local surgical therapy vary from local excision to abdominoperineal resection. Therapy, patterns of failure, and survival were retrospectively examined in 32 patients with anorectal melanoma. Twenty-six patients were treated surgically, 14 with abdominoperineal resection and 12 with local excision. Local recurrence occurred less frequently in patients undergoing abdominoperineal resection (4 [29%] of 14) compared with patients undergoing local excision (7 [58%] of 12) but developed concomitantly with distant or regional metastasis in all but 2 of the 11 patients whose operations failed locally. Inguinal nodal disease developed in 15 patients (47%). Pelvic nodal disease became apparent in only 2 patients (7%). There was no difference in overall survival between the two surgically treated groups (median survival, 19.5 months for patients treated with abdominoperineal resection vs 18.9 months for patients treated with local excision). Therefore, local excision is recommended when technically feasible since these patients eventually succumb to metastasis regardless of surgical therapy.

Anal Canal↗

Breast cancer in young women: issues in local therapy.

Although age has been studied as a prognostic factor in breast cancer, little attention has been paid to its role in the selection and outcome of local therapy. A review of 42 breast cancer patients less than 40 years of age treated at the University of Chicago from 1989 to 1992 demonstrated that of women with stage 0, I, or II disease, 37% had medical contraindications to breast preservation compared with 25% of women over 40. Twenty-one percent of young women eligible for conservation opted for mastectomy and reconstruction compared with 9% of their older counterparts. Only 4% of women in either age group selected mastectomy alone as therapy. The literature on the relationship of age to local failure after breast conservation and the long-term morbidity of the local therapy of breast cancer is reviewed. Further research to clarify issues in local therapy in young patients is proposed.

Adult↗

Axillary dissection in breast cancer revisited.

The pathological status of the axillary nodes remains the single most determining factor for survival, local recurrence and disease-free interval in operable breast cancer. Radical axillary dissection results in better local control with or without systemic disease in all operable cases. In pathologically negative cases, radical axillary dissection decreases local recurrence rates and perhaps prolongs disease-free survival. In pathologically positive cases, radical axillary dissection improves local control only. Radical axillary dissection avoids axillary irradiation and so decreases the risk and the importance of lymphoedema. Perfect axillary dissection does not show a decisive advantage over less complete axillary dissection when the 'quality' of surgery is measured by lymphoscintigraphy, but it should be kept in mind that only total control of the local situation can ensure a patient free of distal spread at the time of first therapy.

Axilla↗