Radioimmunoguided surgery after primary treatment of locally advanced breast cancer.

PURPOSE: To assess the role of radioimmunoguided surgery (RIGS) using a handheld intraoperative gamma-detecting probe (GDP) to identify neoplastic disease after primary chemotherapy in locally advanced breast cancer (LABC) patients injected with iodine 125-labeled monoclonal antibodies (MAbs). PATIENTS AND METHODS: Twenty-one patients with histologically documented LABC were treated with a combined modality approach. After three courses of primary chemotherapy and before modified radical mastectomy, the 125I-radiolabeled MAbs B72.3 (anti-TAG72) and FO23C5 (anti-carcinoembryonic antigen [CEA]) were administered to 11 patients (group A) and 10 patients (group B), respectively. At surgery, a GDP was used to locate the primary tumor and to assess possible tumor multicentricity and the presence of ipsilateral axillary metastases. Routine pathologic examination was performed in neoplastic and normal tissue specimens of all 21 patients. In addition, immunohistochemical assay for TAG72 and CEA expression was performed. RESULTS: In group A patients, RIGS identified primary tumor in seven of 11 patients (63.3%) and unpalpable multicentric tumor lesions were located in two of four (50%). Positive axillary lymph nodes were histologically documented in eight of 11 patients (72.7%) and RIGS identified three of eight (37.5%). In group B, RIGS located the primary tumor lesion in four of 10 patients (40%); in two cases, the tumor was not clinically evident. Multicentricity was observed in one of two patients and lymph node involvement in three of nine (33.3%). No false-positive results were observed in either group A or B. CONCLUSION: RIGS appears to be a safe and reliable technique. However, the MAbs used in this study are not sufficiently specific. RIGS represents a technique for which the full potential for intraoperative assessment of breast cancer lesions can be reached when more specific antibodies become readily available.

Role of B72.3 iodine 125-labeled monoclonal antibody in colorectal cancer detection by radioimmunoguided surgery.

BACKGROUND: Radioimmunoguided surgery (RIGS) by means of radiolabeled monoclonal antibodies and a probe has been reported to be useful in recognizing subclinical tumor deposits during operation. Aim of this study was to understand the limits of this technique and to assess the potential diagnostic use of RIGS in colorectal cancer surgery. METHODS: Monoclonal antibody B72.3 reacting with TAG 72 antigen, labeled with iodine 125, was injected in 32 patients with primary tumors and in 22 patients with recurrent colorectal cancer. One hundred thirty-three suspected tumor sites were evaluated during operation by means of probe and resected with immunohistochemistry as control. RESULTS: Primary tumor sites were localized by RIGS in 60% of cases, and recurrent sites were localized in 82% of cases. There was a significant correlation both for primary (p < 0.001) and recurrent (p < 0.001) tumor sites between intraoperative RIGS findings and TAG 72 tumor antigen expression. Results obtained with the probe were instrumental in modifying the surgical approach in six (27%) of 22 patients with recurrences, allowing the removal of tumor masses that would otherwise have been overlooked. CONCLUSIONS: The results of RIGS seems to be encouraging in terms of clinical use. The potential high diagnostic resolution appears to improve surgical ablation of colorectal cancer, especially in patients with recurrent cancer or suspected recurrent tumors who have negative results for intraabdominal disease by all other roentgenographic criteria with rising carcinoembryonic antigen or TAG 72 antigen levels.

Prognostic role of lymph-node level involvement in patients undergoing axillary dissection for breast cancer.

AIMS: Clinical records of patients undergoing surgery for breast cancer were reviewed in order to evaluate the prognostic role of lymph-node level involvement. METHODS: From 1982 to 1991, 1143 patients had radical mastectomy or conservative surgery with total axillary dissection: 461 patients of mean age 57.1 years (range: 25-89 years) were lymph-node positive (pN1); 369 patients (80%) had radical mastectomy; and 92 patients (20%) had conservative treatment plus post-operative radiotherapy, with the same mean number (n = 16) of lymph nodes collected in the surgical specimen. Data were analysed for the number of positive lymph nodes and level of involvement. RESULTS: Level I, Levels I + II and Levels I + II + III were involved in 44.9, 18 and 21.4% of patients, respectively; 'skip metastases' occurred in 72 of 461 pN1 patients (15.5%). A univariate analysis showed that prognosis was directly related to the number of levels involved (P < 0.001), and skip metastases had the same prognostic role as Level I involvement. The numbers of involved lymph-node levels and metastatic lymph nodes were well correlated; multivariate analysis showed that involvement of Levels I and III was independently correlated with prognosis. After adjustment for age and number of positive lymph nodes, the number of involved lymph-node levels was an independent prognostic factor, with highest predictability when all three lymph-node levels were positive (P = 0.009). CONCLUSIONS: The prognostic value of lymph-node status should be defined not only by the number of metastatic lymph nodes, but also by the number of levels of involvement.

Pre-operative localization of non-palpable lesions in breast cancer by charcoal suspension.

The use of preoperative localization procedures for non-palpable breast lesions (NPBL) is becoming more and more widespread, increasing the detection of early breast cancers. From October 1987 to July 1992, at our Institution, 253 patients (pts) with clinically non-palpable lesions underwent surgical treatment. Of the 253 pts, the lesions have been localized in 95 cases by a needle system, and in the other 158 cases by a dye injection of a 3% sterile charcoal suspension using stereotactic method (118 cases) or sonography (40 cases). The patients' mean age was 53 years (range 30-75). Mammography revealed regular opacities in 133 cases, clustered microcalcification in 75, diffuse microcalcification in 24, opacities with irregular borders in nine and opacities with internal microcalcifications in 12. The histological findings showed benign breast disease in 175 cases (69.2%), borderline breast disease in 23 (9.1%) and malignancy in 55 (21.7%). The benign/malignant/borderline lesions ratio was 3.2:1. The majority (70%) of these malignant lesions were small cancers (less than 1 cm in diameter) and without lymph-node involvement. The biopsy cost (benign/malignant/borderline ratio, patients discomfort and cosmetic result) has been acceptable.

Surgical complications related to peri-operative adjuvant chemotherapy in breast cancer. Results of a prospective, controlled, randomized clinical trial.

From May 1985 to June 1992, 375 patients were enrolled in a prospective controlled randomized clinical trial of peri-operative adjuvant chemotherapy (PAC) associated with long-term adjuvant chemo-endocrinotherapy in order to test the effectiveness of reducing the time interval between surgery and chemotherapy. The short-term surgical complications related to PAC are reported in order to verify whether such treatment might negatively affect the results of breast cancer surgery. One hundred and eighty-nine patients were randomly assigned to the peri-operative treatment, and 186 to the control group. Patients undergoing PAC received one course of cyclophosphamide (600 mg/sqm), epidoxorubicin (60 mg/ sqm), and 5-fluorouracil (600 mg/sqm) (CEF) within 48-72 h following surgery. Pathologically node-positive (N+) patients, who were given peri-operative CEF, had five further cycles of CEF alternated with six cycles of CMF (cyclophosphamide 600 mg/sqm, methotrexate 40 mg/sqm, and 5-fluorouracil 600 mg/sqm). All the other N+ patients received six cycles of CEF alternated with six cycles of CMF, starting within 30 days of surgery. No significant difference in post-operative morbidity was observed as regards median hospital stay (8 days), number of outpatient dressings (3.5 vs 3), seroma (51 (26.9%) vs 45 (24.2%)), lymphatic drainage (400 ml vs 409 ml), and post-operative infections, both local (10 vs 9) and in extraoperative foci (6 vs 7), in the study and control group, respectively. The toxicity of the peri-operative CEF was mainly gastrointestinal (nausea and vomiting, 55%; stomatitis, 3%), with only a small percentage (9%) reaching grades III-IV. Hair loss was the other main side effect (55%) with baldness in only 3%. Post-operative complications following radical breast cancer surgery seem to be primarily related to operative details (type of incision, accurate nerve-sparing technique, bleeding control, closure of subcutaneous and skin, drainage, aseptic technique) rather than to the one course of PAC.

Predictive value of some clinical and pathological parameters on upper level axillary lymph node involvement in breast cancer.

The role of radical axillary dissection in breast cancer management is presently under discussion. In this study we have evaluated the relationship between the pattern of metastatic axillary lymph node involvement by level and some of the main prognostic factors (age of the patient, size, grading, estrogen receptor and progesterone receptor status of the primary tumor) in 185 patients with operable breast cancer. The III level appeared to be involved in 31 (16.8%) out the 108 patients with axillary lymph nodes positive for metastases. A discontinuous pattern of axillary involvement (skip metastases) was observed in about 10% of cases. Logistic regression analysis of the data shows that only G3 is significantly correlated with the risk of III level invasion (p less than 0.05). We conclude that, at present, a selection of possible candidates for a less than radical axillary dissection is not as yet feasible. Since the risk for III level invasion cannot be sufficiently defined.

Perilymphatic injections of recombinant interleukin-2 (rIL-2) partially correct the immunologic defects in patients with advanced head and neck squamous cell carcinoma.

Patients with advanced head and neck squamous cell carcinoma (HNSCC) are severely immunocompromised. In virtually all such patients who have been studied, reduced numbers of circulating CD3+ T-cell-receptor (TCR)alpha/beta+ T lymphocytes, a reduction of natural killer (NK) activity, and a poor induction of lymphokine-activated killer (LAK) cell activity (following in vitro treatment with recombinant interleukin-2 [rIL-2]) have been detected. Recently, however, it has been demonstrated that perilymphatic injections of low doses of rIL-2 may induce a local reduction of tumor masses in these patients. The present study, a cooperative pilot effort on the clinical effects of this route of administration, showed an activation of the lytic machinery in lymphocytes belonging to the T-cell lineage, as well as a potentiation of NK activity in the peripheral blood. These findings demonstrated that the severe immunodeficiency of HNSCC patients may be at least partially corrected by in vivo administration of rIL-2.

A phase I study of recombinant interleukin-2 intraperitoneal infusion in patients with neoplastic ascites: toxic effects and immunologic results.

A phase I study to evaluate the use of i.p. infusion of recombinant interleukin-2 (rIL-2) was planned. The following dose levels were calculated: 0.1, 0.3, 1.0, 3.0 and 10 mg/m2/day for 14 days, but only the second levels were reached. In this trial the acute toxic effects at this dosage included cardiac ischemia, transient liver impairment and septic peritonitis. The maximum tolerated dose (MTD) was 0.3 mg/m2/day for 14 days. In addition, two patients developed peritoneal fibrosis. No objective responses were observed. Therefore, in order to explore the biological activity of low (nontoxic) doses, three patients (one untreated and two previously treated with rIL-2) were infused with 0.01 and 0.03 mg/m2/day for 7 days. Potentiation of cytolytic activities in peritoneal lymphocytes and activation of a lymphokine cascade in the ascitic fluid were observed at doses ranging from 0.03 mg/m2/day to 0.3 mg/m2/day. These findings in association with the toxic effects observed at the MTD suggest the use of the minimum effective dose for future locoregional immunotherapeutic protocols.

Immediate reconstruction of the penis using an inferiorly based rectus abdominis myocutaneous flap.

A new method for reconstruction of the penis using an inferiorly based rectus abdominis myocutaneous flap is described that seems to be particularly suitable for immediate one-stage reconstruction. Function of the residual portion of rectus muscle is preserved, and the abdominal wall is not significantly weakened.

Oral and pharyngeal cancer: combined approach for multimodal therapy.

Five-year results in 60 oral and pharyngeal cancer patients treated with combined approach chemoradiotherapy (39 patients) and chemoradiotherapy plus lymph node surgery (21 patients) are reported. Complete remission (CR) was achieved in 16/39 (41%) patients treated with chemoradiotherapy alone, and in 16/21 (76%) patients who had chemoradiotherapy plus surgery. The number of CR was statistically (chi-square test) higher (p less than 0.025) in the second group. The 5-year actuarial survival was 39.7% in the group of patients treated with chemoradiotherapy plus surgery. After 5 years 53% of the patients who reached CR are living free of disease in the first group and 76% in the second group.

Localization of the sentinel lymph node in breast cancer by combined lymphoscintigraphy, blue dye and intraoperative gamma probe.

Axillary lymph node status represents the most important prognostic factor in patients with operable breast cancer. A severe limitation of this technique is the relatively high rate of false negative sentinel lymph nodes (>5%). We studied 284 patients suffering from breast cancer; 264 had T1 tumors (16 T1a, 37 T1b and 211 T1c), while 20 had T2 tumors. All patients underwent lymphoscintigraphy 18-h before surgery. At surgery, 0.5 mL of patent blue violet was injected subdermally, and the sentinel lymph node (SN) was searched by gamma probe and by the dye method. The surgically isolated SN was processed for intraoperative and delayed examinations. The SN was successfully identified by the combined radioisotopic procedure and patent blue dye technique in 278/284 cases (97.9%). Analysis of the predictive value of the SN in relation to the status of the axillary lymph nodes was limited to 191 patients undergoing standard axillary dissection irrespective of the SN status. Overall, 63/191 (33%) identified SNs were metastatic, the SN alone being involved in 37/63 (58.7%) patients; a positive axillary status with negative SN was found in 10/73 (13.7%) patients with metastatic involvement. In T1a-T1b patients the SN turned out to be metastatic in 9/53 patients (17.0%). In 7/9 patients the SN was the only site of metastasis, while in 2/9 patients other axillary lymph nodes were found to be metastatic in addition to the SN. None of the 44 patients in whom the SN proved to be non-metastatic showed any metastatic involvement of other axillary lymph nodes. Our results demonstrate a good predictive value of SN biopsy in patients with breast cancer; the predictive value was excellent in those subjects with nodules smaller than 1 cm.

[Palliative demolitive surgery]. / Chirurgia demolitiva a scopo palliativo

Nine cases of untreatable tumour in which radical surgery was employed palliatively are presented. Three hemipelvectomies for recurrent rhabdomyosarcoma were performed. In one case, death occurred postoperatively, probably as a result of pulmonary embolism. One patient survived for 8 months, while the other is still alive after three years. Of two cases in which interscapulothoracic disarticulation was performed, survivals of 9 and 5 months were observed in subjects with fibrosarcoma in a mastectomy site and recurrent sarcoma of the humerus with ling metastases. Survival to 7 months was obtained in a case of sarcoma of the maxilla, while three patients with squama cell cancer of the mouth floor, chondrosarcoma of the mandible and botryoid sarcoma of the tonsillar fossa are still living after periods of 10 months to 2 yr. Though devoid of schematic indications, palliative demolition surgery can be considered in borderline cases where the operative risk is not high. Irrespective of "quantity", the "quality" of life remaining to the patients can be made compatible with the psychophysiological limits of the human personality.

[Current status of the classification and clinical staging of primary and secondary tumors of the liver]. / Considerazioni sullo stato attuale della classificazione e stadiazione clinica dei tumori primitivi e secondari del fegato.

Over the past few decades there has been outstanding expansion in the surgical exeresis of primary and metastatic liver tumours and particularly hepatic metastases of colorectal carcinomas. With the advance in surgical technique it becomes increasingly necessary to codify the system for the classification and clinical staging of these conditions for the purposes of correct programming of treatment and assessment of the clinical results obtained. The most commonly used systems of classification and clinical staging are analysed, in particular the classifications proposed by the American Joint Committee on Cancer and D. Manfredi for primary liver tumours and those proposed by Gennari et al and Sugerbaker et al for hepatic metastases of colorectal carcinomas. The selection criteria adopted in each system are analysed as the basis for a more thorough discussion of the problem that is felt to be fundamental for the standardisation of classification and clinical staging systems in the future. Such standardisation is essential for the assessment of the value and limitations of liver surgery in cancer.

[Study on the attitude and smoking habits of the students of a school for professional nurses]. / Indagini sugli atteggiamenti e sulle abitudini al fumo degli allievi delle scuole per infermieri professionali.

A study on 285 students and teachers of a nurse professional school was undertaken in two hospital of Genoa. A questionnaire proposed by World Health Organization and by Italian League Against Cancer was employed to collect data on smoking habits and behaviour. Subjects included in the present study were selectively chosen as they are in a transitional phase between school application and working environment within the hospital practice. Although these sample of hospital personnel showed a slow trend toward quit smoking, the rates of smokers are rather high, both in the youth (55%) and in the teachers. Our results showed that 87% of subjects interview agreed with the necessity to avoid smoking within the hospital environment; young nurses generally lack a specific knowledge about the hazard of smoking and more detailed information is requested for a correct education and prevention of patients' health.

[Anatomo-functional consequences of the radical surgery of the cervico-cephalic region in oncologic patients]. / Le conseguenze anatomo-funzionali della chirurgia demolitiva del distretto cervico-cefalico in pazienti oncologici.

The role of surgery in head and neck cancer treatment is now well established, as it appears the most effective approach to such patients, while other therapies (i.e. chemotherapy, radiotherapy) can be of some help as second choice procedures. Surgery demonstrates however its own pitfalls, as it can often cause secondary anatomo-functional defects. The main problems appear to be related to the impossibility of physiological feeding following composite resection for oral cancer. An immediate reconstruction by transposition of myocutaneous flaps is of the utmost importance, as it reestablishes the preoperative condition lessening hospitalization time and postoperative disabilities. Neurological lesions, an unfrequent major complication of cervical lymphadenectomy, can cover a wide range of seriousness, from hardly detectable sensorial deficits to the impossibility of spontaneous ventilation. In this paper the Authors, on the basis of their experience, describe the measures to be taken in order to avoid secondary lesions (or to minimize their effects) in head and neck cancer surgery.

[Local regional recurrences after radical mastectomy. Studies of 50 cases]. / Recidive loco-regionali dopo mastectomia radicale. Osservazioni su 50 casi.

Resection of locoregional recurrences was performed after mastectomy in 50 cases in the period 1961-1974. An incidence of 2% to 35% is reported for such recurrences, which are due to a variety of factors. In the present series, attention was directed to age at mastectomy and at recurrence, size of primary tumour, presence of axillary metastases, and details of menarche, menopause and pregnancy. Mean age at mastectomy was 50 yr and at recurrence 53 yr. Tumour diameter ranged from 2 to 5 cm in 73% of cases. Lympho node metastases were present in 42%. In 80%, the recurrence was paracicatricial, in 13% parasternal, and in 7% axillary. Treatment consisted of resection, radiochemotherapy or endocrino-ablative management.

[Role of surgery in the prognosis of AIDS and related syndromes. Case reports ]. / Ruolo della chirurgia nella prognosi dell'AIDS e sindromi correlate. Contributo casistico.

The authors review the epidemiologic and etiopathogenetic aspects of AIDS, in agreement with data published in december by the Center for Disease Control and by the WHO for the States, Europe and Italy. In their experience twenty-one patients, with clinical clues of AIDS, undergoing lymph node biopsy, have been analysed (18 LAS-ARC and 3 AIDS) and the role of prophylaxis for the surgical approach to the patient with aids or related syndrome has been underlined.

[Cigarette smoking. A pilot project of dehabituation and experimental research]. / Fumo di sigaretta. Un progetto pilota di disassuefazione e una ricerca sperimentale.

An interdisciplinary approach was adopted in a pilot programme research project as the most effective way to obtain concrete results in curing tobacco-addiction. The various stages and effects of the treatment are analysed as a means of identifying the most appropriate techniques. The early results are reported under separate headings according to treatment type (psychological, neurophysiological, dietary, clinical, chemical).

Surgical treatment of thyroid cancer.

Surgery is the treatment of choice for thyroid cancer, often followed by I131 and thyroid hormone to control the local residual tumor and distant metastasis. Hundred and sixty-two patients with thyroid disease underwent surgery at the Division of Surgical Oncology of the Cancer Institute in Genoa. Thirty cases presented no malignant hot thyroid nodules, 37 of the other 132 cases were cancers (28%). In 23 cases (62%), the pathological diagnosis was papillary carcinoma, in ten cases (27%) follicular carcinoma, in four (11%) medullary carcinoma. In 13 cases (35%) (ten papillary carcinoma, two follicular carcinoma, one medullary carcinoma) the lesion was multicentric. Our data suggest that total thyroidectomy, performed in two steps, in most cases does not carry important post-operative morbidity but offers the greatest potential for cure. In our cases only one patient died (of the cancer). After radical surgery it is possible to detect and treat metastases by I131.

Retroperitoneal infectious myositis.

A case of retroperitoneal infectious myositis is described. The symptoms of infectious myositis may be confused with those of other more frequent soft tissue pathologies (haematoma and sarcomata). This infection is more frequent in countries with a tropical climate. The most frequent aetiological agent is Staphylococcus aureus. This paper reports on the diagnostic and therapeutic problems of this disease as recently observed at the Division of Surgical Oncology of the National Cancer Institute in Genoa.