Successful multimodal therapy of a locally advanced non-small-cell bronchial cancer

HISTORY AND CLINICAL FINDINGS: A chest radiogram, performed on a 60-year-old man with unproductive cough for 3 months, showed a space-occupying lesion in the right upper lobe, and breath sounds were diminished in this area. He had been a heavy smoker. His general condition and nutritional state were good. INVESTIGATIONS: Computed tomography, skeletal scintigraphy, bronchoscopy with biopsy and mediastinoscopy established the diagnosis of a locally advanced non-small-cell bronchial carcinoma (stage IIIB or T2N3M0). TREATMENT AND COURSE: Combined adjuvant treatment was begun in the hope of improving the median survival time of 8 months predicted for this tumour stage. After two cycles of a combined chemotherapy scheme (ifosfamide, carboplatin, etoposide) he received hyperfractionated-accelerated radiotherapy (total dose 45 Gy; 1.5 Gy twice daily) together with carboplatin and vindesine. This was followed by a right upper lobectomy with lymphadenectomy. Full remission was confirmed in both the resected specimen and the lymph nodes. The patients remains free of tumour 30 months after the diagnosis. CONCLUSION: Neoadjuvant treatment can significantly improve the prognosis of non-small-cell bronchial carcinoma in stage III. Such patients should therefore be treated according to the appropriate study protocol, if possible.     

Is preoperative chemotherapy in locally advanced non-small-cell bronchial carcinoma of value?

Although surgeons are able to resect completely locally advanced non-small cell lung cancer with mediastinal lymph node involvement (stage IIIA), the majority of patients succumb from metastatic disease. Therefore, neoadjuvant therapy was introduced in the management of this disease in order to eradicate distant metastases at an early stage. Phase II trials with preoperative chemotherapy in stage IIIA patients have shown that the pathological response (amount of tumour necrosis) and the clearance of mediastinal lymph node correlate with a better survival and is the best predictor for eradication of distant metastases. Indeed, three small randomised phase III studies have demonstrated a survival advantage for preoperative chemotherapy compared to surgery alone. Further studies are required to determine the best neoadjuvant regimen inducing the largest amount of tumour necrosis.     

Induction treatment of locally advanced operable cancers of the esophagus. Prognostic significance of the histologic response

PURPOSE: To compare the effectiveness of topical dorzolamide hydrochloride (Trusopt, Merck and Co., Inc., West Point, PA), a carbonic anhydrase inhibitor, with that of oral acetazolamide (Diamox; Lederle Laboratories, Pearl River, NY) for the management of chronic cystoid macular edema in patients with retinitis pigmentosa. METHODS: A prospective, double-masked, crossover study was conducted in five patients with retinitis pigmentosa who had chronic cystoid macular edema. After baseline visual acuity was measured and a fluorescein angiogram was obtained, each patient was randomly assigned to receive either topical dorzolamide or a placebo for 4 weeks, followed by a crossover for the same period. Oral acetazolamide then was given separately to each patient for 2 weeks. Each phase of the study was followed by a washout period of 4 weeks, during which the patient was taken off all medications. At each visit, best corrected visual acuity was measured, a fluorescein angiogram was obtained, a subjective assessment of the effects on visual function, and any side effects of the medication or placebo were recorded in the form of a questionnaire by an independent observer. RESULTS: Compared with baseline or placebo values, there was no measurable improvement in visual acuity on the Early Treatment Diabetic Retinopathy Study charts with dorzolamide in any of the patients. The visual acuity in three of five patients, however, improved by seven letters or more with acetazolamide. Compared again with baseline or placebo values, fluorescein angiograms of two of five patients showed improvement in macular edema in both eyes with the use of dorzolamide, whereas all five showed improvement with acetazolamide. The improvement in macular edema was more marked with acetazolamide than with dorzolamide. The effect of dorzolamide given three times a day was the same as that when it was given five times a day. One patient indicated that dorzolamide was more effective than acetazolamide in improving visual function, three of five patients believed that acetazolamide was more effective, and one felt that both were equally effective. CONCLUSION: Dorzolamide provided improvement in cases of macular edema on fluorescein angiograms and subjective improvement of visual function in some patients with retinitis pigmentosa with cystoid macular edema. However, there was no measurable improvement in visual acuity with the topical use of this drug. Oral acetazolamide was found to be more effective than dorzolamide in managing macular edema and improving visual acuity.     

Combined resections of the diaphragm and the liver for a locally advanced non-small-cell lung cancer

A 73-year-old man was admitted to our hospital to undergo treatment for right lung cancer (large cell carcinoma) which had directly invaded the liver through the diaphragm, and presented with T3N0M0, stage IIIa disease. A right lower lobectomy was performed with lymph node dissection, combined with a partial resection of the diaphragm and the liver, as well as a reconstruction of the diaphragm using the latissimus dorsi muscle. The patient had an uneventful postoperative course and was free of disease 1 year later at the time when this paper was written.     

Current studies of combined radiotherapy-hormone therapy in localized and locally advanced prostatic cancers

In locally advanced prostate cancer three clinical randomized trials have shown that external irradiation combined with LHRH analogue with or without antiandrogen improved survival: disease-free survival, local recurrence-free survival, metastasis-free survival (P < 0.001). EORTC trial 22863 alone has shown a significant improvement of overall survival (P = 0.001), with an LHRH analogue (goserilin acetate, zoladex) started the first day of irradiation and followed every 4 weeks for 3 years; for RTOG trial 85-31 the same LHRH analogue started during the last week of irradiation and given until relapse increases survival of patients with poor differentiated tumours with gleason score ranging from 8 to 10 (P = 0.03). In locally confined prostate carcinoma randomized trials are ongoing to assess the impact of conventional irradiation or three dimensional conformal radiotherapy with or without adjuvant hormonotherapy.     

Multimodal treatment strategy for locally advanced breast cancer

BACKGROUND AND OBJECTIVE: To determine the efficacy of topical tissue plasminogen activator (tPA) for the resolution of postoperative or inflammatory intraocular fibrinous exudates. PATIENTS AND METHODS: Each treatment consisted of drops of 1 mg/ml tPA given 9 times 5 minutes apart. Records were reviewed and the results at 24 and 48 hours were recorded. Sixty-two patients had a total of 94 treatments. RESULTS: Fibrin exudates following intraocular surgery in 34 patients were treated 44 times. In 6 patients there was a positive result. Fibrin associated with intraocular infection was treated in 9 patients. None showed clear improvement. Nineteen patients had a total of 34 treatments for poorly controlled intraocular pressure (IOP) after glaucoma surgery. Five patients showed adequate control of the IOP, 12 did not change, and 2 had a questionable improvement. Eleven patients had adequate IOP control after additional treatment. Seven required suture lysis, 2 ab interno bleb revision, and 2 YAG capsulotomy or iridotomy to reduce the IOP to an acceptable level. CONCLUSIONS: Within the limits of this retrospective study and taking into account that fibrin may resolve spontaneously, it appears that topical tPA drops are not effective for the liquefaction of intraocular fibrin after surgery or in association with intraocular inflammation. They did not improve IOP control after glaucoma surgery.     

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.     

Weekly paclitaxel and cisplatin with concurrent radiotherapy in locally advanced non-small-cell lung cancer: a phase I study

PURPOSE: Both cisplatin (CDDP) and paclitaxel have shown good antitumor activity in non-small-cell lung cancer (NSCLC) patients and are able to potentiate the antitumor effects of radiation therapy (RT). This study aimed to determine the maximum-tolerated doses (MTDs) of CDDP and paclitaxel (escalated alternately) when given concurrently with RT and to define the nature of the dose-limiting toxicity (DLT). PATIENTS AND METHODS: Chemotherapy-naive patients with locally advanced NSCLC received six weekly administrations of a CDDP-paclitaxel combination with concurrent local RT. The starting doses of CDDP and paclitaxel were 30 mg/m2/wk and 35 mg/m2/wk, respectively. RT was initially given at the dose of 1.2 Gy twice daily for 5 days per week for 5 weeks (total dose, 60 Gy) and at a single daily dose of 2 Gy for 5 days per week for 6 weeks in the last two cohorts of patients. The drug doses were escalated alternately until DLT occurred in more than one third of the patients in a given cohort. RESULTS: Overall, 25 patients were recruited through five different cohorts. All were assessable for toxicity. Esophagitis was the main toxicity and occurred in 16 of 25 patients (64%) and was grade 3 or 4 in five of them. At step 3 (CDDP 35 mg/m2/wk and paclitaxel 45 mg/m2/wk), two of five patients had to discontinue treatment because of severe esophagitis and one of these died of complications related to grade 4 esophagitis. However, keeping the same doses of chemotherapy and replacing hyperfractionation with a standard single-day fraction, weekly doses of CDDP and paclitaxel of 35 mg/m2 and 45 mg/m2 could be safely administered. Neutropenia was by far the most relevant hematologic toxicity and occurred in 33 of 141 weekly delivered courses, but it was of grade 4 in only four courses. Substantial pulmonary or neurologic toxicity was not observed in this study. Two complete responses (CRs) and 13 partial responses (PRs) were observed, for a 60% overall response rate (95% confidence interval [CI], 39% to 79%). The median survival time was 16 months, with a 66% 1-year survival probability. CONCLUSION: CDDP 35 mg/m2/wk and paclitaxel 45 mg/m2/wk can be safely administered with concurrent standard RT. The use of hyperfractionation is associated with a more frequent occurrence of severe esophagitis and requires a reduction of the CDDP dose to 30 mg/m2/ wk. Only future randomized trials will elucidate which of these two approaches (standard or hyperfractionated RT) is the better option to improve the outcome of patients with locally advanced NSCLC.     

A new preoperative immunochemotherapy for the treatment of locally advanced esophageal cancer

A promising preoperative immunochemotherapy regimen for locally advanced esophageal cancer is herein described. A 67-year-old man suffering from severe dysphagia was diagnosed with unresectable esophageal cancer at initial examination because of a tumor of 11 cm in length and suspicion of trachea invasion. Neoadjuvant immunochemotherapy was undertaken for the down-staging. Interleukin-2 (IL-2) (3.5 x 10(5) Japan reference units), nedaplatin (7 mg/m2) and 5-FU (300 mg/m2) were administered intravenously daily for 5 days a week for three weeks. The gross findings of a barium esophagogram and esophagoscopy revealed significant tumor regression in both size and shape. The patient underwent an esophagectomy through a laparotomy followed by a right thoracotomy. The surgical specimens were serially sectioned and examined microscopically. All of the surgical margins were clear (upper and lower margins as well as the adventitia), and there was no evidence of lymph node metastasis. The surgical specimen revealed neoplastic squamous ghost cells surrounding significant lymphocyte infiltration. This appears to be a unique feature of this particular neoadjuvant immunochemotherapy.     

Endoscopically defined treatment strategies in patients with locally advanced esophageal cancer

Sixty-five consecutive, locally advanced esophageal cancer patients were treated by the West Side Medical Center Esophageal Service at the Cook County and University of Illinois hospitals. Each patient was prospectively evaluated with multiple endoscopies including esophagogastroduodenoscopy, bronchoscopy, nasopharyngoscopy, and laryngoscopy. Twenty-four patients (37%) had endoscopic findings that significantly altered therapeutic regimens. Patients identified as having an obvious or impending esophageal fistula or poor performance status were treated in a palliative fashion. Forty (61.5%) patients were considered candidates for treatment with multimodal therapy which included radiation, chemotherapy, and surgery. There was a response rate of 82.5% and a 1-year disease-free survival of 88.9% which was statistically significant when compared to the other patient treatment groups. These data illustrate the necessity of multiple endoscopic evaluation of locally advanced esophageal cancer patients for stratification into appropriate treatment groups. Aggressive treatment afforded selected patients excellent relief of presenting symptomatology, as well as an improved, more acceptable, disease-free survival.     

Methods of surgical treatment of advanced hydronephrosis in children

For the establishment of the therapeutic procedure in advanced hydronephroses the basic criterion is the functional state of their damaged kidney which can be assessed best by scintigraphy. The results of plastic repair of the damaged pelviureteral portion depends on the stage of hydronephrosis and the child's age. The best results were achieved in less damaged kidneys (hydronephroses I and II) in all age groups and in advanced hydronephroses (IV and V) in children under the age of one year. Early assessment of the diagnosis is important for achievement of good results. This is made possible by ultrasound screening. Early surgery can reduce the percentage of nephrectomies.     

Surgical treatment of locally advanced rectal cancer. Options and strategies

To evaluate the contribution of the subsets of T helper lymphocyte (Th) to the development of pulmonary lesion in mycoplasma pneumonia, we compared the pathological findings between Th1 dominant mice (C57BL/6) and Th2 dominant mice (BALB/c) in experimental Mycoplasma pulmonis (M. pulmonis) pneumonia. Mice (ICR, C57BL/6, and BALB/c) were intranasally inoculated with 0.03 ml of a solution containing M. pulmonis (1 x 10(8)) colony forming units per ml. Another M. pulmonis inoculated ICR mice were treated with interleukin-2 (IL2; 4.8 micrograms/day), days 3-9, intracutaneously). All mice were sacrificed at day 14, and the lung specimens were examined. Peribronchial lymphocyte cuffing was more prominent in C57BL/6 mice than that of ICR mice, and intra-alveolar inflammatory-cell infiltration in BALB/c mice was more prominent than in ICR mice. Pathological patterns of the lung in IL-2 treated ICR mice were mimicking those of C57BL/6 mice. These results suggested that pathological patterns of mycoplasma pneumonia in mice might be altered by the imbalance of host T helper lymphocyte subset.     

Deferred treatment of locally advanced nonmetastatic prostate cancer: a long-term followup

PURPOSE: We prospectively investigated long-term survival in select men with locally advanced, nonmetastatic prostate cancer managed with deferred treatment. MATERIALS AND METHODS: A total of 50 patients with prostate cancer clinically outside the prostatic capsule and without distant metastases were included in a surveillance protocol. The men were treated if and when symptoms occurred or upon request. The series was followed until December 1994. No patient was lost to followup. RESULTS: Median patient age at diagnosis was 71 years. All patients were followed more than 144 months or died before then. Actual (cumulative incidence) overall and disease specific survival rates at 5, 10 and 12 years were 68 and 90, 34 and 74, and 26 and 70%, respectively. A third of the patients had not received antitumor treatment at followup or before death. CONCLUSIONS: When managed with deferred treatment nonpoorly differentiated, locally advanced nonmetastatic prostate cancer seems to have a poorer survival outcome than similarly managed clinically localized prostate cancer. However, compared with other treatments and in terms of survival deferred treatment may be an option for select patients with such tumors and a life expectancy of 10 years or less.     

Value and limits of surgery in stage IIIB non-small-cell bronchial cancers

Storage of radon-producing material in two silos and two waste pits is one of the major environmental and occupational issues at a former uranium production facility, now a Superfund site. In addition, up to 100 metric tons of thorium is stored on the northeast side of the site. Concentrations of radium up to 17,600 Bq g(-1) (477,000 pCi g(-1)) or higher for silos and up to 45 Bq g(-1) (1,200 pCi g(-1)) for waste pits have been reported. This study was conducted to identify factors and climatic conditions that contribute to higher radon levels and to assess workers' exposure at the site. Data covering a 12-mo period were compiled from monitoring hourly real-time radon levels at indoor (within 3 buildings) and outdoor (at 14 on-site and 2 off-site monitoring stations) locations and from hourly site-specific meteorological information. The ranges of radon levels were as follows: 1.8-3,655 Bq m(-3) (0.05-98.8 pCi L(-1)) outdoor on-site, 3.7-329 Bq m(-3) (0.1-8.9 pCi L(-1)) outdoor off-site, and 1.8-111 Bq m(-3) (0.05-3.0 pCi L(-1)) indoor on-site. Only radon levels in the vicinity of the storage silos were significantly higher than levels off-site. Radon concentrations showed diurnal variations, with maximum levels occurring in the early morning and minimum levels in the afternoon. Seasonal variation was also observed, with radon levels higher during the summer through early fall and lower during the late winter through spring. Wind speed, relative humidity, and wind direction appeared to be the most significant predictors of radon concentration. The estimated radon dose to workers, calculated by using exposure models and annual average levels of radon in the work area, was below recommended exposure limits. These results suggest that the emission control methods at this site have been effective in maintaining environmental radon contamination and workers' exposure at acceptable levels.     

Therapeutic possibilities of surgical treatment of patients with non-small-cell lung carcinoma and adrenal metastasis

Reports on successful surgical treatment of patients with non-small lung carcinoma and adrenal metastasis are infrequent. For this reason the Authors believe interesting to report a case of a patient with non-small lung cancer and single adrenal metastasis who underwent lung superior lobectomy and, after chemotherapy, adrenalectomy. A relapse was observed one year later in the lumbar region and the patient was reoperated undergoing removal of the recurrence associated to splenectomy and pancreas tail resection; thereafter the patient was treated with local radiotherapy. Forty-one months after the first operation the patient is well and disease free.     

Contribution to the surgical treatment of haematoma and hygroma in adults (author's transl)

Among thirty cases of chronic subdural hematoma and hygroma in patients between 16 and 78 years of age, nine were found on the left side, ten on the right side and eleven were bilateral. The diagnosis was made in all cases by computer assisted tomography. Surgical treatment consisted in evacuating the subdural collection of fluid through two or three enlarged burr-holes, resection of the membranes were accessible through the burr-hole, irrigation of the subdural space and its subsequent drainage. The drain was left in postoperatively until the draining fluid became clear or the subdural space was dry. In one case there was a superficial intracerebral hematoma which obsorbed spontaneously. One patient with a subdural empyema required craniotomy. Only four out of ten patients who were comatose pre-operatively survived. Out of the 30 patients, 24 had a satisfactory postoperative outcome.     

Organ preservation in locally advanced carcinoma of the uterine cervix

The purpose of this study was to demonstrate the potential usefulness of the combination of gadolinium and dysprosium to enhance the different between normal and necrotic liver tissue. Small regions of acute necrosis were induced by injecting 200-300 microliters of 95% alcohol into the liver of 26 rats. MRI was performed 24 hours after necrosis induction, before and immediately after injection of one or both contrast agents. Using a mixed T1/T2-weighted sequence, the signal intensity of (SI) of the normal liver was reduced by 70%, whereas the necrotic regions had more than a 50% increase in SI after double contrast. The region that was enhanced corresponded largely with the region of necrosis as observed postmortem. The lesion size, when identified, was largely underestimated using either of the agents along, albeit using the common pulse sequences. The double contrast effect of simultaneous administration of gadolinium and dysprosium allows accurate delineation of liver necrosis.     

Role of axillary lymph node dissection after tumor downstaging with induction chemotherapy for locally advanced breast cancer

BACKGROUND: Induction chemotherapy has become the standard of care for patients with locally advanced breast cancer (LABC) and currently is being evaluated in prospective clinical trials in patients with earlier-stage disease. To better gauge the role of axillary lymph node dissection in patients with LABC this study was performed to assess initial axillary status on physical and ultrasound examination, axillary tumor downstaging following induction chemotherapy, and the accuracy of physical examination compared with axillary sonography in predicting which patients will have axillary lymph node metastases found on pathologic examination. METHODS: Between 1992 and 1996, 147 consecutive patients with LABC were registered in a prospective trial of induction chemotherapy using 5-fluorouracil, doxorubicin, and cyclophosphamide. Physical and ultrasound examinations of the axilla were performed at diagnosis and after induction chemotherapy. Segmental resection with axillary lymph node dissection or modified radical mastectomy was performed, followed by postoperative chemotherapy and irradiation of the breast or chest wall and regional lymphatics. RESULTS: Following induction chemotherapy, 43 (32%) of the 133 patients with clinically positive lymph nodes on initial examination had axillary tumor downstaging as assessed by physical and ultrasound examination. The sensitivity of axillary sonography in identifying axillary metastases was significantly higher than that of physical examination (62% vs. 45%, P=.012). The specificity of physical examination (84%) was higher than that of sonography (70%), but the difference did not reach statistical significance. Among the 55 patients in whom the findings of both physical and ultrasound examination of the axilla were negative following induction chemotherapy, 29 patients (53%) were found to have axillary lymph node metastases on pathologic examination of the axillary contents. However, 28 (97%) of these patients had either 1 to 3 positive lymph nodes or only micrometastases 2 to 5 mm in diameter. CONCLUSIONS: Preoperative clinical assessment of the axilla by physical examination combined with ultrasound examination is not completely accurate in predicting metastases in patients with LABC following tumor downstaging. However, patients with negative findings on both physical and ultrasound examinations of the axilla may be potential candidates for omission of axillary dissection if the axilla will be irradiated because minimal axillary disease remains. Patients who have positive findings on preoperative physical or ultrasound examinations should receive axillary dissection to ensure local control. A prospective randomized trial of axillary dissection versus axillary radiotherapy in patients with a clinically negative axilla following induction chemotherapy is currently underway.