Five-year survival rates of melanoma patients treated by diet therapy after the manner of Gerson: a retrospective review

OBJECTIVE: Compare 5-year melanoma survival rates to rates in medical literature. DESIGN: Retrospective. SETTING: Hospital in Tijuana, Mexico. PATIENTS: White adult patients (N = 153) with superficial spreading and nodular melanoma, aged 25-72 years. INTERVENTION: Gerson's diet therapy: lactovegetarian; low sodium, fat and (temporarily) protein; high potassium, fluid, and nutrients (hourly raw vegetable/fruit juices). Metabolism increased by thyroid; calorie supply limited to 2600-3200 calories per day. Coffee enemas as needed for pain and appetite. MAIN OUTCOME MEASURE: 5-year survival rates by stage at admission. RESULTS: Of 14 patients with stages I and II (localized) melanoma, 100% survived for 5 years, compared with 79% of 15,798 reported by Balch. Of 17 with stage IIIA (regionally metastasized) melanoma, 82% were alive at 5 years, in contrast to 39% of 103 from Fachklinik Hornheide. Of 33 with combined stages IIIA + IIIB (regionally metastasized) melanoma, 70% lived 5 years, compared with 41% of 134 from Fachklinik Hornheide. We propose a new stage division: IVA (distant lymph, skin, and subcutaneous tissue metastases), and IVB (visceral metastases). Of 18 with stage IVA melanoma, 39% were alive at 5 years, compared with only 6% of 194 from the Eastern Cooperative Oncology Group. Survival impact was not assessed for stage IVB. Male and female survival rates were identical for stages I-IIIB, but stage IVA women had a strong survival advantage. CONCLUSIONS: The 5-year survival rates reported here are considerably higher than those reported elsewhere. Stage IIIA/B males had exceptionally high survival rates compared with those reported by other centers.     

The radiotherapy of inoperable non-small-cell bronchial carcinoma. A retrospective analysis of 427 cases

BACKGROUND: The influence of tumor and patient characteristics on survival as well as acute normal tissue toxicity was retrospectively analyzed. PATIENTS AND METHODS: 427 patients with inoperable non-small cell lung cancer were retrospectively analyzed. Two thirds received a total dose of at least 70 Gy, and one third was irradiated with 60 to 66 Gy (2.0 to 2.5 Gy per fraction; split-course technique). 92% had a Karnofsky performance index of > or = 80%. Kaplan-Meier survival curves were generated and comparisons were made by the log-rank test. Prognostic factors were adjusted for by a proportional hazards analysis. RESULTS: Five-year survival rates (+/- SE) and the median survival times (95% confidence interval) were 2 +/- 2% and 11.1 months (9.1 ... 14.5) after 60 to 66 Gy; 8 +/- 2% and 14.9 months (13.3 ... 16.5) after 70+ Gy. The difference was significant in univariate (p = 0.0013) and multivariate analysis (p = 0.0006). Tumor stage (p = 0.0029: I + II > III; IIIA > IIIB) and gender (p = 0.0387: female > male patients) reached significance in multivariate analysis. Acute pneumonitis and esophagitis were observed in 11% and 9% of cases. CONCLUSIONS: Inoperable non-small cell lung cancer stage I to IIIA should be treated in a curative intention with total doses of about 70 Gy. This is feasible with acceptable normal tissue toxicity. Stage IIIB patients have a particular bad prognosis and should only be treated palliatively.     

Hyperfractionated radiotherapy combined with simultaneous chemotherapy in inoperable non-small cell lung cancer: a pilot study

Between March 1992 and February 1993, hyperfractionated radiotherapy (HRT) (1.2 Gy.fraction-1, twice a day, total dosage of 69.6 Gy) and simultaneous cisplatin (70 mg.m-2, 3rd and 23rd days of HRT) and etoposide (70 mg.m-2, 1-3rd and 20-23rd days of HRT) were applied to 27 patients with inoperable non-small cell lung cancer (NSCLC). Their Karnofsky performance statuses were 70-90%, and mean age was 52 (36-63). Two cases were stage II (one of the patients refused the operation and the other was medically inoperable because of insufficient ventilation), eight were stage IIIA and 17 were stage IIIB. No severe life-threatening grade IV acute toxicity findings were observed. Generally, acute side-effects were transient and did not require discontinuation of treatment. Tumour responses were as follows: complete response in six cases (23%); partial response in 19 cases (70%); and stable disease in two (7%). When complete response rates were compared according to stage, histological type, age group and weight loss, no statistically significant difference was found. Median overall and disease-free survival times were 14 months (95% confidence interval) (95% CI) 11-17 months and 10 months (95% CI 7-13 months), respectively. Twelve and 24 months overall and disease-free survival rates were 56 and 30%, and 36 and 24% respectively. No statistically significant difference was found in overall survival rates among epidermoid and nonepidermoid types, while the difference in disease-free survival was statistically significant. The acute and late complications of our HRT and simultaneous chemotherapy protocol were tolerable and the survival rates were encouraging.     

Inoperable non-small cell lung cancer: a retrospective analysis of 427 patients treated with high-dose radiotherapy

PURPOSE: The influence of patient and treatment characteristics on survival as well as normal tissue toxicity were retrospectively analyzed. METHODS AND MATERIALS: Four hundred twenty seven patients with unresectable non-small cell lung cancer received at least 60 Gy and two-thirds were treated with 70 Gy. RESULTS: Five-year survival rates and median survival time (95% confidence interval) were 2 +/- 2% (mean +/- s.e.) and 11.1 months (9.1-14.5) after 60-66 Gy (median 60 Gy); 8 +/- 2% and 14.9 months (13.3-16.5) after > or = 70 Gy (p = 0.0013). Stage I-II patients had significantly higher survival rates as compared to Stage III patients (p = 0.0015). Within the subgroup of Stage III patients those with Stage IIIA had significantly higher survival rates than Stage IIIB (p = 0.0167). Female patients achieved 5-year survival rates after 70 Gy of 15 +/- 7% as compared to only 7 +/- 2% of their male counterparts. Chemotherapy, histology, Karnofsky status, and age had no influence on survival after univariate and multivariate analysis. Nine percent and 11% of the patients suffered from moderate to severe pneumonitis and esophagitis. CONCLUSION: High-dose radiotherapy of unresectable non-small cell lung cancer with total doses > 60 Gy conventionally fractionated is feasible. With doses of > or = 70 Gy significantly higher survival rates were achieved as compared to 60-66 Gy. Normal tissue toxicity was acceptable. For Stage IIIB patients, however, treatment results are disappointingly low even after 70 Gy with no 5-year survivor.     

The possible advantage of hyperfractionated thoracic radiotherapy in the treatment of locally advanced nonsmall cell lung carcinoma: results of a North Central Cancer Treatment Group Phase III Study

BACKGROUND: A three-arm Phase III randomized trial was performed to compare response rates, time to local or distant progression, and survival for patients with unresectable (Stage IIIA or IIIB) nonsmall cell lung carcinoma treated with standard fractionated thoracic radiotherapy (SFTRT) versus accelerated hyperfractionated thoracic radiotherapy (AHTRT) with or without combination etoposide and cisplatin chemotherapy. METHODS: This trial was initiated in 1992 by the North Central Cancer Treatment Group. Patients with Stage IIIA or IIIB nonsmall cell lung carcinoma were eligible. They were randomly assigned to either SFTRT (6000 centigray [cGy] in 30 fractions) or AHTRT (150 cGy twice daily to a total dose of 6000 cGy, with a 2-week break after the initial 3000 cGy); the AHTRT was given alone or with concomitant cisplatin (30 mg/m2, Days 1-3 and 28-30) and etoposide (100 mg/m2, Days 1-3 and 28-30). RESULTS: A total of 110 patients were entered on study. Eleven patients were declared ineligible or off study on the day of study entry. This analysis was confined to the 99 eligible patients. This article reports mature follow-up, because more than 80% of the patients have died. The median follow-up of living patients was 2.5 years. There were suggestions of improvement in the rates of freedom from local recurrence and survival for patients treated with AHTRT (with or without chemotherapy) as opposed to SFTRT (P = 0.06 and P = 0.10, respectively). The improvement in survival associated with AHTRT (with or without chemotherapy) was statistically significant for the subgroup of patients with nonsquamous cell carcinoma after adjustment for other potentially confounding factors (P = 0.02). No differences in freedom from systemic progression or survival were found in a comparison of AHTRT with chemotherapy and AHTRT without chemotherapy. CONCLUSIONS: These results suggest that treatment of Stage IIIA or IIIB nonsmall cell lung carcinoma with AHTRT with or without chemotherapy may improve freedom from local progression and survival as compared with SFTRT, especially for patients with nonsquamous cell carcinoma. The statistical powers to detect the observed differences in median time to local progression and survival were approximately 55% and 35%, respectively. Therefore, further investigation comparing SFTRT with AHTRT is warranted.     

Adjuvant radiotherapy and chemotherapy for stage II or IIIA non-small-cell lung cancer after complete resection. Provincial Lung Cancer Disease Site Group

GUIDELINE QUESTIONS: 1) Does the use of postoperative, adjuvant radiotherapy or chemotherapy, alone or in combination, improve survival rates among patients with completely resected, pathologically confirmed stage II or IIIA non-small-cell lung cancer (NSCLC)? 2) Does the use of radiotherapy reduce the risk of local recurrence among patients with completely resected stage II or IIIA NSCLC? OBJECTIVE: To make recommendations about the use of postoperative adjuvant radiotherapy and chemotherapy in the treatment of patients with completely resected stage II or IIIA NSCLC. OUTCOMES: Overall survival and disease-free survival are the primary outcomes of interest. A secondary outcome of interest is local disease control. PERSPECTIVES (VALUES): Evidence was collected and reviewed by 4 members of the Lung Cancer Disease Site Group (Lung Cancer DSG) of the Cancer Care Ontario Practice Guidelines Initiative. The evidence-based recommendation resulting from this review was approved by the Lung Cancer DSG, which comprises medical oncologists, radiation oncologists, pathologists, surgeons and a medical sociologist. A community representative was present at 1 meeting during which the recommendation was discussed. QUALITY OF EVIDENCE: One meta-analysis and 22 randomized controlled trials (RCTs) were published between 1962 and 1996. The RCTs compared surgery plus radiotherapy with surgery alone; surgery plus adjuvant chemotherapy with surgery alone; surgery plus radiotherapy with surgery plus both chemotherapy and radiotherapy. Many studies included patients with stage IIIB NSCLC; some included patients with incompletely resected stage I NSCLC or with small cell lung cancer (maximum 10%). Older studies used chemotherapy or radiation that would now be considered inferior according to current standards of practice. BENEFITS: There was no survival benefit with adjuvant radiotherapy alone, although 3 RCTs reported a reduction in the rate of local recurrence among patients treated with adjuvant radiotherapy. The meta-analysis showed that postoperative, cisplatin-based chemotherapy alone reduced the relative risk of death by 13% (hazard ratio [HR] 0.87, 95% confidence interval [CI] 0.74 to 1.02); in combination with radiotherapy it resulted in a 6% reduction in the relative risk of death (HR 0.94, 95% CI 0.79 to 1.11). HARMS: Postoperative adjuvant chemotherapy with alkylating agents was found in the meta-analysis to increase the relative risk of death by 15%. A study involving prolonged adjuvant chemotherapy (busulfan or cytoxan daily for 2 years) reported that 4 of 726 patients had hematologic malignancies. In 1 study, only 53% of patients received all 4 cycles of chemotherapy with cyclophosphamide-doxorubicin-cisplatin (CAP); in another, 22% of patients refused therapy with CAP because of nausea and vomiting. PRACTICE GUIDELINE: There is evidence from RCTs that postoperative radiotherapy reduces rates of local recurrence by 11% to 18% (or 1.6 to 19-fold) among patients with completely resected, pathologically confirmed stage II or IIIA NSCLC. Therefore, if the outcome of interest is a reduction in the frequency of local tumour recurrence, radiotherapy is recommended. However, there is no evidence of a survival benefit from postoperative radiotherapy alone. In a meta-analysis, postoperative chemotherapy with or without radiotherapy resulted in a slightly reduced (statistically nonsignificant) risk of death among patients with surgically resected stage II or IIIA NSCLC. The survival benefit was small and achieved only with chemotherapy regimens that produced substantial toxic effects and that are no longer used. Newer chemotherapy regimens are currently being evaluated as adjuvant therapy, but there is insufficient evidence of benefit at this time to recommend them. Therefore, if the outcome of interest is survival, there is insufficient evidence to recommend current chemotherapy regimens with or without radiotherapy as postoperative, adjuvant the     

Results of surgical treatment of T3 lung carcinoma according to the combined resection of involved organs

A new TNM staging system was decided last year by UICC, consequently T3N0M0 was transferred from stage IIIA to stage IIB. Although T3 is defined to include tumors with direct invasion to adjacent organs. Those are chest wall, parietal pleura, diaphragma and pericardium, however results of surgical treatment according to the combined resection of involved organs described above have not been investigated yet enough. Eighty-nine cases with T3 from 1996 were divided into two groups, patients from 1986 to 1990 and from 1994 to 1998. In the former phase 46 cases were resected and its 5-year survival rate was 15.6%. Better prognosis with significant difference was shown in patients between N0 (5-year survival: 25.1%) and N1 + N2 (5-year survival: 4.0%). In the latter phase 43 cases underwent surgery and its 3-year survival was 24.0%. In the prognoses according to the involved adjacent organs, patients with combined resection of parietal pleura showed the best survival in comparison with patients of chest wall resection and pericardial resection, but there was no significant difference in these 3 groups. Two patients with combined resection of diaphragma are well alive.     

Multidisciplinary approach to potentially curable non-small cell carcinoma of the lung

The management of patients with non-small-cell lung cancer (NSCLC) is still evolving. Newer third-generation chemotherapy (paclitaxel [Taxol]-based; vinorelbine [Navelbine]/ cisplatin [Platinol]) is more effective than second-generation cisplatin-based chemotherapy for patients with stage IIIB and IV disease. The combined use of cisplatin-based chemotherapy with sequential or concurrent radiation therapy has improved the survival of patients with unresectable stage IIIA disease. Neoadjuvant cisplatin-based chemotherapy has improved the survival of patients with resectable stage IIIA disease compared to surgery alone. Combined-modality therapy is a fertile area of innovative clinical investigations for the majority of stage III resectable and potentially curable NSCLC patients, as well as those with locally advanced unresectable stage III disease. We expect therapy to substantially improve over the next few years. Cooperative groups should move quickly to incorporate third-generation chemotherapy into large randomized trials in order to redefine the standard of therapy for patients with this disease.     

High-dose multimodality therapy with autologous stem-cell support for stage IIIB breast carcinoma

PURPOSE: Women with locally unresectable and inflammatory breast carcinoma (IBC) have an approximately 30% 5-year disease-free survival (DFS) rate with conventional multimodality therapy. A short but dose-intensive multimodality phase II trial was designed in an attempt to improve outcome in stage IIIB disease. Mastectomy was performed after high-dose therapy to evaluate pathologic response to treatment. METHODS: Women with newly diagnosed disease received four 2-week cycles of doxorubicin 90 mg/m2 with granulocyte colony-stimulating factor (G-CSF), followed by cyclophosphamide 6,000 mg/m2, thiotepa 500 mg/m2, and carboplatin 800 mg/m2 (CTCb) with marrow and peripheral-blood progenitor cell (PBPC) support. Local therapy consisted of mastectomy and radiotherapy. Tamoxifen (5 years) was begun if the patient was estrogen receptor-positive (ER+). RESULTS: Fifty women (46 stage IIIB [91% IBC], four stage IIIA) entered the study and 47 are assessable. Ten had mastectomy before any systemic therapy (seven with pathologic IBC, three with residual tumor after mastectomy). Eighty percent received full-dose doxorubicin with 60% on schedule. Clinical response rates to induction were 15% complete response (CR), 5% very good partial response (VGPR), 59% partial response (PR), and 21% minor response (MR)/stable disease (SD). Mastectomy after CTCb in 37 patients showed a 14% pathologic CR rate, 29% microscopic foci in breast and/or axilla, and 57% gross tumor. Fifteen (32%) patients have relapsed (median, 17 months post-CTCb). The 30-month DFS is estimated at 64%. For those in pathologic CR, with microscopic, or with gross disease remaining after CTCb, the 30-month DFS is estimated at 100%, 70%, and 38%, respectively. Those with zero, one to three, or > or = four positive nodes at axillary dissection had a median DFS of 31, 18, and 13 months, respectively. CONCLUSION: This short but dose-intensive multimodality approach for stage IIIB breast carcinoma is feasible with encouraging results to date.     

Short-course induction chemoradiotherapy with paclitaxel for stage III non-small-cell lung cancer

BACKGROUND: This study assessed toxicity, tumor response, disease control, and survival after short-course induction chemoradiotherapy and surgical resection in patients with stage III non-small-cell lung carcinoma. METHODS: Forty-five patients with stage III non-small-cell lung carcinoma received 12-day induction therapy of a 96-hour continuous infusion of cisplatin (20 mg/m2 per day), 24-hour infusion of paclitaxel (175 mg/m2), and concurrent accelerated fractionation radiation therapy (1.5 Gy twice daily) to a dose of 30 Gy. Surgical resection was scheduled for 4 weeks later. Postoperatively, a second identical course of chemotherapy and concurrent radiation therapy (30 to 33 Gy) was given. RESULTS: Induction toxicity resulted in hospitalization of 18 (40%) patients for neutropenic fever. No induction deaths occurred. Of 40 (89%) patients who underwent thoracotomy, resection for cure was possible in 32 (71%) patients. Pathologic response was noted in 21 (47%) patients, and 14 (31%) were downstaged to mediastinal node negative (stage 0, I, or II). At a median follow-up of 19 months, 24 patients were alive, 10 with recurrent disease. Of 21 deaths, 16 were from recurrent disease, three were from treatment, and two were unrelated. Recurrent disease was distant in 21 patients, distant and locoregional in 2, and locoregional in 3. The Kaplan-Meier projected 24-month survival is 49%. Projected 24-month survival is 61% for stage IIIA, 17% for stage IIIB (p = 0.035); 84% for pathologic responders, 22% for nonresponders (p<0.001); 83% for downstaged patients (stage 0, I, or II), 33% for those not downstaged (p = 0.005); and 63% for resectable patients, 14% for unresectable patients (p = 0.007). CONCLUSIONS: We conclude that short-course neoadjuvant therapy with paclitaxel (1) has manageable toxicity and a low treatment mortality, (2) results in good tumor response and downstaging, (3) provides excellent locoregional control with most recurrences being distant, and (4) has improved the median survival compared with historical controls. Survival was better in stage IIIA patients, resectable patients, pathologic responders, and patients downstaged to mediastinal node negative disease (stage 0, I, or II).     

Radiation Therapy Oncology Group (RTOG) 88-08 and Eastern Cooperative Oncology Group (ECOG) 4588: preliminary results of a phase III trial in regionally advanced, unresectable non-small-cell lung cancer

BACKGROUND: Regionally advanced, surgically unresectable non-small-cell lung cancer represents a disease with an extremely poor prognosis. External-beam irradiation to the primary tumor and regional lymphatics is generally accepted as standard therapy. The use of more aggressive radiation regimens and the addition of cytotoxic chemotherapy to radiotherapy have yielded conflicting results. Recently, however, results from clinical trials using innovative irradiation delivery techniques or chemotherapy before irradiation have indicated that patients treated with protocols that incorporate these modifications may have higher survival rates than patients receiving standard radiation therapy. PURPOSE: On the basis of these results, the Radiation Therapy Oncology Group (RTOG)-Eastern Cooperative Oncology Group (ECOG) elected to conduct a phase III trial comparing the following regimens: 1) standard radiation therapy, 2) induction chemotherapy followed by standard radiation therapy, and 3) twice-daily radiation therapy. METHODS: Patients with surgically unresectable stage II, IIIA, or IIIB non-small-cell lung cancer were potential candidates. Staging was nonsurgical. Patients were required to have a Karnofsky performance status of 70 or more and weight loss less than 5% for 3 months prior to entry into the trial, to be older than 18 years of age, and to have no metastatic disease. Of the 490 patients registered in the trial, 452 were eligible. The disease in 95% of the patients was stage IIIA or IIIB. More than two thirds of the patients had a Karnofsky performance status of more than 80. Patients were randomly assigned to receive either 60 Gy of radiation therapy delivered at 2 Gy per fraction, 5 days a week, over a 6-week period (standard radiation therapy); induction chemotherapy consisting of cisplatin (100 mg/m2) on days 1 and 29 and 5 mg/m2 vinblastine per week for 5 consecutive weeks beginning on day 1 with cisplatin, followed by standard radiation therapy starting on day 50; or 69.6 Gy delivered at 1.2 Gy per fraction twice daily (hyperfractionated radiation therapy). RESULTS: Toxicity was acceptable, with four treatment-related deaths. Three patients subsequently died of chronic pulmonary complications. Compliance with protocol treatment was acceptable. One-year survival (%) and median survival (months) were as follows: standard radiation therapy--46%, 11.4 months; chemotherapy plus radiotherapy--60%, 13.8 months; and hyperfractionated radiation therapy--51%, 12.3 months. The chemotherapy plus radiotherapy arm was statistically superior to the other two treatment arms (logrank P = .03). CONCLUSIONS: In "good-risk" patients with surgically unresectable non-small-cell lung cancer, induction chemotherapy followed by irradiation was superior to hyperfractionated radiation therapy or standard radiation therapy alone, yielding a statistically significant short-term survival advantage.     

Surgical resection of primary lung cancer. A 13-year experience in Geneva

This retrospective study concerns 683 consecutive patients operated for primary non-small cell lung cancer between 1977 and 1989 (581 men and 102 women with a mean age of 60.3 years). Histology was as follows: squamous in 422 (62%), adenocarcinoma in 207 (30%), broncho-alveolar in 24 (4%) and large-cell in 30 (4%). According to the TNM classification, 304 tumors were graded as stage I (45%), 130 as stage II (19%), 157 as stage IIIA (23%), 62 as stage IIIB (9%) and 19 as stage IV (3%). Surgery consisted of lobectomies in 337 (49%), pneumonectomies in 210 (31%), segmentectomies and wedge resections in 42 (6%), bilobectomies in 41 (6%) and exploratory thoracotomies in 53 (8%). It was curative in 513 cases (75%) and palliative in 170 (25%). 49 patients died within 2 months of the operation (7.2%), while 209 suffered postoperative complications (31%). Mediastinal lymph node dissection was not routinely performed to in this series. However global outcome (30% 5 years survival and 18% at 10 years), compared favorably with that reported by centres that perform mediastinal lymphadenectomy systematically.     

Comprehensive management of arteriovenous malformations

The treatment of arteriovenous malformations depends on the efforts of a multidisciplinary team whose ultimate goal is to achieve better results when compared to the natural history of the pathology. The role of adjuvant treatment modalities such as radiosurgery and endovascular embolization is discussed. Treatment strategies and surgical results from a personal series of 344 patients operated in a ten-year period are reviewed. The Spetzler and Martin classification was modified to include subgroups IIIA (large size grade III AVMs) and IIIB (small grade III AVMs in eloquent areas) to assist the surgical resection criteria. The treatment strategy followed was surgery for grades I and II, embolization plus surgery for grades IIIA, radiosurgery for grades IIIB, and conservative for grades IV and V. According to the new proposed classification 45 (13%) patients were grade I, 96 (28%) were grade II, 44 (13%) grade IIIA, 97 (28%) grade IIIB, 45 (13%) grade IV, and 17 (5%) were grade V. As for surgical results 85.8% of the patients had a good outcome (no additional neurological deficit), 12.5% had a fair outcome (minor neurological deficit), 0.6% had a bad outcome (major neurological deficit), and 1.2% died. These figures indicate that the treatment of arteriovenous malformations can achieve better results compared to the natural history if managed by a well trained group of specialists led by an experienced neurosurgeon.     

Liver transplantation for small hepatocellular carcinoma: the tumor-node-metastasis classification does not have prognostic power

Tumoral recurrence rate and survival of patients with hepatocellular carcinoma (HCC) treated by orthotopic liver transplantation (OLT) depend on tumor stage. Thereby, from the beginning of our program, we selected only patients with solitary tumors < or = 5 cm without vascular invasion, thus avoiding the use of the tumor-node-metastasis (TNM) staging system as a selection tool. The present study reports the results obtained in 58 consecutive patients (52 +/- 8 years, 47 males) with HCC (7 incidentals) transplanted between 1989 and 1995. Transplantation was indicated because of tumor diagnosis in 40 cases and advanced liver failure in 18. Mean tumor size at staging was 28.2 +/- 12.1 mm. No adjuvant treatment was applied during the waiting period (58.9 +/- 45.1 days). The pathological tumor-node-metastasis (pTNM) classification allocated 15 patients to stage I, 19 to stage II, 11 to stage IIIA, and 13 to stage IVA showing preoperative understaging in 43% of the cases with known tumor. After a median follow up of 31 months, only two patients have shown tumor recurrence and fifteen have died, the 1-, 3-, and 5-year survival being 84%, 74%, and 74%. All HCV+ patients remain infected and 94% showed significant liver disease (6 cirrhosis). Six patients have had a second transplant. In conclusion, the application of restrictive criteria not following the TNM staging system prompts excellent results for liver transplantation in patients with HCC, both in terms of survival and disease recurrence, even without applying adjuvant treatment; however, the survival data should be tempered by the appearance of complications that may worsen the long-term prognosis.     

Neuroendocrine differentiation is an independent prognostic factor in chemotherapy-treated nonsmall cell lung carcinoma

BACKGROUND: Neuroendocrine differentiation can be identified in 10-30% of patients with nonsmall cell lung carcinoma (NSCLC) by immunohistochemical or electron microscopic techniques. However, its clinical significance is not well established. METHODS: Tumors from 107 patients with Stage IIIA, IIIB, and IV NSCLC treated with cisplatin/etoposide with or without hydrazine in the North Central Cancer Treatment Group and Mayo Clinic protocols were analyzed immunohistochemically with antibodies to chromogranin A (CGA), Leu 7 (CD 57), and synaptophysin (SY). These results were compared with clinical outcomes. RESULTS: Keratin AE1/AE3, used as a control, was positive in 99.1% of cases; 34.6% had positive staining for at least 1 neuroendocrine marker, and 11.3% had positive staining for 2 or more markers. CGA was positive in 4.7%, Leu 7 in 18.7%, and SY in 24.3% of cases. A significant increase in survival was seen in patients with tumors expressing any one neuroendocrine marker or any combination of neuroendocrine markers (P < or = 0.01). There was no correlation between the presence of neuroendocrine differentiation and either response to chemotherapy or time to disease progression (P > 0.3), nor was there any correlation between chemotherapy response, time to progression, or survival with staining intensity or percent of cells positive per case. CONCLUSIONS: Neuroendocrine differentiation may be of prognostic significance in patients with advanced stage NSCLC treated with chemotherapy.     

Reamed interlocking intramedullary nailing of open fractures of the tibia

One hundred twelve open tibial fractures were treated by reamed interlocking nailing in 108 patients. There were 31 (28%) Grade I fractures, 38 (34%) Grade II, 23 Grade IIIA (21%), and 20 (18%) Grade IIIB fractures. Early amputation was performed in 2 (10%) Grade IIIB fractures for severe crushing injuries. Compartment syndrome complicated 8 (7%) fractures. Mean time to union was 29 weeks for Grade I fractures, 32 weeks for Grade II, 34 weeks for Grade IIIA, and 39 weeks for Grade IIIB. Nonunion complicated 9 (8%) fractures: 1 (3%) Grade I fracture, 2 (5%) Grade II fractures, 3 (13%) Grade IIIA fractures, and 3 (17%) Grade IIIB fractures. Deep infection complicated 4 Grade II fractures (10%) and 2 (11%) Grade IIIB fractures. Reamed locking intramedullary nailing is a safe and effective technique for management of open tibial fractures.     

Staging of breast cancer: what standards should be used in research and clinical practice?

BACKGROUND: Bone scan (BS), chest X-rays (CXR), liver ultrasonography (LUS) and laboratory parameters (LP) are frequently used as routine staging procedures for breast cancer patients. These procedures are not always appropriate in either clinical or research settings, regardless of the stage. The aim of this study was to identify groups of patients with differing risks for metastases in order to select more precise standard staging procedures. PATIENTS AND METHODS: The staging data relating to 406 breast cancer patients consecutively referred to our institution between November 1989 and October 1996 were analysed including pathological TNN grading and biological parameters. All of the cases with a positive or suspicious pre-operatory staging and who proved to have metastatic disease before surgery or during the first six months of follow-up were considered true-positive; all of the other cases with a positive or suspicious initial staging but with no evidence of distant metastasis before surgery and with a disease-free survival longer then six months were considered false-positive. In the same way all cases with negative initial staging who relapsed during the first six months of follow-up were considered false-negative and those with negative initial staging and with a disease-free survival longer then six months were considered true-negative. Statistical analysis was performed using Fisher's exact test. RESULTS: BS, CXR and LUS, 388, 399 and 398 examinations respectively, were considered available, and 17 (4.38%), six (1.5%) and four (1%), respectively, proved to be true-positive. A statistically significant difference was observed when our cases were grouped according to T status (T4 vs. T1-T2-T3, P < 0.01) and nodal status (N0-N1 cases with less than three involved nodes and N1 with more than three positive lymph nodes N2 patients, P < 0.01). CONCLUSIONS: The present study suggests that breast cancer patients can be divided into three subgroups with different detection rates for distant metastases at staging (0.59%, 2.94% and 15.53%), and that the standard practice should be changed. In the first (T1N0 and T1N1 patients with < or = 3 positive lymph nodes--41.13% of the patients) and the second group (T2N0, T2N1 with < or = 3 positive lymph nodes, T3N0 and T3N1 patients with < or = 3 positive lymph nodes--33.49% of the patients) there is no need for a complete set of staging procedures, whereas full procedural staging is needed in the third group of patients (T4, N1 with > 3 lymph nodes and N2, 25.37% of the patients).     

Surgical intervention for patients with stage IV-A hepatocellular carcinoma without lymph node metastasis: proposal as a standard therapy

OBJECTIVE: The aim of this study was to evaluate the effects of surgical treatments for patients with stage IV-A hepatocellular carcinoma (HCC) without lymph node metastasis. SUMMARY BACKGROUND DATA: Nonsurgical therapy for highly advanced HCC patients has yielded poor long-term survival. Surgical intervention has been initiated in an effort to improve survival. METHODS: The outcome of 150 patients who underwent hepatic resection was studied. Survival analysis was made by stratifying stage IV-A HCC patients into two groups-those with and those without involvement of a major branch of the portal or hepatic veins. Those with involvement were further divided into subgroups according to major vascular invasions. RESULTS: Patients who had multiple tumors in more than one lobe without vascular invasion had a significantly better 5-year survival rate (20%) than those with vascular invasion (8%) (p < 0.01). The survival rate of patients with hepatic vein tumor thrombi (10%) was better than the rate for those with tumor thrombi in the inferior vena cava (0%), in whom no patients survived more than 2 years, although the survival rate for those with portal vein tumor thrombi in the first branch (11%) was no different from the rate for that in the portal trunk (4%). The operative mortality decreased from 14.3% in the first 6 years to 1.4% in the following 5 years. CONCLUSIONS: Surgical intervention for stage IV-A HCC patients brought longer survival rates for some patients. We recommend surgical intervention as an effective therapeutic modality for patients with advanced HCC.     

Comparison of imaging TNM [(i)TNM] and pathological TNM [pTNM] in staging of bronchogenic carcinoma

OBJECTIVE: Precise tumor (T) and nodal (N) staging is imperative in non-small cell lung cancer (NSCLC) as it determines subsequent treatment, certainly when considering neoadjuvant treatment for stage IIIA or IIIB disease. To determine the accuracy of present-day computed tomographic (CT) scanning a prospective study was performed comparing imaging TNM [(i)TNM] and pathological TNM [pTNM]. METHODS: In 74 patients with NSCLC without distant metastases (i)TNM was determined on CT findings. The TNM system advocated by the American Joint Committee on Cancer was used. All patients underwent cervical mediastinoscopy. When superior mediastinal nodes were negative this was followed by thoracotomy and pathological examination of the resected specimen and lymph nodes to determine pTNM. RESULTS: The agreement between (i)TNM and pTNM was only 35.1%. The primary tumor (T) was correctly staged in 54.1%, overstaged in 27.0% and understaged in 18.9% of the patients. Invasion of chest wall, pericardium and of major mediastinal structures (T3, T4) was not reliably detected by CT scan. Sensitivity and specificity of CT regarding hilar and mediastinal lymph node staging were 48.3 and 53.3%, positive and negative predictive value 40 and 61.1% and its overall accuracy 51.4%. The nodal (N) factor was correctly determined by CT scan in 35.1%, overstaged in 44.6%, and understaged in 20.3% of the patients. CONCLUSIONS: Even with present-day CT scanners (i)TNM provides no accurate staging and routine mediastinoscopy is necessary for precise mediastinal lymph node staging. Likewise, (i)T3 and (i)T4 determinations are unreliable and should not contraindicate thoracotomy.     

The National Cancer Data Base report on gastric carcinoma

BACKGROUND: The National Cancer Data Base (NCDB) represents a national electronic registry system now encompassing almost 60% of incident cancers in the United States. In combination with other programs of the American College of Surgeons Commission on Cancer, the NCDB offers a working example of voluntary, accurate, and cost-effective "outcomes management" on a both a local and a national scale. METHODS: For the accession years 1985-1993, the NCDB has obtained information on demographics, patterns of care, disease stage, treatment, and outcome for a convenience sample of 57,407 gastric carcinoma cases (1.6% of total NCDB cases). In addition to describing trends, this report focuses on 5-year relative survival for a cohort of 1987-1988 cases staged according to the third edition of the American Joint Committee on Cancer's TNM classification, as well as patterns of care for a cohort of 1992-1993 cases. RESULTS: Stage-stratified 5-year relative survival for the 1987-1988 cohort was as follows: IA, 71%; IB, 56%; II, 37%; IIIA, 18%; IIIB, 11%; IV, 5%. Without noteworthy changes in stage distribution, demographics, or other factors, the proportion of patients treated by total gastrectomy is increasing slightly, but proximal gastrectomy for proximal cancers remains surprisingly popular. The proportion of cases receiving postoperative adjuvant treatment has declined slightly. Presumably because of advanced age and/or medical infirmity, a substantial proportion of U.S. patients with disease at every stage receive no treatment for cancer. CONCLUSIONS: This analysis of patterns of care has revealed unexplained variations in treatment and opportunities for improvement. Treatment of the elderly, infirm patient with gastric carcinoma appears problematic.