[Subjective grading of Barrett's neoplasia by pathologists: correlation with objective histomorphometric variables]. / Subjektive Graduierung von Barrett-Neoplasien durch den Pathologen: Korrelation mit objektiven histomorphometrischen Variablen.

Even though pathologists are trained to recognize the same histological features for the diagnosis and grading of different histological images, not all pathologists are influenced to a similar level of intensity by the same morphological characteristics of the tissue when scoring Barrett's dysplasia/neoplasia. The variables which most pathologists have intuitively chosen to use for scoring of the severity of Barrett's changes are mainly those related to the general tissue architecture, such as nuclear crowding, orientation and stratification. Interestingly, nuclear size is not used by most pathologists but nuclear pleomorphism and symmetry does influence a significant number of pathologists. Maybe the most difficult variables for the human eye to recognize are variables of chromatin texture (such as margination or heterogeneity), the predictive importance of which has been demonstrated in a previously published work. Textural variables may therefore remain the subject of a computerized analysis. Nevertheless, the fact that a few pathologists do actually correlate with nuclear texture in scoring, argues in favor of making further attempts to train pathologists to also rely on texture, similar to cytologists, when scoring Barrett's dysplasia.

Second primary tumors in mycosis fungoides patients: experience at the Northern Israel Oncology Center (1979-2002).

PURPOSE: Mycosis fungoides (MF) patients enjoy longstanding remissions following total skin electron irradiation (TSEI) but run the risk of developing secondary malignancies. Our purpose was to report our experience with the phenomenon of secondary malignancies in MF patients. PATIENTS AND METHODS: From 1979 to 2002, 84 patients with biopsy-proven MF were referred to our department for TSEI, using the modified Christie Hospital translational technique until 1992 and the Stanford technique after 1992. Median total dose was 32 Gy (range 16-44) Christie; 30 Gy (range 15-36) Stanford. Underdosed areas were boosted with a median total dose of 10-20 Gy. RESULTS: During a median follow-up of 73 months (range 2-191) from the end of the TSEI, 12 (15%) patients developed 17 second primary tumors within the irradiated areas and 6 patients developed 7 second primary tumors, either simultaneously with the newly diagnosed MF or prior to introduction of radiation therapy. CONCLUSION: The long-term prognosis was related solely to the second primary. Due to excellent long-lasting response rates following TSEI coupled with long-term survival, and the prognosis mainly associated to the stage and histology of the second malignancy, physicians should be aware of the possibility of second primary tumors.

Primary lymphoma of bone--a retrospective study. Experience at the Northern Israel Oncology Center (1979-2000).

OBJECTIVE: This retrospective study describes our experience with the diagnosis, treatment, results and long-term follow-up of primary bone lymphoma (PBL). PATIENTS AND METHODS: Nineteen patients diagnosed with PBL were reviewed. Seven patients presented with stage I(E) disease, four with stage II(E) (regional lymphadenopathy), and eight with stage IV disease (disseminated bone involvement). Only one stage IV patient exhibited 'B' symptoms. The majority (72%) demonstrated diffuse, large cell, B-type lymphoma. All patients were treated with adriamycin-based chemotherapy and consolidation radiotherapy to the primary site (8 patients: early PBL) or the most bulky area (3 patients: stage IV PBL). RESULTS: Ten stage I(E)/II(E) patients are alive with no evidence of disease (NED) and only one died due to metastatic secondary lung cancer while with NED from his PBL. Eight stage IV patients are alive with NED. Median follow-up for all living patients: 77 months. Side effects were mild and did not necessitate delay in treatment. CONCLUSIONS: Our departmental policy of treating PBL patients with an anthracycline-based regimen and involved field radiotherapy proved to be successful in achieving excellent long-term, disease-free survival. Phase III randomized, controlled, clinical trials will determine the true role of consolidation radiotherapy in PBL, when considering severe late side effects, including radiation-induced bone tumors.

Diagnosis and treatment of primary non-Hodgkin's lymphoma of the parotid gland: a retrospective study - Experience at the Northern Israel Oncology Center (1977-1999).

PURPOSE: The treatment and outcome of primary parotid gland non-Hodgkin's lymphoma (PGL) has rarely been described. This retrospective study documents the clinicopathologic features and treatment results in this relatively rare entity. PATIENTS AND METHODS: This study was conducted on 11 patients diagnosed and treated for primary PGL over a period of 22 years. RESULTS: Of the 4 male and 7 female patients, only one presented with the classic pattern of Sjögren's syndrome (SS) simultaneous with PGL, and only 4 patients demonstrated a low-grade Maltoma type. None of the patients had evidence of disease at the end of the primary treatment; 4 patients are alive and well from 6 months to 10 years after the end of treatment. Four patients relapsed and died due to therapy-resistant disease and 3 patients died of nonmalignant causes while in complete remission. CONCLUSION: The majority of patients with primary non- Hodgkin's lymphoma of the parotid gland present with early- stage disease. Accurate staging is mandatory. Low-grade, localized PGL can be treated successfully with primary radiotherapy alone. The aggressive type of PGL should be treated with combined chemoradiotherapy-based regimens.

Total skin electron irradiation in mycosis fungoides: comparison between a modified Christie Hospital translational technique and the Stanford technique.

Seventy-one patients with mycosis fungoides (MF) were treated by Total skin electron irradiation (TSEI) using either a modified Christie Hospital translational technique (44 pts) or a six dual-field Stanford technique (27 pts). There was no statistical difference in response rate, disease-free survival and overall survival between the two irradiation techniques. However, the Stanford technique was significantly less toxic than the modified Christie Hospital technique.

ATM heterozygosity and breast cancer: screening of 37 breast cancer patients for ATM mutations using a non-isotopic RNase cleavage-based assay.

Based upon the results of several epidemiologic studies, it has been suggested that women who are carriers for a mutation in the ataxia telangiectasia-mutated (ATM) gene are susceptible for the development of breast cancer. Therefore, 37 consecutive breast cancer patients were screened for the presence of a germline ATM mutation using a non-isotopic RNase cleavage-based assay (NIRCA). This paper reports the first use of NIRCA for detection of ATM mutations in breast cancer patients. Using this assay, no ATM mutations were found in our patient population. This result is similar to the findings of other studies that have employed approaches complementary to NIRCA.

Carboplatin and etoposide for recurrent malignant glioma following surgical and radiotherapy failure: A clinical study conducted at the Northern Israel Oncology Center.

BACKGROUND AND OBJECTIVES: We conducted a phase II study using carboplatin and etoposide on patients with recurrent malignant glioma to investigate tumor response. METHODS: From January 1995 to March 1997, 21 patients with recurrent malignant glioma were treated with a carboplatin (300 mg/m(2), day 1)/etoposide (100 mg/m(2), days 1-3) regimen every 3-4 weeks. The following radiologic parameters were evaluated: tumor size, central lucency, degree of contrast enhancement, and mass effect. No patient had received chemotherapy previously. Dose escalation corresponded to hematologic tolerance and to general and neurologic performance status. Most patients were treated postoperatively with involved field radiotherapy followed by a boost to the tumor area, as defined on the presurgery computed tomography scan or on magnetic resonance imaging. Mean interval to introduction of chemotherapy was 8.8 months (range, 7-36 months). Patients received a mean of four cycles [range, 2-8 cycles]. RESULTS: Only 2 patients showed moderate radiological response, while 12 patients died of progressive disease. Mean time to progression following discontinuation of chemotherapy was 5.8 months (range, 1-11 months). The other patients survived with persistent disease and are being treated palliatively. Toxicity was manageable (1, neutropenic sepsis; 1, thrombocytopenia (45,000/mm(3)); 2, temporarily elevated transaminase level; 2, steroid-induced erosive gastritis). CONCLUSIONS: This phase II regimen proved to be ineffective in recurrent malignant glioma. Further studies incorporating innovative drug regimens and schedules are warranted. J. Surg. Oncol., 1999;71:167-170.

Dexamethasone, cytarabine, ifosfamide, and cisplatin as salvage therapy in non-Hodgkin lymphoma.

The authors conducted a phase II study to evaluate a new combination of chemotherapeutic drugs that includes dexamethasone, cytarabine, ifosfamide, and cisplatin as salvage therapy in non-Hodgkin lymphoma after prior exposure to both adriamycin and etoposide. All drugs were administered intravenously over 4 consecutive days. The daily dose of dexamethasone was 20 mg twice daily. The maximal daily doses of cytarabine, ifosfamide, and cisplatin were 75 mg/m2, 1,200 mg/m2, and 20 mg/m2, respectively. Cycles were repeated every 3 weeks. A total of 31 patients were entered in the trial. Thirty patients were evaluable for response. A complete response was seen in 11 patients (37%), and a partial response was noted in six patients (20%). A significantly higher complete response rate was seen in patients with relapsing non-Hodgkin lymphoma compared with those who failed to achieve a complete response with the last chemotherapy (10/14 vs. 1/16; p < 0.013). A complete response continues in two patients who received consolidation with high-dose chemotherapy for more than 49 months and more than 60 months for each patient. Median time to treatment failure and median survival were 3.3 months and 7.5 months, respectively, for the entire group and 11 months and 30 months, respectively, for complete responders. Myelosuppression was pronounced but was usually of short duration. Neutropenic fever developed in 13 patients (42%) and in 15 of 96 cycles (16%). Platelet transfusions were required in seven patients (23%). There was one drug-related death associated with myelotoxicity. Nonhematologic toxicity was not dose limiting. The authors conclude that dexamethasone, cytarabine, ifosfamide, and cisplatin is active and a relatively tolerable regime for patients with non-Hodgkin lymphoma previously treated with adriamycin and etoposide.

Sustained complete remission after chemobiohormonal therapy for metastatic melanoma.

The combination of carmustine, cisplatin, dacarbazine, interferon, and low-dose tamoxifen is widely used in treating metastatic melanoma and was originally reported to achieve a 20% complete response rate. Among 29 patients who completed the authors' phase II study with the regimen, five (17%) achieved complete remission, and the median duration of response was 8 months (range, 2-14 months). The aim of the study was to evaluate briefly the value and toxicity of this regimen in treating metastatic malignant melanoma.

A rare event of 5-fluorouracil-associated peripheral neuropathy: a report of two patients.

5-Fluorouracil (5-FU) is known to cause multifocal cerebral demyelination, which is pathologically related to a central inflammatory demyelinating process. To date, no case of peripheral neuropathy has been described after the administration of 5-FU alone. The authors describe two patients who had peripheral neuropathy that developed while they were receiving 5-FU-based chemotherapy.

Postsurgical etoposide-ifosfamide regimen in poor-risk nonmetastatic osteogenic sarcoma.

This prospective study was designed to test the activity of an ifosfamide-etoposide (VP-16) regimen on poor-risk, nonmetastatic, osteogenic sarcoma. A total of 13 patients with nonmetastatic osteogenic sarcoma with a poor histologic response to primary high-dose methotrexate-doxorubicin (Adriamycin)-cisplatinum chemotherapy received a total of six 5-day courses of ifosfamide (1,800 mg/m2) and etoposide (100 mg/m2) at three weekly intervals. The protocol was well tolerated, with only one case of transient renal failure. At present, eight patients (62%) have been in sustained complete remission with no evidence of recurrent disease for a mean follow-up of 3.4 years (range, 1.5-7.0 years). One patient is alive with lung metastases, and four have died of progressive disease. This prospective, albeit small, study confirms the efficacy of an ifosfamide-VP-16-based regimen in poor-risk, extremity, nonmetastatic osteogenic sarcoma. The demonstrated activity should spark large trials of ifosfamide-containing regimens in osteogenic sarcoma.

Radiation-induced tumors in irradiated stage I testicular seminoma: results of a 25-year follow-up (1968-1993).

BACKGROUND AND OBJECTIVES: Testicular seminoma is a very radiosensitive and curable cancer, with survival rates following radiation therapy within the range of 90-98% without apparent severe side effects. However, long-term survival following exposure to moderate-dose radiation therapy can result in radiation-induced tumors. METHODS: The incidence of radiation-induced tumors was determined in 81 irradiated stage I testicular seminoma patients treated at the Northern Israel Oncology Center (NIOC) from 1968 through 1993. RESULTS: Three (4%) patients developed second cancers within the high-dose volume. Indeed, those patients received a higher than usual dose to the para-aortic and pelvic regions. One patient, who developed inoperable pancreatic carcinoma, was treated with "hockey stick" field and mediastinal irradiation, plus, as a result of relapses, multiple cisplatin and VP-16 based regimens. CONCLUSIONS: The elimination of causative factors through lower total doses and field size reduction may reduce the, albeit very low, incidence of radiation-induced cancer in cured testicular seminoma.

Undifferentiated nasopharyngeal carcinoma: pattern of failure--experience at the Johannesburg Hospital (1989-1994).

The records of 18 African patients with recurrent undifferentiated nasopharyngeal carcinoma (UDNPC) were reviewed. The skeletal system was the most common site of distant metastases. The pattern of skeletal involvement conformed to the general pattern, with the spine and pelvis being the most common sites. We conclude that metastatic UDNPC seen in Southern Africa resembles its North African and Southeast Asian counterparts.

Radiation-induced sarcoma following curative radiotherapy for testicular seminoma: case report and brief review of the literature.

We report a case of radiation-induced retroperitoneal leiomyosarcoma which developed 37 years after the patient received radiation therapy for testicular seminoma. The sarcoma originated within the para-aortic field, extensively involving neighboring organs, soft tissue and muscle tissues, and could be only partially resected. The absolute number of these secondary sarcomas is low, but the risk of developing such neoplasms calls for awareness in the long-term follow-up of cured seminoma patients.

Cisplatin-based chemotherapy in advanced seminoma: experience of the Northern Israel Oncology Center: 1981-1994.

BACKGROUND: The efficacy of cisplatinum combined chemotherapy modalities was investigated in a variety of trials for patients with advanced seminoma. Results regarding remission rates and survival are encouraging. METHODS: Between December 1981 and January 1994, 13 patients with either relapsed (following radiotherapy failure) or primarily advanced seminoma were treated with cisplatin-based chemotherapy at the Northern Israel Oncology Center. RESULTS: Eleven (84%) patients achieved complete clearance of all sites of disease. One patient demonstrated clinically and radiographically remarkable shrinkage of an abdominal mass, and laparotomy revealed fibrotic/necrotic tissue without viable tumor cells. After a mean follow-up of 58 months (range 4-168), 12 patients (92%) are alive and well without evidence of malignancy. One patient, in whom a 2-cm abdominal mass is stable radiographically, is under observation with no sign of tumor activity. Side effects were tolerable; no patient developed chemotherapy-induced sepsis. One patient developed spontaneous pneumothorax a few days after completion of his first chemotherapy cycle, which resolved with treatment. CONCLUSIONS: Our results confirm the efficacy and safety of cisplatin-based chemotherapy in the treatment of advanced seminoma, even in pre-irradiated patients.

Chemotherapy-induced spontaneous pneumothorax in a patient with bulky mediastinal lymphoma: a rare oncologic emergency.

Chemotherapy-induced spontaneous pneumothorax (SP) has been described sporadically in chemosensitive tumors, particularly sarcoma, with multiple lung metastases. We present a patient who developed SP following rapid regression of bulky mediastinal lymphoma. Immediately on chest tube insertion, the lung recovered and further chemotherapy could be delivered uneventfully. We suggest that (1) chemotherapy-induced SP should be included amongst oncologic emergencies and that (2) a high degree of awareness of this complication is required.