Oncologists' identification of mental health distress in cancer patients: Strategies and barriers.

The purpose of this research was to examine oncologists' perspectives on indicators of mental health distress in patients: what strategies they use to identify these indicators, and what barriers they face in this task. Twenty-three oncologists were interviewed, and the grounded theory method of data collection and analysis was used. Oncologists perceived distress to be a normative part of having cancer and looked for affective, physical, verbal and behavioural indicators using a number of strategies. Barriers to identification of mental health distress included difficulty in differentiating between mental health distress and symptoms of the disease, and lack of training. A systematic, time-efficient assessment of symptoms of emotional distress is critical for identification of psychiatric disorders among patients and differentiating normative emotional responses from psychopathology. Clinical bias and misdiagnosis can be a consequence of an ad hoc, intuitive approach to assessment, which can have consequences for patients and their families. Once elevated risk is identified for mental health distress, the patient can be referred to specialised care that can offer evidence-based treatments.

Adjuvant aromatase inhibitor therapy in patients with stage I breast cancer at a regional oncology center in Israel: implementation of a 'switching' policy in postmenopausal patients after initial tamoxifen.

OBJECTIVE: To analyze the implementation of a switching policy of adjuvant aromatase inhibitor (AI) therapy sequentially after tamoxifen in consecutively treated stage I (T1N0M0) hormone receptor (HR)-positive breast cancer (BC) patients. METHODS: The records of 279 consecutive HR-positive BC patients diagnosed between 2002 and 2006 and followed at the Soroka Medical Center were reviewed. RESULTS: Two-hundred-seventeen patients who initially received tamoxifen were suitable for switching and 28 received an AI as initial adjuvant treatment. The switch was accomplished in 82.5% of the 217 patients. Those who switched to an AI had a higher proportion of T1c stage than patients eligible who were not switched, but did not differ in age, histologic grade, or having received chemotherapy. Of the 179 patients who switched, 155 (86.6%) completed at least 4.5-5 years of adjuvant tamoxifen/AI therapy. Eighteen patients discontinued AI therapy prematurely because of toxicity. CONCLUSIONS: In this stage I BC population, despite the toxicities of AI therapy, >84% of eligible patients received an AI as adjuvant therapy. Measures to improve the management of AI toxicity, such as changing to a different AI, may reduce early stopping.

Personalising docetaxel and G-CSF schedules in cancer patients by a clinically validated computational model.

BACKGROUND: This study was aimed to develop a new method for personalising chemotherapeutic and granulocyte colony-stimulating factor (G-CSF) combined schedules, and use it for suggesting efficacious chemotherapy with reduced neutropenia. METHODS: Clinical data from 38 docetaxel (Doc)-treated metastatic breast cancer patients were employed for validating a new pharmacokinetic/pharmacodynamics model for Doc, combined with a mathematical model for granulopoiesis. An optimisation procedure was constructed and used for selecting improved treatment schedules. RESULTS: The combined model accurately predicted observed nadir timing (r=0.99), grade 3 or 4 neutropenia (86% success) and neutrophil counts over time in individual patients (r=0.63), and showed robustness to CYP3A-induced variability in Doc clearance. For average patients, the predicted optimal support for the standard chemotherapy regimen, Doc 100 µg m(-2) tri-weekly, is G-CSF, 300 µg, Q1D × 3, starting day 7 post-Doc. This regimen largely moderates chemotherapy-induced neutrophil nadir and neutropenia duration. The more intensive Doc dose, 150 mg m(-2), is optimally supported by the slightly less cost-effective G-CSF 300 µg, Q1D × 4, 5 days post-Doc. The latter regimen is optimal for borderline patients (2000 neutrophils per µl) under Doc, 100-150 mg m(-2) tri-weekly. CONCLUSIONS: The new computational method can serve for tailoring efficacious cytotoxic and supportive treatments, minimising side effects to individual patients. Prospective clinical validation is warranted.

The impact of the 21-gene recurrence score assay on decision making about adjuvant chemotherapy in early-stage estrogen-receptor-positive breast cancer in an oncology practice with a unified treatment policy.

BACKGROUND: The 21-gene recurrence score (RS) assay has been validated in retrospective studies as prognostic of distant disease recurrence and predictive of the benefit of adjuvant chemotherapy in estrogen-receptor-positive breast cancer (BC). There is limited published data on the impact of the assay on clinical practice, particularly in the context of a single practice with a unified treatment policy. PATIENTS AND METHODS: Between 2006 and 2009, RS was obtained on 135 patients in a single practice with a uniform treatment policy. Treatment recommendations before and after RS result were analyzed retrospectively. Pre-RS treatment recommendations were based on clinicopathological features and Adjuvant! Online (AO) calculated survival advantage. RS and AO survival advantage for adding chemotherapy were compared for each patient. RESULTS: The distribution by risk group of RS was low- 49.6%, intermediate-37.8%, and high-12.6%. In 34 patients (25.2%, 95% confidence interval 17.9% to 32.5%), recommendation for chemotherapy was changed after obtaining assay result. Most changes (70.6%) were from chemotherapy to no chemotherapy. The RS correlated poorly with AO predictions. CONCLUSION: The 21-gene assay, when applied in a consistent manner in early-stage BC, changes treatment recommendations in one-quarter of patients tested.

Stage I breast cancer in a regional oncology practice in Israel 2002-2006: clinicopathologic features, risk estimation and planned therapy of 328 consecutive patients.

We present the clinicopathologic features and treatment plans of 328 consecutive stage I (T1N0M0) breast cancer patients seen at a regional medical center in Israel. Predicted 10-year mortality risk was calculated using the Adjuvant! Online website. The 21-gene recurrence score (RS) (OncotypeDx) was obtained on a minority of patients. Eighty-nine per cent of patients had estrogen receptor (ER) and/or progesterone receptor (PgR) positive tumors. In 43.3% of patients history of an invasive malignancy was reported in a first degree relative and in 15.5% specifically breast and/or ovarian cancer was reported. Chemotherapy was added to endocrine therapy in 59 ER/PgR positive patients, decreasing predicted 10-year mortality risk by a median of 1.8%. Individualized risk estimation by genetic analysis may further decrease the use of chemotherapy in stage I patients. Breast cancer screening may provide an opportunity to identify cancer prone families.

Rectal bleeding and previous anticoagulant treatment in patients with colorectal cancer do not predict outcome.

BACKGROUND: The aim of this study was to determine whether the outcome of patients with colorectal cancer who presented with bleeding and a history of anticoagulant treatment was different from those who did not have bleeding or previous anticoagulant treatment. METHODS: This was a single institution, retrospective study of patients with colorectal cancer with and without a history of rectal bleeding and treatment with anticoagulants, assessed for age, gender, tumor site, stage, recurrence rate, and survival. RESULTS: A total of 621 consecutive patients (309 men) with a mean age of 70 years (range, 36-94 years) diagnosed with colorectal cancer between 1998 and 2004 were studied. Of these, 149 patients (24%) were referred for symptoms of rectal bleeding and 161 patients (26%) had been previously treated with anticoagulants. A total of 592 patients (95%) underwent curative or palliative surgery; endoscopic polypectomy was performed in 3 cases only and in 26 patients (4%) surgery was not performed due to advanced disease or critical illness. Patients with bleeding and a history of anticoagulant treatment presented commonly with stage I cancer. In addition, tumor stage III was less common in patients with previous anticoagulant treatment irrespective of presenting signs. Disease-free and overall survival rates were similar in all groups, irrespective of bleeding at presentation or anticoagulant treatment. CONCLUSIONS: Rectal bleeding and anticoagulant treatment do not affect the outcome of newly diagnosed patients with colorectal cancer.

Retrospective comparison of two different schedules of irinotecan, 5-fluorouracil and folinic acid in previously untreated patients with advanced colorectal carcinoma: a single institution experience.

PURPOSE: To compare efficacy and tolerability of weekly irinotecan combined with 5-fluorouracil (5-FU) bolus and folinic acid (FA) regimen (IFL) versus biweekly irinotecan with infusional 5-FU and FA (FOLFIRI) in patients (pts) with advanced stage colorectal cancer. PATIENTS AND METHODS: Treatments outcome of 86 pts (IFL - 38 pts, FOLFIRI - 48 pts) was evaluated. Chemotherapy regimens were as follows: IFL - intravenous (i.v.) infusion irinotecan 125 mg/m(2) over 90 min and 5-FU 500 mg/m(2) preceded by FA 20 mg/m(2) both given by i.v. bolus injection, all repeated on days 1, 8, 15 and 22 every 6 weeks; FOLFIRI - i.v. irinotecan 180 mg/ m(2) on days 1 and 15 with subsequent FA 200 mg/m(2) administered as a 2-hour infusion and i.v. bolus injection of 400 mg/m(2) 5-FU immediately followed by 22-hour i.v. infusion of 600 mg/m(2) 5-FU on days 1, 2, 15 and 16 every 4 weeks. Treatment continued until disease progression or unacceptable toxicity. RESULTS: A total of 152 (mean - 4) IFL cycles and 328 (mean - 6) FOLFIRI cycles were administered. Average dose intensity was 0.8 and 0.78 respectively. Toxicities were mild and manageable for both regimens evaluated. Overall response rate was 36.8% in IFL arm and 44.7% in FOLFIRI arm. At the median follow-up of 16 months in IFL arm and 14 months in FOPFIRI arm the two year survival was 38% and 45%, the median survival was 18 months and 21.5 months, and the median progression free survival was 6 months and 9.4 months respectively. CONCLUSIONS: In our experience, both IFL and FOLFIRI regimens have acceptable toxicity at a similar level of dose intensity. Compared to IFL, FOLFIRI seems to improve progression-free survival.

Measles virus: evidence of an association with Hodgkin's disease.

The quest for an infectious agent that may account for cases of Hodgkin's disease (HD) especially in young adults has proven vain until lately. We have recently reported findings that suggested the presence of measles virus (MV) antigens and MV RNA in the tissues of patients with HD. Support for an association between MV and HD has been provided by recent epidemiological findings relating the occurrence of HD to exposure to measles in pregnancy and the perinatal period. We now present further evidence of this putative association based on immunohistochemical, reverse transcriptase-polymerase chain reaction (RT-PCR) and in situ hybridisation studies (ISH) on HD tissues. Biopsies from 82 (54.3%) of our cohort of 154 patients showed a positive immunostain with at least two of the anti-measles antibodies used. Latent membrane protein-1 immunostaining for Epstein-Barr virus was positive in 46 (31.1%) of the patients examined. Reverse transcriptase-PCR and ISH for measles RNA were positive in seven and 10 of 28 patients, respectively. Preliminary clinicopathological associations between MV and HD are noted in this study, but no causal relationship can be claimed at this stage.

Toxic epidermal necrolysis associated with gemcitabine therapy in a patient with metastatic transitional cell carcinoma of the bladder.

The authors report on a case of treatment-related toxic epidermal necrolysis in an elderly man receiving chemotherapy (gemcitabine) for transitional cell carcinoma of bladder and discuss the implications of the case.

New candidate virus in association with Hodgkin's disease.

Epidemiologic and molecular investigations of Hodgkin's disease (HD) suggest a strong infectious association. The Epstein-Barr virus (EBV), together with its viral proteins, is expressed in Hodgkin-Reed-Sternberg (HRS) cells in the lymph nodes involved by HD. EBV is more likely to be related to childhood and older adult cases of HD and is much less frequently expressed in young adult HD patients, the group most expected to be associated with an infectious agent. In addition, the "hit and run" theory of EBV infection remains speculative and no other lymphotropic viruses studied to date seem to satisfy the quest for a new candidate virus in young adults with HD. We have recently found preliminary evidence suggesting a possible association between the measles virus (MV) and HD. This evidence is the subject of the present review.

Long-term follow-up of patients with initially benign thyroid fine-needle aspirations.

Fine-needle aspiration (FNA) is currently the most reliable diagnostic means in the clinical work-up of thyroid nodules. However, most of the available data on the diagnostic reliability of thyroid FNA derives from biopsies done just before surgery or from short-term observations, whereas data on the long-term reliability of benign FNA results, is extremely limited. Over the 17-year period between 1979 and 1996, thyroid FNA performed on 849 patients in our endocrine clinic. An initially benign result was reported in 578 patients for a total of 631 nodules. Mean follow-up period was 8.1 +/- 4.4 years (+/-standard deviation [SD]; median, 6.9 years). In order to ensure the completeness of our follow-up data, we supplemented our own patients' data with data from the Israel Cancer Registry for documentation of thyroid malignancy. Sixty-six of the patients with an initially benign FNA diagnosis were rebiopsied during follow-up. Five patients (0.85%) of all those with an initial benign FNA diagnosis, were subsequently found to have thyroid malignancy diagnosed 6 months or more after the initial evaluation. Three of the newly diagnosed malignancies were follicular and two were papillary carcinomas. Three of the patients had elements of being at high-risk: previous head irradiation, previous thyroid surgery with an occult cancer, and a growing goiter, respectively. Only 1 of 35 patients who had more than one benign FNA results was subsequently diagnosed with thyroid malignancy (follicular carcinoma). These results indicate that the rate of subsequent thyroid malignancies in patients with an initial benign FNA diagnosis is low, and thus benign thyroid FNA results provide a high level of long-term assurance. Still, repeating FNA is warranted in patients with longstanding thyroid nodules, particularly if at increased risk for cancer, or if a goiter is found to have changed its morphological characteristics over time.

Post renal transplantation human herpesvirus 8-associated lymphoproliferative disorder and Kaposi's sarcoma.

Post-transplantation lymphoproliferative disorders (PTLDs) and Kaposi's sarcoma (KS) are immunosuppression-related tumours developing in solid organ transplant patients. Although the Epstein-Barr virus (EBV) is detected in the majority of the PTLDs during the first year after transplantation, the proportion of EBV-negative PTLDs has increased in recent years. We report a case of a 17-year-old man who developed severe immune haemolytic anaemia, KS and human herpesvirus 8 (HHV-8)-associated, polymorphic-type PTLD 9 months after allogeneic renal transplantation from his HHV-8-seropositive father. It is suggested that: (i) HHV-8 may be associated with EBV-negative, polymorphous-type PTLD occurring less than 1 year after transplantation, and (ii) PTLD may be listed among other tumours, including KS, Castleman's disease and primary effusion lymphoma (PEL), that are related to HHV-8 infection.

Seroepidemiology and molecular epidemiology of Kaposi's sarcoma-associated herpesvirus among Jewish population groups in Israel.

BACKGROUND: The incidence of classic Kaposi's sarcoma among Jews in Israel is among the highest in the developed world. Kaposi's sarcoma-associated herpesvirus (KSHV or human herpesvirus 8) is causally linked to Kaposi's sarcoma. Very little is known about the prevalence of KSHV in the Middle East or about the modes of transmission in Mediterranean countries. METHODS: From 1992 through 1995, sera were obtained from 1648 adults who had tested positive for hepatitis B virus (HBV) surface antigen 20 years earlier at blood donations; sera were also obtained from 2403 of their family members. All sera were tested for anti-KSHV antibodies with the use of an indirect immunofluorescence assay. To analyze the effects of various factors on the risk of KSHV infection for both the HBV-positive cohort and their families, logistic regression for cluster data and generalized estimating equations were used. All statistical tests were two-sided. RESULTS: Among family members, the seroprevalence of antibodies against KSHV was 9.9% (95% confidence interval [CI] = 8.7% to 11.1%); among the former blood donors who had tested positive for hepatitis B, it was 22% (95% CI = 19.9% to 24.1%). Overall, the best predictor of KSHV status was the place of birth. The most important risk factors found for both husband and wife to test KSHV positive were their own places of birth and their spouse's seropositivity. For a child to test positive, the most important risk factor was maternal seropositivity. CONCLUSIONS: The crude prevalence rate of KSHV among the Jewish population in Israel is 9.9%. Important routes of KSHV transmission in the families studied are spouse to spouse and mother to child. The presence of KSHV in Jews in Israel of all ethnic origins and their high incidence of reported Kaposi's sarcoma suggest that KSHV was introduced into the Jewish population prior to the major Diaspora.

Multimodal treatment of metastatic thymic carcinoma including high-dose chemotherapy with autologous stem cell transplantation: report of a case with more than 4-year disease-free survival.

Thymic carcinoma is a rare epithelial malignancy differentiated from thymoma by the presence of cytologically malignant cells. There are few reports of the treatment of locally advanced or metastatic thymic carcinoma. We describe a patient who sought treatment for thymic carcinoma metastatic to pleura, pericardium, retroperitoneum, and neck nodes. He was treated with neoadjuvant etoposide, ifosfamide, and cisplatin, and underwent resection. We then administered high-dose chemotherapy with autologous stem cell support, followed by radiation therapy. The patient remains in complete remission more than 4 years after diagnosis. To our knowledge, this is the first report of metastatic thymic carcinoma treated with neoadjuvant therapy and postoperative high-dose chemotherapy. Metastatic thymic carcinoma may be curable by aggressive combined therapies.

Acute myocardial infarction in a young man receiving chemotherapy for testicular cancer: case report.

The authors report on a case of treatment-related myocardial infarction in a young man receiving chemotherapy (BEP) for testicular cancer and discuss the implications of the case.

Manifestations of three HHV-8-related diseases in an HIV-negative patient: immunoblastic variant multicentric Castleman's disease, primary effusion lymphoma, and Kaposi's sarcoma.

We describe a 73-year-old HIV negative patient who presented with symptomatic hypoglycemia. Over the course of several months she was diagnosed with three human herpesvirus-8 related diseases: multicentric Castleman's disease, primary effusion lymphoma and Kaposi's sarcoma. No improvement was observed following cytotoxic therapy and she died 16 months after her initial presentation. The etiology of the hypoglycemia remained obscure over the course of this patient's disease. This case is the first report of a patient with three human herpesvirus-8 related diseases, and the first report of severe hypoglycemia as the presenting symptom of any of these diseases.

Differential expression of sialyl and non-sialyl-CD15 antigens on Hodgkin-Reed-Sternberg cells: significance in Hodgkin's disease.

CD15 expression has been used for years to confirm the diagnosis of Hodgkin's disease (HD). Little is, however, known on the relevance of the CD15 antigen to the pathobiology of the disease and there is conflicting evidence as to the prognostic value of its expression. To investigate the significance of the differential expression of CD15 in Hodgkin's disease, a retrospective study of 102 patients with "classical" Hodgkin's disease was performed. Immunohistochemical studies were carried out using antibodies against two types of CD15: non-sialylated CD15 (LeuM1 and 80H5) and sialylated CD15 (FH6 and CSLEX1). Cases that were negative for non-sialylated CD15 or positive for the sialylated variant were stained again following neuraminidase pretreatment. The cohort included 27 patients in whom sequential biopsies were available. Both CD15 expression in its non-sialylated form and absence of sialyl-CD15 expression correlate with a favorable outcome. Subsequent biopsies show a preferential expression of sialyl-CD15, notably in bone marrow metastases. Our findings suggest that, in the progression of HD towards a widely disseminated disease, the LewisX moiety of the CD15 antigen on the tumor cells acquires a sialyl-group. This change may confer on the tumor cells the capacity to metastasize.

Hodgkin's lymphoma in the Bedouin of southern Israel: epidemiological and clinical features.

BACKGROUND: A previous study on Hodgkin's lymphoma in southern Israel found that Bedouin patients had an increased rate of Epstein-Barr virus expression in their tumor cells. OBJECTIVES: To determine the influence of the patients' communities on the pattern of disease in HL. METHODS: We compared the clinical features, demographic data, stage at diagnosis, treatment modality and outcome, as well as laboratory findings, in four community-based subgroups. These groups comprised kibbutz residents (n = 11), Bedouin (n = 19), new immigrants from the former USSR (n = 22), and town-dwellers (n = 82). RESULTS: The Bedouin patients differed significantly from the new immigrants and town-dwellers, particularly regarding the rate of EBV sequences in the tumor tissues, and a poorer response to treatment. The kibbutz patients did not differ significantly from the other populations regarding most of the parameters studied, but showed an intermediate expression of EBV antigens compared to Bedouin patients and the rest of the cohort. CONCLUSIONS: This study indicates that HL may behave differently in different population groups in a given geographic area. Notably, the Bedouin patients showed markedly different clinical and biological patterns of this malignancy.