Colorectal cancer risk, chronic illnesses, operations, and medications: case control results from the Melbourne Colorectal Cancer Study

The associations between colorectal cancer risk and several chronic illnesses, operations, and various medications were examined in 715 colorectal cancer cases and 727 age/sex-matched controls in data derived from a large, comprehensive, population-based study of this cancer conducted in Melbourne, Australia. There was a statistically significant deficit among cases of hypertension, heart disease, stroke, chronic chest disease, and chronic arthritis and a statistically significant excess of "hemorrhoids" among cases, and all of these differences were consistent for both colon and rectal cancer and for both males and females. Although no statistically significant differences were found for other cancers, there were twice as many breast cancers among cases (16) than among controls and also there were 9 uterine cancers among cases and only 2 among controls. There was a statistically significant deficit among cases in the use of aspirin-containing medication and vitamin supplements, and this was consistent for both colon and rectal cancer and for both males and females. There was a statistically significant excess of large bowel polypectomy among cases. The modeling of these significant associations simultaneously in a logistic regression equation indicated that hypertension, heart disease, chronic arthritis, and aspirin use were each independent effects and consistent for both colon and rectal cancer for both males and females and also that these effects were independent of dietary risk factors previously described in the Melbourne study. The possible relevance of these findings towards an understanding of colorectal cancer risk and etiology is discussed.     

Breast lymphoma complicating anti-tumor necrosis factor therapy in rheumatoid arthritis

The relationship between anti-TNF therapy and development of lymphoma in Rheumatoid arthritis (RA) patients is controversial. However lymphomas of unusual types and sites have been reported among RA patients receiving anti-TNF therapy. Primary lymphoma of the breast is a rare entity and has never been reported to occur among RA patients taking anti-TNF therapy. This is the first case of primary lymphoma of the breast reported among RA patients on anti-TNF therapy. Rheumatoid arthritis patients currently on anti-TNF therapy should undergo routine gynecological examination.     

Intermediate lymphocytic lymphoma of the salivary gland

Three patients had a painless mass in the parotid (two patients) or submandibular regions (one patient). These patients were 70, 66, and 65 years of age, respectively. One patient was male and the other two were female. No symptoms suggesting the presence of autoimmune sialadenitis had been noticed, although one patient suffered from rheumatoid arthritis. Histologic study showed that small atypical lymphoid cells with slightly irregular and indented nuclear contours proliferated diffusely and secondary lymph follicles were distributed at random among them. These findings are similar to those that we recently reported for intermediate lymphocytic lymphoma (ILL) of the thyroid gland arising in patients with autoimmune thyroiditis. A high frequency of ILL among our series of salivary lymphomas (three of nine cases) is discussed.     

Large-scale real-world data analyses of cancer risks among patients with rheumatoid arthritis

Rheumatoid arthritis (RA) affects 24.5 million people worldwide and has been associated with increased cancer risks. However, the extent to which the observed risks are related to the pathophysiology of rheumatoid arthritis or its treatments is unknown. Leveraging nationwide health insurance claims data with 85.97 million enrollees across 8 years, we identified 92 864 patients without cancers at the time of rheumatoid arthritis diagnoses. We matched 68 415 of these patients with participants without rheumatoid arthritis by sex, race, age and inferred health and economic status and compared their risks of developing all cancer types. By 12 months after the diagnosis of rheumatoid arthritis, rheumatoid arthritis patients were 1.21 (95% confidence interval [CI] [1.14, 1.29]) times more likely to develop any cancer compared with matched enrollees without rheumatoid arthritis. In particular, the risk of developing lymphoma is 2.08 (95% CI [1.67, 2.58]) times higher in the rheumatoid arthritis group, and the risk of developing lung cancer is 1.69 (95% CI [1.32, 2.13]) times higher. We further identified the five most commonly used drugs in treating rheumatoid arthritis, and the log-rank test showed none of them is implicated with a significantly increased cancer risk compared with rheumatoid arthritis patients without that specific drug. Our study suggested that the pathophysiology of rheumatoid arthritis, rather than its treatments, is implicated in the development of subsequent cancers. Our method is extensible to investigating the connections among drugs, diseases and comorbidities at scale.     

Living with the worry of cancer: health perceptions and behaviors of elderly people with self,vicarious, or no history of cancer

Cancer is a major health threat that has a long-term impact on quality of life and health worries. The present study is focused on two major issues: (1) the impact that a history of cancer has on reactions to other diseases, in addition to cancer and general health worries; and, (2) the impact that having lived with someone who had cancer has on health perceptions and behaviors. All 108 participants had osteoarthritis, a symptomatic but benign disease (49 people have had cancer, 22 had lived with a cancer patient, and 37 had not had any close experience with cancer). Cancer and health worries were lowest among the people with vicarious experience, while monitoring for bodily signs was similar and highest in both cancer experience groups. Reactions to arthritis suggest more vigilance among people who have had self or vicarious experience with cancer, while reactions to ambiguous symptoms suggest vigilance especially among those with a personal history of cancer. Overall, the findings suggest that the effects of self-experience with cancer and of close experience with a cancer patient may be long-term and impact upon both health perceptions and behaviors.     

Occurrence of comorbidities among African-American and Latina breast cancer survivors

Background

The co-occurrence of multiple chronic conditions in cancer patients is common and can have negative impact on cancer and cancer survivorship outcomes. This study aimed to document comorbidity occurrence among African-American and Latina (English language preferred (ELP) and Spanish language preferred (SLP)) breast cancer survivors (BCS).

Methods

Eighty-eight African-American, 95 ELP Latina, and 137 SLP Latina BCS were recruited via case ascertainment from the California Cancer Registry and hospital registries. BCS completed a self-report questionnaire assessing demographic and cancer characteristics, and presence of comorbidities.

Results

Overall, 75 % of BCS reported at least one comorbidity with arthritis (37 %), high blood pressure (37 %), psychological difficulties (29 %), and diabetes (19 %) being most commonly endorsed. SLP Latinas were more likely to report diabetes (29 %), psychological difficulties (42 %), and >3 comorbidities (p?<?0.05). Latina BCS were twice as likely to report osteoporosis and headaches compared to African-Americans; while one in two African-Americans reported hypertension and arthritis. Older age was correlated with arthritis, diabetes, glaucoma, high blood pressure, and osteoporosis.

Conclusions

Our findings suggest that investigating the occurrence of comorbidities across ethnic groups may shed some light in understanding cancer survivorship risk for poor health outcomes and health disparities. Having a better grasp of comorbid conditions may aid in more appropriate early assessment, better follow-up care, surveillance, and management of the cancer and the comorbid condition(s).

Implications for Cancer Survivors

Integrated control and management of comorbidities among cancer survivors has the potential to improve quality care for the whole person, and increase survival and decrease morbidity.     

Prior Medical Conditions and Medication use and Risk of non-Hodgkin lymphoma in Connecticut United States Women

OBJECTIVE: To further investigate the role of prior medical conditions and medication use in the etiology of non-Hodgkin lymphoma (NHL), we analyzed the data from a population-based case-control study of NHL in Connecticut women. METHODS: A total of 601 histologically confirmed incident cases of NHL and 717 population-based controls were included in this study. In-person interviews were administered using standardized, structured questionnaires to collect information on medical conditions and medication use. RESULTS: An increased risk was found among women who had a history of autoimmune disorders (such as rheumatoid arthritis, lupus erythematosus, Sjogren's syndrome, and multiple sclerosis), anemia, eczema, or psoriasis. An increased risk was also observed among women who had used steroidal anti-inflammatory drugs and tranquilizers. A reduced risk was found for women who had scarlet fever or who had used estrogen replacement therapy, aspirin, medications for non-insulin dependent diabetes, HMG-CoA reductase inhibitors, or beta-adrenergic blocking agents. Risk associated with past medical history appeared to vary based on NHL subtypes, but the results were based on small number of exposed subjects. CONCLUSION: A relationship between certain prior medical conditions and medication use and risk of NHL was observed in this study. Further studies are warranted to confirm our findings.     

Carpal tunnel syndrome in sarcoidosis

Sarcoidosis is a systemic disease that may affect the musculoskeletal system. An association between carpal tunnel syndrome (CTS) and sarcoidosis has not been demonstrated. Consecutive patients from the sarcoidosis clinic at our institution were questioned about history and symptoms of carpal tunnel syndrome: hand numbness and nocturnal paresthesias with relief of symptoms by shaking of the hands (flick sign). A physical exam was performed to evaluate for Tinel's and Phalen's signs. A comparison of the presence of arthritis, prednisone treatment, spirometry, and number of organs involved with sarcoidosis was made in patients with a history or clinical findings of CTS versus those without. Eighty-nine patients were evaluated. Thirty-five patients (39%) had nocturnal paresthesias with a positive flick sign. Fourteen patients (16%) had physical findings of CTS. A history of CTS was present in 14 (16%) of the patients, four of which were documented by EMG. There was no significant difference between the frequency of prednisone treatment in patients with or without CTS history, nocturnal paresthesias, or Phalen's sign. There were significantly fewer patients with a positive Tinel's sign who were receiving prednisone. There was a trend toward an increased frequency of wrist arthritis in patients with a history or clinical findings of CTS. There was no significant difference in disease severity, assessed by spirometry or organ involvement, when comparing sarcoidosis patients with or without a history or clinical findings of CTS. Thirty-nine (44%) had symptoms and/or signs of CTS. Even when we adjusted our sarcoidosis population for other factors associated with CTS, the prevalence of symptoms and signs of CTS was much higher in our patient population than in studies of the general population. Our findings suggest that CTS is common in sarcoidosis.     

Malignant lymphomas in autoimmunity and inflammation: a review of risks, risk factors, and lymphoma characteristics.

Certain autoimmune and chronic inflammatory conditions, such as Sj?gren's syndrome and rheumatoid arthritis (RA), have consistently been associated with an increased risk of malignant lymphomas, but it is unclear whether elevated lymphoma risk is a phenomenon that accompanies inflammatory conditions in general. Likewise, it is debated whether the increased risk identified in association with some disorders pertains equally to all individuals or whether it varies among groups of patients with different phenotypic or treatment-related characteristics. It is similarly unclear to what extent the increased lymphoma occurrence is mediated through specific lymphoma subtypes. This update reviews the many findings on risks, risk levels, and lymphoma characteristics that have been presented recently in relation to a broad range of chronic inflammatory, including autoimmune, conditions. Recent results clearly indicate an association between severity of chronic inflammation and lymphoma risk in RA and Sj?gren's syndrome. Thus, the average risk of lymphoma in RA may be composed of a markedly increased risk in those with most severe disease and little or no increase in those with mild or moderate disease. The roles of immunosuppressive therapy and EBV infection seem to be limited. Furthermore, RA, Sj?gren's syndrome, systemic lupus erythematosus, and possibly celiac disease may share an association with risk of diffuse large B-cell lymphoma, in addition to well-established links of Sj?gren's syndrome with risk of mucosa-associated lymphoid tissue lymphoma and of celiac disease with risk of small intestinal lymphoma. However, there is also obvious heterogeneity in risk and risk mediators among different inflammatory diseases.     

Serum metalloproteinases and their inhibitors: markers for malignant potential.

Death from cancer results from the development of metastases or local progression of tumour. Metastasis and local progression may result from the inappropriate activity of metalloproteinases released by tumour cells or of their regulatory peptides. We have developed quantitative assays for interstitial collagenase, stromelysin 1 and tissue inhibitors of metalloproteinase (TIMP) 1 and 2, which have allowed the study of serum levels of these proteins. Sera from 40 patients with prostatic cancer, stored prior to and after 6 and 12 months'' treatment with a gonadotrophin-releasing hormone agonist and an anti-androgen were analysed. Levels were compared with two control groups, comprising 21 patients with active rheumatoid arthritis and 56 age-matched hospital attenders without arthritis or cancer. Contrasting levels have been found in patients with prostatic cancer as compared with hospital controls without cancer and patients with rheumatoid arthritis. Patients with prostatic cancer had higher levels of TIMP-1 and collagenase (P = 0.0001) and lower levels of TIMP-2 (P = 0.003) than controls. Patients with metastatic cancer had significantly higher levels of collagenase than those without metastases (P = 0.02). Patients with rheumatoid arthritis had significantly higher levels of stromelysin than either controls (P = 0.002) or patients with cancer (P = 0.008). Serum tissue inhibitor of metalloproteinase 1 in combination with collagenase levels was as sensitive as prostate-specific antigen as a marker of metastatic disease. These findings provide a basis for the investigation of the role of metalloproteinases and their inhibitors in other malignancies.     

Primary T-cell/histiocyte-rich B-cell lymphoma arising in the trigeminal ganglion in a patient with rheumatoid arthritis

We report a cased of a 68-year-old man with primary T-cell/histiocyte-rich B-cell lymphoma (T/HRBCL) that arose in the trigeminal ganglion. He had a 30-year history of rheumatoid arthritis and presented with progressive left facial pain that had started 3 weeks earlier. Magnetic resonance imaging (MRI) revealed an enhanced mass in the trigeminal ganglion and swelling of the distal part of the trigeminal root. The tumor, subtotally resected via the left anterior petrosal approach, was composed of proliferating CD30- and CD79-positive atypical large polygonal cells with hyperchromatic single or multiple nuclei. CD3-positive small lymphoid cells and CD68-positive histiocytic cells were intermingled with the neoplastic cells. These findings were compatible with T/HRBCL. After whole-brain radiation, his facial pain improved and he was discharged. Postoperatively, he developed transient left sixth nerve paresis. This is the first report of this rare type of B-cell lymphoma arising from the trigeminal ganglion. We posit that his prolonged immunosuppressive treatment for rheumatoid arthritis contributed to its development.     

Alterations of the CD4+, CD8+ T Cell Subsets, Interleukins-1β, IL-10, IL-17, Tumor Necrosis Factor-α and Soluble Intercellular Adhesion Molecule-1 in Rheumatoid Arthritis and Osteoarthritis: Preliminary Observations

Rheumatoid arthritis is a multisystem disease with underlying immune mechanisms. Osteoarthritis is a debilitating, progressive disease of diarthrodial joints associated with the aging process. Although much is known about the pathogenesis of rheumatoid arthritis and osteoarthritis, our understanding of some immunologic changes remains incomplete. This study tries to examine the numeric changes in the T cell subsets and the alterations in the levels of some cytokines and adhesion molecules in these lesions. To accomplish this goal, peripheral blood and synovial fluid samples were obtained from 24 patients with rheumatoid arthritis, 15 patients with osteoarthritis and six healthy controls. The counts of CD4 (+) and CD8 (+) T lymphocytes were examined using flow cytometry. The levels of some cytokines (TNF-alpha, IL1-beta, IL-10, and IL-17) and a soluble intercellular adhesion molecule-1 (sICAM-1) were measured in the sera and synovial fluids using enzyme linked immunosorbant assay. We found some variations in the counts of T cell subsets, the levels of cytokines and sICAM-1 adhesion molecule between the healthy controls and the patients with arthritis. High levels of IL-1beta, IL-10, IL-17 and TNF-alpha (in the serum and synovial fluid) were observed in arthritis compared to the healthy controls. In rheumatoid arthritis, a high serum level of sICAM-1 was found compared to its level in the synovial fluid. A high CD4(+)/CD8(+) T cell ratio was found in the blood of the patients with rheumatoid arthritis. In rheumatoid arthritis, the cytokine levels correlated positively with some clinicopathologic features. To conclude, the development of rheumatoid arthritis and osteoarthritis is associated with alteration of the levels of some cytokines. The assessment of these immunologic changes may have potential prognostic roles.     

Enlarged Supratrochlear Lymphatic Glands in Rheumatoid Arthritis

Three cases of rheumatoid arthritis have been presented, and they all had a destructive arthritis of the elbow joints. In the soft tissues there was evidence of enlarged supratrochlear lymph glands. This is felt to be part of the generalized involvement of the reticuloendothelial system in rheumatoid arthritis. No previous reports have been found in the literature of the radiological sign of enlargement of the supratrochlear glands at the elbow in cases of rheumatoid arthritis.     

Simultaneous Breast Cancer and Kaposi's Sarcoma Complicating Rheumatoid Arthritis

For a number of years we have been following the medical literature to find a relationship between chronic treatment with methotrexate and breast cancer occurrence, because we had had in our clinic a female patient who had had two consecutive cancers following methotrexate treatment for rheumatoid arthritis (RA). We were much surprised to find in some papers that breast cancer incidence is low in women with RA. Since then, we have found several papers explaining the low incidence of breast cancer among women being under NSAIDs, but those papers are not univocal. Methotrexate is a known antifolate agent and it has been demonstrated that dietary shortage of folate is a risk factor for breast cancer development.     

Sarcoid arthritis: a review of clinical features,pathology and therapy

The rheumatic manifestations of sarcoidosis include inflammatory arthritis, periarticular soft tissue swelling, tenosynovitis, dactylitis, bone involvement and myopathy. Two types of arthritis that differ in clinical course and prognosis are recognized. Acute sarcoid arthritis is self-limiting and resolves without permanent sequelae. Chronic sarcoid arthritis although less common can progress to cause joint deformities. There are proliferative and inflammatory changes in the synovium and non-caseating granulomas are seen in half of patients. The pathogenesis of sarcoid arthritis is not well understood, however genetic and environmental factors are important. Drug therapy of sarcoid arthritis with nonsteroidal anti-inflammatory agents, corticosteroids, colchicine, antimalarials and/or immunosuppressive medications is based mainly on open label uncontrolled studies. This review focuses on the current knowledge on the various features of sarcoid arthritis including clinical presentation, course, imaging, and pathology. Recent developments in the usage of anti-tumor necrosis factor therapy for sarcoidosis will be reviewed.     

The clinical pharmacology of methotrexate: new applications of an old drug.

Methotrexate is now used widely for the treatment of acute leukemia, non-Hodgkin's lymphoma, osteogenic sarcoma, choriocarcinoma, breast carcinoma, pulmonary and epidermoid carcinoma, and intrathecal chemotherapy. It is also useful in bone marrow transplantation, severe psoriasis, rheumatoid arthritis, dermatomyositis, Wegener's granulomatosis and sarcoidosis. The recent dramatic intensification of methotrexate therapy can be attributed in part to advances in our understanding of the clinical pharmacology of the folate antagonists, as well as to the combination of positive results and their effective dissemination to medical oncologists. The review summarizes the pharmacologic findings and illustrates how they are currently being applied to the treatment of malignant disease.     

Hsp60 and Hspl0 as antitumor molecular agents

The molecular chaperones Hsp60 and Hsp10 are, according to recent reports, involved in cancer development and progression. We, for instance, have found that their expression varies with distinctive patterns in different malignancies: they are overexpressed in colorectal, exocervical and prostate carcinogenesis, and colorectal cancer progression, but they are downregulated during bronchial carcinogenesis. There is also evidence showing that Hsp60 and Hsp10 can be used as therapeutic agents, for example in rheumatoid arthritis. In view of these findings we want now to call attention to the potential of Hsp60 and Hsp10 in cancer therapy.     

Autoimmune diseases and breast cancer risk by tumor hormone‐receptor status among elderly women

The female preponderance of many autoimmune diseases suggests a possible hormonal etiology. Little research exists on systemic and organ‐specific autoimmune diseases and risk of breast cancer by tumor estrogen receptor (ER)‐ and progesterone receptor (PR)‐ status. Here, we evaluate associations between selected systemic and organ‐specific autoimmune diseases and breast cancer risk overall and by tumor ER‐ and PR‐status. We used linked Surveillance, Epidemiology and End Results (SEER)‐Medicare data, with first female breast cancer cases ages ≥66 years identified by SEER registries (years 1992–2011; N = 209,929). We selected female controls (N = 200,000) from a stratified 5% random sample of Medicare recipients who were alive and breast cancer‐free. We assessed exposures until 12 months before breast cancer diagnosis/selection using Medicare claims data. We estimated odds ratios (OR) and 99.9% confidence intervals (CI) using unconditional and multinomial logistic regression. We found reduced breast cancer risk among those with rheumatoid arthritis (OR = 0.84; 99.9% CI 0.79–0.89), systemic lupus erythematosus (OR = 0.82; 99.9% CI 0.70–0.97) and pernicious anemia (OR = 0.90; 99.9% CI 0.83–0.97) and increased risk among those with psoriasis (OR = 1.16; 99.9% CI 1.06–1.27). Statistically significant alterations in risk for rheumatoid arthritis were limited to ER‐positive (+) breast cancer, whereas those for the other three conditions were further limited to ER+/PR+ breast cancer. However, only differences for rheumatoid arthritis by ER‐status were statistically significant (p‐heterogeneity = 0.0001). The reasons for these associations need to be investigated in future studies accounting for host characteristics and autoimmune disease treatment.     

Fungal arthritis--a rare complication of systemic candidiasis or orthopedic intervention. Review of therapeutic experience with fluconazole

The higher number of implanted artificial joints, the broader use of aggressive treatment regimen, e.g. high-dose chemotherapy and total parenteral nutrition, the increasing use of central venous catheters and a broader use of immunosuppressive drugs are likely to result in a higher incidence of fungal arthritis, especially caused by Candida spp. Therefore, a careful evaluation of the available therapeutic options is necessary. The published clinical data on the therapeutic use of fluconazole in the treatment of fungal arthritis were reviewed. A total of 24 publications report the use of fluconazole in fungal arthritis in 32 patients. The mean duration of therapy was 6 months (maximum duration: 2 years) with an average dosage of 200-400 mg/d (maximum dosage: 800 mg/d). Native arthritis was diagnosed in 27 patients, prosthetic arthritis in 5 patients. In all patients an isolated joint was infected, most frequently the knee joint. Fluconazole was effective and safe in acute therapy alone or in combination with surgery as well as in long term suppression therapy.