卡培他滨相关基因多态性与手足综合征关系的研究进展

近年来,卡培他滨被广泛应用于临床,手足综合征(Hand and foot syndrome,HFS)是卡培他滨的剂量限制性毒性之一,常表现为手、足部的麻木,感觉迟钝,麻刺感,皮肤肿胀或红斑,脱屑、水泡或严重疼痛。它的发生严重影响了患者的化疗效果及日常生活。卡培他滨代谢酶的基因突变在药物疗效和不良反应方面扮演重要角色,尤其是CDA、CES、TP、DPD、TYMS、MTHFR的基因多态性与HFS的关系被广泛研究并取得了一定的进展。本文对卡培他滨代谢酶与HFS的关系进行综述,为确定卡培他滨化疗引起HFS的生物靶点提供参考。     

Muir-Torre syndrome

Muir-Torre syndrome is an autosomal-dominant skin condition of genetic origin, characterised by tumours of the sebaceous gland or keratoacanthoma that are associated with visceral malignant diseases. The cutaneous characteristics of Muir-Torre syndrome are sebaceous adenoma, epithelioma, carcinoma, or multiple keratoacanthomas, whereas visceral malignant diseases include colorectal, endometrial, urological, and upper gastrointestinal tumours. Although Muir-Torre syndrome has a striking familial association and features of autosomal-dominant transmission, it can arise in individuals without a family history or any known mutations. Clinical and biomolecular evidence has suggested that there are two types of Muir-Torre syndrome. The most common is a variant of hereditary non-polyposis colorectal cancer, which is characterised by defects in mismatch repair genes and early-onset tumours. The second type does not show deficiency in mismatch repair and its pathogenesis remains undefined. Diagnosis of these rare sebaceous lesions warrants the search for associated internal malignant diseases: the peculiarity of skin lesions and their biomolecular characterisation with microsatellite instability analysis and immunohistochemistry could be used to identify familial Muir-Torre syndrome, allowing clinicians to tailor a personalised programme to screen for skin and visceral malignant diseases in high-risk individuals.     

The liver: another organ involved in Muir Torre syndrome?

Muir Torre syndrome is a rare autosomal dominant cancer-predisposing syndrome characterized by the occurrence of sebaceous gland neoplasms and/or keratoacanthomas associated with visceral malignancies that belong to the spectrum of hereditary non polyposis colorectal cancer (HNPCC), i.e., tumors of gastrointestinal and genitourinary tracts. Hepatobiliary malignancy in association with Muir Torre syndrome has rarely been reported. Here, we describe a case of Muir Torre syndrome associated with an hepatocellular-carcinoma in a patient with a non-cirrhotic liver and an HNPCC-family with multiple cases of hepatocellular carcinoma.     

Non-Hodgkin's lymphoma in Job's syndrome: a case report and literature review

Job's or hyper immunoglobulin E recurrent infection syndrome (Hyper-IgE syndrome) is a rare, often inherited multisystem disorder, characterized by cutaneous abscesses, pneumonia, elevated IgE levels and skeletal defects. We report a case of a 22-year-old man with Job's syndrome who presented with back pain. He was found to have diffuse large B-cell lymphoma involving his second lumbar vertebrae and spleen. Treatment with dose-adjusted EPOCH-rituximab (DA-EPOCH-R) chemotherapy achieved a complete remission after 4 cycles. A review of reported cases of lymphoma in Job's syndrome indicates an increase in relative risk of 259 (95% confidence interval 102, 416). The cause of the increased risk has yet to be defined but has similarities to a pathogenetic model of AIDS related lymphoma. In previous reports of lymphoma in Job's syndrome, patients presented with extranodal disease and had poor outcomes. With appropriate chemotherapy and hematological support, lymphoma associated with Job's syndrome can achieve complete remission.     

Quantitative models for predicting mutations in Lynch syndrome genes

As genotyping for Lynch syndrome has become widespread, more and more people are being counseled about whether to be genotyped for mutations in mismatch repair genes. Recently a number of quantitative models have been developed to identify potential Lynch syndrome patients and serve as decision aids for patients at genetic counseling clinics. In contrast to existing clinical guidelines that give dichotomous classifications, these models provide a probability that a family or individual has Lynch syndrome. These models have been shown to be useful tools in identifying likely carriers of Lynch syndrome mutations. Correctly used, they have the potential to greatly improve the current diagnosis and management of Lynch syndrome families. To help clinicians and genetic counseling professionals understand the differences among these models and use the models wisely, we review the key features of each model and offer some guidelines on their use.     

Hand-foot syndrome associated with short infusions of combination chemotherapy with gemcitabine and vinorelbine.

The hand–foot syndrome (palmar–plantarerythrodysesthesia) is a side-effect which is associated with severalcytotoxic agents (e.g. 5-fluorouracil, UFT, capecitabine, cytarabine,doxorubicin, liposomal-encapsulated doxorubicin). An association with aprolonged infusion of high doses of vinorelbine has also been described.To date a hand–foot syndrome after gemcitabine or short infusionsof vinorelbine has not been reported before. The patient described herehad a non-small-cell lung cancer stage IIIB disease and developed ahand–foot syndrome after short infusions of standard-dosechemotherapy of a combination with gemcitabine and vinorelbine.     

Acute myeloid leukemia associated with nephrotic syndrome: case report and literature review

The hematological malignancies associated with nephrotic syndrome are mainly Hodgkin's and non-Hodgkin's lymphomas and chronic lymphocytic leukemia. Acute myelogenous leukemia (AML) has rarely been described in association with the nephrotic syndrome. The clinical course of a 44-year-old patient with AML who presented with nephrotic syndrome is described and the clinicopathologic features of the other cases reported in the world literature are reviewed. We could not find a consistent pattern regarding the subtype of leukemia, renal pathology, and temporal relationship between the nephrotic syndrome and the leukemia or the response to treatment. The present case was unique in that the clinical course of the renal disorder correlated with the course of the leukemia responding to treatment with anti-leukemic agents. We conclude that nephrotic syndrome can also be associated with AML. In some cases there is a direct causal effect of the leukemic process on the renal pathology while in others it is exerted indirectly via other complications of the malignancy or the treatment.     

POEMS综合征的诊断和治疗

POEMS综合征是一种罕见的浆细胞疾病,近年来在POEMS的诊断和治疗方面都取得了很大进展。本文将重点阐述POEMS综合征的诊断标准以及早期诊断的要点。在治疗方面,自体造血干细胞移植由于其较好的疗效已经成为年轻POEMS综合征患者的一线治疗。马法兰联合地塞米松也有着较高的缓解率和很好的安全性,可以作为老年或其他不适合移植患者的治疗选择。新药例如来那度胺等给POEMS综合征患者提供了更多的治疗选择。      

Myelodysplastic syndrome

Myelodysplastic syndrome (MDS) is a heterogenous syndrome which has features of refractory anemia and preleukemic state due to the ineffective hematopoiesis of bone marrow cells. MDS is classified by the FAB classification and/or WHO classification, and has an International Prognostic Scoring System (IPSS) for evaluation of the prognosis. Available therapies consist of a variety of modalities from supportive therapy to hematopoietic stem cell transplantation, and are selected according to the condition of each patient.     

Palmar-plantar erythrodysesthesia syndrome associated with short-term continuous infusion (5 days) of 5-fluorouracil

A case of palmar-plantar erythrodysesthesia syndrome (PPES) observed during a 120-h infusion of 5-fluorouracil (5-FU) is presented. This syndrome has been described in the literature after protracted infusion chemotherapy of over 30 days. The agent most frequently associated with this syndrome was 5-FU. A 53-year-old man was admitted to the hospital with a well-differentiated squamous cell carcinoma of the retromolar trigone. The patient received 100 mg/m2 of cisplatin on day 1 and 120-h continuous infusion of 1000 mg/m2 of 5-FU every 3 weeks. After the second course, the patient developed clinical features consistent with PPES. This side effect has not been previously reported with short-term (5-day or 120-h) continuous infusion of 5-FU. Less frequently, the syndrome has also been described with 10-day continuous infusion. The etiopathogenesis of PPES is unclear, but it seems to be dose-dependent and probably related to cutaneous drug accumulation.     

Hepatocellular carcinoma with Pancoast's syndrome as an initial symptom: a case report

Pancoast's syndrome refers to a condition consisting of Horner's syndrome and arm pain that is most commonly found in patients with a lung tumor of the superior sulcus invading the upper ribs or spine, lower brachial plexus and sympathetic chain. We report a 76-year-old female who had a thoracic inlet mass that presented as Pancoast's syndrome, showing profound pain, numbness and weakness of the left upper limb. Further evaluation revealed an increased level of serum alpha-fetoprotein (24278 ng/ml), cryptogenic liver cirrhosis and primary hepatocellular carcinoma with protruding T3 vertebra metastasis that resulted in Pancoast's syndrome. To our knowledge, it is a rare case and only one case has been reported previously.     

Paraneoplastic encephalomyelitis: Is it an oropharyngeal or a lung cancer complication?

This case report describes a patient with a locally advanced oropharyngeal cancer with a simultaneous paraneoplastic encephalomyelitis. To the best of our knowledge, a paraneoplastic neurological syndrome is a rare complication in head and neck cancer, and has previously not been reported in the literature. One year later, following initial treatment, a small cell lung cancer developed, a tumor frequently associated with this type of paraneoplastic syndrome. The dilemma, therefore, is whether this paraneoplastic symdrome was a secondary complication of the tonsilar concurrent cancer or a metachronous paraneoplastic syndrome prior to small cell lung cancer.     

Genetic testing by cancer site: ovary

ABSTRACT: Approximately 1 in every 4 to 5 women with a diagnosis of ovarian cancer has a hereditary gene mutation that is responsible for the development of her cancer. Identifying women at increased risk of developing ovarian cancer due to a hereditary cancer syndrome can allow for early detection or prevention of not only ovarian cancer, but also other cancers, depending on the causative gene. This review focuses on 3 of the most common hereditary ovarian cancer syndromes, hereditary breast and ovarian cancer syndrome (the BRCA1 and BRCA2 genes), Lynch syndrome (also known as hereditary nonpolyposis colorectal cancer syndrome), and Peutz-Jeghers syndrome, including key features, genetics, and management of these syndromes. In addition, newly discovered genes (eg, RAD51C and RAD51D) linked to ovarian cancer are discussed.     

Schnitzler's Syndrome: Increased Levels of Bone Formation and Angiogenesis Factors Are Reduced After Successful Pefloxacin Treatment

Schnitzler's syndrome is characterized by chronic urticaria and monoclonal immunoglobulin (Ig) M gammopathy, with other features including intermittent fever, joint and/or bone pain with radiologic evidence of osteosclerosis, lymphadenopathy, enlarged liver and/or spleen, leukocytosis, and elevated erythrocyte sedimentation rate. The etiology of the syndrome remains obscure, although involvement of various cytokines has been proposed. Bone metabolism and angiogenesis markers are deregulated in Waldenström macroglobulinemia and IgM monoclonal gammopathy of unknown significance, but these markers have not been assessed in Schnitzler's syndrome. Herein, we report a patient with Schnitzler's syndrome who was treated with oral pefloxacin. Serum levels of osteoclast regulators, markers of bone remodeling and angiogenesis cytokines, were measured before treatment and serially after the initiation of treatment. High bone turnover and strikingly elevated levels of angiogenic cytokines were observed at diagnosis. Treatment with pefloxacin resulted in a normalization of the bone remodeling process and a significant reduction of angiogenic cytokines, with rapid and sustained improvement of symptoms, suggesting that these factors might be implicated in the pathophysiology of this syndrome. Furthermore, pefloxacin was proven to be an effective treatment for patients with Schnitzler's syndrome.     

Three molecular pathways model colorectal carcinogenesis in Lynch syndrome

Lynch syndrome is caused by germline mutations of DNA mismatch repair (MMR) genes. MMR deficiency has long been regarded as a secondary event in the pathogenesis of Lynch syndrome colorectal cancers. Recently, this concept has been challenged by the discovery of MMR‐deficient crypt foci in the normal mucosa. We aimed to reconstruct colorectal carcinogenesis in Lynch syndrome by collecting molecular and histology evidence from Lynch syndrome adenomas and carcinomas. We determined the frequency of MMR deficiency in adenomas from Lynch syndrome mutation carriers by immunohistochemistry and by systematic literature analysis. To trace back the pathways of pathogenesis, histological growth patterns and mutational signatures were analyzed in Lynch syndrome colorectal cancers. Literature and immunohistochemistry analysis demonstrated MMR deficiency in 491 (76.7%) out of 640 adenomas (95% CI: 73.3% to 79.8%) from Lynch syndrome mutation carriers. Histologically normal MMR‐deficient crypts were found directly adjacent to dysplastic adenoma tissue, proving their role as tumor precursors in Lynch syndrome. Accordingly, mutation signature analysis in Lynch colorectal cancers revealed that KRAS and APC mutations commonly occur after the onset of MMR deficiency. Tumors lacking evidence of polypous growth frequently presented with CTNNB1 and TP53 mutations. Our findings demonstrate that Lynch syndrome colorectal cancers can develop through three pathways, with MMR deficiency commonly representing an early and possibly initiating event. This underlines that targeting MMR‐deficient cells by chemoprevention or vaccines against MMR deficiency‐induced frameshift peptide neoantigens holds promise for tumor prevention in Lynch syndrome.     

Hereditary ovarian carcinoma.

No woman is at greater risk for ovarian carcinoma than one who is a member of a hereditary ovarian carcinoma syndrome kindred and whose mother, sister, or daughter has been affected with this disease and with an integrally related hereditary syndrome cancer. This article surveys the existing understanding about hereditary ovarian carcinoma. Emphasis is given to its diagnosis, heterogeneity, interpretation, and the application of this information to improving cancer control.     

Insular carcinoid primary in the ovary. A clinicopathologic analysis of 48 cases.

Forty-eight cases of primary insular carcinoid of the ovary were analyzed from a clinicopathologic viewpoint. Sixteen (33%) were associated with preoperative clinical evidence of the carcinoid syndrome. At operation only one ovary was usually enlarged, but in 16% the contralateral ovary was also enlarged by either a dermoid cyst or a mucinous cystadenoma or cystadenocarcinoma. The volume of the carcinoid was the most important determinant of whether the carcinoid syndrome was present. No patient had the syndrome whose carcinoid formed only a small portion of a teratoma. Pure tumors or components of teratomas between 4 and 7 cm in diameter were associated with the syndrome in one-half, and larger carcinoids in two-third of the cases. Prominent acinar differentiation also correlated with the presence of the syndrome. Although the prognosis was nearly always favorable after the removal of the tumor, tricuspid valve damage continued to progress and led to cardiac decompensation in one patient; fatal recurrences developed in two others. The primary insular carcinoid should be distinguished from carcinoid metastatic to the ovary, which is nearly always bilateral, is usually associated with the presence of peritoneal metastases, and has a poor prognosis.     

林奇综合征发生发展的研究进展

林奇综合征是最常见的遗传性结直肠癌综合征,其主要特征是对多系统癌症的易感性,主要表现为结直肠癌和子宫内膜癌的发生.林奇综合征的致癌倾向源于一组错配修复蛋白的基因结构的改变,失活的错配修复蛋白导致基因组中的微卫星高度不稳定性,随着时间的推移,微卫星以及基因组其他部位突变的积累可以影响细胞内重要功能蛋白的数量或活性,从而引...     

Metabolic Syndrome, Insulin Resistance, and Inflammation in Breast Cancer: Impact on Prognosis and Adjuvant Interventions

The metabolic syndrome, a clinical syndrome that includes central obesity, dyslipidemia, hypertension and glucose intolerance, has been associated with diabetes and cardiovascular disease. Recent evidence links it to breast cancer risk and outcome and suggests that existing adjuvant therapies may exacerbate the syndrome and have reduced efficacy when the syndrome is present. Potential mediators of effects of the syndrome on cancer include insulin/insulin-like growth factor, adipocytokines such as leptin, and markers of inflammation such as interleukins, C-reactive protein, and serum amyloid A. Growing epidemiologic, clinical, and preclinical evidence suggests insulin may be a key mediator. Potential interventions include changes in lifestyle (weight loss, increased physical activity) or pharmacologic approaches. Metformin, a drug commonly used to treat diabetes that reduces the hyperinsulinemia and hyperglycemia associated with the metabolic syndrome, shows promise in epidemiologic, preclinical, and clinical work. Interventions trials involving metformin are underway, including a large adjuvant study by the National Cancer Institute of Canada known as NCIC CTG MA.32.