104 research outputs found
Capecitabine and Temozolomide (CAPTEM) in advanced neuroendocrine neoplasms (NENs): a systematic review and pooled analysis
No full textBackground
Retrospective studies and single center experiences suggest a role of capecitabine combined with temozolomide (CAPTEM) in neuroendocrine tumors (NENs).
Methods
We performed a systematic review to assess the efficacy and safety of CAPTEM in patients affected with NENs, with the aim to better clarify the role of this regimen in the therapeutic algorithm of NENs.
Results
A total of 42 articles and 1818 patients were included in our review. The overall disease control rate was 77% (range 43.5%-100%). The median progression free survival ranged from 4 to 38.5 months, while the median overall survival ranged from 8 to 103 months. Safety analysis showed an occurrence of G3-G4 toxicities in 16.4% of the entire population. The most common toxicities were hematological (27.2%), gastrointestinal (8.3%,) and cutaneous (3.2%).
Conclusion
This systematic review demonstrated that CAPTEM was an effective and relatively safe treatment for patients with advanced well-moderate differentiated NENs of gastroenteropancreatic, lung and unknown origin
Metachronous and synchronous cancers in patients with neuroendocrine tumors
No full textIntroduction: Neuroendocrine tumors (NETs) are a heterogeneous group of malignancies with various clinical presentations and growth rates. NET incidence has been estimated to 2.5-5 per 100,000 people per year, and NET prevalence is 35 per 100,000. They are frequently associated with synchronous or metachronous second primary malignancies (SPM). Methods: We retrospectively reviewed our institutional database on NET patients. We report on 30 patients with NETs and SPMs from a series of 262 patients with NETs: 10 patients with synchronous NETs (33.3%) and 20 with metachronous SPMs (66.6%). Results: The median patient age was 67 years. Of the 10 synchronous lesions, 50% were observed in the GI tract. The most common locations of these lesions were the colon (15%) and pancreas (25%). In 2 patients, there was an association of prostate neoplasia with a subsequent NET of the pancreas. Conclusions: Only few studies have examined the association between NETs and SPMs. Our study showed that the risk of second cancer following NETs is increased. In this single-institution retrospective review, our incidence of additional malignancies in patients with NET was 11.4%
Breast metastasis and lung large-cell neuroendocrine carcinoma: first clinical observation
No full textThe lung Large-cell neuroendocrine carcinoma (LCNEC) is a very rare aggressive neuroendocrine tumor with a high propensy to metastasize and very poor prognosis. We report an atypical presentation of lung large-cell neuroendocrine carcinoma was diagnosed from a metastatic nodule on the breast. Our patient is a 59 years-old woman that presented in March 2014 non productive cough. A CT scan showed multiple brain, lung, adrenal gland and liver secondary lesions; moreover, it revealed a breast right nodule near the chest measuring 1.8 cm. The breast nodule and a lung lesions were biopsied and their histology and molecular diagnosis were LCNEC of the lung. To our knowledge, this is the first documented case of breast metastasis from LCNEC of the lung. Furthermore, breast metastasis from extramammary malignancy is uncommon and its diagnosis is difficult but important for proper management and prediction of prognosis. Therefore, a careful clinical history with a thorough clinical examination is needed to make the correct diagnosis. Moreover, metastasis to the breast should be considered in any patient with a known primary malignant tumor history who presents with a breast lump. Anyhow, pathological examination should be performed to differentiate the primary breast cancer from metastatic tumor. Therefore, an accurate diagnosis of breast metastases may not only avoid unnecessary breast resection, more importantly it is crucial to determine an appropriate and systemic treatment
Correlation between squamous intraepithelial lesions (SILs) and bacterial vaginosis
No full textBacterial vaginosis (BV) is a condition that seldom occurs in prepuberal girls or postmenopausal women, suggesting a hormonal component in its aetiology. The precise mechanisms by which BV arises are not fully understood. One proposed mechanism suggests that carcinogenic nitrosamines act either independently or via human papilloma virus (HPV). Human papillomavirus is known to be associated with the development of squamous intraepithelial lesion (SIL). Still today the relationship between BV and SIL is debated. Many confounding factors regarding the relationship between BV and SIL include the presence of HPV and/or other sexually transmitted diseases. In a case-controlled study the correlation between BV, SIL and the presence of HPV was evaluated. BV was diagnosed according to standard criteria: vaginal pH > 4.5; positive amine test or 'whiff' test; presence of clue cells and abnormal discharge. High risk-HPV testing by PCR was performed. X2 Pearson analysis was applied for statistical evaluation of data. The results of the study have shown that BV is not associated with SIL
Clinical management and follow-up of squamous intraepithelial cervical lesions during pregnancy and postpartum
No full textBackground: The incidence of cervical cancer in pregnancy is estimated to be 1-10/10000 pregnancies. Approximately 3% of cervical cancers are diagnosed during pregnancy. The incidence of abnormal Pap smears has been reported to be 5%-8%. Data on the spontaneous evolution of an intraepithelial neoplasia during pregnancy are quite diverse. Of dysplasia cases diagnosed during pregnancy, 10%-70% regress and sometimes even disappear postpartum, while persistence in the severity of cervical neoplasia is reported in 25%-47% and progression occurs in 3%-30%. However, adequate follow-up and definitive management in the postpartum period is important. The objective of the study was to assess proper management of squamous intraepithelial lesion (SIL) during and after pregnancy, to assess regression, persistence and risk of progression and the predictive role of HPV tests. Materials and Methods: Thirty-one out of 721 pregnant women with a diagnosis of low- and high-grade SIL were observed. All patients were triaged using standard colposcopy. The histological diagnosis was assessed by colposcopic direct biopsies. In patients affected by high-SIL with colposcopic findings of suspected micro-invasive lesions, a loop electrosurgical excisional procedure (LEEP) was carried out in pregnancy. High risk HPV tests were performed using PCR. The patients were followed up with cytology and colposcopy every 6-8 weeks during gestation and nine weeks postpartum. They were re-evaluated using cytology, colposcopy and histology for a final diagnosis and, when necessary, submitted to treatment. The patients were followed up for a minimum of 5 years. The HPV test was performed once at 6-8 weeks during gestation and annually during the follow-up. Results: Of the 31 patients with abnormal cytology, histological analysis revealed 10 cervical intraepithelial neoplasia (CIN) 1, 5 CIN 2 and 16 CIN 3. The HPV test at diagnosis was positive for HPV 16 type in 22 cases and negative in 9. Five patients with CIN 2 and 11 with CIN 3 were followed up; 5 patients with CIN 3 with colposcopic findings of suspected microinvasive lesions were submitted to an excisional procedure with LEEP before the 16th week of pregnancy. Conclusion: Performing high-risk HPV tests may improve the follow-up of patients with SIL in pregnancy and postpartum in addition to cytology and colposcopy to indicate persistence/progression of the lesions. Proper management and adequate follow-up could be proposed in pregnancy and postpartum
Laser vaporization in the management of CIN
No full textTo evaluate the effectiveness of laser CO2 vaporization in high-grade cervical intraepithelial neoplasias and to assess the diagnostic reliability of cytology, colposcopy, microbiology and HPV tests in predicting recurrence in a long-term outcome. Forty-four patients affectd by high-grade cervical intraepithelial neoplasia (HG-CIN) were submitted to laser CO2 vaporization and followed-up a minimum of five years. Vaginal smears for microbiological examination were detected. HPV testing was performed by polymerase chain reaction (PCR). The average age of the patients was 19.5 years (range 15-24). The cure rate after a single treatment was 95%. Two cases (5%) revealed HG-CIN persistence after three months. The five year follow-up of all cases submitted to a second laser procedure revealed negative cytologic and colposcopic findings. A higher degree of expertise and experience from the colposcopist and long-term follow-up proves the effectiveness of laser vaporization in the management of CIN in young women. It has been suggested that HPV infection alone may not be sufficient to promote carcinogenesis and that other cofactors could be involved. Microbiological tests are important to identify and treat any inflammation which might represent a cofactor of HPV infection in the pathogenesis of cervical dysplasia. Cytocolposcopic long-term follow-up, microbiological and HPV tests can improve regression of disease.Aims: To evaluate the effectiveness of laser CO(2) vaporization in high-grade cervical intraepithelial neoplasias and to assess the diagnostic reliability of cytology, colposcopy, microbiology and HPV tests in predicting recurrence in a long-term outcome. Methods: Forty-four patients affectd by high-grade cervical intraepithelial neoplasia (HG-CIN) were submitted to laser CO(2) vaporization and followed-up a minimum of five years. Vaginal smears for microbiological examination were detected. HPV testing was performed by polymerase chain reaction (PCR). Results: The average age of the patients was 19.5 years (range 15-24). The cure rate after a single treatment was 95%. Two cases (5%) revealed HG-CIN persistence after three months. The five year follow-up of all cases submitted to a second laser procedure revealed negative cytologic and colposcopic findings. Conclusions: A higher degree of expertise and experience from the colposcopist and long-term follow-up proves the effectiveness o
Cervical intraepithelial neoplasia: Risk factors for persistence and recurrence in adolescents
No full textOne of the most common sexually transmitted infections in adolescents is human papillomavirus. These infections can occur in one or multiple areas of the female genitalia but the vulva is usually the initial site of implantation for HPV. We carried out a long-term follow-up study of adolescents to evaluate the incidence of single or multiple lesions in the lower genital tract, the correlation between sexual behaviour and their localisation and behavioural risk factors for persistence and recurrence of HPV lesions and cervical intraepithelial lesion (CIN). We interviewed 268 women aged 12-21 years who had previously had cytology and/or physical examination suspicious for HPV infection. We asked them information about their lifestyle, sexual behaviour, work, personal or family history of genital warts and school attendance. Those who smoked more than five cigarettes a day were considered "smokers". We have no specific data about oral contraception although we know that none of the patients had used oral contraceptives for more than two years. Two hundred and thirty-four young women between the ages of 12 and 21 years were included in the study. The diagnostic schedule for a complete evaluation included exo- and endocervical cytology, colposcopy and directed biopsy. We found that in 126 out of 234 (53.8%) adolescents using contraceptives, only 85 (36.3%) had used a condom. The sites most frequently affected by lesions were the vulva, perianus and perineum (194/234; 82.9%), and the cervix (125/234; 53.4%). Vaginal lesions were detected in only 29/234 patients (12.3%). In 161 patients, sexual habits, age at first intercourse (p = 0.68), frequency of intercourse (p = 0.49) and number of lifetime partners (p = 0.27) as well as age (p = 0.26) played a role in transmission and incidence of HPV infection but not in the location of the lesions. This could be due to coexistent clinical and subclinical multiple infections as well as transmission via intercourse or from other sources, including tampons. HPV infection is detected by abnormal pap test, but the low correlation with colposcopic and histological findings in this study justify the support of other examinations such as colposcopy and punch biopsy for diagnosis. Moreover more attention should be paid to the psychological aspect of diagnoses and treatment of adolescents compared to older women as there was a high rate of patients lost in our study: 75/234 (32.05%) before LASER surgery and 55/159 (34.59%) during follow-up. Only 12-45% of sexually active adolescent girls had obtained Pap smear screening. In our study we found no correlation between treatment failure and cigarette smoking or between the use of oral contraceptives and persistence/recurrence after LASER surgery
Case Report: The Emerging Role of Ring Chromosome 22 in Phelan-McDermid Syndrome With Atypical Teratoid/Rhabdoid Tumor: The First Child Treated With Growth Hormone
No full textAtypical teratoid/rhabdoid tumors (AT/RTs) in the rhabdoid tumor predisposition syndromes are most often caused by germline mutations of the SMARCB1 gene located in chromosome 22q11.2. Although rarely, it can also result from the constitutional ring chromosome 22 (r22): during mitosis the ring chromosome may lead to an increased rate of somatic mutations, resulting in rhabdoid tumor predispositions when the tumor-suppressor gene SMARCB1 is involved. Individuals with r22 may present similar features as those with Phelan-McDermid syndrome (PMDS) due to 22q13.3 deletion, including the SHANK3 gene. Despite several reports on AT/RT in children with r22 and/or PMDS have been published, the role of constitutional r22 as new oncogenic mechanism for AT/RT is still under investigation. There is not a lot of data available on therapeutic and prognostic implications of r22 in AT/RT and PMDS. Herein, we present the first case of a child with constitutional r22, PMDS and AT/RT of the brain, who is a long term survivor and is been treated with growth hormone. We also describe an unexpected adverse reaction to midazolam
Expression of er, pgr, her-2, and ki-67 in core biopsies and in definitive histological specimens in patients with locally advanced breast cancer treated with neoadjuvant chemotherapy
No full textPurpose: Many studies have indicated that the response to therapy and the prognostic impact of a pathologic complete response after neoadjuvant treatment differ among breast cancer subtypes.
Methods: The aim of our study is to evaluate the effect of this treatment on the expression of estrogen and progesterone receptors, human epidermal growth hormone receptor 2 and Ki67 in breast cancer. We identified 125 patients.
Results: The estrogen receptor modified its expression from positive to negative in 8% patients and from negative to positive in 22%; progesterone in 21% and in 37% cases. Median Ki-67 value was 20.9% at biopsy and 18% after, HER-2 status did not show a remarkable change before or after neoadjuvant chemotherapy (NACT). We have identified a significant reduction in Ki-67 expression levels after chemotherapy in patients with a pathologic response. Detection of pretreatment Ki-67 could identify patients most likely to benefit from NACT.
Conclusions: NACT can change the status of ER, PgR, and Ki-67 expression in patients with breast adenocarcinoma, but it did not exert a significant effect on HER-2 status; HER-2 amplification appears to be more stable. We have identified a prognostic role for a decreased expression of PgR and Ki-67 after preoperative chemotherapy in breast cancer patients
Importin-β/karyopherin-β1 modulates mitotic microtubule function and taxane sensitivity in cancer cells via its nucleoporin-binding region
No full textThe nuclear transport receptor importin-β/karyopherin-β1 is overexpressed in cancers that display genomic instability. It is regarded as a promising cancer target and inhibitors are being developed. In addition to its role in nucleo-cytoplasmic transport, importin-β regulates mitosis, but the programmes and pathways in which it operates are defined only in part. To unravel importin-β's mitotic functions we have developed cell lines expressing either wild-type or a mutant importin-β form in characterised residues required for nucleoporin binding. Both forms similarly disrupted spindle pole organisation, while only wild-type importin-β affected microtubule plus-end function and microtubule stability. A proteome-wide search for differential interactors identified a set of spindle regulators sensitive to mutations in the nucleoporin-binding region. Among those, HURP (hepatoma up-regulated protein) is an importin-β interactor and a microtubule-stabilising factor. We found that induction of wild type, but not mutant importin-β, under the same conditions that destabilise mitotic microtubules, delocalised HURP, indicating that the spatial distribution of HURP along the spindle requires importin-β's nucleoporin-binding residues. Concomitantly, importin-β overexpression sensitises cells to taxanes and synergistically increases mitotic cell death. Thus, the nucleoporin-binding domain is dispensable for importin-β function in spindle pole organisation, but regulates microtubule stability, at least in part via HURP, and renders cells vulnerable to certain microtubule-targeting drugs
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