To quantify the risk of developing post-molar gestational trophoblastic neoplasia (pGTN) beyond the first normal human chorionic gonadotrophin (hCG) in women who have had a complete (CHM) or partial molar pregnancy (PHM) and to re-evaluate the current UK Hydatidiform mole hCG surveillance guidelines.
The Charing Cross Hospital Trophoblast Disease Centre database was screened to identify all registered cases of hydatidiform mole (HM) between 1980 and 2009.
We identified 20,144 cases of HM, comprising 8400 CHM, 9586 PHM, and 2158 cases of unclassified hydatidiform mole (UHM). Twenty-nine cases (20 CHM, 3 PHM and 6 UHM) developed pGTN after the first normal hCG. For CHM the risk of pGTN at the point of hCG normalisation was 1 in 406, and fell rapidly in the first six months of monitoring. For PHM the risk of pGTN at the point of hCG normalisation was 1 in 3195. Women with CHM where hCG normalisation occurred beyond 56days after uterine evacuation of molar tissue were found to have a 3.8-fold higher risk of pGTN.
Our results show that pGTN can occur after hCG normalisation following PHM but the risk is extremely low. Women with CHM have a comparatively higher risk of pGTN after hCG normalisation. Those with CHM where hCG normalises within 56days have a lower risk of pGTN. We have revised the current UK hCG surveillance protocol for PHM to a single additional confirmatory normal urine hCG measurement one month after first normalisation. The protocol for CHM remains unchanged.
Fibro-osseous benign lesions rarely affect the sinonasal tract and are divided into 3 different entities, namely osteoma, fibrous dysplasia and ossifying fibroma. They share several clinical, radiological and histological similarities, but have different behaviours. Ossifying fibroma, and in particular the "juvenile" histological subtype, may have a locally aggressive evolution and a high risk for recurrence if removal is incomplete. The purpose of the present study is to compare the clinical behaviour of ossifying fibroma with the other benign fibro-osseous lesions; highlight different behaviour between the histological subtypes; compare the advantages, limitations and outcomes of an endoscopic endonasal approach with reports in the literature. We retrospectively reviewed 11 patients treated for sinonasal ossifying fibroma at a tertiary care centre. All patients underwent CT scan, and MRI was performed in cases of cranial base involvement or recurrence. Pre-operative biopsy was performed in cases where it was possible to use an endoscopic approach. One patient underwent pre-operative embolisation with ipsilateral visual loss after the procedure. Depending on its location, removal of the tumour was performed using an endoscopic (n = 7), or an external (n = 3) or combined (n = 1) approach. Histopathologically, 5 patients presented the conventional type, 5 the juvenile psammomatoid variant, which was associated in 1 case with an aneurismal bone cyst, and 1 case presented the trabecular juvenile variant. Three patients affected by the juvenile psammomatoid histological variant presented invasion of the skull base and underwent a subtotal removal that subsequently required, due to the regrowth of the remnant, a transbasal approach. Clinical, radiological and histological findings should all be considered to establish differential diagnosis among fibrous osseous lesions. More studies are necessary to conclude if the localisation and extension of the disease at the time of diagnosis is more important than the histological variant. An endoscopic approach is the first choice in most of cases even if an external open approach may be necessary in selected patients.
Triple Negative Breast Cancers (TNBCs) lack the appropriate targets for currently used breast cancer therapies, conferring an aggressive phenotype, more frequent relapse and poorer survival rates. The biological heterogeneity of TNBC complicates the clinical treatment further. We have explored and compared the biological pathways in TNBC and other subtypes of breast cancers, using an in silico approach and the hypothesis that two opposing effects (Yin and Yang) pathways in cancer cells determine the fate of cancer cells. Identifying breast subgroup specific components of these opposing pathways may aid in selecting potential therapeutic targets as well as further classifying the heterogeneous TNBC subtype.
Gene expression and patient clinical data from The Cancer Genome Atlas (TCGA) and the Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) were used for this study. Gene Set Enrichment Analysis (GSEA) was used to identify the more active pathways in cancer (Yin) than in normal and the more active pathways in normal (Yang) than in cancer. The clustering analysis was performed to compare pathways of TNBC with other types of breast cancers. The association of pathway classified TNBC sub-groups to clinical outcomes was tested using Cox regression model.
Among 4729 curated canonical pathways in GSEA database, 133 Yin pathways (FDR < 0.05) and 71 Yang pathways (p-value <0.05) were discovered in TNBC. The FOXM1 is the top Yin pathway while PPARα is the top Yang pathway in TNBC. The TNBC and other types of breast cancers showed different pathways enrichment significance profiles. Using top Yin and Yang pathways as classifier, the TNBC can be further subtyped into six sub-groups each having different clinical outcomes.
We first reported that the FOMX1 pathway is the most upregulated and the PPARα pathway is the most downregulated pathway in TNBC. These two pathways could be simultaneously targeted in further studies. Also the pathway classifier we performed in this study provided insight into the TNBC heterogeneity.
Summarize recent findings regarding the impact of margin status on oncologic outcomes and organ preservation, as well as evaluate possible management policies of close and positive margins after transoral laser microsurgery (TLM) for Tis-T2 glottic carcinomas.
Impact of margin status on survival rates remains controversial, whereas some authors found close and positive margins to be independent risk factors for recurrence and poorer survival rates, others did not find any significant variations compared with negative ones. A common trend can be observed in performing a watchful waiting policy or second look TLM in patients with close-superficial and positive single-superficial margins. Further treatment seems preferable in case of deep and positive multiple superficial margins.
Positive margins are present in up to 50% of patients treated by TLM, even though a high rate of false positivity, reaching 80%, has been described. Close and positive single superficial margins seem to be linked to higher recurrence rates compared with negative margins, even though watchful wait and see policy, especially when performed by adjunctive visual aids like Narrow Band Imaging, maintains good final oncological and organ preservation outcomes. Further treatments are required in case of deep margin positivity.
French patients (≤18years) treated for dysgerminoma between 1985 and 2005 in TGM-85, 90, 95 protocols were included. Treatment was based on primary unilateral oophorectomy followed by prophylactic lymph node irradiation (1985-1998) or a wait-and-see strategy (1998-2005) for localised completely resected tumours (pS1) or by platinum-based chemotherapy for advanced diseases.
Forty-eight patients (median age 12.8 years) were included. Six patients had gonadal dysgenesis. Two had bilateral dysgerminoma. Twenty-eight patients had loco-regional dissemination, seven with para-aortic lymph nodes. None had distant metastases. Primary surgery was performed in 47/48 patients. Among the 15 patients with pS1 tumour: seven did not receive adjuvant treatment, six had lymph node irradiation and two received chemotherapy. Among the 32 patients with advanced tumour, 31 received cisplatinum-based (n = 25) or carboplatin-based (n = 8) regimen with lymph node irradiation for one of them and one did not receive adjuvant treatment. With a median follow-up of 14 years, all patients are alive in complete remission. Five events occurred: 2 contralateral dysgerminomas, 1 peritoneal relapse and 2 second neoplasms (teratoma and melanoma). Bilateral oophorectomy was necessary for 12 patients. Desire of pregnancy was expressed for 17/36 patients with unilateral oophorectomy, which succeeded in 13 cases (5 medically assisted). 2/17 had ovarian failure. The renal function was normal in 24/25 evaluated patients treated with platinum, ifosfamide or irradiation. The hearing function was evaluated on 17/36 patients treated with platinum: 12 Brock grade-0, 3 brock grade-1 and 2 grade-4.
Dysgerminoma has an excellent prognosis even in advanced cases with conservative surgery and platinum-based chemotherapy. However the disease and/or treatment resulted in a high rate of bilateral oophorectomies and a significant impact on future fertility.
To clarify the efficacy of palliative radiotherapy for the relief of symptoms due to skin invasion in patients with breast cancer.
We conducted a multi-institutional prospective observational study of patients who received palliative radiotherapy for skin invasion due to a primary lesion or chest wall recurrence. Bleeding/discharge, offensive odor, pain and QOL scores were evaluated before and 1, 3 and 6 months after radiotherapy.
Twenty-one patients were assessed. Sixteen patients (76%) received 36 Gy in 12 fractions. The mean (±1 SD) score of bleeding/discharge was 1.90 ± 0.89 before radiotherapy, 1.50 ± 0.74 at 1 month, 0.47 ± 0.58 at 3 months, and 0.82 ± 1.04 at 6 months (P = 0.001). The mean score of offensive odor was 1.21 ± 1.38 before radiotherapy, 0.71 ± 0.92 at 1 month, 0.20 ± 0.41 at 3 months, and 0.27 ± 0.62 at 6 months (P = 0.008). The mean score of pain was 2.90 ± 1.22 before radiotherapy, 3.05 ± 1.36 at 1 month, 3.29 ± 1.10 at 3 months, and 3.31 ± 1.54 at 6 months (P = 0.431). The mean total score of QOL-ACD/QOL-ACD-B was 126.2 ± 24.5 before radiotherapy, 130.3 ± 26.3 at 1 month, 136.2 ± 26.6 at 3 months, and 126.6 ± 32.8 at 6 months (P = 0.178).
Palliative radiotherapy for skin invasion in patients with breast cancer might be effective, especially for the relief of bleeding/discharge and offensive odor.
Autologous stem cell transplantation (ASCT) as part of the primary therapy in multiple myeloma (MM) is standard practice. In contrast, the role of a second ASCT (ASCT2) and subsequent lenalidomide maintenance for relapsed disease remains unclear. In this study, we analysed 86 consecutive MM patients with a first relapse after prior ASCT receiving either a second ASCT or conventional chemotherapy. After a median follow-up of 37.7 months since first relapse, 54 (62.8%) patients were still alive and 29 (33.7%) without progression. Sixty-one (71.0%) patients received ASCT2 and had better progression-free survival (PFS) (30.2 versus 13.0 mo; P = .0262) and overall survival (OS) rates (129.6 versus 33.5 mo; P = .0003) compared with 25 (29.0%) patients with conventional treatment. Patients relapsing later than 12 months after ASCT1 benefitted from a second ASCT with better PFS2 (P = .0179) and OS2 (P = .0009). Finally, lenalidomide maintenance after ASCT2 was associated with longer PFS (41.0 vs 21.6 mo; P = .0034) and better OS (not yet reached vs 129.6 mo; P = .0434) compared with patients without maintenance. Our data suggest that a second ASCT and lenalidomide maintenance given at first relapse in MM after prior ASCT are associated with better survival rates.
Non-functioning pituitary adenomas (NFA) are benign pituitary neoplasms not associated with clinical evidence of hormonal hypersecretion. A substantial number of patients with NFA have morbidities related to the tumor and possible recurrence(s), as well as to the treatments offered. Studies assessing the long-term mortality of patients with NFA are limited. Based on the published literature of the last two decades, overall, the standardized mortality ratios in this group suggest mortality higher than that of the general population with deaths attributed mainly to circulatory, respiratory and infectious causes. Women seem to have higher mortality ratios, and assessment of time trends suggests improvement over the years. There is no consensus on predictive factors of mortality but those most consistently identified are older age at diagnosis and high doses of glucocorticoid substitution therapy. Well designed and of adequate power studies are needed to establish the significance of factors compromising the survival of patients with NFA and to facilitate improvements in long-term prognosis.
Whether smoking and metabolic syndrome (MetS) can affect colorectal carcinoma (CRC) prognosis remains debatable. Therefore, the present study aimed to examine the individual and combined effects of smoking and MetS on the prognosis of patients with localized CRC, including stage I to III disease. The relationship among smoking status, MetS, and CRC was assessed in 838 Chinese male patients. Cox proportional hazards regression analysis was used to evaluate CRC prognosis adjusted for clinicopathological variables. Relative excess risk of interaction (RERI), attributable proportion (AP), and synergy index (SI) were used to evaluate additive interactions between smoking and MetS. The presence of MetS was an independent risk factor for low rates of recurrence-free survival (RFS) but not for overall survival (OS). However, smoking was independently associated with both poor RFS and OS. Furthermore, the recurrence risk for current smokers with MetS was 1.62 times as high as the sum of risks in patients exposed to each risk factor alone. In conclusion, current smoking habit is a risk factor for both recurrence and cancer-specific mortality in CRC patients, while MetS is an independent predictor for CRC recurrence. Furthermore, these two factors have an additive effect on the recurrence risk of CRC.