Post-recurrence survival in patients with cervical cancer.

BACKGROUND: Up to 26% of patients with early-stage cervical cancer experience relapse after primary surgery. However, little is known about which factors influence prognosis following disease recurrence. Therefore, our aims were to determine post-recurrence disease-specific survival (PR-DSS) and to identify respective prognostic factors for PR-DSS. METHODS: Data from 528 patients with early-stage cervical cancer who relapsed after primary surgery performed between 2007 and 2016 were obtained from the SCANN study (Surveillance in Cervical CANcer). Factors related to the primary disease and recurrence were combined in a multivariable Cox proportional hazards model to predict PR-DSS. RESULTS: The 5-year PR-DSS was 39.1% (95% confidence interval [CI] 22.7%-44.5%), median disease-free interval between primary surgery and recurrence (DFI1) was 1.5 years, and median survival after recurrence was 2.5 years. Six significant variables were identified in the multivariable analysis and were used to construct the prognostic model. Two were related to primary treatment (largest tumour size and lymphovascular space invasion) and four to recurrence (DFI1, age at recurrence, presence of symptoms, and recurrence type). The C-statistic after 10-fold cross-validation of prognostic model reached 0.701 (95% CI 0.675-0.727). Three risk-groups with significantly differing prognoses were identified, with 5-year PR-DSS rates of 81.8%, 44.6%, and 12.7%. CONCLUSIONS: We developed the robust model of PR-DSS to stratify patients with relapsed cervical cancer according to risk profiles using six routinely recorded prognostic markers. The model can be utilised in clinical practice to aid decision-making on the strategy of recurrence management, and to better inform the patients.

Lung Cancer in the Young.

INTRODUCTION: Median age at diagnosis of lung cancer is 70 years. Its presentation in patients 40 or younger is uncommon and it has been proposed that maybe it is a different disease due to its clinical characteristics and genetic makeup. There are a limited number of studies in this population and they report different clinic-pathological characteristics in comparison with older patients. METHODS: We described the incidence of lung cancer patients diagnosed at age 40 or younger at the Instituto Nacional de Enfermedades Neoplasicas (INEN), Lima-Peru; from 2009 to 2017 and evaluated the characteristic of NSCLC. Epidemiologic and clinic-pathological data was collected from clinical files. Analysis was carried out using SPSSvs19 software. RESULTS: We identified 3823 patients with lung cancer seen at INEN during the study period. Among these, 166 (4.3%) patients were 40 years or younger, and 137/166 (82.5%) were NSCLC. Median age at diagnosis was 36 years (range 14-40 years) and 59.1% of patients were female. A smoking history was present in 14.4% of patients. Frequent symptoms at diagnosis were cough (62.0%), chest pain (51.8%) and dyspnea (40.9%). Adenocarcinoma was the most common histological type (63.3%). Most patients had advanced disease at diagnosis (84.7%). The median overall survival was 8.2 months. CONCLUSIONS: The proportion of young patients with lung cancer in our population is higher than that reported in the most recent literature. Lung cancer in the young is mostly sporadic, more frequent in women, usually adenocarcinoma type and it presents with advanced disease, resulting in a very poor survival.

Coexistence of double gallbladder with cholangiocarcinoma: A case report.

RATIONALE: Gallbladder duplication is a rare congenital disorder, which could cause an increasing risk of complications during surgery. The coexistence of cholangiocarcinoma with double gallbladder is extremely rare, which might lead to an even higher possibility of misdiagnosis and postsurgery complications. PATIENT CONCERNS: A 58-year-old female was presented with abdominal pain and jaundice. Abdominal ultrasonography showed duplication of gallbladder, one of which with a thickened wall and a rough surface. This was also confirmed by an abdominal computed tomography (CT), magnetic resonance imaging (MRI) and magnetic resonance cholangiopancreatography (MRCP) scan. During the surgery, we found a tumor inside one bile duct. The postsurgery pathology showed adenosquamous carcinoma. DIAGNOSES: Gallbladder duplication, cholangiocarcinoma. INTERVENTIONS: The tumor was removed by surgery. OUTCOMES: The patient died of tumor relapse six months after surgery. LESSONS: This is the first reported case with coexistence of gallbladder duplication and cholangiocarcinoma, which was diagnosed by abdominal ultrasound, CT and MRCP, as well as further confirmed in surgery and pathology. This case emphasized the importance of a thorough examination of gallbladder before surgery, especially in those cases with suspected double gallbladder, since each gallbladder could have the possibility of an independent cholangiocarcinoma.

Lung cancer-associated myofibroblasts reveal distinctive ultrastructure and function.

BACKGROUND: Cancer-associated stromal cells interact with carcinoma cells and thus participate in tumor growth. Our aim was to characterize the ultrastructure and contractile properties of stromal cells in collagen gel cultured from lung cancer of various histological types and from tumor-free lung. METHODS: Cells cultured from lung cancer (13 adenocarcinomas, six squamous cell carcinomas, one adenosquamous carcinoma, and one pleomorphic carcinoma) and tumor-free lung were analyzed by transmission electron microscopy and three-dimensional collagen gel contraction assays. The expression of α-smooth muscle actin (α-SMA), a recognized myofibroblast marker, was examined by immunoelectron microscopy from individual cells and by Western blotting from the whole cultured cell population. RESULTS: According to their ultrastructure, the cell lines were composed of fibroblastic and myofibroblastic cells. In electron microscopy, cells of lung cancer exhibited more myofibroblastic features displaying higher amounts of actin belts (p = 0.057) and α-SMA labeling (p = 0.010) than cells from tumor-free lung. Myofibroblasts cultured from lung cancer of smokers expressed less α-SMA labeling (p = 0.013) than counterparts from nonsmokers. Western blotting revealed that cancer-associated fibroblasts expressed more α-SMA (p = 0.006) than cells from tumor-free lung, whereas cells from tumor-free central lung of smokers showed less α-SMA (p = 0.039) than counterparts from nonsmokers. Cells cultured from cancer contracted more in collagen gel than those from tumor-free lung. The contractile capacity in collagen gel correlated with the frequency of extracellular component of fibronexus by transmission electron microscopy. CONCLUSIONS: Lung cancer-associated myofibroblasts are different both ultrastructurally and functionally when compared with cells cultured from tumor-free lung. Smoking altered myofibroblastic phenotype, regardless of their origin.

EGFR and KRAS mutations in Chinese patients with adenosquamous carcinoma of the lung.

Adenosquamous carcinoma (ADSQ) is uncommon in non-small cell lung cancer (NSCLC). The frequency rate of ADSQ was 9.7% of 6990 primary lung cancers resected in our department. Many researches have analyzed genetic and molecular alterations in adenocarcinoma (AD) and squamous cell carcinoma (SQ), but few molecular studies have been conducted on heterogeneous ADSQ. The current study was to investigate gene mutations of epidermal growth factor receptor (EGFR) and Kirsten rat sarcoma viral oncogene (KRAS) and their correlation with clinical variables in Chinese patients with ADSQ. Histologic features were reviewed, and immunohistochemical (IHC) and molecular (EGFR and KRAS) studies were done in 55 Chinese patients with ADSQ. Microscopically, all the tumors demonstrated dual differentiation with varying proportions of AD and SQ. Based on morphological diagnosis, a combination of multiple IHC markers is helpful for accurately discriminating two undifferentiated histologic subtypes of ADSQ. EGFR mutations were identified in 21 (38.2%) patients: 11 mutations were in exon 19, 1 in exon 20, 7 in exon 21 and double mutations were found in two patients. We also found two new mutations, namely, L747-E749del K754A within exon 19 and H850R within exon 21. Moreover, 16 (29.1%) silent mutations Q787Q in exon 20 were found in the series, five of which coexisted with other mutations. EGFR mutations were more frequently found in patients with size of the tumors ≥3cm [19/35 (54.3%); 2/20 (10%); P=0.001] or coexistent double cancer. However, the EGFR mutation was not associated with gender, age, lymph node status, tumor stage and smoking history. KRAS mutations were present in 2 (3.64%) male patients in codon12 (G12C) and none of them showed EGFR mutation. Moreover, identical EGFR and KRAS mutations in both components of ADSQ were further confirmed by microdissection techniques. The data indicated that the incidence of EGFR and KRAS mutations in Chinese patients with ADSQ were similar to those of Asian patients with AD. Furthermore, EGFR silent mutations accounted for a large proportion in ADSQ. Additional prospective studies are needed in order to define the clinical relevance of new and silent mutation variants.

Adenosquamous lung carcinomas: a histologic subtype with poor prognosis.

INTRODUCTION: The aim of this study is to evaluate the prognostic factors and outcome of patients operated for adenosquamous (ADS) carcinoma of the lung, in comparison with adenocarcinoma (AD) and squamous cell carcinoma (SCC). METHODS: a retrospective review of our thoracic cancer surgical database for patients operated for ADS, SCC and AD between January, 1995 and December, 2009 was done. RESULTS: Forty-eight patients (39 males, 81.3%) had ADS; complete tumor resection and lymphadenectomy was accomplished in all patients. A higher stage at presentation was observed in ADS, as compared to AD or SCC (p=0.0001). Three and 5-year survival rates were 25% and 15%. ADS overall survival was worse than AD or SCC (p=0.0005). Three and 5-year survival rates of ADS Stage I were similar to those of Stage IIIA AD or SCC. More than half ADS patients developed distant metastases (MTS) or local recurrences. Brain MTS were the most frequent. Median survival for those patients was 8±2.3 months. Postoperative platinum-based chemotherapy statistically improved patients survival (p=0.02). In the multivariate analysis, the presence of MTS (p=0.001), the tumor perineural invasion (p=0.01) and the tumor stage (p=0.0005) were factors associated with poor prognosis. Adjuvant chemotherapy was a significant positive prognostic factor (p=0.00001). CONCLUSIONS: ADS are uncommon and extremely aggressive lung tumors. Adjuvant chemotherapy should be administered even in Stage I radically resected tumors. A whole brain postoperative prophylactic radiotherapy could be proposed to reduce risk of developing brain MTS.

Cancer of the cervix in Ilorin, Nigeria.

OBJECTIVE: The purpose of this study is to review our experience with carcinoma of the cervix in Ilorin, Nigeria. METHOD: From 1st January 1990 to 31st December 1999, a total of 169 cases of invasive cervical cancer wereseen at the Department of Obstetrics and Gynaecology of the University of Ilorin Teaching Hospital, Ilorin, Nigeria. RESULTS: Carcinoma of the cervix accounted for 63.1 % of histologically confirmed gynaecological cancers. Most of the patients were married 147 (98.7 %) and of low socio-economic status 132 (88.6%). One hundred and three (89.1 %) patients were in the age bracket 40-69 years with highest frequency in 40-49 years age group. The disease is associated with high parity with grandmultiparous patients constituting 119 (79.9 %) of the cases. Irregular vaginal bleeding 109 (73.2 %), vaginal discharge 58 (38.9%) and postcoital bleeding 31(20.5%) were the common symptoms. Nineteen (12.8%) patients reported at the hospital within one month of onset of symptoms. About three quarter ofthe patients had advanced disease and stage III disease was the most common stage 75 (50.4 %). CONCLUSION: This study has shown a high incidence of carcinoma ofcervix at the University of Ilorin Teaching Hospital.

A study of risk factors for ovarian metastases in stage Ib-IIIb cervical carcinoma and analysis of ovarian function after a transposition.

OBJECTIVE: The objective of the present study was to examine the incidence and risk factors of ovarian metastases in cervical carcinoma. The function of transposed ovaries was also studied. METHODS: In order to analyze the risk factors of ovarian metastases, 255 slides of pathological specimens were reassessed by multivariate logistic regression analysis. Fifty-six patients were studied prospectively on the basis of the function of transposed ovaries. Basal body temperature and serum hormone levels were analyzed. RESULTS: Ovarian metastasis was identified in 2 of 485 (0.4%) patients with squamous cell carcinoma and in 12 of 146 (8.2%) patients with nonsquamous tumors of the cervix. Histologic type (P = 0.0014) and blood vessel invasion (P = 0.0433) were significant independent risk factors for ovarian metastases, as revealed by multivariate logistic regression analysis. Cumulative survival curves of preserved ovaries showed a significant (P < 0.005) decline in the group with postoperative radiotherapy. CONCLUSION: Preservation of ovarian function should be pursued in patients with squamous cell carcinoma of the cervix, provided that the patient has no other risk factor (blood vessel invasion) for ovarian metastases. Moreover, sufficient attention should be paid to the proper handling of ovarian blood vessels during surgery, in order to shield and protect them from exposure to scattered radiation administered during postoperative radiotherapy.

Prognostic significance of serum tumour markers in carcinoma of the cervix.

PURPOSE: The purpose was to evaluate the prognostic significance of serum tumour markers and other potential prognostic factors in cervical cancer. MATERIALS AND METHODS: Five hundred and thirty-one patients with cervical cancer were studied. The pre-treatment levels of SCC (squamous cell carcinoma antigen), TPA (tissue polypeptide antigen), CEA (carcinoembryonic antigen), CA125 and hCG (human chorionic gonadotrophin) were assayed in these patients. Possible association between raised tumour markers and potential prognostic factors and their prognostic significance were sought by univariate and multivariate Cox analysis. RESULTS: SCC was raised in 65% of squamous cell carcinoma of the cervix and TPA was raised in 50%. Other markers were raised in less than 25%. No tumour markers were raised more than 30% in adenocarcinoma of the cervix. Raised SCC and TPA were related to advancing age, stage and grade of differentiation. Univariate analysis showed that age, stage, grade, raised SCC and TPA were significant prognostic factors on survival. Multivariate Cox analysis showed that stage was the most significant factor. CONCLUSION: Stage, age, grade of differentiation, raised pre-treatment levels of SCC and TPA were significant prognostic factors in cervical cancer using univariate analysis. However, only stage remains the most important independent prognostic factor in multivariate analysis. The prognostic value of these other factors in early stage disease needs further exploration.