Poor Prognosis In Young Patients Research Articles

Comparison between three age-stratified cohorts reveals poor prognosis of young patients with tongue carcinoma.

ObjectivesInvestigation of the prognosis of young patients with tongue carcinoma has been the focus of several recent studies aimed at improving future precision treatment. Most studies have been two-cohort investigations comparing young and older patients, who have wide discrepancies in prognosis. Older patients, especially those aged >70 years, often have a poor general condition. This affects the prognosis of the older cohort and accounts for the discrepancies observed in two-cohort studies. Accordingly, in this study, older patients (aged ≥71 years) were separated and compared to young and middle-aged patients.MethodsA total of 257 patients with oral tongue carcinoma referred during 2011–2017 were analyzed. Patients were sorted into young (aged ≤40 years), middle-aged (aged ≥41 and ≤70 years), and older (aged ≥71 years) groups. Overall survival (OS) and disease-free survival (DFS) were compared among the groups. Furthermore, patterns of recurrence rates were compared.ResultsCompared with young patients, there was no difference in OS or DFS for older patients (hazard ratio [HR]: 1.2, 95% confidence interval [CI]: 0.5–2.7 and HR: 0.7, 95% CI: 0.4–1.2, respectively) in a multivariate analysis. There was also no difference in OS (HR: 0.6, 95% CI: 0.3–1.3) for middle-aged patients. However, middle-aged patients had low recurrence rates (HR: 0.5, 95% CI: 0.3–0.8). With respect to the recurrence type, middle-aged patients had a low local recurrence rate (HR: 0.3, 95% CI: 0.1–0.7).ConclusionThree-cohort studies should be conducted to evaluate whether the prognosis of young patients with tongue carcinoma is truly poor in terms of future precision treatment.

Progesterone Receptor Is a Haploinsufficient Tumor-Suppressor Gene in Cervical Cancer

Tumor-suppressor genes (TSG) are often deleted or transcriptionally suppressed in cancer. PGR codes for progesterone receptor (PR), a transcription factor whose function depends on its ligand. Although PR expression is often undetectable in cervical cancer, its relevance to the endocrine-related etiology of this prevalent gynecological disease remains unclear. In this study, we show that the deletion of one Pgr allele in cervical epithelium promoted spontaneous cervical cancer in human papilloma viral oncogene-expressing transgenic mice as efficiently as the ablation of both Pgr alleles. We also show that tumors arising in the transgenic mice with one or both Pgr alleles did not express PR or expressed at the reduced levels compared with the normal epithelium. PR status correlated with estrogen receptor α (ERα) status in the mouse model and the Cancer Genome Atlas (TCGA) dataset. TCGA data analyses revealed that PGR expression significantly decreased in cervical cancer and that the biallelic deletion of PGR was rare. Furthermore, low PGR expression was associated with poor prognosis in young patients with cervical cancer. These discoveries point to PGR as a haploinsufficient TSG in the uterine cervix. They also raise the possibility that the restoration of PGR expression may improve the survival rate. IMPLICATIONS: The decreased expression of PR may increase the risk of cervical cancer in human papillomavirus-infected women. VISUAL OVERVIEW: http://mcr.aacrjournals.org/content/molcanres/19/1/42/F1.large.jpg.

Abstract P5-12-08: The effect of adjuvant endocrine therapy adherence on breast cancer prognosis according to age group

Abstract Background: It is well known that the young age at the diagnosis of breast cancer is a bad prognostic factor, by many previous studies. In a study of breast cancer adherence to adjuvant endocrine therapy (AET), younger patients were found to have significantly lower adherence. Therefore, the poor prognosis of young patients, with hormone receptor positive breast cancer, should be figured out whether it is due to the difference in adherence. And we aimed to analyze the effect of medication adherence for 4.5 years on subsequent prognosis, after the treatment completion. Methods: A total of 5,928 patients with stage I~III hormonal receptor positive breast cancer, who underwent surgery at Asan Medical Center from January 1997 to December 2009 were included in this retrospective analysis. Patients with no history of AET, follow-up loss, early breast cancer recurrence within 4.5 years from initial treatment were excluded. The number of days of treatment gap was estimated by subtracting the duration of medication coverage from the intervals between prescription dates. A descriptive analysis of prescription gap according to age distribution was done. And a multivariate Cox regression for the risk of distant metastasis of breast cancer by AET adherence, grouped by; no gap, gap1, gap2 (gap1: prescription gap within median, gap2: gap over median) according to age group (grouped by the age at diagnosis of <40, 40~59, and ≥60), was conducted. Results: The AET adherence was best in the middle-age group, showing the smallest number of days in treatment omission (130.9/4264, mean of total prescription gap/number of patients), compared with young (194.9/959) or old group (159.4/705). When adjusted with cancer stage, histologic grade, adjuvant treatment of chemotherapy or radiation therapy, type of AET agent, the risk of distant metastasis with increasing gaps tended to increase in the younger age group but it showed no significance between three gap-groups (p=0.063). The risk was significantly increased in the older age group, that the hazard ration (HR) in gap1 group was 2.534 (95% CI: 0.845~7.599, p=0.097), and 3.820 (95% CI 1.485~9.828, p=0.005) in gap2 group. With the reference of middle-age-no gap group, younger-no gap group showed significantly high HR (1.853, 95% CI: 1.008~3.407, p=0.047). In older age groups, only gap2 group showed significantly high HR (2.605, 95% CI: 1.443~4.703, p=0.001). However, in the risk of distant metastasis, the interaction between the gap and age difference was not statistically significant (p = 0.487). Conclusion: In distant metastasis after AET completion, both adherence and age at diagnosis showed a strong correlation. This suggests that survival after 4.5 years in young patients could be more affected by other factors (besides compliance with medication). This implicates that the prophylactic effect of AET after the end of the routine medication period is less significant. Further analysis including patients with early recurrence is needed in the future. Citation Format: Yura Lee, Hee Jeong Kim, Sun Ok Kim, Jong Won Lee. The effect of adjuvant endocrine therapy adherence on breast cancer prognosis according to age group [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P5-12-08.

Independent factors FOR poor prognosis in young patients with stage I-III breast cancer.

SUMMARYBreast cancer is the most common malignancy in the population of women under 40 years of age. Young age is an independent factor for poor prognosis. In this research, we tried to establish other factors for poor prognosis in stage I-III breast cancer. The following parameters were observed: tumor size, lymph node status, histologic grade, hormonal receptor status, Ki-67 prognostic index, Her2 neu status, histologic type of the tumor, local recurrence and metastases. Logistic regression was used to evaluate the effect of specific factors on the probability of lethal outcome and development of distant metastases. Our patients showed a predominance of T1 tumor (49.4%), had positive lymph nodes (62%) and most of them were pN1 (61.2%). Up to one-third of patients had triple negative status. Ki-67 proliferation index was high (25%). Multicentric tumor was detected in 23% of patients. There was no difference in overall survival between the two types of surgical procedures. Patients with pN0 status had better overall survival. Breast cancer in the population of young women has a more aggressive nature. Study results indicated positive lymph node status as an independent factor for poor prognosis of stage I-III breast cancer.

Are basketball players more likely to develop Hirayama disease?

Hirayama disease is a rare neurological disease affecting primarily men in the second to third decades. To date there are only few reports from Italy.We report the case of three young basketball players who presented with clinical, electrophysiological and MRI findings suggestive for Hirayama disease.Although the pathophysiology of the disease is still unknown, several hypotheses have been suggested and two of these are the disproportionate growth of cervical spine and cervical cord/roots during adolescence and the chronic traumatism.We think that, in our cases, the height of basketball players combined with the constant stress caused by the sport, could have contributed to the development of the Hirayama disease.With this report we would stress the importance to be careful to consider this pathology in order to avoid misdiagnosis predictive of poor prognosis in young patients.

Poor prognosis of young patients with colorectal cancer: a retrospective study.

The present study aimed to explore the survival outcomes of patients with colorectal cancer (CRC) aged 35 years and younger. This retrospective cohort study included a total of 995 patients with CRC treated between January 2003 and September 2011. The patients were assorted into the young (aged 18-35 years) and older (aged 36-75 years) groups. The clinical characteristics and survival outcomes of the patients in the young group were compared with those of the patients in the older group for evaluation. Compared with the older group, a significantly higher number of patients in the young group had right-sided colon cancer (30.9 vs. 19.6%, P=0.026), high histologic grade tumor (14.7 vs. 6.4%, P=0.021), and stage III disease (50.0 vs. 35.5%, P=0.016). In stage III disease, compared with the older group, the patients in the young group had worse survival outcome in terms of 5-year overall survival (OS, P=0.007), cancer-specific survival (CSS, P=0.010), and disease-free survival (DFS, P=0.039). Multivariate analysis revealed that age ≤35years was an independent risk factor in terms of 5-year OS (hazard ratio [HR]=1.68; 95% confidence interval [CI]: 1.12-2.54; P=0.012), CSS (HR=1.74; 95% CI: 1.15-2.65; P=0.009), and DFS (HR=1.58; 95% CI: 1.06-2.35; P=0.024). The young patients with CRC aged 35years and younger had worse prognosis compared with older patients, especially for stage III disease.

Chronic interstitial pneumonia in young patients undergoing lung transplantation or autopsy: clinico-radiologic-pathologic observations from a single institution.

To retrospectively evaluate high-resolution computed tomography (HRCT) findings and clinical diagnoses of chronic interstitial pneumonia (IP) with a poor prognosis in young patients (≤50years). HRCT images of 8 men and 7 women (mean age 34.8years) obtained before lung transplantation or autopsy were reviewed. After reviewing whole lung specimens and pathologic diagnoses, all patients were clinically diagnosed according to the 2010 idiopathic pulmonary fibrosis/usual interstitial pneumonia (IPF/UIP) consensus statement. HRCT images revealed intralobular reticular opacity, air cysts, ground glass opacity, traction bronchiectasis, and interlobular septal thickening. Intralobular reticular opacity was the most extensive finding. Abnormal findings existed predominantly in both the peripheral and lower lung zones in only 1 patient. Classifications of HRCT patterns were "UIP" (n=2), "inconsistent with UIP" (n=11), and "indeterminate UIP" (n=2). Multidisciplinary diagnoses were "IPF/UIP" (n=1), "possible IPF/UIP" (n=1), "IP with connective tissue disease" (n=7), "fibrotic nonspecific IP" (n=1), and "unclassified IP" (n=5). The most extensive HRCT finding was intralobular reticular opacity. Most HRCT images differed from typical IPF/UIP, and IPF/UIP was uncommon in young patients with chronic IP with a poor prognosis.

New Mutations of the ID1 Gene in Acute Myeloid Leukemia Patients

Objectives: Overexpression of the inhibitor of DNA binding 1 (ID1) protein is found in many types of cancer. In acute myeloid leukemia (AML), the expression of ID1 is induced by abnormal tyrosine kinases, such as FLT3 and BCR-ABL. High level expression of ID1 is associated with poor prognosis in young patients. We aimed to explore the ID1 mutation and its prognosis in AML patients. Methods: Two hundred and sixty-three AML patients were included. Cytogenetic results and ID1 mutation were compared. The ID1 gene was amplified by nested PCR, and the mutation was identified by direct sequencing. Results: Four new ID1 mutations (G40C, A124G, A230G, A349G) were identified in the normal karyotype patients. The A349G mutation, located in the nuclear export signal domain of the ID1 protein, was predicted by the in silico method as a damaged protein. Meanwhile, another new mutation, A290G, found in cases with 11q23 deletion, corresponded to the amino acid 97 in the helix 1 position of the ID1 protein. It could interfere with the dimerization of ID1 and EST-1, leading to a disruption of cell proliferation. Conclusions: In this study, we found 5 mutations in 260 AML patients. ID1 mutations were not commonly observed in AML. This may differ in other hematologic malignancies. Further studies in other types of hematologic malignancy will help to clarify the importance of ID1 mutations.

Treatment of aplastic anemia with antithymocyte globulin, cyclosporin A, methylprednisolone, danazol and recombinant human granulocyte-colony stimulating factor.

The main purpose of the present study was to determine the response rate to immunosuppressive therapy combined with recombinant human granulocyte-colony stimulating factor (rhG-CSF) and its efficacy for preventing infections in patients with severe aplastic anemia. The treatments included one course of antithymocyte globulin, cyclosporin A, methylprednisolone, danazole and rhG-CSF. Three patients had very severe aplastic anemia and two had moderate aplastic anemia. One patient relapsed 13 months following the first course of therapy and received a second course. Five patients received six courses of treatment and the response rate at 6 months was 83.3%. All patients achieved an absolute neutrophil count of greater than 1.0 x 10(9)/L within 40 days. All patients with a complete response are transfusion-free and doing well. All five patients are currently alive and have not had any episode of infection for 17-53 months. The results of the study indicate that this therapy may improve the poor prognosis of young patients with severe aplastic anemia. It has a good response rate and induces a rather rapid increase in the neutrophil count, which protects against life-threatening bacterial and fungal infections.

Gastric Cancer in Young Patients Who Underwent Curative Resection

Although several studies demonstrated the poor prognosis of young patients with gastric cancer, there were few reports about the survival of young patients who underwent radical surgery. We retrospectively reviewed the hospital records of 697 patients with curatively resected locally advanced gastric cancer to compare the pathologic findings and prognosis of young patients (aged < 40 years; 91 patients) with those of older (aged > or = 40 years; 606 patients) patients. There were no significant differences in location of tumors, Borrmann types, tumor invasion, and pathologic stage between both age groups. Despite the male predominance in older patients, the male-to-female ratio was nearly equal in young patients (p = 0.022). A significantly higher percentage of young patients showed poorly differentiated histology including signet ring cell and undifferentiated carcinoma than older patients (p < 0.0001). Adjuvant chemotherapy was more frequently performed in the young patients with a variety of different regimens (85.7 vs. 72.3%; p = 0.009). The 5-year overall survival rate revealed no statistically significant differences between the young and older patients (53.1 vs. 56.6%; p = 0.820). In conclusion, the young patients with curatively resected locally advanced gastric cancer showed similar survival compared to that of older patients.

Intracapsular fractures of the femoral neck in young patients

The details of the aetiology, treatment and outcome of acute intracapsular fractures for 58 fractures in 57 patients aged less than 60 years, were prospectively studied. The majority of the injuries were sustained by low energy trauma. Eighty-four per cent united uneventfully. There was a non-union rate of 7 per cent, and avascular necrosis rate of 10 per cent. Better results were obtained from closed than open reduction. The results do not support the commonly held view that this injury carries a poor prognosis in young patients.