Favorable Prognosis Factor Research Articles

Stimulated Thyroglobulin at Recombinant Human TSH-Aided Ablation Predicts Disease-free Status One Year Later

Thyroglobulin (Tg) levels measured at the time of remnant ablation after thyroid hormone withdrawal (THW) were shown to have prognostic value in predicting disease-free status. Our objectives were to determine whether stimulated Tg levels, measured at the time of remnant ablation performed under recombinant human TSH (rhTSH) stimulation, has value in predicting absence of detectable disease 1 year after radioiodine therapy and to compare the results obtained with this approach with a cohort of patients submitted to ablation after THW. This was a prospective observational study. The study included 293 consecutive patients treated for a differentiated thyroid carcinoma with no initial evidence of distant metastasis. All patients were submitted to a total or near-total thyroidectomy, followed by ablation either under rhTSH (n = 151) or endogenous TSH stimulation (n = 142). Patients with positive Tg antibodies were excluded. The predictive value of Tg at ablation was assessed by receiver operating characteristic curve analysis. In the rhTSH group, 96 patients (73.3%) were considered disease-free at 1 year. Stimulated Tg at ablation after rhTSH was found to be an independent prognostic indicator of disease persistence 12 months later. The highest-accuracy cutoff value for absence of detectable disease was defined as 7.2 ng/mL, with a negative predictive value of 90%. In the THW group, Tg at ablation also proved to have independent predictive value. Using the same threshold (7.2 ng/mL), the negative predictive value of Tg was 95% in the THW group. When rhTSH was used, stimulated Tg at ablation had independent predictive value for disease-free status 1 year later. A low stimulated Tg at rhTSH-aided ablation may be considered a favorable prognosis factor.

Characteristics and clinical outcome of T1 breast cancer: A national multicenter retrospective cohort study.

566 Background: T1N0M0 breast cancer (BC) are generally considered as carrying good prognosis and cancer-specific survival rates after 5 to 10 years are as high as 90 or 95% in many studies. However, they constitute a heterogeneous group and many studies identified biologically-defined at-risk patients within T1 BC. The objectives of our study were to describe the main characteristics of T1a, b, and c (11-15mm) BC and to identify prognostic factors for survival. Methods: We retrospectively collected the medical files of all patients diagnosed with BC who underwent sentinel lymph node biopsy (SLNB) between January 1999 and December 2008 in 13 French sites and examined overall survival (OS) and Relapse-free survival (RFS) in T1a, T1b and T1c 11-15 mm. Results: Among 8,100 women operated, 5,423 had T1 tumors (708 T1a, 2,208 T1b and 2,508 T1c 11-15mm). T1a differed significantly from T1b tumors with respect to several parameters : younger age, more frequent negative hormonal status and positive HER2 status, less frequent lymphovascular invasion (LVI), exhibiting a mix of favorable and poor prognosis factors. After a median follow-up of 60.5 months, OS rate was 97.6% (95CI: 97.1-98) at 60 months, 95.4%(94.5-96.4) at 84 months and 90.7% (85.2-96.4) at 120 months. No significant difference was observed between T1a, T1b and T1c tumors (p=0.335). RFS rates were 94% (95CI: 93.8-95.2), 92.1% [91.1-93.2] and 83.8% (77.6-90.5) at 60, 84 and 120 months respectively. RFS was significantly higher in T1b tumors (95.9%, 95CI: 95-96.9) as compared to T1a (93.2%, 91-95.4) or T1c tumors (93.8%, 92.8-94.9), p=0.0099. In multivariate analysis, SBR tumor grade, hormone therapy and LVI were independent prognostic factors for RFS, while hormone therapy and SBR grade were independently associated with OS. Conclusions: Relatively poor outcome of patients with T1a tumors might be explained by a high frequency of risk factors in this subgroup (frequent negative hormone receptors and HER2 overexpression) and by a less frequent administration of adjuvant systemic therapy (endocrine treatment and chemotherapy). Tumor size might not be the main determinant of prognosis in T1 breast cancer.

Prognosis of the intrahepatic cholangiocarcinoma after resection: hepatitis B virus infection and adjuvant chemotherapy are favorable prognosis factors

AimThe incidence and mortality associated with intrahepatic cholangiocarcinoma is increasing in many countries and documentation of disease outcome is sparse. The present study was undertaken to investigate the prognostic factors for intrahepatic cholangiocarcinoma (ICC) following surgical resection. The impact of pre-existing HBV virus infection and adjuvant chemotherapy on the overall survival was also evaluated.MethodsClinical and pathological data were collected retrospectively from 81 patients undergoing surgery for ICC between 2005 and 2011, at The Henan Province Tumor Hospital and the First Affiliated Hospital of Zheng Zhou University. Survival and prognosis were analyzed using the Kaplan-Meier method and COX regression model.ResultsThe population included 37 patients who were HBsAg + or anti-HBc+, 21 patients who were anti-HBs + positive and 18 patients who received adjuvant chemotherapy. The overall 1- and 3-year survival rates were 51% and 20%, respectively. The median survival was 12.2 months. Univariate analysis identified the following prognostic factors: HBV virus infection or HBV vaccine prior to resection (P = 0.017); adjuvant chemotherapy (P = 0.001); preoperative serum CA19-9 (> 200 U/mL; P = 0.015); GGT (> 64 U/L; P = 0.008), ALP (> 119 U/L; P = 0.01); lymph node metastasis (P = 0.005); radical resection (P = 0.021); intrahepatic metastasis (P = 0.015) and diabetes (P = 0.07). Multivariate analysis identified chronic HBV infection (RR = 0.583; P = 0.041), anti-HBs positivity (RR = 0.680; P = 0.050), adjuvant chemotherapy (RR = 0.227; P < 0.001), lymph node metastasis (RR = 2.320; P = 0.001), and intrahepatic duct stones (RR = 0.473; P = 0.032) as independent prognostic factors.ConclusionsHBV virus infection or HBV vaccination prior to resection, together with adjuvant chemotherapy, were independently associated with improved survival in patients undergoing surgery for ICC.

Identification of Common Prognostic Gene Expression Signatures with Biological Meanings from Microarray Gene Expression Datasets

Numerous prognostic gene expression signatures for breast cancer were generated previously with few overlap and limited insight into the biology of the disease. Here we introduce a novel algorithm named SCoR (Survival analysis using Cox proportional hazard regression and Random resampling) to apply random resampling and clustering methods in identifying gene features correlated with time to event data. This is shown to reduce overfitting noises involved in microarray data analysis and discover functional gene sets linked to patient survival. SCoR independently identified a common poor prognostic signature composed of cell proliferation genes from six out of eight breast cancer datasets. Furthermore, a sequential SCoR analysis on highly proliferative breast cancers repeatedly identified T/B cell markers as favorable prognosis factors. In glioblastoma, SCoR identified a common good prognostic signature of chromosome 10 genes from two gene expression datasets (TCGA and REMBRANDT), recapitulating the fact that loss of one copy of chromosome 10 (which harbors the tumor suppressor PTEN) is linked to poor survival in glioblastoma patients. SCoR also identified prognostic genes on sex chromosomes in lung adenocarcinomas, suggesting patient gender might be used to predict outcome in this disease. These results demonstrate the power of SCoR to identify common and biologically meaningful prognostic gene expression signatures.

Prognostic analysis of surgical resection for patients with liver metastases from colorectal carcinoma

Objective To assess the indication and efficacy of surgical treatment for patients with hepatic metastases from colorectal carcinoma. Methods Clinical data of 75 patients with hepatic metastases from colorectal carcinoma undergoing surgery from January 2000 to December 2007 were analyzed retrospectively. Results Among 75 patients,62 patients were found to have synchronous hepatic metastasis and 13 patients were found to have metachronous hepatic metastases. 70 patients underwent resection of hepatic metastases and complications occurred in 10 patients. The 1,3 and 5-year survival rates were 74. 67%, 58.67% and 28.00%respatectomy. Univariate analysis revealed that solitary metastasis was a significant factor for favorable prognosis after surgery . The expression of preoperative CEA, Dukes stage, the number of hepatic metastases, status of lymph node metastasis and histological differentiation of the primary colorectal carcinoma were all significant factors for prognosis after surgery. Conclusion The hepatic metastases from colorectal cancer should be treated by a surgical approach. T earlier stage of clinical pathology, higher differentiation extent, metastases less than 2, and low-level expression of preoperative CEA predict a better survival. Key words: Colorectal carcinoma; Liver metastasis; Surgical treatment; Prognosis

TET2 mutation is an independent favorable prognostic factor in myelodysplastic syndromes (MDSs)

AbstractOncogenic pathways underlying in the development of myelodysplastic syndromes (MDS) remain poorly characterized, but mutations of the ten-eleven translocation 2 (TET2) gene are frequently observed. In the present work, we evaluated the prognostic impact of TET2 mutations in MDS. Frameshift, nonsense, missense mutations, or defects in gene structure were identified in 22 (22.9%) of 96 patients (95% confidence interval [CI], 14.5-31.3 patients). Mutated and unmutated patients did not significantly differ in initial clinical or hematologic parameters. The 5-year OS was 76.9% (95% CI, 49.2%-91.3%) in mutated versus 18.3% (95% CI, 4.2%-41.1%) in unmutated patients (P = .005). The 3-year leukemia-free survival was 89.3% (95% CI, 63.1%-97.0%) in mutated versus 63.7% (95% CI, 48.2%-75.4%) in unmutated patients (P = .035). In univariate analysis (Cox proportional hazard model), the absence of TET2 mutation was associated with a 4.1-fold (95% CI, 1.4-12.0-fold) increased risk of death (P = .009). In multivariate analysis adjusted for age, International Prognostic Scoring System, and transfusion requirement, the presence of TET2 mutation remained an independent factor of favorable prognosis (hazard ratio, 5.2; 95% CI, 1.6-16.3; P = .005). These results indicate that TET2 mutations observed in approximately 20% of patients, irrespective of the World Health Organization or French-American-British subtype, represent a molecular marker for good prognosis in MDS.

Diffuse large B-cell lymphoma with a high number of epithelioid histiocytes (lymphoepithelioid B-cell lymphoma): a study of Osaka Lymphoma Study Group

The aim of this study was to clarify whether diffuse large B-cell lymphoma (DLBCL) with a high number of epithelioid histiocytes (DLBCL-EH) could have distinctive clinicopathological characteristics. Clinicopathological findings in 22 cases with DLBCL-EH and, as a control, 96 cases with ordinary type of DLBCL were analyzed. There were ten men and 12 women with ages ranging from 38 to 91 (median, 64) years. The primary site was lymph node in 16 cases, extranodal organs in three, and unknown in three. Stage of disease was I in five cases, II in three, III in nine, and IV in five. Histologically, there was a diffuse proliferation of large lymphoid cells admixed with numerous clusters of epithelioid histiocytes sprinkling throughout the lesions. Immunohistochemically, the large lymphoid cells were CD20(+), CD15(-), and CD3(-) and positive for CD10, bcl-6, and MUM1 in nine (41%), eight (36%), and 12 (55%) of 22 cases, respectively. Epstein-Barr virus positive rate was higher in DLBCL-EH (23.8%) than that in ordinary DLBCL (4.5%; P<0.05). Clonality analysis revealed monoclonal bands in all of the examined 20 cases with DLBCL-EH. Multivariate analysis revealed the prominent epithelioid reaction to be an independent factor for favorable prognosis. These findings suggest that DLBCL-EH could be a specific morphological variant of DLBCL associated with a better prognosis.

Prognostic factors in adolescents and young adults (AYA) with high-risk soft tissue sarcoma (STS) treated by adjuvant chemotherapy: A study based on two pooled European Organisation for Research and Treatment of Cancer (EORTC) clinical trials

10573 Background: We conducted a retrospective study pooling data from two clinical trials in high risk STS patients with the objective to compare two different age groups: 15 - 29 years (AYA population) and ≥ 30 years. The aim was to determine prognostic factors for the AYA population. Methods: Patients selected for analysis were treated in two randomized trials of adjuvant chemotherapy in STS (EORTC 62771 and 62931). A total of 793 patients were included with a median follow-up (FU) of 8.74 years (AYA population: n = 161, median FU 9.46 years; patients ≥ 30 years: n = 632, median FU 8.62 years). Study endpoints were overall survival (OS) and relapse-free survival (RFS). The variables of the multivariate analysis were gender, subtype and grade, tumor size and localization (limb vs. other), absence or presence of local recurrence and treatment (control arm vs. adjuvant chemotherapy). Results: Patients’ characteristics were globally similar with two exceptions, histological subtype (p = 0.0043) and tumor size (p &lt; .0001). The commonest sarcoma subtype in the AYA population was synovial sarcoma (29 %), whereas leiomyosarcoma (18 %), malignant fibrous histiocytoma (MFH, 16 %) and liposarcoma (15 %) were more frequent in patients ≥ 30 years. For OS, independent favorable prognostic factors were low grade and small tumor size for both groups; radical resection and MFH or liposarcoma subtype were factors of favorable prognosis for patients ≥ 30 years only. For RFS, favorable prognostic factors were small tumor size and low grade for both groups; tumor location in the extremities was a factor of favorable prognosis for the AYA population only, whereas radical resection and adjuvant chemotherapy treatment were favorable factors for patients ≥ 30 years only. Conclusions: On the basis of these data, significant differences could be found concerning prognostic factors between the AYA population and older patients. Interestingly, adjuvant chemotherapy was associated with improved RFS only in patients ≥ 30 years. The results may have further implications on the treatment of STS patients in different age groups as well as the design of future clinical trials. No significant financial relationships to disclose.

Prognostic analysis of patients with pancreatic head adenocarcinoma less than 2 cm undergoing resection

To investigate the differences in clinicopathological features between patients with pancreatic cancer greater or less than 2 cm situated over the pancreatic head and the prognostic factors for survival of patients with pancreatic cancer < 2 cm over the pancreatic head. From 1983 to 2006, 159 patients with histologically proven pancreatic adenocarcinoma (PAC) at the pancreatic head undergoing curative resection at the Department of Surgery, Chang Gung Memorial Hospital, Taipei, Taiwan were reviewed, comprising 123 cases of large (L)-PAC (tumor > 2 cm) and 36 cases of small (S)-PAC (tumor </= 2 cm). We compared the clinicopathological characteristics and prognosis of L-PAC and S-PAC patients. The clinicopathological characteristics of S-PAC were investigated to clarify the prognosis predictive factors of S-PAC. One hundred and fifty-nine PAC patients, aged 16-93 years (median, 59.0 years) with a tumor at the pancreatic head undergoing intentional curative resection were investigated. The S-PAC and L-PAC patients had similar demographic data, clinical features, and tumor markers (a similar positive rate of carcinoembryonic antigen and carbohydrate antigen 19-9). There were also similar rates of lymph node metastasis, portal vein invasion, stage distribution, tumor differentiation, positive resection margin, surgical morbidity and mortality observed between the two groups. During a follow-up period ranging from 1.0 to 122.7 mo (median, 10.9 mo), S-PAC and L-PAC patients had a similar prognosis after resection (P = 0.4805). Among the S-PAC patients group, patients with higher albumin level (> 3.5 g/dL) had more favorable survival than those with lower albumin levels, which was the only favorable predictive prognostic factor. Meanwhile, early-staged (stage I, II) S-PAC patients tended to have a more favorable outcome than late-stage (stage III, IV) S-PAC patients, but this was not statistically significant. S-PAC patients should not be regarded as early PAC. Only higher albumin level (> 3.5 g/dL) and early stage disease (stage I, II) were the favorable prognosis factors for S-PAC patients.

Chromosome 1p and 19q deletions in malignant glioneuronal tumors with oligodendroglioma-like component

Malignant glioneuronal tumors (MGNT) are suggested to be a new entity of glioma defined morphologically as any malignant glioma showing immunohistoichemical evidence of neuronal differentiation. We encountered seven cases of MGNT with oligodendroglioma-like component and investigated alternations of chromosome 1p and 19q in these tumors. Seven patients ranged from 33 to 62 years of age, four females and three males. Immunohistochemical study of these tumors was performed using neuronal markers (synaptophysin, neurofilament, beta-tubulin, chromogranin A and NeuN), astrocytic marker (GFAP) and Ki-67. We undertook a molecular cytogenetic study of tumor specimens obtained from seven patients using fluorescence in situ hybridization (FISH) with DNA probes mapping to chromosome 1p36, 1q25, 19p13 and 19q13. Histologically, these tumors resembled anaplastic oligodendroglioma. Immunohistochemically, tumor cells were immunoreactive for synaptophysin (7/7), neurofilament (6/7), beta-tubulin (5/7), chromogranin A (4/7), NeuN (2/7) and GFAP (7/7). The Ki-67 labeling index ranged from 4.5% to 20.7%. FISH analysis demonstrated either 1p or 19q deletion in all seven cases (100%) and both 1p and 19q deletions in five cases (71%). The 1p deletion was detected in six of seven cases (86%) and 19q deletion was also detected in six (86%). 1p and 19q deletions were present in MGNT, especially those with oligodendroglial components. We suggest that the oligodendroglial-like feature was associated with not only 1p or 19q loss but also differentiation along neuronal cell lines as a factor of favorable prognosis in glial tumors. It is inappropriate to make a diagnosis of oligodendroglioma based only on morphological resemblance to oligodendroglia.

Reply to the Letter to the Editor from Oudejans et al

In Response:We appreciate the comments in the letter by Oudejans et al. about whether the presence of CTLs is a favorable or unfavorable factor for prognosis in diffuse large B-cell lymphoma (1, 2). Whereas the studies by their group (2, 3) and others (4) find that a high percentage of CTLs are associated with poor outcome, there are also other studies besides our own showing that high numbers of CD8+ T cells in diffuse large B-cell lymphoma may be associated instead with superior survival (5, 6). The tissue site distribution of diffuse large B-cell lymphoma in each study is likely one explanation of the different results. For example, 46% of cases in our study were extranodal, and there was a trend toward different patterns of T-cell distribution (and tumor prognosis) in those cases compared with the nodal tumors.However, we agree that the study methodologies can also affect the result, including particular immunostaining protocols, antibodies used, method of quantitation, and selection of analyzed areas. In our study, we counted the absolute granzyme B+ cells in areas of most dense intratumoral infiltration, expressed as cell number per high-power field. In contrast, Oudejans' group randomly selected tumor areas using an automatic scanning stage and expressed the granzyme B+ cells as the percentage of granzyme B+ cells divided by the total CD3+ cells. These different methods can yield different results even in the same study. For example, in the article by Riemersma et al. (3), the absolute number of granzyme B+ cells in diffuse large B-cell lymphoma of the central nervous system/brain was lower than that in skin and nodal tumors, but the percentage of CTLs (number of granzyme B+ cells / number of CD3+ cells) showed the reverse result.We would also emphasize that the interaction between the immune system and diffuse large B-cell lymphoma is complex, with differential T-cell and dendritic cell responses. In our study, we hypothesized that the cooperative action of infiltrating dendritic cells and CTLs in a subset of diffuse large B-cell lymphoma may contribute to a favorable prognosis by boosting dendritic cell–associated T-cell immunity. Whether this immunotherapy strategy can be used to boost responses in diffuse large B-cell lymphoma remains to be determined empirically. In view of the current progress, however, it may be clinically feasible in the near future (7).

Epidermal growth factor receptor mutation, but not sex and smoking, is independently associated with favorable prognosis of gefitinib‐treated patients with lung adenocarcinoma

Epidermal growth factor receptor (EGFR) mutations have been reported as a predictive factor for favorable prognosis of gefitinib-treated patients with lung adenocarcinoma. However, its confounding with sex and smoking makes it unclear whether the EGFR mutation is independently associated with prolonged patient survival. In this study, we analyzed a large-scale database to discriminate the survival impact of EGFR mutations against those of sex and smoking after gefitinib therapy. EGFR mutations in exon19 and exon21 named drug-sensitive EGFR mutations were examined to investigate the impact of EGFR mutation, sex, and smoking status on survival of 362 gefitinib-treated patients with lung adenocarcinoma. Drug-sensitive EGFR mutations were detected in 169 patients (46.7%). The multivariate analysis including EGFR, sex, and smoking status showed that drug-sensitive EGFR mutations were significantly related to longer overall survival (OS) (P < 0.001) and progression-free survival (PFS) (P < 0.001). In addition, we investigated the impact of sex and smoking status according to EGFR mutation status, and the impact of EGFR mutation status according to sex and smoking status on survival. Sex and smoking status were not significantly associated with longer OS and PFS according to EGFR mutation status. Drug-sensitive EGFR mutations were significantly associated with longer OS and PFS according to sex or smoking status. Our results indicated that drug-sensitive EGFR mutations were the only independent factor for longer survival of patients treated with gefitinib, suggesting that patient selection based on EGFR mutation status for gefitinib therapy will lead to a better outcome for patients with lung adenocarcinoma.

Constitutive phosphoinositide 3-kinase/Akt activation represents a favorable prognostic factor in de novo acute myelogenous leukemia patients

AbstractThe phosphoinositide 3-kinase (PI3K/Akt) pathway is activated in acute myelogenous leukemia (AML) and is promising for targeted inhibition. Ninety-two patients with primary AML were analyzed for PI3K/Akt constitutive activation. Fifty percent of the patients presented with constitutive PI3K activation (PI3K +). No difference was observed between PI3K + and PI3K − groups concerning age, sex, white blood cell count, lactate dehydrogenase (LDH) level, bone marrow blast cells, French-American-British (FAB) classification, cytogenetics, RAS or nucleophosmin (NPM) mutations. Slightly more FLT3-ITD was detected in the PI3K − group (P = .048). The complete remission rate was similar between the 2 groups. With a median follow-up of 26 months, we observed for PI3K + and PI3K − patients, respectively, 56% and 33% overall survival (P = .001) and 72% and 41% relapse-free survival (P = .001). Constitutive PI3K/Akt activity is a favorable prognosis factor in AML, even after adjustment for FLT3-ITD, and may confer a particular sensitivity to chemotherapy. A better understanding of the downstream effectors of the PI3K/Akt pathway is needed before targeting in AML.

Dysplasie et conflits de hanche de 20 à 50 ans

Anterior hip pain in young adult (20 to 50) has two main causes: secondary osteo-arthritis on development dysplasia of the hip, and femoro-acetabular impigement (FAI). This symposium had two parts: the first one analyses long-term results of nonprosthetic surgery (283 osteotomies and shelfs at 15 years FU). The second part concerned the different syndromes with acute anterior hip pain, especially due to FAI and to labral tears.In hip dysplasia, 56 shelf operations, 100 proximal femoral varus osteotomies associated or not with a shelf arthroplasty, and 127 Chiari osteotomies were examined with 10 years minimum follow-up. Only 15% of patients were lost at follow-up before 10 years and average follow-up was 15 years.Results were considered as satisfactory when the Merle d’Aubigné rating was 15/18 or more. The 3 main factors of good prognosis were: a complete correction of both femoral and acetabular dysplasia; age at operation under 40; a moderate arthritis (grade I or II according to De Mourgues and Patte). In single acetabular dysplasia with 3 favorable prognosis factors (no coxa valga, age under 40, arthritis 1 or 2), 85% good results were achieved at 15 years. When patients were over 40 at operation, or in arthritis grade over 2, only 55% of good results were observed. Varus osteotomies, associated or not with shelf arthroplasties, achieved also 85% goods results at 15 years when the 3 favorable prognosis factors were present. Similar good results were also obtained by Chiari osteotomy, but this operation was associated with 12% complications, and more that 25% of lasting limping. Therefore, with 85% good results at 15 years (and often over 20 years), non prosthetic surgery. performed at 30-35 years, achieved better functional results than total hip arthroplasty, longer lasting, and not jeopardizing any further possibility of prosthetic surgery. As concerns acute anterior pain of the hip, the clinical and imaging patterns of the different syndromes have been precised: femoro-acetabular impigement by cam (or by pincer), labral tears in hip dysplasia. There were distinguished from the other secondary impigements, for example by acetabular malposition due to pelvis anteflexion or by other hip diseases: over use arthritis, coxa retrorsa, etc. Several examples of typical syndromes were presented to support the recommended imaging techniques. The results of the speakers with different surgical treatments were reported as well as concerns open surgery than arthroscopic treatment (60 cases).

Neoadjuvant chemotherapy in invasive bladder cancer

The role of neoadjuvant chemotherapy in muscle-invasive bladder cancer has been clarified by recent randomized studies and meta-analyses, which all showed that cisplatin-based, combination chemotherapy offers a significant survival advantage. Preoperative chemotherapy results in downstaging in a significant percentage of patients, which is an independent factor of favorable prognosis. Nevertheless, the optimal sequence of perioperative chemotherapy remains undefined. The authors examine the results of large Phase II and randomized studies as well as the role of neoadjuvant chemotherapy in the context of bladder preservation strategies. Finally, issues of improving therapeutic efficacy and directing clinical research are discussed.

Increased Intratumor Vα24-Positive Natural Killer T Cells: A Prognostic Factor for Primary Colorectal Carcinomas

Human invariant natural killer T (NKT) cells are novel, distinct lymphocyte populations with a restricted T-cell receptor repertoire (Valpha24-Vbeta11). They play a pivotal role in immunoregulation and in antitumor activities. This study focused on Valpha24+ NKT cells in colorectal carcinomas and their clinicopathologic significance. Valpha24+ NKT-cell infiltration immunohistochemistry was studied in a total of 103 colorectal carcinoma cases. The degree of NKT-cell infiltration in tumors was evaluated as low (<7 NKT cells/5 HPF) or high (> or =7 NKT cells/5 HPF). The correlation between the degree of infiltrated Valpha24+ NKT cells and clinicopathologic variables was studied statistically. A small number of Valpha24+ NKT cells were found in the normal colorectal mucosa (2.6 +/- 3.7 cells/5 HPF); however, their number increased remarkably in colorectal carcinomas (15.2 +/- 16.3 cells/5 HPF; P = 0.0003) and a majority showed phenotype of activation. Higher NKT-cell infiltration was more frequent in women than in men (P = 0.034) and correlated with fewer lymph node metastases (P = 0.042). Patients with high NKT-cell infiltration showed higher overall (P = 0.018) as well as disease-free (P = 0.0006) survival rates. Intratumor NKT-cell infiltration was an independent prognostic factor for the overall (P = 0.033) and disease-free (P = 0.0064) survival rates. Increased infiltration of Valpha24+ NKT cells was observed in colorectal carcinomas. Higher Valpha24+ NKT-cell infiltration in colorectal carcinomas was an independent prognostic factor for favorable prognosis.

Upregulation of bikunin in tumor-infiltrating macrophages as a factor of favorable prognosis in ovarian cancer

Objective. This study was carried out to clarify the localization of bikunin, a Kunitz-type protease inhibitor, and relation between expression of individual bikunin protein and ovarian cancer progression. Methods. We performed a retrospective study on the immunohistochemical expression of bikunin, urokinase-type plasminogen activator (uPA) and macrophages (CD68) in surgical specimens derived from 89 ovarian cancer patients to investigate correlations between the expression of bikunin and the clinicopathologic features and the prognosis. Furthermore, bikunin and uPA levels were measured by immunoblot analysis. Results. Immunohistochemical staining revealed that the localization of bikunin was similar to that of CD68 for macrophages. We identified high expression of bikunin in 40 (45%) of 89 ovarian cancers. The results of Western blot analysis showed a significant correlation with immunohistochemical data. There was a significant inverse correlation between bikunin levels and uPA levels in ovarian cancer tissues. High bikunin expression was an independent predictor for disease-free survival ( P = 0.040) and overall survival ( P = 0.042). The 5-year survival rate of the 49 patients with low bikunin expression in ovarian cancers was 39%, whereas that of the other 40 patients with high bikunin expression was 63%. In addition, macrophage-derived bikunin protein was induced by exogenous IL-6. Conclusion. Bikunin derived from tumor-infiltrating macrophages might be a prognostic indicator as an antiinvasive factor supplied from macrophages within and around the tumor possibly through down-regulation of tumor-associated uPA expression.

Malignant germ cell tumors: Clinical characteristics, treatment, and outcome. A report from the study group for Pediatric Solid Malignant Tumors in the Kyushu Area, Japan

Purpose: This study aims to assess the prognostic factors and optimal treatments for malignant germ cell tumors (MGCT) in childhood. Methods: Among 117 MGCT, the clinical features were analyzed. Regarding the histology, there were 89 embryonal carcinomas, 13 dysgerminomas, 4 choriocarcinomas, and 11 others. The prognostic factors and treatments were assessed based on the 5-year survival rate. Results: (1) Stage: 100% for stage I (n = 54), 75.0% for stage II (n = 4), 67.3% for stage III (n = 14), and 54.8% for stage IV (n = 33); Unknown: n = 12. (2) Primary site: 93.4% for the testis (n = 52), 86.7% for the ovary (n = 31), 56.9% for the sacrococcygeal (n = 21), and 60.6% for others (n = 12); unknown: n = 1. (3) Surgical intervention for primary tumor: 100% for stage I with a complete resection (n = 53), 78.4% for stage III, IV with a complete resection (n = 26), and 33.3% for stage III, IV with an incomplete resection (n = 21). (4) Type of chemotherapy for the stage III and IV: 83.9% for the PVB (cisplatin, vinblastin, bleomycin; n = 13), 66.7% for the VAC (vincristine, actinomycin D, cyclophosphamide; n = 6), and 47.1% for other regimens (n = 25). Conclusions: An early stage, a diagnosis under 1 year of age and a primary site in the gonads were favorable prognosis factors, whereas histologic findings of choriocarcinoma and liver or lung metastasis were unfavorable. Radical complete resection alone is a sufficient treatment for localized MGCT. The PVB regimen is optimal chemotherapy for advanced MGCT; however, high-risk cases still may require more aggressive treatment. J Pediatr Surg 37:1703-1706. Copyright 2002, Elsevier Science (USA). All rights reserved.

Prognostic value of hypercapnia in patients with chronic respiratory failure during long-term oxygen therapy.

Hypercapnia observed in patients with chronic respiratory failure may not be an ominous sign for prognosis when they are receiving long-term oxygen therapy (LTOT). In this study, we selected 4,552 patients with chronic obstructive pulmonary disease (COPD) and 3,028 with sequelae of pulmonary tuberculosis (TBsq) receiving LTOT from 1985 to 1993 throughout Japan and prospectively analyzed their prognoses. The hypercapnic patients (PaCO2 >= 45 mm Hg) had a better prognosis than the normocapnic patients (35 <= PaCO2 < 45 mm Hg) for TBsq, but no difference was found between the two groups with COPD. Furthermore, Cox's proportional hazards model revealed that in TBsq hypercapnia was an independent factor for favorable prognosis, and that the relative risk for mortality was 0.76 in patients with 45 <= PaCO2 < 55 mm Hg, 0.64 for those with 55 <= PaCO2 < 65 mm Hg, and 0. 49 for patients with PaCO2 >= 65 mm Hg against normocapnic patients. This favorable effect of hypercapnia in TBsq was particularly apparent in the patients without severe airway obstruction. Even a rise of 5 mm Hg or more in PaCO2 over the initial 6- to 18-mo follow-up period was not associated with poor prognosis in TBsq, although it was in COPD. From these findings, we conclude that hypercapnia should not be generally considered an ominous sign for prognosis in those patients who receive LTOT.

Troubles sphinctériens de la myélopathie aiguë transverse de l'enfant. Aspects diagnostiques, pronostiques, rééducatifs

Neurogenic sphincter dysfunction may result from acute transverse myelopathy. The aim of this paper is to study the course of such a dysfunction and to propose management techniques. The files of 21 children admitted at the mean age of 8 years 5 months (2 to 14 years, 8 months) for acute transverse myelopathy were retrospectively studied. Bladder sphincter dysfunction occurred in the first days of disease in 85% of these patients. Abnormal perception of micturition was one of the most constant and specific symptoms. Anorectal function was also impaired. Complete regressive course was noted in 38% of patients, minor sequellae in 39% and major sequellae beyond 6 months of course in 23%. None upper tract deterioration was noted after 3 years of course. Factors of favorable prognosis were early motor function recovery (especially recommencement of walking before 20 days) and early management of bladder dysfunction (inability to void had better prognosis than urinary incontinence). Early systematic bladder drainage in case of inability to void might be essential for improved prognosis.