Favorable Survival Prognosis Research Articles

ALDH1A1-overexpressing cells are differentiated cells but not cancer stem or progenitor cells in human hepatocellular carcinoma.

Aldehyde dehydrogenase 1A1 (ALDH1A1) is considered to be a cancer stem cell marker in several human malignancies. However, the role of ALDH1A1 in hepatocellular carcinoma (HCC) has not been well elucidated. In this study, we investigated the relationship between ALDH1A1 and clinicopathological findings and examined whether ALDH1A1 deserves to be a cancer stem cell marker in HCC. Sixty HCC samples obtained from surgical resection were collected for immunohistochemical (IHC) staining. Of these 60 samples, 47 samples of HCC tumorous and non-tumorous tissues were evaluated with qRT-PCR. There was no significant difference in the ALDH1A1-mRNA level between tumorous and non-tumorous tissues. Tumorous ALDH1A1-mRNA level had no relationship with the clinicopathological features. Immunoreactivity of ALDH1A1 was classified into two groups based on the percentage of ALDH1A1-overexpressing cells. The ALDH1A1-high group was significantly associated with low serum levels of α-fetoprotein, small tumor diameter, very little lymphovascular invasion, more differentiated pathology and good stage. The ALDH1A1-high group showed more favorable prognosis for recurrence-free survival. In double-staining IHC, ALDH1A1 was not co-expressed with BMI1, EpCAM, CD13, CD24, CD90 and CD133, which reported as cancer stem cell markers in HCC. In conclusion, ALDH1A1-overexpressing cells could appear to be differentiated cells rather than cancer stem cells in HCC.

Retrospective analysis of unknown primary cancers with malignant pleural effusion at initial diagnosis.

Malignant pleural effusion (MPE) can occur during the progression of various cancers. However, factors, such as the incidence of MPE associated with different types of cancers and its potential for diagnosing previously undetected cancers, are unknown. Moreover, MPE may accompany potentially curable cancers or those with a favorable survival prognosis with adequate treatment. The present study determined the types of cancers accompanied by MPE at initial diagnosis and investigated appropriate related methods for diagnosing previously unknown cancers. We retrospectively reviewed the medical records of 35 patients with MPE at initial cancer diagnosis between 2004 and 2012. We evaluated the patient characteristics, final diagnosis, and diagnostic processes. Of the 35 patients, 10 had lung cancer, seven ovarian or peritoneal cancer, four malignant pleural mesothelioma, one breast cancer, one lymphoma, one pancreatic cancer, and 11 had cancers of unknown origin. Diagnoses of the primary lesions were confirmed using the MPE cellblock method for seven of 11 patients (63.6%), by excisional biopsy or aspiration from other sites in four of nine patients, by exploratory laparotomy in two of three patients, and by peritoneal washing cytology in five patients. Lung cancer and cancer of unknown origin are major causes of MPE at initial presentation. However, these groups also contain cancers that are curable and those with good long-term prognosis. The MPE cellblock method represents an accurate method for identifying cancer origin.

A matched-pair analysis comparing 5x4 Gy and 10x3 Gy for metastatic spinal cord compression (MSCC) in patients with favorable survival prognoses.

BackgroundIt is currently not possible to get an approval of our ethics committee for a randomized trial cmparing 5x4 Gy and 10x3 Gy for MSCC that includes patients with favorable survival prognoses. Therefore, this matched-pair study following strict matching criteria was perfomed instead.MethodsIn this study, 142 receiving 5x4 Gy were retrospectively matched (1:1) to 142 patients receiving 10x3 Gy with respect to ten characteristics. These characteristics included age, gender, performance status, tumor type, involved vertebrae, other bone metastases, visceral metastases, interval between tumor diagnosis and MSCC, pre-RT ambulatory status, and time developing motor deficits.ResultsOn multivariate analysis, post-RT motor function was associated with performance status (p < 0.001), tumor type (p < 0.001), and time developing motor deficits (p < 0.001). RT was successful in 76% of patients receiving 5x4 Gy and 69% receiving 10x3 Gy (p = 0.14). Pre.RT ambulatory status showed a strong trend with respect to local control (LC) of MSCC in the multivariate analysis (p = 0.058). 1-year LC rates were 87% after 5x4 Gy and 93% after 10x3 Gy (p = 0.16). On multivariate analysis, survival (OS) was associated with performance score (p < 0.001), visceral metastases (p < 0.001), and pre-RT ambulatory status (p = 0.004). 1-year OS rates were 68% after 5x4 Gy and 73% after 10x3 Gy (p = 0.64).ConclusionsIn patients irradiated for MSCC who had favorable survival prognoses, post-RT motor function, LC and OS were not significantly different after 5x4 Gy and after 10x3 Gy.

DACH1 inhibits lung adenocarcinoma invasion and tumor growth by repressing CXCL5 signaling.

Whole-genome and transcriptome sequencing of non-small cell lung cancer (NSCLC) identified that DACH1, is a human homolog of drosophila gene dac, is involved in NSCLC. Here we showed that expression of DACH1 was significantly decreased in human NSCLC tissues and DACH1 abundance was inversely correlated with tumor stages and grades. Restoration of DACH1 expression in NSCLC cells significantly reduced cellular proliferation, clone formation, migration and invasion in vitro, as well as tumor growth in vivo. Unbiased screen and functional study suggested that DACH1 mediated effects were dependent in part on suppression of CXCL5. There was an inverse correlation between DACH1 mRNA levels and CXCL5 in both lung cancer cell lines and human NSCLC tissues. Kaplan-Mier analysis of human NSCLC samples demonstrated that high DACH1 mRNA levels predicted favorable prognosis for relapse-free and overall survival. In agreement, high CXCL5 expression predicted a worse prognosis for survival.

Tumor Immunology, toward a Success Story?

PROOF OF IMMUNOSURVEILLANCE AND THE IMMUNOEDITING CONCEPT The beginning of the second millennium marked a turning point for tumor immunity, on the basis of a series of data obtained in mice and in humans. The enhanced susceptibility of immunodeficient mice to the formation of chemically induced or spontaneous tumors clearly showed that the immune system can eliminate nascent tumors (1). A few years later, the investigations showing that high densities of T cells, particularly with a Th1 and cytotoxic polarization, in different locations of a primary tumor, correlate with favorable prognosis for disease-free and overall survival in large series of cancer patients also strongly supported the fact that a natural immune reaction controls invasion and metastasis (2). Most importantly, these results also proved the establishment of a long-term memory against cancers and suggested that it could be reactivated with tumor vaccines. Such breakthroughs had major consequences for the tumor immunity field. They paved the way for a new era for tumor immunology, building on solid foundations, and leaving behind more than 50 years of errances since the concept of tumor immunosurveillance had been put forward. However, tumors develop, invade tissues locally, metastasize in distant organs, and ultimately cancer can be life threatening. During these last 10 years, we also learnt that the immune system “sculpts” tumors, leading to the formation of tumor variants that escape immunosurveillance, and/or inducing suppressive conditions that facilitate tumor outgrowth. Thus, cancer immunotherapy should aim at boosting anti-tumor immunity by breaking immune tolerance or using adoptively transferred expanded tumor infiltrating lymphocytes (already present in the tumor). This last approach has yielded promising results in terminally ill cancer patients.

IB-02 * ROLE OF TUMOR INFILTRATING LYMPHOCYTES AND PDL1 EXPRESSION IN GLIOBLASTOMA (GBM) AND BRAIN METASTASES (BM): COMPARATIVE ANALYSIS

BACKGROUND: Differences in the adaptive immune response to various kinds of brain tumors have been poorly characterized. METHODS: We immunostained 287 neurosurgical specimens: 170 BM (lung cancer: 77 (45.3%); breast cancer: 17 (10.0%); melanoma 44 (25.9%); renal cell carcinoma 10 (5.9%) others 22 (7.7%)) and 117 GBM for CD3 (n = 287), CD8 (n = 287), PD1 (n = 287) and PDL1 (n = 234) and used previously published semiquantitative evaluation criteria. RESULTS: TIL infiltration of variable density (sparse to dense) was found in 161/170 (94.7%) BM and 78/117 (66.6%) GBM. TILs were predominantly present in the tumor stroma and perivascular areas in BM and in perivascular area in GBM. Dense infiltration with CD3+ TILs (p < 0.001), CD8+ TILs (p < 0.001) and PD1+ TILs (p < 0.001) was observed more frequently in BM than GBM. Among BM, we found significant differences in the composition of immune infiltrates with renal cell carcinoma BM showing the highest density of CD3+ and PD1+ TILs. Membranous PDL1 expression on tumor cells was evident in 25/117 (21.4%) BM and 44/117 (37.6%) GBM. Expression of PDL1 in over 5% of tumor cells was more frequently observed in GBM than in BM (p = 0.006). Dense infiltration of CD3+ TILs (9 vs. 12 months; p = 0.015) correlated with favorable survival prognosis in BM patients, while no prognostic impact of TIL infiltration was evident in GBM. Expression of PDL1 in over 5% of tumor cells was not associated with survival prognosis in BM (11 vs. 11 months; p = 0.395) or GBM (15 vs. 14 months; p = 0.859). CONCLUSION: We found high TIL densities and prognostic impact of CD3+ immune infiltrates in BM. GBM was characterized by sparse TIL infiltrates, higher expression of PDL1 and lack of prognostic impact of immune infiltrates. Our results indicate clinically relevant differences in the immune response to brain tumor types and may be of interest for studies with immunomodulatory agents.

Low mRNA expression levels of kallikrein-related peptidase 4 (KLK4) predict short-term relapse in patients with laryngeal squamous cell carcinoma

Several members of the family of tissue kallikrein and kallikrein-related peptidases have been suggested as promising tumor biomarkers with important prognostic significance. However, only one (KLK11) has already been studied in laryngeal squamous cell carcinoma (LSCC) as a potential biomarker for LSCC diagnosis and/or prognosis. Our study investigated the prognostic value of kallikrein-related peptidase-4 (KLK4) mRNA expression as a molecular tissue biomarker in LSCC. For this purpose, KLK4 mRNA expression analysis was performed in 116 cancerous and 74 paired non-cancerous laryngeal tissue specimens obtained from patients that had undergone surgical treatment for primary LSCC. A remarkable downregulation of KLK4 mRNA expression was discovered in laryngeal tumors, compared to non-cancerous laryngeal tissue specimens. KLK4 mRNA expression was also shown to distinguish LSCC from non-cancerous laryngeal tissues. Furthermore, low KLK4 mRNA expression was shown to predict poor disease-free survival, independently of the histological grade and size of the malignant tumor as well as patient TNM stage. According to Kaplan-Meier survival analysis, low KLK4 mRNA expression predicts short-term relapse even among patients with well-differentiated tumors or those at an early TNM stage. Thus, KLK4 mRNA positivity could be regarded as a novel independent indicator of favorable prognosis for the disease-free survival of LSCC patients.

Outcome of platinum-based chemotherapy for non-small-cell lung cancer patients with pleural dissemination detected during surgery

Pleural dissemination detected by computed tomography (CT) is considered to be unfavorable for patients with non-small-cell lung cancer (NSCLC). However, the prognosis of NSCLC patients who are diagnosed with pleural dissemination at the time of surgery has yet to be adequately elucidated. To assess the outcomes of platinum-based chemotherapy in NSCLC patients in whom pleural dissemination was detected during exploratory thoracotomy with or without a videoscope, the clinical records of NSCLC patients who were admitted to Shizuoka Cancer Center between September, 2002 and April, 2009 were reviewed. A total of 19 patients were included in this study, 12 males and 7 females, with a median age of 65 years. All patients were diagnosed with adenocarcinoma and 6 were epidermal growth factor receptor (EGFR) gene mutation-positive. The median number of treatment cycles of first-line platinum-based chemotherapy was 4 (range, 1-6 cycles) and the objective response rate was 21% [95% confidence interval (CI): 8.5-43]. The median progression-free and overall survival were 10.4 (95% CI: 6.3-18.4) and 50.5 months (95% CI: 32.5-98.0), respectively. Of the 18 patients with reported disease progression, 9 (50%) developed locoregional tumor progression. In conclusion, NSCLC patients in whom pleural dissemination is detected during surgery tend to have a favorable prognosis for survival. Systemic chemotherapy and additional local treatment may improve their clinical outcomes.

Expression of CLDN1 and CLDN10 in lung adenocarcinoma in situ and invasive lepidic predominant adenocarcinoma

BackgroundNon-mucinous bronchioloalveolar carcinoma (BAC) is considered the early stage of lung adenocarcinoma and is classified as the lung adenocarcioma in situ (AIS) by the International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society. This study was designed to investigate the gene expression differences between AIS (formerly non–mucinous BAC) and invasive lepidic predominant adenocarcinoma (LPA, formerly non-mucinous BAC pattern with >5 mm invasion, mixed type adenocarcinoma with BAC features) and to investigate the mechanism of the progression of lung adenocarcinoma in situ to invasive adenocarcinoma.MethodsGene expression analysis was performed by using Agilent 4 × 44 K Whole Human Genome Oligo Microarray on 10 fresh frozen tissue samples of AIS and LPA, respectively. Real time RT-PCR was used to validate the differential expression of 13 genes selected by cDNA microarray on fresh frozen tissue samples from 41 patients with lung adenocarcinoma and 4 genes were confirmed. These 4 genes were then validated by western blotting. Immunohistochemical staining for these validated genes was performed on formalin-fixed, paraffin-embedded tissue samples from 81 cases of lung adenocarcinomna.ResultsWe identified a 13 gene expression signature by comparative analysis of gene expression. Expression of these genes strongly differed between AIS and LPA. Four genes (MMP-2, c-fos, claudin 1 (CLDN1) and claudin 10(CLDN10)) were correlated with the results of microarray and real time RT-PCR analyses for the gene-expression data in samples from 41 patients with lung adenocarcinoma. As confirmed by western blotting, the expression levels of MMP-2 and c-fos were higher in LPA than those in AIS; the expression levels of CLDN1 and CLDN10 in LPA were lower than those in AIS. Immunohistochemical staining for these genes in samples from 81 cases of lung adenocarcinoma demonstrated the expressions of CLDN1 and CLDN10 were correlated with overall survival of patients with lung adenocarcinoma.ConclusionsCLDN1 and CLDN10 may play important roles in the development of AIS to LPA. Overexpression of CLDN1 and CLDN10 indicates a favorable prognosis for overall survival in some patients with lung adenocarcinoma. Expression of CLDN10 may be regulated by the c-fos pathway.

Leptomeningeal Carcinomatosis in Non–Small-Cell Lung Cancer Patients: Impact on Survival and Correlated Prognostic Factors

The incidence of leptomeningeal carcinomatosis (LC) has increased in patients with metastatic non-small-cell lung cancer (NSCLC) because of recent improvements in survival. The clinical features and prognostic factors of LC in NSCLC patients, however, have not been well identified. The aim of this study was to identify the clinical features and prognostic factors of NSCLC patients with LC. One hundred and forty-nine consecutive NSCLC patients with cytologically proven LC diagnoses between 2001 and 2009 at Samsung Medical Center were retrospectively reviewed. The median age was 58 years (range, 34-80) with most patients (135, 95%) having histology indicating adenocarcinoma. Twenty-six patients (17.4%) had LC at the initial presentation of lung cancer. Treatment for LC consisted of intrathecal chemotherapy (ITC) alone in 44 patients, ITC plus systemic therapy in 18 patients, ITC plus radiotherapy in 29 patients, all three treatments in 18 patients, and other treatments without ITC in 20 patients. Twenty patients received only supportive care. The median follow-up duration was 34 months and the median overall survival from diagnosis of LC was 14 weeks (95% confidence interval [CI] 12, 16). In univariate analysis, encephalopathy, Eastern Cooperative Oncology Group (ECOG) performance status, low initial cerebrospinal fluid (CSF) glucose, high initial CSF protein, high initial CSF white blood cell count, treatment with ITC, systemic therapy with epidermal growth factor receptor tyrosine kinase inhibitors or cytotoxic chemotherapy, whole-brain radiotherapy (WBRT), ventriculoperitoneal (VP) shunt operations, and negative cytologic conversion after ITC were identified as variables that had prognostic influence on survival. In multivariate analysis, poor ECOG performance status (p = 0.026), high protein level of CSF (p = 0.027), and high initial CSF WBC count (p = 0.015) remained significant predictors of poor prognosis for survival, whereas ITC (p < 0.001), EGFR-TKI use (p = 0.018), WBRT (p = 0.009), and VP shunt operation (p = 0.013) remained significant predictors of favorable prognosis for survival. Even though the prognosis of LC from NSCLC is poor, small subsets of these patients survive longer. Our results suggest that more active treatment strategies including ITC, WBRT, and EGFR-TKI use might improve clinical outcomes in NSCLC patients with LC and good performance status, low initial CSF protein and WBC counts.

The effectiveness of oral rehydration solution at various concentrations as a storage media for avulsed teeth.

Following avulsion, the periodontal ligament (PDL) cells are at risk of necrosis. To achieve a favorable survival prognosis, the PDL cells must be kept viability. Therefore, immediate replantation is considered as the treatment of choice and in case it is not possible, storing the tooth in an appropriate storage media should be considered. Oral Rehydration Solution (ORS) is a glucose-electrolyte solution which can keep the optimal osmolality as well as pH and can even provide nutrients which are necessary for cellular growth. The present study aimed to evaluate the effectiveness of different concentrations of ORS in maintaining the viability of the PDL cells at different time points. PDL cells were obtained from healthy extracted human premolars. Then, 8×10³ cells were seeded in each well of 96-well plate. Afterwards, each well was treated with ORS in three different concentrations and DMEM for 1, 3, 6, and 9 hours. Cell viability was determined by using the MTT assay. One way-ANOVA and post hoc (LSD) test were used for comparing the study groups. According to the results, 25% and 50% concentrations of ORS were more effective in preserving the PDL cell viability and could maintain 79.98% and 68.34% of the PDL cells, respectively, at least for the last experimental time point (up to 9 hours). Therefore, our findings indicate that ORS might be a suitable storage medium for avulsed teeth.

414PD - Is Brain-Only Metastatic Breast Cancer A Distinct Entity?

ABSTRACT Background Up to 40% of metastatic breast cancer patients (pts) are diagnosed with brain metastases (BM) during their course of diseases. Some case reports and small patient series have indicated that breast cancer pts with the brain as only metastatic site (“brain-only”) may have a more favourable prognosis than BM pts with more widespread metastatic disease. Methods We identified all breast cancer pts with BM treated at our institution between 1990 and 2011. For each patient, full information on follow up and administered therapies was mandatory for inclusion. Estrogen-receptor (ER), progesterone-receptor and HER2 status were determined according to standard protocols. We performed statistical analyses including computation of survival probabilities. Results Overall, 223 female pts (26.0% luminal subtype; 47.5% HER2 subtype; 26.5% triple negative subtype) with BM of metastatic breast cancer were included in this study. In 60/223 pts (26.9%) the brain was the first metastatic site. Brain as first metastatic site was significantly less common in the HER2-positive subtype than in luminal and triple negative subtypes (p = 0.005). 38/223 (17%) of BM pts did not develop extracranial metastases (ECM) during their disease course and were classified as “brain-only” cases. Brain-only metastatic behaviour was not associated with breast cancer subtype or number of BM. The median OS of the brain-only pts was 11 months (range 0-69) and was significantly longer than in pts with BM and ECM (5 months, range 0 to 104) (p = 0.007). High KPS (p = 0.02), single BM (p Conclusions Among breast cancer pts with BM, brain-only metastatic behaviour is not associated with breast cancer subtype, but with favourable survival prognosis. Exploitation of all multimodal treatment options is warranted in breast cancer pts with brain-only metastatic disease, as long-term survival is not uncommon in this patient population. Disclosure All authors have declared no conflicts of interest.

Effect of Functional Status on Survival in Patients With Stroke: Is Independent Ambulation a Key Determinant?

Chiu H-T, Wang Y-H, Jeng J-S, Chen B-B, Pan S-L. Effect of functional status on survival in patients with stroke: is independent ambulation a key determinant? ObjectiveTo investigate the effect of functional status, measured using the Modified Rankin Scale (MRS), at 3 months after stroke on survival in patients with stroke. DesignCohort study. SettingReferral medical center. ParticipantsPatients with stroke (N=1032). InterventionsNot applicable. Main Outcome MeasureSurvival after stroke. ResultsThe Kaplan-Meier survival curves stratified by the 3-month MRS score showed 2 clear groups of patients with 3-month MRS scores of 0 to 3 (able to walk without assistance) and 4 or 5 (unable to walk without assistance). Accordingly, we grouped the patients into a high function (HF) group (3-month MRS≦3) and a low function (LF) group (3-month MRS≧4). Multiple Cox regression analysis showed that the LF group had significantly poorer survival (adjusted hazard ratio=4.69; 95% confidence interval [CI], 2.89–7.60; P<.001) than the HF group. Other significant risk factors of higher mortality were older age, history of diabetes mellitus, and heart disease. ConclusionsThis study showed a significant influence of the 3-month MRS score on stroke survival. Moreover, independent ambulation may be a major determinant of a favorable survival prognosis. This finding suggests a potential role of rehabilitation in promoting stroke survival by maximizing ambulation function.

Dose‐escalation of whole‐brain radiotherapy for brain metastasis in patients with a favorable survival prognosis

Patients with brain metastases who have a favorable survival prognosis may benefit from intensive treatments, including neurosurgery and radiosurgery. However, many patients cannot receive such treatments, and whole-brain radiotherapy (WBRT) alone is their only option. The most common WBRT schedule is 30 grays (Gy) in 10 fractions. In this retrospective study, the authors investigated whether these patients benefit from a dose escalation beyond 30 Gy. Data from 109 patients who received 30 Gy in 10 fractions were compared with 75 patients who received 40 Gy in 20 fractions. All patients had a favorable survival prognosis. Both groups were compared for local control (LC) and overall survival (OS). Subgroup analyses were performed for patients who had less radiosensitive tumors (N = 27) and for other patients (N = 157). The LC rate at 1 year was 28% after 30 Gy and 44% after 40 Gy (P = .064). On multivariate analysis, the 40 Gy dose was associated with improved LC (P = .047). The survival rate at 1 year was 50% after 30 Gy and 61% after 40 Gy (P = .007). On multivariate analysis, the 40 Gy dose was associated with improved OS (P = .008). On subgroup analysis of patients who had less radiosensitive tumors, the 1-year LC rate was 7% after 30 Gy and 38% after 40 Gy (P = .031); and the 1-year OS rate was 40% and 73%, respectively (P = .008). On subgroup analysis of patients who had other tumor types, the 1-year LC rate was 31% after 30 Gy and 45% after 40 Gy (P = .26); and the 1-year OS rate was 52% and 59%, respectively (P = .08). Escalation of the WBRT dose beyond 30 Gy resulted in better outcomes, particularly for patients who had less radiosensitive tumors.

Dose escalation of radiotherapy for Metastatic Spinal Cord Compression (MSCC) in patients with relatively favorable survival prognosis

Local control of metastatic spinal cord compression (MSCC) is particularly important for long-term survivors. Radiotherapy alone is the most common treatment for MSCC. The most frequently used schedule world wide is 30 Gy/10 fractions. This study investigated whether patients with favorable survival prognoses benefit from a dose escalation beyond 30 Gy. Data from 191 patients treated with 30 Gy/10 fractions were matched to 191 patients (1:1) receiving higher doses (37.5 Gy/15 fractions or 40 Gy/20 fractions). All patients had favorable survival prognoses based on a validated scoring system and were matched for age, gender, tumor type, performance status, number of involved vertebrae, visceral or other bone metastases, interval from tumor diagnosis to radiotherapy, ambulatory status, and time developing motor deficits. Both groups were compared for local control, progression-free survival, overall survival, and functional outcome. Local control rates at 2 years were 71% after 30 Gy and 92% after higher doses (p=0.012). Two-year progression-free survival rates were 68% and 90%, respectively (p=0.013). Two-year overall survival rates were 53% and 68%, respectively (p=0.032). Results maintained significance in the multivariate analyses (Cox proportional hazards model; stratified model) with respect to local control (p=0.011; p=0.012), progression-free survival (p=0.010; p=0.018), and overall survival (p=0.014; p=0.015). Functional outcome was similar in both groups. Motor function improved in 40% of patients after 30 Gy and 41% after higher doses (p=0.98). Escalation of the radiation dose beyond 30 Gy resulted in significantly better local control, progression-free survival, and overall survival in patients with favorable survival prognoses.

The role of radiotherapy for metastatic epidural spinal cord compression

Radiotherapy alone is the most common treatment for metastatic epidural spinal cord compression (MESCC). Decompressive surgery followed by radiotherapy is generally indicated only in 10-15% of MESCC cases. Chemotherapy has an unclear role and may be considered for selected patients with hematological or germ-cell malignancies. If radiotherapy alone is given, it is important to select the appropriate regimen. Similar functional outcomes can be achieved with short-course radiotherapy regimens and longer-course radiotherapy regimens. Longer-course radiotherapy is associated with better local control of MESCC than short-course radiotherapy. Patients with a more favorable survival prognosis (expected survival of ≥6 months) should receive longer-course radiotherapy, as they may live long enough to develop a recurrence of MESCC. Patients with an expected survival of <6 months should be considered for short-course radiotherapy. A recurrence of MESCC in the previously irradiated region after short-course radiotherapy may be treated with another short-course of radiotherapy. After primary administration of longer-course radiotherapy, decompressive surgery should be performed if indicated. Alternatively, re-irradiation can be performed using high-precision techniques to reduce the cumulative dose received by the spinal cord. Larger prospective trials are required to better define the appropriate treatment for the individual patient.

Resection and Anastomosis of the Descending Colon in 43 Horses

To determine (1) the short- (to hospital discharge) and long- (>6 months) term survival, (2) factors associated with short-term survival, and (3) the perioperative course for horses with resection and anastomosis of the descending colon. Multicentered case series. Horses (n=43) that had descending colon resection and anastomosis. Medical records (January 1995-June 2009) of 7 equine referral hospitals were reviewed for horses that had descending colon resection and anastomosis and were recovered from anesthesia. Retrieved data included history, results of clinical and clinicopathologic examinations, surgical findings, postsurgical treatment and complications, and short-term survival (hospital discharge). Long-term survival was defined as survival > or =6 months after hospital discharge. Of 43 horses, 36 (84%) were discharged from the hospital. Twenty-eight of 30 horses with follow-up information survived > or =6 months. No significant associations between perioperative factors and short-term survival were identified. Lesions included strangulating lipoma (n=27), postfoaling trauma (4), infarction (4), intraluminal obstruction (2), and other (6). Common postoperative complications included fever and diarrhea. During hospitalization 7 horses were euthanatized or died because of septic peritonitis (3), endotoxemia (3), and colic and ileus (1). Descending colon resection and anastomosis has a favorable prognosis for hospital discharge and survival > or =6 months. The most common cause of small colon incarceration was strangulating lipoma. Complications include postoperative fever and diarrhea but the prognosis is good after small colon resection and anastomosis.

Transcriptional Profiles Predict Disease Outcome in Patients with Cutaneous T-Cell Lymphoma

Average survival of cutaneous T-cell lymphoma (CTCL) is associated with clinical stage at diagnosis, where stage I has a favorable survival prognosis, whereas patients with more advanced stages succumb to their disease within 5 years. Although the majority of patients present with an early-stage CTCL, 15% to 20% of them will inevitably progress. Current state-of-the-art clinical criteria cannot identify individuals with stage I disease who are at risk of progression. The purpose of the current work is to gain novel molecular insight into the pathophysiology of CTCL to be able to identify patients with poor versus favorable prognosis. Our previous work used microarray analysis of skin biopsies from 62 CTCL patients to perform an unsupervised analysis of gene expression, which revealed three distinct transcription profile clusters. In the present study, we used reverse transcription-PCR to confirm gene expression levels for a subset of representative genes in each cluster. We also performed a Kaplan-Meier analysis of survival and disease progression based on the 6 years of clinical follow-up. Our reverse transcription-PCR results confirmed the upregulation of representative genes for each cluster, whereas clinical analysis documents that all stage I cases that progressed to stage II and beyond were in poor and intermediate prognosis clusters 1 and 3 and none were in favorable prognosis cluster 2. This analysis also identified certain genes that were preferentially expressed in favorable (e.g., WIF-1) versus poor (e.g., IL-17F) prognosis clusters. This work suggests that it may be possible to stratify CTCL patients into low-risk, intermediate-risk, and high-risk groups based on gene expression.

Reply to: The definition of locally advanced pancreatic cancer

Sir, We would like to thank Zanini et al (2010) for their critical discussion of our data from a randomised phase II trial in locally advanced pancreatic cancer (LAPC) that was recently published in this journal (Wilkowski et al, 2009). During the previous years, LAPC has been increasingly recognised as a separate disease entity in malignant pancreatic disorders. With the use of systemic gemcitabine-based chemotherapy, LAPC has a favourable survival prognosis compared with metastatic pancreatic cancer; however, the value of chemoradiotherapy still remains controversial in this stage of disease (Chauffert et al, 2008). We fully agree with Zanini et al that a unique, internationally standardised and accepted definition of LAPC is not yet established to date, and that such an approach is strongly recommend for future clinical trials in LAPC. Currently, different study groups still apply individual definitions for LAPC (Chauffert et al, 2008; Crane et al, 2009) and this definition probably is still mostly influenced by the definition of ‘resectability' of the involved surgeon. A first step for the formulation of standardised criteria defining the respectability status in pancreatic cancer (e.g., ‘resectable' vs ‘borderline resectable' vs ‘unresectable') is included in the current version of the NCCN guidelines for pancreatic adenocarcinoma (http://www.nccn.org, V.I.2009). At the time when our phase II study was designed in 2001, the criteria for defining LAPC included in the study protocol were a first attempt to standardise the LAPC definition in the setting of a prospective multi-centre clinical trial. However, the authors are fully aware of the limitations of such an approach, as critically formulated by Zanini et al. In fact, much more future research will be necessary in order to better characterise LAPC clinically and biologically. Besides, currently – as recently reported in a study by Morak et al – the classification of a tumour as LAPC may still depend on the diagnostic possibilities and on the experience of a clinical institution (Morak et al, 2009).

Postoperative Complications and Survival after Enterolith Removal from the Ascending or Descending Colon in Horses

To compare incidence of postoperative complications and survival of horses that had surgery for enterolithiasis of the ascending (AC) or descending (DC) colon. Case series Horses (n=236) that had celiotomy for AC (n=97) or DC (n=139) enterolithiasis. Medical records (1999-2005) were reviewed for signalment, presenting clinical signs, surgical findings, postoperative complications, and short-term survival until discharge. Information on performance and survival > or = 1 year was obtained by telephone or mailed questionnaire. Number of postoperative complications did not differ between groups (P=.76). The most frequently identified short-term complications for all horses were incisional problems, gastric ulceration, ileus, diarrhea, fever, and anorexia. Horses with DC enteroliths had a significantly higher incidence of anorexia (P=.04) and fever (P=.01). The most common complications after hospital discharge were incisional problems, laminitis, weight loss, and colic. Although more DC horses were euthanatized intraoperatively (P=.02), no differences were detected for horses that survived until discharge (P=.18) or > or = 1 year after discharge (P=.47). Number or type of postsurgical complications or survival after surgery was not influenced by enterolith location and horses have a favorable prognosis for long-term survival after enterolith removal, regardless of site of obstruction in the colon. Incidence of postoperative complications and survival are not affected by the site of enterolith obstruction in the colon.