Retrospective analysis of treatment outcomes for extranodal NK/T-cell lymphoma (ENKL), nasal type, stage I-IIE: single institute experience of combined modality treatment for early localized nasal extranodal NK/T-cell lymphoma (ENKL)

Extranodal natural killer/T-cell lymphoma (ENKL) is a very aggressive disease frequently involving the nasal cavity and upper aerodigestive tract. We retrospectively reviewed the treatment outcomes and treatment-associated complications of the patients with stage I–II early localized ENKL. A total of 24 patients were included. All patients were treated with combined chemoradiotherapy. Three, sixteen, and five patients were initially treated with radiation therapy, chemotherapy, and surgical procedures, respectively. Nine patients underwent hematopoietic stem cell transplantation (HSCT), and four patients administered immunotherapy with pegylated-interferon alpha. The mean observation time was 71.6 months (range, 29.7–183.6 months). Twenty patients achieved complete remission; thus, the overall response rate was 83.3 %. The 5-year overall survival (OS) and relapse-free survival (RFS) rates were 70.3 % and 62.2 %, respectively. In univariate analysis, HSCT was a significant prognostic indicator for OS and RFS. By combining HSCT, the 5-year OS and RFS rates were 100.0 % vs. 52.5 % (p?=?0.018) and 88.9 % vs. 45.7 % (p?=?0.045), respectively. Also, absence of B symptoms was a good prognostic factor for RFS, the 5-year RFS rate, 75.0 % vs. 25.0 % (p?=?0.010), and B symptoms were significant for RFS in multivariate analysis (odds ratio?=?7.4, confidence interval?=?1.6~34.1, p?=?0.011). However, a total of four cases of grade 3 toxicities were reported. Radiation dose range (≤4,500 vs. >4,500 cGy) was significantly correlated with late complications, as more severe complications occurred more frequently with a radiation dose >4,500 cGy (p?=?0.026, in multivariate analysis). For more efficient treatment of ENKL, chemotherapy, HSCT, and/or immunotherapy can be combined with radiation therapy to prolong long-term survival and achieve good local control. Also, lower radiation dose could be administered to avoid severe late complications.     

Identification of prognostic immunophenotypic features in cancer stromal cells of high-grade neuroendocrine carcinomas of the lung

Purpose

The immunophenotypes of cancer stromal cells have been recognized as prognostic factors of cancer. The purpose of this study was to analyze the prognostic markers of high-grade neuroendocrine carcinomas of the lung (HGNEC; both small cell carcinoma and large cell neuroendocrine carcinoma) by examining the immunophenotypes of cancer stromal cells.

Materials and methods

One hundred and fifteen patients who underwent a complete resection of HGNEC were included in this study. We examined the presence of CD204-positive tumor-associated macrophages (TAMs), Foxp3-positive regulatory T cells (Tregs), and podoplanin-positive cancer-associated fibroblasts (CAFs) to evaluate the prognostic values of these markers.

Results

The number of CD204-positive TAMs and Foxp3-positive Tregs did not influence the overall survival (OS) or the relapse-free survival (RFS) of the patients. However, patients with podoplanin-positive CAFs had a significantly better prognosis than those with podoplanin-negative CAFs [OS: p = 0.002, RFS: p = 0.002, 5-year overall survival (5YR): 74 vs. 45 %]. According to subgroup analyses, patients with podoplanin-positive CAFs displayed a better prognosis for both small cell carcinoma (OS: p = 0.046, 5YR: 74 vs. 46 %) and large cell neuroendocrine carcinoma (OS: p = 0.020, 5YR: 74 vs. 45 %). Moreover, in multivariate analyses, the podoplanin status of the CAFs was shown to be a statistically significant independent predictor of recurrence.

Conclusion

The presence of podoplanin-positive CAFs had a favorable prognostic value, suggesting that the evaluation of podoplanin expression by CAFs would lead to a novel risk classification of patients.     

Can serum dynamics of carcinoembryonic antigen level during neoadjuvant chemoradiotherapy in rectal cancer predict tumor response and recurrence? A multi-institutional retrospective study

Purpose

We evaluate whether the change of carcinoembryonic antigen (CEA) level before and after preoperative chemoradiotherapy (CRT) in rectal cancer affects tumor response and recurrence or not.

Methods

We retrospectively analyzed 1447 rectal cancer patients who underwent preoperative CRT followed by curative surgery. All patients received preoperative radiotherapy of 50.4 Gy in 28 fractions with 5-fluorouracil or capecitabine. Total mesorectal excision was performed 4 to 8 weeks after preoperative CRT. CEA levels were checked before and after CRT. Clinical and pathologic factors were analyzed for tumor response and recurrence.

Results

Post-CRT CEA level (cutoff value, 2.5 ng/mL) was not a significant factor for tumor response on the multivariate analysis (p = 0.095). Patients were categorized according to the pre- and post-CRT CEA level (group A: pre-CRT CEA ≤5 ng/mL; group B: pre-CRT CEA >5 ng/mL and post-CRT CEA ≤2.5 ng/mL; group C: pre-CRT CEA >5 ng/mL and post-CRT CEA >2.5 ng/mL). The relapse-free survival (RFS) at 5 years was significantly higher in group A than in groups B and C (82.6 vs. 73.7 % vs. 72.2 %, p < 0.001). The overall survival (OS) at 5 years was significantly higher in group A than in groups B and C (90.1 vs. 84.4 % vs. 83.4 %, p < 0.001). However, there is no significant difference for RFS and OS between groups B and C (all, p > 0.05).

Conclusions

Decline of elevated CEA level (>5 ng/mL) during preoperative chemoradiotherapy has no significant effect on tumor response and recurrence in rectal cancer.

     

Outcomes and prognostic factors of first relapsed acute promyelocytic leukemia patients undergoing salvage therapy with intravenous arsenic trioxide and chemotherapy

Arsenic trioxide (ATO) is an effective therapy for relapsed acute promyelocytic leukemia (APL) patients; however, the optimal treatment strategy remains unclear, and knowledge of the prognostic factors is still limited. We retrospectively analyzed the outcomes of 64 consecutive first relapsed APL patients (12 with molecular relapse and 52 with hematologic relapse). Patients received re-induction with intravenous ATO-based regimens. Patients who achieved a CR2 were offered further courses of alternating ATO/conventional chemotherapy with or without stem cell transplantation (SCT). With a median follow-up of 27 months (range, 6–57) in the molecular relapsed subgroup, the 3-year relapse-free survival (RFS) and overall survival (OS) rates were 81.5 % and 100 %, respectively. With a median follow-up of 38 months (range, 0–129) in the hematologic relapse group, the 3-year RFS and OS rates were 57.1 % and 72.1 %, respectively. Furthermore, in the hematologic relapse group, we compared the outcome between relapsed patients after previous ATO therapy (n?=?20) with those who did not receive prior ATO therapy (n?=?32). The CR2 rate was 80 % (16/20) vs. 93.8 % (30/32), (p?=?0.189). However, the relapse rate was 68.8 % (11/16) vs. 33.3 % (10/30), (p?=?0.03). The 4-year OS rate was 62.4 % vs. 71.2 %, (p?=?0.816), and the 4-year RFS rate was 29.8 % vs. 66.2 % (p?=?0.023). The results indicate that, irrespective of frontline therapy with ATO, salvage therapy with an ATO-based regimen remains effective. However, the long-term survival for those patients who received previous ATO-based treatment was inferior compared to those who did not receive prior ATO. In addition, the alternating ATO/chemotherapy strategy can be a post-remission treatment option in a subset of patients.     

MicroRNAs 103 and 107 link type 2 diabetes and post-menopausal breast cancer

Type 2 diabetes mellitus (T2DM) increases the incidence of post-menopausal breast cancer (PMBC). This study is intended to determine whether microRNA-103/107 (miR-103/107) should be regarded as a potential molecular link between T2DM and PMBC. Samples of serum from 90 patients with T2DM and/or PMBC were collected. Samples of serum from 20 non-diabetic post-menopausal women were used as the control. The body mass index (BMI) of patients with T2DM and PMBC was lower than the BMI of patients with only T2DM or PMBC (p?<?0.05). The expression of miR-103/107 was higher in the serum of T2DM patients compared with that in control samples (2.80?±?0.46/36.29?±?3.41 vs 0.88?±?0.25/8.59?±?1.91, p?<?0.05). The expression of miR-103/107 in the serum of PMBC patients was higher than that in T2DM patients (5.06?±?0.92/49.59?±?6.99 vs 2.80?±?0.46/36.29?±?3.41, p?<?0.05) but lower than that in patients diagnosed with both T2DM and PMBC (7.67?±?0.87/63.24?±?8.58, p?<?0.05). miR-103/107 was positively correlated with the homeostasis model assessment-insulin resistance (HOMA-IR) index (r?=?0.71, 0.685, p?<?0.01). The expression of miR-103/107 was an independent factor of the HOMA-IR index (β?=?0.638, 0.073, p?=?0.02, 0.01). There were higher levels of estradiol (E2) in patients with T2DM and/or PMBC than that in the control group. High expression of miR-103/107 results in insulin resistance and is associated with overweight or obese patients with T2DM and PMBC through elevated levels of E2. miR-103/107 may be a potential molecular link between T2DM and PMBC.     

Effect of irbesartan on development of atrial fibrosis and atrial fibrillation in a canine atrial tachycardia model with left ventricular dysfunction,association with p53

Effects of an angiotensin II receptor blocker, irbesartan (IRB), on the development of atrial fibrosis and atrial fibrillation (AF) were assessed in a canine model of atrial tachycardia remodeling (ATR) with left ventricular dysfunction, together with its possible association with involvement of p53. Atrial tachypacing (400 bpm for 4 weeks) was used to induce ATR in beagles treated with placebo (ATR-dogs, n = 6) or irbesartan (IRB-dogs, n = 5). Non-paced sham dogs served as control (Control-dogs, n = 4). ATR- and IRB-dogs developed tachycardia-induced left ventricular dysfunction. Atrial effective refractory period (AERP) shortened (83 ± 5 ms, p < 0.05), inter-atrial conduction time prolonged (72 ± 2 ms, p < 0.05), and AF duration increased (29 ± 5 s, p < 0.05 vs. baseline) after 4 weeks in ATR-dogs. ATR-dogs also had a larger area of atrial fibrous tissue (5.2 ± 0.5 %, p < 0.05 vs. Control). All these changes, except for AERP, were attenuated in IRB-dogs (92 ± 3 ms, 56 ± 3 ms, 9 ± 5 s, and 2.5 ± 0.7 %, respectively; p < 0.05 vs. ATR for each). In ATR-dogs, p53 expression in the left atrium decreased by 42 % compared with Control-dogs (p < 0.05); however, it was highly expressed in IRB-dogs (+89 % vs. ATR). Transforming growth factor (TGF)-β1 expression was enhanced in ATR-dogs (p < 0.05 vs. Control) but reduced in IRB-dogs (p < 0.05 vs. ATR). Irbesartan suppresses atrial fibrosis and AF development in a canine ATR model with left ventricular dysfunction in association with p53.     

Predicting survival for multiple myeloma patients using baseline neutrophil/lymphocyte ratio

The neutrophil/lymphocyte ratio (NLR) at diagnosis has been shown to be a prognostic factor for survival in solid tumors. The NLR at diagnosis as a prognostic factor for multiple myeloma (MM) has not been studied. Therefore, the focus of the study was the correlation of NLR with the proven prognostic parameters in patients with MM. A total of 151 MM patients who fulfilled the International Myeloma Working Group (IMWG) criteria were enrolled in the study by a retrospective review of the patients' records. One hundred fifty-one age- and gender-matched healthy controls were also included in the study. NLR was calculated using data obtained from the complete blood count (CBC). NLR was significantly higher in MM patients than the control group (2.79?±?1.82 vs. 1.9?±?0.61, respectively; p?<?0.0001). The median follow-up on living patients in this study was 41 months. NLR at the diagnosis was found to be an independent predictor for overall survival (OS) and event-free survival (EFS) by univariate and multivariate analysis. Patients with a NLR <2 at diagnosis experienced superior OS compared with patients with a NLR ≥2 (5-year OS rates were 87.5 and 42.4 %, respectively; p?<?0.0001). In a similar fashion, superior EFS was observed in patients with a NLR <2 at the diagnosis compared with patients with a NLR ≥2 (5-year EFS rates were 88.4 and 41.8 %, respectively, p?<?0.0001). This study suggests that NLR at the diagnosis is a simple, inexpensive, possible prognostic factor to assess clinical outcomes in MM patients.     

Liver transplantation for hepatocellular carcinoma exceeding the Milan criteria: a single-center experience

Purpose

To establish a prognostic prediction system for patients with hepatocellular carcinoma (HCC) exceeding Milan criteria after liver transplantation (LT).

Methods

A total of 130 patients undergoing LT for HCC exceeding Milan criteria were enrolled into the study. Independent predictors for relapse-free survival (RFS) were adopted to establish a grading system to predict the risk of post-LT tumor recurrence.

Results

Multivariate Cox analysis revealed that tumor size >10 cm [vs. ≤5 cm: relative risk (RR) = 4.214, P < 0.001], preoperative alpha fetoprotein > 400 ng/ml (vs. ≤400 ng/ml: RR = 1.657, P < 0.001), extrahepatic invasion (RR = 2.407, P = 0.005) and vascular invasion (RR = 1.917, P = 0.013) were independent predictors for RFS. The risk index of each patient was defined as the sum of the RR obtained in the Cox analysis for RFS. The risk of tumor recurrence was classified into four grades: grade I—risk index equal to 0, grade II—risk index from 0 to 2, grade III—risk index from 2 to 6 and grade IV—risk index >6. RFS rates of patients with grade I–IV (n = 35, 46, 30 and 19) were 87.5, 57.8, 34.7 and 0 % in 1 year; and 74.4, 41.7, 14.4 and 0 % in 5 years. Both of overall survival (OS) and RFS correlated well with the risk index grade. Patients with grade I achieved comparable prognostic outcomes with the Milan group patients (n = 119) (5-year OS = 73.7 vs. 74.7 %, P = 0.748; 5-year RFS = 74.4 vs. 85.7 %, P = 0.148).

Conclusions

The new grading system was proved to be a promising system in predicting the patient prognosis after LT for HCC exceeding Milan criteria.     

Improved prognostic stratification power of CIBMTR risk score with the addition of absolute lymphocyte and eosinophil counts at the onset of chronic GVHD

The CIBMTR chronic graft-versus-host disease (cGVHD) risk score can be refined and improved for better prognostic stratification. Three hundred and seven consecutive patients diagnosed with cGVHD by the NIH consensus criteria were retrospectively reviewed and had the CIBMTR risk score applied and analyzed. The CIBMTR risk score was successfully validated in our cohort (n = 307). The 3-year overall survival (OS) rates in each risk group (RG) were 82.5 ± 11.3% (RG1), 79.4 ± 3.0% (RG2), 71.8 ± 6.3% (RG3), and 27.3 ± 13.4% (RG4). A significantly lower OS rate and higher non-relapse mortality (NRM) were noted in RG4 compared to the other RGs. However, there were no differences in OS or NRM among RG1 to 3. To improve prognostic stratification power of the CIBMTR risk score, we incorporated the absolute lymphocyte (ALC) and eosinophil count (EC) at time of cGVHD into the CIBMTR risk score. Lower ALC (<1.0 × 10⁹/L, HR 1.94, p = 0.014) and lower EC (<0.5 × 10⁹/L, HR 3.27, p = 0.014) were confirmed as adverse risk factors for OS. Patients were stratified into four revised risk groups (rRG). The 3-year OS rates were 93.3 ± 6.4% (rRG1, score 0–3), 84.9 ± 3.4% (rRG2, score 4–6), 70.9 ± 4.4% (rRG3, score 7–9), and 32.0 ± 1.1% (rRG4, score ≥ 10) (p < 0.001). The 3-year NRM rates were 0.0% (rRG1), 6.7 ± 0.4% (rRG2), 18.4 ± 0.7% (rRG3), and 57.7 ± 5.1% (rRG4) (p < 0.001). The revised CIBMTR risk score was superior to the original CIBMTR risk score for OS (p < 0.001). The revised CIBMTR risk score including ALC and EC at the onset of cGVHD improved the prognostic stratification power of the CIBMTR risk score for long-term outcomes.     

Tumor burden score predicts tumor recurrence of non-functional pancreatic neuroendocrine tumors after curative resection

BackgroundTo investigate the feasibility of Tumor Burden Score (TBS) to predict tumor recurrence following curative-intent resection of non-functional pancreatic neuroendocrine tumors (NF-pNETs).MethodThe TBS cut-off values were determined by a statistical tool, X-tile. The influence of TBS on recurrence-free survival (RFS) was examined.ResultsAmong 842 NF-pNETs patients, there was an incremental worsening of RFS as the TBS increased (5-year RFS, low, medium, and high TBS: 92.0%, 73.3%, and 59.3%, respectively; P < 0.001). TBS (AUC 0.74) out-performed both maximum tumor size (AUC 0.65) and number of tumors (AUC 0.5) to predict RFS (TBS vs. maximum tumor size, p = 0.05; TBS vs. number of tumors, p < 0.01). The impact of margin (low TBS: R0 80.4% vs. R1 71.9%, p = 0.01 vs. medium TBS: R0 55.8% vs. R1 37.5%, p = 0.67 vs. high TBS: R0 31.9% vs. R1 12.0%, p = 0.11) and nodal (5-year RFS, low TBS: N0 94.9% vs. N1 68.4%, p < 0.01 vs. medium TBS: N0 81.8% vs. N1 55.4%, p < 0.01 vs. high TBS: N0 58.0% vs. N1 54.2%, p = 0.15) status on 5-year RFS outcomes disappeared among patients who had higher TBS.ConclusionsTBS was strongly associated with risk of recurrence and outperformed both tumor size and number alone.     

The superiority of allogeneic hematopoietic stem cell transplantation from unrelated donor over chemotherapy for adult patients with high-risk acute lymphoblastic leukemia in first remission

For adult patients with acute lymphoblastic leukemia (ALL), allogeneic hematopoietic stem cell transplantation (allo-HSCT) from HLA-matched related donors (MSD) is recommended for standard and high-risk patients. The role of unrelated donor transplantation (URD) in first remission has not been fully determined. We sought to compare directly the outcome of URD allo-HSCT and chemotherapy in patients with high-risk ALL. In this single-center retrospective analysis, we included 74 consecutive adult patients with high-risk ALL in first complete remission (CR) and without a sibling donor, in which 32 patients received URD allo-HSCT in CR1 with busulfan-cyclophosphamide preparation regimen and in vivo T-cell depletion with anti-T-lymphoglobulin (ATG). The remaining 42 patients received chemotherapy consolidation and maintenance only in first remission. With median follow-up of 18 months, in the URD allo-HSCT group, the relapse rate (RR) was 30.6 ± 11.4 % which was significantly lower than that of the chemotherapy group (80.5 ± 10.1 %, p < 0.001), while non-relapse mortality (NRM) was higher (16.4 ± 6.7 % vs. 0, p = 0.028). Overall, 3-year leukemia-free survival (LFS) was superior in the URD allo-HSCT group compared to chemotherapy group (57.8 ± 10.6 vs. 19.5 ± 10.5 %, p = 0.002), as was 3-year overall survival (OS, 63.5 ± 13.3 vs. 31.6 ± 10.6 %, p = 0.016). URD HSCT was the only factor associated with improved OS, LFS and reduced RR in multivariate analysis. Based on our data, URD allo-HSCT significantly reduced the relapse in high-risk ALL and the benefit translated into improvement in both LFS and OS. Prospective studies based on availability of HLA-matched URD are warranted to evaluate the precise role of URD transplantation in adult ALL.     

Underweight status at diagnosis is associated with poorer outcomes in adult patients with acute myeloid leukemia: a retrospective study of JALSG AML 201

Recent studies have described various impacts of obesity and being overweight on acute myeloid leukemia (AML) outcomes in adult patients, but little is known about the impact of being underweight. We compared the outcomes of underweight patients to those of normal weight and overweight patients. Adult patients with AML who registered in the JALSG AML201 study (n = 1057) were classified into three groups: underweight (body mass index [BMI] < 18.5, n = 92), normal weight (BMI 18.5–25, n = 746), and overweight (BMI ≥ 25, n = 219). With the exception of age and male/female ratio, patient characteristics were comparable among the three groups. Rates of complete remission following induction chemotherapy were similar among the three groups (p = 0.68). We observed a significant difference in overall survival (OS), disease-free survival (DFS), and non-relapse mortality (NRM) between underweight and normal weight patients (3-year OS 34.8 vs. 47.7%, p = 0.01; DFS 28.6 vs. 39.8%, p = 0.02; 1-year NRM 6.2 vs. 2.6%, p = 0.05), but not between underweight and overweight patients. In multivariate analysis, underweight was an independent adverse prognostic factor for OS (p < 0.01), DFS (p = 0.01), and NRM (p = 0.04). During the first induction chemotherapy, the incidences of documented infection (DI) and severe adverse events (AEs) were higher in underweight patients than those in normal weight patients (DI 16 vs. 8.1%, p = 0.04; AE 36 vs. 24%, p = 0.05). In conclusion, underweight was an independent adverse prognostic factor for survival in adult AML patients.     

Prognostic significance of baseline nutritional index for patients with esophageal squamous cell carcinoma after radical esophagectomy

Background

Radical esophagectomy is the cornerstone of curative treatment for patients with resectable esophageal squamous cell carcinoma (ESCC). Patient survival after surgery for ESCC is mainly associated with pathological tumor progression. Recently, the impact of baseline immune-nutritional status of various types of patients with cancer on survival has been highlighted. The purpose of the present study was to investigate the association between the baseline prognostic nutritional index (PNI) and postoperative short- and long-term results after esophagectomy for patients with ESCC.

Methods

In total, 202 patients with ESCC who underwent radical esophagectomy at our institution between 2002 and 2010 were enrolled. PNI was calculated as 10× serum albumin (g/dL) + 0.005 × total lymphocyte counts (per mm³). Receiver operating characteristic (ROC) curves were generated for multiple logistic regression analysis using 5-year overall survival as the endpoint to determine an optimal PNI cutoff value, in which patients were classified into two groups: high PNI and low PNI. We evaluated the significance of PNI on postoperative morbidity and long-term survival using univariate and multivariate analyses.

Results

The mean PNI was 48.9 ± 4.6 (range 37.2–64.0). The area under the ROC curve in multiple logistic regression analysis was 0.5367. The projected 5-year survival rate was optimal at a PNI of 44.1. Hence, the PNI cutoff point was set at 44, with subjects classified by PNI level into the low (PNI <44) or high (PNI ≥44) PNI groups. Of 202 patients, 173 (85.7 %) and 29 (14.3 %) were classified as having high and low PNI, respectively. No significant differences were noted between the two groups regarding patient background, including age, sex, pT, pN, and pStage, or postoperative complications. However, overall survival (OS) and relapse-free survival (RFS) were significantly worse in the low PNI group than in the high PNI group. The 5-year OS and RFS rates in the high PNI vs. low PNI groups were 67.2 vs. 41.2 % (P = 0.007) and 61.5 vs. 38.8 % (P = 0.008), respectively. Multivariate analysis revealed that PNI was a significant prognostic factor for both OS (hazard ratio, 1.826; 95 % confidence interval, 1.015–3.285; P = 0.044) and RFS (hazard ratio, 1.862; 95 % confidence interval, 1.121–3.095; P = 0.016).

Conclusion

Preoperative PNI is an independent prognostic marker of both OS and RFS for patients with potentially curative ESCC. A careful follow-up for tumor recurrence after surgery is required for ESCC patients with low PNI.

     

Prognostic Impact of Node-Spreading Pattern in Surgically Treated Small-Cell Lung Cancer: A Multicentric Analysis

Objective

Although surgery in selected small-cell lung cancer (SCLC) patients has been proposed as a part of multimodality therapy, so far, the prognostic impact of node-spreading pattern has not been fully elucidated. To investigate this issue, a retrospective analysis was performed.

Methods

From 01/1996 to 12/2012, clinico-pathological, surgical, and oncological features were retrospectively reviewed in a multicentric cohort of 154 surgically treated SCLC patients. A multivariate Cox proportional hazard model was developed using stepwise regression, in order to identify independent outcome predictors. Overall (OS), cancer-specific (CSS), and Relapse-free survival (RFS) were calculated by Kaplan-Meier method.

Results

Overall, median OS, CSS, and RFS were 29 (95 % CI 18–39), 48 (95 % CI 19–78), and 22 (95 % CI 17–27) months, respectively. Lymphadenectomy was performed in 140 (90.9 %) patients (median number of harvested nodes: 11.5). Sixty-seven (47.9 %) pN0-cases experienced the best long-term survival (CSS: 71, RFS: 62 months; p < 0.0001). Among node-positive patients, no prognostic differences were found between pN1 and pN2 involvement (CSS: 22 vs. 15, and RFS: 14 vs. 10 months, respectively; p = 0.99). By splitting node-positive SCLC according to concurrent N1-invasion, N0N2-patients showed a worse CSS compared to those cases with combined N1N2-involvement (N0N2: 8 months vs. N1N2: 22 months; p = 0.04). On the other hand, the number of metastatic stations (p = 0.80) and the specific node-level (p = 0.85) did not affect CSS. At multivariate analysis, pN+ (HR: 3.05, 95 % CI 1.21–7.67, p = 0.02) and ratio between metastatic and resected lymph-nodes (RL, HR: 1.02, 95 % CI 1.00–1.04, p = 0.03) were independent predictors of CSS. Moreover, node-positive patients (HR: 3.60, 95 % CI 1.95–6.63, p < 0.0001) with tumor size ≥5 cm (HR: 1.85, 95 % CI 0.88–3.88, p = 0.10) experienced a worse RFS.

Conclusions

In selected surgically treated SCLC, the long-term survival may be stratified according to the node-spreading pattern.

     

Allogeneic hematopoietic cell transplantation with reduced-intensity conditioning following FLAMSA for primary refractory or relapsed acute myeloid leukemia

Patients with primary refractory or relapsed acute myeloid leukemia (AML) have a dismal prognosis. We report a retrospective single center analysis of aplasia-inducing chemotherapy using fludarabine, cytarabine, and amsacrine (FLAMSA) followed by reduced-intensity conditioning (RIC) for allogeneic hematopoietic cell transplantation (HCT) in 62 consecutive primary refractory or relapsed AML patients. Two-year event-free survival and overall survival (OS) were 26 and 39 %, respectively. Risk stratification according to cytogenetic and molecular genetic markers showed superior survival in patients in the intermediate-1 risk group (2-year OS 70 %) compared to the intermediate-2 risk (2-year OS 34 %, p?=?0.03) and adverse risk (2-year OS 38 %, p?=?0.06) group. The use of HLA-matched versus HLA-mismatched donors had no significant influence on survival (p?=?0.98). Two-year OS in the elderly subgroup defined by age ≥60 years was 31 % compared to 46 % in the group of younger patients <60 years (p?=?0.19). Cumulative incidence of non-relapse mortality at 2 years adjusted for relapse as competing risk was 20 % for patients <60 years and 26 % for older patients (p?=?0.55). Chronic graft-versus-host disease was associated with a statistically significant superior survival (p?<?0.01). FLAMSA-RIC followed by allogeneic HCT enables long-term disease-free survival in primary refractory or relapsed AML even in the elderly patient population.     

Granulocyte-Colony Stimulating Factor Reduces Cardiomyocyte Apoptosis and Ameliorates Diastolic Dysfunction in Otsuka Long-Evans Tokushima Fatty Rats

Background

In recent studies, granulocyte-colony stimulating factor (G-CSF) was shown to improve cardiac function in myocardial infarction and non-ischemic cardiomyopathies. The mechanisms of these beneficial effects of G-CSF in diabetic cardiomyopathy are not yet fully understood. Therefore, we investigated the mechanisms of action of G-CSF on diabetic cardiomyopathy in a rat model of type 2 diabetes.

Methods

Seventeen-week-old OLETF (Otsuka Long Evans Tokushima Fatty) diabetic rats and LETO (Long Evans Tokushima Otuska) rats were randomized to treatment with 5 days of G-CSF (100 μg/kg/day) or with saline. Cardiac function was evaluated by serial echocardiography performed before and 4 weeks after treatment. We measured expression of the G-CSF receptor (GCSFR) and Bcl-2, as well as the extent of apoptosis in the myocardium.

Results

G-CSF treatment significantly improved cardiac diastolic function in the serial echocardiography assessments. Expression of G-CSFR was down-regulated in the diabetic myocardium (0.03?±?0.12 % vs. 1?±?0.15 %, p?<?0.05), and its expression was stimulated by G-CSF treatment (0.03?±?0.12 % vs. 0.42?±?0.06 %, p?<?0.05). In addition, G-CSF treatment increased the expression of Bcl-2 in the diabetic myocardium (0.69?±?0.06 % vs. 0.26?±?0.11 %, p?<?0.05), consistent with the reduced cardiomyocyte apoptosis (9.38?±?0.67 % vs. 17.28?±?2.16 %, p?<?0.05).

Conclusions

Our results suggest that G-CSF might have a cardioprotective effect in diabetic cardiomyopathy through up-regulation of G-CSFR, attenuation of apoptosis by up-regulation of Bcl-2 expression, and glucose-lowering effect. Our findings support the therapeutic potential of G-CSF in diabetic cardiomyopathy.     

Hepatitis C viral load predicts tumor recurrence after curative resection of hepatocellular carcinoma regardless of the genotype of hepatitis C virus

Purpose

To clarify the prognostic impact of the hepatitis C virus (HCV) genotype after curative resection for hepatocellular carcinoma (HCC).

Methods

A total of 199 patients who underwent a curative hepatic resection for HCV-related HCC were reviewed. The clinical outcomes were compared between patients infected with HCV genotype 1b (n = 160) and those infected with other genotypes (n = 39).

Results

With a comparable median HCV viral load (6.0 vs. 5.8 log₁₀ IU/mL, p = 0.17), the 3-year recurrence-free survival (RFS) rates (25 vs. 20 %, p = 0.65) and the 5-year overall survival (OS) rates (72 vs. 65 %, p = 0.73) were similar between the two groups. A multivariate analysis confirmed that HCV viral load of +1.0 log₁₀ IU/mL [hazard ratio (HR), 1.48], major vascular invasion (HR, 3.20), recurrent tumor (HR, 1.77), and preoperative des-gamma carboxyprothrombin level >40 mAu/mL (HR, 1.64) were independent predictors of tumor recurrence, while the HCV genotype was not a significant risk factor. When the population was stratified according to the HCV viral load, a significant difference was observed in the RFS rate for both genotype 1b (p = 0.003) and the other genotypes (p = 0.037) at HCV viral load of 5.3 log₁₀ IU/mL.

Conclusions

The HCV genotype does not affect the surgical outcomes of patients with HCC. A lower HCV viral load is advantageous regardless of the HCV genotype.     

Prognostic significance of neutrophil/prealbumin ratio for intrahepatic cholangiocarcinoma undergoing curative resection

Background

This study aimed to clarify the prognostic significance of neutrophil/prealbumin ratio index (NPRI) for overall survival (OS) and recurrence free survival (RFS) of ICC after curative surgery.

Heat shock protein 22 overexpression is associated with the progression and prognosis in gastric cancer

Purpose

The heat shock protein 22 (HSP22) is associated with tumor proliferation and protects tumor cell from apoptosis in many malignancies. However, the role of HSP22 in gastric cancer has not been thoroughly elucidated. The aim was to determine the relationship of HSP22 expression with clinicopathological parameters and prognosis in gastric cancer and estimate the alteration of HSP22 expression after neoadjuvant chemotherapy.

Methods

HSP22 and matrix metallopeptidase 9 (MMP-9) antigen expressions were evaluated by immunohistochemistry in 129 gastric carcinoma samples. Univariate and multivariate analyses were performed to determine the association between HSP22 expression and prognosis. The response of HSP22 was assessed in 47 patients who received neoadjuvant chemotherapy.

Results

HSP22 protein expression was significantly associated with tumor size, depth invasion, lymph node metastasis and stage of disease (all P < 0.05). In univariate and multivariate analyses, HSP22 was an independent prognostic factor for both overall survival (OS) and recurrence-free survival (RFS) (P = 0.003 and P = 0.004, respectively). Furthermore, HSP22 overexpression was associated with a poor prognosis in all patients and in patients subgroups stratified by tumor size, depth invasion and lymph node metastasis. In addition, HSP22 was significantly correlated with MMP-9 among 129 gastric cancer tissues (P < 0.001). Patients who had MMP-9 overexpression had poor OS and shorter RFS. Moreover, the alteration of HSP22 was not comparable in 47 patients who underwent neoadjuvant chemotherapy.

Conclusions

HSP22 plays an important role on tumor aggressiveness and prognosis and may act as a promising target for prognostic prediction.