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.

     

Tumor necrosis could reflect advanced disease status in patients with diffuse large B cell lymphoma treated with R-CHOP therapy

Tumor necrosis (TN) can lower responsiveness to chemotherapy and confer basic resistance to anti-cancer therapy. We investigated the association of TN with poor clinical features and outcome in diffuse large B cell lymphoma (DLBCL). We examined the presence or absence of TN in 476 DLBCL patients of who received rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) therapy. Eighty-nine (18.7 %) patients had TN at diagnosis. Patients with TN had a progression-free survival (PFS) and overall survival (OS) of 39.3 and 46.7 %, whereas patients without TN had a PFS and OS of 73.4 and 82.6 %. Adverse clinical factors of poor Eastern Cooperative Oncology Group performance status ≥ grade 2 (p?=?0.005), elevated lactate dehydrogenase ratio >1 (p?<?0.001), advanced Ann Arbor stage (p?=?0.002), and bulky disease (p?=?0.026) were more prevalent in the TN group than the non-TN group. Cox regression model analysis revealed TN as an independent prognostic factor for PFS and OS in DLBCL (PFS, hazard ratio [HR]?=?1.967, 95 % confidence interval [CI]?=?1.399–2.765, p?<?0.001; OS, HR?=?2.445, 95 % CI?=?1.689–3.640, p?<?0.001). The results indicate that TN could reflect adverse clinical features and worse prognosis in DLBCL patients receiving R-CHOP therapy.     

Impact of distal embolization on myocardial perfusion and survival among patients undergoing primary angioplasty with glycoprotein IIb–IIIa inhibitors: insights from the EGYPT cooperation

Even though primary angioplasty is able to obtain TIMI 3 flow in the vast majority of STEMI patients, epicardial recanalization does not guarantee optimal myocardial perfusion, that remain suboptimal in a relatively large proportion of patients. Large interest has been focused in recent years on the role of distal embolization as major determinant of impaired reperfusion. The aim of the current study was to investigate in a large cohort of STEMI undergoing primary angioplasty with Gp IIb–IIIa inhibitors the impact of distal embolization on myocardial perfusion and survival. Our population is represented by patients undergoing primary angioplasty for STEMI included in the EGYPT database. Distal embolization was defined as an abrupt ‘‘cutoff’’ in the main vessel or one of the coronary branches of the infarct-related artery, distal to the angioplasty site. Myocardial perfusion was evaluated by angiography or ST-segment resolution, whereas infarct size was estimated by using peak CK and CK-MB. Follow-up data were collected between 30 days and 1 year after primary angioplasty. Data on distal embolization were available in a total of 1182 patients (71% of total population). Distal embolization was observed in 132 patients (11.1%). Patients with distal embolization were older (P < 0.001), with larger prevalence of diabetes (P = 0.01), previous MI (P = 0.048) and advanced Killip class at presentation (P = 0.018), abciximab administration (P < 0.001), with a lower prevalence of smoking (P = 0.04). Patients with distal embolization had more often poor preprocedural recanalization (P = 0.061), less often postprocedural TIMI 3 flow (P < 0.001), postprocedural MBG 2–3 (P < 0.001), complete ST-segment resolution (P = 0.021) and larger infarct size (CK-MB: 328 ± 356 U/l vs. 259 ± 226 U/l, P = 0.012). The impact of distal embolization on myocardial perfusion was confirmed after correction for baseline confounding factors as evaluated by MBG 2–3 (adjusted OR [95% CI] = 3.14 [2.06–4.77], P < 0.0001) but not complete ST-segment resolution (adjusted OR [95% CI] = 1.23 [0.84–1.92], P = 0.26). At 208 ± 160 days follow-up, distal embolization was associated with a significantly higher mortality (9.2% vs. 2.7%, HR [95% CI] = 3.41 [1.73–6.71], P < 0.0001), that was confirmed after correction for baseline confounding factors (adjusted HR [95% CI] = 2.23 [1.1–4.7], P = 0.026). This study showed among STEMI patients treated with Gp IIb–IIIa inhibitors, that distal embolization is independently associated with impaired myocardial perfusion and survival.     

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

Purpose

The present study aimed to explore the survival outcomes of patients with colorectal cancer (CRC) aged 35 years and younger.

Methods

This retrospective cohort study included a total of 995 patients with CRC treated between January 2003 and September 2011. The patients were assorted into the young (aged 18–35 years) and older (aged 36–75 years) groups. The clinical characteristics and survival outcomes of the patients in the young group were compared with those of the patients in the older group for evaluation.

Results

Compared with the older group, a significantly higher number of patients in the young group had right-sided colon cancer (30.9 vs. 19.6%, P = 0.026), high histologic grade tumor (14.7 vs. 6.4%, P = 0.021), and stage III disease (50.0 vs. 35.5%, P = 0.016). In stage III disease, compared with the older group, the patients in the young group had worse survival outcome in terms of 5-year overall survival (OS, P = 0.007), cancer-specific survival (CSS, P = 0.010), and disease-free survival (DFS, P = 0.039). Multivariate analysis revealed that age ≤35 years was an independent risk factor in terms of 5-year OS (hazard ratio [HR] = 1.68; 95% confidence interval [CI]: 1.12–2.54; P = 0.012), CSS (HR = 1.74; 95% CI: 1.15–2.65; P = 0.009), and DFS (HR = 1.58; 95% CI: 1.06–2.35; P = 0.024).

Conclusions

The young patients with CRC aged 35 years and younger had worse prognosis compared with older patients, especially for stage III disease.

     

Surgical Resection for Pulmonary Carcinoid: Long-Term Results of Multicentric Study—The Importance of Pathological N Status,More Than We Thought

Background

Histological subdivision into typical (TC) and atypical (AC) is crucial for treatment and prognosis of lung carcinoids but can be also very challenging, even for experts. In this study, we aimed to strengthen or reduce the prognostic value of several pathological, clinical, or per-operative factors some of which are still controversial.

Methods

We retrospectively reviewed clinical records related to 195 patients affected by TC (159) or AC (36) surgically treated between 2000 and 2014, in three different centers. Survival and subtypes comparison analyses were performed to identify potential prognostic factors.

Results

TCs showed a lower rate of nodal involvement than ACs (N0 = 94.9%; N1 = 1.9%; N2 = 3.2% in typical and N0 = 63.8%; N1 = 16.6%; N2 = 19.4% in atypical carcinoids, respectively, p < 0.0001). Long-term oncological results of resected carcinoids were significantly better in TCs than ACs with higher 5- and 10-year overall survival rates (97.2 and 88.2% vs. 77.9 and 68.2%, respectively; p = 0.001) and disease-free survival rates (98.2 and 90.3% in typical and 80.8 and 70.7% atypical carcinoids, respectively; p = 0.001). Risk factors analysis revealed that AC subtype [HR 4.33 (95% CI 1.72–8.03), p = 0.002], pathological nodal involvement [HR 3.05 (95% CI 1.77–5.26), p < 0.0001], and higher SUV_max [HR 4.33 (95% CI 1.03–7.18), p = 0.002] were independently and pejoratively associated with overall survival. Factors associated with a higher risk of recurrence were AC subtype [HR 6.13 (95% CI 1.13–18.86), p = 0.002]; nodal involvement [HR 5.48 (95% CI 2.85–10.51), p < 0.0001]; higher Ki67 expression level [HR 1.09 (95% CI 1.01–1.20), p = 0.047]; and SUV_max [HR 1.83 (95% CI 1.04–3.23), p = 0.035].

Conclusion

Surgery for lung carcinoids allows satisfactory oncological results which mainly depend on carcinoid subtype dichotomy, pathological nodal status, and SUV_max.

     

Final analysis of the randomised PEAK trial: overall survival and tumour responses during first-line treatment with mFOLFOX6 plus either panitumumab or bevacizumab in patients with metastatic colorectal carcinoma

Purpose

To report planned final overall (OS) and progression-free survival (PFS) analyses from the phase II PEAK trial (NCT00819780).

Methods

Patients with previously untreated, KRAS exon 2 wild-type (WT) metastatic colorectal cancer (mCRC) were randomised to mFOLFOX6 plus panitumumab or bevacizumab. The primary endpoint was PFS; secondary endpoints included OS, objective response rate, duration of response (DoR), time to response, resection and safety. Treatment effect by tumour RAS status was a prespecified objective. Exploratory analyses included early tumour shrinkage (ETS) and depth of response (DpR).

Results

One hundred seventy patients had RAS WT and 156 had RAS WT/BRAF WT mCRC. Median PFS was longer for panitumumab versus bevacizumab in the RAS WT (12.8 vs 10.1 months; hazard ratio (HR) = 0.68 [95% confidence intervals (CI) = 0.48–0.96]; p = 0.029) and RAS WT/BRAF WT (13.1 vs 10.1 months; HR = 0.61 [95% CI = 0.42–0.88]; p = 0.0075) populations. Median OS (68% OS events) for panitumumab versus bevacizumab was 36.9 versus 28.9 months (HR = 0.76 [95% CI = 0.53–1.11]; p = 0.15) and 41.3 versus 28.9 months (HR = 0.70 [95% CI = 0.48–1.04]; p = 0.08), in the RAS WT and RAS WT/BRAF WT populations, respectively. Median DoR (11.4 vs 9.0 months; HR = 0.59 [95% CI = 0.39–0.88]; p = 0.011) and DpR (65.0 vs 46.3%; p = 0.0018) were improved in the panitumumab group. More panitumumab patients experienced ≥30% ETS at week 8 (64 vs 45%; p = 0.052); ETS was associated with improved PFS/OS. No new safety signals occurred.

Conclusions

First-line panitumumab + mFOLFOX6 increases PFS versus bevacizumab + mFOLFOX6 in patients with RAS WT mCRC.

     

Preoperative patient-related factors associated with prognosis after esophagectomy for esophageal cancer

Background

To investigate the impact of the preoperative patient-related factors on survival after esophagectomy in patients with esophageal cancer.

Methods

We retrospectively reviewed 140 patients with esophageal cancer who underwent esophagectomy. Preoperative comorbidities, nutritional and inflammation status including the neutrophil to lymphocyte ratio and Glasgow prognostic score (GPS), and their pathological findings were analyzed to assess their relationships with prognosis.

Results

Univariate analysis demonstrated that a history of cardiovascular disease (CVD), a GPS of 1 or 2, lack of neo-adjuvant chemotherapy (NAC), no thoracoscopic esophagectomy, blood loss volume ≥255 ml, the number of lymph node metastasis (LNM) ≥2, lymphatic invasion, venous invasion, and residual cancer were associated with poor survival. Multivariate analysis revealed that a history of CVD [hazard ratio (HR) 2.129; 95% confidence interval (CI) 1.327–4.226; P = 0.041], a GPS of 1 or 2 (HR 3.232; 95% CI 1.516–6.437; P = 0.003), LNM ≥2 (HR 3.133; 95% CI 1.355–7.760; P = 0.007), and pathological residual cancer (HR 2.429; 95% CI 1.050–5.105; P = 0.039) were independently associated with poor survival, and NAC was associate with better survival (HR 0.289; 95% CI 0.118–0.667; P = 0.003).

Conclusions

Preoperative patient-related factors including a history of CVD and a GPS of 1 or 2 were predictors of poor prognosis after esophagectomy in patients with esophageal cancer.

     

Autologous stem cell transplantation in first remission is associated with better progression-free survival in multiple myeloma

Autologous stem cell transplant (ASCT) is standard consolidation therapy in management of multiple myeloma (MM) patients. We reviewed records of all consecutive MM patients who underwent ASCT with high-dose melphalan at our center from year 2002 to 2016. A total of 141 ASCT were conducted (90 males and 51 females) with median age of 55 years (23–68 years). Median time from diagnosis to transplant was 7 months (3–79), with majority of patients underwent transplant in first remission, while 17 (12%) patients received transplant beyond first remission. Eighty-three percent patients obtained CR/VGPR post-ASCT. Transplant-related mortality was 2.1%. At a median follow up of 54 months, mean overall survival (OS) and progression-free survival (PFS) group were 128.3 months (95% C.I. 111.9–144.7 months) and 73.8 months (95% C.I. 57.7–89.9 months), respectively. On univariate analysis, OS was adversely affected by renal insufficiency (p?=?0.024), while OS was better with CR/VGPR post-ASCT (p?<?0.001) and lenalidomide maintenance therapy (p?=?0.009). PFS was affected by CR/VGPR pre-ASCT (p?=?0.021), CR/VGPR post-ASCT (p?<?0.001), and transplant in first remission (p?=?0.034). On multivariate analysis, lenalidomide maintenance (versus thalidomide) (p?=?0.007) and CR/VGPR response post-ASCT (p?=?0.0003) were found to be predictors for better OS and CR/VGPR response at transplant for better PFS (p?=?0.038). Transplant in first remission versus beyond first remission showed a trend for better PFS (p?=?0.073). Conclusion: Majority of patients obtained CR/VGPR post-ASCT. Longer PFS was seen with patients who were transplanted in first remission.     

Impact of front line relative dose intensity for methotrexate and comorbidities in immunocompetent elderly patients with primary central nervous system lymphoma

Primary central nervous system lymphomas (PCNSL) are non-Hodgkin lymphomas strictly localized to the CNS, occurring mainly in elderly patients with comorbidities. Current treatment in fit patients relies on high-dose methotrexate and high-dose cytarabine. The aim of this study was to evaluate the efficacy and feasibility of this treatment in elderly patients and to assess potential prognostic factors associated with survival. We conducted a retrospective study in two centers between January 2008 and September 2015 including 35 elderly immunocompetent patients who received first-line treatment with high-dose methotrexate. With a median follow-up of 19.8 months (range: 1.7–73.4 months), median overall survival (OS) was 39.5 months (95% confidence interval (95% CI): 18.3–60.7) and median progression-free survival (PFS) was 25.8 months (95% CI: 5.2–46.4). In univariate analysis, administration of high-dose cytarabine and achieving a relative dose intensity for methotrexate >?75% were associated with increased OS (p?=?0.006 and p?=?0.003, respectively) and PFS (p?=?0.003 and p?=?0.04, respectively) whereas comorbidities, defined by a CIRS-G score ≥?8, were associated with decreased OS and PFS (p?=?0.02 and p?=?0.04, respectively). A high MSKCC score was associated with decreased OS (p?=?0.02). In multivariate analysis, administration of high-dose cytarabine was associated with increased OS and PFS (p?=?0.02 and p?=?0.007, respectively). Comorbidities and relative dose intensity for methotrexate are important for the prognosis of elderly patients with PCNSL. These results must be confirmed in prospective trials.     

The gentamicin-collagen implant and the risk of distant metastases of rectal cancer following short-course radiotherapy and curative resection: the long-term outcomes of a randomized study

Purpose

A previous randomized study conducted by our group showed that application of gentamicin-collagen implant (GCI) into the pelvic cavity after total mesorectal excision (TME) reduced the incidence of distant metastases. Therefore, we decided to conduct a confirmatory study.

Methods

Patients with rectal cancer were included in the study if they met the following criteria: adenocarcinoma of the rectum, preoperative short-term radiotherapy (5?×?5 Gy), and WHO performance score 0–1.

Results

One hundred seventy-six patients were randomly assigned either to an experimental group in which GCI was applied (n?=?81) or to a control group without GCI (n?=?81). Median follow-up was 80 months. Cumulative incidence of distant metastases at 5 years was higher in the control group compared to the experimental group: 23.5 vs 8.6% (HR 2.4 [95% CI 1.1–5.5], P?= 0.005). Overall survival (OS), disease-free survival (DFS), and cancer-specific survival (CSS) did not differ between the experimental group and the control group: HR 0.95 [95% CI 0.55–1.70], P?= 0.864; HR 0.85 [95% CI 0.50–1.45], P?= 0.548, and HR 0.5 [95%CI 0.22–1.22], P?= 0.093, respectively. The predefined by the protocol subgroup analysis for yp stage III disease showed better DFS in the experimental group compared to the control group; HR 0.47 [95%CI 0.23–0.97], P?= 0.042).

Conclusions

The results confirmed our previous finding that GCI applied in the pelvis significantly reduced the rate of distant metastases in patients after radical rectal cancer resection.

     

Fostamatinib,an oral spleen tyrosine kinase inhibitor,in the treatment of rheumatoid arthritis: a meta-analysis of randomized controlled trials

Fostamatinib is a selective inhibitor of spleen tyrosine kinase which has a role in the pathogenesis of RA. Multiple RCTs have been performed to study the effects of fostamatinib. The objective of this study was to perform a meta-analysis to analyze the efficacy and safety of fostamatinib in the management of RA. We searched PubMed, EMBASE and Cochrane CENTRAL through 11/9/15. Random effect model was used to estimate odds ratio (OR) and 95 % confidence interval. We measured outcomes with efficacy analysis using ACR20/50/70 response criteria and safety with adverse events. Five studies were included in the meta-analysis with total of 2105 patients including 1419 in fostamatinib group and 686 in placebo. Fostamatinib was effective in achieving ACR20, ACR50 and ACR70 responses compared to placebo (48 vs. 32.8 %, OR 1.86, 95 % CI 1.32–2.62, P = 0.0004, I ² 63 %; 26.4 vs. 12.5 %, OR 2.50, 95 % CI 1.93–3.23, P < 0.00001, I ² 0 % and 12.7 vs. 4.4 %, OR 3.00, 95 % CI 1.99–4.51, P < 0.00001, I ² 0 %, respectively). Response to fostamatinib was rapid and significant effect on ACR20 response was seen by week 1 (OR 3.70, 95 % CI 2.33–5.87, P < 0.00001, I ² 42 %). Safety analysis showed an increased risk of infection (OR 1.59, 95 % CI 1.2–2.11; P = 0.001; I ² 0 %), diarrhea (OR 3.54; 95 % CI 2.43–5.16; P < 0.00001; I ² 2 %), hypertension (OR 2.55, 95 % CI 1.54–4.22, P = 0.0003; I ² 42 %) and neutropenia (OR 5.68, 95 % CI 1.97–16.42, P = 0.001, I ² 35 %) and showed a trend toward the increase in ALT ≥3 times ULN (OR 1.76, 95 % CI 0.99–3.13; P = 0.05; I ² 0 %). This meta-analysis concludes that fostamatinib has moderate effect in the treatment of RA with mostly mild-to-moderate adverse events and dose-dependent, transient neutropenia and hypertransaminasemia.     

CONUT: a novel independent predictive score for colorectal cancer patients undergoing potentially curative resection

Background

Controlling nutritional status (CONUT) score, calculated from serum albumin and total cholesterol concentrations and total lymphocyte count, is reportedly valuable for nutritional assessment. This study investigated whether CONUT score was predictive of outcomes in colorectal cancer (CRC) patients undergoing surgical resection.

Methods

Preoperative CONUT scores were retrospectively evaluated in 417 CRC patients who underwent potentially curative resection at Kumamoto University Hospital from March 2005 to August 2014. Patients were divided into four groups based on preoperative CONUT scores: normal, light, moderate, and severe. The associations of CONUT score with clinicopathological factors, patient survival, and postoperative complications were examined.

Results

CONUT score correlated significantly with age (P < 0.001), body mass index (P = 0.005), carcinoembryonic antigen (P = 0.002), and carbohydrate antigen 19-9 (P = 0.005) concentrations. Overall survival (OS) rate was significantly lower in patients with moderate/severe than light or normal CONUT scores. CONUT score was independently prognostic of OS [moderate/severe vs. normal, hazard ratio = 5.92, 95 % confidence interval (CI) 2.30–14.92; P < 0.001)]. Patients with moderate/severe CONUT scores were at greater risk for complications, especially for severe complications. Multivariate analysis showed that CONUT score was independently predictive of severe complications (moderate/severe vs. normal, odds ratio = 4.51, 95 % CI 1.89–10.74; P < 0.001).

Conclusions

CONUT score may predict survival and postoperative severe complications in CRC patients undergoing potentially curative resection. Management of CRC patients may need consideration of host nutritional status.

     

Association of bone marrow fibrosis with inferior survival outcomes in chronic myelomonocytic leukemia

The impact of bone marrow fibrosis grade on the prognosis of patients with chronic myelomonocytic leukemia (CMML) remains controversial. Therefore, we examined the records of 82 patients diagnosed with CMML at our institution and summarized baseline characteristics and molecular profiles by subgroups of absent or mild (grades 0/1) and moderate (grade 2) fibrosis. Cox proportional hazards models were constructed to assess the prognostic significance of fibrosis grade. Grade 2 fibrosis was identified in 63 patients (76.8%), grade 1 in 16 patients (19.5%), and grade 0 in 3 patients (3.7%). Grade 2 fibrosis was associated with reduced hemoglobin levels (median 9.75 vs 11.0 g/dL in grade 0/1; p?=?0.04) and increased percentages of ringed sideroblasts (7.5 vs 0%; p?=?0.008). In multivariable analysis, grade 2 fibrosis was an independent predictor of poor overall survival (OS; 95% CI 1.32–6.35; HR 2.90; p?=?0.008), but not event-free survival (EFS; 95% CI 0.62–2.67; HR 1.28; p?=?0.50). Absolute neutrophil count (ANC) was found to impact OS (95% CI 1.01–1.09; HR 1.05; p?=?0.009), while both ANC (95% CI 1.00–1.07; HR 1.04; p?=?0.04) and peripheral blood blast percentage (95% CI 1.02–1.32; HR 1.16; p?=?0.02) impacted EFS. These results implicate fibrosis grade is an important indicator of prognosis, with high-grade fibrosis predicting inferior survival. Given the prevalence of marrow fibrosis in CMML, fibrosis grading should be incorporated into prognostic assessment and therapeutic decision-making.     

Open surgery (OS) versus endovascular aneurysm repair (EVAR) for hemodynamically stable and unstable ruptured abdominal aortic aneurysm (rAAA)

Endovascular aneurysm repair (EVAR) is an alternative treatment for ruptured abdominal aortic aneurysms (rAAA) in hemodynamically (hd) stable patients. Treatment for patients with hd-unstable rAAA remains controversial. The aim of this study was to compare the outcomes of EVAR and open surgery (OS) in hd-stable and hd-unstable rAAA patients using meta-analysis. The first part of this study included 48 articles that reported the treatment outcomes of rAAA managed with EVAR (n = 9610) and OS (n = 93867). The second part, which is the focus of this study, included 5 out of 48 articles, which further reported treatment results in hd-stable (n = 198) and hd-unstable (n = 185) patients. When heterogeneity among the groups was observed, a random-effects model was used to calculate the adjusted odds ratios (OR) or in cases of non-heterogeneity, a fixed-effects model analysis was employed. In the first part of this study, the in-hospital mortality rate was found to be lower in the EVAR group than in the OS group (29.9 vs 40.8 %; OR 0.59; 95 % CI 0.52–0.66; P < 0.01). In the second part of this study, 383 patients from 5 articles were included: 152 patients were treated by EVAR, and 231 were treated by OS. The total mortality was 147/383 (38.4 %), while the mortality of the EVAR group and the OS group was 25.7 % (39/152) and 46.8 % (108/231), respectively. In the hd-stable group, the in-hospital mortality after EVAR was significantly lower than that after OS [18.9 % (18/95) vs 28.2 % (29/103); OR 0.47; 95 % CI 0.22–0.97; P = 0.04]. For the hd-unstable rAAA patients, the in-hospital mortality after EVAR was significantly lower than that after OS [36.8 % (21/57) vs 61.7 % (79/128); OR 0.40; 95 % CI 0.20–0.79; P < 0.01]. This study indicated that compared with OS, EVAR in hd-unstable rAAA patients is associated with improved outcomes. Available publications are currently limited; thus, the best treatment strategy for this subgroup of patients remains unclear. Further clinical studies are needed to provide more detailed data, such as the shock index and long-term results.     

Hyperfibrinogenemia is a poor prognostic factor in diffuse large B cell lymphoma

Diffuse large B cell lymphoma (DLBCL) is the most common subtype of non-Hodgkin lymphomas worldwide. Previous studies indicated that hyperfibrinogenemia was a poor predictor in various tumors. The purpose of our study was to evaluate the prognostic effect of hyperfibrinogenemia in DLBCL. Data of 228 patients, who were diagnosed with DLBCL in our hospital between May 2009 and February 2016, were analyzed retrospectively. The Kaplan-Meier method and Cox regression were performed to find prognostic factors associated with progression-free survival (PFS) and overall survival (OS). Receiver operator characteristic (ROC) curve and the areas under the curve were used to evaluate the predictive accuracy of predictors. Comparison of characters between groups indicated that patients with high National Comprehensive Cancer Network-International Prognostic Index (NCCN-IPI) score (4–8) and advanced stage (III–IV) were more likely to suffer from hyperfibrinogenemia. The Kaplan-Meier method revealed that patients with hyperfibrinogenemia showed inferior PFS (P?<?0.001) and OS (P?<?0.001) than those without hyperfibrinogenemia. Multivariate analysis showed that hyperfibrinogenemia was an independent prognostic factor associated with poor outcomes (HR?=?1.90, 95% CI: 1.15–3.16 for PFS, P?=?0.013; HR?=?2.65, 95% CI: 1.46–4.79 for OS, P?=?0.001). We combined hyperfibrinogenemia and NCCN-IPI to build a new prognostic index (NPI). The NPI was demonstrated to have a superior predictive effect on prognosis (P?=?0.0194 for PFS, P?=?0.0034 for OS). Hyperfibrinogenemia was demonstrated to be able to predict poor outcome in DLBCL, especially for patients with advanced stage and high NCCN-IPI score. Adding hyperfibrinogenemia to NCCN-IPI could significantly improve the predictive effect of NCCN-IPI.     

Tumor characteristics associated with malignant large bowel obstruction in stage IV colorectal cancer patients undergoing chemotherapy

Purpose

Little is known about predictable clinical factors associated with the occurrence of malignant large bowel obstruction (MLBO) in incurable stage IV colorectal cancer (CRC) patients undergoing medical treatment. This study investigates the clinical characteristics associated with MLBO that occurred while patients with stage IV CRC were receiving chemotherapy.

Methods

A total of 216 patients who were diagnosed with stage IV CRC without bowel obstruction and who received chemotherapy between May 2005 and June 2012 were retrospectively included in this study. Patients were divided into an “obstruction group” and a “non-obstruction group” based on whether they did or did not develop MLBO during chemotherapy or follow-up, respectively. The initial endoscopic findings and clinical information were retrospectively reviewed and compared between the two groups.

Results

Forty-six patients (21.3 %) developed MLBO during the treatment or follow-up periods. The mean duration between diagnosis and MLBO was 9.8 ± 9.3 months. After adjusting for clinically relevant factors, MLBO development was independently associated with the following factors: higher initial tumor-occupying circumference (HR 1.030 [95 % CI, 1.012–1.049], P = 0.001), longer initial horizontal tumor width (HR 1.035 [95 % CI, 1.011–1.059], P = 0.004), primary tumor location at a turning point in the colon (HR 2.404 [95 % CI, 1.185–4.877], P = 0.015), and the presence of primary tumor ulceration at presentation (HR 3.767 [95 % CI, 1.882–7.538], P < 0.001). MLBO development was not associated with tumor response to chemotherapy.

Conclusion

In patients with stage IV CRC, MLBO development during chemotherapy treatment is associated with tumor ulceration, location, circumference, and width at diagnosis.

     

Non-driver mutations in patients with <Emphasis Type="Italic">JAK2</Emphasis>V617F-mutated polycythemia vera or essential thrombocythemia with long-term molecular follow-up

JAK2V617F monitoring and NGS of non-driver genes was performed in 100 patients with polycythemia vera (PV) or essential thrombocythemia (ET) with long molecular follow-up. Patients who did not progress to myelofibrosis (MF) or acute myeloid leukemia (AML) after more than 10 years (n?=?50) showed a low frequency of mutations at first sample (18%) and an incidence rate of 1.7 new mutations?×?100 person-years. Mutations were detected at first sample in 83% of PV/ET patients who later progressed to AML (n?=?12) with these patients having a rate of 25.6 mutations?×?100 person-years. Presence of mutations at diagnosis was the unique risk factor for acquiring a new genetic event (HR 2.7, 95% CI 1.1–6.8, p?=?0.03) after correction for age, PV diagnosis, and total duration of hydroxyurea (HU) exposure. Patients with additional mutation at first sample showed a higher probability of developing cytopenia under HU therapy and a higher risk of AML (HR 12.2, 95% CI 2.6–57.1, p?=?0.001) with mutations in ASXL1 (p?<?0.0001), TP53 (p?=?0.01), SRSF2 (p?<?0.0001), IDH1/2 (p?<?0.0001), and RUNX1 (p?<?0.0001) being associated with a higher probability of AML. Myelofibrotic transformation was more frequent in patients with additional mutations, especially in SF3B1 (p?=?0.02) and IDH1/2 (p?<?0.0001) although a persistently high or a progressive increase of the JAK2V617F allele burden while receiving cytoreduction was the strongest predictor of MF transformation (HR 10.8, 95% CI 2.4–49.1, p?=?0.002). In conclusion, NGS may be useful to identify a minority of PV and ET patients with high genetic instability and increased risk of AML transformation.     

The prognostic value of signet ring cell histology in stage I/II colon cancer—a population-based,propensity score-matched analysis

Background

Previous research associated signet ring cell histology in colon cancer patients with poor survival outcomes. The aim of this study was to analyze the prognostic significance of signet ring cell histology on overall and cancer-specific survival in patients with localized colon cancer.

Methods

Stage I and II colon cancer patients treated with surgical resection between 2004 and 2015 were identified in the Surveillance, Epidemiology, and End Results (SEER) database. Overall survival (OS) and cancer-specific survival (CSS) were assessed using risk-adjusted Cox proportional hazards regression models and propensity score methods.

Results

Eighty-eight thousand nine hundred fifty-eight stage I–II colon cancer patients were identified. Overall, 446 (0.5%) showed signet ring cell histology. In unadjusted analyses, the 5-year OS and CSS rates of patients with signet ring cell histology were 65.8 and 83.1%, respectively, compared with 74.3 and 88.7% in patients with non-signet ring cell adenocarcinoma (p values: OS, p?<?0.001; CSS, p?<?0.001). Neither in risk-adjusted Cox proportional hazard regression analysis (OS: hazard ratio (HR), 0.96 (95% CI, 0.82–1.12%) p?=?0.616; CSS: HR, 1.01 (95% CI, 0.79–1.28%) p?=?0.946) nor with propensity score matching (OS: HR, 0.96 (95% CI, 0.82–1.14%) p?=?0.669 and CSS: HR: 1.09 (95% CI: 0.84–1.40%) p?=?0.529), a survival disadvantage was found for signet ring cell histology.

Conclusion

This is the first propensity score-adjusted population-based investigation on exclusively stage I and II colon cancer patients providing compelling evidence that signet ring cell histology does not negatively impact survival in stage I and II colon cancer after risk-adjusting for known prognostic factors. Therefore, standard treatment strategies can be applied in these patients.

     

Paced QRS duration and myocardial scar amount: predictors of long-term outcome of right ventricular apical pacing

Long-term right ventricular apical pacing (RVAP) is reportedly associated with heart failure (HF) development. However, the predictors of pacing-induced HF (PHF) remained unclear. We retrospectively enrolled 234 patients without structural heart disease who underwent a permanent pacemaker implantation with RVAP between 1982 and 2004. RVAP-induced HF was defined as left ventricular ejection fraction decrease >5 % with HF symptom without other HF development etiology. The QRS duration of a paced beat (pQRSd) and myocardial scar score were analyzed from each patient’s 12-lead ECG. During a mean 15.6 years (range 3.3–30.0 years), 48 patients (20.5 %) patients developed RVAP-induced HF. The PHF group patients had a longer pQRSd (192.4 ± 13.5 vs. 175.7 ± 14.7 ms in non-PHF patients, p < 0.001) and a higher myocardial scar score (5.2 ± 1.9 vs. 2.7 ± 1.9, respectively p < 0.001). In multivariate Cox regression analysis, old age at implantation [Hazard ratio (HR) 1.62, 95 % confidential interval (CI) 1.22–2.16, p = 0.001], a longer pQRSd (HR 1.54, 95 % CI 1.15–2.05, p = 0.003), a higher myocardial scar score (HR 1.23, 95 % CI 1.03–1.49, p = 0.037), and a higher percentage of ventricular pacing (HR 1.31, 95 % CI 1.01–1.49, p = 0.010) were independent predictors of PHF. Based on the results of the receiver-operating characteristic (ROC) curve, the pQRSd cutoff was 185 ms (AUC 0.79, sensitivity 66.7 %, specificity 76.3 %) and myocardial scar score cutoff value was 4 (AUC 0.81, sensitivity 81.3 %, specificity 66.1 %). The pQRSd was positively correlated with scar score (r = 0.70, p < 0.001). pQRSd ≥185 ms and/or myocardial scar score ≥4 might be independent long-term prognostic markers of PHF.     

Comorbidities,repeated hospitalizations,and age ≥ 80 years as indicators of anemia development in the older population

Anemia represents a common condition among the elderly; however, its prevalence and causes are not well known. This retrospective analysis was performed on 981 patients aged ≥?60 in Poland over 2013–2014. The prevalence of anemia was 17.2% and increased with age. The predominant causes of anemia were the following: anemia of chronic disease (33.1%), unexplained anemia (28.4%), deficiency anemia (22.5%, including iron deficiency 13%), and chemo-/radiotherapy-induced anemia (8.9%). In the multivariate logistic regression model, factors increasing the risk of anemia were the following: age?≥?80 years (OR 2.29; 95%CI 1.19–4.42; P?=?0.013), the number of comorbidities (two diseases OR 2.85; 95%CI 1.12–7.30; P?=?0.029, three diseases OR 6.28; 95%CI 2.22–17.76; P?=?0.001, four diseases OR 4.64; 95%CI 1.27–17.01; P?=?0.021), and hospitalizations (OR 1.34; 95%CI 1.13–1.58; P?=?0.001). After a 2-year follow-up, the cumulative survival among patients without anemia in relation to the group with anemia was 90.76 vs. 78.08% (P?<?0.001). In the multivariate model, anemia (HR 3.33, 95%CI 1.43–7.74, P?=?0.005), heart failure (HR 2.94, 95%CI 1.33–6.50, P?=?0.008), and cancer (HR 3.31, 95%CI 1.47–7.49, P?<?0.004) were all significantly correlated with mortality. In patients ≥?60 years, the incidence of anemia increases with age, number of comorbidities, and frequency of hospitalizations and has an adverse impact on survival.