Neoadjuvant Imatinib in Locally Advanced Gastrointestinal Stromal Tumors (GIST): The EORTC STBSG Experience

Background

Preoperative imatinib therapy of locally advanced GIST may facilitate resection and decrease morbidity of the procedure.

Methods

We have pooled databases from 10 EORTC STBSG sarcoma centers and analyzed disease-free survival (DFS) and disease-specific survival (DSS) in 161 patients with locally advanced, nonmetastatic GISTs who received neoadjuvant imatinib. OS was calculated from start of imatinib therapy for locally advanced disease until death or last follow-up (FU) after resection of the GIST. DFS was calculated from date of resection to date of disease recurrence or last FU. Median FU time was 46 months.

Results

The primary tumor was located in the stomach (55 %), followed by rectum (20 %), duodenum (10 %), ileum/jejunum/other (11 %), and esophagus (3 %). The tumor resection after preoperative imatinib (median time on therapy, 40 weeks) was R0 in 83 %. Only two patients have demonstrated disease progression during neoadjuvant therapy. Five-year DSS/DFS rates were 95/65 %, respectively, median OS was 104 months, and median DFS was not reached. There were 56 % of patients who continued imatinib after resection. Thirty-seven GIST recurrences were diagnosed (only 5 local relapses). The most common mutations affected exon 11 KIT (65 %). Poorer DFS was related to primary tumor location in small bowel and lack of postoperative therapy with imatinib.

Conclusions

Our analysis comprising the largest group of GIST patients treated with neoadjuvant imatinib in routine practice indicates excellent long-term results of combined therapy in locally advanced GISTs.     

Partial laryngectomy for naïve pT3N0 laryngeal cancer: Systematic review on oncological outcomes

The first aim was to define the oncologic outcomes of open partial laryngectomy (OPL) in naïve pT3 laryngeal cancer. The second aim was to analyze the outcomes after OPL versus total laryngectomy (TL). A literature search was conducted in three databases (MEDLINE, EMBASE, and Cochrane Library) until January 2022. In 805 patients treated with OPL, 5-year OS, DSS, DFS and LFS were 80.5% (95% CI 70.6–87.6), 83.4% (95% CI 75.7–89), 77.4% (95% CI 66.3–85.7) and 77.9% (95% CI 68.7–85), respectively. Three articles compared TL versus OLP: 5-year OS, DSS and DFS risk difference were 0.100 (95% CI −0.092 to 0.291), 0.067 (95% CI −0.085 to 0.220) and 0.018 (95% CI −0.164 to 0.201) respectively. OPL for selected pT3 laryngeal cancer is able to guarantee a high percentage of oncological success. Accurate patient selection is of utmost importance to differentiate advanced disease amenable to conservative surgery.     

Long-term Outcomes After Bladder-preserving Tri-modality Therapy for Patients with Muscle-invasive Bladder Cancer: An Updated Analysis of the Massachusetts General Hospital Experience

Background

Tri-modality therapy (TMT) is a recognized treatment strategy for selected patients with muscle-invasive bladder cancer (MIBC).

Gastrointestinal stromal tumor (GIST)--medical rarities?

Although their overall incidence is low, GISTs are distinctive subgroup of gastrointestinal mesenchymal tumors which express CD117 or platelet derived growth factor receptor alpha (PDGFRA). Considered as rare digestive cancers, tumors like schwannomas, neurofibromas, gastrointestinal leiomiomas are now reclassified as GIST based on immunohistochemistry studies. GIST are more frequent in stomach (40-70%), small bowel (20-40%), colon (5-15%), meanwhile locations such as mesentery, omentum, retro peritoneum in less of 5%. 10 GIST patients were surgically managed during 2004-2009. 5 gastric and 5 small bowel GIST. Most with symptomatic disease: palpable tumor, abdominal pain, anemia, fatigue, superior digestive hemorrhage or occlusion. Imagistic diagnosis consisted of: barium swallow, abdominal sonography, CT and PET-CT. Confirmation was made by hystopathological exam and immunohistochemistry. All patients had more or less wide surgical resections. For some patients there was also a specific adjuvant treatment. All patients survived after surgery. The principle of surgery for GIST is RO resection of the tumor. Tumor rupture or R1 resection of the primary tumor has a negative impact on disease free survival. Some patients (great volume tumors, R1 or R2 resection) had adjuvant treatment. Imatinib mesylate and derivates showed a significant improvement of recurrence free survival with one condition: permanent treatment. Surgery remains the mainstay of treatment in patients with localized, resectable GIST. Recurrence rate of 17-21% and 5 years survival rate of 48-70%, even in resectable GIST, impose an adjuvant treatment.     

Is hepatic resection justified for non-colorectal non-neuroendocrine liver metastases? A systematic review and meta-analysis

BackgroundHepatic resection (HR) is effective for colorectal or neuroendocrine liver metastases. However, the role of HR for non-colorectal non-neuroendocrine liver metastases (NCNNLM) is unknown. This study aims to perform a systematic review and meta-analysis on long-term clinical outcomes after HR for NCNNLM.Methodselectronic search was performed to identify relevant publications using PRISMA and MOOSE guidelines. Primary outcomes were 3- and 5-year overall survival (OS) and disease-free survival (DFS). Secondary outcomes were post-operative morbidity and 30-day mortality.ResultsThere were 40 selected studies involving 5696 patients with NCNNLM undergone HR. Pooled data analyses showed that the 3- and 5-year OS were 40% (95% CI 0.35–0.46) and 32% (95% CI 0.29–0.36), whereas the 3- and 5-year DFS were 28% (95% CI 0.21–0.36) and 24% (95% CI 0.20–0.30), respectively. The postoperative morbidity rate was 28%, while the 30-day mortality was 2%. Subgroup analysis on HR for gastric cancer liver metastasis revealed the 3-year and 5-year OS of 39% and 25%, respectively.ConclusionsHR for NCNNLM may achieve satisfactory survival outcome in selected patients with low morbidities and mortalities. However, more concrete evidence from prospective study is warrant in future.     

Strictureplasty vs resection in small bowel Crohn''s disease: an evaluation of short-term outcomes and recurrence

AIM: To compare postoperative adverse events and recurrence following strictureplasty or bowel resection in patients with small bowel Crohn's disease (CD). METHOD: A literature search was performed to identify studies published between 1980 and 2006 comparing outcomes of CD patients undergoing either strictureplasty or bowel resection. Hazard ratios were calculated from Kaplan-Meier plots of cumulative recurrence data. Quality assessment of the included studies was performed. Random-effect meta-analytical techniques were employed. Sensitivity analysis and assessment of heterogeneity were performed. RESULTS: Seven studies comprising 688 CD patients (strictureplasty n = 311, 45%; resection with or without strictureplasty n = 377, 55%) were included. Patients undergoing strictureplasty alone had a lower risk of developing postoperative complications than those who underwent resection (OR = 0.60, 95% CI: 0.31-1.16) although this was not statistically significant (P = 0.13). Surgical recurrence after strictureplasty was more likely than after resection (OR = 1.36, 95% CI: 0.96-1.93, P = 0.09). Patients who had a resection had a significantly longer recurrence-free survival than those undergoing strictureplasty alone (HR = 1.08, 95% CI: 1.02-1.15, P = 0.01). CONCLUSION: Patients with small bowel CD undergoing strictureplasty alone may have fewer postoperative complications than those undergoing a concomitant bowel resection. However, surgical recurrence maybe higher following strictureplasty alone than with a concomitant small bowel resection. Patients may require appropriate preoperative counselling regarding the pros and cons of each operative technique.     

Prostate cancer with tertiary Gleason pattern 5 in prostate needle biopsy: clinicopathologic findings and disease progression

Significance of tertiary Gleason pattern/grade 5 on prostatectomy has been studied, but its significance on biopsy remains uncertain. Recent International Society of Urological Pathology consensus conference recommended that biopsy Gleason score is generated by adding tertiary grade 5 to the primary grade. We examined the preoperative clinical and biopsy findings in 53 patients with biopsy tertiary pattern 5 and 119 patients with primary/secondary biopsy pattern 5. Prostatectomy findings and prostate-specific antigen (PSA) failure rates were compared in surgically treated patients. Cause-specific and all-cause mortality were compared in patients treated nonsurgically. At presentation, age, gland volume, PSA, and biopsy cancer volume were similar in patients with tertiary and primary/secondary grade 5. Only 20 patients underwent prostatectomy and 152 were treated nonsurgically. Regardless of the pattern, patients treated by prostatectomy were younger (P=0.003), had lower PSA (P=0.001), and less cancer on biopsy (P=0.0001). Prostatectomy findings and PSA failures were not significantly different in patients with tertiary grade 5 versus primary/secondary pattern 5. In nonsurgically treated patients, patients with primary pattern 5 compared with those with tertiary pattern 5 had a significantly higher risk of all-cause mortality [adjusted hazard ratio (HR): 2.33, 95% confidence interval (CI): 1.10-4.90, P=0.026] and cause-specific mortality (adjusted HR: 7.52, 95% CI: 2.84-19.87, P<0.001). In contrast, patients with secondary pattern 5 had a comparable all-cause mortality risk to patients with tertiary pattern 5 (adjusted HR: 1.04, 95% CI: 0.47-2.32, P=0.92), but had a marginally higher risk of cause-specific mortality than patients with tertiary pattern 5 (adjusted HR: 2.13, 95% CI: 0.75-6.10, P=0.16).     

Liver resection versus liver transplantation for hepatocellular carcinoma within Milan criteria: a meta-analysis of 18,421 patients

BackgroundOutcomes after liver resection (LR) and liver transplantation (LT) for hepatocellular carcinoma (HCC) are heterogenous and may vary by region, over time periods and disease burden. We aimed to compare overall survival (OS) and disease-free survival (DFS) between LT versus LR for HCC within the Milan criteria.MethodsTwo authors independently searched Medline and Embase databases for studies comparing survival after LT and LR for patients with HCC meeting the Milan criteria. Meta-analyses and metaregression were conducted using random-effects models.ResultsWe screened 2,278 studies and included 35 studies with 18,421 patients. LR was associated with poorer OS [hazard ratio (HR) =1.44; 95% confidence interval (CI): 1.14–1.81; P<0.01] and DFS (HR =2.71; 95% CI: 2.23–3.28; P<0.01) compared to LT, with similar findings among intention-to-treat (ITT) studies. In uninodular disease, OS in LR was comparable to LT (P=0.13) but DFS remained poorer (HR =2.95; 95% CI: 2.30–3.79; P<0.01). By region, LR had poorer OS versus LT in North America and Europe (P≤0.01), but not Asia (P=0.25). LR had inferior survival versus LT in studies completed before 2010 (P=0.01), but not after 2010 (P=0.12). Cohorts that underwent enhanced surveillance had comparable OS after LT and LR (P=0.33), but cohorts undergoing usual surveillance had worse OS after LR (HR =1.95; 95% CI: 1.24–3.07; P<0.01).ConclusionsMortality after LR for HCC is nearly 50% higher compared to LT. Survival between LR and LT were similar in uninodular disease. The risk of recurrence after LR is threefold that of LT.     

Long-term prognostic factors after thrombolysis for lower limb ischemia

OBJECTIVE: This study assessed prognostic factors regarding long-term outcome for amputation and death among patients who underwent intra-arterial thrombolysis due to lower limb ischemia. METHODS: Consecutive patients with intra-arterial thrombolysis due to lower limb ischemia treated at the Department of Vascular Diseases, University Hospital of Malm?, between January 1, 2001, and December 31, 2005, were retrospectively reviewed. A multivariate Cox regression analysis was performed to determine independent predictors for amputation and death. RESULTS: A total of 220 intra-arterial thrombolysis procedures were performed in 195 patients (46% women). Median age was 73 years. Complete and partial thrombolysis was obtained in 41% and 38%, respectively. Hemorrhagic complications were documented in 33%, but only 6% (13 of 220) were interrupted. The amputation rate was 26% and mortality was 35% during a median follow-up of 32 months. Degree of lysis (hazard ratio [HR], 4.8; 95% confidence interval [CI], 2.4-9.7; P < .001), motor deficit at admission (HR, 4.0; 95% CI, 1.8-8.7; P = .001), foot ulcers (HR, 7.2; 95% CI, 2.2-23.4; P = .001), and ischemic heart disease (HR, 2.3; 95% CI, 1.1-4.8; P = .024) remained as independent factors associated with amputation. Renal insufficiency (HR, 2.4; 95% CI, 1.4-4.2; P = .003), ischemic heart disease (HR, 2.1; 95% CI, 1.2-3.7; P = .007), cerebrovascular disease (HR, 2.2; 95% CI, 1.2-4.0; P = .009), foot ulcers (HR, 3.2; 95% CI, 1.2-8.6; P = .019), and acute lower limb ischemia (HR, 3.4; 95% CI, 1.1-10.1; P = .028) remained as independent factors associated with mortality. CONCLUSIONS: Thrombolysis is successful, with few major complications in most patients with lower limb ischemia. Patients with ischemic heart disease and foot ulcers are at higher long-term risk for both amputation and death. A lesser degree of lysis and motor deficit were associated with higher amputation rates. The presence of such negative prognostic factors may help clinicians to deny further invasive vascular treatment. Renal insufficiency, cerebrovascular disease, and acute lower limb ischemia were associated with increased mortality.     

TP53 mutation is associated with a poor outcome for patients with hepatocellular carcinoma: evidence from a meta-analysis

Background

Various studies examined the relationship between p53 mutation with the clinical outcome in patients with hepatocellular carcinoma (HCC), but yielded conflicting results.

Methods

Electronic databases updated to July 2013 were searched to find relevant studies. A meta-analysis was conducted with eligible studies which quantitatively evaluated the relationship between p53 mutation and survival of patients with HCC. Survival data were aggregated and quantitatively analyzed.

Results

We performed a meta-analysis of 9 studies that evaluated the correlation between p53 mutation and survival in patients with HCC. Combined hazard ratios suggested that p53 mutation had an unfavorable impact on overall survival (OS) [hazard ratio (HR) =1.46, 95% confidence interval (CI): 1.15-1.76], and disease free survival (DFS) (HR =2.57, 95% CI: 1.46-3.68) in patients with HCC. The significant heterogeneity (P=0.035) was observed among 8 studies for OS, however no significant heterogeneity (P=0.597) was observed among 5 studies for DFS.

Conclusions

p53 mutation indicates a poor prognosis for patients with hepatocellular carcinoma.     

Prognostic significance of postoperative in-hospital complications in elderly patients. I. Long-term survival

To determine the impact of in-hospital postoperative complications on long-term survival, we prospectively studied consecutive patients > or = 70 yr of age undergoing noncardiac surgery. Potential clinical risk factors were measured and evaluated for their association with the occurrence of long-term postoperative mortality. Long-term survival was determined by using the Kaplan-Meier method. Multivariate correlates of survival were analyzed with the Cox proportional hazards model. The survival of the study group was also compared with the age- and gender-matched general United States population. Five hundred seventeen patients who survived the initial hospitalization were studied. The mean follow-up duration was 28.6 +/- 12.8 mo. One hundred sixty-four of 517 patients (31.7%) were deceased at the time of follow-up. A history of cancer (hazard ratio [HR] 2.44, 95% confidence interval [CI] 1.78-3.38, P < 0.0001), ASA physical status >II (HR 2.27, 95% CI 1.61-3.21, P < 0.0001), neurologic disease (HR 1.59, 95% CI 1.13-2.24, P = 0.008), age (HR 1.42 per decade, 95% CI 1.11-1.81, P = 0.005), postoperative pulmonary complications (HR 2.41, 95% CI 1.30-4.48, P = 0.005), and renal complications (HR 6.07, 95% CI 2.23-16.52, P < 0.0001) were significant independent predictors of decreased long-term survival. Compared with the United States population, patients with complications had a greater increase in mortality risk in the first 3 mo after surgery (HR 7.3 versus general population) than those without complications (HR 2.9, P = 0.023). An effort to improve perioperative care delivery to elderly surgical patients must include measures to minimize in-hospital postoperative complications, particularly those involving the pulmonary and renal systems.     

New onset vasomotor symptoms but not musculoskeletal symptoms associate with clinical outcomes on extended adjuvant letrozole – Analyses from NCIC CTG MA.17

PurposeNew onset symptoms on adjuvant aromatase inhibitors for hormone receptor positive early breast cancer may associate with clinical outcomes. We performed this exploratory analysis of the association of new onset musculoskeletal (MSK) and vasomotor (VM) symptoms with clinical outcomes in the NCIC CTG MA.17 trial 5 years of extended adjuvant endocrine therapy with letrozole after tamoxifen.MethodsSymptoms were collected at baseline, 1, 6, and every 12 months on study. Multivariate Cox Models adjusting for age, nodal status, duration of tamoxifen and prior chemotherapy were used to compare disease-free survival (DFS), distant disease-free survival (DDFS), and overall survival (OS) based on data collected before, and after, the unblinding between women with VM or MSK symptoms and those without.ResultsData post-unblinding showed new VM symptoms on extended letrozole significantly improved DFS and DDFS when occurring 1 month (DFS HR 0.52, 95% CI, 0.28–0.96; p = 0.04; DDFS HR 0.49, 95% CI, 0.24–0.99; p = 0.046) and 6 months (DFS HR 0.43, 95% CI, 0.24–0.78; p = 0.006; DDFS HR 0.44, 95% CI, 0.22–0.85; p = 0.02) after treatment initiation. Those with new VM symptoms at 12 months also had a significantly better DFS (HR 0.47, 95% CI 0.26, 0.84; P = 0.01) and a trend in improved DDFS. Only a trend to improved OS was found for those with VM symptoms 6 month after treatment. No significant improvement was found for those with new MSK symptoms at any time point or for any endpoint.ConclusionsNew onset VM symptoms with extended letrozole may be useful in predicting treatment benefit.     

Statins are independently associated with reduced mortality in patients undergoing infrainguinal bypass graft surgery for critical limb ischemia

OBJECTIVE: Evidence suggesting a beneficial effect of cardioprotective medications in patients with lower extremity atherosclerosis derives largely from secondary prevention studies of heterogeneous populations. Patients with critical limb ischemia (CLI) have a large atherosclerotic burden with related high mortality. The effect of such therapies in this population is largely inferred and unproven. METHODS: The Project of Ex-Vivo vein graft Engineering via Transfection III (PREVENT III) cohort comprised 1404 patients with CLI who underwent lower extremity bypass grafting in a multicenter, randomized prospective trial testing the efficacy of edifoligide for the prevention of graft failure. Propensity scores were used to evaluate the influence of statins, beta-blockers, and antiplatelet agents on outcomes while adjusting for demographics, comorbidities, medications, and surgical variables that may influence drug use. Primary outcomes were major adverse cardiovascular events < or =30 days, vein graft patency, and 1-year survival assessed by Kaplan-Meier method. Potential determinants of 1-year survival were modeled using a multivariate Cox regression. RESULTS: In this cohort, 636 patients (45%) were taking statins, 835 (59%) were taking beta-blockers, and 1121 (80%) were taking antiplatelet drugs. Perioperative major adverse cardiovascular events (7.8%) and early mortality (2.7%) were not measurably affected by the use of any drug class. Statin use was associated with a significant survival advantage at 1 year of 86% vs 81% (hazard ratio [HR], 0.71; 95% confidence interval [CI], 0.52-0.98; P = .03) by analysis of both unweighted and propensity score-weighted data. Use of beta-blockers and antiplatelet drugs had no appreciable impact on survival. None of the drug classes were associated with graft patency measures at 1 year. Significant predictors of 1-year mortality by Cox regression modeling were statin use (HR, 0.67; 95% CI, 0.51-0.90; P = .001), age >75 (HR, 2.1; 95% CI, 1.60-2.82; P = .001), coronary artery disease (HR, 1.5; 95% CI, 1.15-2.01; P = .001), chronic kidney disease stages 4 (HR, 2.0; 95% CI, 1.17-3.55; P = .001) and 5 (HR, 3.4; 95% CI, 2.39-4.73; P < .001), and tissue loss (HR, 1.9; 95% CI, 1.23-2.80; P = .003). CONCLUSIONS: Statin use is associated with improved survival in CLI patients 1 year after surgical revascularization. Further studies are indicated to determine optimal dosing in this population and to definitively address the question of relationship to graft patency. These data add to the growing literature supporting statin use in patients with advanced peripheral arterial disease.     

高危胃肠间质瘤的临床病理特征及预后分析

目的分析高危胃肠间质瘤（GIST）临床特征及预后影响因素。 方法回顾性分析2009年8月至2016年2月乐山市人民医院收治的241例高危GIST患者临床资料,分析其临床特征及预后影响因素。 结果男女比例为1.131,年龄构成以中老年为主,40岁以上人群构成比达90.87%（219/241）。原发部位以胃和小肠为主,胃50例（20.75%）,小肠121例（50.21%）。首发症状以消化道症状为主,临床表现不典型。R0切除232例（96.27%）,术后复发转移率为25.31%（61/241）,1、3、5年无复发生存率分别为97.23%、86.56%和75.86%,无复发生存时间为（53.12±13.08）个月。肿瘤最大径（RR=4.780,95% CI：3.716~6.052）、核分裂像（RR=5.411,95% CI：2.195~7.119）是影响高危GIST 5年无复发生存率的独立危险因素,服用靶向药物是保护因素（RR=0.504,95% CI：0.288~0.883）,差异有统计学意义（P<0.001）。 结论高危GIST临床特征不明显,预后受核分裂像、肿瘤最大径和服用靶向药物影响。     

Anatomic versus non-anatomic resection of hepatocellular carcinoma with microvascular invasion: A systematic review and meta-analysis

The efficacy of anatomical resection (AR) and non-anatomical resection (NR) in the treatment of hepatocellular carcinoma (HCC) patients with microvascular invasion (MVI) remains unknown. This study compared the safety and outcomes of these surgical procedures. A systematic literature search was conducted. The main outcomes were overall survival (OS), disease-free survival (DFS). Overall hazard ratio (HR) was calculated from Kaplan–Meier plots and outcomes using random-effects models. There was no significant difference in postoperative complications between the AR and NR groups (risk ratio [RR]: 0.92, 95% confidence interval [CI]: 0.72–1.17, p = 0.496). OS was higher with AR at 1 year (RR: 0.66, 95% CI: 0.45–0.98, p = 0.037), 3 years (RR: 0.64, 95% CI: 0.50–0.82, p = 0.000), and 5 years (RR: 0.76, 95% CI: 0.65–0.89, p = 0.001). AR was associated with a higher OS rate (HR: 0.62, 95% CI: 0.47–0.82, p = 0.001). AR was associated with improved DFS at 1 year (RR: 0.65, 95% CI: 0.52 to 0.82, p = 0.000), 3 years (RR: 0.75, 95% CI: 0.66 to 0.86, p = 0.000), and 5 years (95% CI: 0.75 to 0.94, p = 0.002). Compared with NR, AR had significant advantages on overall HR of DFS (HR: 0.64, 95% CI: 0.45 to 0.91, p = 0.012). In conclusion, AR was associated with higher rates of OS and DFS in HCC patients with MVI. Thus, for well-presented liver function HCC patients which are predicted to have positive MVI, AR is recommended.     

Prognostic factors for primary gastrointestinal stromal tumours: are they the same in the multidisciplinary treatment era?

Purpose

Gastrointestinal stromal tumours (GISTs) are the most common mesenchymal tumour of the gastrointestinal tract. The introduction of tyrosine kinase inhibitors (TKIs) has lead to increasing use of combination of medical and surgical therapy. The aim of this study was to look at outcomes from a series of surgically treated GISTs and determine prognostic factors in the context of multimodal therapy.

Methods

We analysed 104 single surgeon’s patients with GIST. End points of the study were disease-specific survival (DSS), disease-free survival (DFS) and post-operative complications.

Results

Three- and 5-year DSS rates were 96.7 and 94.6 %. On univariate analysis, clear resection margins were predictive of DSS. Patients with R2 resection had a worse prognosis (3-year DSS rate of 83.3 %; 5-year DSS rate of 62.5 %) compared to patients with R0 (3-year DSS rate of 98 %; 5-year DSS rate of 98 %) or R1 resection (3-year DSS rate of 100 %; 5-year DSS rate of 100 %) (R0 vs R1 vs. R2 p = 0.001). Pre-operative factors associated with R2 resection were clinical metastatic disease (p < 0.001), non-gastric tumour site (p = 0.002) and large tumour diameter (p = 0.031). Three- and 5-year DFS rates were 65.5 and 59.8 %. Serosal perforation (p = 0.013) and mitotic rate (p = 0.05) were found to be independently predictive of increased DFS. The presence of serosal perforation was associated with tumour site (p = 0.018), mitotic rate (p = 0.035), tumour diameter (p < 0.001), growth pattern (p = 0.007) and age (p = 0.040).

Conclusions

In the multidisciplinary management of GIST, serosal perforation may represent an additional predictor of recurrence along with mitotic rate. Complete macroscopic surgical resection is the most reliable prognostic factor, and an aggressive surgical approach should be advocated.     

Whether histologic subtyping affect the oncological outcomes of patients with papillary renal cell carcinoma: evidence from a systematic review and meta-analysis

BackgroundWhether the histologic subtype (type 1 and type 2) of papillary renal cell carcinoma (pRCC) is a tool to predict the prognosis is of great debate. This study is aimed to evaluate the prognostic significance of histologic subtype in patients with pRCC after surgery through a systematic review and meta-analysis.MethodsWe searched PubMed, the Web of Science, Cochrane library and EMBASE databases to identify studies published until January 20, 2021 according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. Studies were deemed eligible if they compared the overall survival (OS), cancer specific survival (CSS), recurrence-free survival (RFS) or disease-free survival (DFS) between patients with type 1 or type 2 pRCC. And the corresponding hazard ratios (HRs) and 95% conference intervals (CIs) were collected for meta-analysis and further subgroup analysis.ResultsOverall 22 studies with a total of 4,494 patients were considered eligible and included for the systematic review and meta-analysis. The pooled results showed that type 2 pRCC was associated with a worse OS (pooled HR 1.61, 95% CI: 1.10–2.36, P=0.02) and CSS (pooled HR 1.59, 95% CI: 1.00–2.51, P=0.05). However, the subgroup analysis yielded the same result as the initial analysis only when the HRs were extracted from univariate analysis. In studies with multivariate analysis, type 2 pRCC was not statistically associated with a worse OS (pooled HR 1.22, 95% CI: 0.97–1.53, P=0.27), CSS (pooled HR 1.16, 95% CI: 0.67–2.00, P=0.60), and DFS (pooled HR 1.33, 95% CI: 0.93–1.91, P=0.12) compared to type 1 pRCC.DiscussionHistologic subtype is not an independent prognostic factor for patients with pRCC, although the result needs to be taken with caution. And studies with retrospective study design, larger sample size and longer follow-up period are required to verify these results.     

Gastrointestinal stromal tumors: actin expression, a new prognostic factor?

The aim of this study is to analyze the clinical outcome of gastrointestinal stromal tumors (GISTs) and to determine new prognostic factors. We perform a retrospective study of all the patients diagnosed with GIST in any location and operated on between 2000 and 2008 at our institution. We analyzed 35 patients, 16 males (45.7%) and 19 females (54.3%), with a mean age of 64 +/- 13.8 years. The tumors were located in the stomach in 22 patients (62.9%), in the small bowel in 10 (28.6%), and the retroperitoneum in three (8.6%). Referring to gastric GIST, endoscopy revealed an ulceration in the mucosa in five cases, suggesting an epithelial neoplasm. In all these cases, pathology of the biopsy specimen was nonconclusive. Survival rate at 1 and 5 years was 94.3 and 88.6 per cent, respectively. Disease-free survival at 1 and 2 years was 91.4 and 88.6 per cent, respectively. Analyzing prognostic factors, a lower disease-free survival was observed among patients with constitutional syndrome at diagnosis (P = 0.000), small bowel GIST (P = 0.037), and tumors not expressing actin (P = 0.015). A lower global survival was observed among men (P = 0,036), patients with an abdominal mass (P = 0.033) or with constitutional syndrome (P = 0.007) at diagnosis and tumors at a retroperitoneal location (P = 0.0002). Gastric GIST may be confused with epithelial neoplasms, modifying the surgery. In our patients, masculine gender, constitutional syndrome and abdominal mass at diagnosis, small bowel and retroperitoneal location, and actin negative tumors are bad prognostic factors.     

Outcome Following Local‐Regional Recurrence in Women with Early‐Stage Breast Cancer: Impact of Biologic Subtype

Local‐regional recurrence (LRR) after breast‐conserving therapy (BCT) can result in distant metastasis and decreased disease‐free survival (DFS). This study examines factors associated with DFS following LRR. The initial population included 2,233 consecutive women who underwent BCT from 1998 to 2007. Biologic subtype was approximated using a combination of estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), and tumor grade. Cumulative incidence of DFS after LRR was calculated. The association of clinical, pathologic, and treatment parameters with DFS was evaluated using a Cox regression model. At a median follow‐up of 105 months, 82 patients (3.7%) had a LRR. Of these, 66 (80%) were in‐breast and 16 (20%) involved the ipsilateral lymph nodes. Twenty patients subsequently developed distant metastases. Five‐year DFS after initial recurrence was 69.6% for the overall cohort. On univariate analysis, triple‐negative disease (ER/PR/HER2 negative, TNBC) was associated with reduced DFS (HR = 3.8; 95% CI: 1.8–8.1; p < 0.001). Other factors associated with reduced DFS were larger tumor size (HR = 1.3; 95% CI: 1.03–1.6; p = 0.02), shorter interval from initial diagnosis to LRR (HR = 0.98 per month; 95% CI: 0.97–0.99; p = 0.02), and no salvage surgery (HR = 0.2; 95% CI: 0.09–0.5; p = 0.001). On multivariate analysis, TNBC remained the most significant factor associated with reduced DFS (HR = 4.8; 95% CI: 2.25–10.4; p < 0.001). Compared to women with luminal A disease, those with TNBC had significantly worse DFS (37.5% versus 88.3% at 5 years; p < 0.001). Women with TNBC who developed LRR were at high risk of subsequent recurrence. Efforts should be targeted toward both preventing initial recurrence and decreasing subsequent metastasis.     

Recipient-donor race mismatch for African American liver transplant patients with chronic hepatitis C

African American (AA) recipient-donor race mismatch has been associated with graft loss and mortality, but studies of an association between race mismatch and hepatitis C virus (HCV) disease severity are lacking. HCV-infected adults from 4 US centers who underwent liver transplantation for the first time (n = 1093) were followed for a median of 3.05 years to determine the rates of advanced HCV disease (bridging fibrosis or cirrhosis) and graft failure; 11% of the patients were AA. The unadjusted cumulative rate of advanced fibrosis was higher in AAs than non-AAs (56% and 40% at 4 years, respectively, (P < 0.01), and 59% and 56% for AA recipient-donor-matched patients and AA recipient-donor-mismatched patients, respectively (P = 0.89). In adjusted models, both AA recipient race [hazard ratio (HR) = 1.47, 95% CI = 1.06-2.03, P = 0.02] and AA recipient-donor mismatch (versus match; HR = 1.48, 95% CI = 1.03-2.12, P = 0.03) were significant predictors of advanced fibrosis; other independent predictors were donor age (HR = 1.21, P < 0.01) and cytomegalovirus infection (HR = 1.55, P < 0.01). The 4-year unadjusted cumulative rates for HCV-associated graft loss were 10% and 17% for non-AAs and AAs, respectively (P < 0.01), and 0% and 21% for AA recipient-donor-matched patients and AA recipient-donor-mismatched patients, respectively (P < 0.01). In adjusted models, AA recipient-donor-mismatched patients had a 62% higher rate of graft loss than non-AA recipients (HR = 1.62, 95% CI = 1.14-2.29, P < 0.01), and AA recipient-donor-matched patients had a 76% lower rate of graft loss/mortality (HR = 0.24, 95% CI = 0.06-0.97, P = 0.05). In conclusion, AA recipient-donor-mismatched patients who are infected with HCV are at high risk for advanced HCV disease and HCV-related graft loss and constitute a patient group that will benefit from new therapeutic strategies for preventing graft loss.