微血管模式、密度及影像学参数对涎腺腺样囊性癌预后的关系

目的探讨微血管模式、密度以及影像学参数与涎腺腺样囊性癌预后的相关性。方法收集涎腺腺样囊性癌患者148例,免疫组化染色方法检测血管内皮细胞CD31、CD105单克隆抗体表达及检测涎腺肿瘤组织的微血管密度(MVD),比较CT灌注参数、微血管密度(MVD)参数在良恶性肿瘤之间的差异及相关性。结果 CD31在恶性肿瘤组中的表达明显高于良性肿瘤组,但两组之间比较差异无统计学意义(P>0.05);CD105在恶性肿瘤组中的表达明显高于良性肿瘤组,但两组之间比较差异无统计学意义(P>0.05);恶性肿瘤组灌注参数BF、BV、PS值明显高于良性组,差异比较具有统计学意义(P<0.05),而两组的MTT参数比较差异不具有统计学意义(P>0.05);采用Spearman分析肿瘤各灌注各参数值与MVD的相关性,结果显示BF、PS、BV、MTT与MVD之间呈正相关性。结论 CT灌注参数可较准确地定量分析肿瘤血流灌注状态,微血管密度(MVD)、CD105可特异性标记肿瘤新生血管内皮细胞,在涎腺腺样囊性癌的预后的评价中发挥着有积极作用。     

儿童急性淋巴细胞白血病并发急性胰腺炎的临床特点分析

目的:分析儿童急性淋巴细胞白血病(acute lymphoblastic leukemia,ALL)并发急性胰腺炎(acute pancreatitis,AP)患儿的临床特点。方法:收集2013年2月至2020年2月天津市儿童医院收治的ALL并发AP患儿11例,均采用中国儿童白血病协作组-急性淋巴细胞白血病-2008(CCLG-ALL 2008)方案联合化疗,总结患儿的危险度分层、主要临床表现、发生胰腺炎的所处治疗阶段、发病原因、培门冬酶(polyethylene glycol conjugated asparaginase,PEG-ASP)的累积用量,整理患儿的胰酶指标、影像学检查、血常规、肝肾功能、血脂血糖、凝血功能等化验结果,对比患儿治疗效果及转归,分析其临床特点。结果:全组11例患儿中,男性7例,女性4例,年龄范围1～14岁,中位年龄6岁;急性B淋巴细胞白血病(type B acute lymphoblastic leukemia,B-ALL)10例,急性T细胞型淋巴母细胞白血病(type T acute lymphoblastic leukemia,T-ALL)1例;初始联合...     

Vibration-Induced Nystagmus in Patients with Unilateral Peripheral Vestibular Disorders

This study was done to clarify the clinical significance of vibration-induced nystagmus (VIN) and to calculate the sensitivity and the specificity of the vibration test. One hundred and twelve patients with unilateral peripheral vestibular disorders and thirty normal subjects were enrolled into this study. However, patients with spontaneous nystagmus were excluded. Vibration stimuli (approximately 100 Hz) were presented to the mastoids and the forehead. Patients and normal subjects also underwent head shaking nystagmus (HSN) test and caloric testing. Among the 112 patients, 91(81 %) showed VIN which were mainly horizontal. VIN was more frequently elicited on the mastoids than on the forehead. In the majority of patients (76 cases), the direction of VIN was toward the healthy side, whereas patients with Meniere’s disease (15 cases), showed nystagmus toward the affected side. None of 30 normal subjects showed VIN. Whereas HSN was found in 70 (63 %) patients and 9 (30 %) in normal subjects. Among 112 patients, 10 showed a canal paresis (CP) value of caloric testing less than 25 %, while 32 with a CP value between 25 and 40 %, 48 with a CP value between 40 and 70 %, and 22 with a CP value no less than 70 %. It is notable that with increasing CP value on caloric testing, VIN was more likely to be elicited. So VIN test is a simple, non-invasive and well-tolerated clinical test that indicates unilateral peripheral vestibular dysfunction. VIN test had greater sensitivity and specificity than HSN test in the diagnosis of unilateral peripheral vestibular disorders.     

Pharmacokinetics of oral etoposide in patients with hepatocellular carcinoma

Etoposide dosage in patients with liver dysfunction remains controversial. Since etoposide has a hepatic component to its clearance (CL) and shows a high degree of protein binding, hepatic impairment could affect etoposide disposition. However, the empiric recommendation that the dose of etoposide be decreased in such patients may reduce systemic exposure and be detrimental to its antitumor activity. To address these issues we studied the pharmacokinetics (PK) of etoposide in patients with hepatocellular carcinoma (HCC) and underlying cirrhosis (n= 17) treated with daily oral etoposide. Unbound etoposide was obtained by ultrafiltration. Etoposide concentrations (total and free drug) were measured by high-performance liquid chromatography (HPLC) and analyzed by noncompartmental equations. The patients had mild or moderate liver dysfunction. Albuminemia was in the normal range for all the patients. Creatininemia was normal in all but two patients. PK results (mean and range) showed that etoposide disposition was unchanged in patients with liver dysfunction. We found slightly high etoposide bioavailability [F, 61% (17–95%)] and clearance [CL, 1.1 (0.7–2.3) l h⁻¹ m⁻²] resulting in a normal degree of systemic exposure (AUC_oral 27 μg h ml⁻¹). Normal protein binding [PB 93.2% (84.4–98.1%)] contributed to a normal level of exposure to free drug (AUC_{f, oral} 1.9 μg h ml⁻¹). The distribution volume [V_SS 8.4 (6.1–13.2) l/m²] and the effective half-life [t _1/2eff, 5.1 (3.0–9.6) h] were normal. Median CL and protein binding did not differ in the seven patients with total bilirubin value of >1.2 mg/dl as compared with the ten patients with total bilirubin levels of ≤1.2 mg/dl (1.3 versus 1.0 l h⁻¹ m⁻² and 92.5% versus 93.4%, respectively). In agreement with this PK finding, we observed no clinical evidence of increased toxicity in patients with hyperbilirubinemia as compared with patients with normal bilirubinemia (mean WBC decrease 38% versus 47%). The only case of severe (grade 4) hematological toxicity was observed in one patient with reduced glomerular filtration. Since the pharmacological effects of etoposide correlate with the level of systemic exposure to the free drug, our data suggest that no dose reduction is needed in patients with HCC. It is even possible to increase the dose intensity in patients with favorable PK parameters under appropriate hematological and therapeutic drug monitoring. Received: 11 May 1998 / Accepted: 5 August 1998     

Hepatic imaging response to radioembolization with yttrium-90-labeled resin microspheres for tumor progression during systemic chemotherapy in patients with colorectal liver metastases

Background

To assess response and the impact of imaging artifacts following radioembolization with yttrium-90-labeled resin microspheres (⁹⁰Y-RE) based on the findings from a central independent review of patients with liver-dominant metastatic colorectal cancer (mCRC).

Methods

Patients with mCRC who received ⁹⁰Y-RE (SIR-Spheres^®; Sirtex Medical, Sydney, Australia) at nine US institutions between July 2002 and December 2011 were included in the analysis. Tumor response was assessed at baseline and 3 months using either the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.0 or 1.1. For each lesion, known artifacts affecting the interpretation of response (peri-tumoral edema and necrosis) were documented. Survivals (Kaplan-Meier analyses) were compared in responders [partial response (PR)] and non-responders [stable (SD) or progressive disease (PD)].

Results

Overall, 195 patients (mean age 62 years) received ⁹⁰Y-RE after a median of 2 (range, 1-6) lines of prior chemotherapy. Using RECIST 1.0 and RECIST 1.1, 7.6% and 6.9% of patients were partial responders, 47.3% and 48.1% had SD, and 55.0% and 55.0% PD, respectively. RECIST 1.0 and RECIST 1.1 showed excellent agreement {Kappa =0.915 [95% confidence interval (CI): 0.856-0.975]}. Peri-tumoral edema was documented in 32.8%, necrosis in 48.1% and both in 57.3% of cases (using RECIST 1.0). Although baseline characteristics were similar in responders and non-responders (P>0.05), responders survived significantly longer in an analysis according to RECIST 1.0: PR median (95% CI) 25.2 (range, 9.2-49.4) months vs. SD 15.8 (range, 9.3-21.1) months vs. PD 7.1 (range, 6.0-9.5) months (P<0.0001).

Conclusions

RECIST 1.0 and RECIST 1.1 imaging responses provide equivalent interpretations in the assessment of hepatic tumors following ⁹⁰Y-RE. Radiologic lesion responses at 3 months must be interpreted with caution due to the significant proportion of patients with peri-tumoral edema and necrosis, which may lead to an under-estimation of PR/SD. Nevertheless, 3-month radiologic responses were predictive of prolonged survival.     

全身炎症反应指数对胶质瘤患者临床预后影响及与IDH1突变的关系

目的 探讨全身炎症反应指数(SIRI)对胶质瘤患者临床预后影响及与IDH1突变的关系。方法 收集2006年8月—2015年11月于我院神经外科行手术治疗的80例神经胶质瘤患者。应用ROC曲线确定SIRI判断患者术后生存状态的最佳临床分界值,并依此分组。采用Kaplan-Meier和Log-rank法分析两组患者术后生存情况。Cox比例风险回归模型分析临床预后因素。应用免疫组织化学和DNA测序方法检测IDH1突变情况。结果 低SIRI组术后中位无进展生存时间(Progress free survival,PFS)和中位总生存时间(Overall survival,OS)分别为46.90个月和57.90个月,而高SIRI组术后中位PFS和中位OS分别为31.78个月和47.22个月;两组术后中位PFS和中位OS比较差异具有统计学意义(P＜0.05)。经单因素和多因素分析,年龄、手术情况、WHO分级、SIRI、IDH1突变是神经间质瘤独立预后的因素。低SIRI组伴有IDH1突变的神经胶质瘤患者预后较好。结论 SIRI是神经胶质瘤独立的预后因素,具有简单、方便、可重复性强等特点,可用来预测神经胶质瘤患者的预后。     

Elevated 12- and 20-hydroxyeicosatetraenoic acid in urine of patients with prostatic diseases

The role of eicosanoids (metabolites of arachidonic acid) in prostate diseases is receiving increased attention. We investigated the relationship between the concentrations of urinary free acids of 12- and 20-hydroxyeicosatetraenoic acids (12- and 20-HETE) and the benign prostatic hypertrophy (BPH) and prostate cancer (Pca). Urinary concentrations of 12-HETE and 20-HETE of BPH and Pca patients were significantly higher than normal subjects. After removal of the prostate gland, the urinary concentrations of these eicosanoids decreased to concentrations similar to the normal subjects. These results suggest that urinary free acids of 12-HETE and 20-HETE indicate an abnormality of the prostate gland.     

Metastatic colorectal cancer presenting with bone marrow metastasis: a case series and review of literature

With advances in treatment, patients with metastatic colorectal cancer (CRC) are now living longer with an apparent increase in the incidence of bone and bone marrow metastases (BMM). Common sites of metastatic disease from CRC include the liver and lungs with bone metastasis rarely occurring in the absence of visceral metastatic disease. We report a series of three patients presenting with isolated bone and BMM leading to a diagnosis of primary CRC. We have reviewed the literature regarding diagnosis, potential mechanisms leading to the development of osseous metastasis and outcome. A high level of clinical suspicion and in-depth understanding of the natural history of these rare metastases may guide future management and treatment decisions.     

Allergic reaction to chlorambucil in chronic lymphocytic leukemia presenting with fever and lymphadenopathy

Chronic lymphocytic leukemia (CLL) is commonly treated with the alkylating agent chlorambucil. Allergic reactions to this chemotherapy are rare. Previous reports include urticaria, angioedema, rashes, toxic epidermal necrolysis, drug fever and one case of immune hemolytic anemia. We report 2 cases that had the identical symptoms of acute onset of high fever and progressive lymphadenopathy. These symptoms disappeared with conservative management. Neither of the patients were treated for infection or disease progression. When the patients were rechallenged with chlorambucil, identical reactions recurred. There was no cross-reactivity with the alkylating agent cyclophosphamide or other types of chemotherapy. This type of reaction to chlorambucil has not been described previously. It is important to recognize this as an allergic reaction. These reactions could be confused with the onset of infection, progression of disease or even a Richter's transformation.     

Sarcopenia with systemic inflammation can predict survival in patients with hepatocellular carcinoma undergoing curative resection

BackgroundThis study aimed to examine the prognostic significance of sarcopenia combined with systemic inflammation in patients who underwent curative hepatectomy for hepatocellular carcinoma (HCC).MethodsBetween January 2010 and July 2019, we identified 159 patients with HCC who underwent curative hepatectomy at three institutional centers. We retrospectively analyzed clinicopathological outcomes, surgical outcomes, platelet lymphocyte ratio (PLR) as a systemic inflammatory marker, and computed tomography (CT)-assessed sarcopenia at the third lumbar vertebra level (L3).ResultsSarcopenia was noted in 74 (46.5%) of 159 patients and was significantly associated with male sex, low body mass index (BMI), and high PLR. In the multivariate analysis, sarcopenia [hazard ratio (HR): 2.127, P=0.026] and high PLR (HR: 1.971, P=0.038) were associated with a decrease in overall survival (OS) but not in recurrence-free survival (RFS). The combination of sarcopenia and PLR status stratified the 5-year OS into 82.0% (non-sarcopenia and a low PLR), 68.3% (sarcopenia or a high PLR), and 44.4% (sarcopenia and a high PLR) (P=0.001). In the multivariate analysis, “sarcopenia and a high PLR” and “sarcopenia or a high PLR” were revealed to be significant predictors of OS (HR: 4.300, P=0.001 and HR: 2.723, P=0.010, respectively).ConclusionsSarcopenia and high PLR were significantly associated with poor OS. The combination of these two factors may be useful for predicting survival of patients with HCC undergoing curative hepatectomy.     

Effect of the systemic immune-inflammation index on postoperative complications and the long-term prognosis of patients with colorectal cancer: a retrospective cohort study

BackgroundColorectal cancer (CRC) is one of the most common malignant tumors of the digestive tract. Surgery is the main way to cure CRC, but the postoperative complication rate and recurrence rate remain high. The systemic immune-inflammation (SII) index reflects a patient’s systemic inflammatory state and immune state. Postoperative recurrence and the occurrence of complications are closely related to the inflammatory state and immune state. Thus, the SII index may have some value in predicting postoperative complications and the long-term prognosis of CRC patients, but relevant studies are currently lacking. The present study sought to examine the effect of the SII index on the postoperative complications and long-term prognosis of patients with CRC.MethodsFrom January 2014 to January 2017, the data of 440 patients with CRC who had been admitted to the Affiliated Hospital of Guangdong Medical University were retrospectively collected, and the patients were equally divided into the high and the low SII groups according to their preoperative SII index levels. The postoperative complication rate and postoperative progression-free survival (PFS) and mortality between the 2 groups were compared.ResultsCompared to the low SII group, the incidence of postoperative infection in the high SII group was significantly increased (15.45% vs. 9.09%, P=0.042), mortality was significantly increased at 5 years postoperatively (20.91% vs. 7.27%, P<0.001), and PFS was significantly shortened (P<0.001). The SII index had certain predictive value for postoperative infection in CRC patients, and the area under the curve (AUC) was 0.645 [95% confidence interval (CI): 0.559–0.731, P=0.001]. The SII index also had certain predictive value for the progression of CRC patients within 5 years of surgery, and the AUC was 0.670 (95% CI: 0.610–0.729, P<0.001). Additionally, the SII index had certain predictive value for death within 5 years of surgery in patients with CRC, and the AUC was 0.660 (95% CI: 0.593–0.726, P<0.001). CRC patients with postoperative infection had a significantly shorter PFS period than those who did not develop postoperative infection (P=0.029).ConclusionsThe SII index has certain predictive value for the diagnosis of postoperative infectious complications and the long-term prognosis of CRC patients.     

Prognostic value and association of sarcopenic obesity and systemic inflammatory indexes in patients with hepatocellular carcinoma following hepatectomy and the establishment of novel predictive nomograms

BackgroundThe specific impacts of sarcopenic obesity (SO) on hepatocellular carcinoma (HCC) and the association between SO and systemic inflammation remain unclear. This study aimed to investigate the prognostic value and association of SO and systemic inflammation with outcomes after hepatectomy for HCC and develop novel nomograms based on SO and inflammatory indexes for survival prediction.MethodsWe retrospectively enrolled 452 patients with HCC who underwent radical hepatectomy between January 2012 and March 2015 in Fujian Provincial Hospital as the training cohort. In addition, 275 patients during the same period were enrolled as the external validation cohort. Patients were classified into different groups according to the presence of sarcopenia and obesity. Different inflammation indexes were evaluated to select the best predictor of overall survival (OS) and recurrence-free survival (RFS). Univariate and multivariate logistic regression were performed to investigate the associations between inflammatory indexes and SO. The inflammatory indexes with the highest predictive values and SO were selected for subgroup analyses to establish a novel classification system: the SOLMR grade. SOLMR grades identified in the multivariate Cox analysis were selected to construct novel nomograms for OS and RFS.ResultsSO (P<0.001) was an independent risk factor for OS and RFS. The lymphocyte‐monocyte ratio (LMR) had the highest areas under the receiver operating characteristic (ROC) curves (AUCs) for OS (P<0.001) and RFS (P<0.001) and was identified as an independent factor of SO (P=0.001). SO and the LMR were selected to establish the SOLMR grade. Multivariate Cox analysis revealed that SOLMR grade was a significant independent predictor of OS (P<0.001) and RFS (P<0.001). Nomograms based on SOLMR grades were generated and accurately predicted 1-, 3- and 5-year OS and RFS in HCC patients. The C-index of the novel nomograms was higher than those of the other conventional staging systems (P<0.001).ConclusionsBoth SO and the LMR were independent risk factors for OS and RFS in HCC patients after hepatectomy. The LMR was an independent factor of SO. The novel nomograms developed from the SOLMR grading system combining SO with the LMR provide good prognostic estimates of the outcomes of HCC patients.     

Acute erythroblastic leukemia presenting as acute undifferentiated leukemia: a report of two cases with ultrastructural features

This report describes two elderly patients with acute leukemia in which blast cells were undifferentiated with conventional light microscopy (L.M.) and cytochemistry. Blast cells were identified as belonging to the erythroblastic line by their ultrastructural features: glycogen deposits, lipidic vacuoles, cytoplasmic ferritin molecules and rhopheocytotic invagination. Moreover, blast cells were surrounding a central macrophage. Thus, these two patients had acute erythroblastic leukemia which differs from erythroleukemia (M6 of FAB classification) in which blast cells present myeloblastic characteristics.     

HER2-positive,trastuzumab-resistant metastatic esophageal cancer presenting with brain metastasis after durable response to dual HER2 blockade: a case report

We here report a case of a patient diagnosed with human epithelial growth factor receptor 2 (HER2)-amplified esophageal adenocarcinoma. The patient responded well to trastuzumab-based chemotherapy initially, but progressed with liver metastases. Her treatment was then switched to dual HER2 blockade with both trastuzumab and lapatinib in combination with capecitabine. She tolerated therapy and responded remarkably well with radiographic resolution of liver metastases. Unfortunately, she developed multiple brain metastases in the absence of extracranial progression. Discordant negative expression of HER2 and subclonal mutations in brain lesions were discovered, which, at least in part, explained her brain metastases in the presence of capecitabine and lapatinib, as both agents are known to be able to cross the blood brain barrier. The potential mechanism for dual HER2 blockade is discussed in the context of HER2-positive, trastuzumab-resistant, advanced esophageal cancer. The incidence of brain metastasis in advanced gastro-esophageal cancer has been reported to be extremely low, but is expected to increase with more effective systemic therapy. The intratumoral heterogeneity between the metastases, local recurrences and the primary tumor is definitely noteworthy.