Patients With Colorectal and Renal Cell Carcinoma Diagnoses Appear to Be at Risk for Additional Malignancies

BackgroundSmall studies have demonstrated that patients who have both colorectal and renal cell carcinoma may be at increased risk for the development of additional malignancies. A possible genetic basis has been suggested. Our study describes the clinicopathologic features of these patients and clarifies the relationship of this cohort with Lynch syndrome (LS).MethodsPatients with primary CRC and RCC treated at our institution were identified. Medical records were reviewed for demographic and clinical information. Immunohistochemical staining for mismatch repair (MMR) proteins was performed on tumor tissue when possible.ResultsDuring the study period, 24,642 patients were treated for CRC and 7,366 were treated for RCC at our institution. One hundred seventy-nine patients had both diagnoses, with 101 patients eligible for inclusion in our cohort. Tumors were typically early stage. The 2 cancers presented as synchronous lesions in 42% of patients. Thirty-two patients had 1 additional primary malignancy, 7 patients had 2 additional primary malignancies, and 3 patients had 3 additional primary malignancies. No patient had a family history that met the Amsterdam II criteria (AC) for LS, but 50% had family members with 1 malignancy. One of 10 colorectal tumors analyzed for the absence of MMR protein expression demonstrated the absence of MSH6, but the corresponding RCC demonstrated intact expression of all 4 MMR proteins.ConclusionIt is rare for patients to be diagnosed with both CRC and RCC. The clinicopathologic features of this cohort and the results of immunohistochemical analysis performed on a sample of these patients do not suggest LS. However, the high rate of additional carcinomas suggests a need for careful follow-up. Multicenter longitudinal studies are warranted to further understand the natural history and possible genetic basis for this entity.     

Pathologic complete response to neoadjuvant FOLFOX in combination with bevacizumab in unresectable metastatic colorectal carcinoma

A 32-year-old Asian male presented with perforated sigmoid colorectal cancer (CRC) and large, unresectable hepatic metastasis. After surgery for his primary tumor, he received 6 months of FOLFOX (5-fluorouracil/leucovorin/ oxaliplatin) plus bevacizumab and achieved a partial response. He underwent hepatic metastasectomy and was found to have had a complete pathologic response (pCR) to treatment. The literature regarding pCR with chemotherapy in CRC and the implications for further management is discussed herein.     

马来酸罗格列酮对糖耐量异常患者循环血单核细胞的抑制作用及其机制的研究

目的:探讨马来酸罗格列酮对糖耐量异常患者循环血单核细胞分泌MCP-1的抑制作用及其机制。方法:将空腹血糖受损和糖耐量受损80例患者随机分为试验组和对照组,每组40例。试验组口服马来酸罗格列酮4mg/d,连续24周,对照组不服用马来酸罗格列酮。两组试验对象均予严格控制糖尿病饮食、减轻体重,未应用其它抗糖尿病药物。分别于24周前后采血,在体外实验中,以梯度离心的方法分离循环血单核细胞,培养24h,在终浓度为0.01mg/L的内毒素诱导下分泌MCP-1,用酶联免疫吸附实验分析方法测定培养液MCP-1水平,以评价马来酸罗格列酮治疗前后单核细胞对低剂量内毒素刺激反应性的改变;用改良后的流式细胞技术测量马来酸罗格列酮治疗前后单核细胞产生的活性氧自由基的变化,探讨单核细胞MCP-1降低机制。结果:在体外低剂量内毒素诱导实验中,试验组24周前循环血单核细胞分泌MCP-1水平为4 256.0ng/L(2 748.6～5 562.0ng/L),治疗24周后MCP-1降低到1 053.8ng/L(623.5～3 374.0ng/L),MCP-1水平降低显著(P<0.01)。试验组24周前、后单核细胞产生的活性氧自由基分别为(110±24)U、(56±18)U(P<0.01),而对照组24周前、后单核细胞产生活性氧自由基分别为(98±26)U、(106±24)U,两组比较,差异无统计学意义(P>0.05)。结论:马来酸罗格列酮通过降低单核细胞内MCP-1的上游产物活性氧自由基而直接抑制单核细胞分泌MCP-1,从而降低血浆MCP-1水平。     

匹维溴胺对腹泻型肠易激综合征模型大鼠结肠组织AQP3表达影响

目的 观察匹维溴胺对腹泻型肠易激综合征(D-IBS)模型大鼠血清以及结肠组织血管活性肠肽(vasoactive intestinal peptide,VIP)含量、结肠组织水通道蛋白3(aquaporin 3, AQP3)表达的影响,探讨其治疗D-IBS的作用机制.方法 采用慢性应激与束缚相结合方法建立D-IBS大鼠模型.采用ELISA法检测VIP含量;采用Real time-PCR法和SABC免疫组化法检测AQP3的表达.结果 在血清和结肠组织中VIP的含量,与对照组[(3.092±0.613)ng/ml,(3.811±0.275)ng/ml]比较,模型组[(10.460±1.666)ng/ml,(4.495±0.341) ng/ml]与匹维溴胺组[(5.639±1.163)ng/ml,(4.063±0.534)ng/ml]均升高(P＜0.05),尤以模型组升高的更为明显(P＜0.01);两组AQP3的表达均下调(P＜0.01),尤以模型组AQP3蛋白表达下调显著.结论 匹维溴胺治疗D-IBS的作用机制之一,可能与抑制结肠组织中VIP分泌和上调AQP3表达有关.     

范金茹教授治疗颈性眩晕经验举隅

范金茹教授为首批全国优秀中医临床人才,在诊治眩晕类疾病方面积累了丰富经验。颈性眩晕多表现为眩晕、头颈部疼痛、恶心、呕吐、耳鸣等,严重影响了人们的生活质量。范师认为颈性眩晕为本虚标实之证,病位在头颈,肝肾亏虚为本,病性因素多为痰瘀。强调分急性期、缓解期治疗,注重气之升降--引痰饮血瘀下行而出,津气上行以荣脑。自拟颈痹眩晕方,为升降散合泽泻汤加减而成,组方精当,临床运用每获良效。     

Ultrasonography and ultrasound-guided fine-needle aspiration biopsy of head and neck lesions: A surgical perspective

A head and neck ultrasound-guided fine-needle aspiration clinic was set up to determine the role of ultrasound and ultrasound-guided fine-needle aspiration in the evaluation of patients with lesions in this region. One hundred ninety-five lesions were biopsied by ultrasound-guided fine-needle aspiration in 203 patients. Ultrasound detected 2 or more lesions in 14 (48%) of 29 patients with a clinically solitary thyroid nodule. Three (8.8%) of 34 lesions thought to be within the parotid gland were determined to be external. A pronounced learning curve was evident in the technique of ultrasound-guided fine-needle aspiration, particularly for nonpalpable disease. Adequacy of sampling for each 3-month period was 71%, 89%, and 94%, respectively. Seventy-four percent of central aspirations were satisfactory compared to 54% of peripheral aspirations. Ultrasound-guided fine-needle aspiration did not alter the clinical staging of metastatic neck disease in 8 patients having 10 neck dissections but proved useful in detecting nodal recurrence in 3 irradiated necks that did not proceed to surgery. The smallest node to harbor malignancy had 4-mm maximal axial diameter. We conclude that ultrasound and ultrasound-guided fine-needle aspiration are valuable adjuncts to the clinical examination.     

Clinical examination following preoperative chemoradiation for rectal cancer is not a reliable surrogate end point.

PURPOSE: Clinical assessment of rectal cancer response to preoperative combined-modality therapy (CMT) using digital rectal examination (DRE) has been proposed as a means of assessing efficacy of therapy. However, because the accuracy of this approach has not been established, we conducted a prospective analysis to determine the operating surgeon's ability to assess response using DRE. PATIENTS AND METHODS: Ninety-four prospectively accrued patients with locally advanced rectal cancer (T3/4 or N1) were evaluated with DRE and sigmoidoscopy in order to determine the following tumor characteristics: size, location, mobility, morphology, and circumference. Following preoperative CMT (50.40 Gy with fluorouracil-based chemotherapy) and under general anesthesia, the same surgeon estimated tumor response based on changes in these tumor characteristics, assessed via DRE. Percent pathologic tumor response was determined prospectively by a single pathologist using whole mount sections of the resected cancer. RESULTS: Clinical assessment using DRE underestimated pathologic response in 73 cases (78%). In addition, DRE was able to identify only 3 of 14 cases (21%) with a pathologic complete response. There were no clinical overestimates of response. None of the clinicopathologic tumor characteristics examined had a significant impact on DRE estimation of response. CONCLUSION: Clinical examination underestimates the extent of rectal cancer response to preoperative CMT. Given the inaccuracy of DRE following preoperative CMT, it should not be used as a sole means of assessing efficacy of therapy nor for selecting patients following CMT for local surgical therapies.     

Immunohistochemical null-phenotype for mismatch repair proteins in colonic carcinoma associated with concurrent <Emphasis Type="Italic">MLH1</Emphasis> hypermethylation and <Emphasis Type="Italic">MSH2</Emphasis> somatic mutations

Microsatellite instability, a well-established driver pathway in colorectal carcinogenesis, can develop in both sporadic and hereditary conditions via different molecular alterations in the DNA mismatch repair (MMR) genes. MMR protein immunohistochemistry (IHC) is currently widely used for the detection of MMR deficiency in solid tumors. The IHC test, however, can show varied staining patterns, posing challenges in the interpretation of the staining results in some cases. Here we report a case of an 80-year-old female with a colonic adenocarcinoma that exhibited an unusual “null” IHC staining pattern with complete loss of all four MMR proteins (MLH1, MSH2, MSH6, and PMS2). This led to subsequent MLH1 methylation testing and next generation sequencing which demonstrated that the loss of all MMR proteins was associated with concurrent promoter hypermethylation of MLH1 and double somatic truncating mutations in MSH2. These molecular findings, in conjunction with the patient’s age being 80 years and the fact that the patient had no personal or family cancer history, indicated that the MMR deficiency was highly likely sporadic in nature. Thus, the stringent Lynch syndrome type surveillance programs were not recommended to the patient and her family members. This case illustrates a rare but important scenario where a null IHC phenotype signifies complex underlying molecular alternations that bear clinical management implications, highlighting the need for recognition and awareness of such unusual IHC staining patterns.