Expression of CA 72-4 (TAG-72) in the fluid contents of pancreatic cysts. A new marker to distinguish malignant pancreatic cystic tumors from benign neoplasms and pseudocysts.

OBJECTIVE: The authors evaluated cyst fluid CA 72-4 as a tumor marker in the differential diagnosis of pancreatic cystic lesions. SUMMARY BACKGROUND DATA: Pancreatic cystic lesions include inflammatory pseudocysts, serious cystadenomas, and mucinous tumors. Mucinous tumors can be further subdivided into mucinous cystadenocarcinomas and premalignant mucinous cystic neoplasms. The clinical and radiologic features of these lesions are unreliable to make a preoperative diagnosis of these diagnostically difficult lesions. Analysis of aspirated cyst fluid was proposed as an aid to making the preoperative differential diagnosis. Currently, a number of parameters have been reported as useful markers in cyst fluid aspirates, including the tumor markers carcinoembryonic antigen and CA 15.3, enzymes (amylase, lipase, and amylase isoenzymes), relative viscosity, and cytologic analysis. However, owing to the rarity of pancreatic cystic tumors, experience with cyst fluid analysis is limited. To define additional markers that might be useful in the differential diagnosis of pancreatic cysts, the authors measured the tumor-associated glycoprotein 72 (TAG-72) in aspirates from 19 pancreatic cystic lesions. METHODS: Cyst fluid from 19 pancreatic cysts was obtained by needle aspiration. The tumor marker TAG-72 was measured by a commercial (CA 72-4) immunoassay. RESULTS: Cyst fluid CA 72-4 levels in mucinous cystadenocarcinomas were markedly elevated (mean, 10,027 U/mL; range, 780 to 34,853 U/mL) compared with that in pseudocysts (mean, 3.8 U/mL; range, < 3 to 5.7 U/mL) and serous cystadenomas (mean and range, < 3 U/mL; p < 0.001). The level of CA 72-4 in benign mucinous cystic neoplasms was intermediate (mean, 44.2 U/mL; range, < 3 to 137 U/mL), but it was statistically different from either carcinomas (p = 0.009) or benign cysts (p < 0.001).     

Telomerase activity in malignant and benign renal tumors

OBJECTIVES: An important characteristic of malignant cells is their unlimited replicative potential, their immortality. In conferring this immortality, the enzyme telomerase is believed to play a crucial role. The detection of telomerase activity provides new knowledge regarding the biologic growth behavior of tumors and offers new diagnostic and therapeutic tools. METHODS: In the present study the sensitive TRAP assay (telomeric repeat amplification protocol) was used to examine 44 malignant renal tumors and 8 benign tumors of the kidney and 52 specimens of normal renal tissue for telomerase activity. RESULTS: Telomerase activity was detected in 63% of tissue samples obtained from histologically confirmed renal cell carcinomas. In cases of renal cell carcinoma restricted to the kidney, telomerase activity was detected in 58%. In cases in which tumor growth has progressed beyond the limits of the organ, telomerase activity was found in 69%. This stage dependence, however, did not reach statistical significance. No correlation to tumor grading was observed. Telomerase activity was found less frequent in chromophobe renal cell carcinomas. Neither the 8 benign renal tumors (4 oncocytomas and 4 angiomyolipomas) nor the specimens of normal kidney showed any evidence of telomerase activity. CONCLUSIONS: The proportion of remarkable slow-growing renal cell carcinomas showing telomerase activity is less than in other malignancies and may correlate with biologic growth behavior. Possible explanations include the presence of an alternative pathway, called ALT (alternative lengthening of telomeres) and an association with the loss or presence of the telomerase suppressor on the short arm of chromosome 3. Prolonged follow-up will be of special interest to determine whether lack of telomerase activity predicts favorable outcome.     

Antibody array profiling reveals serum TSP-1 as a marker to distinguish benign from malignant prostatic disease

BACKGROUND: Blood protein markers that provide more accurate or earlier diagnosis of prostate cancer should have a positive impact on prostate cancer treatment and management. METHODS: Serum samples from control subjects and patients with benign or malignant prostatic disease were analyzed on antibody arrays targeting multiple candidate prostate cancer markers and detected with two-color, rolling-circle amplification (TC-RCA). The measurements of certain antibodies were validated using immunoblots, immunoprecipitation/mass spectrometry, and sandwich immunoassays. RESULTS: Several potential disease-associated protein alterations were uncovered. The most significant was thrombospondin-1, which was strongly elevated in patients with benign prostatic disease and repressed in patients with prostate cancer. Thrombospondin-1 levels did not correlate with prostate-specific antigen (PSA) levels and differentiated benign from malignant disease with 79% sensitivity and 81% specificity. CONCLUSIONS: The measurement of thrombospondin-1 could be used to assist the decision to obtain a biopsy in men with suspected prostate cancer, which could lead to a reduction in the number of unnecessary prostatic biopsies.     

Plasma D-lactic acid level: a useful marker to distinguish perforated from acute simple appendicitis

Early diagnosis of perforated appendicitis is important for reducing morbidity rates. The aim of this study was to determine the value and utility of plasma D-lactic acid levels in identifying the type of appendicitis. In this clinical study, plasma D-lactic acid levels were assessed in 44 consecutive paediatric patients (23 with acute appendicitis, 21 with perforated appendicitis) before laparotomy. D-lactic acid levels were determined by an enzymatic spectrophotometric technique using a D-lactic acid dehydrogenase kit. Patients with perforated appendicitis had higher D-lactic acid levels (3.970 +/- 0.687 mg/dL) than patients in the control group (0.478 +/- 0.149 mg/dL) and patients with acute appendicitis (1.409 +/- 0.324 mg/dL; p < 0.05). For a plasma D-lactic acid level greater than 2.5 mg/dL, the sensitivity and specificity of the D-lactic acid assay were 96% and 87%, respectively. The positive predictive value was 87%, the negative predictive value was 96%, and the diagnostic value was 91%. These results suggest that the measurement of plasma D-lactic acid levels may be a useful adjunct to clinical and radiological findings in distinguishing perforated from acute non-perforated appendicitis in children.     

Endoscopic ultrasound guided radiofrequency ablation,for pancreatic cystic neoplasms and neuroendocrine tumors

AIM: To outline the feasibility, safety, adverse events and early results of endoscopic ultrasound (EUS)-radiofrequency ablation (RFA) in pancreatic neoplasms using a novel probe.METHODS: This is a multi-center, pilot safety feasibility study. The intervention described was radiofrequency ablation (RF) which was applied with an innovative monopolar RF probe (1.2 mm Habib EUS-RFA catheter) placed through a 19 or 22 gauge fine needle aspiration (FNA) needle once FNA was performed in patients with a tumor in the head of the pancreas. The Habib™ EUS-RFA is a 1 Fr wire (0.33 mm, 0.013”) with a working length of 190 cm, which can be inserted through the biopsy channel of an echoendoscope. RF power is applied to the electrode at the end of the wire to coagulate tissue in the liver and pancreas.RESULTS: Eight patients [median age of 65 (range 27-82) years; 7 female and 1 male] were recruited in a prospective multicenter trial. Six had a pancreatic cystic neoplasm (four a mucinous cyst, one had intraductal papillary mucinous neoplasm and one a microcystic adenoma) and two had a neuroendocrine tumors (NET) in the head of pancreas. The mean size of the cystic neoplasm and NET were 36.5 mm (SD ± 17.9 mm) and 27.5 mm (SD ± 17.7 mm) respectively. The EUS-RFA was successfully completed in all cases. Among the 6 patients with a cystic neoplasm, post procedure imaging in 3-6 mo showed complete resolution of the cysts in 2 cases, whilst in three more there was a 48.4% reduction [mean pre RF 38.8 mm (SD ± 21.7 mm) vs mean post RF 20 mm (SD ± 17.1 mm)] in size. In regards to the NET patients, there was a change in vascularity and central necrosis after EUS-RFA. No major complications were observed within 48 h of the procedure. Two patients had mild abdominal pain that resolved within 3 d.CONCLUSION: EUS-RFA of pancreatic neoplasms with a novel monopolar RF probe was well tolerated in all cases. Our preliminary data suggest that the procedure is straightforward and safe. The response ranged from complete resolution to a 50% reduction in size.     

良恶性胰腺神经内分泌肿瘤的影像学表现及鉴别诊断

目的探讨胰腺神经内分泌肿瘤的影像学表现及鉴别良恶性肿瘤的价值。方法回顾性分析18例经手术病理证实的胰腺神经内分泌肿瘤的影像学及病理资料,比较良恶性肿瘤的特征差异。结果 18例共检出18个病灶,包括神经内分泌瘤13个,神经内分泌癌5个;功能性肿瘤6个、无功能性12个。13例病灶形态规则,12例肿瘤边缘清晰;增强扫描动脉期16例肿瘤呈高密度强化,等密度、低密度强化各1例。良恶性肿瘤间最大径、肿瘤形态、边缘、强化方式及侵袭性差异均有统计学意义(P均0.05);功能性与无功能性肿瘤最大径差异有统计学意义(P0.05)。结论胰腺神经内分泌肿瘤的影像学表现有一定特点,对鉴别诊断良恶性肿瘤具有一定价值。     

Claudin-6 is a nonspecific marker for malignant rhabdoid and other pediatric tumors

Claudins are tight junction proteins with claudin-6 (CLDN6) expression mostly restricted to embryonic and fetal life. Previously reported gene expression microarray analysis showed an increased level of CLDN6 in atypical teratoid rhabdoid tumors (AT/RT) compared with other central nervous system (CNS) tumors and sarcomas. However, there exist conflicting data on expression of CLDN6 as assessed by immunohistochemistry in CNS tumors. We established membranous staining as a specific and reproducible method for evaluating CLDN6 expression based on fetal and adolescent controls. We then evaluated a large group (257) of pediatric tumors using tissue microarrays, including: 47 malignant rhabdoid tumors (MRTs), (31 AT/RTs and 16 non-CNS MRTs); 67 small, round, blue cell tumors (10 Wilms tumors, 10 embryonal rhabdomyosarcomas, 10 neuroblastomas (NBs), 10 synovial sarcomas (SSs), 9 hepatoblastomas (HBs), 9 alveolar rhabdomyosarcomas, and 9 Ewings sarcomas); and 143 CNS tumors (24 medulloblastomas, 21 pilocytic astrocytomas, 14 astrocytomas grade II/III, 13 gangliogliomas, 12 glioblastomas, 12 ependymal tumors, 11 choroid plexus tumors, 10 meningiomas, 8 dysembryoplastic neuroepithelial tumors, 8 oligodendrogliomas, 4 craniopharyngiomas, 2 germinomas, 2 primitive neuroectodermal tumors (PNET), and 2 central neurocytomas). CLDN6 expression was seen in 12 of 31 (39%) AT/RTs, 7 of 16 (44%) non-CNS MRTs, 5 of 10 (50%) Wilms tumors, 1 of 9 (11%) HBs, 2 of 2 (100%) germinomas, 1 of 2 (50%) CNS PNETs, 1 of 24 (4%) medulloblastomas, and 1 of 10 (10%) meningiomas. Ten of 11 (91%) choroid plexus tumors showed apical staining but no concentric membranous staining. Although CLDN6 is expressed in both AT/RTs and MRTs, it is not a specific biomarker as it is expressed in a variety of other pediatric CNS and soft tissue tumors.     

术中超声在机器人辅助胰腺良性-低度恶性肿瘤手术中的应用价值

目的总结分析术中超声(Intraoperative ultrasound,IOUS)在机器人辅助胰腺良性-低度恶性肿瘤手术中的应用价值与经验。 方法回顾性分析2019年10月至2021年10月期间,术前诊断为胰腺良性-低度恶性肿瘤并由解放军总医院第一医学中心肝胆胰外科医学部行IOUS辅助下机器人胰腺肿瘤手术患者的临床及IOUS资料。 结果在147例患者中,IOUS能发现并定位全部肿瘤,130例(88.4%)可以明确肿瘤与主胰管的关系,23例(15.6%)在IOUS指导下改变了手术方式;IOUS辅助机器人胰腺肿瘤手术的平均手术时间(183.3±75.1)min,术后中位住院时间7 d,发生B级及以上胰瘘22例(15.0%),出现Clavien-Dindo Ⅲ级以上严重并发症15例(10.2%),无90 d死亡患者。 结论IOUS可以在术中辅助肿瘤定位,明确肿瘤与胆管、胰管的关系,发现术前影像学检查遗漏的隐匿病灶,在肿瘤切除后判断主胰管的连续性并判断胰管支撑管的位置,有利于手术决策的制订和减少术后并发症的发生,IOUS的应用为机器人辅助胰腺良性-低度恶性肿瘤手术的安全顺利实施提供了有利保障。     

Podoplanin is a highly sensitive and specific marker to distinguish primary skin adnexal carcinomas from adenocarcinomas metastatic to skin

Distinction of primary skin adnexal carcinomas from cutaneous metastasis of adenocarcinomas is challenging. In this study, we evaluated podoplanin immunoreactivity in a series of primary skin adnexal tumors and adenocarcinomas metastatic to skin using a D2-40 antibody. The initial test series were composed of a total of 93 cases including 32 primary skin adnexal carcinomas, 46 benign primary adnexal tumors, and 15 cutaneous metastatic adenocarcinomas. We found that variable D2-40 reactivity was seen in all of the primary cutaneous carcinomas including sebaceous carcinomas (10/10), squamous cell carcinomas (10/10), porocarcinomas (4/4), trichilemmal carcinomas (4/4), skin adnexal carcinomas not otherwise specified (4/4), and in the majority of benign skin adnexal tumors. In contrast, no podoplanin immunoreactivity was seen in any of the 15 (0/15) cutaneous metastases. To confirm the initial findings and to further explore the utility of podoplanin reactivity in the distinction of these tumors, we also examined a test set of 35 unknown cases, including 21 adenocarcinomas metastatic to skin and 14 primary adnexal tumors, in a blinded fashion. In this test set of cases, podoplanin was negative in 22 cases and positive in 13 cases. Of the 22 podoplanin negative cases, 20 were proven to be metastatic adenocarcinoma. Of the 13 D2-40 positive cases, 12 were proven to be primary adnexal tumors. Our results suggest that podoplanin can be a useful tool to distinguish primary skin adnexal carcinomas form adenocarcinomas metastatic to skin with high sensitivity (94.5%) and specificity (97.2%).     

Evaluation of ornithine decarboxylase activity as a marker for tumor growth rate in malignant tumors

Ornithine decarboxylase (ODC) is a rate-limiting enzyme in the synthesis of polyamines. Polyamines regulate DNA synthesis by a mechanism that is not fully understood. High levels of polyamines and ODC activity are associated with rapid cell growth, particularly in tumor tissues. The aim of this study was to determine whether ODC activity as a marker for rapid alterations in tumor growth could be used to investigate whether nutritional support in cancer patients stimulates tumor cell proliferation. Weight-losing head and neck cancer patients and tumor-bearing mice (MCG 101, C57/BL) were studied during different feeding regimens. The ODC activity in tumor tissue was investigated in relation to the following variables: (1) histopathologic differentiation; (2) DNA content; and (3) bromodeoxyuridine (BrdUrd) incorporation into DNA. After the animals were starved for 24 hours, a significant reduction of tumor growth was demonstrated in the experimental tumor along with a reduction of ODC activity, an accumulation of cells in the G0G1 phase, and a reduction of cells incorporating BrdUrd into DNA. Refeeding after 24 hours generated a response by all variables. Tumor biopsy specimens from patients with head and neck cancer malignancies demonstrated aneuploidy in the cells of 70% of the patients. High ODC activity in tumor tissue was demonstrated mainly among poorly differentiated tumors, and ODC activity was correlated with the compartment size of aneuploidic cells in the tumor. High ODC activity indicated a poor short-term survival (1 year). It was concluded that experimental tumor growth is highly dependent on host feeding. However, there was no evidence supporting the claim that nutritional support to cancer patients stimulates tumor cell proliferation. Determination of ODC activity may be used to monitor rapid changes in DNA synthesis and may have prognostic significance for survival.     

From needles to numbers: can noninvasive imaging distinguish benign and malignant adrenal lesions?

Adrenal masses are a relatively common finding on computed tomography (CT) and magnetic resonance imaging (MRI). Until recently, adrenal biopsy, resection, or clinical follow-up were the only methods of distinguishing benign adenomas from malignancies. On the basis of their higher lipid content, adenomas have characteristic appearances on CT and MRI that can be used to separate them from non-lipid-containing lesions such as metastases. CT densitometry with or without contrast media and chemical shift MRI (CSI) are two examples of techniques with adequate sensitivity (50–90%) and excellent specificity (>95%) for adrenal adenomas. While the need for invasive tissue sampling is reduced because of these techniques, it is eliminated because lesions not meeting the criteria for adenomas are not always malignant. However, CT densitometry and CSI are likely to reduce significantly the need for histology sampling of incidentally discovered adrenal masses due to the high specificity of these new techniques.     

胰腺中段切除术治疗良性和低度恶性胰腺颈体部肿瘤：附32例报告

目的：探讨胰腺中段切除术（MP）治疗良性和低度恶性胰腺颈体部肿瘤的疗效。 方法：回顾性分析2005年8月—2013年2月收治的32例胰腺颈体部良性和低度恶性肿瘤行MP患者资料（MP组）,并与同期因良性和低度恶性胰腺肿瘤行胰十二指肠切除术（PD）的30例（PD组）和行胰体尾切除术（DP）的36例（DP组）患者资料进行比较。 结果：MP组、PD组、DP组平均手术时间分别为（180.8±56.4）、（279.6±79.2）、（190.4±62.3）min;平均术中出血量分别为（196.5±185.7）、（482.6±288.5）、（320.7±240.3）mL;胃肠道功能恢复时间分别为（3.6±1.6）、（5.2±2.3）、（4.1±1.9）d;新增糖尿病例数分别为1、5、9例;术后需要补充胰酶例数分别为0、8、5例,以上指标3组间差异均有统计学意义（均P<0.05）。MP组、PD组、DP组术后胰瘘发生率（18.8%、12.5%、25.0%）以及其他围手术期指标差异均无统计学意义（均P>0.05）。平均随访38个月,各组均无肿瘤复发。 结论：MP治疗良性或低度恶性胰腺颈体部肿瘤是一项合理的技术,能更好地保护胰腺外分泌和内分泌功能。