Clinical significance of K-ras and c-erbB-2 mutations in pancreatic adenocarcinoma and chronic pancreatitis

Background: The differentiation of chronic pancreatitis (CP) from pancreatic adenocarcinoma (PA) remains the great challenge for clinicians. The purpose of this study was to compare the prevalence of K-ras and c-erbB-2 mutations in PA and CP in order to evaluate their usefulness in differential diagnosis of those diseases. Methods: The study included 49 patients who underwent Whipple resection or distal pancreatectomy for pancreatic adenocarcinoma (26 subjects) or chronic pancreatitis (23 subjects). DNA from pancreatic tissue was analyzed for K-ras codon 12 and c-erbB-2 mutations with PCR amplifications. Results: The K-ras gene mutation has been shown in 20 (76.9%) PA cases and in 8 (34.8%) CP cases (p<0.01). Prevalence of c-erbB-2 amplification in patients with PA was 17 (65.3%), which was not different from CP, 16 (56.5%) (p=0.58). There was a significant correlation between K-ras mutation and lymph node metastases (p=0.025) as well as between K-ras mutation and G3 tumor differentiation (p=0.037). Overall median survival in patients with PA was 9.5 mo. There was no relationship between presence of K-ras (p=0.58) or c-erbB-2 (p=0.17) mutation and survival time in PA patients. Conclusion: Those results may indicate that both K-ras and c-erbB-2 play a role in pancreatic carcinogenesis, however only K-ras may provide an additional tool in differential diagnosis of CP and PC.     

p53、Ki-67基因表达与膀胱癌生物学特性的研究

目的 探讨p53、Ki-67基因表达与膀胱移行细胞癌(BTCC)病理分级、临床分期及复发的关系.方法 收集149例BTCC患者的临床资料及p53、Ki-67表达阳性率.结果 Ⅰ～Ⅱ级BTCC p53、Ki-67阳性率分别为58.8%、64.7%,低于Ⅲ级BTCC p53、Ki-67的阳性率(80.014%、90.0%)(P<0.05,P<0.01);浸润型BTCC的p53、Ki-67基因表达阳性率(80.0%、92.3%)均高于浅表型BTCC阳性率(50.0%、52.4%)(P<0.01).在高分级、高分期BTCC组p53、Ki-67联合表达率(73.3%、73.8%)高于低分级、低分期BTCC组(45.4%、32.1%)(P<0.05).p53、Ki-63共同表达阳性者复发率为37.2%,单一阳性或阴性表达者复发率16.1%,两组复发率有显著性差异(P<0.05).结论 p53、Ki-67基因表达与BTCC的临床分期、病理分级相关,提示p53、Ki-67蛋白过度表达的BTCC高度恶性和预后不良;p53、ki-67基因共同表达阳性组复发率较单一阳性或阴性组复发率高,提示p53和ki-67基因联合表达与BTCC复发可能有相关性.     

Lumican蛋白在胰腺导管腺癌间质中的表达及其与Ki-67、VEGF及突变型P53表达的相关性

目的:观察细胞外基质蛋白Lumican在胰腺导管腺癌(pancreatic ductal adenocarcinoma,PDA)中表达特征,分析Lumican与Ki-67、VEGF、突变型P53等肿瘤恶性表型相关分子的关联.方法:采用免疫组织化学染色(IHC)和逆转录-聚合酶链式反应(RT-PCR)检测PDA原发灶及对应癌旁胰腺组织中Lumican表达.IHC检测PDA原发灶Ki-67、VEGF及突变型P53表达.用SPSS软件行统计学分析.结果:PDA原发灶中,Lumican表达在mRNA及蛋白质水平均明显高于癌旁胰腺组织.就该蛋白在癌灶中的分布特性而言,Lumican蛋白主要定位于癌间质,阳性表达率为83.0%(83/100).低分化PDA中,癌间质过表达Lumican与TNM分期相关(x2=6.446,P<0.05),与年龄、性别、淋巴结转移、远处转移等无明显相关.高中分化PDA中,癌间质过表达Lumican与临床病理特征无关,而与Ki-67(r=-0.28,P=0.017)、VEGF(r=-0.264,P=0.025)及突变型P53(r=-0.253,P=0.032)表达呈明显负相关.结论:Lumican在PDA原发灶中表达高于癌旁胰腺组织,主要分布于癌间质.Lumican在癌间质过表达与低分化PDA的TNM分期相关,与高、中分化PDA的Ki-67、VEGF及突变型P53表达呈负相关.     

Staining for p53 and Ki-67 increases the sensitivity of EUS-FNA to detect pancreatic malignancy

AIM: To investigate whether tumor marker staining can improve the sensitivity of endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) to diagnose pancreatic malignancy.METHODS: Patients who underwent EUS-FNA were retrospectively identified. Each EUS-FNA specimen was evaluated by routine cytology and stained for tumor markers p53, Ki-67, carcinoembryonic antigen (CEA) and CA19-9. Sensitivity, specificity, positive and negative predictive values (PPV and NPV), and positive and negative likelihood ratios (PLR and NLR) were calculated in order to evaluate the performance of each test to detect malignancy.RESULTS: Sixty-one specimens had complete sets of stains, yielding 49 and 12 specimens from pancreatic adenocarcinomas and benign pancreatic lesions due to pancreatitis, respectively. Cytology alone had sensitivity and specificity of 41% and 100% to detect malignancy, respectively. In 46% of the specimens, routine cytology alone was deemed indeterminate. The addition of either p53 or Ki-67 increased the sensitivity to 51% and 53%, respectively, with perfect specificity, PPV and PLR (100%, 100% and infinite). Both stains in combination increased the sensitivity to 57%. While additional staining with CEA and CA19-9 further increased the sensitivity to 86%, the specificity, PPV and PLR were significantly reduced (at minimum 42%, 84% and 1, respectively). Markers in all combinations performed poorly as a negative test (NPV 26% to 47%, and NLR 0.27 and 0.70).CONCLUSION: Immunohistochemical staining for p53 and Ki-67 can improve the sensitivity of EUS-FNA to diagnose pancreatic adenocarcinoma.     

Prevalence and clinical significance of combined K-ras mutation and p53 aberration in pancreatic adenocarcinoma

Summary Conclusion This study could not attribute survival differences to the coincident acquisition of two common genetic alterations, K-ras mutation and p53 overexpression in pancreatic adenocarcinoma patients. Additionally, our data indicate the converse to be true: Those patients lacking both K-ras mutation and aberrant p53 expression showed the shortest survival when compared with cases showing either alteration or both. This study also showed the negative effect of K-ras mutation and p53 expression on pancreas cancer patient's survival after treatment with either radiation therapy or chemotherapy. Background Mutations of the oncogene K-ras at codon 12 are reported to be the most common genetic alteration in pancreatic carcinoma, whereas either overexpression or mutation of the tumor suppressor p53 gene is considered the most common genetic alteration in neoplasia of all types. p53 overexpression has been attributed to survival differences in pancreatic carcinoma, but such association is still controversial. No studies have fully documented the combined incidence of K-ras and p53 alterations in pancreatic adenocarcinoma, or their combined effect on patient survival in a large case series. The influence of radiation or chemotherapy in groups showing both, either, or neither mutation is also undocumented. Methods Paraffin-embedded tissue sections from 76 cases of pancreatic adenocarcinoma were cut for DNA extraction for K-ras analysis and immunohistochemical staining for aberrant p53 expression. K-ras mutation was determined by single-strand conformation polymorphism (SSCP) and slot-blot allele-specific oligonucleotide (ASO) hybridization of PCR-amplified DNA product. p53 expression was scored on the basis of percent nuclear staining with the MAb DO7. Results Sixty-four of 76 cases (84%) showed K-ras mutation, p53 expression, or both. K-ras was mutated in 55 of 76 cases (72%). p53 was expressed in 33 of 76 cases (43%). Twenty-four of 76 cases (31%) showed both K-ras mutation and p53 expression. The presence of both alterations was not related to significant differences in tumor grade, stage, or survival compared to either alteration alone. A sizable subset (16% of cases) lacked either alteration, and surprisingly, this group showed the shortest median survival compared to those with K-ras mutation, p53 expression, or both (p=0.024). Patients whose tumors were K-ras-negative showed the greatest difference in median survival with radiation therapy (median survival 30.8 mo vs 7.8 mo with no radiation,p=0.005).     

P53 and Ki-67 overexpression in gastroesophageal reflux disease – Barrett's esophagus and adenocarcinoma sequence

Gastroesophageal reflux disease (GERD) is a major risk factor for the development of esophageal adenocarcinoma (ACE). Many molecular alterations occur in esophageal carcinogenesis, yet the exact mechanism of ACE development remains unknown. This study aims to determine p53 protein and Ki-67 expression in esophageal mucosa of patients with GERD and study the correlation between these markers and the progression from normal squamous epithelium to esophagitis, columnar epithelium with or without intestinal metaplasia and ACE. We analyzed p53 protein and Ki-67 expression in biopsies of 200 patients with GERD and 35 patients with ACE. Those biopsies were classified into five groups: (i) G1 normal squamous epithelium (58); (ii) G2 esophagitis (80); (iii) G3 columnar epitheliums without intestinal metaplasia (30); (iv) G4, columnar epitheliums with intestinal metaplasia (32); and (v) G5 ACEs (35). p53 protein overexpression was found in 7% (4) of G1, 37.5% (30) of G2, 30% (9) of G3, 62.5% (20) of G4, and 71.4% (25) of G5 (p < 0.001). Ki-67 index increased according to the severity of histopathological diagnoses. Ki67 index was 21.3 ± 19.5% in G1, 38.8 ± 24.9% in G2, 37.7 ± 26.3% in G3, 52.8 ± 24.6% in G4, and 57.1 ± 25.1% in G5 ( P < 0.001). Linear correlation between p53/Ki67 expression and the multistep progression from squamous epithelium to ACE was observed ( P < 0.001 and P < 0.05). Our results indicate that overexpression of p53 and increased Ki-67 could be associated with the development and progression to ACE in patients with GERD.     

Prior history of acute pancreatitis predicts poor survival in patients with resectable pancreatic ductal adenocarcinoma

Background/objectivesMounting evidence has suggested that acute pancreatitis (AP) is a risk factor for pancreatic ductal adenocarcinoma (PDAC), but its role in survival in PDAC patients was rarely investigated. The objective was to investigate the association of a history of AP with survival among PDAC patients who underwent surgical resection.MethodsA retrospective cohort study comprising 632 patients who were diagnosed with resectable PDAC was conducted. Survival was evaluated by history of AP prior to a diagnosis of PDAC using Kaplan-Meier methods and log-rank tests. Multivariate analyses for mortality were estimated using the Cox proportional hazards model. Propensity score matching methods were used to balance the difference of clinical characteristics between patients with and without AP history.ResultsThe log-rank tests showed that patients with a history of AP had a worse overall survival than those without a history of AP (p = 0.006). The multivariable-adjusted hazard ratio (HR) for mortality comparing participants with AP to those without AP was 1.808 (95% CI: 1.241–2.632, p = 0.002). Patients with a recent history of AP (<2 years), rather than patients with a remote history of AP (≥2 years), were found to have significantly worse survival (p = 0.014) than those without a history of AP. After adjusted for PSM, history of AP remained an independent survival predictor of PDAC following surgical resection.ConclusionsOur findings indicate that a history of AP, especially a recent history of AP, is associated with poor survival among patients with resectable pancreatic ductal adenocarcinoma.     

Serum cytokine profiles in patients with pancreatic cancer and chronic pancreatitis

BackgroundChronic pancreatitis (CP) may cause tumor-like lesions, creating a challenge in distinguishing between CP and pancreatic ductal adenocarcinoma (PDAC) in a patient. Given that invasive surgery is a standard cancer treatment, we aimed to examine whether a noninvasive diagnostic tool utilizing serum cytokines could safely differentiate between PDAC and CP.MethodsA pre-operative serum panel comprising 48 inflammatory cytokines, CA19-9, and C-reactive protein (CRP) was analyzed, consisting of 231 patients, 186 with stage I–III PDAC and 45 with CP. We excluded PDAC patients who underwent neoadjuvant therapy and those CP patients with other active malignancies. The laboratory variables most associated with PDAC diagnosis were assessed using logistic regression and selected using the lasso method.ResultsThe cytokines CTACK, GRO-α, and β-NGF were selected alongside CA19-9 and CRP for our differential diagnostic model. The area under the curve (AUC) for our differential diagnostic model was 0.809 (95% confidence interval [CI] 0.738–0.880), compared with 0.791 (95% CI 0.728–0.854) for CA19-9 alone (not significant).ConclusionsWe found that inflammatory cytokines CTACK, GRO-α, and β-NGF alongside CA19-9 and CRP may help distinguish PDAC from CP.     

Prognostic role of p53 and Ki-67 immunohistochemical expression in patients with surgically resected lung adenocarcinoma: a retrospective study

Objective

p53 mutations and the Ki-67 protein are frequently observed in various types of human cancer; the abnormal expression of p53 and Ki-67 in the tumor is associated with poor survival of lung cancer patients. We aimed to assess the prognostic role of immunohistochemical (IHC) expression of p53 and Ki-67 in lung adenocarcinoma tissue.

Methods

Tumor samples from 136 patients who had undergone surgical resection for lung adenocarcinoma were retrospectively evaluated for p53 and Ki-67 expression by immunohistochemistry. Associations of clinical and pathologic variables with p53 and Ki-67 were determined using the χ² test. After excluding two patients (follow-up loss), 134 cases were evaluated for associations between p53, Ki-67, clinical and pathologic variables, and survival by using the Cox proportional hazards regression model and Kaplan-Meier method.

Results

In the 136 patients, p53 was positive in 71.0% (93/131), and Ki-67 showed high in 49.2% (61/124). Unlike p53, Ki-67 was associated with male sex, smoking, and poor tumor differentiation (P=0.004, P=0.001 and P=0.006). Of these, poor tumor differentiation strongly was correlated with high level of Ki-67 expression (P=0.008). Neither p53 nor Ki-67 was associated with increased risk of death (P=0.318, P=0.053); however, age ≥60 years and lymph node involvement were significant predictors of death (P=0.039 and P=0.042). The log-rank test revealed a significant association between Ki-67 and lower survival in all patients (χ²=5637; P=0.018); however, the risk was limited to stage III cases (χ²=5.939; P=0.015). Unlike p53, patients with high level of Ki-67 expression showed lower 3-year actuarial survival than those without (log-rank test, χ²=4.936; P=0.026).

Conclusions

IHC expression of Ki-67 in lung adenocarcinoma tissue shows stronger association with poor tumor differentiation, and negatively affects patients’ survival in advanced-stage lung cancer; however, the role of p53 on patient outcome needs further study.     

Gallbladder carcinoma: the role of p53 protein overexpression and Ki-67 antigen expression as prognostic markers

BackgroundThe overexpression of p53 protein and the expression of Ki-67 antigen may affect the survival of patients with gallbladder carcinoma. This association has been tested in a series of 41 patients with relatively early carcinoma of the gallbladder.MethodsForty-one surgical specimens from patients with a postoperative histological diagnosis of gallbladder carcinoma were studied. All patients were operated by simple cholecystectomy only because the tumours were not advanced and/or their general condition was poor. Patients submitted to radical operations were excluded. p53 expression was calculated from nuclear staining according to the intensity and extent of positive cells, as graded on a scale from 1 to 3; a combined score of >3 was considered as overexpression. Ki-67 expression was calculated by the MIB-I index: the percentage of positively stained tumour cell nuclei out of the total tumour cells counted (n = 1000); >20% of stained cells was considered positive.ResultsTwenty-nine gallbladder carcinomas (71%) overexpressed p53 protein in the cell nuclei. No significant differences were found in relation to cell differentiation on the level of tumour infiltration through the gallbladder wall. Five-year survival of patients with gallbladder carcinoma overexpressing p53 was 17.2%, while survival of patients without p53 overexpression was 30% (not significant). Twenty-four cases (58.5%) were considered positive for the MIB-I index. There were no differences between the grade of cell differentiation and wall infiltration. Five-year survival of the patients with a MIB-I positive index was 9.2% as opposed to 27.7% for those with a negative index (not significant).Conclusionsp53 protein nuclear overexpression and Ki-67 protein expression in gallbladder carcinoma were not related to histological differentiation, level of gallbladder wall invasion or patient survival.     

Serum endocannabinoids in assessing pain in patients with chronic pancreatitis and in those with pancreatic ductal adenocarcinoma

Background: The endocannabinoid system plays a substantial role in analgesia.

Aim: To analyze N-arachidonoylethanolamine (AEA), N-oleoylethanolamine (OEA), linoleoyl ethanolamide (LEA), α-linoleoyl ethanolamine (α-LNEA), N-palmitoylethanolamine (PEA) and N-stearoyl ethanolamine (SEA) in two groups of patients having chronic pancreatic diseases.

Patients and methods: Twenty-six patients with chronic pancreatitis, 26 patients with pancreatic ductal adenocarcinoma and 36 healthy subjects were studied. The visual analogic scale (VAS) was used for assessing pain immediately before the venipuncture to obtain blood in all subjects. Six endocannabinoids were measured in serum of the patients enrolled.

Results: Only OEA, LEA and PEA serum levels were significantly higher in patients with pain as compared to those without. Using the cutoff values, the sensitivity and specificity of the various endocannabinoids in evaluating pain in patients with chronic pancreatitis and in those with pancreatic ductal adenocarcinoma were: 44.2% and 95.6% for AEA, 83.7% and 73.3% for LEA, 88.4% and 91.1% for LNEA, 81.4% and 82.2% for OEA, 81.4% and 88.9% for PEA, 86.0% and 88.9% for SEA, respectively.

Conclusion: Endocannabinoids are not useful in assessing pain in patients with chronic pancreatic diseases and they cannot replace a simple method such as VAS for assessing the pain and its intensity.     

胰腺癌组织Survivin与Ki-67的表达及其意义

目的:探讨Survivin和Ki-67在胰腺癌组织中的表达及其与临床病理特征的关系．方法:采用免疫组织化学技术检测各期胰腺癌86例及癌旁组织78例中Survivin和Ki-67的表达水平,并结合病理特征进行分析。结果:胰腺癌旁组织或良性肿瘤旁组织不表达Survivin 蛋白．胰腺癌组织Survivin阳性表达率为87．9％,显著高于胰岛细胞癌(12．7％)或胰岛细胞瘤(5．2％)(P<0．01),而且Survivin表达程度与肿瘤分化程度、淋巴结转移相关(P<0．05)．Ki-67蛋白在胰腺癌组织中阳性表达率为 94．4％,显著高于胰岛细胞癌或胰岛细胞瘤组(P<0．01), 并与胰腺癌组织分化程度相关(P<0．05)．两种蛋白表达有高度相关性(r=0．87)．结论:Survivin和Ki-67在胰腺癌组织中过表达,并且与胰腺癌病理特征密切相关．Survivin可能是反应胰腺癌预后不良的指标．     

慢性胰腺炎增生性胰管上皮细胞线粒体DNA突变的意义

目的探讨慢性胰腺炎增生性胰管上皮细胞线粒体DNA调控序列D-环突变的意义。方法利用PCR技术扩增46份来自11例慢性胰腺炎不同程度的胰腺导管增生性上皮细胞和其各自正常组织的线粒体DNA全序列。使用核苷同源序列（BLAST）分析病变组织的线粒体DNA。结果9份标本D-环共有15个突变点，增生性导管上皮细胞D-环至少存在一个以上异常点。异常D-环随病变进展程度呈进行性增加趋势．从单纯性导管上皮细胞肥大性增生的26．1％增至腺瘤样增生的80．0％（P〈0．01）。结论D-环异常程度与病变程度近乎呈平行性发展，异常D-环可作为检测增生性胰管上皮性组织病变的标志物。     

Clinical relevance of p53 index and expression of proliferating cell nuclear antigen and Ki-67 in gastric cancer

The prognostic value of the immunohistochemical expression of p53 protein, proliferating-cell nuclear antigen (PCNA) and Ki-67 antigen was evaluated in a series of 116 stage I–II gastric cancer patients. The staining for p53 protein (staining frequency and intensity) in malignant cells was expressed as a p53 index. Similarly, the staining frequency and intensity for PCNA and Ki-67 were evaluated. The p53 index was independent of the stage and differentiation grade, but significantly related to DNA ploidy, S-phase fraction and mitotic activity. A high p53 index was a sign of inferior survival, compared to a low or intermediate index. p53-negative tumours were also associated with poor survival. In a multivariate analysis, only the depth of tumour infiltration and the presence of nodal metastases were independent prognostic factors in stage I–II gastric cancer. PCNA expression and Ki-67 antigen expression were not related to the stage, ploidy, proliferative activity or p53 expression, and they had no impact on survival. The results indicate that p53 protein expression may be of prognostic significance in gastric cancer, while PCNA and Ki-67 antigen expression have no predictive value. Received: 2 February 1998 / Accepted: 16 June 1998     

肺癌组织中P53和Ki-67的表达及意义

目的 观察P53和Ki-67在肺癌组织中的表达状况及其与病理和临床特征的意义.方法 采用免疫组织化学SP法检测233例肺癌组织中P53和Ki-67的表达,结合临床资料进行分析.结果 肺癌组织中P53和Ki-67的阳性表达率分别为80.7％和99.6％,其中低阳性表达率分别占了阳性表达率的44.2％和57.2％.P53的表达与肺癌组织类型无明显关系,而Ki-67的表达与肺癌组织类型有一定关系,鳞癌以高表达为主,而腺癌与细支气管肺泡癌以低表达为主;P53在淋巴结转移组的阳性表达率为95.0％,高于无淋巴结转移组,而Ki-67的表达与淋巴结是否转移无明显关联.结论 肺癌组织中P53和Ki-67阳性表达率高,但低阳性表达的病例占了相当的比例,两者可能共同参与了肺癌的发生、发展,P53与肺癌淋巴结转移的关系可能更大,而Ki-67的阳性表达程度与病理类型有关.     

Expression of COX-2, PCNA, Ki-67 and p53 in gastrointestinal stromal tumors and its relationship with histopathological parameters

AIM： To investigate the expression of Cyclooxygenase-2 （COX-2）, proliferating cell nuclear antigen （PCNA）, Ki-67 and p53 in gastrointestinal stromal tumors （GISTs） and its relationship with histopathological parameters.
METHODS： Twenty-five GISTs were examined by light microscopy and immunohistochemistry, c-kit, CD34, SMA, S-100 protein, COX-2, PCNA, Ki-67 and p53 were detected immunohistochemically and the relationship was evaluated among histopathologic parameters such as mitotic index （MI）, tumor grade, tumor size, COX-2, PCNA, Ki-67 and p53.
RESULTS： COX-2 protein expression was found in 19 of 25 （76%） of the tumors, and expression was noted in the cytoplasm of the tumor cells, p53 was significantly related to MI and tumor grade but no relationship was found between COX-2, proliferation markers and MI, tumor grade and tumor size.
CONCLUSION： COX-2 is expressed in most GISTs and it may play an important role in the proliferation and progression of these tumors or a useful marker to identify GIST. Although immunohistochemical assessment of p53 can be used for distinguishing the risk groups of GISTs, tumor size and mitotic rate should be considered at the same time.     

Cyclooxygenase (COX)-2 immunoreactivity and relationship to p53 and Ki-67 expression in colorectal cancer

The tumor-suppressive effects of nonsteroidal antiinflammatory drugs (NSAIDs) have been suggested to be due to a reduction in cyclooxygenase (COX)-2 activity, although the effects of COX-2 in the colonic mucosa and in colorectal cancer have not been determined. Ki-67 immunoreactivity in cancers is also attracting attention, as Ki-67 reflects cell proliferation, while p53 immunoreactivity is also of interest, as it reflects the malignancy of colorectal lesions. Accordingly, to determine these correlation, we investigated the distribution and intensity of COX-2, p53 and Ki-67 expression in both cancerous and non-cancerous tissues from patients with sporadic and ulcerative colitis (UC)-associated colorectal cancer. We selected 21 colorectal cancer specimens, obtained by surgical resection or colonoscopic biopsy, from 21 patients, including 3 with UC (13 men and 8 women; aged 42–78 years). Histological examination of hematoxylin and eosin-stained specimens revealed that 9 were well differentiated; 11, moderately differentiated; and 1 was a poorly differentiated adenocarcinoma. We used anti-COX-2, p53, and Ki-67 antisera to perform immunohistochemical staining by the labelled streptavidin biotin method and then assessed and graded the staining intensity and distribution. COX-2 staining was more intense in cancer tissue than in non-cancerous areas. Colorectal cancers associated with UC were not stained intensely. COX-2, p53, and Ki-67 positivity rates in were 38.1%, 38.1%, and 47.6%, respectively. There were no relationships among the distributions or intensities of COX-2, p53, and Ki-67 expression. Our results indicate that colorectal cancer tissues overexpress COX-2, but that there are no relationships between COX-2, p53, and Ki-67 expression, suggesting that COX-2 expression may not be related to cell proliferation or to the grade of malignancy. However, it is necessary to determine whether COX-2 in cancer tissue is involved in carcinogenesis or whether it is simply a product of cancer. (Received: July 7, 1998; accepted: Oct. 23, 1998)     

Metastatic pancreatic adenocarcinoma associated with chronic calcific pancreatitis and a heterozygous SPINK1 N34S mutation

Contrary to patients with a cationic trypsinogen gene (PRSS1) mutations, Serine protease inhibitor Kazal-type 1 (SPINK1) heterozygote gene mutation carriers have a very low penetrance for acute, acute recurrent and/or chronic pancreatitis. Despite this, heterozygote SPINK 1 gene mutation patients have a similar age of onset of pancreatitis as PRSS 1 gene mutation patients. While the substantially elevated risk of pancreatic cancer in patients with PRSS1 gene mutations with chronic pancreatitis has been well established, little is known about the risk of pancreatic cancer in SPINK 1 gene mutation carriers with pancreatitis. We describe a case of malignant pancreatic cancer diagnosed in a young patient with chronic pancreatitis who is a SPINK 1 heterozygote gene mutation carrier. The risk of pancreatic cancer in gene mutation patients with chronic pancreatitis, in addition to screening options and management options for these patients is discussed.     

Role of dual-point 18F-FDG-PET/CT in the diagnosis of pancreatic adenocarcinoma,in patients with and without concomitant chronic pancreatitis: Comparison with CECT and EUS

PurposeThe aim of this study was to evaluate the diagnostic performance of dual-time-point-PET/CT, CECT and EUS + FNA in diagnosing pancreatic-ductal-adenocarcinomas (PDAC), in context of concomitant Chronic Pancreatitis (CP).Methods18F-FDG-PET/CTs were prospectively acquired in 22 confirmed CP and 23 confirmed PDAC patients (calculated for 90% power); and cut-offs of 2.2 for early-SUV(～1hr), 2.4 for delayed-SUV(～3hr) and 1.36 for Retention-index (RI), were derived. These cut-offs were validated in PET/CTs of 75 patients (51.9 ± 13.3years; 54 men) with pancreatic masses of unknown nature. Comparisons were made with triple-phase-CECT (73 patients) and EUS + FNA (54 patients). Histopathology was obtained in 68 patients (including all PDACs) and 7 were followed up for minimum of 2 years.ResultsIn patients without concomitant CP, sensitivity, specificity and accuracy for diagnosing malignancy in standard-acquisition-PET/CT, dual-time-point-PET/CT, CECT and EUS + FNA were 97.4%, 83.3%, 94.0%; 97.4%, 75.0%, 92%; 94.6%, 66.7%, 87.8% and 92.6%, 88.9%, 91.7% respectively. Corresponding values in patients with concomitant CP were 88.9%, 57.1%, 80.0%; 100%, 57.1%, 88%; 82.4%, 57.1%, 75% and 100%, 100%, 100% respectively. In lesions ≤2 cm (AJCC-T1), dual-time-point-PET/CT was the most sensitive (95.8%). ROC-analysis revealed significantly higher area-under-the-curve for RI over early-SUV (p = 0.002) in cases with concomitant CP only. In patients with confirmed liver-metastases, PET/CT and CECT identified 15/16 and 13/16 lesions. PET/CT identified additional lung-metastases in 3 and bone-metastasis in one patient.ConclusionIn patients without concomitant CP and with larger lesions, PET/CT and CECT are equivocal as screening modalities, with no benefit of dual-time-point-PET/CT acquisitions. However, in patients with concomitant CP and smaller lesions, dual-time-point PET/CT is better; with sensitivity comparable to EUS + FNA.