ErbB2 oncogene antibodies differentiate between the normal and diseased pancreas, and between chronic pancreatitis and pancreatic cancer

Histological differentiation between chronic pancreatitis and pancreatic cancer, especially in biopsy material, remains challenging and the frequent association of 'secondary' chronic pancreatitis (due to ductal obstruction) with pancreatic cancer causes additional diagnostic problems. Our study, using anti-ErbB2 antibodies from Santa Cruz and Dako in tissues from the normal pancreas, chronic pancreatitis and pancreatic cancer showed that these antibodies discriminate between primary chronic pancreatitis and 'secondary' chronic pancreatitis due to pancreatic cancer. Tissues from 28 pancreatic cancer patients, 15 chronic pancreatitis patients and 12 organ donors or early autopsy cases were subjected to immunohistochemical studies using polyclonal ErbB2 antibodies from Santa Cruz and Dako. The Santa Cruz antibody immunoreacted with islet cells in all tissues from the normal pancreas and pancreatic cancer but not in any chronic pancreatitis specimen. The Dako antibody showed a membrane staining of ductal and ductular cells only in chronic pancreatitis cases but in none of the normal or cancer specimens. Moreover, in chronic pancreatitis cases, ductular cells were stained with the Santa Cruz antibody only in the severe form, but not in the mild or moderate form of the disease. The utilized ErbB2 antibodies discriminate between the normal pancreas, chronic pancreatitis and pancreatic cancer. Hence, these antibodies seem to present an additional useful aid in the surgical pathology of pancreatic diseases.     

不同部位胰腺癌的误诊分析

目的分析不同部位胰腺肿瘤的误诊情况,提高胰腺癌诊断率,降低误诊误治率。方法回顾性分析222例胰腺癌患者的误诊原因。结果 222例中50例患者被误诊,误诊率为22.5%。发病部位不同,其误诊情况也不同,其中胰头癌140例,误诊34例(24.3%),误诊为胃炎和胰腺炎。胰体癌16例,误诊9例(56.3%),误诊为腰椎间盘突出症和贲门失迟缓症。胰尾癌41例,误诊5例(12.2%),误诊为胃炎和腰椎间盘突出症。全胰癌24例,误诊2例(8.3%),均误诊为胰腺炎。结论胰腺癌早期临床症状不典型,极易发生误诊,且不同部位误诊率及误诊情况各有不同,应该重视胰腺癌的早期临床表现,避免误诊的发生。     

Recurrent Candida sepsis with prolonged respiratory failure and severe liver dysfunction

Systemic mycoses, especially pulmonary diseases and septicemia are observed increasingly at intensive care units. Essential risk factors for development of candidosis are the expanded use of antibiotics and immunocompromised patients, caused either as a result of a severe underlying disease or iatrogenically induced after organ transplantation. Candida albicans is the most frequent pathogen in microbiological findings. Blood cultures are only positive in massive fungemia. We report a 50-year-old patient with recurrent Candida-septicemia: rupture of the distal esophagus after dilatation because of cardiac achalasia with mediastinal emphysema and mediastinitis. Severe acute respiratory distress syndrome after aspiration with septic shock and acute renal failure at the beginning. Long-term mechanical ventilation, continuous renal replacement therapy and multifarious antibiotic therapy. Early microbiological samples of several positive blood cultures and bronchoalveolar lavages revealed the presence of Candida albicans. In the further clinical course, detection of Pseudomonas species in bronchoalveolar lavages and Staphylococci as well as Enterococci in a number of positive blood cultures. Later on development of a severe liver dysfunction with test results that showed an intrahepatic cholestasis. Because of coagulation failure commencement of artificial liver support with the MARS-system (molecule adsorbent recirculating system). Decrease of high bilirubin levels was accompanied by improvement of clinical condition of the patient. In the following course, repeated severe systemic infections with phases of septicemia or rather septic shock and detection of Candida in several positive blood cultures and bronchoalveolar lavages. In each case increasing bilirubin levels with signs of intrahepatic cholestasis and each time improvement with antimycotic therapy (voriconazol, caspofungin and fluconazol). The patient showed more and more signs of immunodeficiency in the sequel. The clinical appearance of candidosis is manifold. Systemic Candida infections are frequent in patients with immunodeficiency. A recurrent Candida septicemia with prolonged respiratory failure and severe liver dysfunction in form of cholestatic hepatosis, that improved several times with antimycotic therapy in combination with evidence based intensive care measures and artificial organ support is a comparatively rare event.     

胰腺癌患者行内镜逆行胰胆管造影术放置胰管支架后发生胰腺炎的危险因素分析

目的:确定胰腺癌患者行内镜逆行胰胆管造影术放置胰管支架后发生胰腺炎的危险因素。方法:收集2016年4月至2018年7月62名初次接受内镜逆行胰胆管造影术,并在术中插入了胰腺支架预防术后急性胰腺炎的胰腺癌患者的资料。其中术后发生急性胰腺炎患者24例,未发生胰腺炎患者38例,采用固定回归和随机效应的Logistic回归模型对ERCP术放置胰管支架后发生胰腺炎患者进行建模。结果:Logistic回归显示年轻、女性、高血压、插管时间超过60 min、胰管支架放置于胰头、插管次数为ERCP术放置胰管支架后发生胰腺炎的危险因素。高血压、插管时间超过60 min、胰管支架放置于胰头为其独立危险因素。结论:高血压,插管时间过长和胰管支架放置在胰头部位,决定了胰腺癌患者行内镜逆行胰胆管造影术放置胰管支架后更容易发生胰腺炎。     

Cytologic examination of pure pancreatic juice in the diagnosis of pancreatic carcinoma. The endoscopic retrograde intraductal catheter aspiration cytologic technique.

BACKGROUND. Although cytologic examination of pure pancreatic juice obtained with a duodenofiberscope has been useful for the diagnosis of pancreatic carcinoma, the rate of false-negative results is reported to be high. To eliminate these false-negative results, the authors developed a new technique, endoscopic retrograde intraductal catheter aspiration cytology, especially for an accurate cytologic diagnosis of carcinoma of the body or tail of the pancreas. METHODS. The accuracy of conventional cytologic examination of pure pancreatic juice was assessed in 25 patients with pancreatic carcinoma, 29 patients with pancreatitis, and 52 control subjects. Pure pancreatic juice was collected from the pancreatic duct by endoscopic cannulation using a videoimaging duodenoscope after intravenous administration of secretin. The new endoscopic retrograde intraductal catheter aspiration technique was used in four patients with carcinoma of the body or tail of the pancreas and five patients with localized pancreatitis in whom a correct diagnosis was not made by previous cytologic examination of pure pancreatic juice. RESULTS. Positive cytologic findings were obtained in 76% of the patients with pancreatic carcinoma. Positive cytologic results were more frequent in patients with carcinoma of the head of the pancreas than in those with carcinoma of the body or tail. By the new technique, positive cytologic results were obtained in all of the patients with pancreatic carcinoma. This technique caused no severe complications. CONCLUSIONS. This procedure of endoscopic retrograde intraductal catheter aspiration cytology seems useful for diagnosis of pancreatic carcinoma.     

Pancreatic injury in patients with septic shock: A literature review

Sepsis and septic shock are life threatening condition associated with high mortality rate in critically-ill patients. This high mortality is mainly related to the inadequacy between oxygen delivery and cellular demand leading to the onset of multiorgan dysfunction. Whether this multiorgan failure affect the pancreas is not fully investigated. In fact, pancreatic injury may occur because of ischemia, overwhelming inflammatory response, oxidative stress, cellular apoptosis and/or metabolic derangement. Increased serum amylase and/or lipase levels are common in patients with septic shock. However, imaging test rarely reveal significant pancreatic damage. Whether pancreatic dysfunction does affect the prognosis of patients with septic shock or not is still a matter of debate. In fact, only few studies with limited sample size assessed the clinical relevance of the pancreatic injury in this group of patients. In this review, we aimed to describe the epidemiology and the physiopathology of pancreatic injury in septic shock patients, to clarify whether it requires specific management and to assess its prognostic value. Our main finding is that pancreatic injury does not significantly affect the outcome in septic shock patients. Hence, increased serum pancreatic enzymes without clinical features of acute pancreatitis do not require further imaging investigations and specific therapeutic intervention.     

Recurrent Pancreatic Arteritis and Vasculogenic Relapsing Pancreatitis in Rheumatoid Arthritis – A Retrospective Clinicopathologic and Immunohistochemical Study of 161 Autopsy Patients

The aim of this study was to determine: the prevalence, and histological characteristics of vasculitis in the pancreas, and to follow the formal pathogenesis of multifocal pancreatitis due to arteritis and/or arteriolitis (multifocal vasculogenic pancreatitis). A randomized autopsy population of 161 in-patients with rheumatoid arthritis (RA) was studied. Systemic vasculitis (SV) complicated RA in 36 (22.36%) of 161 cases; tissue samples of pancreas were available for histologic evaluation in 28 patients. Pancreatitis and vasculitis were characterized histologically and immunohistochemically. Vasculogenic, multifocal pancreatitis was not recognized clinically. Vasculitis of the pancreatic arterioles and small arteries (branches of splenic artery, upper and lower gastroduodenal arteries) can lead to local ischaemia and to regressive changes in the pancreas. This vasculogenic process is more or less widespread and multifocal, depending on the number of involved vessels and is followed by reactive inflammation, depending on the stages of the pathological process. Because of the recurrent nature of vasculitis with time these regressive changes accumulate within the pancreas and may contribute to an unexpected circulatory failure and sudden death of the patient. Vasculogenic microinfarcts in the pancreas may be clinically characterized by unexplained recurrent abdominal symptoms and spontaneous remissions which insidiously may lead to metabolic failure resistant to therapy.     

合并慢性胰腺炎的胰腺癌癌旁增生性胰管上皮细胞线粒体DNA突变的意义

目的 探讨合并慢性胰腺炎的胰腺癌癌旁增生性胰管上皮细胞线粒体DNA调控序列（D—loop）突变的意义。方法 利用PCR技术,扩增胰腺导管增生性细胞、癌细胞及其各自正常的胃黏膜上皮细胞的线粒体DNA D—loop。核苷酸序列同源性对比分析,观察病变细胞的D-loop突变频率。结果 癌细胞和增生性病变细胞至少存在一个以上的突变点,总突变点为31。突变类型：线粒体DNA 11／12为同质性突变,1／12为异质性突变。D—loop突变频率随病变进展程度呈进行性增加的趋势,异常D—loop由PanIN1的33．3％增加到PanIN3的75,0％（P〈0．01）。结论 胰腺导管上皮细胞病变存在着异常D—loop,D—loop异常程度与病变发展程度呈平行性发展。异常D-loop可作为检测胰腺导管上皮性细胞病变的标志物。     

降钙素原在化疗致粒细胞减少伴发热患者中的临床意义

背景与目的：以往研究显示血清降钙素原可用于发热性疾病的诊断及其严重程度的评估。该研究旨在探讨血清降钙素原在化疗致粒细胞减少伴发热患者中的临床意义。方法：回顾性分析2012年1月—2014年12月以化疗致粒细胞减少伴发热收入复旦大学附属肿瘤医院ICU治疗的147例患者的临床资料。根据患者临床症状、体征、病原生物学特征确定患者有无感染,进而分为感染组及发热原因不详组。根据患者感染严重程度又将感染组分为脓毒症组、严重脓毒症组及脓毒性休克组,分析比较各组血清降钙素原的变化。结果：降钙素原大于0.935 ng/mL为临界值诊断粒细胞减少伴感染患者的敏感度为90.5%,特异度为90.0%,曲线下面积为0.905。感染组与发热原因不详组比较,降钙素原显著增高[1.805(1.268~2.523) ng/mLvs 0.555(0.398~0.818) ng/mL,P<0.001]。亚组分析表明,严重脓毒症组与脓毒症组比较,血清降钙素原水平明显增高[13.885(7.600~17.961) ng/mLvs 1.805(1.268-2.563) ng/mL,P<0.001];脓毒性休克组血清降钙素原水平显著高于严重脓毒症组[23.800(20.050~30.478) ng/mLvs 13.885(4.955~19.133) ng/mL,P<0.001]。结论：血清降钙素原检测可用于粒细胞减少伴感染患者的诊断及感染严重程度的判断。     

Intraoperative pancreatic biopsy--a diagnostic dilemma

The intraoperative diagnostic dilemma of pancreatic cancer vs. chronic pancreatitis often remains unresolved. In the literature, diagnosis based on intraoperative pancreatic biopsy is a matter of controversy. Our study comprised 70 patients with a suspected space occupying pancreatic process who were operated on with the primary goal of arriving at a speedy and precise diagnosis, according to which the appropriate surgery for the specific patient would be performed. Frozen section showed that 44 patients had malignancy of the pancreas; in three patients, there was a false-negative result. In four patients, the histological picture was consistent with chronic pancreatitis. In the remaining 19 patients, biopsy was not performed and the diagnosis was made on the basis of intraoperative inspection and palpation of pancreas. On reviewing the patients, we found that the surgical risk involved in biopsy is quite low and that a high price was paid for diagnosis by inspection and palpation alone. The risk vs. benefit aspect of intraoperative pancreatic biopsy is discussed.     

Pancreatic pseudocyst or a cystic tumor of the pancreas？

Pancreatic pseudocysts are the most common cystic lesions of the pancreas and may complicate acute pancreatitis, chronic pancreatitis, or pancreatic trauma. While the majority of acute pseudocysts resolve spontaneously, few may require drainage. On the other hand, pancreatic cystic tumors, which usually require extirpation, may disguise as pseudocysts. Hence, the distinction between the two entities is crucial for a successful outcome. We conducted this study to highlight the fundamental differences between pancreatic pseudocysts and cystic tumors so that relevant management plans can be devised. We reviewed the data of patients with pancreatic cystic lesions that underwent Jntervention between June 2007 and December 2010 in our hospital. We identified 9 patients （5 males and 4 females） with a median age of 40 years （range, 30-70 years）. Five patients had pseudocysts, 2 had cystic tumors, and 2 had diseases of undetermined pathology. Pancreatic pseudocysts were treated by pseudocystogastrostomy in 2 cases and percutaneous drainage in 3 cases. One case recurred after percutaneous drainage and required pseudocystogastrostomy. The true pancreatic cysts were serous cystadenoma, which was treated by distal pancreatectomy, and mucinous cystadenocarcinoma, which was initially treated by drainage, like a pseudocyst, and then by distal pancreatectomy when its true nature was revealed. We conclude that every effort should be exerted to distinguish between pancreatic pseudocysts and cystic tumors of the pancreas to avoid the serious misjudgement of draining rather than extirpating a pancreatic cystic tumor. Additionally, percutaneous drainage of a pancreatic pseudocyst is a useful adjunct that may substitute for surgical drainage.     

Lymphoma-Associated Pancreatitis as a Presenting Manifestation of Immunoblastic Lymphoma

A 55 year old man presented with clinical signs and symptoms of subacute pancreatitis of unknown aetiology. Two weeks later, inguinal lymphadenopathy developed and a lymph node biopsy revealed a B cell immunoblastic lymphoma. Computerized tomography showed enlargement of the pancreas and immaging features consistent with pancreatitis. Administration of VACOP-B combination chemotherapy achieved complete resolution of the pancreatic mass and the enlarged lymph nodes. We consider this patient to have had lymphoma associated pancreatitis. This case represents a rare clinical presentation of lymphoma suggesting an alternative aetiology of subacute pancreatitis in some cases.     

Immunohistochemical analysis of p53 and MIB-1 in tissue specimens obtained from endoscopic ultrasonography-guided fine needle aspiration biopsy for the diagnosis of solid pancreatic masses

Endoscopic ultrasonography-guided fine-needle aspiration biopsy (EUS-FNAB) has been shown to be a highly accurate technique for distinguishing benign from malignant pancreatic masses. In this study, we examined p53 immunohistochemical analysis in FNAB specimens obtained from solid pancreatic diseases, and prospectively evaluated clinical applications for the diagnosis of malignancy in combination routine histological examination. Tissue specimens obtained from 62 pancreatic masses (51 pancreatic cancers and 11 chronic pancreatitis) by EUS-FNAB were evaluated by routine histological examination and p53 immunostaining. The conventional EUS-FNA diagnostic test statistics for the pancreatic masses were as follows: 76% sensitivity, 91% specificity and 79% accuracy. p53 protein overexpression was observed in 67% patients with pancreatic cancer, but not in patients with chronic pancreatitis. If the diagnosis of malignancy was made using the combination of p53 protein overexpression and conventional histological examination, the diagnostic test statistics changed as follows: 90% sensitivity, 91% specificity and 92% accuracy. p53 immunostaining in combination with routine histological examination of EUS-FNAB may improve the diagnostic accuracy for pancreatic cancer.     

Reversible grade 4 hyperbilirubinemia in a patient with UGT1A1 7/7 genotype treated with irinotecan and cetuximab

Irinotecan-induced gastrointestinal toxicities are common and typically present in the form of diarrhea or nausea and vomiting. However, severe hyperbilirubinemia (grade 3/4) has not been previously reported in association with this chemotherapeutic agent. We report a case of prolonged grade 4 hyperbilirubinemia after a single dose of irinotecan at 125 mg/m(2). This severe toxicity was attributed to a UGT1A1 7/7 genotype and resolved to grade 2 after 8 weeks of supportive care. This case outlines the possibility of severe hepatic toxicity with moderate doses of irinotecan in patients with a UGT1A1 7/7 genotype. Despite the severity and prolonged duration of the associated irinotecan-induced hepatic toxicity, the management of similar cases should focus on intensive supportive measures because the toxicity is likely to resolve eventually.     

Comparative studies on the expression of tumor-associated glycoprotein (TAG-72), CA 19-9 and DU-PAN-2 in normal, benign and malignant pancreatic tissue

Expression of tumor-associated glycoprotein (TAG-72) was examined by immunohistochemistry in pancreatic specimens from normal donors, and from patients with chronic pancreatitis and pancreatic cancer, and was compared with expression of CA 19-9 and DU-PAN-2. In the normal pancreas, TAG-72 was expressed in fewer ductal and ductular cells than were CA 19-9 (p less than 0.05) and DU-PAN-2 (p less than 0.01 and 0.001 respectively), whereas in chronic pancreatitis all 3 antigens were expressed in ductal cells but only CA 19-9 and DU-PAN-2 in ductular cells (p less than 0.001). In the specimens from normal pancreas and chronic pancreatitis cases, TAG-72 was localized in the Golgi region, whereas CA 19-9 and DU-PAN-2 showed diffuse cytoplasmic and glycocalyx patterns. In pancreatic cancer, although the rate of expression of all 3 antigens was similar, their cellular localization differed significantly: only TAG-72 was expressed in the Golgi region (p less than 0.001), whereas CA 19-9 showed mainly glycocalyx (p less than 0.05) and/or intra-luminal patterns (p less than 0.01) compared with that of the other 2 antigens. We conclude that, due to differences in expression of TAG-72 in benign versus malignant cells, the monoclonal antibody against TAG-72 (B72.3) may be suitable for radio-immunodetection or radio-immunotherapy of pancreatic cancer.     

Pancreatic islet cell tumours presenting as recurrent acute pancreatitis: Imaging features in three cases

We present three cases of recurrent pancreatitis that occurred in patients with small islet cell tumours of the pancreas which were obstructing the main pancreatic duct. This is a very uncommon presentation of pancreatic islet cell tumours. The radiological findings in these cases are shown and the implications for imaging of ‘idiopathic’ relapsing pancreatitis are discussed.     

Role of endoscopic retrograde cholangiopancreatography in differentiating pancreatic cancer coexisting with chronic pancreatitis

The pancreatographic appearance and the clinical presentation of ten patients presenting with adenocarcinoma of the head of the pancreas coexisting with chronic pancreatitis were compared with those of 45 patients with chronic pancreatitis (CP), without malignancy, investigated at the same time period. All ten patients, had typical pancreatographic findings of CP, combined with an elongated narrowing of the duct of Wirsung. Marked localized irregularity of the adjacent main duct and of side branches were found in all ten patients. Such findings were not detected in the other 45 patients with CP only. Ultrasonography or computed tomography have detected a definite pancreatic mass in only five of these patients, and in six patients with CP without malignancy. It is concluded that endoscopic retrograde cholangiopancreatography is highly accurate in detecting pancreatic cancer coexisting with CP. It is primarily helpful in elderly patients having severe degrees of CP to rule out cancer.     

CAM 17.1--a new diagnostic marker in pancreatic cancer.

CAM 17.1-Ab is a recently described monoclonal antibody that detects a mucus glycoprotein with high specificity for intestinal mucus, particularly in the colon, small intestine, biliary tract and pancreas. We investigated the expression and release of CAM 17.1 in pancreatic carcinoma cell lines and tissue specimens of normal pancreas, chronic pancreatitis and pancreatic cancer. CAM 17.1 was weakly expressed on normal ductal cells and chronic pancreatitis, whereas it was overexpressed in pancreatic cancer. Serum analysis using a new enzyme-linked antibody sandwich assay (CAM 17.1/WGA) of patients with chronic pancreatitis, pancreatic cancer or other gastrointestinal cancer and of healthy blood donors revealed a high sensitivity (67%) and excellent specificity (90%) of CAM 17.1/WGA assay in pancreatic cancer. In comparison with the tumour marker CA19-9, the sensitivity of the CAM 17.1/WGA assay was similar to the sensitivity of CA 19-9 (67% and 76%, P = 0.22), whereas the specificity of CAM 17.1/WGA assay was higher than in CA 19-9 (90% compared with 78% in chronic pancreatitis, P > 0.05).