Pancreatic cancer presenting as a Sister Mary Joseph's nodule: case report and update of the literature

Cutaneous metastasis of an occult malignancy to the umbilicus has come to be known as a Sister Mary Joseph's nodule (SMJN). More than 400 cases of this well-described clinical presentation of advanced gastrointestinal and gynecologic cancers have been reported. Pancreatic cancer presenting as a SMJN is a rare phenomenon. In most series, the pancreas is the source of a SMJN in 7% to 9% of cases. We report a case of pancreatic adenocarcinoma in which the initial presenting sign was a SMJN. We also reviewed the published literature from the last 100 years on this phenomenon by conducting a detailed PubMed search. Including this case, we identified 57 cases of SMJN originating from the pancreas. The clinical patient characteristics with regard to age, male-female ratio, race, and prognosis of these cases were similar to that of pancreatic cancer in general. In contrast, 91% of these cases originated in the tail and body of the pancreas rather than the head of the pancreas. This case emphasizes that pancreatic cancer should be considered in the differential diagnosis of umbilical metastasis.     

Sister Mary Joseph��s nodule derived from pancreatic cancer

Background/Purpose

Umbilical metastases known as Sister Mary Joseph??s nodules (SMJNs) occur rarely. They are an uncommon clinical or radiographic finding, and are rare as the first sign of a malignant disease. Pancreatic cancer presenting as an SMJN is a rare phenomenon, and is the source of an SMJN in 9% of cases.

Case presentation

We experienced four cases of SMJN derived from pancreatic cancer. All cases originated in the tail and/or body of the pancreas.

Discussion

Herein, we introduce a case with pathognomonic imaging findings. We also present the results of our review of recently published papers about SMJN, done by conducting a PubMed search.     

A case of Sister Mary Joseph's nodule as a presenting sign of gastric cancer]

The cutaneous metastasis of a visceral malignancy to the umbilicus is known as "Sister Mary Joseph's nodule (SMJN)". It is considered to be a predictor of poor prognosis because it mostly occurs in advanced, metastasizing cancer. However, it is a very rare condition as an initial presenting sign of primary cancer. We recently encountered a 48-year-old man presented with an umbilical lump. The lesion was a firm, ill-delineated, painful nodule with regular surface in the umbilicus. Abdominal computed tomography showed a 2.2 cm sized, ill-defined, delayed enhancing mass at the periumbilical area accounting for umbilical nodule. Diffuse irregular thickening of peritoneum and diffuse wall thickening of stomach implied the diagnosis of gastric cancer. Esophagogastroduodenoscopy revealed diffuse nodular infiltrative lesion from cardia through body of the stomach, compatible with Bormann type 4 advanced gastric cancer. Later, histopathologic confirmation showed a presence of signet ring cell adenocarcinoma from biopsy specimens. We experienced a case presenting with an umbilical metastasis as the first sign of gastric adenocarcinoma. It is thought that direct extension of tumor through the peritoneum might be the route for umbilical metastasis. Careful examination of all umbilical lesions must be needed for the early diagnosis of internal malignancy.     

Pancreatic cancer proteome: the proteins that underlie invasion, metastasis, and immunologic escape

BACKGROUND & AIMS: Pancreatic cancer is a highly lethal disease that has seen little headway in diagnosis and treatment for the past few decades. The effective treatment of pancreatic cancer is critically relying on the diagnosis of the disease at an early stage, which still remains challenging. New experimental approaches, such as quantitative proteomics, have shown great potential for the study of cancer and have opened new opportunities to investigate crucial events underlying pancreatic tumorigenesis and to exploit this knowledge for early detection and better intervention. METHODS: To systematically study protein expression in pancreatic cancer, we used isotope-coded affinity tag technology and tandem mass spectrometry to perform quantitative proteomic profiling of pancreatic cancer tissues and normal pancreas. RESULTS: A total of 656 proteins were identified and quantified in 2 pancreatic cancer samples, of which 151 were differentially expressed in cancer by at least 2-fold. This study revealed numerous proteins that are newly discovered to be associated with pancreatic cancer, providing candidates for future early diagnosis biomarkers and targets for therapy. Several differentially expressed proteins were further validated by tissue microarray immunohistochemistry. Many of the differentially expressed proteins identified are involved in protein-driven interactions between the ductal epithelium and the extracellular matrix that orchestrate tumor growth, migration, angiogenesis, invasion, metastasis, and immunologic escape. CONCLUSIONS: Our study is the first application of isotope-coded affinity tag technology for proteomic analysis of human cancer tissue and has shown the value of this technology in identifying differentially expressed proteins in cancer.     

Role of abnormal lipid metabolism in development,progression, diagnosis and therapy of pancreatic cancer

There is growing evidence that metabolic alterations play an important role in cancer development and progression. The metabolism of cancer cells is reprogrammed in order to support their rapid proliferation. Elevated fatty acid synthesis is one of the most important aberrations of cancer cell metabolism. An enhancement of fatty acids synthesis is required both for carcinogenesis and cancer cell survival, as inhibition of key lipogenic enzymes slows down the growth of tumor cells and impairs their survival. Based on the data that serum fatty acid synthase (FASN), also known as oncoantigen 519, is elevated in patients with certain types of cancer, its serum level was proposed as a marker of neoplasia. This review aims to demonstrate the changes in lipid metabolism and other metabolic processes associated with lipid metabolism in pancreatic ductal adenocarcinoma (PDAC), the most common pancreatic neoplasm, characterized by high mortality. We also addressed the influence of some oncogenic factors and tumor suppressors on pancreatic cancer cell metabolism. Additionally the review discusses the potential role of elevated lipid synthesis in diagnosis and treatment of pancreatic cancer. In particular, FASN is a viable candidate for indicator of pathologic state, marker of neoplasia, as well as, pharmacological treatment target in pancreatic cancer. Recent research showed that, in addition to lipogenesis, certain cancer cells can use fatty acids from circulation, derived from diet (chylomicrons), synthesized in liver, or released from adipose tissue for their growth. Thus, the interactions between de novo lipogenesis and uptake of fatty acids from circulation by PDAC cells require further investigation.     

Resectability of presymptomatic pancreatic cancer and its relationship to onset of diabetes: a retrospective review of CT scans and fasting glucose values prior to diagnosis

BACKGROUND: The timeline of progression of pancreatic cancer from resectable to unresectable disease is unknown. New-onset diabetes often occurs in pancreatic cancer. It is unclear if the cancer is resectable at the onset of diabetes. We (a) determined the resectability of pancreatic cancer on abdominal CT scans done prior to clinical diagnosis and (b) correlated resectability with onset of diabetes. METHODS: All CT scans done at diagnosis or before pancreatic cancer diagnosis were reviewed and pancreatic changes classified as normal, potentially resectable, or unresectable pancreatic cancer. Fasting blood glucose values obtained at and prior to diagnosis were available in 18 patients. The date of onset of diabetes and the interval between onset of diabetes and diagnosis of cancer were noted. RESULTS: Thirty patients fulfilled inclusion criteria. Prior to diagnosis, 28 patients had 38 CT scans done at a median of 18 months (range 1-41) before cancer diagnosis. At cancer diagnosis, only 7/30 patients could undergo margin-negative surgical resection. CT scans done >/=6 months prior to diagnosis showed either a normal pancreas (N = 20) or a resectable mass (N = 6); none had unresectable cancer. The mean interval between onset of diabetes and diagnosis of pancreatic cancer was 10 months (range 5-29 months). At the onset of diabetes, 3 patients had normal pancreas, 6 had resectable, and 4 had unresectable pancreatic cancer. CONCLUSIONS: Pancreatic cancer is frequently undetectable or resectable on CT scans done >/=6 months prior to clinical diagnosis. At onset of diabetes, pancreatic cancers are generally resectable.     

Enlarged pancreas: not always a cancer

Pancreatic fat accumulation has been described with various terms including pancreatic lipomatosis, pancreatic steatosis, fatty replacement, fatty infiltration, fatty pancreas, lipomatous pseudohypertrophy and nonalcoholic fatty pancreas disease. It has been reported to be associated with type 2 diabetes mellitus, acute pancreatitis, pancreatic cancer and the formation of pancreatic fistula. The real incidence of this condition is still unknown. We report a case of pancreatic steatosis in a non-obese female patient initially diagnosed with a mass in the head of the pancreas. Magnetic resonance imaging(MRI) was carried out to define the characteristics of the pancreatic mass. MRI confirmed the diagnosis of fat pancreas. Enlarged pancreas is not always a cancer, but pancreatic steatosis is characterized by pancreatic enlargement. MRI could give a definite diagnosis of pancreatic steatosis or cancer.     

New-onset diabetes and pancreatic cancer.

BACKGROUND & AIMS: Although many individuals with pancreatic cancer have diabetes, the association between new-onset diabetes mellitus and the subsequent incidence of pancreatic cancer is unclear. METHODS: We conducted a retrospective cohort study to estimate the incidence of pancreatic cancer subsequent to a new diabetes diagnosis and to evaluate factors associated with a subsequent pancreatic cancer diagnosis. We used the Veterans Health Administration National Patient Care Database to assemble a cohort of 1,421,794 US veterans without prior diabetes or pancreatic cancer diagnoses. We recorded coding for new diabetes diagnoses (> or =2 International Classification of Diseases-9 codes for diabetes within a 12-month period), pancreatic cancer, age, sex, race, and common gastrointestinal symptoms. RESULTS: A total of 36,631 (2.6%) of the 1,421,794 veterans were diagnosed with new-onset diabetes in 1999; 149 subsequently received a diagnosis of pancreatic cancer. Pancreatic cancer incidence in patients with new-onset diabetes (83.8/100,000 person-years) was 2.2-fold higher (95% confidence interval, 1.84-2.56) than in nondiabetics, and was highest during the first 2 years after diabetes diagnosis. One additional pancreatic cancer was diagnosed for every 332 new diabetics over 6 years. A subsequent pancreatic cancer diagnosis (among new-onset diabetics) was associated independently with younger age groups, changes in bowel habits, constipation, epigastric pain, and malnutrition. CONCLUSIONS: New-onset diabetes was associated with a significantly increased rate of pancreatic cancer diagnosis, particularly in the first 2 years after diabetes diagnosis. Factors associated with pancreatic cancer diagnosis included younger age groups and the presence of gastrointestinal symptoms. The absolute incidence of pancreatic cancer was low.     

Risk factors for the development of pancreatic cancer in familial pancreatic cancer kindreds

BACKGROUND & AIMS: Approximately 10% of pancreatic cancers are inherited, but the factors that affect tumorigenesis in familial pancreatic cancer are unknown. We sought to determine whether smoking or other factors could predict cancer risk in familial pancreatic cancer kindreds. METHODS: We conducted a nested case-control study including 251 members of 28 families. All families included 2 or more members with pancreatic cancer. We determined the effects of smoking, young age of onset within the family, diabetes mellitus, sex, and number/standing of affected relatives on the risk of pancreatic cancer. RESULTS: Smoking was an independent risk factor for familial pancreatic cancer (odds ratio [OR], 3.7; 95% confidence interval [CI], 1.8-7.6), and the risk was greatest in males and subjects younger than 50 (OR, 5.2 and OR, 7.6, respectively). Smokers developed cancer 1 decade earlier than nonsmokers (59.6 vs. 69.1 years; P = 0.01), and the number of affected first-degree relatives also increased risk (OR, 1.4; 95% CI, 1.1-1.9 for each additional family member). Diabetes was not a risk factor for pancreatic cancer, although diabetes was associated with pancreatic dysplasia. One third of families demonstrated genetic anticipation, as the mean age of onset decreased by 2 decades between generations. CONCLUSIONS: Smoking is a strong risk factor in familial pancreatic cancer kindreds, particularly among males and those under age 50. Persons with multiple affected first-degree relatives are also at increased risk. These factors may be useful in selecting candidates for pancreatic cancer screening. Members of families with multiple pancreatic cancers should be counseled not to smoke.     

谐波造影增强内镜超声对胰腺癌与局灶型胰腺炎的鉴别诊断价值

目的 探讨谐波造影增强内镜超声（CH-EUS）对胰腺癌与局灶型胰腺炎鉴别诊断的价值.方法 选择上海长海医院经CH-EUS检查诊断为胰腺癌和局灶型胰腺炎患者,以内镜超声引导下细针穿刺术（EUS-FNA）或组织病理学及6个月以上随访结果作为最终诊断,评价CH-EUS对胰腺癌与局灶型胰腺炎的鉴别诊断效果,并分析两者的CH-EUS图像特征.结果 共有56例患者入选本研究,平均年龄（56±12）岁.最终诊断局灶型胰腺炎21例,胰腺癌35例.CH-EUS显示的正常胰腺组织增强时相与周围组织同步,达峰显著,呈均匀等增强.胰腺癌增强时相多数晚于正常胰腺组织,消退快,达峰不显著,94.3％ （33/35）的病灶内部呈不均匀低增强,1例高增强者为癌肿内部有较多高强化的分隔,1例均匀等增强者为慢性胰腺炎癌变.局灶型胰腺炎增强多数表现为与正常胰腺组织等时相,达峰显著,76.2％（16/21）呈均匀等增强.CH-EUS鉴别局灶型胰腺炎与胰腺癌的灵敏度为90.5％,特异度97.1％,准确率94.6％,阳性预测值95.0％,阴性预测值94.4％,阳性似然比31.7,阴性似然比0.1.结论 CH-EUS可以实时、清晰地显示胰腺肿瘤的血供情况,能对胰腺癌和胰腺局灶型炎症的鉴别诊断提供有力帮助,是一种有价值的临床诊断新方法.