JOP. Journal of the Pancreas

Solid-Pseudopapillary Neoplasm of the Pancreas: Case Series and Literature Review

José Roberto Alves — 2015-05-20

The solid-pseudopapillary neoplasm of the pancreas is a rare disease, although since 2000, it has been often identified. The current study aims to present a 10-case series of solid-pseudopapillary neoplasm of the pancreas and a literature review on the topic. The cohort consisted of nine female patients and one male. The mean age in the group was 31.2 year-old. These patients underwent surgical treatment at the University Hospital between May 2007 and July 2014. Since there was a previous systematic literature review on solid-pseudopapillary neoplasm of the pancreas (prior to September 20^th, 2012), a complementary review was done after this period using PubMed’s data base. The search identified 225 studies on this subject, but only 13 were selected for detailed analysis, after applying the inclusion and exclusion criteria. As a result, most of the information about the disease’s epidemiology, clinical manifestations, malignity risk factors, metastasis and relapse were gathered, however, early diagnosis remained a challenge. Radical surgical resection is established as the standard treatment protocol for the disease, it is also recommended to perform metastasectomy, vascular resections and/or resections of other compromised organs in order to ensure therapeutic success in 95% of the cases. However, a post-operative follow up of at least 5 years is required to identify the possibility of relapses. Further studies are still needed mainly to define this disease’s true prevalence among men, protocols for early diagnosis and the possible role of adjuvant therapies.

Image: Intraoperative picture demonstrating a SPN in pancreatic head attached to the portal vein.

Pancreatic Steatosis: What Should Gastroenterologists Know?

Varayu Prachayakul — 2015-05-20

When hyperechoic pancreatic parenchyma is observed on endoscopic or transabdominal ultrasound, fat infiltration of the pancreas is suspected. This condition was first reported by Ogilvie in 1993 and is termed fatty pancreas, pancreatic lipomatosis, non-alcoholic fatty pancreas, or pancreatic steatosis. Diagnosis of this condition mostly relies on imaging tools such as magnetic resonance imaging, computed tomography, or ultrasonography rather than histology. Although the condition is rare, it has clinical significance. There are multiple hypotheses regarded the etiology of this condition, listing factors such as viral infections, toxins, and congenital syndromes as possible causes. Metabolic syndrome and diabetes mellitus correlated with this condition. However, other etiologies should also be considered to aid specific treatment. In addition to a correlation between pancreatic steatosis and metabolic syndrome, relationships between pancreatic steatosis and worsened severity and prognosis of pancreatic cancer, increased complications after pancreatic surgery, and acute pancreatitis were reported. Gastroenterologists should be well informed about this condition for better care of these patients.

Image: Siriraj Hospital. Bangkok, Thailand.

Pancreatic Tuberculosis: An Overview

Mohammad Bagher Miri — 2015-05-20

Pancreatic tuberculosis is a rare occurrence in either immune-competent or immune-suppressed host. Pancreatic tuberculosis most commonly afflicts the region of the head and the uncinate process of the pancreas. It is often misdiagnosed due to low index of suspicion and masquerading of its symptoms as more common pancreatic conditions such as pancreatic malignancy. However, Endoscopic ultrasound fine needle aspiration sampling with an acid-fast smear is essential for establishing the diagnosis of pancreatic tuberculosis. If the diagnosis is delayed, pancreatic tuberculosis can be fatal. Pancreatic tuberculosis responds well to standard anti-tuberculous drugs.

Image: Taleghani Hospital. Tehran, Iran.

Autoimmune Pancreatitis: A Succinct Overview

Juan Putra — 2015-05-20

Autoimmune pancreatitis is a rare type of chronic pancreatitis with characteristic clinical, radiologic, and histopathologic findings. Diagnosis of autoimmune pancreatitis is often challenging due to its low incidence and nonspecific clinical and radiologic findings. Patients with autoimmune pancreatitis and pancreatic cancer share similar clinical presentations, including obstructive jaundice, abdominal pain and weight loss. Due to these overlapping features, autoimmune pancreatitis patients are often misdiagnosed with pancreatic cancer and undergo unnecessary surgery. International consensus diagnostic criteria for autoimmune pancreatitis lists 5 cardinal features to establish the diagnosis of autoimmune pancreatitis. These features include imaging, serology, other organ involvement, histopathology of the pancreas, and response to steroid therapy. Endoscopic ultrasound-guided fine needle aspiration is a routine diagnostic tool for pancreatic lesions. It is usually utilized to exclude a malignant process in autoimmune pancreatitis patients, since its role to establish a definitive diagnosis of autoimmune pancreatitis is often limited. Endoscopic ultrasound-guided-tru-cut biopsy and endoscopic ultrasound-guided fine needle using a large gauge needle (19 to 22 gauges) have been the preferred methods to obtain tissue samples for histologic evaluation. Lymphoplasmacytic infiltrates, fibrotic stroma, mildly atypical epithelial cells, periphlebitis, and obliterative periphlebitis are the common histologic findings of type 1 autoimmune pancreatitis. Meanwhile, granulocytic pancreatic ductal epithelial damage and ductal obliteration are the histologic characteristics of type 2 autoimmune pancreatitis. Immunohistochemical and molecular studies may be helpful to support the diagnosis of AIP in biopsy materials.

Image: Permanent section of the fine needle aspirate showing venulitis.

Advances in Pancreatic Cancer: The Role of Metabolomics

Vy Nguyen — 2015-05-20

Metabolomics is an emerging scientific field focusing on compounds, also known as metabolomes that are produced by biologic systems. Metabolomes represent phenotypic end-products of living entities, and are of particular interest as they represent a novel group of biomarkers that can be used for diagnosis, monitoring response to treatments, and more recently as potential therapeutic agents for benign but more so for malignant diseases. One of the main factors associated with improved survival of patients affected by malignancies is early diagnosis, particularly for those tumors with poor prognosis such as pancreatic cancer. Currently, there are no diagnostic tests for the screening of pancreatic cancer, and although novel biomarkers continue to be discovered, none has yet to be proven useful for this purpose. The main aims of this paper are to review the current literature and to summarize the most relevant advances in the field of metabolomics applied to pancreatic adenocarcinoma.

Image: Dalhousie University. Halifax, Nova Scotia, Canada.

Future Directions in Pancreatic Cancer Therapy

David Orchard-Webb — 2015-05-20

Pancreatic cancer is a major disease burden that is essentially incurable at present. However significant understanding of the molecular basis of pancreatic cancer has been achieved through sequencing. This is allowing the rational design of therapeutics. The purpose of this review is to introduce the molecular basis of pancreatic cancer, explain the current state of molecular therapy and provide examples of the ongoing developments. These include improvements in chemotherapy, small molecule inhibitors, vaccines, immune checkpoint antibodies, and oncolytics.

Image: University of Leeds. Leeds, UK.

Acquired 5-Fluorouracil Resistance in Human Pancreatic Carcinoma Cells. A Paradigm for Chemoresistance Mechanisms in Pancreatic Cancer

Marvin Schober — 2015-05-20

Context Pancreatic ductal adenocarcinoma is a dismal disease with one of the worst prognoses amongst solid tumors. Its ability to develop chemoresistance mechanisms towards cytotoxic drugs is the main cause of treatment failure. Objective Here, we have established a drug-resistance model for pancreatic cancer in which Capan-1 pancreatic carcinoma cells (designated Capan-1 5-FU2000) acquired 5-fluorouracil (5-FU) resistance and were used as a paradigm to reveal alterations in intracellular signaling cascades that. Those alterations may contribute to the circumvention of apoptosis during the course of the disease, culminating in treatment failure. Methods We made use of 2-D-gelelectrophoresis, mass-spectrometry, sandwich-ELISA and western blotting to compare the proteomic expression patterns of respective mediators involved in pro- and antiapoptotic as well as inflammatory processes in both cell lines. An ATP-based chemosensitivity assay validated the chemoresistant phenotype of the Capan-1 5-FU2000 clones. Results We detected specific changes in our resistant cell clones in particular a decreased expression of S100A4. We also found a decreased basal phosphorylation of SAPK/JNK and P38. The expression of the pro-apoptotic mediators Bok and Bad was down- and up-regulated in these cells, respectively. In case of NfkB p65 and IkB-alpha treatment with 5-FU (2,000 µg/mL for 96 h) markedly induced phosphorylation in native Capan-1 cells. In contrast in resistant clones it decreased phosphorylation of NfkB p65 and did not affect IkB-alpha phosphorylation. Basal phosphorylation of S6-ribosomal-protein was markedly increased in resistant clones, treatment with 5-FU decreased this phosphorylation, while in native Capan-1 cells it was vice versa. Conclusion Thus we can conclude that several pathways were found to be altered in chemoresistant Capan-1 5-FU2000 cells. Moreover these alterations are most likely the consequence of a multistep adaption towards gradual cytotoxic exposure finally culminating in a chemoresistant phenotype. Interfering with these pathways may possibly reverse the phenotype and thus open up alternative treatment options.

Image: Effect of 5-FU treatment on NfkB p65 phosphorylation in native and 5-FU resistant cells.

Outcome of Laparoscopic Surgery in Patients with Cystic Lesions in the Distal Pancreas

Kim V Ånonsen — 2015-05-20

Context Recent guidelines for the management of cystic lesions of the pancreas recommend observation for selected neoplasms using imaging criteria. However, current imaging modalities lack diagnostic accuracy, and the indication for surgery is debated. Objective In this study we have explored the outcome of laparoscopic distal pancreatic resections in all patients referred with potential pancreatic cystic neoplasms, with histological diagnosis as endpoint. Methods Between 1997 and 2009 all patients referred to our tertiary referral centre having a cystic neoplasm of the distal pancreas accepted for surgery were included in the present observational study. Results A total of 69 patients were included. Sixty-two patients underwent distal pancreatectomies, in whom 19 were spleen-preserving, and 7 enucleations were performed. Two procedures were converted to open technique. The lesions removed in 27 patients (39%) were either malignant or premalignant. The final diagnoses were serous cystic neoplasm (n=29), mucinous cystic neoplasm (n=12), pseudocyst (n=11), solid pseudopapillary neoplasm (n=10), intraductal papillary mucinous neoplasm (n=5) and other (n=2). Overall morbidity was 33%; 56% of the complications were classified as mild. Fistula rate was 10%. One patient died postoperatively from a cerebral haemorrhage. Conclusion Most complications after laparoscopic distal resection of cystic pancreatic lesions are mild, but the proportion of patients with benign lesions (61%) has to be reduced by focused preoperative investigations. Endoscopic ultrasound examination (EUS), enabling aspiration of cyst fluid and fine needle aspiration is an additional option for the preoperative workup.

Image: Histological diagnosis of the resected specimens.

A Lower Cyst Fluid CEA Cut-Off Increases Diagnostic Accuracy in Identifying Mucinous Pancreatic Cystic Lesions

David X Jin — 2015-05-20

Context Carcinoembryonic antigen analysis of pancreatic cyst fluid is the tumor marker of choice for preoperatively differentiating mucinous from non-mucinous cystic lesions. Objective We aim to determine the most accurate cyst carcinoembryonic antigen cut-off value for distinguishing mucinous cysts from non-mucinous cysts with a focus on discriminating intraductal papillary mucinous neoplasms. Methods The results of pancreatic cyst aspiration carcinoembryonic antigen levels from a single center were retrospectively collected and evaluated for a diagnosis of a mucinous cyst and an assessment of malignancy using surgical histology as the diagnostic standard in 86 patients. Results The median cyst carcinoembryonic antigen level (ng/mL) was significantly higher in mucinous cysts compared with non-mucinous cysts (218 vs. 4.4; P=0.0006) and in intraductal papillary mucinous neoplasms compared with non-mucinous cysts (135 vs. 4.4; P=0.0027). A cyst carcinoembryonic antigen cut-off of 30.7 ng/mL was most accurate (87.2%) for differentiating mucinous from non-mucinous cysts and specifically for differentiating intraductal papillary mucinous neoplasms from non-mucinous cysts (82.7%). Cyst carcinoembryonic antigen levels were not significantly different between malignant and non-malignant mucinous cysts (68.5 vs. 238.1; P=0.51). Conclusions Pancreatic cyst fluid carcinoembryonic antigen can accurately differentiate histologically verified mucinous lesions, including intraductal papillary mucinous neoplasms, from non-mucinous lesions with an optimal cut-off that is much lower than previously reported values. Cyst carcinoembryonic antigen levels are not a reliable predictor of malignancy.

Image: Sensitivity and specificity curves of cyst fluid CEA levels for differentiating mucinous from non-mucinous cysts.

The Risk of Contracting Drug-Induced Pancreatitis during Treatment for Pulmonary Tuberculosis

Natalya Gubergrits — 2015-05-20

Context Pulmonary tuberculosis and especially multi-drug-resistant tuberculosis remain a pressing health problem. Objective The aim of this study was to establish how often standard preparations for the treatment of tuberculosis, such as isoniazid and rifampicin, lead to acute pancreatitis. Methods Two hundred and eighty patients with pulmonary tuberculosis were investigated by clinical chemistry and ultrasonography to determine in how many cases the use of isoniazid and rifampicin was followed by elevation of pancreatic isoamylase or lipase or by sonographic signs of acute pancreatitis with and without occurrence of acute upper abdominal symptoms. Results Acute pancreatitis definitely occurred in 22 (8%) and probably in 36 (13%) of the patients. In 21 (8%) there was merely an asymptomatic serum elevation of pancreatic enzymes and no pathologic sonographic signs in the pancreas. Conclusions Acute pancreatitis is a frequent occurrence after administration of isoniazid and rifampicin and must be considered whenever upper abdominal symptoms are found in patients treated with these drugs.

Image: Donetsk National Medical University. Donetsk, Ukraine.

Diagnosis and Management of Haemorrhagic Complications Following Hepatopancreatobiliary Surgery

Anitha Balakrishnan — 2015-05-20

Context Post-operative haemorrhage is a known complication of hepatopancreatobiliary surgery. Prompt treatment minimizes mortality and morbidity; however, there is currently little uniformity in the management of this complication. Objective The total numbers of pancreatectomies or liver resections were identified using hospital episode statistic data. Methods Patients who experienced post-operative bleeding were identified with keyword searches of all discharge letters, imaging reports and the theatre-coding database for the period between January 2005 and December 2011. Treatment modalities for control of haemorrhage as well as morbidity, mortality, length of stay and survival were examined. Results Thirty-four of the 768 pancreatic and liver resections performed experienced post-operative haemorrhage. More patients bled following pancreatectomies (6.1%) compared to hepatectomies (2.5%). Bleeding was controlled using endoscopic, interventional radiological or surgical methods; re-laparotomy provided definitive management in the majority of patients. Post-pancreatectomy haemorrhage was associated with significantly increased mortality (P=0.004). Length of stay was increased following haemorrhage post-pancreatectomy or hepatectomy (P<0.05). Conclusions Our study highlights the substantial increase in mortality and length of stay following post-pancreatectomy and post-hepatectomy haemorrhage. Re-laparotomy was frequently required for control of bleeding. Our proposed management algorithm based on the timing and site of bleeding may standardize treatment in this heterogeneous group.

Image: Algorithm for the management of late post-resectional haemorrhage.

Hydropic Gallbladder in Three Patients with Poorly Controlled Diabetes Mellitus: What Constitutes Optimal Management?

Yezaz A Ghouri — 2015-05-20

Context Long-standing diabetes mellitus results in autonomic nervous system dysfunction, leading to gastroparesis and cholecystoparesis. The latter can result in hydropic gallbladder, a condition that arises from the accumulation of mucinous secretions within the gallbladder, usually caused by obstruction of the cystic duct, but not in the case of the patients with diabetes that we have illustrated. Case report We describe three patients who presented with non-specific abdominal discomfort at the time of admission for complications of poorly controlled diabetes and were subsequently found to have hydropic gallbladder. We theorize that hydropic gallbladder may be a result of a natural progression of gallbladder dysfunction in poorly controlled diabetics with autonomic neuropathy. In our cases the risk of perioperative mortality was high at the time of presentation. No surgical intervention was performed except in one case with the most significant sized gallbladder, and underwent a temporizing cholecystostomy. Conclusions The development of hydropic gallbladder in patients with non-obstructed cystic ducts highlights the complexities of management of patients with functional biliary pain. The rome committee on functional biliary and pancreatic disorders has defined the characteristics of this pain. There is a need for guidelines to direct appropriate assessment of hydropic gallbladder in diabetics and also to determine the indications for cholecystectomy.

Image: HIDA scan showing a low ejection fraction of the gallbladder after administration of CCK.

Diffuse Pancreatic Mucinous Cystic Neoplasm Treated by Total Pancreatectomy

Hongyi Chen — 2015-05-20

Context Multifocal or diffuse mucinous cystic neoplasm are uncommon and may be difficult to distinguish from multifocal intra-ducal mucinous neoplasm or diffuse serous cystadenoma. Case report A forty-seven-year old lady with vague abdominal pain was noted to have cystic lesions ranging from 5 to 20 mm throughout her pancreas. The cysts had enlarged over several years of observation. There was no evidence of pancreatic duct dilatation or communication with the pancreatic duct on magnetic resonance imaging. Cyst fluid analysis for carcinoembryonic antigen and amylase were non-diagnostic. A total pancreatectomy was performed, with histology confirming numerous cysts lined by mucus producing cells, without obvious ovarian-like stroma. The stroma did however demonstrate positive staining for oestrogen receptor and smooth muscle actin. These findings were most consistent with a mucinous cystic neoplasm, despite the apparent absence of typical ovarian like stroma. Conclusion Multifocal or diffuse pancreatic mucinous cystic neoplasm are uncommon and may be suspected when imaging demonstrates multiple pancreatic cysts without communication with the pancreatic duct or pancreatic duct dilation. Surgical resection is indicated due to the increased risk of malignancy.

Image: Sectioning of the pancreas demonstrates multiple cysts without any clear communication with the pancreatic duct and no evidence of pancreatic duct dilatation.

Spleen Autotransplantation Following Laparoscopic Distal Pancreatosplenectomy and Cholecystectomy

Sung Hwan Lee — 2015-05-20

Context The lifelong risk of post-splenectomy overwhelming sepsis is major complication after splenectomy. Laparoscopic distal pancreatectomy is an accepted as safe, and adequate procedure for pancreatic pathologies requiring resection of the distal part of the pancreas. However, attempts to preserve the spleen are not always successful and sometimes require unnecessary splenectomy. Spleen autotransplantation can be regarded as inducing iatrogenic splenosis in the abdominal cavity. Case report In this report, we present a case of spleen autotransplantation (about 30 g of splenic tissue) following laparoscopic distal pancreatectomy and inadvertent splenectomy for benign intraductal papillary tumor of the pancreas. Conclusion This procedure may be the last option spleen preservation considered in the era of laparoscopic distal pancreatectomy.

Image: Laparoscopic view after completion of spleen autotransplantation.

Pancreatic Panniculitis: A Rare Manifestation of Acute Pancreatitis

Ronak Patel — 2015-05-20

Context Pancreatic panniculitis is a very rare complication associated with pancreatic disease and perhaps even a presage to pancreatic pathology. Case report We present a case of pancreatic panniculitis in a 61 year old patient who was treated for sudden onset of abdominal pain associated with nausea and vomiting secondary to acute pancreatitis of unknown etiology. He subsequently developed skin lesions consistent with pancreatic panniculitis which gradually improved after resolution of his acute condition and treatment with topical steroid cream. Conclusion We discuss and review the literature along with highlighting for the readers the important clinical and histopathologic features of acute pancreatitis associated pancreatic panniculitis.

Image: Initial dermatologic manifestation on lower extremities.

Acinar Cell Cystadenoma of Retroperitoneum: A Case Report and the Literature Review

Ming-Zhang Song — 2015-05-20

Context Acinar cell cystadenoma of pancreas is a very rare pancreatic cystic lesion. It is also a benign lesion without malignant potential. Because it is normal tissue with abnormal figuration, acinar cell transformation is also named. Case report We reported a thirty-seven-year-old female noticed to have a cystic lesion closely in contact with the pancreatic tail by abdominal CT scan. After operation, the cystic lesion was analyzed and acinar cell cystadenoma arising from retroperitoneum was confirmed. Conclusion Literature review revealed only one case of retroperitoneal acinar cell cystadenoma was reported before and the pathogenesis is still unknown.

Image: Loculated cystic lesion with watery clear fluid over retroperitoneum.

Carcinosarcoma of the Pancreas: How a Common Blood Disorder Can Hide an Extremely Rare Tumour

Anastasios Katsourakis — 2015-05-20

Context Sarcomas represent a relatively rare malignancy. Primary sarcomas of the pancreas represent an extremely rare pathology. Case report We report a case of primary pancreatic carcinoma that presented with anaemia. The patient underwent a Kausch-Whipple operation, and, 16 months after the operation, the patient is disease free. Conclusion This unique case describes an extremely rare gastrointestinal tumour that was found during the patient's anaemia assessment.

Image: Gastro-duodenoscopy demonstrating a tumor at the ampulla of Vater.

Consecutive Laparoscopic En-Block Left Pancreato-Nephro-Splenectomy and Later Pancreaticoduodenectomy: Pushing Back the Limits of Laparoscopic Pancreatic Resections

Ignasi Poves — 2015-05-20

Context Laparoscopic distal pancreatectomy is a widely accepted treatment for non-malignant lesions of the left pancreas. However, the role of laparoscopy in more complex procedures such as pancreaticoduodenectomy or treatment of pancreatic adenocarcinoma remains controversial. Case report A seventy-seven-year-old woman underwent surgery twice: first for a PADC of the tail infiltrating the spleen and left kidney, and then for a second PADC of the neck and head of the pancreas diagnosed during follow-up (11 months) of the first tumor. In both procedures a totally laparoscopic approach was applied. The first procedure was an en-bloc resection including the left kidney, spleen and left pancreas. Final diagnosis showed a PADC (49x42x40 mm) involving one of the 17 lymph nodes harvested (R0). Postoperative course was uneventful, and lasted five days. Later, due to the appearance of a new tumor in the right pancreas, an extended pylorus-preserving PD was performed with the patient in supine position with the legs apart. In the postoperative period she presented chylous ascites and required hospitalization for 17 days. Definitive biopsy showed a 2 cm PADC (PanIn 2 and 3 lesions in the rest of the gland). Two out of 21 nodes isolated were found to be affected (R0). No chemotherapy was administered after the second operation. Conclusions Our report may help to redefine the limits of laparoscopy in pancreatic oncologic surgery. It describes several features of added technical difficulty, and may prompt further reflection on the current limits and indications of laparoscopic pancreatectomy.

Image: Positioning of the trocars and incision.

Mild Cystic Fibrosis. A Case Report

Domenico Dell’Edera — 2015-05-20

Context Cystic fibrosis is the most common autosomal recessive genetic disease in Caucasian population. Extending knowledge about the molecular pathology on the one hand allows better delineation of the mutations in the cystic fibrosis transmembrane regulator gene and the other to dramatically increase the predictive power of molecular testing. Case report This study wants to underline that the identification of individuals with atypical cystic fibrosis can sometimes present particular difficulties of interpretation. Conclusion On that ground, if there is a strong clinical suspicion, it is always advisable the biochemical study by performing the sweat test, followed by sequencing of the cystic fibrosis transmembrane regulator gene.

Image: Madonna delle Grazie Hospital. Matera, Italy.

Response of Chick B Islets to Insulin Secretagogues is Comparable to those of Human Islet Equivalents

Bhawna Chandravanshi — 2015-05-20

Context The B islets isolated from 3-5 day old chick respond well to glucose challenge in a similar fashion to those isolated from mouse pancreas. Objective To compare insulin secretory response of chick B islets with that of human islet equivalents generated from stem cells. Methods Human umbilical cord mesenchymal stem cells were differentiated into hIEqs employing three step sequential serum free protocols. Results Immunofluorescence staining demonstrated insulin, C peptide and Glut 2 positivity of both these islets. Static insulin stimulation of these islets in response to glucose, metformin and gamma amino butyric acid resulted in increased insulin secretion as compared to basal glucose stimulation. Our results demonstrate that insulin secretory response of Chick B islets to metformin and gama amino butyric acid is comparable to those of hIEqs. Moreover, both chick and hIEqs could be successfully cryopreserved and revived in a commercially available cryomix (Cryostore 5^®), indicating resemblance in their behavior at sub-zero temperatures. Conclusion Present study advocates Chick islets as an alternative source for diabetes research and islet banking.

Image: Isolated Chick B islets.