Standard versus extended lymphadenectomy in radical surgical treatment for pancreatic head carcinoma.

PURPOSE: The primary aim of this study was to evaluate the benefit of extended lymphadenectomy in pancreaticoduodenectomy (PD) and to estimate its impact on long-term survival in patients with pancreatic head carcinoma. Secondary endpoints included perioperative mortality, postoperative morbidity and predictors of survival in patients undergoing standard versus extended lymphadenectomy for pancreatic head carcinoma. METHODS: From January 2007 to December 2010, 60 patients with potentially resectable pancreatic head carcinoma were operated using pylorus-preserving pancreatoduodenectomy (PPPD) at the Clinic for Digestive Surgery, Clinical Center of Serbia, Belgrade. Intraoperatively patients were randomly stratified into two groups: the first group (N1=30) underwent PPPD with standard lymphadenectomy whilst the second group (N2=30) was operated with PPPD with extended lymphadenectomy. None of the patients received adjuvant treatments. RESULTS: The number of retrieved lymph nodes, mean operating time and postoperative hospital stay were greater in patients with extended lymphadenectomy . Cox regression analysis showed that stage and lymph node metastasis were independent prognostic factors for survival. CONCLUSION: Extended lymphadenectomy in PPPD did not improve long-term survival in patients with resectable pancreatic head carcinoma and led to comparable and similar morbidity and mortality rates to those after standard lymphadenectomy.

The importance of choice of resection procedures in T1 and T2 stage of carcinoma of the ampulla of Vater.

PURPOSE: The ampulla of Vater (AV), with its strategic location and its remarkable predisposition to the development of various malignant tumors, makes it very challenging for surgery. In this study we aimed to examine the prognostic factors in the treatment of early-stage carcinoma of the AV as well as to contribute to the choice of optimal surgical procedure. METHODS: We analyzed 109 AV patients, hospitalized at the Clinical Center of Serbia from January 1999 to December 2008 and we compared the clinicopathological features, analyzed intra- and postoperative data, recurrences and survival, according to duodenopancreatectomy (DP) or local resection (LR). RESULTS: DP was performed in 83 and LR in 26 patients. Overall survival (OS) was significantly influenced by the pathological (p) tumor stage (pT1/T2 vs pT3/T4), pathological nodal stage (pN0 vs pN1), perineural and vascular invasion, grade of tumor differentiation (G1 vs G3), and resection margin status (R0 vs R1). Kaplan-Meier analysis showed 64% 5-year overall survival of patients with pT1/T2 stage in the group with DP, and 58% in the group with LR (p>0.05). Survival analysis of pN1 patients in these two groups showed statistically significant difference (DP 49.67 vs LR 28.68 months, p<0.05). Postoperative complications occurred more frequently in patients treated with DP, compared with LR. Tumor recurrence occurred in 23.07% of LR patients and in 4.0% of DP patients, in pT1/T2 stage. The rate of in-hospital mortality was not significantly different in DP (9.78%) vs LR (0%) patients (p>0.05). CONCLUSION: Resection is mandatory for all proven AV tumors, and DP is the treatment choice. LR, due to reduced morbidity and mortality, might be recommended in elderly patients with comorbidities and in patients with stage pT1/T2, pN0 and well differentiated (G1,G2) tumors.

Angiotensin-converting enzyme gene insertion/deletion polymorphism in patients with chronic pancreatitis and pancreatic cancer.

The purpose of this study was to determine the frequency of angiotensin-converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism and to investigate its role as a potential risk factor in patients with chronic pancreatitis and pancreatic cancer. Deletion polymorphism of the 287-bp fragment of intron 16 of the ACE gene results in higher levels of circulating enzyme and therefore may represent a risk factor for disease development. The study included 55 patients with chronic pancreatitis, 45 patients with pancreatic cancer and 128 healthy subjects. The presence of I and D variants in the ACE gene was analyzed by a polymerase chain reaction (PCR) method. Distribution of ACE ID genotypes was analyzed by means of logistic regression. When chronic pancreatitis and pancreatic cancer groups were compared in the univariate analysis, the following factors were identified as statistically significant predictors of pancreatic disease: age, gender, smoking, fat intake, ACE II genotype and ACE DD genotype. However, in the multivariate analysis, only age, gender and smoking were singled out as predictors for the occurrence of pancreatic disease. Our findings indicate that the ACE I/D polymorphism could play a role in the development of chronic pancreatitis and pancreatic cancer through interaction with other genetic and environmental factors.

Comparison of Preoperative Evaluation with the Pathological Report in Intraductal Papillary Mucinous Neoplasms: A Single-Center Experience.

The key to the successful management of pancreatic cystic neoplasm (PCN), among which intraductal papillary mucinous neoplasm (IPMN) is the one with the highest risk of advanced neoplasia in resected patients, is a careful combination of clinical, radiological, and histopathological findings. This study aims to perform the comparison of a preoperative evaluation with pathological reports in IPMN and further, to evaluate and compare the diagnostic performance of European evidence-based guidelines on pancreatic cystic neoplasms (EEBGPCN) and Fukuoka Consensus guidelines (FCG). We analyzed 106 consecutive patients diagnosed with different types of PCN, among whom 68 had IPMN diagnosis, at the Clinical Center of Serbia. All the patients diagnosed with IPMNs were stratified concerning the presence of the absolute and relative indications according to EEBGPCN and high-risk stigmata and worrisome features according to FCG. Final histopathology revealed that IPMNs patients were further divided into malignant (50 patients) and benign (18 patients) groups, according to the pathological findings. The preoperative prediction of malignancy according to EEBGPCN criteria was higher than 70% with high sensitivity of at least one absolute or relative indication for resection. The diagnostic performance of FCG was shown as comparable to EEBGPCN. Nevertheless, the value of false-positive rate for surgical resection showed that in some cases, overtreating patients or treating them too early cannot be prevented. A multidisciplinary approach is essential to adequately select patients for the resection considering at the same time both the risks of surgery and malignancy.

EUS diagnosis of ectopic opening of the common bile duct in the duodenal bulb: a case report.

Among the various congenital anomalies of the biliary system, an ectopic opening of the common bile duct (CBD) in the duodenal bulb is extremely rare. ERCP is essential for diagnosing the anomaly. A 55-year-old male was admitted to hospital for severe right upper quadrant abdominal pain, followed by fever, chills, elevated body temperature and mild icterus. The diagnosis of ectopic opening of CBD in the duodenal bulb was established on endoscopic ultrasonography (EUS), which clearly demonstrated dilated CBD, with multiple stones and air in the lumen, draining into the bulb. A normal pancreatic duct, which did not drain into the bulb, was also observed. This finding was confirmed on ERCP and surgery. As far as we know, this is the first case of this anomaly diagnosed by EUS. Ectopic opening of the CBD in the duodenal bulb is not an incidental finding, but a pathologic condition which can be associated with clinical entities such as recurrent or intractable duodenal ulcer, recurrent biliary pain, choledocholithiasis or acute cholangitis. Endoscopic ultrasonography features allow preoperative diagnosis of this anomaly and can replace ERCP as a first diagnostic tool in such clinical circumstances. Embryology of the anomalies of the extrahepatic biliary tree has been also reviewed.

Primary retroperitoneal mucinous cystadenoma: A case report.

Primary retroperitoneal mucinous cystic tumors are extremely rare. These tumors can be classified as a primary retroperitoneal mucinous cystadenoma with or without borderline malignancy or primary retroperitoneal mucinous cystadenocarcinoma. The most common of these is primary retroperitoneal mucinous cystadenoma, which almost always occurs in female patients; only ten cases have been reported in males. The most common clinical findings for this tumor type include nonspecific abdominal pain and a palpable abdominal mass. A definitive diagnosis is usually obtained from histopathology after surgical excision. Here, we report the case of a 60-year-old female patient who complained of abdominal pain that had been present for 3 mo and presented with a palpable abdominal mass. Multidetector computed tomography scanning revealed a large, unilocular cystic mass in the left retroperitoneal space. Surgical intervention was performed and the tumor was completely removed. Histopathologic examination confirmed that the tumor was a primary retroperitoneal mucinous cystadenoma. Two years after surgery, the patient remains disease free.

Laparoscopic distal pancreatectomy for intrapancreatic accessory spleen: case report.

INTRODUCTION: Accessory spleens can be found in up to 10% of the population, and their intrapancreatic occurrence is considered uncommon. When present, the intrapancreatic accessory spleen is usually found in the tail of the pancreas in about 1.7% of adult individuals. The infrequent presence of the accessory spleen in the pancreatic tissue could lead to inappropriate diagnosis and hence therapeutic approach, as they are commonly presented as a hypervascular node in the tail of the pancreas on abdominal CT and MRI, mimicking a well differentiated tumor of the pancreas or non-functioning pancreatic neuroendocrine tumor. CASE OUTLINE: We present a 70-year-old female in whom a preoperative evaluation finding was highly suggestive of a non-functioning neuroendocrine tumor of the pancreatic tail. We performed spleen preserving laparoscopic distal pancreatectomy, and histopathological examination revealed the intrapancreatic accessory spleen. CONCLUSION: Although infrequent, the presence of the intrapancreatic accessory spleen must be considered in the differential diagnosis of pancreatic tail tumors.

A Case of Autoimmune Cholangitis Misdiagnosed for Cholangiocarcinoma: How to Avoid Unnecessary Surgical Intervention?

INTRODUCTION: Autoimmune cholangitis or immunoglobulin G4-associated cholangitis (IAC) has been recently regarded as a new clinical and histopathological entity and is a part of a complex autoimmune disorder--IgG4-related systemic disease (ISD). ISD is an autoimmune disease with multi-organic involvement, characterized with IgG4-positive plasmocytic infiltration of various tissues and organs with a consequent sclerosis, which responds well to steroid therapy. Most commonly affected organs are the pancreas (autoimmune pancreatitis, [AIP]) and the common bile duct (IAC). IAC and cholangiocarcinoma (CCA) share many clinical, laboratory and imaging findings. CASE OUTLINE: We present a case of a 60-year-old male with a biliary stricture of a common bile duct, which was clinically considered as a bile duct carcinoma and treated surgically. Definite histopathological findings and immunohistochemistry revealed profound chronic inflammation, showing lymphoplasmacytic IgG-positive infiltration of a resected part of a common bile duct, highly suggestive for the diagnosis of IAC. In addition, postoperative IgG4 serum levels were also increased. CONCLUSION: It is of primary clinical importance to make a difference between IAC and CCA, in order to avoid unnecessary surgical intervention. Therefore, IAC should be considered in differential diagnosis in similar cases.

EUS mini probes in diagnosis of cystic dystrophy of duodenal wall in heterotopic pancreas: a case report.

Cystic dystrophy of the duodenal wall is a rare condition characterized by the development of cysts in heterotopic pancreatic tissue localized in the duodenal wall. A 38-year-old man was admitted to the hospital for abdominal pain and vomiting after food intake. The diagnosis of acute pancreatitis was initially suspected. Abdominal ultrasound examination revealed thickening of the second portion of duodenal wall within which, small cysts (diameter, less than 1 cm) were present in the vicinity of pancreatic head. The head of pancreas appeared enlarged (63 mm x 42 mm) and hypoechoic. Upper endoscopy and barium X-ray series were performed revealing a severe circumferential deformation, as well as 4 cm long stenosis of the second portion of the duodenum. CT examination revealed multiple cysts located in an enlarged, thickened duodenal wall with moderate to strong post-contrast enhancement. We suspected that patient had cystic dystrophy of duodenal wall developed in the heterotopic pancreas and diagnosis was confirmed by endoscopic ultrasound (EUS). Endoscopic ultrasound (EUS) revealed circular stenosis from the duodenal bulb onwards. A twenty megaHertz mini-probe examination further showed diffuse (intramural) infiltration of duodenal wall limited to the submucosa and muscularis propria of the second portion of duodenum with multiple microcysts within the thickened mucosa and submucosa. Patient was successfully surgically treated and pancreatoduodenectomy was performed. The pathological examination confirmed a diagnosis of cystic dystrophy of a heterotopic pancreas. Endoscopic ultrasonography features allow preoperative diagnosis of cystic dystrophy of a heterotopic pancreas in duodenal wall, with intraluminal 20 MHz mini probe sonography being more efficient in cases of luminal stenosis.

Drain amylase value as an early predictor of pancreatic fistula after cephalic duodenopancreatectomy.

AIM: To determine predictors of clinically relevant pancreatic fistulas (CRPF) by measuring drain fluid amylase (DFA) in the early postoperative period. METHODS: This prospective clinical study included 382 patients with periampullary tumors that were surgically resected at our department between March 2005 and October 2012. A cephalic duodenopancreatectomy (DP) was performed on all patients. Two closed suction drains were placed at the end of the surgery. The highest postoperative DFA value was recorded and analyzed during the first three postoperative days and on subsequent days if the drains were kept longer. Pancreatic fistula (PF) was classified according to the International Study Group of Pancreatic Fistula (ISGPF) criteria. Postoperative complications were defined according to the Dindo-Clavien classification. All data were statistically analyzed. The optimal thresholds of DFA levels on the first, second and third postoperative days were estimated by constructing receiver operating curves, generated by calculating the sensitivities and specificities of the DFA levels. The DFA level limits were used to differentiate between the group without PF and the groups with biochemical pancreatic fistula (BPF) and CRPF. RESULTS: Pylorus-preserving duodenopancreatectomy was performed on 289 (75.6%) patients, while the remaining patients underwent a classic Whipple procedure (CW). The total incidence of PF was 37.7% (grade A 22.8%, grade B 11.0% and grade C 3.9%). Soft pancreatic texture (SPT) was present in 58.3% of patients who developed PF. Mortality was 4.2%. The median DFA value on the first postoperative day (DFA1) in patients who developed PF was 4520 U/L (range 350-99000 U/L) for grade A fistula (BPF) with a SPT and a diameter of the main pancreatic duct (MPD) of ≤ 3 mm. For grade B/C (CRPF), the median DFA1 value was 8501 U/L (range 377-92060 U/L) with a SPT and MPD of ≤ 3 mm. These values were significantly higher when compared to the patients who did not have PF (122; range 5-37875 U/L). The upper limit of DFA values for the first 3 postoperative days in the examined stages of PF were: DFA1 1200 U/L for the BPF and CRPF; DFA3 350 U/L for BPF and DFA3 800 U/L for CRPF. The determined values were highly significant and demonstrated a reliable diagnostic test for both BPF and CRPF. CONCLUSION: DFA1 ≥ 1200 U/L is an important predictive factor for PF of any degree. The trend of DFA3 (decrease of < 50%) compared to DFA1 is a significant factor in the differentiation of CRPF from transient BPF.

Structural and functional analysis of SMAD4 gene promoter in malignant pancreatic and colorectal tissues: detection of two novel polymorphic nucleotide repeats.

BACKGROUND: The tumor suppressor gene SMAD4 (DPC4) encodes for the common intracellular mediator of the TGF-ß superfamily pathway, which regulates numerous cellular processes, such as cell proliferation, cell differentiation, apoptosis, cell fate and migration. This study was aimed to investigate the presence of genetic variants in SMAD4 gene promoter in malignant pancreatic and colorectal tissue and to analyze their functional consequences. METHODS: The study was performed on genomic DNA isolated from malignant tissue samples obtained on surgery from 50 patients with pancreatic carcinoma and 50 patients with colorectal cancer. Screening for mutations within an 800bp-long fragment of the SMAD4 gene promoter was performed by DNA sequencing and two mononucleotide repeats, at positions -462 and -4, were found to be polymorphic in malignant tissue. The exact number of thymidines in the tracts -462T(15) and -4T(12) was determined by PCR with fluorescently labeled primers followed by capillary electrophoresis. Functional analysis of -462T(15)/-4T(12) haplotypes was performed by luciferase reporter assays. RESULTS: Haplotype -462T(14)/-4T(10) was found in 85% of pancreatic cancer tissues, but it was not present in any of colorectal cancer tissues. Statistically significant reduction (p<0.001) in activity was observed in the haplotype -462T(14)/-4T(10) in comparison with the haplotypes -462T(15)/-4T(12) and -462T(14)/-4T(11). CONCLUSION: Results of this study indicate that novel genetic variant -4T(10) in the SMAD4 gene promoter affects its activity and that element -4T(12) may play a role in transcriptional regulation of SMAD4 gene expression. Obtained results, though preliminary, also indicate that SMAD4 gene promoter haplotype -462T(14)/-4T(10) may represent a genetic marker of potential relevance for pancreatic and colorectal cancer. The findings of this study should be confirmed by further investigation in these two and other tumors, on larger number of patients and with different tumor stages. Translational research aimed at investigating potential application of mononucleotide repeats -462T(15) and -4T(12) in SMAD4 gene promoter as molecular markers in cancer may also prove useful.

Invasive lobular breast cancer presenting an unusual metastatic pattern in the form of peritoneal and rectal metastases: a case report.

Gastrointestinal metastases from invasive lobular breast cancer are uncommon with the stomach and small intestines being the most common metastatic sites. Peritoneal and rectal metastases are very rare and only rarely occur as the first manifestation of disease. We herein report the case of a 47-year-old woman who presented with abdominal carcinomatosis as a first sign of invasive lobular breast carcinoma (ILC). Identifying the most important immunohistochemical markers for ILC: gross cystic disease fluid protein 15, estrogen and progesterone receptors enabled a correct diagnosis. After a six year disease-free period, relapse occurred with severe obstruction due to rectal metastasis from lobular breast carcinoma. Since there was no widespread metastatic disease, surgery with concomitant hormonal therapy was performed.

Gastric multicentric glomangioma: a case report of this rare cause of abdominal pain.

BACKGROUND: A glomus tumor is a rare neoplasm derived from glomus cells, specialized cells that surround small blood vessels which are important in regulating peripheral blood flow. Glomangiomas are a subset of glomus tumors. They are usually localized in the skin and subcutaneous tissue. They have also been reported in viscera, most notably in the gastrointestinal tract. CASE REPORT: A case of gastric multicentric glomangioma is described in an 18-year-old male who presented with chronic continuous abdominal pain over a 4-6 month period. Preoperative diagnosis, operative findings, histology, and immunohistochemistry of the tumor are discussed in detail. CONCLUSIONS: Case reports of this rare tumor are important because of the paucity of studies noted in the gastro-intestinal literature as a result of poor identification prior to the advent of modern immunohistochemistry. The significance of accurately diagnosing a gastrointestinal glomangioma is crucial for appropriate treatment.

[Surgical treatment of pain in chronic pancreatitis].

INTRODUCTION: The principal indication for surgical intervention in chronic pancreatitis is intractable pain. Depending upon the presence of dilated pancreatic ductal system, pancreatic duct drainage procedures and different kinds of pancreatic resections are applied. OBJECTIVE: The objective of the study was to show the most appropriate procedure to gain the most possible benefits in dependence of type of pathohistological process in chronic pancreatitis. METHOD: Our study included 58 patients with intractable pain caused by chronic pancreatitis of alcoholic genesis. The first group consisted of 30 patients with dilated pancreatic ductal system more than 10 mm. The second group involved 28 patients without dilated pancreatic ductal system. Pain relief, weight gain and glucose tolerance were monitored. RESULTS: All patients of Group I (30) underwent latero-lateral pancreaticojejunal--Puestow operation. 80% of patients had no pain after 6 month, 13.6% had rare pain and 2 patients, i.e. 6.4%, who continued to consume alcohol, had strong pain. Group II consisting of 28 patients was without dilated pancreatic ductal system. This group was subjected to various types of pancreatic resections. Whipple procedure (W) was done in 6 patients, pylorus preserving Whipple (PPW) in 7 cases, and duodenum preserving cephalic pancreatectomy (DPCP) was performed in 15 patients. Generally, 89.2% of patients had no pain 6 month after the operation. An average weight gain was 1.9 kg in W group, 2.8 kg in PPW group and 4.1 kg in DPCP group. Insulin-dependent diabetes was recorded in 66.6% in W group, 57.1% in PPW group and 0% in DPCP group. CONCLUSION: According to our opinion, DPCP may be considered the procedure of choice for surgical treatment of pain in chronic pancreatitis in patients without dilatation of pancreas ductal system because of no serious postoperative metabolic consequences.