Single-institution validation of the international consensus guidelines for treatment of branch duct intraductal papillary mucinous neoplasms of the pancreas

Background

The international consensus guidelines (the guidelines) for management of intraductal papillary mucinous neoplasms (IPMNs) of the pancreas recommend surgical resection of branch duct IPMNs with any of the following features: cyst size >30 mm, mural nodules, main pancreatic duct diameter >6 mm, positive cytology, and symptoms. The aim of this study was to evaluate the usefulness of these guidelines for resection of branch duct IPMNs.

Methods

We reviewed 84 consecutive patients with branch duct IPMNs who underwent surgical resection at our hospital between January 1984 and December 2007.

Results

Sixty-nine patients had indications for resection according to the guidelines. Malignant IPMNs had significantly larger cysts than benign tumors (P = 0.026). Patients with malignant IPMNs had significantly more indications for resection than those with benign IPMNs (2.6 ± 1.0 vs. 1.7 ± 0.9, P < 0.001), and 36 of the 37 patients with malignant IPMNs had indications. The sensitivity of the guidelines for predicting malignancy was 97.3%. One of 15 patients without indications had malignancy, and the specificity was low (29.8%).

Conclusions

The guidelines show a high sensitivity for predicting malignancy of branch duct IPMNs, but the specificity is low. The cyst size and the total number of indications in each patient should be taken into account when predicting the risk of malignancy for branch duct IPMNs.     

Characterization of K-ras gene mutations in association with mucinous hypersecretion in intraductal papillary-mucinous neoplasms

Background/Purpose

Intraductal papillary-mucinous neoplasms (IPMNs) of the pancreas have a favorable prognosis. However, invasive ductal carcinomas of the pancreas show a rapid progression. The aim of this study was to investigate gene mutations in pure pancreatic juice from IPMN patients and to define these genetic mutations in relation to the histopathological and clinical features of IPMNs.

Methods

Twenty-two patients with IPMN, 21 patients with ductal carcinoma, and 20 patients with normal pancreas or chronic pancreatitis were recruited for this study. We measured the main pancreatic duct’s largest diameter and the maximum size of a dilated branch was assessed by ultrasonography or endoscopic ultrasonography. Pure pancreatic juice was collected and was investigated for K-ras, p16, and p53 mutations.

Results

Mutant K-ras gene was detected in 13 of the 22 patients (59.1%) with IPMNs. Different kinds of mutations were detected in the same patient in 4 cases. In the 13 patients with mutant K-ras gene, the diameter of the most dilated part of the main pancreatic duct was 2–8 mm (average, 4.5 mm) and in 7 patients with wild-type K-ras gene, the diameter was 2–5 mm (average, 2.7 mm). There was a significant difference in the diameter of the main pancreatic duct between patients with and without the mutant K-ras gene (P = 0.0323).

Conclusions

The incidence of K-ras mutation may be associated with the hypersecretion of mucin.     

Duodenum-preserving total pancreatectomy for pancreatic neoplasms

Background/Purpose

Total pancreatectomy (TP) is sometimes performed to treat low-grade malignant neoplasms that are spreading to the entire pancreas. However, TP impairs quality of life, due to the resulting loss of pancreatic exocrine and endocrine function, and an organ-preserving procedure should be chosen to minimize the impact of pancreatic dysfunction. Recently, we performed four duodenum-preserving TPs (DPTPs) on patients with low-grade malignant neoplasms of the entire pancreas and we introduce our operative technique and results herein.

Methods

DPTP is performed with the objective of preserving the arterial arcade of the posterior pancreas so as to maintain good blood flow in the duodenum and common bile duct. Care must also be taken to preserve the splenic artery and vein to protect the spleen. When patients are also undergoing a bile duct resection, an end-to-side choledochoduodenostomy is also performed to reconstruct the biliary tract.

Results

Patient 1: DPTP with preservation of the spleen, conserving splenic vessels, was performed on a patient with hereditary pancreatic carcinoma with pancreatic intraepithelial neoplasia-3 (PanIN-3). Patient 2: DPTP with splenectomy was performed on a patient with multiple metastases of the entire pancreas from renal cell carcinoma. Patient 3: DPTP with preservation of the common bile duct and the spleen, conserving splenic vessels, was performed on a patient with minimally invasive carcinoma derived from intraductal papillary mucinous neoplasm (IPMN). Patient 4: DPTP with preservation of the spleen, conserving splenic vessels, was performed on a patient with minimally invasive carcinoma derived from IPMN. No deaths or morbidity occurred. All patients were placed on pancreatic enzyme replacement therapy and given a daily dose of insulin of approximately 30 U. Complete professional rehabiliation was achieved in all patients. All patients except one gained weight, and the hemoglobin A1c (HbA1c) levels have been maintained at around 7%.

Conclusions

DPTP is a useful organ-preserving procedure for low-grade malignant neoplasms spreading within the entire pancreas. This procedure minimizes the impact of pancreatic dysfunction and allows the patient to maintain good nutrition after surgery.     

Intraductal papillary mucinous neoplasm of the pancreas: clinical characteristics and treatment outcomes of 118 consecutive patients from a single center

Background/Purpose

Appropriate surgical treatment strategies based on clinicopathological findings are unavailable for intraductal papillary mucinous neoplasm (IPMN) of the pancreas. We investigated the clinical features of pancreatic IPMN in a single-center database in order to design an optimal surgical strategy.

Methods

The medical records of 118 consecutive patients who had undergone surgical resection between August 1994 and December 2004, in whom IPMN was histologically confirmed, were reviewed retrospectively for radiological and pathological findings.

Results

Most of the invasive carcinomas in these patients were detected as the main-duct type (88.5%). The type of tumor (main-duct type vs branched-duct type), the tumor size, and the dilated duct size were significant predictive factors associated with malignancy. The relative risk of malignancy was greatest at 13-mm or more ductal dilation in the main-duct type (Odds ratio, 4.1), at 35-mm or more tumor size (Odds ratio, 7.6), and for main-duct type (Odds ratio, 3.9). Major pancreatic resections such as total pancreatectomy and pancreatoduodenectomy were performed in 14.5% and 69% of the patients, respectively. There was a 19.5% rate of incomplete resection, with these patients having a positive resection margin. However, significant recurrence did not occur in patients with a benign IPMN lesion which remained at the resection margin. The overall postoperative survival rate at 5 years was 98.2% for benign IPMN and 65.3% for malignant IPMN.

Conclusions

Function-preserving strategies, based on the clinical status of the patient, are necessary in order to avoid possible severe metabolic complications following extended pancreatectomy in patients with benign IPMN because of the low recurrence rate and good prognosis of this entity, irrespective of margin status.

     

Serine protease inhibitor Kazal type 1 and epidermal growth factor receptor are expressed in pancreatic tubular adenocarcinoma, intraductal papillary mucinous neoplasm, and pancreatic intraepithelial neoplasia

Background

Serine protease inhibitor Kazal type 1 (SPINK1) is expressed in normal human pancreatic acinar cells and in a variety of tumors, and binds to the epidermal growth factor receptor (EGFR), mediating cell proliferation through the mitogen-activated protein kinase cascade in pancreatic cancer cell lines. Here, we aimed to assess SPINK1 and EGFR expression in various neoplastic lesions, including tissues demonstrating precancerous changes.

Methods

Surgical specimens of pancreatic ductal adenocarcinoma (n = 23), intraductal papillary mucinous neoplasm (IPMN; n = 21), pancreatic neoplasms other than ductal adenocarcinoma (n = 8), chronic pancreatitis (n = 11), and pancreatic intraepithelial neoplasia (PanIN) lesions within the resected specimens were analyzed immunohistochemically for SPINK1 and EGFR expression.

Results

Sixty-five PanIN-1A, 32 PanIN-1B, 17 PanIN-2, and 6 PanIN-3 were identified. Both SPINK1 and EGFR were expressed in almost all PanIN lesions. All tubular ductal adenocarcinoma, IPMN, and mucinous cystadenocarcinoma samples (neoplasms of ductal origin) expressed SPINK1, whereas acinar cell carcinoma, anaplastic carcinoma, adenosquamous carcinoma, insulinoma, and islet cell carcinoma did not. EGFR was expressed in 87 % of tubular adenocarcinoma and 48 % of IPMN lesions. Among IPMN lesions, malignant lesions (IPMC) expressed EGFR more often than benign lesions (IPMA) did. Scattered expression of EGFR was observed in normal pancreatic ducts and within the tubular complex within chronic pancreatitis lesions.

Conclusions

These results indicate that SPINK1 plays a role as a growth factor, signaling through the EGFR pathway in pancreatic ductal adenocarcinoma and neoplasms, and that the EGFR is involved in the malignant transformation of IPMN.     

Size of mural nodule as an indicator of surgery for branch duct intraductal papillary mucinous neoplasm of the pancreas during follow-up

Background

A mural nodule is a strong predictive factor for malignancy in branch duct intraductal papillary mucinous neoplasm (IPMN) of the pancreas, but the nodule size has hardly been considered. The aim of this study was to investigate whether a mural nodule of 10?mm was appropriate as an indicator of surgery for IPMN during follow-up.

Methods

The follow-up outcomes of 100 patients who had branch duct IPMN without mural nodules or who had branch duct IPMN with mural nodules of less than 9?mm in a tertiary care setting were investigated retrospectively. The patients underwent abdominal ultrasound (US) every 3?months and additional imaging examinations or cytologic examination of pancreatic juice when necessary. Surgery was recommended to them when a mural nodule developed or when a nodule enlarged and reached 10?mm.

Results

During an average follow-up period of 97?months, branch duct IPMNs developed mural nodules that reached 10?mm in 5 patients (0.62% per year). In one patient the IPMN was revealed to be non-invasive carcinoma by resection, 1 IPMN was shown to be malignant by further follow-up, and 3 were not resected because of refusal or the patient??s age. In 7 patients, mural nodules stayed within 9?mm. The remaining 88 patients lacked mural nodules in their branch duct IPMNs throughout the follow-up. The occurrence of invasive carcinoma around the IPMN was not indicated by imaging examinations in any patient. Univariate analysis showed that the size of the cyst at baseline significantly predicted the development of a mural nodule that reached 10?mm during follow-up (P?=?0.05).

Conclusions

A mural nodule of 10?mm is appropriate as an indicator of surgery in the follow-up of branch duct IPMN.     

Borderline resectable pancreatic cancer: rationale for multidisciplinary treatment

Background

Borderline resectable pancreatic cancer (BRPC) appears to be most frequently related to a positive surgical margin and has a poor prognosis after resection. However, few reports are available on differences in tumor characteristics and prognoses among resectable pancreatic cancer (PC), BRPC, and unresectable PC.

Methods

Records of 133 patients resected for pancreatic ductal adenocarcinoma and 185 patients treated as locally advanced PC (LAPC) were reviewed.

Results

Twenty-four patients who initially underwent resection (BRPC-s) and 10 patients who were initially treated as LAPC (BRPC-n) met the criteria for BRPC. Prognosis of BRPC was significantly better than that of unresectable PC, but was significantly worse than that of resectable PC. BRPC-s showed more frequent nerve plexus invasion (P < 0.01), portal vein invasion (P < 0.01), and loco-regional recurrence (P = 0.03) than resectable PC. The positive surgical margin rate was not significantly higher in BRPC-s (29%) than in resectable PC (19%) (P = 0.41).

Conclusions

BRPC had a poorer prognosis with more local failure than resectable PC although prognosis of BRPC was significantly better than that of unresectable PC. Considering the tumor and treatment characteristics, multidisciplinary treatment including resection is required for BRPC.     

Spleen and gastrosplenic ligament preserving distal pancreatectomy under a minimum incision approach assisted by laparoscopy

Background

As a modification of hand-assisted laparoscopic pancreatectomy, we devised a method of spleen and gastrosplenic ligament preserving distal pancreatectomy, in which pancreatic resection is performed under direct vision extracorporeally.

Methods

The distal pancreas and spleen are pulled out of the peritoneal cavity through the minilaparotomy at the epigastrium following hand-assisted laparoscopic dissection of the distal pancreas. Spleen-preserving pancreatectomy is performed safely under direct vision. The gastrosplenic ligament is also preserved to prevent splenic volvulus after the operation. The transected main pancreatic duct is doubly ligated, and the transected pancreatic stump is sewn manually. The preserved spleen and splenic vessels are placed back in the peritoneal cavity after resection.

Results

In the current study (n = 3), overall morbidity rate, including splenic volvulus and pancreatic fistula, was 0%.

Conclusion

Preservation of the gastrosplenic ligament and extracorporeal preparation of the transected pancreatic stump under direct vision are useful measures in spleen-preserving distal pancreatectomy under a minimum incision approach assisted by laparoscopy.     

Dysplasia at the surgical margin is associated with recurrence after resection of non-invasive intraductal papillary mucinous neoplasms

Background

The significance of a positive margin in resected non-invasive pancreatic intraductal papillary mucinous neoplasms (IPMN) remains controversial. The aim of this study was to determine recurrence rates when dysplasia was present at the final surgical margin.

Methods

A prospectively maintained database identified 192 patients undergoing resection of non-invasive IPMN. Pathological, peri-operative and recurrence data were analysed.

Results

Ductal dysplasia was identified at the final surgical margin in 86 patients (45%) and defined as IPMN or Pancreatic Intraepithelial Neoplasia PanIN in 38 (20%) and 54 (28%) patients, respectively. At a median follow-up of 46 months, 40 (21%) patients recurred with 31 developing radiographical evidence of new cysts, 6 re-resected for IPMN and 3 diagnosed with pancreatic cancer within the remnant. Of those with margin dysplasia, 31% developed recurrent disease compared with 13% in those without dysplasia (P = 0.002). On multivariate analysis, margin dysplasia was associated with a three-fold increased risk of recurrence (P = 0.02). No relationship between dysplasia and development of pancreatic cancer was found.

Discussion

In this study, dysplasia at the margin after a pancreatectomy for non-invasive IPMN was associated with recurrence in the remnant gland, but not at the resection margin. While this finding may warrant closer follow-up, it does not identify a gland at higher risk for the subsequent development of invasive disease.     

Clinical usefulness of repeated pancreatic juice cytology via endoscopic naso-pancreatic drainage tube in patients with pancreatic cancer

Background

Cytological examination of pancreatic juice obtained during endoscopic retrograde cholangiopancreatography (ERCP) is well established, but its sensitivity for pancreatic cancer has not been satisfactory. The aim of this study was to evaluate the usefulness of repeated pancreatic juice cytology (PJC) via the endoscopic naso-pancreatic drainage (ENPD) tube in patients with pancreatic cancer compared with conventional PJC.

Methods

We retrospectively investigated 139 patients with pancreatic disease. Between April 2004 and November 2007, conventional PJC was performed in 56 patients with pancreatic cancer and 23 with benign pancreatic stricture. Between January 2008 and November 2010, ENPD was used in 40 patients with pancreatic cancer and 20 with benign pancreatic stricture. The ENPD tube was placed into the main pancreatic duct for up to 3 days, and cytological samples of pancreatic juice were collected up to 6 times in total.

Results

Sensitivity, specificity, positive predictive value, negative predictive value, and overall accuracy of the ENPD method for pancreatic cancer were 80, 100, 100, 71, and 87 %, respectively, revealing significantly higher sensitivity than the conventional method (p = 0.0001). Sensitivities according to tumor location and size were 90 % (19/21), 69 % (9/13), and 67 % (4/6) in the head, body, and tail of the pancreas, 88 % (7/8), 79 % (19/24), and 75 % (6/8) in tumors with a diameter less than 20 mm including carcinoma in situ, 21–40, and greater than 41 mm, respectively.

Conclusions

The ENPD method was found to have high diagnostic yield, especially for tumors less than 20 mm or located in the pancreatic head, and might be useful for the diagnosis of early-stage pancreatic cancer.     

For which type of chronic pancreatitis is the “Hamburg procedure” indicated?

Background

A pancreatic duct diameter (PDD) ranging from 4 to 5 mm is regarded as “normal”. The “large duct” form of chronic pancreatitis (CP) with a PDD > 7 mm is considered a classical indication for drainage procedures. In contrast, in patients with so-called “small duct pancreatitis” (SDP) with a PDD < 3 mm, extended resectional procedures are suggested including, as an “ultima ratio”, even total pancreatectomy.

Methods

Between 1992 and 2008, among a total of 978 patients who were treated for CP, 51 suffered from SDP and underwent longitudinal “V-shaped excision” of the anterior aspect of the pancreas. The interval between symptoms and surgery varied from 12 to 123 months. Median follow-up was 87 months (range 32–131 months). A pain score was used as well as a multidimensional psychometric quality-of-life questionnaire.

Results

Hospital mortality was 0%. The perioperative morbidity (30 days) was 19.1%. Median pain score decreased by 95.5%. Global quality of life index increased in median by 53.6% (range 37.5–80%). In 35 patients (75%), complete pain relief was achieved. The impairment of exocrine and endocrine pancreatic function after surgery was statistically not significant.

Conclusions

Longitudinal “V-shaped excision” of the ventral pancreas is a secure and effective approach for SDP, achieving significant improvement in quality of life and pain relief. While sparing patients from unnecessary, extended resectional procedures, it appears not to result in substantial deterioration of exocrine and endocrine pancreatic function.     

Patient allocation based on preoperative assessment of pancreatic fibrosis to secure pancreatic anastomosis performed by trainee surgeons: a prospective study

Background

A fragile or non-fibrotic pancreas increases the risk of postoperative pancreatic fistula (POPF) after pancreatic head resection, whereas pancreatic fibrosis decreases the risk. The degree of pancreatic fibrosis can be estimated using the time-signal intensity curve (TIC) of the pancreas, obtained with dynamic magnetic resonance imaging (MRI). We have investigated whether trainee surgeons can perform pancreatic anastomosis safely, without the occurrence of POPF, when patients are selected carefully based on a preoperative assessment of pancreatic fibrosis.

Methods

Seventy-two consecutive patients who underwent pancreatic head resection were enrolled in this prospective trial. Dynamic contrast-enhanced MRI of the pancreas was performed preoperatively in all patients who, based on their pancreatic TIC profile, were then allocated to one of two groups: Group A comprised patients with type I pancreatic TIC, signifying a normal pancreas without fibrosis (n = 46); Group B comprised patients with type II or III pancreatic TIC, signifying a fibrotic pancreas (n = 26). An end-to-side duct-to-mucosa pancreaticojejunostomy was performed in all patients, with all patients in Group A operated on by two experienced surgeons, and all patients in Group B operated on by one of eight trainee surgeons at various stages of training.

Results

There was no operative mortality. POPF developed in 19 patients: 12 patients with grade A POPF and seven with grade B. All except one of the POPF occurred in Group A patients. The POPF in the one patient from Group B was grade A (p < 0.001).

Conclusions

A trainee surgeon can perform a secure pancreatic anastomosis without the occurrence of POPF in patients with a pancreas displaying a fibrotic pancreatic TIC on dynamic MRI scans.     

Pancreatic cancer causing acute pancreatitis: a comparative study with cancer patients without pancreatitis and pancreatitis patients without cancer

Background/purpose

Although pancreatic cancer produces upstream obstructive pancreatitis, acute pancreatitis is a less common manifestation of pancreatic cancer. This study aimed to clarify the subgroup of pancreatic cancer patients who present with an episode of acute pancreatitis (Group I) in comparison with a matched group of pancreatic cancer patients without pancreatitis (Group II) and another group of acute pancreatitis patients without pancreatic cancer (Group III).

Methods

This was a retrospective comparative study of 18 patients in Group I, 300 patients in Group II and 141 patients in Group III.

Results

The mean age of Group I was 63.7 years and the male to female ration was 1:0.3. Serum CA 19-9 levels were elevated in 80 %. The main pancreatic duct was incompletely obstructed in 7 patients. There were no significant differences in location of tumor, clinical stage, resection rate and survival months between Group I and II. Acute pancreatitis secondary to pancreatic cancer was more likely to be mild (94 vs. 72 %, p < 0.05) and relapsed (39 vs. 16 %, p < 0.05) compared with Group III.

Conclusions

Anatomic evaluation of the pancreas should be performed in patients with acute pancreatitis with no obvious etiology, even if the pancreatitis is mild, to search for underlying malignancy.     

Pancreatic duct replication is increased with obesity and type 2 diabetes in humans

Aims/hypothesis

In a high-fat-fed rat model of type 2 diabetes we noted increased exocrine duct replication. This is a predisposing factor for pancreatitis and pancreatic cancer, both of which are more common in type 2 diabetes. The aim of the study reported here was to establish if obesity and/or type 2 diabetes are associated with increased pancreatic ductal replication in humans.

Methods

We obtained pancreas at autopsy from 45 humans, divided into four groups: lean (BMI <25 kg/m²); obese (BMI >27 kg/m²); non-diabetic; and with type 2 diabetes. Pancreases were evaluated after immunostaining for the duct cell marker cytokeratin and Ki67 for replication.

Results

We show for the first time that both obesity and type 2 diabetes in humans are associated with increased pancreatic ductal replication. Specifically, we report that (1) replication of pancreatic duct cells is increased tenfold by obesity, and (2) lean subjects with type 2 diabetes demonstrate a fourfold increase in replication of pancreatic duct cells compared with their lean non-diabetic controls.

Conclusions/interpretation

Pancreatic duct cell replication is increased in humans in response to both obesity and type 2 diabetes, potentially providing a mechanism for the increased risk of pancreatitis and pancreatic cancer in those with obesity and/or type 2 diabetes.     

Neuronostatin Ameliorates Sodium Taurocholate-Induced Acute Pancreatitis in Rats

Background and Aims

Neuronostatin is encoded in the preprosomatostatin gene and exerts important physiological actions on neuronal and cardiovascular regulation and metabolism in diverse tissues. An intraperitoneal injection of neuronostatin can induce c-Jun expression in the periphery of pancreatic islets. Because of the relatively high amount of neuronostatin present in the pancreas, it is necessary to investigate the effects of neuronostatin on pancreas. Furthermore, little is known about the effect of neuronostatin on acute pancreatitis.

Methods

Neuronostatin (30, 60, and 120 nmol) was injected in to the external jugular vein 30 min before retrograde infusion of 2 % sodium taurocholate into the pancreaticobiliary duct. After 6 h, histological damage of the pancreas was evaluated by pancreas weight and paraffin section. A blood sample was collected to determine the serum amylase and lipase activities.

Results

In our findings, neuronostatin groups had a reduction in interstitial edema, acinar cell vacuolization, and inflammatory infiltration of the pancreas compared with the model group. Biochemical data showed that serum amylase and lipase activities were significantly decreased in neuronostatin-pretreated groups by comparison with the model group.

Conclusions

Histopathologic examination suggests that neuronostatin ameliorated the histological damage of sodium taurocholate-induced acute pancreatitis in rats. The biochemical analysis was consistent with that obtained from histopathologic examination, which was toward a trend of attenuating acute pancreatitis. In summary, neuronostatin might be potentially capable of ameliorating pancreatic damage in acute pancreatitis in rats.     

Surgical technique for complete resection of the extrahepatic portion of the common bile duct and the ampulla of Vater for tumors of the ampulla of Vater

Background

Ampullary tumors have to be completely resected, but substantial morbidity and mortality rates are associated with pancreaticoduodenectomy (PD). Local resection can be the procedure of choice in selected ampullary lesions for high-risk patients.

Methods

Preoperative examination indicated that the ampullary tumor extended into the common bile duct without evidence of pancreatic duct involvement and no definite invasion into either the duodenum or the pancreas. We performed a complete resection of the extrahepatic bile duct and the ampulla of Vater, including the tumor, without performing PD by dissecting the intrapancreatic bile duct from the pancreas both downward towards the ampulla of Vater and upward using a transduodenal approach.

Results

The operation was successfully completed, and the postoperative course was uneventful, with the exception of a minor pancreatic fistula from retropancreatic dissection. The final pathological examination demonstrated well-differentiated tubular adenocarcinoma limited to the mucosa with negative surgical margins.

Conclusion

Complete resection of the extrahepatic bile duct and the ampulla of Vater through a transduodenal approach can be a feasible and safe surgical procedure for selected ampullary tumors in high-risk patients.     

Histopathological study of invasive ductal carcinoma (IDC) of the pancreas without associated cancerous occlusion of the main pancreatic duct

Backgroud/Purpose

Invasive ductal carcinoma (IDC) of the pancreas may be associated with cancerous occlusion of the main pancreatic duct (MPD) in its growth process, but at quite low a frequency; there are patients who do not develop this occlusion.

Methods

This study examined the histological features of surgical specimens from 8 patients with IDC without MPD occlusion, in comparison to 32 patients with IDC with this occlusion (controls). The pancreatic duct was identified by confirming the presence of mural elastic fibers on the wall of the pancreatic duct. Immunohistochemical staining was done with Ki-67 antibody.

Results

The frequency of IDC without MPD occlusion was very low (5.0% [2/40] patients at Kurume University and 3.1% [4/126] patients at Juntendo University). The number of intraductal carcinoma components was 1.5 ± 1.1 per specimen in the IDCs without occlusion and 5.9 ± 2.4 in the controls (P < 0.001). The Ki-67 labeling index was 18.0 ± 11.7% in the IDCs without occlusion and 30.0 ± 12.1% in the controls (P < 0.05). The number of intraductal carcinoma components and the Ki-67 labeling index were significantly lower in the IDCs without occlusion than in the controls.

Conclusions

Our findings suggested that these two types of IDC could have different biological features.     

Increased K-ras mutation and expression of S100A4 and MUC2 protein in the malignant intraductal papillary mucinous tumor of the pancreas

Purpose

The purpose of this study was to document the biological changes during the progression of intraductal papillary mucinous neoplasm of the pancreas (IPMN) and to identify biological markers capable of differentiating benign and malignant IPMN.

Methods

Forty-one patients with IPMN who underwent resection between 1994 and 2003 were enrolled in this study. The paraffin-embedded tumors from 27 with benign IPMNs and from 14 with IPMCs were subjected to immunohistochemical staining and DNA extraction. Direct DNA sequencing analysis for K-ras mutation and immunohistochemical staining using 17 biological markers was performed.

Results

K-ras mutations at codon 12 and 13 were detected in 13 of 37 (38.2%) of the IPMNs: in 5 of 24 (20.8%) of benign IPMNs, and in 8 of 13 (61.5%) of malignant IPMNs (p = 0.028). The expression of S100A4 and MUC2 were increased in malignant IPMNs. S100A4 was expressed in 2 (7.4%) of 27 benign IPMNs, and 6 (42.9%) of 14 malignant IPMNs (p = 0.007). MUC2 was expressed in 2 (7.4%) benign IPMNs, and in 9 (64.3%) malignant IPMNs (p < 0.001).

Conclusion

K-ras mutation and the expression of S100A4 and MUC2 (especially in intestinal subtype) were found to be related to malignancy in IPMN, and may be useful for the diagnosis and for assessing the biological behavior of IPMN.     

Does revision of resection margins based on frozen section improve overall survival following pancreatoduodenectomy for pancreatic ductal adenocarcinoma? A meta-analysis

Background

Margin status is the main surgical determinant of long-term outcome in pancreatic cancer. Intraoperative frozen section (IOFS) detects microscopic positive margins at a stage when margin revision is possible. The aim of this study was to determine if IOFS driven-revision of pancreatic resection margin(s) improves overall survival (OS) in pancreatic cancer.

Efficacy of multi-detector computerized tomography scan, endoscopic ultrasound, and laparoscopy for predicting tumor resectability in pancreatic adenocarcinoma

Background

Definitive treatment for pancreatic adenocarcinoma is surgical resection. Endoscopic ultrasound (EUS), multi-detector computerized tomography scan (MDCT), and laparoscopy are current preoperative methods for assessing the resectability in this malignancy. This study compared the efficacy of these methods in predicting the resectability of pancreatic adenocarcinoma.

Methodology

One hundred and fifty-seven patients considered for resection of pancreatic adenocarcinoma in two centers in Iran were evaluated. All of the patients were evaluated by MDCT and/or EUS; ones that had resectable tumor in imaging were assessed by laparoscopy/laparotomy. Patients undergoing pancreaticoduodenectomy were followed for 2 years.

Results

The majority (67 %) were male. The mean age was 66 years. The lesion was situated in the head of pancreas in 127 cases (81 %). Tumor resectability rate according to the MDCT scan/EUS, laparoscopy, and laparotomy was 6 %, 5 %, and 3 %, respectively. Only 3 % of the pancreatic adenocarcinoma cases were resectable at the time of diagnosis. Fifty percent of patients predicted to have resectable tumor according to MDCT/EUS and 37.5 % of cases that had resectable disease in laparoscopy were found to have unresectable lesions at laparotomy and or postsurgical follow up.

Conclusions

Prognosis continues to be dismal for pancreatic adenocarcinoma, and better methods to assess tumor resectability are needed.