Extrapancreatic Nerve Plexus Invasion Research Articles

Impact of resection margin status on survival after operation for pancreatic head cancer with extrapancreatic nerve plexus invasion

Extrapancreatic nerve plexus (PL) invasion of pancreatic ductal adenocarcinoma (PDAC) is an important factor for determining resectability and surgical method. We sought to clarify the characteristics of PDAC with PL invasion and clinical impact of the resection margin status on prognosis for PDAC with PL invasion. A total of 242 patients with pancreatic head cancer who underwent pancreatectomy were evaluated. Clinicopathological data and patient survival were analyzed. Pathological PL invasion was observed in 68 patients (28.1%). Patients with PL invasion had significantly shorter disease-free survival (DFS) and showed trends toward worse overall survival (OS) than those without PL invasion. While multivariate analysis revealed that PL invasion was not an independent prognostic factor, PL invasion was associated with extensive venous invasion and a high percentage of lymph node metastases, both of which were independent factors affecting DFS and OS. Among patients with PL invasion, there was no significant difference in DFS and OS between the R0 and R1 resection groups. PL invasion is a common pathological feature of aggressive PDAC with high propensity for invasiveness and metastatic potential. The microscopic resection margin status may not affect the survival of pancreatic head cancer patients with PL invasion.

Extrapancreatic Nerve Plexus Invasion on Imaging Predicts Poor Survival After Upfront Surgery for Anatomically Resectable Pancreatic Cancer.

This study aimed to analyze the risk factors for poor survival of the patients with anatomically resectable pancreatic ductal adenocarcinoma (PDAC), focusing on detailed computed tomography (CT) findings of tumor extent to the peripancreatic tissue. The study included 192 patients who underwent upfront pancreaticoduodenectomy for anatomically resectable PDAC. Preoperative CT images were rereviewed by an experienced radiologist for the pattern of tumor extension to the surrounding tissue: biliary, duodenal, serosal, retroperitoneal, portal venous, arterial, extrapancreatic nerve plexus, and other-organ invasion. Imaging findings and other clinical data that could be obtained before surgery were evaluated for their association with a shorter disease-specific survival (DSS) and recurrence-free survival (RFS). Of the 192 anatomically resectable PDAC patients, extrapancreatic nerve plexus invasion was observed on CT in 38 patients (20%), and this finding was independently associated with a shorter DSS (hazard ratio, 2.258; P < 0.001) and RFS (hazard ratio, 2.665; P < 0.001). The median survival of patients with and without extrapancreatic nerve plexus invasion on CT was 19.7 versus 38.5 months (P < 0.001). Extrapancreatic nerve plexus invasion was shown as an only CT finding associated with a shorter DSS and RFS after upfront surgery for the patients with anatomically resectable PDAC.

Validation and clinical usefulness of pre- and postoperative systemic inflammatory parameters as prognostic markers in patients with potentially resectable pancreatic cancer

BackgroundSeveral preoperative systemic inflammatory parameters, such as the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR), prognostic nutritional index (PNI), and Glasgow prognostic score, have been reported to be associated with the prognosis of solid tumors. In this study, we compared pre- and postoperative hematological inflammatory parameters and validated their prognostic significance in pancreatic cancer patients who underwent surgical resection. MethodsClinical records from 211 consecutive pancreatic cancer patients who underwent surgical resection at our institution were retrospectively analyzed. The optimal cutoff values of hematological inflammatory parameters, including lymphocyte count, NLR, PLR, LMR, and PNI, were determined by time-dependent receiver-operating characteristic analysis. ResultsThe postoperative neutrophil count and serum albumin level were significantly decreased in patients who underwent pancreatoduodenectomy (PD group) and in those who underwent distal pancreatectomy (DP group) compared to the levels at baseline. The postoperative lymphocyte count, monocyte count, and platelet count were significantly increased in the DP group compared to those at baseline. As a result, the postoperative NLR and PNI significantly decreased in both groups. The multivariate analysis identified intraoperative peritoneal washing cytology, administration of adjuvant therapy, tumor size, extrapancreatic nerve plexus invasion, and preoperative PLR as independent prognostic factors for overall survival. ConclusionsSystemic inflammatory responses were altered after pancreatic resection in pancreatic cancer patients. Preoperative PLR may be a useful prognostic marker in pancreatic cancer patients undergoing surgical resection.

Prognostic impact of M2 macrophages at neural invasion in patients with invasive ductal carcinoma of the pancreas

BackgroundNeural invasion is a characteristic pattern of invasion and an important prognostic factor for invasive ductal carcinoma (IDC) of the pancreas. M2 macrophages have reportedly been associated with poor prognosis in various cancers. The aim of the present study was to investigate the prognostic impact of M2 macrophages at extrapancreatic nerve plexus invasion (plx-inv) of pancreatic IDC. MethodsParticipants comprised 170 patients who underwent curative pancreaticoduodenectomy for pancreatic IDC. Immunohistochemical examination of surgical specimens was performed by using CD204 as an M2 macrophage marker, and the area of immunopositive cells was calculated automatically. Prognostic analyses of clinicopathological factors including CD204-positive cells at plx-inv were performed. ResultsPlx-inv was observed in 91 patients (53.5%). Forty-eight patients showed a high percentage of CD204-positive cell area at plx-inv (plx-inv CD204%high). Plx-inv CD204%high was an independent predictor of poor outcomes for overall survival (OS) (P<0.001) and disease-free survival (DFS) (P<0.001). Patients with plx-inv CD204%high showed a shorter time to peritoneal dissemination (P<0.001) and locoregonal recurrence (P<0.001). In patients who underwent adjuvant chemotherapy, plx-inv CD204%high was correlated with shorter OS (P=0.011) and DFS (P=0.038) in multivariate analysis. ConclusionsPlx-inv CD204%high was associated with shortened OS and DFS and early recurrence in the peritoneal cavity and locoregional space. The prognostic value of plx-inv CD204%high was also applicable to patients who received adjuvant chemotherapy. High accumulation of M2 macrophages at plx-inv represents an important predictor of poor prognosis.

Analysis of tumor‐induced lymphangiogenesis and lymphatic vessel invasion of pancreatic carcinoma in the peripheral nerve plexus

Cancer cells can metastasize throughout the body by various mechanisms, including the lymphatic system, resulting in tumor-induced lymphangiogenesis that can profoundly affect patient survival. The aim of the present study was to examine the role of lymphangiogenesis in the metastasis of pancreatic cancer to the peripheral nerve plexus. Immunohistochemistry was performed to analyze specimens obtained from 70 ductal adenocarcinoma patients. The markers used included lymphangiogenic factor vascular endothelial growth factor (VEGF)-C, the lymphatic-specific marker D2-40, and cytokeratin 19, an independent prognostic factor for pancreatic tumors. The relationship between survival rate and invasion of both the lymphatic vessels and peripancreatic nerve plexus (PNP) was evaluated, with clearly elevated lymphatic vessel density (LVD) in tissues adjacent to the cancer tissues. In fact, LVD levels were higher in adjacent tissues than in localized cancer tissues, and lymphatic vessel invasion into tissues adjacent to the tumor was significantly correlated with both PNP invasion (P = 0.005) and lymph node metastasis (P = 0.010). Correspondingly, LVD in tissues adjacent to the tumor was correlated with both invasion of lymphatic vessels surrounding the tumor (P = 0.024) and VEGF-C expression (P = 0.031); in addition, VEGF-C expression was correlated with invasion of lymphatic vessels around the tumor (P = 0.004). Survival rates were significantly lower in patients in whom there was peritumor lymphatic vessel invasion (P < 0.001), extrapancreatic nerve plexus invasion (P = 0.001), and/or lymph node metastasis (P < 0.001). Based on these results, lymphatic invasion associated with adjacent tumor growth likely contributes to the development of metastatic tumors that invade the PNP.

Evaluation of surgical resection for pancreatic carcinoma at a Japanese single cancer institute.

Surgical resection is a radical treatment option for pancreatic carcinoma (PC); however, it is still difficult to cure and patient prognosis is poor at this stage. We examined the demographics, surgical records and outcome in 64 patients with hilar PC undergoing surgical resection. Pancreatoduodenectomy (PD) was carried out in 48 patients, distal pancreatectomy (DP) in 14 and total pancreatectomy in two. Postoperative complications were observed in 18 patients (28%) but no hospital deaths. All stage I patients showed carcinoma in situ of intraductal papillary mucinous carcinoma (IPMC). Postoperative adjuvant chemotherapy was performed in 15 patients (23%) using gemcitabine or S-1. Cancer recurrence was observed in 36 patients (56%) and 31 died of carcinoma. The 5-year cancer-free and overall survival rate was 12% and 14%, respectively. CA19-9 level, morphological type, T category, lymph node metastasis, extrapancreatic nerve plexus invasion, retropancreatic tissue invasion, distal bile duct invasion, duodenal invasion and arterial system invasion were significant poor prognostic factors; however, portal vein system invasion was not significantly associated with prognosis. Cancer infiltration at bile duct cut-end and dissected peripancreatic tissue margin and presence of residual tumor showed a poor prognosis. Surgical prognosis in only non-invasive IPMC was satisfactory. Radically extended surgical resection is necessary and newly effective adjuvant chemotherapy is a promising modality to improve patient survival in PC patients.

Correlation of apparent diffusion coefficient measured by diffusion‐weighted MRI and clinicopathologic features in pancreatic cancer patients

The aim of this study was to evaluate the clinical usefulness of diffusion-weighted magnetic resonance imaging (DWI) in patients with pancreatic cancer by comparing the apparent diffusion coefficient (ADC) value with clinicopathologic features. Twenty-two consecutive patients (12 men, 10 women; mean age 64.4 years) with pancreatic cancer underwent DWI before surgery. We retrospectively investigated the correlations between tumor ADC value and clinicopathologic features. Apparent diffusion coefficient value was significantly lower for pancreatic cancer than for noncancerous tissue (P < 0.001). Receiver operating characteristic analysis yielded an optimal ADC cutoff value of 1.21 × 10(-3) mm(2)/s to distinguish pancreatic cancer from noncancerous tissue. There was a significant negative correlation between ADC value and tumor size (r = -0.59, P = 0.004) and between ADC value and number of metastatic lymph nodes (r = -0.56, P = 0.007). Tumors with low ADC value had a significant tendency to show high portal venous system invasion (P = 0.02) and extrapancreatic nerve plexus invasion (P = 0.01). Apparent diffusion coefficient value appears to be a promising parameter for detecting pancreatic cancer and evaluating the degree of malignancy of pancreatic cancer.

Assessment of Peripancreatic Fat Infiltration of Pancreatic Ductal Adenocarcinoma by Multidetector-Row Computed Tomography: Correlation to Extrapancreatic Nerve Invasion and Surgical Outcomes

disease-free survival. The tumor stage was not associated with intrapancreatic nerve invasion. (P=0.255) However, a larger tumor size (P=0.024), a higher incidence of lymphatic invasion (P=0.036), and the presence of extrapancreatic nerve plexus invasion (P<0.001), were identified as independent factors associated with a higher incidence of intrapancreatic nerve invasion. Conclusion: Intrapancreatic nerve invasion may be useful as a predictor for recurrence after pancreaticoduodenectomy in patients with invasive ductal carcinoma of the pancreas.

Abstract 3107: Semaphorin 4D – plexin B1 signaling in pancreatic ductal adenocarcinoma reflects tumor aggressiveness

Abstract Purpose: Semaphorins are a large family of proteins that provide axonal guidance in neuronal tissues and regulate cell motility in many types of cells. In recent studies, Semaphorin 4D (Sema4D) has been demonstrated to enhance the motility and invasiveness of cancer cells through its receptor, plexin B1, in vitro and also to increase the metastatic potential of breast cancer in vivo. However, the expression patterns and functions of Sema4D in pancreatic cancer remain unknown. Experimental Design: We examined the expressions of Sema4D and plexin B1 in surgically resected specimens of pancreatic ductal adenocarcinoma by immunohistochemistry, and also the effect of Sema4D stimulation on the invasiveness of pancreatic cancer cells. Results: Immunohistochemical staining revealed that Sema4D was expressed on the T cells and B cells in the cancer stroma. Plexin B1 was expressed in the cancer cells, whereas its expression was only faintly detected in the normal pancreatic ductal cells. Tumors with higher expression levels of Sema4D showed a significantly higher tendency towards lymph node metastasis (p = 0.0068), distant metastasis (p = 0.036), extrapancreatic nerve plexus invasion (p = 0.0073), and a poor prognosis (p = 0.024). Increased expression of both Sema4D and plexin B1 was associated with an additive worsening of the prognosis, independent of the tumor-node-metastasis classification and the World Health Organization tumor grade (p = 0.045). Stimulation with Sema4D caused a significant increase in the invasiveness of pancreatic cancer cells, and the knockdown of plexin B1 by siRNA could block the enhanced invasive activity by Sema4D. Conclusion: Sema4D could play a role in the interactions between the tumor cells and the tumor microenvironment in pancreatic cancer. In the context of numerous attempts currently ongoing to target the tumor stroma, our findings provide insight into new molecular targets for the development of treatments for pancreatic cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3107. doi:10.1158/1538-7445.AM2011-3107

Intrapancreatic Nerve Invasion as a Predictor for Recurrence After Pancreaticoduodenectomy in Patients With Invasive Ductal Carcinoma of the Pancreas

Neural invasion is a distinct route for the spread of pancreatic carcinoma. However, the clinicopathologic significance of neural invasion, with particular reference to intrapancreatic nerve invasion, remains to be elucidated. One hundred fifty-three patients who underwent pancreaticoduodenectomy for invasive ductal carcinoma of the pancreas between 2004 and 2008 were retrospectively examined. The clinical and histopathologic factors, including intrapancreatic nerve invasion, were analyzed in these patients. The relationships between the degree of intrapancreatic nerve invasion and disease-free survival, as well as various histopathologic factors, were investigated. There were significant differences in the degree of intrapancreatic nerve invasion with regard to disease-free survival (P < 0.001). A lack of lymph node metastases (P = 0.001), lower incidence of intrapancreatic nerve invasion (P = 0.001), and negative surgical margin (P = 0.011) significantly increased the disease-free survival. The tumor stage was not associated with intrapancreatic nerve invasion (P = 0.255). However, a larger tumor size (P = 0.024), a higher incidence of lymphatic invasion (P = 0.036), and the presence of extrapancreatic nerve plexus invasion (P < 0.001) were identified as independent factors associated with a higher incidence of intrapancreatic nerve invasion. Intrapancreatic nerve invasion may be useful as a predictor for recurrence after pancreaticoduodenectomy in patients with invasive ductal carcinoma of the pancreas.

Number of Metastatic Lymph Nodes, but Not Lymph Node Ratio, Is an Independent Prognostic Factor after Resection of Pancreatic Carcinoma

This study evaluated the prognostic significance of the number of metastatic lymph nodes and the ratio of metastatic nodes to total number of examined lymph nodes (lymph node ratio, LNR) after resection of pancreatic carcinoma. Records of 119 consecutive patients with pancreatic ductal carcinoma, who underwent R0 or R1 pancreatectomy with regional node dissection, were reviewed retrospectively. Clinical factors, pathologic factors including number of metastatic nodes and LNR, and survival were analyzed by univariate and multivariate analyses. Overall survival rates were 78%, 28%, and 20% at 1, 3, and 5 years, respectively. The median numbers of evaluated lymph nodes and involved nodes were 28 and 3, respectively. Univariate analysis revealed that tumor location, postoperative adjuvant chemotherapy, tumor differentiation, choledochal invasion, portal or splenic vein invasion, extrapancreatic nerve plexus invasion, resection margin status, node status, number of involved nodes, LNR, International Union against Cancer (UICC) pT factor, and UICC stage correlated significantly (p < 0.05) with increased survival. By multivariate analysis, negative node metastasis (p = 0.008) and 0 or 1 involved node (p = 0.004), but not LNR, correlated independently with longer survival. The 1-, 3-, and 5-year survival rates of patients with 0 or 1 metastatic node and patients with 2 or more metastatic nodes were 91%, 48%, and 40% and 66%, 10%, and 0%, respectively. The number of metastatic nodes, but not LNR, is one of the most powerful prognostic factors after resection of pancreatic carcinoma.

Prognostic Impact of Para‐aortic Lymph Node Metastasis in Pancreatic Ductal Adenocarcinoma

The aim of the present study was to clarify the prognostic impact of para-aortic lymph node metastasis in pancreatic ductal adenocarcinoma. Medical records of 103 consecutive patients with pancreatic ductal adenocarcinoma, who underwent pancreatic resection with regional and para-aortic lymph node dissection were reviewed retrospectively. Clinicopathological factors and survival were compared between patients with and without para-aortic lymph node metastasis. Tumor size (p = 0.045), extrapancreatic nerve plexus invasion (p = 0.043), UICC pT factor (p = 0.026), and surgical margin status (p = 0.002) were associated significantly with para-aortic lymph node metastasis. Postoperative adjuvant chemotherapy (p < 0.001) and absence of extrapancreatic nerve plexus invasion (p = 0.041) were associated independently with longer survival, but para-aortic lymph node metastasis (p = 0.078) was not associated significantly with survival by multivariate analysis. The 2- and 5-year survival rates and median survival time of patients with and without para-aortic lymph node metastasis were 12, 0%, 12.4 months and 49, 23%, 14.5 months, respectively, and there was a significant difference in survival between the two groups by a log-rank test (p < 0.001). Postoperative adjuvant chemotherapy significantly improved the survival of patients with para-aortic lymph node metastasis (p = 0.025). The prognosis of patients with para-aortic lymph node metastasis is poor in pancreatic ductal adenocarcinoma. However, postoperative adjuvant chemotherapy may improve survival.

MDCT findings of extrapancreatic nerve plexus invasion by pancreas head carcinoma: correlation with en bloc pathological specimens and diagnostic accuracy

To elucidate the multi-detector row computed tomography (MDCT) findings of extrapancreatic nerve plexus (PLX) invasion by pancreas head carcinoma (PhC) by "point-by-point" correlation with en bloc pathological specimens and to assess their diagnostic accuracy. Each pathological section of PhC and adjusted double oblique multiplanar reconstruction MDCT images were correlated in 554 sections from 37 patients. The diagnostic accuracy of the MDCT patterns derived was assessed by blind reading. PLX invasion with fibrosis showed mass or strand shape (85.6%) or coarse reticula (13.3%). The CT findings were divided into fine reticular and linear, coarse reticular, mass and strand, and nodular patterns. PLX invasion was revealed pathologically in 92% of the regions of investigation showing the mass and strand pattern and 63% of the coarse reticular pattern (all continuous with PhC), and they were highly suggestive of PLX invasion by PhC on MDCT images (p < 0.001). Sensitivity, specificity, accuracy, and positive and negative predictive values of these MDCT findings in the diagnosis of PLX invasion were 100% (25/25), 83.3% (10/12), 94.6% (35/37), 92.6% (25/27) and 100% (10/10), respectively. The mass and strand pattern and the coarse reticular pattern continuous with PhC on MDCT images were highly suggestive of PLX invasion by PhC.

Long-term outcomes of extended radical resection combined with intraoperative radiation therapy for pancreatic cancer

Systemic and/or local recurrence often occurs even after curative resection for pancreatic cancer (PC). To prevent local relapse we adopted an extended radical resection combined with intraoperative radiation therapy in patients with PC, and all the patients were followed for more than 5 years. We assessed the long-term outcomes of 41 patients who underwent this combined therapy. The cumulative survival curve in this series was depicted using the Kaplan-Meier method. Statistical analyses were performed using the log-rank test. The actual 5-year survival rate was 14.6%, with a median survival time of 17.6 months. Six patients have been 5-year survivors. Local recurrence occurred in only 2 patients (5.0%). Cancer-related death occurred in 32 patients, 18 of whom had liver metastases. The patients with liver metastases had a significantly shorter survival time than those with other cancer-related causes of death. Patients with n3 lymph node involvement, extrapancreatic nerve plexus invasion, and stage IV disease had significantly poorer prognoses than patients without these characteristics. Our combined therapy for patients with PC contributed to local control; however, it provided no survival benefit, because of liver metastases.

Nerve Plexus Invasion in Pancreatic Cancer

Although extrapancreatic nerve plexus (PLX) invasion is an important prognostic factor in pancreatic carcinoma, the spreading patterns of carcinoma via PLX have not been carefully explored because of the complex anatomical structures around the pancreas. Fifty-eight patients underwent pancreaticoduodenectomy for carcinoma of the head of the pancreas. The patterns of PLX invasion were evaluated by careful pathological examination. The relationship between tumor location considering the embryological structure of the pancreas and the site of PLX invasion was investigated with an immunohistochemical study using pancreatic polypeptide. Forty-six patients (79%) had PLX invasion. The typical patterns of PLX invasion were detected by pathological examination. Patients with carcinoma in ventral pancreas frequently had pancreatic head plexus 1, pancreatic head plexus 2, and superior mesenteric arterial plexus invasion. Patients with carcinoma in dorsal pancreas had invasion into common hepatic artery plexus and plexus within the hepatoduodenal ligament. A significant correlation between tumor location and the site of PLX invasion was observed. Extrapancreatic nerve plexus invasion by carcinoma of the head of the pancreas could be divided into 2 patterns based on an embryological structure of the pancreas and the location of the tumor. These results about PLX invasion may provide important information to determine surgical strategy for carcinoma of the head of the pancreas.

Gemcitabine併用放射線化学療法が奏功し膵頭十二指腸切除術を施行しえた進行膵癌の1例

Gemcitabine併用放射線化学療法が奏功し膵頭十二指腸切除術を施行しえた進行膵癌の1例

Postoperative Adjuvant Chemotherapy Improves Survival after Surgical Resection for Pancreatic Carcinoma

Pancreatic carcinoma is one of the most aggressive types of gastrointestinal malignancy, and its prognosis remains extremely dismal. The aim of this study was to identify useful prognostic factors for patients undergoing surgical resection for pancreatic carcinoma. Medical records of 89 patients with pancreatic carcinoma who underwent surgical resection were retrospectively reviewed. Univariate and multivariate models were used to analyze the effect of various clinicopathological factors on long-term survival. There were no operative deaths. Overall 1-, 2-, and 5-year survival rates were 59, 28, and 7%, respectively (median survival time, 12.1 months). Univariate analysis revealed that postoperative adjuvant chemotherapy, portal vein invasion, lymph node metastasis, extrapancreatic nerve plexus invasion, surgical margin status, UICC pT factor, and UICC stage were significantly associated with long-term survival (P < 0.01). Furthermore, use of postoperative adjuvant chemotherapy and absence of extrapancreatic nerve plexus invasion were found to be significant independent predictors of a favorable prognosis using a Cox proportional hazard regression model (P < 0.05). These results suggest that postoperative adjuvant chemotherapy may improve survival after surgical resection for pancreatic carcinoma and that extrapancreatic nerve plexus invasion indicates a poor prognosis for long-term survival.

Clinical Implications of Combined Portal Vein Resection as a Palliative Procedure in Patients Undergoing Pancreaticoduodenectomy for Pancreatic Head Carcinoma

The clinical implications of combined portal vein resections are controversial. One-hundred and forty-nine consecutive patients underwent macroscopically curative pancreatectomies for pancreatic head carcinoma between January 1, 1996 and December 31, 2004. Portal vein resection was performed in 86 patients (58%). Data on surgical mortality, morbidity, perioperative outcome, pathological factors, initial recurrence site, and survival were retrospectively compared between the patients with and without portal vein resection. The incidence of postoperative pancreatic fistula was lower among patients who underwent portal vein resection. The median survival period was 14 months for the portal vein resection group and 35 months for the non-portal vein resection group, respectively. Combined portal vein resection was a significant predictor of poor survival using a multivariate analysis. Portal vein resection was strongly associated with larger tumor size, the degree of retropancreatic tissue invasion, the presence of extrapancreatic nerve plexus invasion, lymph node metastases, and positive cancer infiltration at the surgical margins. Portal vein resection at the time of pancreaticoduodenectomy can be safely performed. However, most of patients requiring portal vein resection do not achieve a potentially curative resection or a favorable survival term. As a result, the aggressive application and the strict selection of portal vein resection might reduce the incidence of positive surgical margins, enabling long-term survival in patients who do not require portal vein resection.

Clinical Significance of Intraportal Endovascular Ultrasonography for the Diagnosis of Extrapancreatic Nerve Plexus Invasion by Pancreatic Carcinoma

Background/Aims: The extrapancreatic nerve plexus (PL) invasion is a common feature of pancreatic cancer and affects the outcome of the patients after surgical resection. IPEUS with high-resolution probes can visualize the PL invasion with high overall accuracy rate. The aim of this study is to evaluate the clinical significance of the PL invasion diagnosed intraoperatively by intraportal endovascular ultrasonography (IPEUS). Methods: IPEUS was performed in 64 patients who underwent the pancreatic resection. Several clinicopathological factors were studied in patients with or without PL invasion. Results: There were 18 cases in which PL invasion was confirmed pathologically. IPEUS showed 94% sensitivity, 98% specificity and 97% accuracy for the diagnosis of the PL invasion with the false-positive rate of 5.6%. The 1-, 2- and 3-year survival in 18 patients with PL invasion was 30, 6 and 0% in comparison to 52, 32 and 18% in those 46 patients without PL invasion and the difference was statistically significant (p = 0.008). A significant correlation was found between PL invasion and the portal vein invasion, invasion of the margins or pTNM stage. Conclusions: According to current results, the prognosis of the cases with PL invasion is very poor and indication for resection is doubtful. We conclude that the cases in which PL invasion is diagnosed by IPEUS are not indicated for extended resection and correct diagnosis of PL invasion is important not only to predict the outcome but also to decide the surgical procedure for obtaining negative margins while improving the quality of life after surgery.

Detection of extrapancreatic nerve plexus invasion of pancreatic adenocarcinoma. Cytokeratin 19 staining and K-ras mutation.

Neural invasion is known to be one of the aggressive characteristics of pancreatic adenocarcinoma. However, there have been no systematic studies on intraoperative examination of neural invasion of pancreatic carcinomas after wide dissection of the retroperitoneum, particularly at the surgical margin. We performed intraoperative immunostaining on the frozen sections of several excised plexus specimens, using peroxidase-labeled anti-cytokeratin 19 antibody in 17 cases of resectable pancreatic carcinoma. Postoperatively, we also tried to detect occult micrometastasis by direct sequencing of the K-ras gene in the same samples. Intraoperative staining for cytokeratin 19 was positive in 4 of 17 (23.5%) cases. Patients with margin-positive neural invasion had significantly worse prognosis than patients who were margin negative (P < 0.05). One patient had micrometastasis in the nerve plexus, revealed by K-ras mutation, whereas neither cytokeratin 19 staining nor postoperative pathological investigation detected involvement of the analyzed portion. In the four patients margin-positive for cytokeratin 19 staining, the diagnosis of neural invasion by cytokeratin 19 staining was in agreement with the K-ras gene analysis. Intraoperative staining for cytokeratin 19 is useful for detecting pancreatic cancer involvement of the neural plexus margin. The results can be also utilized as a prognostic indicator during the follow-up period.