Intratumoral tertiary lymphoid organ is a favourable prognosticator in patients with pancreatic cancer.

BACKGROUND: Host immunity has critical roles in tumour surveillance. Tertiary lymphoid organs (TLOs) are induced in various inflamed tissues. The aim of this study was to investigate the clinicopathological and pathobiological characteristics of tumour microenvironment in pancreatic ductal carcinoma (PDC) with TLOs. METHODS: We examined 534 PDCs to investigate the clinicopathological impact of TLOs and their association with tumour-infiltrating immune cells, the cytokine milieu, and tissue characteristics. RESULTS: There were two different localisations of PDC-associated TLOs, intratumoral and peritumoral. A better outcome was observed in patients with intratumoral TLOs, and this was independent of other survival factors. The PDC tissues with intratumoral TLOs showed significantly higher infiltration of T and B cells and lower infiltration of immunosuppressive cells, as well as significantly higher expression of Th1- and Th17-related genes. Tertiary lymphoid organs developed with an association with arterioles, venules, and nerves. These structures were reduced in an association with cancer invasion in PDC tissues, except for those with intratumoral TLOs. The PDC tissues with intratumoral TLOs had capillaries consisting of mature endothelial cells covered by pericytes. CONCLUSIONS: Our results suggest that the presence of intratumoral TLOs represents a microenvironment that has an active immune reaction, and shows a relatively intact vascular network retained.

Proposal to modify the International Union Against Cancer staging system for perihilar cholangiocarcinomas.

BACKGROUND: The International Union Against Cancer (UICC) staging system for perihilar cholangiocarcinoma changed in 2009. The aim of this study was to validate and optimize the UICC system for these tumours. METHODS: This retrospective study was conducted in eight Japanese hospitals between 2001 and 2010. Perihilar cholangiocarcinoma was defined as a cholangiocarcinoma that involves the hilar bile duct, independent of the presence or absence of a liver mass component. The stratification ability of the UICC tumour node metastasis (TNM) system was compared with that of a modified system. RESULTS: Of 1352 patients, 35.9, 44.8 and 12.6 per cent had Bismuth type IV tumours, nodal metastasis (N1) and distant metastasis (M1) respectively. T4 tumours (43.2 per cent) and stage IVA (T4 Nany M0; 36.3 per cent) disease were most common. Survival was not significantly different between patients with T3 versus T4 tumours (P = 0.284). Survival for patients with stage IVA disease was comparable to that for patients with stage IIIB tumours (T1-3 N1 M0) (P = 0.426). Vascular invasion, pancreatic invasion, positive margin, N1 and M1 status were identified as independent predictors of survival. When Bismuth type IV tumours were removed from the T4 determinants and N1 tumours grouped together, the modified grouping had a higher linear trend χ2 and likelihood ratio χ2 compared with the original system (245.6 versus 170.3 respectively and 255.8 versus 209.3 respectively). CONCLUSION: The present data suggest that minimal modification with removal of Bismuth type IV tumours from the T4 determinants and bundling of N1 disease may enhance the prognostic ability of the UICC system. However, this requires validation on an independent data set.

Left hepatic trisectionectomy for advanced perihilar cholangiocarcinoma.

BACKGROUND: Data on outcomes of left hepatic trisectionectomy (LT) for perihilar cholangiocarcinoma are limited. The aim of this study was to clarify short- and long-term outcomes of LT for perihilar cholangiocarcinoma. METHODS: Patients with perihilar cholangiocarcinoma who underwent LT between January 2000 and October 2011 were analysed. Surgical variables, mortality, morbidity (Clavien grade I-V), recurrence sites and survival were compared between subjects who underwent LT, right hemihepatectomy or left hemihepatectomy. RESULTS: A total 214 patients underwent resection for perihilar cholangiocarcinoma, 25 (11·7 per cent) of whom underwent LT, 88 (41·1 per cent) right hemihepatectomy and 94 (43·9 per cent) left hepatectomy. There were no deaths among those who had LT, but 20 patients developed complications. The incidence of grade IIIa complications was significantly higher among patients who underwent LT than in patients who had right or left hemihepatectomy (P = 0·001 and P < 0·001 respectively). Only one patient developed a grade IIIb or IV complication (liver failure) after LT. The overall 5-year survival rate after LT was 39 per cent and median survival was 45 months. There were no significant differences in survival between patients who underwent LT and those who had a right or left hemihepatectomy. CONCLUSION: LT may provide a good outcome for advanced perihilar cholangiocarcinoma.

Immune cell infiltration as an indicator of the immune microenvironment of pancreatic cancer.

BACKGROUND: The host immune reaction is represented by immune/inflammatory cell infiltrates. Here we systematically analysed tumour-infiltrating immune/inflammatory cells in pancreatic ductal carcinoma (PDC) and evaluated their clinicopathological impact. METHODS: Using immunohistochemistry, we examined tumour-infiltrating CD68(+) pan-macrophages, HLA-DR(+)CD68(+) M1 macrophages (M1), CD163(+) or CD204(+) M2 macrophages (M2), CD66b(+) neutrophils (Neu), CD4(+) T cells (CD4(+)T), CD8(+) T cells (CD8(+)T), and FOXP3(+)CD4(+) regulatory T cells (Treg) in 212 cases of PDC, and conducted correlation and survival analyses using the Kaplan-Meier method and Cox proportional hazards model. RESULTS: Higher levels of tumour-infiltrating pan-macrophages, M2, Neu, or the ratio of Tregs to CD4(+)T (%Treg) were significantly associated with shorter survival, whereas higher levels of tumour-infiltrating CD4(+)T, CD8(+)T, or the ratio of M1 to pan-macrophages (%M1) were significantly associated with longer survival. Survival analysis of pairs of these variables revealed that some of the resulting patient groups had exclusively longer survival. We then connected the apparently related factors, and two significant variables emerged: tumour-infiltrating CD4(+)T(high)/CD8(+)T(high)/%Treg(low) and tumour-infiltrating %M1(high)/M2(low). Multivariate survival analysis revealed that these variables were significantly correlated with longer survival and had a higher hazard ratio. CONCLUSION: Tumour-infiltrating CD4(+)T(high)/CD8(+)T(high)/%Treg(low) and %M1(high)/M2(low) are independent prognosticators useful for evaluating the immune microenvironment of PDC.

Gauze packing as damage control for uncontrollable haemorrhage in severe thoracic trauma.

INTRODUCTION: The usefulness of thoracic damage control (DC) for trauma requiring a thoracotomy is not established. The aim of this study was to clarify the usefulness of thoracic packing as DC surgery. METHODS: This was a retrospective case series study of 12 patients with thoracic trauma suffering uncontrollable intrathoracic haemorrhage and shock who underwent intrathoracic packing. Our thoracic DC technique consisted of ligation and packing over the bleeding point or filling gauze in the bleeding spaces as well as packing for the thoracotomy wound. The success rates of intrathoracic haemostasis, changes in the circulation and the volume of discharge from the thoracic tubes were evaluated. RESULTS: Packing was undertaken for the thoracic wall in five patients, for the lung in four patients, for the vertebrae in two patients and for the descending thoracic aorta in one patient. Haemostasis was achieved successfully in seven cases. Of these, the volume of discharge from the thoracic tube exceeded 400 ml/hr within three hours after packing in three patients, decreased to less than 200 ml/hr within seven hours in six patients and decreased to 100ml/hr within eight hours in six patients. Systolic pressure could be maintained over 70 mmHg by seven hours after packing. CONCLUSIONS: Intrathoracic packing is useful for some patients, particularly in the space around the vertebrae, at the lung apex, and between the diaphragm and the thoracic wall. After packing, it is advisable to wait for three hours to see whether vital signs can be maintained and then to wait further to see if the discharge from the thoracic tube decreases to less than 200 ml/hr within five hours.

Hepatic artery reconstruction following ablative surgery for hepatobiliary and pancreatic malignancies.

OBJECTIVE: Hepatic artery (HA) reconstruction is an important part of resective surgery for advanced hepatobiliary and pancreatic malignancies, but few reports have been published. To identify indications for HA reconstruction, we retrospectively analyzed our surgical procedures and outcomes. METHODS: En-bloc resection of advanced hepatobiliary and pancreatic malignancies followed by HA reconstruction was performed in 35 patients. Patients ranged in age from 27 to 81 years and included 18 men and 17 women. The primary site of cancer included the bile duct in 22 patients, the pancreas in 7, and others in 6. Reconstruction of the HA was necessitated by HA resection due to direct cancer invasion in 29 patients and by accidental arterial injury during surgical procedure in 6 patients. RESULTS: The HA was reconstructed with end-to-end anastomosis between hepatic arteries in 17 patients. Transposition of an intra-abdominal artery, such as the gastroepiploic artery, was required in 14 patients, and arterial grafting was required in 4 patients. Although the HA patency was achieved in 30 patients, 4 cases of arterial thrombosis and 1 case of arterial rupture developed postoperatively. The overall RFS time was analyzed in all patients, and mean and median RFS times were 18 and 9 months, respectively. CONCLUSION: Although oncologic outcomes remain poor, HA resection and reconstruction can be performed in selected patients. We believe that the method of first choice for HA reconstruction is end-to-end anastomosis between HAs. A vascular autograft should be used only in selected cases.

Prognostic significance of overexpression of c-Met oncoprotein in cholangiocarcinoma.

BACKGROUND: Cholangiocarcinoma (CC) is a highly malignant carcinoma. We attempted to clarify the prognostic significance of c-Met overexpression and its association with clinicopathological factors in patients with CC. PATIENTS AND METHODS: One hundred and eleven patients with intrahepatic CC (IHCC) and 136 patients with extrahepatic CC (EHCC) who had undergone curative surgery were divided immunohistologically into c-Met(high) and c-Met(low) groups. Clinicopathological factors and outcomes were compared between the groups. c-Met and epidermal growth factor receptor (EGFR) expression was also examined in 10 CC cell lines. RESULTS: The positivity of c-Met was 45.0% in IHCC and 68.4% in EHCC; c-Met(high) expression was demonstrated in 11.7% of IHCC and 16.2% of EHCC. c-Met(high) expression was significantly correlated with the 5-year survival rate for CC overall (P=0.0046) and for IHCC (P=0.0013), histopathological classification in EHCC, and for EGFR overexpression in both IHCC and EHCC. Coexpression and coactivation of c-Met and EGFR were also observed in CC cell lines. Multivariate analysis revealed that c-Met(high) expression was an independent predictor of poor overall and disease-free survival in patients with IHCC. CONCLUSIONS: c-Met overexpression is associated with EGFR expression and is a poor prognostic factor in CC.

Extended right hemihepatectomy for gallbladder carcinoma involving the hepatic hilum.

BACKGROUND: Major hemihepatectomy for advanced gallbladder carcinoma remains controversial as it is associated with serious postoperative complications and poor prognosis. METHODS: All those who underwent extended right hemihepatectomy were identified from a database of patients with gallbladder carcinoma who had surgical resection between 1999 and 2009. The clinicopathological data for these patients were analysed retrospectively. RESULTS: A total of 126 patients underwent surgical resection, 35 of whom had extended right hemihepatectomy. There were no deaths, but 16 patients had complications. The mean(s.d.) duration of operation and blood loss were 564(206) min and 1472(1268) ml respectively. No blood transfusions were needed in 28 patients. Tumour stage (International Union Against Cancer, sixth edition) was IIA in four, IIB in four, III in 15 and IV in 12 patients. The overall 5-year survival rate was 17 per cent with a median survival of 2·2 years. Three patients survived more than 5 years. The presence of hepatic metastases and gallbladder carcinoma originating from the cystic duct were indicators of poor prognosis. CONCLUSION: Extended right hemihepatectomy for gallbladder cancer is safe and may contribute to long-term survival in selected patients.

Tumour necrosis is a postoperative prognostic marker for pancreatic cancer patients with a high interobserver reproducibility in histological evaluation.

BACKGROUND: Tumour necrosis reflects the presence of hypoxia, which can be indicative of an aggressive tumour phenotype. The aim of this study was to investigate whether histological necrosis is a useful predictor of outcome in patients with pancreatic ductal carcinoma (PDC). METHODS: We reviewed histopathological findings in 348 cases of PDC in comparison with clinicopathological information. We counted small necrotic foci (micronecrosis) as necrosis, in addition to massive necrosis that had been only defined as necrosis in previous studies. The reproducibility of identifying histological parameters was tested by asking five independent observers to blindly review 51 examples of PDC. RESULTS: Both micronecrosis and massive necrosis corresponded to hypoxic foci expressing carbonic anhydrase IX detected by immunohistochemistry. Multivariate survival analysis showed that histological necrosis was an independent predictor of poor outcome in terms of both disease-free survival (DFS) and disease-specific survival (DSS) of PDC patients. In addition, metastatic status, and lymphatic, venous, and intrapancreatic neural invasion were independent prognostic factors for shorter DFS and metastatic status, margin status, lymphatic invasion, and intrapancreatic neural invasion were independent prognostic factors for DSS. The interobserver reproducibility of necrosis identification among the five independent observers was 'almost perfect' (κ-value of 0.87). CONCLUSION: Histological necrosis is a simple, accurate, and reproducible predictor of postoperative outcome in PDC patients.

A randomised phase III trial comparing gemcitabine with surgery-only in patients with resected pancreatic cancer: Japanese Study Group of Adjuvant Therapy for Pancreatic Cancer.

BACKGROUND: This multicentre randomised phase III trial was designed to determine whether adjuvant chemotherapy with gemcitabine improves the outcomes of patients with resected pancreatic cancer. METHODS: Eligibility criteria included macroscopically curative resection of invasive ductal carcinoma of the pancreas and no earlier radiation or chemotherapy. Patients were randomly assigned at a 1 : 1 ratio to either the gemcitabine group or the surgery-only group. Patients assigned to the gemcitabine group received gemcitabine at a dose of 1000 mg m(-2) over 30 min on days 1, 8 and 15, every 4 weeks for 3 cycles. RESULTS: Between April 2002 and March 2005, 119 patients were enrolled in this study. Among them, 118 were eligible and analysable (58 in the gemcitabine group and 60 in the surgery-only group). Both groups were well balanced in terms of baseline characteristics. Although heamatological toxicity was frequently observed in the gemcitabine group, most toxicities were transient, and grade 3 or 4 non-heamatological toxicity was rare. Patients in the gemcitabine group showed significantly longer disease-free survival (DFS) than those in the surgery-only group (median DFS, 11.4 versus 5.0 months; hazard ratio=0.60 (95% confidence interval (CI): 0.40-0.89); P=0.01), although overall survival did not differ significantly between the gemcitabine and surgery-only groups (median overall survival, 22.3 versus 18.4 months; hazard ratio=0.77 (95% CI: 0.51-1.14); P=0.19). CONCLUSION: The current results suggest that adjuvant gemcitabine contributes to prolonged DFS in patients undergoing macroscopically curative resection of pancreatic cancer.

Clinicopathological and prognostic significance of EGFR, VEGF, and HER2 expression in cholangiocarcinoma.

Epidermal growth factor receptor (EGFR), vascular endothelial growth factor (VEGF), and human epidermal growth factor receptor 2 (HER2) have been considered as potential therapeutic targets in cholangiocarcinoma, but no studies have yet clarified the clinicopathological or prognostic significance of these molecules. Immunohistochemical expression of these molecules was assessed retrospectively in 236 cases of cholangiocarcinoma, as well as associations between the expression of these molecules and clinicopathological factors or clinical outcome. The proportions of positive cases for EGFR, VEGF, and HER2 overexpression were 27.4, 53.8, and 0.9% in intrahepatic cholangiocarcinoma (IHCC), and 19.2, 59.2, and 8.5% in extrahepatic cholangiocarcinoma (EHCC), respectively. Clinicopathologically, EGFR overexpression was associated with macroscopic type (P=0.0120), lymph node metastasis (P=0.0006), tumour stage (P=0.0424), lymphatic vessel invasion (P=0.0371), and perineural invasion (P=0.0459) in EHCC, and VEGF overexpression with intrahepatic metastasis (P=0.0224) in IHCC. Multivariate analysis showed that EGFR expression was a significant prognostic factor (hazard ratio (HR), 2.67; 95% confidence interval (CI), 1.52-4.69; P=0.0006) and also a risk factor for tumour recurrence (HR, 1.89; 95% CI, 1.05-3.39, P=0.0335) in IHCC. These results suggest that EGFR expression is associated with tumour progression and VEGF expression may be involved in haematogenic metastasis in cholangiocarcinoma.

Randomized clinical trial of hepatectomy using intermittent pedicle occlusion with ischaemic intervals of 15 versus 30 minutes.

BACKGROUND: The optimal ischaemic interval during hepatectomy with intermittent pedicle occlusion (IPO) remains to be established. The aim of the present randomized clinical trial was to compare the short-term outcome of hepatectomy using IPO with an ischaemic interval of 15 versus 30 min. METHODS: Between October 2002 and September 2004, 108 consecutive patients scheduled to undergo hepatectomy without bilioenterostomy were enrolled. During liver transection, IPO was performed with an ischaemic interval of either 15 min with 5 min of reperfusion (standard group, SG) or 30 min with 5 min of reperfusion (prolonged group, PG). After randomization and subsequent exclusion of certain patients, 44 patients in the SG and 48 in the PG were analysed. RESULTS: The mean(s.d.) bilirubin ratio (serum total bilirubin level on day 2 after operation divided by the preoperative level) was 1.6(0.8) in the SG and 1.7(0.8) in the PG (P = 0.874). The transection area per unit transection time was significantly greater in the latter group (median (range) 1.0 (0.4-2.1) versus 0.8 (0.0-1.5) cm(2)/min; P = 0.046). CONCLUSION: There was no difference in the bilirubin ratio when IPO was carried out for 30 or 15 min. By extension of IPO to 30 min, a greater resection area per unit time was possible with preservation of remnant liver function.

Spontaneous regression of hepatocellular carcinoma with complete necrosis: case report.

Spontaneous regression of hepatocellular carcinoma is rare phenomenon. A 74-year-old man was found to have a hepatocellular carcinoma with intrahepatic metastases in the lateral segment of the liver. Before surgery, he developed severe cholangitis due to choledocholithiasis and was treated endoscopically. The tumor marker level decreased markedly, and hepatectomy was performed. The resected tumor demonstrated complete necrosis.

CT imaging of intrabiliary growth of colorectal liver metastases: a comparison of pathological findings of resected specimens.

The objective of this study was to assess the usefulness of CT in the pre-operative evaluation of macroscopic intrabiliary tumour growth of colorectal liver metastases. 25 metastatic nodules of 18 patients who underwent an initial hepatectomy for colorectal liver metastasis were retrospectively evaluated. The CT appearance and pathological findings of the resected specimens were correlated. A number of unusual peritumoral features associated with intrabiliary tumour growth were detected by pre-operative CT. These were classified into three patterns: (1) thickened portal tract; (2) intrahepatic bile duct dilatation; and (3) a wedge-shaped area with enhancement. In 8 (32%) of the 25 nodules the portal tract was depicted as thicker than usual and these features were found proximal to the tumour in three instances, distal to the tumour in four instances, and both proximal and distal in one instance. All of the three intrabiliary tumours larger than 30 mm resulted in thickening of the portal tract. Intrahepatic bile duct dilatation was detected in association with 10 (40%) of 25 nodules. Bile duct dilatation was observed in more than one segment when intrabiliary tumour reached the hepatic hilus from the tumour. The presence of bile duct dilatation was not related to either the size of the tumour or the extent of intrabiliary tumour growth. An abnormally high density wedge-shaped area on contrast enhanced CT was another feature indicating intrabiliary tumour growth and was seen in association with four nodules. Such areas were seen in the liver parenchyma distal to the tumour on three occasions, or encompassing the tumour on one accasion. This wedge-shaped area appeared as a well demarcated dark red-brown region in the cut surface of the resected specimen. CT was useful for detecting the presence of intrabiliary tumour growth with these three patterns of radiological findings in patients with liver metastases from colorectal cancer

Implications of peritoneal washing cytology in patients with potentially resectable pancreatic cancer.

BACKGROUND: The aim of this study was to assess the implications of positive peritoneal washing cytology for management of patients with potentially resectable pancreatic cancer. METHODS: Cytological examination of peritoneal washings was performed in 134 patients who underwent surgical resection for pancreatic adenocarcinoma. The clinicopathological findings and the relationship between cytology results (including cytomorphology) and survival were investigated. RESULTS: One hundred and fourteen patients (85 per cent) had negative cytology results (group 1). Excluding one patient with atypical cells, positive cytology results were obtained in 19 patients (14 per cent): 16 patients without macroscopic peritoneal metastases (group 2) and three patients with minimal macroscopic peritoneal metastases (group 3). The patients in group 2 had significantly larger (P < 0.001) and more advanced (P = 0.022) tumours than those in group 1. However, there were no significant differences in postoperative cumulative survival rates between groups 1 and 2 (P = 0.347). Two patients in group 2 are long-term survivors (40 and 58 months). In cytomorphological analyses, the presence of clusters with ragged edges and isolated carcinoma cells can be considered to indicate a high risk of peritoneal recurrence. CONCLUSION: Positive cytology does not directly predict peritoneal carcinomatosis and, while associated with advanced disease, does not contraindicate radical surgery.

A new staging system for mass-forming intrahepatic cholangiocarcinoma: analysis of preoperative and postoperative variables.

BACKGROUND: The objective of this study was to analyze the clinicopathologic variables and the postoperative outcome in patients with mass-forming intrahepatic cholangiocarcinoma (ICC) to identify important factors for predicting postresection prognosis. Although it has been reported that mass-forming ICC has a different etiology and biologic features compared with hepatocellular carcinoma (HCC), patients with ICC have been dealt with clinicopathologically in the same manner as patients with HCC. METHODS: Sixty patients who underwent hepatectomy for mass-forming ICC with curative intent between 1981 and 1999 were studied. Fourteen preoperative clinical and diagnostic parameters and 12 postoperative surgicopathologic parameters were analyzed. RESULTS: The rate of operative mortality in this patient cohort was 5%, and the overall 1-year, 3-year, and 5-year survival rates were 68%, 35%, and 29%, respectively, with a median survival of 19.6 months. A multivariate analysis revealed that independent negative prognostic factors were 1) hepatic regional lymph node metastasis, 2) multiple tumor presentation, 3) symptomatic tumor, and 4) the presence of vascular invasion. Using these factors, a new staging system was devised: Stage I disease was defined as a solitary tumor without vascular invasion, Stage II disease was defined as a solitary tumor with vascular invasion, Stage IIIA disease was defined as multiple tumors with or without vascular invasion, Stage IIIB disease was defined as any tumor with regional lymph node metastasis, and Stage IV disease was defined as any tumor with distant metastases. The Kaplan-Meier estimated 3-year survival rate and the median survival for each subgroup were 74% for patients with Stage I disease (median survival is the time when the cumulative survival rate of some patients' group declined to 50%; thus, the median survival could not be calculated in patients with Stage I disease because survival was 74% at the latest follow-up), 48% and 26.2 months for patients with Stage II disease, 18% and 16.8 months for patients with Stage IIIA disease, and 7% and 11.2 months for patients with Stage IIIB disease, respectively (P < 0.0001). None of the patients met the criteria for Stage IV disease. CONCLUSIONS: The current results support the use of a new staging system for patients with ICC that is simple and predicts well the differences in survival after patients undergo hepatic resection.

Treatment strategy for small hepatocellular carcinoma: comparison of long-term results after percutaneous ethanol injection therapy and surgical resection.

This comparative study was conducted to clarify the efficacy of percutaneous ethanol injection (PEI) and surgical resection in the treatment of small hepatocellular carcinomas (HCC). Thirty-nine patients treated by PEI and 58 who underwent hepatic resection for small HCC (smaller than 3 cm and 3 or less in number) during the same period were enrolled. The surgery group included more patients with large and multiple bilobar nodules than the PEI group. The histological differentiation of the treated tumors became worse in the surgery patients than in those treated by PEI. On the other hand, the PEI group included more patients with a poor hepatic reserve, according to Child-Pugh grading, the ICG test, and the serum total bilirubin value. The 1-, 3-, and 5-year overall survival rates were almost identical between the 2 cohorts (100%, 82.1%, and 59.0%, respectively, in the PEI group; 96.6%, 84.4%, and 61.5%, respectively, in the surgery group) (P =.96). During the follow-up period, 33 of 39 (85%) and 41 of 58 (71%) patients developed tumor recurrence after PEI and surgery, respectively. Cumulative 1-, 3-, and 5-year tumor-free survival rates in the PEI group were 63.4%, 30.3%, and 9.7 %, whereas those in the surgery group were 75.5%, 44.7%, and 25.7%, respectively (P =.10). Our overall findings show that local therapy can achieve an actual 5-year survival rate of around 60% for patients with small HCC with the proper selection of treatment. A prospective randomized comparative trial is required to settle this longstanding issue.

Invasive carcinoma derived from intraductal papillary-mucinous carcinoma of the pancreas: clinicopathologic and immunohistochemical study of eight cases.

Most intraductal papillary-mucinous carcinomas (IPMCs) of the pancreas are resectable and curable, but some develop into frankly invasive carcinomas. We studied the clinicopathologic features of eight cases of invasive carcinoma derived from IPMC (IC-IPMC) of the pancreas. The patients were aged 54-75 years (mean, 66.6 years); six were male and two were female. The mean tumor size was 7.7 cm (range 5.5-10.5 cm). Two patients without lymph node metastasis had no peripancreatic invasion, and survived longer (115 and 20 months). Three out of four patients with extrapancreatic invasion died of their tumors or developed tumor recurrence within a year. One patient with evidence of liver and lymph node metastasis at the time of first surgery again showed metastatic tumor 21 months later. One patient died of another cause. We also performed a comparative study of the immunohistochemical features of IC-IPMCs in 9 IPMCs (including minimally invasive cases) and 15 ductal adenocarcinomas. CEA cytoplasmic positivity was observed in most of the IC-IPMCs (87.5%) and ductal adenocarcinomas (93.3%), but in only 1 IPMC (11.1%). The frequency of p53 nuclear staining in ductal adenocarcinoma (73.3%) was higher than in IPMC (33.3%) or IC-IPMC (37.5%). In conclusion, IC-IPMC with extrapancreatic invasion should be treated as ductal carcinoma because of its aggressive behavior after resection. Some IPMCs might progress to invasive carcinoma via pathways that are different from those followed by ductal adenocarcinomas.