Surgical strategy for liver metastases of neuroendocrine tumors.

BACKGROUND/AIMS: Little information is available about the long-term prognosis after hepatectomy for liver metastases of neuroendocrine tumors (NETs). To clarify the prognosis for liver metastases of NETs after hepatectomy and to identify a practical and useful surgical indication for hepatic metastases of NETs. METHODOLOGY: Twenty-four patients with NET were divided into 2 groups: the nHM group (patients without hepatic metastasis, n=13) and the HM group (patients with hepatic metastasis or recurrences, n=11). Hepatectomy was indicated for metastases or disease recurrences in the liver if R0 resection was expected to be achievable. Patient clinicopathological features, mode of recurrences and treatment for them were evaluated retrospectively. RESULTS: The median follow-up period for the 24 patients was 34 months (range 7-69) and the disease specific survival rate was 82% at 5 years. DSS at 5 years did not differ between patients with and without hepatic recurrence (91% vs. 75% respectively, p=0.6144), even though the histological grade and the MIB-1 index were higher in the HM group. CONCLUSIONS: Patient prognosis was acceptable following our policy of hepatectomy for NET liver metastases. Survival could be improved by intensive multimodal treatment.

Presurgical assessment of flow variability in an azygos vein aneurysm using 4D-flow MRI.

Azygos vein aneurysm (AVA) is necessary to prevent pulmonary embolism due to the outflow of a thrombus or rupture of the aneurysm. However, there is no established modality to assess the properties of AVA. Time-resolved three-dimensional phase-contrast magnetic resonance imaging (4D-flow MRI) has been used to examine the hemodynamics in various fields. We report a case of AVA to evaluate the flow variability and adhesions of surrounding tissues using 4D-flow MRI. The findings of the study suggested aneurysm turbulence and the absence of thrombi. The cine image, which showed a sliding wall synchronized to the heartbeat, indicated no adhesion to the superior vena cava. Based on these results, the thoracoscopic approach was deemed possible preoperatively. Thoracoscopic AVA resection was performed, and the postoperative course was uneventful. This study documented the utility of 4D-flow MRI for a detailed evaluation of AVA.

Identification of Novel Diagnostic Markers for Malignant Pleural Mesothelioma Using a Reverse Translational Approach Based on a Rare Synchronous Tumor.

Although the routine use of immunohistochemistry has improved the accuracy of histopathologic diagnosis in clinical practice, new methods for discovering novel diagnostic markers are still needed. We sought new diagnostic markers for malignant pleural mesothelioma (MPM) using a reverse translational approach with limited archival tissues from a very rare case. Total RNA extracted from formalin-fixed paraffin-embedded (FFPE) tissues of a synchronous collision tumor consisting of MPM and pulmonary adenocarcinoma (PAC) was employed for gene expression profiling (GEP) analysis. Among the 54 genes selected by GEP analysis, we finally identified the following two candidate MPM marker genes: PHGDH and TRIM29. Immunohistochemical analysis of 48 MM and 20 PAC cases showed that both PHGDH and TRIM29 had sensitivity and specificity almost equivalent to those of calretinin (sensitivity 50% and 46% vs. 63%, and specificity 95% and 100% vs. 100%, respectively). Importantly, of the 23 epithelioid MMs, all 3 calretinin-negative cases were positive for TRIM29. These two markers may be diagnostically useful for immunohistochemical distinction between MPMs and PACs. This successful reverse translational approach based on FFPE samples from one very rare case encourages the further use of such samples for the development of novel diagnostic markers.

Colonic varices treated with embolization after pancreatoduodenectomy with portal vein resection: a case report.

BACKGROUND: Pancreatoduodenectomy with resection of the portal vein or superior mesenteric vein confluence has been safely performed in patients with pancreatic head cancer associated with infiltration of the portal vein or superior mesenteric vein. In recent years, left-sided portal hypertension, a late postoperative complication, has received focus owing to increased long-term survival with advances in chemotherapy. Left-sided hypertension may sometimes cause fatal gastrointestinal bleeding because of the rupture of gastrointestinal varices. Here, we present a case of colonic varices caused by left-sided portal hypertension after pancreatoduodenectomy with portal vein resection. CASE PRESENTATION: A 69-year-old man diagnosed with pancreatic head cancer was referred to our department for surgery after undergoing chemotherapy with nine courses of gemcitabine and nab-paclitaxel. Computed tomography showed a mass 25 mm in diameter and in contact with the portal vein. He had undergone subtotal stomach-preserving pancreatoduodenectomy with portal vein resection. Four centimeters of the portal vein had been resected, and end-to-end anastomosis was performed without splenic vein reconstruction. We had to completely resect the right colic vein, accessary right colic vein, and middle colic vein due to tumor invasion. The pathological diagnosis was ypT3, ypN1a, ypM0, and ypStageIIB, and he was administered TS-1 as postoperative adjuvant chemotherapy. Seven months after therapeutic radical surgery, he presented with melena with progressive anemia. Computed tomography revealed transverse colonic varices. He was offered interventional radiology. Trans-splenic arterial splenic venography showed that transverse colonic varices had developed as collateral circulation of the splenic vein and inferior mesenteric vein system. An embolic substance was injected into the transverse colonic varices, which halted the progression of the anemia caused by melena. Fifteen months after therapeutic radical surgery, local recurrence of the tumor occurred; he died 28 months after the surgery. CONCLUSIONS: When subtotal stomach-preserving pancreatoduodenectomy with portal vein resection is performed without splenic vein reconstruction, colonic varices may result from left-sided portal hypertension. Interventional radiology is an effective treatment for gastrointestinal bleeding due to colonic varices, but it is important to be observant for colonic necrosis and new varices.

DJ-1 is a useful biomarker for invasive extrahepatic cholangiocarcinoma.

We have previously reported that DJ-1 protein is up-regulated in cholangiocarcinoma compared with non-neoplastic epithelium of the bile duct in a study using liquid-chromatography mass spectrometry-based proteomics. The aim of this study was to clarify whether DJ-1 expression offers a biomarker for patients with invasive extrahepatic cholangiocarcinoma (EHCC) who undergo surgical resection with curative intent. Positive immunohistochemical (IHC) staining of DJ-1 was significantly more frequent in the cytoplasm of 96 invasive EHCCs (n = 28, 29.2%) than in that of 66 non-neoplastic epithelial lesions adjacent to invasive EHCC (n = 7, 10.6%; P = .006). No significant difference in clinicopathological features was evident between invasive EHCC patients with negative (n = 68) and positive (n = 28) IHC staining. However, negative IHC staining for DJ-1 in cytoplasm was selected as an independent risk factor for adverse prognosis on multivariate analysis (P = .004, hazard ratio 2.13, 95% confidence interval 1.28-3.57). Serum levels of DJ-1 in 16 invasive EHCC patients with metastasis were compared with 12 invasive EHCC patients without metastasis. Serum levels of DJ-1 tended to be higher in 16 patients with metastasis (median, 40.9 ng/ml) than in 12 patients without (27.6 ng/ml, P = .137). In addition, patients with high serum levels (≥ 40 ng/ml) of DJ-1 tended to have metastasis more frequently than those without (P = .054, Fisher's exact test). We concluded that IHC staining pattern and serum level of DJ-1 in patients with invasive EHCC might be predictive of prognosis and metastasis, respectively.

Differential detection of cytoplasmic Wilms tumor 1 expression by immunohistochemistry, western blotting and mRNA quantification.

Wilms tumor 1 (WT1) is considered to be a promising target of cancer treatment because it has been reported to be frequently expressed at high levels in various malignancies. Although WT1-targeted cancer treatment has been initiated, conclusive detection methods for WT1 are not established. The present study aimed to consolidate immunohistochemistry for WT1 with statistical basis. Transfected cells with forced WT1 expression yielded specific western blot bands and nuclear immunostaining; cytoplasmic immunostaining was not specifically recognized. Immunohistochemistry, western blotting, and quantitative reverse transcriptase-polymerase chain reaction were performed in 35 human cell lines using multiple WT1 antibodies and their results were quantified. Relationships among the quantified results were statistically analyzed; the nuclear immunostaining positively correlated with western blot bands and mRNA expression levels, whereas cytoplasmic immunostaining did not. These results indicate that nuclear immunostaining reflects WT1 expression but cytoplasmic immunostaining does not. The nuclear immunostaining was barely (3/541) observed in primary cancer of esophagus, bile duct, pancreas and lung. Although the present study has some limitations, the results indicate that the cytoplasmic immunostaining does not correlate with actual WT1 expression and prompts researchers to carefully evaluate target molecule expression in treatment of cancer.