Yoko Maekawa

CEA producing primary hepatic carcinoid

Imaging studies of a hepatic tumor in a 53-year-old woman with elevated serum levels of neuron-specific enolase (NSE), carcinoembryonic antigen (CEA) and 5-hydroxyindole acetic acid (5HIAA) revealed a hypervascular tumor in the right lobe. Grossly, the brownish tumor was measured 13.5x12 cm with four daughter nodules. Microscopically, the majority of these columnar and round tumor cells had ribbon-or rosette-like patterns with the expression of neuroendocrine marker proteins, such as Grimelius, NSE, chromogranin A, and synaptophysin, and moderate expression of CEA but without the expression of cytokeratin nos 7,8,14,18,19 and OV-6; the minority had glandular patterns with a strong expression of CEA but without the expression of cytokeratin nos 7,8,14,18,19 and OV-6. Ultrastructurally, most tumor cells contained populations of electron-dense core granules ranging between 100 and 200 nm in diameter. After hepatectomy, serum CEA, NSE, and 5HIAA reverted to normal ranges and persisted for 19 months. These findings suggested that the diagnosis of primary hepatic carcinoid was tenable and that the tumor might derive from hepatic stem cells which acquired the additional nature of producing CEA without cytokeratins characteristic of hepatocytes or bile duct cells. Some molecular based approaches have attributed unique biological behavior and histogenesis to this carcinoid tumor.

Percutaneous hepatic venous isolation and extracorporeal charcoal hemoperfusion for high-dose intraarterial chemotherapy in patients with colorectal hepatic metastases

The results of treating 12 consecutive patients with unresectable colorectal hepatic metastases with a hepatic arterial infusion of high-dose Adriamycin, 100–120 mg/m2, using hepatic venous isolation (HVI) and charcoal hemoperfusion (CHP) are reported herein. Adriamycin was administered over 5–15 min under extracorporeal drug elimination by HVI-CHP. HVI was percutaneously accomplished by either the double-balloon technique using a Fogarty occlusion catheter (8/22F) or a balloon-tipped catheter (16F). During the infusion, isolated hepatic venous blood was filtered by CHP and pumped into the left axillary vein. There were no lethal complications, and good hemodynamic tolerance to HVI-CHP was confirmed. Tumor liquefaction accompanied by a sharp decrease in serum carcinoembryonic antigen levels by more than 50% of pretreatment levels was observed in 6 of the 12 patients 1 month after treatment. Apart from chemical hepatitis, which developed in 11 (92%) of the patients, the Adriamycin toxicities were well controlled following the development of nausea and vomiting in 2 patients (17%), leukopenia <2,000/mm3 in 3 (25%), and gastric ulcer in 1 (8%). These results indicate that this method is a safe and useful procedure for otherwise hazardous high-dose intraarterial chemotherapy in patients with unresectable hepatic tumors.

Extracorporeal cisplatin removal using direct hemoperfusion under hepatic venous isolation for hepatic arterial chemotherapy: an experimental study on pharmacokinetics.

This study was undertaken to pharmacokinetically evaluate the efficacy of direct hemoperfusion under hepatic venous isolation (HVI-DHP) to cisplatin (CDDP) removal during hepatic arterial infusion. CDDP (2–4 mg/kg) was administered continuously to mongrel dogs through the hepatic artery for 10 min. Plasma levels and tissue concentrations were then compared between animals receiving CDDP alone (group 1, n=4) and those treated with additional HVI-DHP for 20 min (group 2, n=6). The peak CDDP levels in the right external jugular vein (systemic level) were 6.10±1.31 (mean±SD) and 1.41±0.12 μg/ml in groups 1 and 2 at a dosage of 2 mg/kg, respectively (P<0.01). The estimated drug removal rates in group 2 animals at dosages of 2 and 4 mg/kg were 45.7 (mean, n=5) and 46.9% (n=1), respectively. The tissue concentrations of CDDP of the liver 30 min after the initiation of infusions were similar in both groups. The values of the liver, the heart, and the kidney were 1.90±0.55, 0.50±0.16, and 3.90±2.50 μg/g of wet tissue weight, respectively, in group 1. In contrast, tissue levels of the heart and the kidney in group 2 animals were significantly reduced, with the values at a dosage of 2 mg/kg being 0.21±0.03 μg/g (P<0.01) and 0.86±0.53 μg/g (P<0.05), respectively. This study demonstrated that the extrahepatic distribution of CDDP during hepatic arterial infusion can be reduced significantly by the concomitant use of HVI-DHP.

Multiple hypervascular liver nodules in a heavy drinker of alcohol

Abstract  A case of hypervascular nodules in the liver, but without hepatitis B or C virus infection in a 38‐year‐old woman with a history of alcohol abuse is presented. An ultrasound disclosed 1–2‐cm hypoechoic tumors in the right and left lobes. Magnetic resonance imaging showed high‐intensity tumors at both the T1‐weighted and T2‐weighted sequences. Incremental dynamic computed tomography and hepatic angiography revealed hypervascular tumors. Ultrasound‐guided needle biopsy revealed no evidence of hepatocellular carcinoma, metastatic liver cancer, hemangioendothelioma, inflammatory pseudotumors or pseudolymphoma, but demonstrated stellate‐scar fibrosis septa, which contained small unpaired arteries without hyperplasia dividing the nodule. Moreover, marked pericellular fibrosis, neutrophilic infiltration and Mallory bodies were observed in the cytoplasm. There was no evidence of bile duct proliferation. From these findings, the diagnosis of alcohol‐induced fibrosis, distinctly different from focal nodular hyperplasia, was tenable. Further studies may provide insights into the pathogenesis of nodule formation and hypervascularity in heavy drinkers of alcohol.

Cranial-to-caudal approach for radical lymph node dissection along the surgical trunk in laparoscopic right hemicolectomy

Complete mesocolic excision with central vascular ligation is considered to contribute to superior oncological outcomes after colon cancer surgery [1]. For advanced right-sided colon cancer, this surgery sometimes requires lymph node (LN) dissection along the superior mesenteric vein (SMV), with division of the middle colic vessels, or their right branches, at origin [2]. Here, we present cranially approached radical LN dissection along the surgical trunk during laparoscopic right hemicolectomy. The omental bursa is first opened wide, and the gastrocolic trunk of Henle is exposed, using the right gastroepiploic vessels and the accessory right colic vein (ARCV) as landmarks. After division of ARCV, SMV and middle colic vein (MCV) are identified. After dividing MCV at its root, LN dissection along SMV is conducted in a cranial-to-caudal manner. Concurrently, the middle colic artery, or its right branch, is exposed and divided at origin. The transverse colon is then raised ventrally, and LN dissection along SMV using a cranial-to-caudal approach is again performed. The ileocolic and right colic vessels are divided at origin. The ascending and transverse mesocolon, including the pedicles, are then separated from the retroperitoneal tissues, pancreatic head, and duodenum, using a medial approach. The key characteristics in this procedure consist of easy access to pancreas, early division of ARCV and middle colic vessels at origin, and easy dissection along SMV. We performed a laparoscopic colectomy using this approach for 18 patients with right-sided colon cancer. The mean operative time and blood loss were 288 min and 83 ml, respectively. The mean number of harvested LNs was 24. There were 6 cases with positive LN metastasis. There were no recurrent cases at a median follow-up period of 24 months. We consider this approach to be safe and useful for radical LN dissection along SMV for right-sided colon cancers.

Eosionophilic pseudotumor of the liver due to Ascaris suum infection

A case of eosinophilic pseudotumor of the liver due to Ascaris (A) suum is described in a 34-year-old-man with a high serum level of immunoglobulin E and hypereosinophilia ascribed to a history of atopic dermatitis since childhood. Multiple hepatic hypoechoic nodules detected by ultrasound were confirmed as low-density nodules on computed tomography (CT), and as low and high signal intensity lesions on T1-and T2-weighted magnetic resonance imaging (MRI), respectively. CT during arteriography (CTA) and arterial portography revealed multiple nodules with ring-shaped enhancement and perfusion defect, respectively. Biopsied liver tissue specimens did not contain tumor cells or atypical cells; instead, they showed marked infiltration of eosinophils with necrosis and Charcot-Leyden crystals in the portal tracts and hepatic sinusoides, suggesting parasitic infection, although neither larvae nor eggs were detected. The diagnosis of visceral larva migrans (VLM) due to A. suum was based on immunoserological tests. The patient was a habitual consumer of raw bovine liver, which may explain the A. suum infection. After drug therapy with albendazole, the hypoechoic nodules disappeared. Differential diagnoses and the possible transfection route of A. suum are discussed.

Surgical outcomes of intracorporeal circular-stapled esophagojejunostomy using modified over-and-over suture technique in laparoscopic total gastrectomy

AbstractBackground Esophagojejunostomy in laparoscopic total gastrectomy (LTG) is a technically demanding procedure. Although several methods have been reported to date, none is considered consistently reliable. We developed a simple method for intracorporeal circular-stapled esophagojejunostomy using a modified over-and-over suture technique. The surgical outcomes of our technique were evaluated in comparison with those of open total gastrectomy (OTG).MethodsFrom April 2012 to August 2014, reconstruction using this method in LTG was performed for 21 consecutive patients with gastric cancer (LTG group). Their surgical outcomes were compared with those of 27 patients with gastric cancer who underwent OTG without splenectomy (OTG group) between January 2011 and April 2014.ResultsEstimated blood loss was significantly lower, and the postoperative hospital stay was significantly shorter in the LTG group than in the OTG group. The operating time and the number of harvested lymph nodes were similar between the two groups. The incidence of overall complications did not differ significantly between the two groups. Anastomotic leakage developed in one of the 21 patients in the LTG group and in two of the 27 patients in the OTG group. Anastomotic stenosis was observed in one patient in the LTG group.ConclusionsWe consider this method as simple and feasible for most laparoscopic surgeons with basic laparoscopic suturing skills. This method might help LTG to become an accepted standard surgical option for treatment of patients with gastric cancer.

Development of multicentric hepatocellular carcinoma after completion of interferon therapy

6 international units (IU) of IFNα, 3 days a week for a total of 24 weeks. After the IFN therapy, the patient demonstrated a normal serum ALT level, and was continuously negative for HCV-RNA, and histology improved from chronic active hepatitis to chronic persistent hepatitis. Follow-up studies with ultrasonography (US) every 3 months and computed tomography (CT) every 6 months revealed no space-occupying lesion (SOL) for 3 years after IFN treatment.US-guided biopsies of two 15-mm hypoechoic SOLs in segments eight (S8) and seven (S7) 34 and 74 months, respectively, after IFN treatment showed well-differentiated hepatocellular carcinoma (HCC). Clinical data, imaging studies, and histologic examinations showed that both tumors were multicentric HCC. Further studies may provide insights into the possible role of HCV in hepatocarcinogenesis in patients demonstrating HCV eradication by IFN treatment.

Correlation between Insulin Resistance and Outcome of Pegylated Interferon and Ribavirin Therapy, Hepatic Steatosis, Hepatic Fibrosis in Chronic Hepatitis C-1b and High Viral Load

Background/Aims: Insulin resistance (IR) has been reported to be an independent predictor of treatment outcome in chronic hepatitis C patients. Methods: We analyzed the relationship between IR and the outcome of pegylated interferon and ribavirin (PEG-IFN/RBV) therapy, taking into account host factors of body mass index and histological index, such as rate of fatty change and fibrosis. Japanese patients (n = 30; 19 men and 11 women; median age 60.0 ± 8.7 years) with chronic hepatitis C-1b with a high viral load were treated with PEG-IFN-α2b/RBV for 48 weeks. Results: Sustained virological response (SVR) was seen in 60% (18/30) and non-SVR in 40% (12/30). HOMA-IR (homeostasis model of assessment-insulin resistance index) at the start and at 24 weeks of treatment showed no statistical difference between SVR and non-SVR. Correlation was observed between HOMA-IR and body mass index (r = 0.45, p = 0.013). Among 20 patients, steatosis and fibrosis were assessed by biopsy. Correlation was observed between HOMA-IR and steatosis (r = 0.57, p = 0.0093), whereas no correlation was observed between HOMA-IR and fibrosis. Conclusion: A larger prospective study is needed to clarify the role of IR in the outcome of PEG-IFN/RBV combination therapy and hepatic fibrosis in Japanese patients.

Primary Sclerosing Cholangitis and Hepatitis C Virus Infection

Two cases of primary sclerosing cholangitis with hepatic C virus infection in a 62-year-old man and a 60-year-old woman are presented. The infection in the man was eradicated with interferon therapy in 1992. Seven years thereafter, endoscopic retrograde cholangiography revealed a diffuse 2.5-cm-long stenotic lesion in the common bile duct which was consequently resected. Histological examination of the resected specimen revealed proliferation of epithelial cells, plasma cell infiltration, and fibrosis in the submucosal layer of the common bile duct. The human leukocyte antigen DR loci were 2 and 9. In the woman, a 6-month course of interferon therapy in 1992 failed to eradicate the infection. Cholangiography in 1999 revealed multiple narrowings and dilatations of intra- and extrahepatic bile ducts. Ultrasound guided biopsy of the liver in 1992 had revealed onionskin lesions around the bile duct epithelium in the portal tract. The human leukocyte antigen DR locus was 2. From these findings, the 2 cases were diagnosed as primary sclerosing cholangitis. Further studies may provide insights into the relation between the pathogenesis of the disease and the infection.