Visualization of giant virus particles and development of "VIRAMOS" for high school and university biology course.

Several educational trials on handling viruses and or virology have been reported. However, given their small size, direct visualization of these viruses under a microscope has been rarely performed. The so-called "giant viruses" are larger than other viruses with a particle size greater than 200-300 nm. This enables their direct visualization under a light microscope more easily than other viruses. In this study, we developed two new types of teaching material for learning about viruses and cellular organisms using mimivirus, one of the well-known giant viruses. One teaching material involves using glass slides with enclosed mimivirus particles, and another is a paper-based teaching material, named VIRAMOS (http://tlab-edusys.azurewebsites.net/content/viramos_en.pdf). Using these, students can investigate and learn about viruses and cellular organisms. © 2019 International Union of Biochemistry and Molecular Biology, 47(4):426-431, 2019.

Fatal hypermagnesemia induced by preoperative colon preparation in an elderly woman: report of a case.

An 85-year-old woman with rectal carcinoma was referred to our hospital for surgical treatment. She had a history of constipation treated with oral magnesium oxide. She received 34 g of magnesium citrate (Magcolol P(®)) orally for 2 days as a mechanical bowel preparation prior to the operation. Just before the operation, she suddenly developed nausea, vomiting, and cyanosis and went into cardiac arrest. Despite support by mechanical ventilation, dopamine, dobutamine, and norepinephrine, she exhibited repeated bradycardia that was nearly fatal and required temporary pacing. The following day, her laboratory tests revealed marked hypermagnesemia (14.3 mg/dL). After a hemodialysis session, she recovered dramatically and all vasopressors were withdrawn. We conclude that preoperative mechanical bowel preparation with magnesium-containing cathartics can cause fatal hypermagnesemia in elderly patients even if their renal function is normal.

[A case of successful treatment with intra-arterial infusion chemotherapy with cisplatin for advanced hepatocellular carcinoma with portal vein tumor thrombus].

A 69-year-old man with recurrent hepatocellular carcinoma (HCC) in S7/8 after radiofrequency ablation therapy (RFA)was admitted to our hospital. Serum alpha-fetoprotein and protein induced by vitamin K absence or antagonists (PIVKA-II) were elevated to 367 ng/mL and 18,973 mAU/mL, respectively. Abdominal computed tomography scan revealed that the size of the tumor was 56 mm and a portal vein tumor thrombus progressed from the right anterior branch to the left main branch(Vp3). The clinical stage was cT3N0M0, cStage III(JPS). He received 3 courses of intra-arterial infusion chemotherapy with cisplatin(CDDP IA-call)into the right hepatic artery at a dose of 65 mg/m2 every 2 months. Elevated serum alpha-fetoprotein(AFP)and PIVKA-II markedly decreased and returned to normal levels after the second course of treatment. The liver tumor and portal vein tumor thrombus disappeared, and only arterioportal shunting remained. The response to treatment was partial response (PR) and complete response (CR), according to the Response Evaluation Criteria In Solid Tumors and the modified version, respectively. He has been alive for more than 1 year without recurrence. CDDP is an effective treatment for advanced HCC with portal vein tumor thrombus.

[Analysis of breast reconstruction with a tissue expander and implant after ipsilateral breast tumor recurrence in patients undergoing breast-conserving surgery].

Mastectomy is recommended for ipsilateral breast tumor recurrence (IBTR) after breast-conserving surgery plus radiotherapy(breast-conserving treatment). However, the number of patients who receive radiation therapy such as breast- conserving treatment in the hope of breast reconstruction is increasing. Radiation therapy has a significant magnifying effect on the difficulties of breast reconstruction. In the study presented here, we compared the patients who underwent mastectomy+ breast reconstruction with a tissue expander and an implant after IBTR and breast-conserving treatment (irradiation group, n=5) with patients who underwent mastectomy+breast reconstruction with a tissue expander and an implant at the time of the first breast cancer operation (non-irradiation group, n=21). The parameters compared were background, complications, reconstruction success rate, and capsular contraction. A significant difference was not observed between the 2 groups. Complications after operation, specifically capsular contracture, are reported to be more frequent in the radiation group than in the non-irradiation group. However, with appropriate explanation of the risks, this surgery is an option for patients who strongly desire breast reconstruction.

[A case of advanced cholangiolocellular carcinoma successfully treated by neoadjuvant chemotherapy with gemcitabine followed by radical resection].

A 57-year-old woman who was diagnosed with cholangiolocellular carcinoma underwent neoadjuvant chemotherapy with gemcitabine (GEM). The clinical stage was cT3N1M1 (right adrenal grand),cStage IVB (JPS) with invasion to the inferior vena cava (IVC). We were willing to perform hepatectomy if the response to chemotherapy was stable disease (SD) or better according to the Response Evaluation Criteria In Solid Tumors. After 2 courses of preoperative chemotherapy with GEM, SD was obtained. She underwent right lobectomy of the caudate lobe and resection of the right adrenal gland. The IVC was also resected and reconstructed. The pathological diagnosis was as follows: cholangiolocellular carcinoma, im (-), eg, fc(-), sf(-), s0, n0, vp0, vv0, va0, b1, p0, sm(-), 200 µm, pT2N0M0, pStage II, and Cur A2. The IVC was not invaded and the right adrenal gland was diagnosed with adrenocortical adenoma. She underwent continuing adjuvant chemotherapy with GEM for 4 months without recurrence. Therapy for cholangiolocellular carcinoma has not yet been established, but multimodal treatment with GEM and surgical resection is potentially effective for cholangiolocellular carcinoma.

[Two cases of lower bile duct recurrence resected by pancreatoduodenectomy after hepatectomy for hilar cholangiocarcinoma].

We report 2 rare cases of lower bile duct recurrence resected by pancreatoduodenectomy after hepatectomy for hilar cholangiocarcinoma. Case 1: A 74-year-old man underwent extended right hepatectomy for hilar cholangiocarcinoma (JSBS classification: pT1N0M0, fStage I, fCur A, negative cut end). The serum carbohydrate antigen 19-9 level was elevated 18 months after hepatectomy, but abdominal computed tomography showed no signs of recurrence. However, lower bile duct recurrence was revealed by subsequent magnetic resonance imaging, positron-emission tomography, and endoscopic retrograde cholangiopancreatography. Twenty months after hepatectomy, pancreatoduodenectomy was performed, and the pathological findings showed lower bile duct carcinoma(JSBS classification: pT3N0M0, fStage III, fCur A). The patient survived without recurrence 12 months after a secondary operation. Case 2: A 68-year-old woman underwent extended right hepatectomy for hilar cholangiocarcinoma(JSBS classification: pT3N2M0, fStage IVa, fCur B, negative cut end). Twelve months after hepatectomy, dilatation of the remaining lower bile duct was observed by abdominal computed tomography. Endoscopic retrograde cholangiopancreatography revealed lower bile duct stenosis with suspected malignancy, and positron-emission tomography scan detected increased fluorodeoxyglucose uptake at the stenosis. Fourteen months after the hepatectomy, pancreatoduodenectomy was performed and the pathological findings showed lower bile duct carcinoma(JSBS classification: pT4N2M0, fStage IVb, fCur B). The patient died of local recurrence 6 months after the secondary operation.

[A case of primary neuroendocrine carcinoma of the bile duct].

A 74-year-old man presented to a physician with a chief complaint of jaundice. He was diagnosed with bile duct carcinoma and admitted to our hospital. Laboratory data revealed abnormally elevated levels of total bilirubin, serum hepatic transaminase, and CA19-9. Endoscopic retrograde cholangiopancreatography revealed neoplastic stenosis from the hilus hepatis to the common bile duct. Abdominal computed tomography (CT) revealed an enhancing tumor in the hilus hepatis bile duct, and positron emission tomography-CT (PET-CT) revealed abnormal fluorodeoxyglucose accumulation in the tumor. Under a diagnosis of hilar cholangiocarcinoma, the patient underwent an extended right hepatectomy and left hepatico -jejunostomy. Immunohistochemically, the tumor cells were positive for neuroendocrine markers such as chromogranin A, synaptophysin, and CD56. The tumor was diagnosed as primary neuroendocrine carcinoma of the bile duct. The patient exhibited multiple liver metastasis 6 months after the operation. Transcatheter arterial chemoembolization (TACE) was performed for the liver metastasis. Although TACE exerted a cytoreductive effect temporarily, multiple liver abscesses developed. The patient died of liver failure 16 months after the operation. We report this rare case of primary neuroendocrine carcinoma of the bile duct.

Immunohistochemical consistency between primary tumors and lymph node metastases of gastric neuroendocrine carcinoma.

BACKGROUND: Gastric neuroendocrine carcinoma (G-NEC) is a rare, highly malignant tumor that exhibits aggressive growth leading to vascular invasion, distant metastasis and extremely poor prognosis. We studied the clinicopathological findings of seven patients at our institute to better under this disease. METHODS: Seven cases of G-NEC were identified among 1,027 cases of gastric carcinoma that underwent gastrectomy at Kansai Rousai Hospital between 2002 and 2010. We studied the pathological and immunohistochemical features of gastric neuroendocrine carcinomas at both the primary site and metastatic lymph nodes. RESULTS: The mean patient age was 73 years (range 63 to 86 years). There were no females in this series. The final staging was Stage I in one case, Stage II in two, Stage III in two and Stage IV in two. A total of 31 metastatic lymph nodes were found in these patients. This study revealed that the ratio of neuroendocrine cells was similar between the primary and metastatic sites, which tended to show the same expression patterns of neuroendocrine markers. CONCLUSIONS: Metastatic lymph nodes showed heterogeneous immunohistochemical expression patterns similar to the primary sites. G-NEC is far advanced at diagnosis and rapidly reaches the lymph nodes retaining its heterogeneity, carrying a worse prognosis than common gastric cancer. MINI ABSTRACT: G-NEC grows rapidly and metastasizes to the lymph nodes, retaining its pathological and immunohistochemical heterogeneity even at the metastatic sites.

[A case whose lung metastasis was detected and resected eleven years after resection of primary colon cancer].

In July 1999, a 79-year-old man underwent sigmoidectomy and D3 lymphadectomy for sigmoid colon cancer (ss, n(-), stage II, cur A). In September 2000, hepatectomy of right lobe and cholecystectomy were performed for his liver metastasis. Every three to six months follow-up had been kept since adjuvant chemotherapy (200 mg/day of 5-FU per os for two years) completed. Eleven years and two months after sigmoidectomy (in September 2010), a chest X-ray examination detected a small nodule in upper area of his right lung, which was diagnosed as either primary lung cancer or metastatic lung tumor followed by chest CT scan and PET-CT examination. In November 2010, laparoscopy-assisted partial resection of his right lung was performed. Histochemical examination of the resected lung tumor resulted cytokeratin 7(-), cytokeratin 20(+) and TTF-1(-), confirming its final diagnosis as lung metastasis from sigmoid colon cancer. He has been alive for six months without any recurrence since resection of his lung metastasis. It was a very rare case to have more than ten-year interval between colon cancer resection and detection of its lung metastasis. However, when we diagnosed the patient with lung tumor, who had undergone a colorectal resection, we should consider if he had a lung metastasis from colorectal cancer.

[Clinical outcomes in patients with brain metastasis from gastric cancer].

Brain metastasis from gastric cancer is uncommon and difficult to treat. Patients with brain metastasis had a poor prognosis with simultaneous and multiple metastases to other organs. Four patients with brain metastasis were reported. All patients were male with the median age of 76 years and the diagnosis was stage IA in one, stage IIIA in 2 and stage IV in one. Three patients underwent gastrectmy and one patient in stage IV received chemotherapy as the initial treatment. An interval between the initial treatment and the diagnosis of brain metastasis was 11, 24, 30 and 83 months, respectively. The symptoms of brain metastasis were stagger in two, unconsciousness in one and headache in one. The treatment for brain metastases were a surgical resection for two lesions larger than 3 cm and gamma-knife radiotherapy was performed for the other lesions. The duration of survival from the treatment for brain metastasis was 45, 48, 58 and 94 days, respectively. Multidisciplinary treatment, including a surgical resection and stereotactic radiosurgery such as gamma-knife for brain metastasis is thought to improve the quality of life, but not prolong survival due to metastases to other organs. The development of effective systemic treatment will be necessary in order to prolong survival.

[Wallflex duodenal stenting for gastric outlet obstruction caused by inoperable advanced gastric cancer].

INTRODUCTION: Wallflex duodenal stent (WDS) placement for gastric outlet obstruction caused by malignant disease has been covered by health insurance in Japan since April 2010. We have placed five-WDS for three gastric outlet obstructions caused by inoperable advanced gastric cancer. CASE 1: A 67-year-old male diagnosed as having Stage IV gastric cancer with liver, lung, and lymph node metastases underwent a WDS placement during first-line chemotherapy. He was able to consume a soft diet orally for about five months thereafter. He underwent a WDS replacement for stent obstruction by tumor ingrowth and finally died due to the primary tumor 11 months after the first visit. CASE 2: A 63-year-old male diagnosed as having Stage IV gastric cancer with liver and lymph node metastases underwent a WDS placement during the first-line chemotherapy. He was able to consume a soft diet orally for about three months thereafter. He died due to the primary tumor six months after the first visit. CASE 3: A 72-year-old male diagnosed as having Stage IV gastric cancer with liver and lymph node metastases underwent a WDS placement during the first-line chemotherapy. He was able to consume a soft diet orally for about four months and subsequently received the fourth-line chemotherapy. He underwent a WDS replacement for stent obstruction by tumor ingrowth and finally died due to the primary tumor nine months after the first visit. CONCLUSIONS: WDS stent placements for gastric outlet obstruction caused by inoperable advanced gastric cancer were performed safely and enabled the consumption of a soft diet orally for at least three months. This approach is expected to be a safe and effective treatment option.

[Pure laparoscopic surgery for repeat hepatectomy].

In this study, we evaluate the capability of pure laparoscopic surgery for repeat hepatectomy. From June 2010 through March 2011, 15 cases of primary hepatectomy (hepatocellular carcinoma 11, liver metastasis 4) and 6 cases of re-hepatectomy patients (all cases were hepatocellular carcinoma) were underwent pure laparoscopic hepatectomy. As for the liver function in primary hepatectomy and re-hepatectomy, liver damage A/B was 8/7 and 2/4, median ICG R15 was 18 (4- 42) % and 30 (10-35) %, respectively. As for operative variables in primary hepatectomy and re-hepatectomy, the median operative duration was 265 (105-673) minutes, 296 (157-475) minutes, the median amount of bleeding was 10 (small amount-2,000) cc, 25 (small amount-140) cc, and the median post-operative hospital stay was 10 (6-17) days and 11 (6-24) days, respectively. Primary hepatectomy and re-hepatectomy represented equal clinical outcomes, although re-hepatectomy patients had lower hepatic function compared with primary hepatectomy patients.

[Successful treatment of advanced esophageal cancer with lymph node metastases by docetaxel, cisplatin and 5-FU followed by salvage lymphadenectomy--a case report].

We present a case of advanced esophageal cancer with multiple lymph node metastases successfully treated by combination therapy of docetaxel, cisplatin and 5-FU (DCF) followed by salvage lymphadenectomy. The patient was a 60-year-old female with the diagnosis of squamous cell carcinoma of the middle thoracic esophagus. The clinical stage diagnosis was cT2N4M0, cStage IVa. Systemic chemotherapy with DCF was started as the initial treatment. The changes noted on endoscopy and CT scan in the primary lesion and lymph nodes after two cycles of DCF were judged as complete response (CR). However, recurrence was diagnosed in the left cervical lymph nodes based on FDG uptake on FDG-PET. Salvage cervical lymphadenectomy was performed. Thereafter, the patient again achieved CR after the second administration of DCF for upper mediastinal lymph node recurrence. At present, she is still alive three years after the first visit. Combination therapy of DCF and salvage lymphadenectomy is potentially effective for advanced esophageal cancer with lymph node metastases.

Multidrug resistant cancer cells susceptibility to cytotoxic taxane diterpenes from Taxus yunnanensis and Taxus chinensis.

Twelve taxane diterpenes (1-12), which were isolated previously from the EtOH extract of the aerial parts of Taxus yunnanensis or Taxus chinensis, were evaluated for cytotoxicity against the multidrug resistant cancer cells KB-VIN and KB-7d. Compounds and showed significant cytotoxicity in these cell lines. Compounds and also demonstrated significant activity against KB-7d. The biflavonoid isolated from T. yunnanensis was only marginally cytotoxic against the A549 (lung) cell line, but a simple methoxylated analogue (14) was inactive.