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A 78-year-old man without hepatitis virus B or C underwent right hemi-hepatectomy and lymph node dissection for a tumor 5 cm in diameter located in the hepatic hilum of the posterior segment of the liver with portal vein thrombi extending into the main portal trunk and a tumor 1.5 cm in diameter in the peripheral side of segment 5 of the liver. Histopathologically, the former was diagnosed as intrahepatic cholangiocarcinoma and the latter as hepatocellular carcinoma(HCC). Five months after the surgery, intrahepatic and lymph node metastases were diagnosed based on computed tomography(CT); therefore, chemotherapy with S-1 for 3 months and gemcitabine and cisplatin(GC)for 5 months was administered, after which the metastatic lesions were not detected. Nineteen months after the surgery, partial resection of segment 2 of the liver was performed for a tumor 3 cm in diameter, which was diagnosed as HCC histopathologically. Two years after the second surgery, 2 recurrent nodules in the liver in segments 3 and 4 were detected on CT. Platinum-based hepatic arterial infusion chemotherapy(HAIC)and transcatheter arterial chemoembolization(TACE)were performed, and chemotherapy with GC was then administered for 7 months. For a new tumor detected in segment 1 in the liver, TACE was performed 17 months after initial HAIC. Seventy-four months after the initial surgery, 5 new nodules less than 1 cm in diameter were detected, and chemotherapy with sorafenib was administered for 5 months, after which the patient died of coronavirus disease 2019.

A 76-year-old woman had underwent 5-fluorouracil(5-FU), oxaliplatin(L-OHP)combination therapy(mFOLFOX6)as first-line chemotherapy for peritoneal recurrence after resection of sigmoid colon cancer. She showed severe general fatigue and disturbance of consciousness on the second day of the 12th course of chemotherapy. Computed tomography of the head detected no abnormal findings in the central nervous system. The laboratory results revealed a marked hyperammonemia. She was diagnosed as a disturbance of consciousness due to hyperammonemia and treated her with branched- chain amino acid solution. Then the disturbance of consciousness resolved on the following day. After changing the regimen of chemotherapy, the disturbance of consciousness was not found. Recently, it has been reported that high-dose 5-FU regimen such as mFOLFOX6 causes hyperammonemia as a rare adverse event. We should take hyperammonemia into account when disturbance of consciousness occurs during high-dose 5-FU chemotherapy.

A 77-year-old man presented with biliary colic and was diagnosed with descending colon cancer and cholelithiasis.During the surgery, a mass was detected in the upper jejunum, located 5 cm from the Treitz ligament on the anal side.Open left hemicolectomy with partial jejunal resection was performed.The mass in the small intestine was diagnosed as solitary small intestinal metastasis of colon cancer through immunohistopathological examination.Isolated intestinal metastases of colorectal cancers are rare.Furthermore, synchronous metastases are rare among these cases.A previous study reported poor prognosis in patients with small intestinal metastasis; therefore, more studies on the small intestinal metastasis of colorectal cancer are necessary.

The patient was a 67-year-old man with multiple liver metastases from sigmoid colon cancer and had received capecitabine, oxaliplatin, and bevacizumab(CAPOX plus Bev)combination chemotherapy. After 11 courses of this therapy, he had a rupture of esophageal varices and was treated with endoscopic variceal ligation(EVL). Esophageal varices are rare during the course of oxaliplatin-based chemotherapy. More studies are necessary for early detection of esophageal varices during this therapy.

A 71-year-old man underwent right hemi-hepatectomyfor a hepatocellular carcinoma(HCC)measuring 18 cm in diameter. The pathological diagnosis was poorlydifferentiated HCC. Ten months after the surgery, computed tomographyrevealed a nodule 12mm in diameter in the right lung as well as 2 nodules measuring 19 and 11mm in diameter in the retroperitoneum at the cranial aspect of the left kidney. Four months later, the nodule in the right lung had enlarged to 44 mm, while the 2 nodules in the retroperitoneum had enlarged to 68mm and 34 mm. These nodules were resected and histopathologicallydiagnosed as metastasis from HCC. Twenty-one months after liver resection, computed tomographyrevealed nodules 16 and 25mm in diameter in the retroperitoneum around the urinarybladder and jejunum, respectively. One month later, intussusception resulted from the jejunal tumor. Laparoscopic surgerywas performed for both tumors, which were diagnosed as metastases from HCC. Twenty-five months after liver resection, metastasis from the HCC appeared in the left adrenal grand, at the site of the jejunal anastomosis, and in the fattytissue around the right scapula. Twenty-nine months after liver resection, the patient died of respiratoryfailure from multiple metastases in the left lung.

A 68-year-old man presented with generalfatigue due to anemia. Gastrointestinalendoscopy showed a tumor approximately 60mm in diameter in the lesser curvature of the angle of the stomach. Large cell neuroendocrine carcinoma was diagnosed by biopsy of a tumor specimen. Computed tomography revealed bulky regional lymph node metastases, solitary liver metastasis, and left adrenal metastasis. After three courses of combined chemotherapy with S-1 and CDDP, the gastric lesion and lymph node metastases shrunk, but the liver metastasis and left adrenal metastasis enlarged. After three courses of combined chemotherapy with ramucirumab and paclitaxel, the liver metastasis and left adrenal metastasis also shrunk, and no other new metastatic lesions appeared. Accordingly, total gastrectomy with lymph nodes dissection, partial resection of the liver and left adrenalectomy were performed for a curative resection. The histological findings revealed neuroendocrine carcinoma and adenocarcinoma of the stomach. The lesions of the liver and lymph nodes were all burned out, and a tiny metastatic lesion of neuroendocrine carcinoma was left in the left adrenal gland. S-1 was administrated for 3 months after surgery. The patient has been alive for 16months without recurrence after surgery.

Recent studies indicated that isolated pulmonary metastases could define a favorable subgroup in metastatic pancreatic cancer. We report a case of isolated pulmonary metastases after curative resection of pancreas head cancer treated with chemotherapy and pulmonary metastasectomy survived for 79 months after recurrence. A 72-year-old male underwent pancreatoduodenectomy for pancreas head cancer. Adjuvant chemotherapy was done with gemcitabine hydrochloride (GEM)for 6 months and then S-1 for 2 months. Twenty-seven months after surgery, 2 small metastatic nodules in the left lung was detected. Chemotherapy with GEM was performed but the lesions grew larger very slowly. A new metastatic nodule was detected in the right lung 40 months after surgery and pleural effusion was detected 52 months after surgery. Then combination chemotherapy with GEM and S-1 was performed for 3 months followed chemotherapy with S-1 alone. Seventytwo months after surgery, chemotherapy with GEM was performed again because of patient's intolerance to S-1. Ninety months after initial surgery, pulmonary metastasectomy of the right lung was performed because of its resistance to chemotherapy. Chemotherapy with GEM was started again 4 months after pulmonary metastasectomy but serum levels of tumor markers remained increase. Combination chemotherapy with GEM and nab-paclitaxel was started 8 months after pulmonary metastasectomy but the patient died 16 months after pulmonary metastasectomy.

We describe a nematode larva in a subcutaneous nodule excised from a 44-year-old Chinese male who had been living in Japan for 15 years. Morphological features suggested that the worm was a dioctophimatid nematode. PCR amplification and sequencing of small subunit ribosomal DNA and mitochondrial cytochrome subunit c oxidase genes allowed us to identify the larva as the giant kidney worm, Dioctophyme renale (Goeze, 1972). This is the first molecularly confirmed human case of a dermal D. renale infection.

Nature restoration activities are important as environmental and agricultural countermeasures in rural regions. In order to gain an overview of how development of agricultural communities is carried through the collaboration of farmers, local residents, NPO's, and other organizations in an environmentally friendly manner, analysis was carried out of the applications to participate in 207 activities comprising the “Nature Restoration Activities in Rural Areas Contest” hosted by, among others, The Ministry of Agriculture, Forestry, and Fisheries. Results showed that the scope of the activities has broadened rapidly since 1995, generally as a result of burgeoning concern over decline in numbers of wildlife species and deterioration of agricultural land and copses. Also revealed was that the activities now span a diverse range, centered on nature regeneration, and including environmental improvements to the habitat of organisms in irrigation channels and other locations, and environmental education about rice fields and ponds. It was clear from this study that activities including the development of branded agricultural produce and the maintenance and improvement of facilities for contact with nature were being undertaken for the purposes of improving the local economy and society.

症例は67歳の女性,下腹部痛と血便を主訴に受診し入院となった. CT検査にて骨盤腔内にガスと液体貯留を有する嚢腫様病変と,それに接するS状結腸壁の壁肥厚を認めた.入院翌日に下腹部激痛を訴え, X線写真で両横隔膜下に遊離ガス像を認めた. S状結腸膀胱痩とそれに起因する汎発性腹膜炎を疑い手術を行った.術中所見では多量の膿性腹水を認めたが膀胱は正常であり子宮体部に穿孔を認めた. S状結腸に腫瘍を認め子宮体部背側に癒着していたが浸潤の有無は不明であった. S状結腸癌に伴った子宮留膿腫破裂による汎発性腹膜炎と診断し,単純子宮全摘術・S状結腸切除術を施行した.病理組織学的には,子宮は炎症著明であったが子宮内膜・筋層にS状結腸癌の腫瘍細胞を認めなかった.本症例はS状結腸癌に伴った子宮留膿腫破裂による汎発性腹膜炎をきたした稀な症例であった.

症例は96歳の男性.開腹の既往歴はない.心窩部痛を主訴に来院し,腹部単純X線と腹部CT検査で小腸の拡張を認めイレウスの診断で入院となる.イレウス管を留置し,保存的治療を行うも症状が改善しないため入院9日目に開腹術を施行した. S状結腸間膜左葉に直径2cmの欠損を認め,回盲部より約40cm口側の回腸がRichter型に嵌頓していた.用手的に嵌頓を解除し,嵌頓部の腸管は損傷を認めず切除を要しなかった.ヘルニア門は切開開放とし手術を終了した. S状結腸間膜内ヘルニアは腹腔内ヘルニアのなかでも稀で,その本邦報告例は自験例を含め22例であった.入院から手術までの期間は平均9.39日であり,術前に診断し得たのは1例のみであった. S状結腸間膜内ヘルニアを含む内ヘルニアの診断は極めて困難であり,原因不明のイレウスでは可及的早期の手術を考慮する必要があると考えられた.

We examined the course of a primary hepatic neuroendocrine carcinoma (PHNEC) patient and analyzed the postoperative outcome of all reported PHNEC cases.A literature search for PHNEC cases was performed using PubMed. All reported cases and our present patient were analyzed in this study. Survival analysis was performed using the Kaplan-Meier method. Risk factors for the recurrence of PHNEC following hepatic resection were investigated.A total of 43 patients were analyzed in this study. The 3-, 5-, and 7-year overall survival rates were 55%, 48%, and 48%, respectively. The 3-, 5-, and 7-year overall survival rates in surgery patients were 78% each, and 25%, 17%, and 17%, respectively in nonsurgery patients. Lymph node metastasis posed a significant risk factor for postoperative recurrence.Hepatic surgery is an appropriate therapeutic treatment for PHNEC without distant metastasis nor lymph node metastasis. Adjuvant chemotherapy might be necessary for PHNEC patients with lymph node metastases.

最近10年間に経験した閉鎖孔ヘルニアの10例について検討した.年齢は56～87歳,平均77.8歳と高齢で,平均体重35.6kgと痩せた患者が多かった.8例が女性で,分娩回数は平均4.3回と多産傾向がみられた. Howship-Romberg徴候は6例に認められた.骨盤部CTを施行した最近の7例は術前診断可能であった.嵌頓臓器は8例で小腸がRichter型に嵌頓し, 1例に小腸係蹄が嵌頓していた.壊死あるいは穿孔を伴っていたため,腸切除を施行したのは3例であった.ヘルニア門の修復は, 2例に腹膜縫合と卵巣の縫着を, 1例に閉鎖膜縫合を施行した.最近の7例に対してはポリプロピレンメッシュを用いて閉鎖孔を閉鎖した.本症の診断には骨盤部CTが非常に有用で,メッシュを用いた修復は容易でかつ根治的な治療法であり,腸切除を必要とする症例でも使用可能と考えられた.

虫垂憩室と虫垂癌はそれぞれまれな疾患である. 今回我々は, その両者が併存した症例を経験したので若干の文献的考察を加えて報告する.患者は67歳の女性. 右下腹部痛を主訴に来院し, 急性虫垂炎の診断で手術を施行した. 腹腔内には膿性腹水が貯留し, 切除した虫垂の虫垂間膜側に憩室を2個認め, その1つが穿孔していた. 病理組織学的に憩室は仮性憩室で, 憩室穿孔部は好中球の浸潤が著明であった. また, 虫垂根部に印環細胞癌を認め, 奬膜下層まで浸潤していた. 術後38日目にリンパ節郭清を伴う回盲部切除術を施行したが, 切除標本には遺残腫瘍はなく, リンパ節転移も認めなかった.虫垂憩室と虫垂癌の併存例は本邦では自験例を含め3例のみ報告され, きわめてまれな症例と考えられた.

A human colon cancer cell line, OCUC-LM1(LM), was established from a liver metastasis in our laboratory. Intrasplenic injection of LM into nude mice was repeated three and five times, and the daughter cell lines were designated as LM-H3 and LM-H5 respectively. The level of sialyl Lewis A (SLA) in the supernatant of LM-H3 and LM-H5 was 3 and 4.5 times higher than that of LM respectively. Flow cytometric analysis of SLA expression showed that the peak channel for LM was 113; for LM-H3, 126; and for LM-H5, 146. The mean fluorescence intensity of LM was 102.3 +/- 43.5; for LM-H3, 126.2 +/- 28.4; and for LM-H5, 144.8 +/- 23.4. In endothelial cell adhesion assays, the percentages of adherent LM-H3 and LM-H5 cells were significantly higher than for LM. The activity of alpha1-->4 fucosyltransferase was higher in LM-H3 and LM-H5 than in LM, but there was no difference in alpha2-->3 sialyltransferase activities for type 1 chain among the cell lines. Our results suggest that SLA expression is associated with acquisition of a high capacity for liver metastasis of colon cancer; increased SLA expression is due mainly to increased fucosyltransferase activity.

It is known that angiogenesis plays an important role in the growth and metastasis of solid tumours. Several angiogenic factors have been identified and platelet-derived endothelial cell growth factor (PD-ECGF) is thought to be one such factor. Recently, it was reported that thymidine phosphorylase (dThdPase) is identical to PD-ECGF. Using immunohistochemical staining with an anti-dThdPase antibody, we investigated the correlation between dThdPase expression and the microvessel density in 120 gastric carcinomas. The microvessel density, determined by immunostaining for factor VIII-related antigen, was significantly higher in dThdPase-positive tumours than in dThdPase-negative tumors. There was a significant correlation between dThdPase expression and the increment of microvessel density. Moreover, regarding distant organ metastasis, the frequency of hepatic metastasis was significantly higher (P < 0.01) in patients with dThdPase-positive tumours than in those with dThdPase-negative tumors. In summary, it was suggested that dThdPase expression is closely associated with the promotion of angiogenesis and hepatic metastasis in gastric carcinoma. Images Figure 1

膵癌細胞を用い, 肝転移における糖鎖抗原発現, ELAM-1接着との関連, サイトカインの関与ならびに糖鎖合成阻害剤 (BZN) による転移抑制の可能性を検討した.SW1990は約90%と高率に肝転移をきたし, sialyl-Lea, Lex発現およびヒト臍帯血管内皮細胞 (HUVECs) ならびにELAM-1への接着性と相関した. 末梢血単核球とSW1990との混合培養にて, サイトカイン (TNF-α, IL-1β) の上澄み中への強い産生がみられ, 同上澄みにてHUVECs上にELAM-1の発現が誘導された.SW1990のBZN処理にて, 糖鎖抗原発現およびELAM-1接着, さらにヌードマウス脾内注射による肝転移は有意に抑制され, BZNの新しい転移抑制法としての応用の可能性が示唆された.

PURPOSE We investigated the correlation between tumor angiogenic activity and progression of gastric carcinoma using immunohistochemical staining with antifactor VIII-related antigen (F-VIII RAg) antibody. MATERIALS AND METHODS One hundred twenty-four specimens resected from patients with gastric carcinoma were investigated by staining with a monoclonal antibody against F-VIII RAg. Correlations between the microvessel count (the mean number of microvessels in the five areas of highest vascular density at 200 times magnification), various clinicopathologic factors, and prognosis were studied. RESULTS The microvessel count increased with histologic stage. The microvessel count was significantly higher in patients with lymph node metastases than in those without such metastases. Moreover, in patients with a high microvessel count (> or = 16), prognosis was significantly poorer than in those with low count (< 16). Multivariate analysis indicated that the microvessel count is an independent prognostic factor in patients with gastric cancer. According to the mode of recurrence, the frequency of hepatic metastases was significantly increased in patients with a high count. CONCLUSION Microvessel count may be a good prognostic indicator and may be useful as a predictor for the mode of recurrence in patients with gastric carcinoma.

Various types of granulocyte colony-stimulating factor (G-CSF)-producing malignant tumors have been reported. However, a G-CSF-producing colorectal cancer is rare. We present a case of G-CSF-producing ascending colon cancer. An 81-year-old man was referred to our hospital with right lower abdominal pain. A colon fiberscopy revealed an ascending colon tumor, and histological examination revealed tubular adenocarcinoma. He was admitted due to worsening abdominal pain. Although laboratory data showed an elevated white blood cell (WBC) count of 17000/mm3 with 77.8% neutrophils, elevated C-reaction protein (CRP) was insignificant (1.06 mg/dL), and he was afebrile. Because computed tomography indicated that the tumor penetrated into surrounding tissue, a semi-urgent ileocecal resection was performed. An abscess was not located. The tumor was staged as T3N2aM0 and as stage IIB according to the TNM classification. Microscopically, significant neutrophil infiltration between cancer cells was observed, suggesting the presence of a G-CSF-producing tumor. Immunohistochemical staining using a G-CSF antibody revealed cytoplasmic staining in cancer cells. The serum concentration of G-CSF upon admission was 334 pg/mL. After surgical resection, the WBC count decreased to within a normal range. These findings confirmed the diagnosis of G-CSF-producing ascending colon cancer. The prognosis of G-CSF-producing tumors is considered to be poor. Early diagnosis and surgical treatment are needed for patients with G-CSF-producing tumors, and continuous careful follow-up is required.

癌の浸潤, 転移は多方面よりの検討がなされており, 特に近年細胞遊走刺激因子の関与が注目されている. 今回2種のヒト膵癌細胞株SW1990およびPANC-1を用い遊走能と肝転移能との関連, さらに培養上澄中における遊走刺激因子産生の可能性について検討を行った. SW1990, PANC-1のTranswell chamberを用いたMTT法による浸潤, 遊走能はそれぞれ22.6, 7.3%および33.3, 13.6%であり, SW1990が強い浸潤, 遊走能を示し, in vivoにおける肝転移能との相関が認められた.さらにSW1990無血清培養上澄添加にてPANC-1の遊走能は濃度依存性に増強し, SW1990より遊走刺激因子産生の可能性が示唆された. SW1990培養上澄添加にてPANG1は仮足を伸長した線維芽細胞様形態変化を示し, また無処理群ではヌードマウス脾内注射にて肝転移は認めなかったが, 処理群では類洞内への微小肝転移形成を認め, 同因子が浸潤, 転移に関与する重要な一因であることが示唆された.

Eight patients with inoperable advanced gastric cancer were treated with combination chemotherapy of S-1, low-dose cisplatin(CDDP)and Lentinan. S-1 80 mg/ m² was orally administered for 2 weeks followed by 1-week rest, CDDP 15 mg/ m² and Lentinan 2 mg/body were given intravenously on day 1 and 8. One complete response and four partial responses were observed for an overall response rate of 63%(5 of 8 patients). Only one patient developed over grade 3 toxicity leukocytopenia. Many patients could be maintained by long-term continuous treatment. Since combination chemotherapy of S-1/low-dose CDDP/Lentinan for advanced gastric cancer was very tolerable, it could be used for a long time.

A 61-year-old man with esophagus invasive advanced gastric cancer and peritoneum dissemination underwent three courses of S-1/CDDP/Lentinan (LNT) combination neoadjuvant chemotherapies (T3N1P1H0, Stage IV) (It is S-1 80 mg/m2,CDDP 15 mg/m2 and LNT 2 mg/body twice/week for two weeks) since down staging was obtained. We performed the surgery of total gastrectomy, splenectomy, D2 lymph node dissection, and Roux-en Y reconstruction in March 2008. With the surgical examination, there was no ascites and peritoneal dissemination. Although there was serious infiltration, we were able to remove it. In the histopathological effect judgment, it was Grade 1b. We changed the therapy to S-1 alone after the same chemotherapy for six months. One year after the operation, he is still alive one year after the surgery.

A scale model study was carried out to clarify the source mechanisms of acoustic emissions induced.by excavating an underground flat opening. AE signals during excavation were detected by six accelerometers embeded in the strata model and their source mechanisms were determined from two dimensional moment tensor inversion.The experimental results confirmed that the source mechanisms of acoustic emissions depended on their source location relative to the opening. The AE waveforms from the front of the opening showed compression or double-couple type of source mechanism. The more the source location was remote from the opening, the more double-couple type became predominant. On the other hand, the AE signals above the opening showed broad spectra in their source mechanisms including tensile type as well.A numerical experiment by FEM suggests that moment tensor of AE around an underground opening reflects stress tensor by which the fracture criterion of the focal region of AE is satisfied.

Proliferations of cancer cells and mesenchymal cells are necessary for the formation of hepatic metastasis. Endothelial cells and hepatic stellate cells (HSCs), which exist in the extrasinusoidal space and produce extracellular matrix, are present in hepatic lobules as mesenchymal cells. In this study we investigated the contribution of colon cancer cells to endothelial cells and HSCs in the formation of hepatic metastasis. We collected serum-free conditioned medium (SFCM) of LM-H cells, which are highly liver metastatic colon cancer cells. The SFCM of LM-H cells significantly enhanced proliferation and migration of human umbilical vein endothelial cells (HUVECs) and enhanced the proliferation and migration of HSCs derived from rats. On investigating the growth factors in the SFCM of LM-H cells, we found vascular endothelial growth factor (VEGF) and platelet-derived growth factor (PDGF). The proliferation of HUVECs was inhibited by anti-VEGF antibody, and that of HSCs was inhibited by anti-PDGF antibody. The angiogenesis inhibitor TNP-470 significantly decreased the number of hepatic metastases of LM-H cells in nude mice. In conclusion, the VEGF and PDGF that colon cancer cells produce are important factors in the structural reorganization of hepatic metastasis. The angiogenesis inhibitor TNP-470 seems to be a potent agent for inhibiting hepatic metastasis of colon cancer.

We investigated the expression of vascular endothelial growth factor (VEGF) in 175 colorectal carcinomas by immunohistochemistry. VEGF expression was correlated with advanced TNM stage (III, IV), advanced T stage (T3, T4), vessel involvement, lymph node metastasis, and liver metastasis. With regard to the prognosis, both overall and relapse-free survival was significantly poorer, and furthermore, the hematogenous recurrences were significantly more commonly found in the patients with VEGF-positive tumors. VEGF expresion in colorectal carcinomas may have a substantial value in predicting those patients at high risk for hematogenous recurrence after surgery.

The clinical importance of microvessel quantitation as a prognostic indicator in invasive breast cancer was examined. This study included 155 patients with invasive breast cancer, with a median follow-up of 82 months. Microvessels were identified by immunohistochemical staining for factor VIII-related antigen in formalin-fixed, paraffin-embedded primary tumours. For each tumour, microvessels were counted within a 200 x magnification field in the area of highest microvessel density. Microvessel counts (MVCs) had no correlation with tumour size, lymph node status or histological grade. When patients were classified by MVC, higher counts were associated with shorter disease-free survival and overall survival (P < 0.025 and P < 0.01 respectively). Multivariate analysis showed that MCV is an independent prognostic factor. Microvessel quantitation may be a useful predictor for identifying breast cancer patients at high risk for relapse and death. Images Figure 1

Reaction of ethyl 2,3-butadienoate with aldehydes in the presence of DABCO gave ethyl 2-(1-hydroxyalkyl)-2,3-butadienoate (2) in 41–54% yields. The reaction in the presence of butyl lithium gave 2 in 36–60% yields accompanied by ethyl 2,4-di(1-hydroxyalkyl)-2,3-butadienoate.