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Supplementary Figures S1-S2 from Rapid Detection of Epidermal Growth Factor Receptor Mutations in Lung Cancer by the SMart-Amplification Process

Purpose: A positive response to gefitinib in non–small cell lung cancer (NSCLC) has been correlated to mutations in epidermal growth factor receptor (EGFR) gene. Previous reports have been based mainly on diagnostic screening by sequencing. However, sequencing is a time-consuming and complicated procedure, not suitable for routine clinical use.Experimental Design: We have developed rapid, simple, and sensitive mutation detection assays based on the SMart Amplification Process (SMAP) and applied it for analyzing EGFR gene mutations in clinical samples. By using SMAP, we can detect mutations within 30 min including sample preparation. To validate the assay system for potential use in clinical diagnostics, we examined 45 NSCLC patients for EGFR mutations using sequencing and SMAP.Results: The outcomes of the SMAP assay perfectly matched the sequencing results, except in one case where SMAP was able to identify a mutation that was not detected by sequencing. We also evaluated the sensitivity and specificity of SMAP in mutation detection for EGFR. In a serial dilution study, SMAP was able to find a mutation in a sample containing only 0.1% of the mutant allele in a mixture of wild-type genomic DNA. We also could show amplification of mutated DNA with only 30 copies per reaction.Conclusions: The SMAP method offers higher sensitivity and specificity than alternative technologies, while eliminating the need for sequencing to identify mutations in the EGFR gene of NSCLC. It provides a robust and point-of-care accessible approach for a rapid identification of most patients likely to respond to gefitinib.

Background: Fucosylated haptoglobin detected by Pholiota squarrosa lectin (PhoSL) that had specificity for fucose alpha 1-6 was reported as an effective biomarker for several gastrointestinal diseases. The aim of this study was to verify Fucosylated haptoglobin detected by Pholiota squarrosa lectin (PhoSL-HP) as a pancreatic cancer (PC) marker using a new method of PhoSL-ELISA. Methods: PhoSL-HP in sera from 98 PC patients and 158 non-PC samples including 32 intraductal papillary mucinous neoplasm (IPMN) patients, 21 chronic pancreatitis (CP) patients and 105 non-pancreatic disease controls (NPDC) were measured. We compared sensitivities, specificities and areas under the curves (AUC) of PhoSL-HP, CA19-9 and CEA as single markers. We also evaluated PhoSL-HP as combination marker by comparing AUC of CA19-9 combined with PhoSL-HP or CEA. Results: The sensitivities of PhoSL-HP, CA19-9 and CEA for PC were 58%, 76% and 42%, respectively. Although the specificity of PhoSL-HP for NPDC was inferior to both of CA19-9 and CEA, that for pancreatic diseases was higher than both of CA19-9 and CEA. Combined CA19-9 with PhoSL-HP, the AUC was significantly higher at 0.880 than single use of CA19-9 at 0.825 in case of distinguishing PC from other pancreatic diseases. In contrast, the AUC of CA19-9 was not elevated significantly when combined with CEA. Conclusion: PhoSL-HP would be a useful marker for PC and have sufficient complementarity for CA19-9. (C) 2019 Published by Elsevier B.V. on behalf of IAP and EPC.

Objective: To assess the safety and efficacy of “polyhedral fenestration technique” (PFT), which we newly developed, in combined hepatectomy and cyst fenestration (CHCF) for symptomatic polycystic liver disease (PLD). Summary of background data: CHCF for PLD has been reportedly less efficacious for its invasiveness because 50% to 70% patients suffered recurrent symptoms after CHCF. Methods: Patient characteristics, intra- and early postoperative variables were compared between 5 PLD patients undergoing CHCF performed with PFT (PLD group) and 95 patients with diseases other than PLD receiving hepatectomy without biliary reconstruction during the same period (Control group) to assess safety of PFT. Chronological changes in total liver volume (TLV) measured by computed tomography (CT) volumetry as well as recurrent symptoms after CHCF were investigated to assess long-term outcomes. Results: Although ≧ Clavien-Dindo grade 2 complications were more common in the PLD group than in the Control group (PLD vs Control, 5/5[100%] vs 27/95[28%], p=0.004), patient characteristics, intra-, and early postoperative variables, including ≧ Clavien-Dindo grade 3 complications, were comparable among the 2 groups. Postoperative observational period of the 5 PLD patients ranged 30 to 88 months with a median of 63. CT volumetry revealed that TLV continued to reduce up to 1 year after surgery and thereafter retained less than 0.5 times of preoperative TLV in all patients. Recurrent liver enlargement or recurrent symptoms were not observed in any of the 5 PLD patients. Conclusions: Although our case series was very small, newly-developed PFT in CHCF for PLD yielded acceptable safety and excellent long-term outcomes.

A right-sided hepatectomy with total caudate lobectomy is indicated for colorectal-cancer liver metastases (CLM) and hepatocellular carcinomas (HCC) located in the caudate lobe with extension to the right lobe of the liver. Caudate-lobe resection (i.e. segmentectomy 1 according to the Brisbane terminology) is one of the most difficult types of hepatectomy to carry out radically and safely. The deep portion of hepatic transection around the caudate lobe, hepatic veins and inferior vena cava is a critical source of massive bleeding. Prolonged transection can increase blood loss.We analyzed the outcome of 10 patients who underwent right-sided hepatectomy with caudate lobectomy using a modified liver hanging maneuver (mLHM) in comparison with 16 patients who underwent the operation without mLHM.Blood loss during liver transection and blood loss per unit area of cut surface were significantly less in the mLHM group (p=0.014 and 0.015, respectively). In patients diagnosed pathologically with liver impairment, transection time was significantly shorter in the mLHM group (p=0.038), as were red blood cell transfusion volume (p=0.042) and blood loss (p=0.049) during transection.Use of mLHM can potentially improve surgical outcomes by reducing blood loss and transection time, which are especially important for patients with liver impairment.

症例は60歳代，女性．平成19年夏頃より，約半年毎に右下腹部痛を繰り返し，近医にて虫垂炎と診断され保存的加療で軽快していた．平成21年7月，右下腹部痛出現．近医を受診し血液検査ではWBC 7,700/μl，CRP 1.5mg/dlと炎症所見は軽度であったが，腹部CT検査で虫垂の腫大を認め，当科紹介受診となった．臨床症状は軽快していたが，繰り返す右下腹部痛の既往があり，虫垂炎の術前診断で待機的に虫垂切除術を施行した．虫垂は赤黒色に腫大していたが，粘膜面に肉眼上隆起性病変は認めなかった．病理組織検査では虫垂原発印環細胞癌，切除断端陽性と診断されたため，初回手術後，22日後に開腹下に回盲部切除術（D2）を施行した．術後病理組織診断はsignet-ring cell carcinoma，mp，n0，stageIで現在外来で経過観察中である．虫垂原発印環細胞癌の1例を経験したので文献的考察を加えて報告する．

Purpose: Aberrant activation of epidermal growth factor receptors (EGFR/HER1) by ligand stimulation or heterodimerization with human epidermal growth factor 2 (HER2) is considered to play an important role in the development of colorectal carcinoma. Amphiregulin (AR) is a ligand of EGFR that might be related to the development and progression of gastrointestinal tumors. The aim of this study was to determine the AR, EGFR, and HER2 protein expression levels and to evaluate their prognostic relevance to the clinical course of colorectal cancer. Experimental Design: The AR, EGFR, and HER2 protein levels in primary tumors of colorectal cancer (n = 106) were examined using immunohistochemistry. Metastatic sites in liver specimens (n = 16) were also analyzed in the same manner. Results: Thirteen (81.6%) metastatic lesions of the liver stained positive for AR. Among the primary lesions of colorectal cancer, 58 (54.7%) stained positive for AR, 13 (12.3%) stained positive for EGFR, and 5 (4.7%) stained positive for HER2. When the relationships between each protein expression level and the clinicopathologic factors were examined, only the AR expression level was significantly related to liver metastasis (P = 0.0296). A multivariate analysis of liver metastasis proved that AR expression was an independent prognostic factor of liver metastasis from colorectal cancer (P = 0.0217). Conclusions: AR expression in primary lesions of colorectal cancer is an important predictive marker of liver metastasis.

症例は59歳の男性で, 糖尿病の加療目的で入院中, 腹部CTで膵頭部に嚢胞性腫瘤を指摘された. 画像上, 膵頭部の分枝型IPMCの診断で膵頭十二指腸切除術を施行した. 病理組織学的診断は微小浸潤型IPMCで切除断端は癌陰性であった. 術後4か月目から腫瘍マーカーの上昇を認め, 6か月目の腹部CTで残膵に3cm大の腫瘍を認めたため, 残膵癌の診断で残膵全摘を施行した. 病理組織は高度な脈管浸潤を伴った中分化型管状腺癌で, 癌とその周囲組織ともに膵管内の腺腫成分や乳頭状増殖は認めず, 全切片で浸潤型発育を示していた. また, 初発IPMCではMUC1陽性, MUC2陽性でK-ras変異陰性であったのに対し, 残膵浸潤癌ではMUC1陽性, MUC2陰性, K-ras変異陽性であった. 以上より, 本症例におけるIPMCと残膵浸潤癌の発生源は異なるものと考えられた.

Transcriptional initiation is a key step in the control of mRNA synthesis and is intimately related to chromatin structure and histone modification. Here, we show that the ubiquitylation of H2A (ubH2A) correlates with silent chromatin and regulates transcriptional initiation. The levels of ubH2A vary during hepatocyte regeneration, and based on microarray expression data from regenerating liver, we identified USP21, a ubiquitin-specific protease that catalyzes the hydrolysis of ubH2A. When chromatin is assembled in vitro, ubH2A, but not H2A, specifically represses the di- and trimethylation of H3K4. USP21 relieves this ubH2A-specific repression. In addition, in vitro transcription analysis revealed that ubH2A represses transcriptional initiation, but not transcriptional elongation, by inhibiting H3K4 methylation. Notably, ubH2A-mediated repression was not observed when H3 Lys 4 was changed to arginine. Furthermore, overexpression of USP21 in the liver up-regulates a gene that is normally down-regulated during hepatocyte regeneration. Our studies revealed a novel mode of trans-histone cross-talk, in which H2A ubiquitylation controls the di- and trimethylation of H3K4, resulting in regulation of transcriptional initiation.

A key feature of the smart amplification process version 2 (SMAP-2) is the ability to suppress mismatch amplification by using a unique asymmetric primer design and Thermus aquaticus MutS (Taq MutS). However, we report here that use of SMAP-2 for polymorphism determination of the UGT1A1*28 allele required a further ancillary approach for complete background suppression. The UGT1A1*28 allele is a microsatellite copy number polymorphism. This is the first reported SMAP-2 assay designed for genotyping genetic variations of microsatellites. We found that by the addition of a primer to the amplification reaction, called a competitive probe (CP), assay specificity could be significantly enhanced. Including sample preparation time and use of a CP-enhanced SMAP-2 assay, we could rapidly detect the UGT1A1*28 polymorphism within 60 min. To test our method, we compared results from PCR sequencing and the CP-enhanced SMAP-2 assay on 116 human blood samples for UGT1A1*28 polymorphism and demonstrated perfect concordance. These results illustrate the versatility of SMAP-2 for molecular diagnostics and provide a new approach for enhancing SMAP-2 assay specificity.

Purpose: A positive response to gefitinib in non–small cell lung cancer (NSCLC) has been correlated to mutations in epidermal growth factor receptor (EGFR) gene. Previous reports have been based mainly on diagnostic screening by sequencing. However, sequencing is a time-consuming and complicated procedure, not suitable for routine clinical use. Experimental Design: We have developed rapid, simple, and sensitive mutation detection assays based on the SMart Amplification Process (SMAP) and applied it for analyzing EGFR gene mutations in clinical samples. By using SMAP, we can detect mutations within 30 min including sample preparation. To validate the assay system for potential use in clinical diagnostics, we examined 45 NSCLC patients for EGFR mutations using sequencing and SMAP. Results: The outcomes of the SMAP assay perfectly matched the sequencing results, except in one case where SMAP was able to identify a mutation that was not detected by sequencing. We also evaluated the sensitivity and specificity of SMAP in mutation detection for EGFR. In a serial dilution study, SMAP was able to find a mutation in a sample containing only 0.1% of the mutant allele in a mixture of wild-type genomic DNA. We also could show amplification of mutated DNA with only 30 copies per reaction. Conclusions: The SMAP method offers higher sensitivity and specificity than alternative technologies, while eliminating the need for sequencing to identify mutations in the EGFR gene of NSCLC. It provides a robust and point-of-care accessible approach for a rapid identification of most patients likely to respond to gefitinib.

Massive arterial hemorrhage is, although unusual, a life-threatening complication of major pancreatobiliary surgery. Records of 351 patients who underwent major surgery for malignant pancreatobiliary disease were reviewed in this series. Thirteen patients (3.7%) experienced massive hemorrhage after surgery. Complete hemostasis by transcatheter arterial embolization (TAE) or re-laparotomy was achieved in five patients and one patient, respectively. However, 7 of 13 cases ended in fatality, which is a 54% mortality rate. Among six survivors, one underwent selective TAE for a pseudoaneurysm of the right hepatic artery (RHA). Three patients underwent TAE proximal to the proper hepatic artery (PHA): hepatic inflow was maintained by successful TAE of the gastroduodenal artery in two and via a well-developed subphrenic artery in one. One patient had TAE of the celiac axis for a pseudoaneurysm of the splenic artery (SPA), and hepatic inflow was maintained by the arcades around the pancreatic head. One patient who experienced a pseudoaneurysm of the RHA after left hemihepatectomy successfully underwent re-laparotomy, ligation of RHA, and creation of an ileocolic arterioportal shunt. In contrast, four of seven patients with fatal outcomes experienced hepatic infarction following TAE proximal to the PHA or injury of the common hepatic artery during angiography. One patient who underwent a major hepatectomy for hilar bile duct cancer had a recurrent hemorrhage after TAE of the gastroduodenal artery and experienced hepatic failure. In the two patients with a pseudoaneurysm of the SPA or the superior mesenteric artery, an emergency re-laparotomy was required to obtain hemostasis because of worsening clinical status. Selective TAE distal to PHA or in the SPA is usually successful. TAE proximal to PHA must be restricted to cases where collateral hepatic blood flow exists. Otherwise or for a pseudoaneurysm of the superior mesenteric artery, endovascular stenting, temporary creation of an ileocolic arterioportal shunt, or vascular reconstruction by re-laparotomy is an alternative.

Although the usefulness of antimicrobial prophylaxis for clean-contaminated surgery has been recognized, only a few randomized controlled studies on the duration of administration after hepatectomy have been performed. We investigated the duration of antimicrobial prophylaxis after hepatectomy.The subjects were 180 patients who underwent hepatectomy without reconstruction of the biliary or intestinal tract between April 2003 and March 2006 at our department. The patients were randomly allocated to groups to be treated with flomoxef sodium as antimicrobial prophylaxis for 2 days (89 patients) or 5 days (91 patients), including the operation day. The presence or absence of systemic inflammatory response syndrome (SIRS) and infections was investigated.No significant differences were noted in patient background between the two groups. Infections occurred in seven and six patients in the 2 day and 5 day treatment groups (7.9% and 6.6%), respectively, showing no significant difference between the two groups. No significant difference was noted when the cases were divided into surgical site infections and remote infections. The positive rate of SIRS was significantly higher in the 2 day treatment group than in the 5 day treatment group on days 2 and 3 after surgery. The risk factors in patients who developed infections were blood loss, operation time and the complication of biliary fistula.Two day administration of flomoxef sodium may be sufficient for antimicrobial prophylaxis after hepatectomy. However, when SIRS is positive on post-operative day 2, and induction of liver failure is of concern, it may be safer to continue antimicrobial drug administration until SIRS is eliminated.

We investigated efficacy of microwave ablation plus hepatectomy for multiple colorectal liver metastases. Clinicopathologic data were analyzed retrospectively for 71 consecutive patients with four or more bilobar liver metastases from colorectal cancer who underwent hepatectomy with or without microwave ablation. Overall, no significant differences were found and as well as disease-free survival between 19 patients with resection/ablation and 52 patients with resection (p = 0.18 and 0.93). Multivariate analysis selected prehepatectomy carcinoembryonic antigen concentration in serum as an independent prognosticator for survival (p = 0.04), but not resection/ablation vs. resection. In the patients with combined resection/ablation, recurrences occurred near the resection or ablation line in only 3 patient (30%, although multiple tumors (≥ 4) were the most common liver recurrence pattern (60%). Microwave ablation plus hepatic resection expanded indications for surgery to treat multiple bilobar liver metastases.

胆嚢摘出術の術後胆汁漏の原因として副肝管および異所性肝内胆管末梢枝の損傷などが報告されている.今回腹腔鏡下胆嚢摘出術の際に確認された胆汁漏に対する検索でLuschka管を確認できた1例を経験したので報告する.症例は61歳,男性.胆嚢結石に対し腹腔鏡下胆嚢摘出術施行.術後麻酔からの覚醒時にドレーンから胆汁様排液を認めた.再気腹し検索したところ胆嚢管断端や総胆管からの胆汁瘻は認めずLuschka管を認めた.開口部をクリップを用いて閉鎖した.胆嚢摘出の際,手術は胆嚢側に沿って行い,索状組織がある場合にはクリップをかけて切離することが肝要であり,異所性胆管たとえばLuschka管,副肝管,異所性肝内胆管末梢枝などの存在も念頭に置く必要があると考えられた.

Recent advances have extended indications for hepatectomy to include multiple bilobar colorectal liver metastases (CLM). Staging systems based on the biological malignancy of primary and metastatic tumors provide appropriate indications for hepatectomy in CLM. However, suitability for resection in patients with complex and extensive hepatic metastases is controversial.A medline search was performed to identify papers reporting the resection for CLM. Techniques, indication, and results were reviewed.If the anticipated remnant liver volume is small (25-40% of total), suggesting a high risk of postoperative liver failure, portal vein embolization (PVE) is recommended prior to hepatectomy. However, curative resections are not always possible. Specifically in synchronous multiple bilobar CLM, two-stage hepatectomy, comprising bilateral hepatectomy and primary resection with or without PVE, can prevent growth of ipsilateral metastatic nodules in the remnant liver and reduce surgical risk. Several local ablation techniques can complement surgery if hepatic resection alone increases the risk of postoperative liver failure or is not curative. Chemotherapy combined with targeted treatment can suppress recurrence and extend indications for hepatectomy by reducing the size and number of primary irresectable tumors.PVE or staged procedure combining with local ablation or neoadjuvant, downstaging or adjuvant therapies extends indications for hepatectomy to include multiple bilobar CLM. The 5-year survival rate for multiple bilobar CLM treated with alternating hepatectomy and chemotherapy is comparable to the values reported for single and hemilateral CLM.

Postoperative infections after hepatectomy sometimes lead to fatal hepatic failure, but the mechanism of the hepatic failure is unclear. Wistar rats underwent 90% hepatectomy, and were then divided into three groups: (i) the SAL group, injected with normal saline; (ii) the LPS group, injected with lipopolysaccharide (LPS) every day for 1 week; and (iii) the LPS plus TGF-Ab (LPS+TGF-Ab) group, injected with LPS with anti-transforming growth factor-β1 (TGF-β1) antibody. We investigated survival rates, TGF-β1 expression in the liver, liver regeneration by proliferating cell nuclear antigen labeling index, hepatocyte apoptosis by single stranded DNA labeling index, and perisinusoidal fibrosis using Masson's trichrome staining. The LPS group (30.4%) had a significantly lower survival rate than the SAL group (84%) and tended to be lower than the LPS+TGF-Ab group (49.4%). Liver regeneration in the LPS group was significantly lower than in the other groups. In the LPS group, hepatocyte apoptosis and perisinusoidal fibrosis was significantly more remarkable, and TGF-β1 expression was significantly higher than in the SAL group. TGF-β1 enhanced by LPS plays an important role in the mechanism of hepatic failure by infections after hepatectomy, especially in inhibition of liver regeneration, and induction of hepatocyte apoptosis and perisinusoidal fibrosis.

症例は55歳, 男性. 体重減少の精査から膵頭部癌を診断された. 術前診断はPV (+) のT4N2M0でStage IVbの膵頭部癌で, 膵頭十二指腸切除術, D3リンパ節郭清, 門脈合併切除再建を行った. 術後の病理診断はpPV (-) であったが, pRP (+), pPLph (+) でfSsage IVbであった. また, 肝転移好発因子である静脈侵襲vがv3であったため, 術後6週目からゲムシタビン併用全肝照射療法を開始した. 10Gy照射, ゲムシタビンは200mg/m2で3回投与後より発熱が生じ, さらに14Gy照射後に全身の発疹が見られた. 治療開始後26日に呼吸困難が出現し, 胸部X線撮影で間質性肺炎と診断された. ただちにステロイド療法を開始し, 症状は劇的に改善し, 照射開始後41日目に軽快退院した. 本療法は少量のゲムシタビンと放射線療法の併用だが, 肺が照射野に入る全肝照射時には間質性肺炎が起こる可能性があることを念頭に置くべきである.

食道癌手術術後の退院基準の選択肢として在宅経腸栄養療法 (HEN) を組み込むことの妥当性を検討するために,食道癌術後にHENを行った症例の解析を行った.術後経口摂取不良の原因では反回神経麻痺に関係するものが多く,そのためにHENが導入されていた.しかし, HEN導入症例の67% (24/36例)では,経口摂取不良の原因が明らかでなかった.詳細な評価可能なHEN施行群9例とHEN非施行群14例の比較では,術後在院期間 (p=0.90), 術後3, 6, 12カ月の体重変化 (p=0.97, 0.38, 0.11), 栄養指標 (prognostic nutritional index) の変化は (p=0.99, 0.91, 0.95) と差はみられなかった.また, 22.2% (8/36例)では, HENを施行したが術後12カ月体重が減少し続けHENの終了時期が不適切であったと考えられた. HENを行った患者およびその家族に対するアンケート (10例)の結果では,施行に困難を感じていた症例は少なかったが (10%), 施行上のサポート体制の充実を希望していた.術後経口摂取不良症例の退院基準のひとつとしてHENの導入を組み込むことが可能であり, HENの終了については,慎重に判断する必要があると考えられた.

【目的】転移性肝癌に対する局所凝固療法の有用性について検討した.【対象】当科で局所凝固療法を施行した転移性肝癌は15例21病変であった.施行理由はH3多発肝転移例の切除対側葉13病変,肝切除拒否4病変,呼吸機能不良4病変であった.【結果】マイクロターゼ凝固療法16病変,ラジオ波焼灼療法は5病変であった.腫瘍径は, 1cm未満7例, 1-2 cm 10例, 2-3 cm 2例, 3 cm以上2例で,平均腫瘍径は1.7cmであった.平均観察期間8.3ヵ月で2cm未満の9病変に再発を認めなかったが, 4病変(19%)に局所再発を認めた. H3肝転移7例に対しMCTを併用した肝切除を施行し, 4例は無再発生存中であるが, 3例は多発肺転移と残肝多発再発のため死亡した.【結語】 2 cm未満の病変に対しては局所凝固療法が有効である.切除不能H3多発肝転移に対して,局所凝固療法を併用することで,根治切除の可能性を広げることができると考えられた.

The essential minimum of hepatic segmentectomy combined with caudate lobectomy (parenchyma-preserving hepatectomy) has been recommended particularly for high-risk patients with hilar bile duct cancer to minimize the risk of postoperative liver failure. This quality control study investigated whether parenchyma-preserving hepatectomy is a "noble option" in the surgical treatment of hilar bile duct cancer. A total of 53 patients with hilar bile duct cancer underwent surgical resection. These patients were retrospectively classified into a major hepatectomy group (major Hx, n=30), a parenchyma-preserving hepatectomy group (preserving Hx, n=11), and a hilar bile duct resection group (HBDR, n=12). A preserving Hx consisted of caudate lobectomy, either alone (n=3), or combined with resection of segment 4 (S4, n=4), or S58 (n=3) or S458 (n=1). The preserving Hx was used for high-risk patients in whom tumor tissue was diagnosed to be Bismuth type I and II by preoperative selective percutaneous transhepatic cholangiography. The mean numbers of hepatico-jejunostomies were 2.8, 4.8, and 4.6 in the respective groups. Mortality rates including hospital death were 13.3%, 0%, and 0% respectively. Morbidity rates were 46.7%, 54.5%, and 33.3%. The preserving Hx group encountered no liver failure (T.Bil>10 mg/dl, encephalopathy) but acquired hyperbilirubinemia (T.Bil>5 mg/dl), pulmonary insufficiency and other complications at the same frequency as in the major Hx group. The survival rates in the three groups were 35.6%, 52.5%, and 48.6% at 3 years and 25.2%, 14.9%, and 24.3% at 5 years respectively. Curability rates (R0 to R1+2) were 76.7%, 54.5% and 50.0%, respectively. Preserving Hx tended to result in higher frequencies of positive transmural margins (e.g., cancer cells remaining around the right hepatic artery or the portal vein). Preserving hepatectomy for high-risk patients should be limited strictly to patients who do not have tumors which are not invading adjacent organs (e.g., T2) nor a segmental duct and are confined longitudinally to the right or the left.

拡大肝切除後の遷延した高ビリルビン血症に対して, 集学的治療を実施し, 奏効した症例を経験したので報告する. 症例は58歳の男性. 診断はS状結腸癌術後の転移性肝癌でS1, S5以外の全亜区域に転移巣を認めた. これに対し, 2回に分けて肝切除を施行した. 術直後から発熱とビリルビン値の上昇を認め, 肝不全に陥った. 血液培養からMethicillin-resistant Staphylococcus epidermidis, Enterococcus faecalisが検出され, 肝生検にてディッセ腔側の肝細胞索に線維化を認めた. 残肝は, 術後43日で術前体積の96%まで腫大した. 感染が制御された後も, 高ビリルビン血症が依然として持続した. これに対し, 高圧酸素療法, 利胆剤, フェノバール, ステロイド投与を実施し, ビリルビン値が改善した. 感染制御後に使用した利胆剤とステロイドによる肝細胞, 胆管上皮保護作用や, 高圧酸素療法による肝細胞の酸素化作用が有効であった可能性が示唆された.

1区域以内の肝切除100例を,流入血遮断により無阻血(N群),全肝遮断(P群),選択的遮断(S群)の3群に分類し,全肝阻血と選択的阻血の適応,問題点を検討した.なお,遮断は15分間の阻血, 5分間解除を原則とした.慢性肝炎(慢肝)・硬変例では, N群の術後第14病日のGOT値がP群に比較し低値(P

Background Multiple organ metastases from colorectal carcinoma may be considered incurable, but long survival after both liver and lung resection for metastases has been reported. Methods A retrospective analysis of 48 patients who underwent lung resection for metastatic colorectal cancer between 1992 and 1999 was undertaken. Twenty-seven patients had lung metastasis alone, 15 had previous partial hepatectomy, and six had previous resection of local or lymph node recurrence. The relationship of clinical variables to survival was assessed. Survival was calculated from the time of first pulmonary resection. Results Five-year survival rates after resection of lung metastasis were 73 per cent in patients without preceding recurrence, 50 per cent following previous partial hepatectomy and zero after resection of previous local recurrence. Independent prognostic variables that significantly affected survival after thoracotomy were primary tumour histology and type of preceding recurrence. There was no significant difference in survival after lung resection between patients who had sequential liver and lung resection versus those who had lung resection alone. Conclusion Sequential lung resection after partial hepatectomy for metastatic colorectal cancer may lead to long-term survival.

Portosystemic shunt is a common complication in patients with portal hypertension. Mesenteric varix is one of the collaterals that can cause post-transplant liver dysfunction. In this case report, a 45-year-old woman underwent living relative donor liver transplantation for alcoholic cirrhosis. Although the early postoperative course was uneventful, she was readmitted for treatment of liver hypofunction. Fatty change in the graft liver was confirmed by histopathology of the biopsy specimen. The venous phase of a superior mesenteric angiogram revealed large-caliber mesenteric varices comprising portosystemic venous shunts. Surgery was performed to ligate the shunts. The intraoperative color Doppler ultrasonography showed hepatofugal portal blood flow, which was corrected to hepatopetal blood flow by clamping the shunt vessels. The portal pressure was moderately elevated from 13.6 cm to 21.8 cm H(2)O. Two shunt vessels were ligated and divided. Her liver function returned to nearly normal thereafter. We recommend that descending collaterals be divided during liver transplantation.

大腸以外を原発とする転移性肝癌の肝切除意義を考察した.原発部位は胃癌10例,卵巣癌6例, gastrointestinal stromal tumor (GIST) 4例,その他9例であった. 胃癌同時性切除7例の累積生存率は非切除36例に比べ良好であったが(P

症例は65歳男性.直腸癌(P-Rb)の診断で腹仙骨腹式直腸切断術,D3リンパ節郭清,骨盤内臓神経両側部分温存術を施行した.術後に会陰皮下膿瘍を合併し,培養でMSSAとEnterococcus faecatisが検出されたが抗生剤投与と洗浄で軽快,術後31日目に退院した.術後72日目から発熱と大腿部痛が出現し再入院となった.入院時には左腰部の叩打痛と左腸腰筋肢位を認めた.腹部CTにて左腸腰筋から骨盤内に連続する膿瘍陰影があったため,抗生剤投与を開始すると共に,超音波ガイド下にドレナージチューブを挿入した.膿汁培養でMRSAが検出されたため抗生剤をTeicoplaninへ変更し,チューブ洗浄を続けることにより腸腰筋膿瘍は軽快した.膿瘍発生機序は,腹膜外経路で閉鎖腔に留置した開放式ドレーンの逆行性感染により閉鎖腔から腸腰筋前面に感染したものと考えられた.予防には閉鎖式ドレーンの使用が,治療には超音波ガイド下のドレナージが有用と思われた.

大腸癌肝転移切除後の残肝再発機序の検討から至適術式を考察した. 肝転移切除後の残肝再発危険因子は, tw陽性 (p

症例は48歳女性.意識障害を主訴に近医を受診.低血糖を指摘されて,当院内科を受診.精査の結果,膵インスリノーマの診断で,手術目的に外科転科となった.術前画像検査では,膵頭部下縁に径1cm大の血流に富んだ腫瘍を認めた.また,内科で施行した選択的動脈内カルシウム負荷試験では膵体部背側膵動脈領域に腫瘍の局在が疑われた.開腹下において肝円索より門脈内にカニュレーションし,術中に間欺的門脈血インスリン値測定を行った.腫瘍圧迫によりインスリン値の急増を認め,腫瘍摘出直後より速やかに正常に戻り,完全摘除を確信した.これらの変化は末梢血中インスリン値測定よりも明らかであった.以上より,肝円索からの術中門脈血採血は簡便でインスリン値を鋭敏に反映し,インスリノーマの局在診断や完全摘除の指標に有用であると考えられた.

症例は73歳,男性.右季肋部痛で発症し肝右葉に腫瘤を指摘された.画像所見上,肝前区域に表面に癌臍様の陥凹を伴う最大径8cmの腫瘤を認め, dynamic CT,血管造影の所見から, combined typeの胆管細胞癌と診断した.切除標本の組織所見では低分化と高分化の混在する肝細胞癌と診断されたが,腫瘍内にpeliosis hepatisに類似した大小多数の血液腔(peliotic change)を認め,その内腔は大部分が器質化していた.通常,肝細胞癌に内包されるpeliotic changeはdynamic CT,血管造影で持続する濃染像を示すとされるが,本症例ではpeliotic change内の血液の器質化により造影効果を示さず,術前診断を困難にしたものと考えられた.

Background: Radical lymph node dissection in surgery for advanced gallbladder cancer is controversial. The purpose of this study is to evaluate the role of lymph node dissection based on the clinico-pathologic results. Patients: Seventy-three patients who underwent radical surgery including systematic dissection of the N1+N2 region lymph node plus some of the para-aortic nodes were reviewed. Results: pT1 patients had no lymph node metastasis, but pT2 and pT3/pT4 patients had lymph node metastasis at a rate of 50.0% (13/26) and 83.3% (25/30), respectively. As infiltration of the hepatoduodenal ligament (Binf) became severe, the rate and extent of lymph node metastasis increased. There were four 5-year survivors with lymph node involvement. The 5-year survival rates are 77.0% in pN0 cases and 27.3% in pN1 cases (P

肝門部上部胆管癌44例を対象に, 予後規定因子と術後放射線療法 (post operative radiotherapy: PORT) の治療効果を検討した. 切除例は32例で切除率は72.7%であった. 切除例の平均観察期間は20.6か月で, 1, 3, 5生率は79.9%, 59.8%, 39.3%であった. 単変量解析ではリンパ節転移の有無とPORTの有無が, 多変量解析ではPORTの有無が予後規定因子と考えられた. 1, 3生率は, 根治度A, BかつPORT (-) 群の83.3%, 40.0%に対して根治度CかつPORT (+) 群では100%, 53.3%と, 根治度CでもPORTにより根治度A, Bと同等の生存率が得られた. PORT施行例では組織学的にhm2, em2において局所再発を認めず, 特に肝側胆管断端, 剥離面の癌遺残に対する再発抑制効果があると思われた.

Should right hepatic artery reconstruction be performed if the artery is accidentally injured during surgery? We report the outcome of three cases where the right hepatic artery was injured during lymph node dissection for malignant diseases of the pancreas and periampullary region. In one case, we performed left hepatic artery resection for the removal of cancer invasion, and also, reconstruction of the right and the left hepatic arteries. Multiple liver abscesses occurred and continued to develop until death due to cancer recurrence 7 months after the operation. In the other 2 cases with only right hepatic injury, no marked postoperative complications occurred. Although bile duct ischemia might be a possible major complication of right hepatic artery injury, arterial blood flow to the bile duct is conserved through translobar collaterals in the liver from the left hepatic artery, if it is preserved. We conclude that hepatic artery reconstruction is not needed when the left hepatic artery has been preserved.

症例は20歳の男性で,脳性麻痺で当院小児科に通院中であった. 5月7日腹部膨満のため浣腸,補液の処置をうけて帰宅した.しかし翌5月8日増悪したため麻痺性腸閉塞の診断で当科に紹介入院した.入院時腹部単純X線写真では腹部全体に著明に拡張した腸管ガス像を認めたが脳性麻痺による麻痺性腸閉塞と考え,保存的に経過観察とした. 5月10日炎症所見が増大し腹部CT検査上,腹腔内遊離ガス像を認めたことから汎発性腹膜炎の診断で緊急開腹術を施行した.開腹すると移動盲腸が腸間膜を軸に反時計周りに270度捻転し絞扼され著明に拡張していた.盲腸壁は壊死しており,前壁に穿孔を認めた.壊死腸管を含め回盲部を23cmにわたり切除し,回腸人工肛門,上行結腸粘液瘻を造設した.術後経過は順調で第10病日から経口摂取可能となり第38病日に小児科に転科し,併存する痙攣発作に対する6カ月の治療の後退院した.

A 71-year-old woman was admitted to the hospital because of obstructive jaundice in June 1998. There were previous histories of undergoing a rihgt colectomy for ascending colon cancer on May 18, 1993 and an extended left lobectomy of the liver for hepatic metastasis on July 31 1997. After admission an abdominal CT showed a 2.5cm diameter solid tumor at the retropancreatic head region. We diagnosed the mass as retropancreatic lymph node involvement from metastatic lesion of the liver. We performed pancreatoduodenectomy because there was no evidence of other metastasis. The patient has no signs of recurrence one year after the operation. It is suggested that resection for the lymph nede involvement from hepatic metasitasis which is derived from colorectal cancer is beneficial to prolong the survival time, if no other metastic foci are present.

症例は65歳の男性で, 肝硬変の診断で他院にて加療中, 下血を認め, Hb 4.9g/dlの貧血を呈し精査目的で入院となった. 上部消化管内視鏡検査で十二指腸下行脚に静脈瘤を認めた. 低緊張性十二指腸造影検査では, 同部位に境界明瞭, 表面平滑な陰影欠損として描出された. 経皮経肝門脈造影で, 後下膵十二指腸静脈が主たる流入路, 精巣静脈が流出路で下大静脈とのシャントを認めたため, 後下膵十二指腸静脈に対し経皮経肝門脈塞栓術を施行した. いったん軽快退院となったが, 術後約2か月後に下血・貧血が再度認められたため, 再入院となった. 精巣静脈造影検査で, 十二指腸静脈瘤が残存していたため, 開腹下に静脈瘤を結紮切除後, 残存した静脈瘤内にエタノールアミンオレイトを注入し, 術中硬化療法を施行した. 術後2年経過した現在再発なく経過良好である.十二指腸静脈瘤に結紮術および術中硬化療法は安全かつ確実で有用な治療法であった.

進行, または肝機能不良肝細胞癌32例にマイクロウェーブ凝固壊死療法 (MCT) を行い, その意義を検討した. 非切除の理由は肝予備能不良14例, 過量肝切除となるもの15例, 腎不全2例, 高齢1例であった. 臨床病期はI, II, IIIが2例, 16例, 14例, StageはI, II, III, IV-Aが2例, 6例, 8例, 16例, 平均腫瘍径は3.2cm, 平均焼灼腫瘍数は2.5個であった. 原発例が13例, 再発例が19例であった. 経皮経肝的23例 (経皮群) 開腹下に9例 (開腹群) 行った. 1年と3年累積生存率は46.5%と37.2%, 臨床病期, Stage間で有意差はなく, 腫瘍径3cm以下, 腫瘍個数2個以下, 異時性多中心性発癌例は生存率が良好であった (p

A rare case of jejunal perforation caused by a metastatic tumor from gastric cancer after subtotal gastrectomy is reported. An 82-year-old man had undergone subtotal gastrectomy for advanced cancer, which penetrated serosa without invasion of adjacent structures with no distant metastasis, with conclusive stage IIIb, resulting in conclusive curability B in September 1992. On October 10, 1994, he was admitted with a chief complaint of abdominal pain. A chest roentgenogram showed free air below the right diaphragm. Although an upper GI series did not reveal a perforated lesion, an emergency operation was performed for the diagnosis of panperitonitis due to bowel perforation. There was a perforated lesion in the jejunum located 35cm distal from the Treitz ligament, and two other tumors were located 62cm and 94cm distal from the Treitz ligament. In the mesenterium, metastatic lymph nodes were swollen like beads but no peritoneal dissemination was found. Partial resection of the jejunum including the perforated lesion and the other two tumors was performed. Histologically, all metastatic tumors showed poorly differentiated adenocarcinoma similar to the primary gastric cancer, and the intramural tumor showed mocosal and serosal layer involvement. It was thought that a metastatic tumor of the small intestine from the primary gastric cancer had caused the jejunal perforation.