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Objective To analyze large-scale data obtained from telephone cancer consultations and clarify sex differences in the information sought by callers to guide future cancer survivor support. Methods We qualitatively analyzed 10,534 cases of telephone consultations with cancer patients. The relationships between callers’ words and sex were visualized through a correspondence analysis, and the keywords extracted were visualized with a dependency relationship to the words “worry” and “anxiety,” which had a high prevalence in the text data. Results Most of the male callers sought consultation about stomach cancer (11.8%), the consultations were predominantly about “suspicion of having cancer” (25.2%), and males indicated that the goal was to gather accurate information. Female callers mostly sought consultation about breast cancer (18.4%) were mainly interested in learning about “treatment” (31.0%), and mostly used the keywords "worry" and "anxiety." The total number of callers without a definitive diagnosis accounted for 20% of all consultations. Conclusions Healthcare providers need to understand unique sex-based coping styles and perform regular follow-ups. There is also a need for online platforms that provide information from the patient’s perspective. Practical implications Providing a cancer consultation support system and easy-to-understand medical information will improve communication between survivors, their families, and medical staff.

Background: The probable role of cyclo-oxygenase-2 (COX-2) in the development of hepatocellular carcinoma (HCC) in patients with chronic liver diseases has been accepted to be relevant. The purpose of the present study was to determine whether overexpressed COX-2 in the background liver affects the clinical course of hepatitis C virus (HCV)-related cirrhosis patients after curative surgery for HCC. Methods: Twenty-nine clinical stage I HCC patients with HCV-related cirrhosis, who underwent curative surgery, were enrolled in the present study (22 men and seven women, age range 53–73 years; follow-up period; range 22–159 months, median 61 months). The COX-2 expression in the cirrhotic liver was examined by immunohistochemistry using the avidin–biotin–peroxidase complex technique on paraffin-embedded formalin-fixed tissue. The COX-2 expression was scored, then correlated with monitored alanine aminotransferase (ALT) levels during the follow-up period after surgery, response to alternative therapy aiming to improve elevated ALT levels, and recurrence/survival after surgery. Results: The COX-2 expression scores were significantly higher in the high-ALT group than in the low-ALT group (Mann–Whitney, P = 0.010), and were significantly higher in non-responders to the alternative therapy than in responders (Mann–Whitney, P = 0.028). The higher COX-2 expression in the cirrhotic liver was the significant independent risk factor for residual liver recurrence (Cox multivariate analysis, P = 0.014), but not for survival. Conclusions: Overexpressed COX-2 in the background liver may play an important role in prolonged acceleration of necroinflammation, resistance to the alternative therapy, and recurrence/new development of HCC in HCV-related cirrhosis patients.

Background: Although the standard 3-week capecitabine regimen (1250 mg/m 2 twice daily for 2 weeks followed by a 1-week rest) has shown superior activity and improved safety over bolus 5-fluorouracil/leucovorin in two large randomized phase III trials in Europe and in the United States, only a 4-week regimen of capecitabine (828 mg/m 2 twice daily for 3 weeks) has been studied in Japan. Therefore, we performed a phase II study to investigate the 3-week regimen of capecitabine in Japanese patients with metastatic colorectal cancer (MCRC). Methods: Previously untreated patients with MCRC received oral capecitabine 1250 mg/m 2 twice daily for 2 weeks. Treatment was repeated every 3 weeks. Blood and urine samples were collected for pharmacokinetic analysis. Results: Sixty patients were enrolled. The overall response rate was 35% [95% confidence interval (CI), 23–48%], and 52% of patients had stable disease. The median time to progression was 5.5 months (95% CI, 4.2–6.7 months). The median overall survival was 20.2 months (95% CI, 16.6–27.8 months). The most frequently occurring adverse drug reaction was hand-foot syndrome (all-grade 73%; grade 3 13%). Diarrhea, anorexia, nausea and stomatitis were each seen in 37% of patients. The pharmacokinetic profiles of capecitabine and its metabolites were similar to those reported in Caucasian patients. Conclusions: The 3-week regimen of capecitabine was effective and well tolerated in Japanese patients with MCRC as well, and could be used as the basic regimen for future combination therapies.

症例1は50歳の女性で, 直腸癌の診断で当院紹介された. 直腸Raに2型病変を認め, CT上傍大動脈リンパ節腫大が見られた. 低位前方切除術施行し, 術中迅速組織診で傍大動脈リンパ節転移陽性であった. 術後化学療法を1クール施行し, 傍大動脈リンパ節腫大は消失したが術後4年9か月のCTで再び傍大動脈リンパ節転移再発を認めた. 化学療法4クール施行後, リンパ節腫大は消失した. 術後8年9か月時点で再発なく経過中である. 症例2は29歳の男性で, 下血にて前医入院し, 精査加療目的で当院転院した. 歯状線に接して粘膜下腫瘍様隆起を認め, 生検で小細胞癌の診断となった. 化学療法3クールと放射線照射を施行し腫瘍の縮小を得た後, 腹会陰式直腸切断術を施行した. 原発巣, リンパ節共に腫瘍細胞を認めず, 加療後19か月現在無再発生存中である. 直腸原発小細胞癌は予後不良だが集学的治療が著効する例もあることから積極的な治療が望まれる.

症例は75歳の女性で, 1997年1月にS状結腸癌に対して切除術を受けた (well, se, ly1, v0, n0; Stage II). 術後, 追加治療せず外来経過観察としたが, 2002年11月より血清CEA値の上昇を認め, 2003年3月の腹部CTで脾臓に4×2cm大の腫瘤像が確認された. 全身F-18 fluorodeoxyglucose positron emission tomographyでは同部に強い集積が認められたため, 脾臓転移を疑い2003年5月脾摘術を施行した. 病理組織学的に前回切除されたS状結腸癌の脾臓転移と診断した. その後も補助化学療法を行わず, 術後19か月経過した現在, 再発なく生存中である. 大腸癌の脾臓への孤立性転移はまれであり, 若干の文献的考察を加えて報告する.

目的:大腸癌に対する腹腔鏡補助下大腸切除手術(LAC)と開腹手術(OPEN)のリンパ節郭清が同等の質であるかをリンパ節の採取個数で比較検討した.対象と方法:右半結腸切除,S状結腸切除,直腸高位前方切除が施行された大腸癌手術症例77例.リンパ節採取個数を各リンパ節領域ごとに比較検討した.結果:右半結腸切除21例(LAC:OPEN;12例:9例),S状結腸切除41例(26例:15例),前方切除15例(8例:7例)であった.腫瘍径による補正後の摘出リンパ節個数は(以下LAC:OPEN),右半結腸切除;1群(15.4±1.3:17.5±3.6),主幹2群(8.7±1.0:8.2±0.7),壁在2群(10.8±1.6:15.3±2.9),主幹3群(7.5±1.0:7.6±0.8),S状結腸切除;1群(12.3±1.3:13.1±1.5),主幹2群(8.2±1.2:8.1±1.2),壁在2群(7.0±1.4:5.7±0.9),主幹3群(6.8±1.0:6.4±1.3),前方切除;1群(12.5±2.3:12.4±2.7),主幹2群(9.3±1.4:9.7±2.3),壁在2群(6.8±2.4:5.6±1.3),主幹3群(5.0±0.9:5.3±1.3)であった.考察:LACとOPENで以上の3種類の術式においてリンパ節郭清はほぼ同等であることが示唆された., Aim: This study was conducted to evaluate. The number of dissected lymph nodes between laparoscopyassisted colectomy (LAC) and open colectomy (OPEN). Methods: Seventy-seven patients who underwent hemi-colectomy (LAC: OPEN; 12cases: 9cases), sigmoidectomy (LAC: OPEN; 26cases: 15cases) and high anterior resection (LAC: OPEN; 8cases: 7cases) at Kanagawa Cancer Center were entered in this study. The number of dissected lymph nodes at each N1, paracolic N2, central N2, and central N3 area was compared. Results: In Hemi-colectomy, N1 area was LAC: OPEN =15.4±1.3 : 17.5±3.6 (p = 0.548), Central N2 was 8.8±1.0 : 8.2±0.7 (p = 0.684) , Paracolic N2 was 10.8±1.6 : 15.3±2.9 (p = 0.176), and Central N3 was 7.5±1.0 : 7.6 ± 0.8 (p = 0.966) . In sigmoidectomy, Nl was 12.3±1.3 : 13.1±1.5 (p = 0.675) , Central N2 was 8.2±1.2 : 8.1±1.2 (p = 0.945) , Paracolic N2 was 7.0±1.4 : 5.7±0.9 (p = 0.522) , Central N3 was 6.8±1.0 : 6.4±1.3 (p = 0.808) . In Anterior resection, N1 was 12.5±2.3 : 12.4±2.7 (p = 0.969) , Central N2 was 9.3±1.4 : 9.7±2.3 (p = 0.863) , Paracolic N2 was 6.8±2.4 : 5.6±1.3 (p = 0.689) , and Central N3 was 5.0±0.9 : 5.3±1.3 (p=0.879). Conclusion: The results suggested that quality of lymph node dissection in LAC was equal to that of OPEN.

はじめに: 大腸癌根治手術後の早期再発発見を目的としたintensive follow up法の妥当性を検討した. 対象および方法: 1986～2001年までの大腸癌根治度A症例のうち単発再発を認めた126例を対象とした. 4か月に1回のCTにより再発を発見された症例をintensive群(以下, I群, n=66), 1年に1 回のCTにより再発を発見された症例をconventional群 (以下, C群, n=60) に分類し, 生存期間 (ST), 無再発期間 (DFI), 再発後生存日数 (SAR) をretrospectiveに検討した. 結果: DFIはI群が467日, C群が690日で有意差を認めたがSARはそれぞれ943日, 767日であり有意差はなかった. また臓器別に検討すると肺再発のSARはI 群で1,296日, C 群で925日であり有意差はないものの改善される傾向を認めた. 考察: CTによる大腸癌術後intensive follow upは再発後生存日数の向上には寄与しなかった. しかし腫瘍マーカー, 問診でスクリーニングが困難な肺再発においては再発後生存日数が向上する可能性が示唆された.

Background and Objectives The aggressiveness and greater malignant potential of cancers are characterized by several biological phenomena such as accelerated growth invasiveness, and the ability to form distant metastasis. Thus, knowledge of such biological difference may be a more accurate prognosticator for cancer patients. Tumor growth depends on the degree of imbalance between cell production and loss. This study aimed to clarify a possible role for the modified prognosticator, growth index (GI); defined as the difference between Ki-67 (%) and single-stranded DNA (ssDNA) (%) labeling indices, in patients undergoing curative resection for hepatocellular carcinoma (HCC). Methods Tissue specimens were obtained from 40 HCC patients who underwent curative surgery. Immunohistochemical staining was performed using the avidin–biotin–peroxidase-complex method. Results The GI in HCC ranged from −1.90% to 28.65%, median 3.73. GI was related to histologic grade, intrahepatic metastasis, and pathologic T stage. Cumulative survival was poorer in patients with higher GI (≧median value). Multivariate analysis demonstrated that GI is an independent prognosticator along with vascular invasion and intrahepatic metastasis. Conclusions The higher GI values were significantly associated with histologic aggressive features of HCCs, and GI was a significant independent prognosticator in HCC patients after curative resection. J. Surg. Oncol. 2005;92:331–336. © 2005 Wiley-Liss, Inc.

症例は69歳の男性.平成15年6月6日から,他院で診断された左肺癌に対して放射線化学療法を施行していたが, 6月24日ごろより粘血便が出現した.腹部に所見はみられず,大腸内視鏡検査で直腸Rs内に球状の腫瘤を認め,生検では壊死組織であった.腸重積発症の恐れがあるため,平成15年8月22日にS状結腸切除術を施行した.手術所見ではS状結腸が直腸Rs内に陥入して重積様の所見を呈していた.切除標本ではS状結腸内腔に著明に突出した球状腫瘍を認め,その口側に2型進行癌が隣接して存在していた.球状腫瘤は組織学的に紡錐形細胞が索状配列しており,隣接するS状結腸浸潤癌近傍の粘膜下から発生し,これを押し上げていると考えられた.免疫染色ではc-kit, CD34, SMA, S100ともに陰性であり広義のGISTと診断された.結腸GISTの報告例は20例と少なく,さらにこのような肉眼形態は非常に稀であるため,本邦報告例の集計とともに報告する.

We examined whether sustained alleviation of inflammation as monitored by serum alanine aminotransferase (ALT) levels was associated with longer survival in hepatectomized hepatocellular carcinoma (HCC) patients with hepatitis C virus-associated liver cirrhosis (HCV-LC). Thirty-four hepatectomized patients with HCV-LC and HCC as a single nodule, and for whom more than 5 years had elapsed after the hepatectomy, were studied. They had no histologic evidence of portal or hepatic vein invasion. They were subdivided into two groups according to their serum ALT levels in the 2 years after hepatectomy: the low ALT group comprised 13 patients whose serum ALT levels showed a sustained low level below 80 IU, and the high ALT group comprised 21 patients whose serum ALT levels showed several peaks or plateaus above 80 IU. The patients had been followed-up prospectively with frequent ultrasonography and magnetic resonance imaging or computed tomography for recurrence for > 5 years. The survival period, non-recurrence interval and number of recurrences were observed. Recurrences were treated with transcatheter chemoembolization in all cases. The cumulative survival rate in the low ALT group was significantly better than that in the high ALT group (P < 0.05). The 5-year survival in the low ALT group was as high as 92.3% (12 of 13) compared with 33.3% (7 of 21) in the high ALT group (P < 0.05). The cumulative non-recurrence rate in the low ALT group was also significantly better than that in the high ALT group (P < 0.01). The survival period correlated well with the interval until the first recurrence (r = 0.545, P = 0.006). There was a tendency for the number of recurrences in the low ALT group (1.5 +/- 0.4, mean +/- SE) to be fewer than that in the high ALT group (2.2 +/- 0.4), although this was not significant. Sustained alleviation of inflammation, as indicated by low ALT levels, provides a survival advantage mainly due to the longer non-recurrence interval, and possibly because of fewer recurrences, in hepatectomized HCC patients with HCV-LC.

目的: 大腸癌におけるリンパ節転移個数の予後予測における有用性を検討する.対象: 1990年から2000年までに治癒切除された大腸癌 (肛門管癌除く) 患者815例 (男性487例女性328例, 62.7歳). stage 0 33例, stage I 174例, stage II 220例, stage IIIa 192例, stage IIIb 136例, stage IV 60例. リンパ節転移個数は0個, 1～3個 (1個, 2～3個), 4個以上の3群 (4群) に分け, n因子は大腸癌取扱い規約に従い検討した.結果: 術後生存日数において単変量解析でn因子はn2, n3, n4の各群間に有意差はみられなかった. リンパ節転移個数は各群間に有意差をみた. 深達度, 肝転移, 腹膜播種, 遠隔転移を加えた多変量解析は両者有意な予後規定因子となったが, n因子のrelative riskはn3とn4の間で逆転したのに対し転移個数は1次関数的に増加した. 無再発日数においても単変量解析で転移個数はすべての群で有意差がみられたが, n因子はn2, n3, n4の間に有意差はみられなかった. 多変量解析ではn因子が有意ではあるがrelative riskはn4群がn3群に比べ低値 (n3 6.760, n4 5.722) となったのに対し, リンパ節転移個数ではすべて1次関数的に増加した.結語: リンパ節転移個数は生存率再発予測について, 単変量でも多変量解析でもn因子より有用である. リンパ節転移についてはその部位と共に転移個数についても考慮すべきであり, これらを術中所見の判定に用いることにより, 適切な大腸癌のリンパ節郭清の一助となると考えられた.

症例は50歳の女性. 1996年6月注腸検査, 大腸内視鏡検査で肛門縁から10cmの直腸に2型病変をみとめ生検でanaplastic squamous cell carcinomaであった. 術前CTにて傍直腸, 大動脈周囲, 左腸骨動脈周囲にリンパ節腫大を認めた. 8月12日低位前方切除術施行, 術中迅速診にて大動脈周囲リンパ節に転移陽性であり, 根治度Cであった. 病理組織診では直腸原発の小細胞癌と診断した. 肺小細胞癌に準じ術後CDDP40mg×2日, VP-16 100mg×3日(1クール)の化学療法を施行した. 化学療法が奏効し術後9MのCTにて傍大動脈リンパ節腫大消失CRを得て以後2001年2月まで42か月, 再発なく経過中である. 小細胞癌の直腸原発例はまれであり, 1クールにもかかわらず化学療法が奏効した1例を経験したので報告する.

Background/Purpose: Congenital absence of the portal vein (CAPV) is a subtype of congenital portosystemic shunt, which can cause a broad spectrum of clinical manifestations. The authors report on 4 patients with CAPV including a boy with CAPV-associated encephalopathy, which was resolved effectively by liver transplantation (LT). Methods: The case records of 4 pediatric patients with CAPV who were referred to the author's institution between 1984 and 1999 were reviewed. Results: The patients (3 boys and 1 girl) ranged in age at diagnosis from 0.8 to 14 years. Two patients had growth retardation or disturbed consciousness, and the other 2 had no specific manifestations. Not only high serum levels of bile acids, ammonia, and transaminases but also low plasma levels of branched-chain amino acids were common laboratory findings. The absent portal vein was replaced by a large portosystemic shunt, which connected the splanchnic vein to the inferior vena cava or the left renal vein. Two patients survived without any symptoms, but 1 with growth retardation died of hepatic failure. The other with encephalopathy did not respond to medical therapy and underwent LT, which resolved symptoms and metabolic disorders effectively. Conclusions: Patients with CAPV do not always have a good prognosis. They should be followed up with careful observation of their symptoms, hepatic function, and metabolic abnormalities. LT might be indicated for patients with symptomatic CAPV unresponsive to medical therapy. J Pediatr Surg 36:1026-1031. Copyright © 2001 by W.B. Saunders Company.

We investigated whether or not a high serum alanine aminotransferase (ALT) level is associated with a more rapid recurrence of hepatocellular carcinoma (HCC) in hepatectomized patients with hepatitis C virus (HCV)-associated liver cirrhosis (LC) (HCV-LC) and HCC. Thirty-three hepatectomized patients with HCV-LC and HCC of a single nodule who had no histologic evidence of portal or hepatic vein invasion and who had been followed up for more than 3 years were included in the study. They were subdivided into two groups according to their serum ALT levels, ALT being a well-known marker of inflammatory necrosis in the liver. Seventeen patients whose serum ALT levels showed several peaks or plateaus above 80 international units (IU) were designated as the high ALT group, and 16 patients whose serum ALT levels showed a sustained low level below 80 IU until the first recurrence were designated as the low ALT group, and the interval between hepatectomy and the first recurrence was observed. In the high ALT group, HCC recurred within 3 years in 70.6% of the patients. In contrast, it recurred in only 18.8% of the low ALT group within the same period (p < 0.05). There was a significant difference (p = 0.0201) between the two groups in the cumulative nonrecurrence rate. The mean interval in recurrent patients between hepatectomy and the first recurrence in the high ALT group (23.6 ± 2.8 months; mean ± SE) was significantly (p < 0.02) shorter than that in the low ALT group (49.3 ± 9.7 months). The expected interval between hepatectomy and recurrence was as short as 2.8 ± 0.5 years (mean ± SE) in the high ALT group, compared with 5.8 ± 0.7 years in the low ALT group (p < 0.05). These results showed that the recurrence of HCC was accelerated in the high ALT group, suggesting that suppression of the rise in ALT level after hepatectomy by treatment with anti-inflammatory drugs may prolong the interval until recurrence by about 2 years in hepatectomized patients with HCC and HCV-LC.

A total of 32 patients, who had undergone surgical currative resection of colorectal cancer liver metastasis, were retrospectively analyzed. Recurrences were observed in 75% of the 32 patients. These recurrences were hepatic in 33.3% of patients with recurrence, intra-and extrahepatic in 37.5% and extrahepatic in 29.2%. The residual liver recurrence rate was significantly higher in H2H3 cases than in H1 cases. The five year survival rate of H1 cases was 50.0%, while none of the H2H3 patients survived more than three years. Advanced wall invasion in the primary tumor was unfavorable prognostic indicator in H1 cases, without statistical significance. The patients who underwent adjuvant intrahepatic arterial chemotherapy had a favorable residual liver recurrence rate and survival rate, but this did nor reach statistical significance. To prolong survival in patients with undetected extrahepatic residual disease at the time of hepatic resection, effective adjuvant therapy, combining hepatic arterial chemotherapy and systemic chemotherapy, is required.

To examine whether the marked increase in DNA synthesis of hepatocytes in cirrhotic liver might elicit multicentric hepatocarcinogenesis, we examined the relationship between new development of hepatocellular carcinoma (HCC) and the bromodeoxyuridine (BrdU) labeling index (LI) of hepatocytes in the residual liver of hepatectomized patients with liver cirrhosis (LC) and HCC. Eighteen hepatectomized patients with LC and HCC, whose resected liver revealed neither portal nor hepatic vein invasion by histologic examination, were studied (to exclude cases with intrahepatic metastasis). DNA synthesis activity of hepatocytes from the residual cirrhotic liver was measured by a BrdU/anti-BrdU in vitro method. The incidence of HCC recurrence was studied during a 3-year follow-up period. Among 18 patients, 9 patients had recurrence and 9 did not. The average BrdU LI in the recurrent patients was 2.6 +/- 1.3% and was significantly higher than that in patients without recurrence (1.4 +/- 0.5%, P < 0.05). All five patients who had a BrdU LI of 2.4% or above showed recurrence within 3 years, as compared with 4 of 13 (30.8%) patients with BrdU LI of less than 2.4% (P < 0.05). Our data indicate that abnormally high DNA synthesis in hepatocytes in the background cirrhosis might lead to the development of multicentric carcinogenesis in human cirrhotic liver, and in the residual cirrhotic liver of hepatectomized patients with HCC and LC, it may be a predictor of new development of HCC.

BACKGROUND There is a concept that a cancer often maintains some of the traits of the background tissue cells. Thus, the possibility exists that the DNA synthetic activity of the hepatocytes in cirrhotic tissue affects that of hepatocellular carcinoma (HCC) cells. METHODS DNA synthesis activity of hepatocytes from background cirrhotic tissue and HCC cells from cancerous tissue was studied in 30 patients with liver cirrhosis (LC) and HCC who had undergone hepatectomy; the study was done using the bromodeoxyuridine (BrdU)-anti-BrdU in vitro method. The correlation between the BrdU labeling index (LI) of hepatocytes from noncancerous cirrhotic tissue and that of HCC cells was studied. The relationship between both BrdU LI values and the survival after hepatectomy also was studied. RESULTS A significant correlation (r = 0.572; P < 0.001) was identified between the BrdU LI for HCC and that for noncancerous cirrhotic tissue. A significant correlation (r = -0.572; P < 0.05) was found between the BrdU LI of HCC cells and the survival after hepatectomy. A significant correlation (r = -0.678; P < 0.01) was observed between the BrdU LI of the noncancerous cirrhotic tissue and the survival. CONCLUSIONS It was concluded that a significant correlation existed between DNA synthesis of hepatocytes from the background cirrhotic tissue and that of HCC cells and that DNA synthesis activity of hepatocytes from noncancerous cirrhotic tissue and that of HCC cells from cancerous tissue could predict the survival of patients with HCC who had undergone hepatectomy.

A 60-year-old man, with a high risk GIST of the rectum, suspected of the infiltration to the prostate and measuring 10 cm in diameter, underwent resection after neoadjuvant therapy of imatinib mesylate. Perineal approach was added because intraperitoneal dissection was not enough, however, the infiltration to the prostate was denied completely due to a reduction in the tumor size, thus total peritoneal resection was avoided. It seems that neoadjuvant therapy with imatinib mesylate is useful for resectability and for the preservation of the functions of ambient organs.

Bromodeoxyuridine (BrdU) labeling indices (LI) of liver biopsied specimens from 27 control liver cirrhosis patients (control LC) without hepatocellular carcinoma (HCC), 26 cirrhotic patients with HCC, and from 6 control subjects were examined using an in vitro BrdU labeling technique. The mean BrdU LI +/- S.E. of HCC cancerous portion, HCC non-cancerous cirrhotic portion, control LC, and control subjects were 6.6 +/- 0.8%, 2.7 +/- 0.3%, 1.7 +/- 0.3% and 0.25 +/- 0.09%, respectively. Interestingly, there was a significant difference (p less than 0.025) between the non-cancerous LC portion and control LC. While 25 of 26 non-cancerous LC portion of HCC patients were in the high LI group (greater than or equal to 1.4%), 15 of 27 in the control LC were in the low LI group (less than 1.4%) (p less than 0.001). Of the 12 control LC with high LI, 6 developed HCC within 2 years, whereas only one of the 15 control LC with low LI developed HCC (p less than 0.05). In conclusion, HCC may develop in cirrhotic patients with high DNA synthetic potency.

This study was conducted to evaluate the effects of lateral lymph node dissection (LLD) on overall survival, disease-free survival, and local recurrence for the patients with lower rectal cancer.From 1990 through 2000, 169 consecutive patients with T2 (TNM classification) or more advanced, extended lower rectal cancer (located below the peritoneal reflection) underwent curative resection at Kanagawa Cancer Center were reviewed. One hundred and forty-three patients who underwent LLD and the 26 patients who did not were entered in this study.Cox's multivariate regression analysis showed T stage (TMN classification), N stage (TNM classification), and LLD were found to be significantly related to the rates of both cumulative survival and disease-free survival. That mean LLD was identified as a significant prognostic factor. But disease-free survival did not differ significantly between the patients who underwent LLD and those who did not undergo LLD in stage I, II, or III disease (p = 0.3681, p = 0.1815, and p = 0.0896, respectively). The local recurrence rate was similar in patients who received LLD (17.5 percent) and in those who did not receive LLD (23.1 percent; p = 0.498). But 7 patients with lateral lymph node metastasis (33.3 percent) remained disease free. And these patients had local lateral lymph node metastasis and benefited from LLD.LLD can substantially improve outcomes in selected patients at high risk for lateral lymph node metastasis. A randomized controlled clinical study is necessary to clarify the role of LLD in the treatment of rectal cancer.

Japanese general rules for the staging of colorectal cancer conventionally classify lymph node metastasis into three groups according to location with respect to the primary tumor. Skip metastasis, in which distant nodes are positive but regional nodes are negative, is often encountered but poorly understood. We studied the clinicopathological features of skip metastasis in colorectal cancer.The location of positive nodes was classified in 323 patients with Dukes' stage C colorectal cancer. Skip n2 lymph node metastasis was defined as positive N2 metastasis without negative N1 or N3 metastasis. Clinicopathological findings and survival were compared between the patients with skip n2 metastasis (skip n2 group) and those with n1 (n1 group) or n2 metastasis (n2 group).There were 211 patients in the n1 group, 91 in the n2 group, and 21 in the skip n2 group. Pathological examination showed that the skip n2 group had fewer positive nodes than the n1 and n2 groups, but was positioned between these groups with respect to the degree of lymphatic invasion. Cumulative survival was significantly poorer in the n2 group than in the skip n2 group (p = 0.039 by log-rank test). Survival was similar in the skip n2 group and n1 group. There was also no difference in survival between patients in the skip n2 group and patients with one, two, or three N1 metastases.Lymph nodes with skip n2 metastasis are most likely sentinel nodes of the primary tumor in patients with colorectal cancer. The prognosis of patients with skip n2 metastasis is therefore better than that of patients with n2 metastasis and similar to that of patients with n1 metastasis.

Duodenal adenoma is rare, and there have been very few case reports of flat elevated type adenoma. We report a case of flat elevated type carcinoma in adenoma of the duodenum with gastric cancer. A 58-year-old man was referred to our hospital for gastric cancer. Endoscopic examination revealed the gastric cancer and a flat elevated tumor in the descending part of the duodenum, measuring 6 cm in diameter. The biopsy specimen of the duodenal lesion was diagnosed as adenoma. Distal gastrectomy and segmental partial resection of the duodenum were performed with no complication. Histologically, the gastric cancer was poorly differentiated adenocarcinoma with submcosal invasion and without lymph node metastasis, and the duodenal tumor was a well differentiated carcinoma in villous adenoma. The duodenal adenocarcinoma was limited to the mucosal layer and the resected margins were free of tumor. It is difficult to distinguish a carcinoma from a benign elevated lesion in the duodenum. Therefore, a resection of the whole tumor is necessary. Though endoscopic resection is the first choice of therapy, a surgical partial resection is necessary when it is difficult. Then, a segmental resection may be one of the useful procedures of surgery.

HCFU and UFT were reported effective in adjuvant chemotherapy for colorectal cancer. This investigation was planned as a randomized study to compare the usefulness of combination therapies with mitomycin C (MMC)+HCFU and MMC+UFT as postoperative adjuvant chemotherapy in patients with colorectal cancer following curative resection, in terms of survival rate, recurrence rate, and adverse drug reactions. A total of 501 patients consisting of 252 patients with stage III/IV colon cancer (Colorectal Cancer Handling Rules, 4th Ed.) for which macroscopic curative resection was possible and 249 patients with stage II/III/IV rectal cancer (ibid, 4th Ed.) were registered from 40 participating institutions. The patients were randomly allocated to two groups with colon cancer and rectal cancer employed as stratification factors. Beginning on Day 14 after surgery, HCFU at 300 mg/day was administered to one group and UFT at 300 mg/day or 400 mg/day to another group, both orally and daily for one year. MMC 6 mg/m2 was administered intravenously to both groups on the day of surgery and the day following. Among the 501 patients, 496 patients (99%) were eligible. The 5-year survival rates were 77.1% for the MMC+ HCFU group and 79.2% for the MMC+UFT group, with the 5-year recurrence-free survival rates were 76.1% and 72.9%, respectively, neither showing a significant difference between the groups. Adverse drug reactions appeared in 23% of patients in the MMC+HCFU group and in 19% in the MMC+UFT group, with no serious reactions. One year after surgery the administration completion rates were good, at 82% for the MMC+HCFU group and 83% for the MMC+UFT group. No clear difference in effectiveness was noted between MMC+HCFU therapy and MMC+UFT therapy as postoperative adjuvant chemotherapy for colorectal cancer. The administration completion rates were good, and no serious adverse drug reactions were observed for either therapy. It was thus considered that both therapies could be administered safely, and both were useful as postoperative adjuvant chemotherapies for colorectal cancer. It is considered necessary to compare them with standard therapies in Western countries in the future.

Negative ions are considered to have potential health benefits, but few studies have examined their effects in vivo. We studied water-generated negative ions (WNI) with respect to physical properties as well as immunologic activation and anti-tumor activity (inhibition of carcinogenesis and tumor growth) in mice. Electrically, generated negative ions (ENI) served as control. Water-generated negative ions had a long life, significantly enhanced the cytotoxic activity of natural killer cells, and significantly decreased the incidence of cancer and inhibited tumor growth. Anti-tumor effects were attributed to enhancement of natural killer cell activity. The mechanisms and applications of negative ions warrant further investigation.

The clinical impact of survivin on human cancer pathogenesis and prognosis has been investigated. To clarify the clinical effect of survivin on tumor behavior and prognosis of patients with hepatocellular carcinoma (HCC), the expression of survivin mRNA in 40 samples of HCC tissue and matched-adjacent liver tissue, as well as 7 healthy hepatic tissue samples were measured by a real-time reverse transcription polymerase chain reaction. The expressed level of survivin mRNA (log copies/microg total RNA) in healthy liver tissue was 1.95+/-0.44, in morbid liver tissue adjacent to the tumors was 4.79+/-0.96, and in HCC tissue was 5.87+/-0.73 (values are mean +/- SD and P0.001). The amount of survivin mRNA in HCC tissues correlated negatively with the apoptotic indices (r=-0.573 and P0.001) and correlated positively with the proliferation indices (r=0.433 and P=0.005). Expression of survivin was significantly related with histologic grade (P=0.011) and pathological tumor stage (P=0.017). Patients with HCC tumors that had a large amount of survivin mRNA (or = mean) had lower survival rate (P=0.030), but multivariate analysis showed only Ki-67 labeling index, histologic grade, and pathologic T stage to be the independent prognosticators. These findings indicate that survivin is associated with reduced tumor cell apoptosis, increased tumor cell proliferation, and histologically aggressive tumor features, and may play an important role in tumor progression of HCC. However, further examination is needed to clarify its predictive significance for HCC patients.

Tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) in plasma has been reported to be related to disease progression in patients with colorectal cancer. However, the prognostic significance of plasma TIMP-1 has not been clarified.Concentrations of TIMP-1 protein were measured by enzyme-linked immunosorbent assay in plasma samples of 87 preoperative patients who subsequently underwent resection, and prognosis was compared. The cut-off value of plasma TIMP-1 was defined as 170 ng/ml.When clinicopathological factors between patients with positive and those with negative plasma TIMP-1 were analyzed, significant differences were observed in lymph node metastasis, serosal invasion, curability and Dukes' classification. Univariate analysis of these factors demonstrated that depth of invasion, metastases to lymph nodes, peritoneum, liver and distant organ, lymphatic and vessel invasions, curability. Dukes' classification and plasma TIMP-1 concentration were significant. By multivariate analysis excluding patients with distant or peritoneal metastases, histological type, lymphatic invasions, lymph node metastasis and plasma TIMP-1 were retained in the final model.These results suggested that plasma TIMP-1 may be a useful prognostic marker for survival in patients with colorectal carcinoma.

This phase II study evaluated a modified Japanese capecitabine regimen as first-line treatment for advanced/metastatic colorectal cancer. Sixty patients received oral capecitabine 828 mg/m(2) twice daily for 3 weeks every 4 weeks. In the 56 efficacy-evaluable patients, the overall response rate was 26.8% (95% CI 15.8-40.3%) and 21 patients (37.5%) had stable disease. The median duration of response and overall survival times were 7.4 months (range 4.3-13.8) and 17.6 months (95% CI 14.1-20.5), respectively. The most frequent non-hematological treatment-related adverse events (all grades) were hand-foot syndrome (62.7%), anorexia (28.8%), diarrhea (22.0%) and fever (22.0%). There was no grade 3/4 diarrhea. The most common grade 3/4 laboratory abnormalities were lymphocytopenia (30.5%) and hyperbilirubinemia (35.6%). We conclude that the modified Japanese intermittent regimen of capecitabine is effective and well tolerated as first-line treatment for advanced colorectal cancer, and is worthy of further study in larger phase III studies.

Platelet-derived endothelial cell growth factor (PD-ECGF) is one of the angiogenic factors. The aim of this study was to examine the PD-ECGF concentrations in hepatocellular carcinoma, background liver, and normal liver tissues, and to elucidate their significance on clinicopathological outcomes.The concentration of PD-ECGF in the tissue extract was determined by enzyme-linked immunosorbent assay.PD-ECGF concentrations were significantly higher in hepatocellular carcinoma and background liver tissues compared with normal control liver (p = 0.003, p = 0.001, respectively). PD-ECGF concentrations in hepatocellular carcinoma tissues were positively correlated with intratumoral arteriole densities (r = 0.667, p = 0.009), and were higher in less differentiated carcinomas (p = 0.039). However, tumor PD-ECGF concentration did not affect the patients' disease-free survival rates. Those in the background liver tissues were positively correlated with histological activity index scores (r = 0.650, p = 0.001) and serum alanine aminotransferase levels (r = 0.0452, p = 0.035).PD-ECGF is up-regulated in hepatocellular carcinoma and the corresponding hepatitis liver. The PD-ECGF concentrations in hepatocellular carcinoma correlated positively with microvessel density, lower differentiation, yet not with patients' prognosis. The concentrations of PD-ECGF in the corresponding hepatitis liver correlated positively with the degree of active hepatitis.

Percutaneous microwave coagulation therapy (PMCT) and radio frequency ablation therapy (RFA) as treatments for metastatic liver cancer were examined. PMCT or RFA was administered for 18 metastatic liver cancer lesions (primary lesion: 11 colon rectal cancer, one esophagus cancer, one thyroid cancer, one pancreatic cancer, one pheochromocytoma) in 16 patients from July 1999 to March 2002. RFA was performed 1 time for 12 minutes in principle, using a Cool-tip RF system from Radionics. Patients had a mean age of 58.8 years and the mean diameter of the neoplasms was about 22 mm. Critical complications were not seen. The rate of partial recurrence was 35.3% as of March, 2002, in an average observation period of 7.3 months. On the other hand, with the medical treatment for the hepatocellular carcinoma provided during this period, the rate of partial recurrence was 14.8%. The treatment of metastatic liver cancer by PMCT and RFA is associated with a high rate of a recurrence as compared with hepatocellular carcinoma, and needs to be examined to discover ways of adaptation and improvement of the technology.

Background and Aim: Hepatocellular carcinoma (HCC) is unique in that its carcinogenesis is related to inflammatory changes and regenerative activities in the background liver. Although there are some data on cyclooxygenase (COX)-2 expression in HCC by immunohistochemical studies, little is known about the possible role of COX-2 in inducing hepatitis and/or carcinoma. To elucidate whether COX-2 is involved in a part of these processes, we attempted to examine COX-2 mRNA both in the adjacent non-tumoral liver and in HCC. Methods: Twenty-two matched sets of adjacent liver and HCC specimens were analyzed for COX-2 mRNA expression using a real-time quantitative reverse transcription polymerase chain reaction. Cyclooxygenase-2 protein expression was also determined by immunohistochemistry. Results: Cyclooxygenase-2 mRNA expression was significantly higher in the adjacent liver than in HCC (P = 0.016). Cyclooxygenase-2 mRNA expression in adjacent liver tissues was positively correlated with the modified histological activity index scores (r = 0.575, P = 0.006), the serum alanine aminotransferase levels (r = 0.536, P = 0.010), and the Ki-67 labeling indices (r = 0.698, P = 0.001). In contrast, COX-2 mRNA expression in HCC was not correlated with any of the clinicopathological features. Conclusions: Cyclooxygenase-2 is expressed at higher levels in the adjacent liver than in HCC, and it may be associated with high levels of necroinflammation and regeneration in the background liver. Conversely, COX-2 may have a lesser role in the progression of HCC.

The relationship between the recurrence of hepatocellular carcinoma (HCC) and the serum alanine aminotransferase (ALT) level was studied in hepatectomized patients with hepatitis C virus (HCV)-associated cirrhosis and HCC.Twenty-six hepatectomized patients with HCV-associated cirrhosis and HCC whose resected specimens showed neither portal vein nor hepatic vein invasion by HCC histologically were divided into 2 groups: 15 patients who had no recurrence 3 years after surgery (Group A) and 11 patients whose disease recurred 1-3 years after surgery (Group B). The patients' serum ALT levels during this period were examined.In Group A, serum ALT generally showed sustained low levels80 international units (INU) in 12 patients (80%). In contrast, ALT levels in Group B showed several peaks or plateaus80 INU in all patients except 2. The recurrence rate of HCC in the hepatectomized patients with sustained low levels of ALT was 14.3% (2 of 14 patients) at 3 years, and was significantly lower (P0.01) than that in those patients whose ALT levels showed several peaks or plateaus80 INU (9 of 12 patients; 75.0%). The average level of mode of ALT in Group A (48.8 +/- 26.0 INU) was significantly smaller than that in Group B (101.1 +/- 47.3 INU) (P0.005).The importance of hepatocytic necrosis in the recurrence of HCC in hepatectomized patients with cirrhosis and HCC of HCV origin was demonstrated and the significance of subsiding hepatic necroinflammatory process in the prevention of HCC recurrence suggested.

In the process of liver regeneration, the participation of various types of growth stimulators and changes in immune responses have been reported. Here, we examined the growth of subcutaneously transplanted AH130 cells and Walker 256 cells after partial hepatectomy. In the case of tumor cells being transplanted on the same day as partial hepatectomy, the increase in tumor size in hepatectomized rats was significantly greater compared with that in non-treated rats or in those having undergone a simple laparotomy. When the transplantation of tumor cells was done on the 7th day after partial hepatectomy, however, the increase was less marked. We also examined the effect of serum obtained from rats after partial hepatectomy on the in vitro growth of these tumor cells. Growth enhancement was observed with medium containing serum drawn from rats 1 to 4 days after partial hepatectomy. These results suggest that the growth of tumor cells was stimulated during liver regeneration and that some humoral factors participated in the process. Furthermore, as the conditions of the in vitro method appear to mimic those of the in vivo method, the in vitro approach should be very useful for analysis of the factors responsible.

To clarify sex differences in DNA synthesis in hepatocellular carcinoma (HCC), bromodeoxyuridine labeling indices (BrdU LI) of HCC cells included in tumor biopsy specimens from 12 consecutive male patients and from 5 consecutive female patients all with liver cirrhosis and HCC were examined using an in vitro labeling technique. The mean BrdU LI +/- SE of HCC from male patients (7.7 +/- 0.8%) was significantly (P less than 0.05) higher than that from female patients (4.4 +/- 1.0%). While 7 of the 12 male HCC patients belonged to the high DNA synthesis group (BrdU LI greater than or equal to 7.0%), none of the 5 female HCC patients showed high DNA synthesis (P less than 0.05). We conclude that DNA synthesis in HCC was higher in males than in females.

With the aim of examining increasing deoxyribonucleic acid (DNA) synthesis of liver cirrhotic tissue when hepatocellular carcinoma (HCC) is developing, bromodeoxyuridine labeling indices (BrdU LI) of liver biopsy specimens from 19 control cirrhotic (control LC) patients without HCC, 19 cirrhotic patients with HCC, and from six control subjects were examined using an in vitro labeling technique. The mean BrdU LI +/- SD of HCC cancerous portion, HCC non-cancerous cirrhotic portion, control LC, and of control subjects were 7.2 +/- 2.9%, 3.3 +/- 1.5%, 2.1 +/- 1.7%, and 0.25 +/- 0.09%, respectively. Interesting enough, there was a significant difference (P less than 0.05) between the non-cancerous cirrhotic portion and control LC. Although all 17 non-cancerous cirrhotic portion belonged to the high LI group (greater than or equal to 1.5%), 10 of 19 in the control LC belonged to the low LI group (less than 1.5%) (P less than 0.001). The authors conclude that HCC would develop in the cirrhotics with high DNA synthetic potency.

ThymidineのanalogueであるBrdUに対するモノクローナル抗体を用いて肝細胞癌(以下HCC),肝硬変(以下LC),慢性活動性肝炎(以下CAH),アルコール性肝線維症(以下Al-F)等の各種肝疾患時の肝のDNA合成を免疫組織学的に検討した.即ち,上記疾患の肝生検組織をBrdUを含んだ培養液とincubationしBrdU摂取をin vitroで測定した.取り込みが最も高率であったのはHCC癌部でL.I.は5.7±0.9%であり,次いでHCC非癌硬変部(3.4±0.4%),さらにHCCの無いLC (2.3±0.7%), Al-F (2.4±0.7%)であった.一方,CAHでは1.0±0.1%と予想外に低かった.HCC癌部は,HCC非癌硬変部(p

ThymidineのanalogueであるBromodeoxyuridine(以下BrdU)に対するモノクロナール抗体を用いて原発性肝癌(以下HCC) 16例の腫瘍細胞のDNA合成を免疫組織学的に検討した.方法は0.1%にBrdUを含んだRPMI1640液と肝生検組織をincubationし,BrdU摂取率をin vitroで測定した.Labeling Index (L.I.)のMean±SEは7.06±2.71%で症例間で2.6%から12.7%と大きな差異がみられた.又,HCCのL.I.は他の消化器癌に比べて概して低値であった.次にHCCの組織学的差異によるBrdU L.I.の検討ではL.I. 5%未満では全てtrabecular typeであったのに対し,5%以上ではpseudoglandular typeやsolid typeが高頻度にmixしていた.一方,Edmondson & Steiner'sの異型度分類とBrdU L.I.との関係では,より異型度の高いIII型がL.I. 10.64±2.10%で,I～II型の5.87±1.61%に比べ有意に高く,異型度とDNA合成能との相関が示唆された.

For anticancer effects on metastatic lymph node, activated carbon adsorbed anticancer drugs were injected preoperatively into the present study, the adsorption isotherm of activated carbon adsorbed aclarubicin (ACR) was measured and its stability in solution was investigated. The adsorption isotherms of 5-FU and MMC were prepared and compared with that of aclarubicin. In the adsorption isotherm of CH-40 activated carbon, the amount of ACR adsorbed was better than that of 5-FU and MMC. The amount of ACR adsorbed for CH-1500 activated carbon was also better than that for CH-40 activated carbon. The stability of ACR adsorbed on activated carbon solution decreased as the concentration of the activated carbon increased. The stability when the activated carbon and ACR concentration ratio was constant in saline solution was 100% after 2 hours and 40% after 7 days.