Search

1996年4月∼2002年3月に当科において放射線療法を施行した肝細胞癌患者21例を対象とし，脈管侵襲を伴う肝細胞癌に対する放射線療法の治療効果と予後について検討を行った．また，治療前後での食道胃静脈瘤・腹水等随伴所見の変化についても検討した．結果はMinor Response以上の奏効例が全体の21例中5例（23.8%）であった．また，門脈侵襲症例では15例中3例（20.0%）に奏効を得た．食道胃静脈瘤は10例中1例（10.0%）で改善，5例（50.0%）で悪化が見られた．また，治療前に腹水を認めた13例は全例で改善は見られなかった．放射線療法開始から死亡までの平均生存期間は242日（25∼949日）であった．放射線療法は肝細胞癌に対しての集学的治療の一つとして一部症例では効果の期待しうる治療法と考えられた．

症例は44歳男性．1992年12月よりC型慢性肝炎にて当科に通院していた．1993年，肝生検にて慢性活動性肝炎と診断し，Interferonα-2a 600万単位を6カ月間投与したが無効であった．腹部超音波検査にて経過を見ていたが，2003年1月に直径約35mm大の低エコー腫瘤を門脈・下大静脈間に認めた．悪性リンパ腫を疑い開腹術を勧めたが拒否されたため経過観察をしていたところ，1年後の2004年1月には直径14×26mmまで自然縮小していた．しかし，同年12月には最大径78mmまで増大し体表から触知可能となったため，超音波ガイド下腫瘍生検施行した．病理結果よりdiffuse large B cell lymphomaと診断した．2005年3月10日よりRituximab併用CHOP療法を開始し，腫瘍縮小を認めた．C型慢性肝炎では，肝門部リンパ節腫大は比較的高頻度に認められるが，悪性リンパ腫の発生も念頭に経過観察すべきと思われた．

To define the relationship between hepatitis viruses including GBV-C/HGV and lymphoproliferative disorders, we investigated the prevalence of HBV, HCV and GBV-C/HGV infection in patients with non-Hodgkin's lymphoma (NHL) and acute lymphocytic leukemia (ALL). A total of 43 subjects (26 males and 17 females, mean age 59.0 years old) consisting of 33 NHL and ten ALL patients were studied. All serum samples were tested for HBsAg, anti-HBc, HBV-DNA, anti-HCV, HCV-RNA and GBV-C/HGV-RNA. We compared these patients with two sets of control subjects. Control subjects (1) consisted of 45 age and sex matched subjects who underwent colonoscopy from July 1995 to June 1996, and control subjects (2) consisted of 10 599 subjects who received a general medical check-up in Toyama prefecture. HBsAg, anti-HBc and HBV-DNA were detected in the serum of 1/33 (3.0%), 15/33 (45.5%), and 0/33 (0%) of NHL patients, and 1/10 (10.0%), 5/10 (50.0%), and 1/10 (10.0%) of ALL patients, respectively. No significant differences were detected among each group compared with control subjects (1). Anti-HCV and HCV-RNA were detected in the serum of 4/33 (12.1%) NHL patients, but in none of the ten ALL patients. In contrast, none of the control subjects tested positive for both anti-HCV and HCV-RNA while 2/45 (4.4%) were positive for anti-HCV. Thus, the positive rate of HCV-RNA in NHL patients showed a tendency to be high compared with control subjects (1). GBV-C/HGV-RNA was not detected in the serum of lymphoproliferative disorders patients or control subjects (1). In NHL patients, the positive rate of anti-HCV was significantly higher than that of control subjects (2) ( P

The serum levels of pancreatitis-associated protein (PAP) were measured in 196 patients with digestive diseases and 15 healthy subjects by an enzyme-linked immunosorbent assay. The serum PAP levels were significantly elevated in the patients with gastric, colorectal, biliary tract, hepatocellular, or pancreatic cancers compared with the healthy subjects. After curative resection of the tumor, serum PAP levels were significantly decreased. The serum PAP levels were not related to clinicopathological factors except for the tumor size of pancreatic cancer. There were some cases of PAP-positive and carcinoembryonic antigen (CEA) or carbohydrate antigen (CA) 19-9 -negative gastric and colorectal cancers. The serum PAP levels were also significantly elevated in the patients with acute pancreatitis compared with those in not only the healthy subjects but also the patients with chronic pancreatitis. The peak PAP levels were significantly correlated with the severity of acute pancreatitis and reflected the clinical healing of the disease. The peak of serum PAP was significantly delayed compared with those of other pancreatic enzymes. These results suggest that the increase of serum PAP levels in patients with gastrointestinal cancers reflects an ectopic expression of PAP in cancer cells and that increased serum levels of PAP in acute pancreatitis are correlated with the disease severity and are prolonged than those of other pancreatic markers.

症例は45歳の男性. 1995年2月1日に慢性骨髄性白血病に対して同種骨髄移植を行い, 急性移植片対宿主病合併のため免疫抑制療法を受けていた. 症状は軽快し, 一時退院となったが, 6月22日 (移植後141日目) 肺炎を発症し再入院となった. 7月30日より前額部に水疱性皮疹 (皮膚生検で単純ヘルペス感染 (HSV) と診断) が出現した. このときALT2394IU/l, AST21031U/lとトランスアミナーゼの急上昇を示す肝障害を認め, 血小板数2.4万/μl, FDP61.3μg/dlとDICの合併も認めた. 8月5日, 肺炎の増悪による呼吸不全により死亡した. 剖検では, 肝小葉中心性に出血性凝固壊死を認め, HSV-2のポリクローナル抗体を用いた免疫染色からもHSV-2感染による肝障害と推察された. 免疫能の低下した宿主においては, HSV感染により重症肝炎を呈する場合があり留意すべきと考えられた.

症例は66歳, 女性. 平成8年4月, 右胸水の精査目的に初回入院. B型肝硬変による肝性胸水と診断, 利尿剤投与にて軽快した. その後, 胸水はコントロールされていたが, 平成9年11月より胸水の増量と呼吸困難の増悪があり平成10年2月に再入院. 入院後, 利尿剤, アルブミン製剤の投与を行うも胸水は難治性であった. そこでOK-432, 塩酸ミノサイクリンによる胸膜癒着術を繰り返し行ったが無効であり, その理由として腹腔より流入する腹水による癒着剤の希釈が考えられた. そこで胸腔・腹腔間の圧較差を減らし, 腹水流入を防ぐ目的で経鼻持続陽圧気道圧法を併用し胸膜癒着術を行ったところ効果がみられ, 胸水は改善した. 肝性胸水に対する胸膜癒着術は癒着剤の希釈のため無効の場合が多いとされるが, 近年, 睡眠時無呼吸症候群の治療に応用されている経鼻持続陽圧気道圧法の併用によりその奏効率が高まると思われた.

症例は34歳, 男性. 平成7年6月白血球増多症の精査のため当科初診. WBC 2, 3500/μl, Ph1染色体陽性であり慢性骨髄性白血病 (CML) と診断, 同年11月1日HLAの一致した38歳の姉より同種骨髄移植を施行した. 移植前の血液検査では, 患者はHBs抗原陽性, HBe抗体陽性, DNAポリメラーゼ陰性のHBVキャリアーで, ドナーはHBs抗体陽性, HBc抗体陽性でありHBVに対する免疫が成立していると考えられた. 移植後, ALTは36日目に134IU/lまで上昇し, 41日目にHBs抗原陰性, HBs抗体陽性となり以後ALTは一旦正常化した. その後移植片対宿主病の合併を認めたがCMLの再発はみられず平成9年3月までの15カ月間HBs抗原陰性, HBs抗体陽性の状態は持続した. 本症例ではドナーのHBVに対する免疫移行によりレシピエントにメジャーセロコンバージョンが起こったものと考えられた.

症例は, 15歳男児. 黄疸と食欲不振を主訴に入院し, 症状出現13日目に肝性昏睡II度となった. 肝障害の原因は不明で, 非A非B非C型劇症肝炎亜急性型と診断し血漿交換療法を1週間行うも改善せず肝性昏睡IV度へと進展した. 父親をdonorとする生体部分肝移植 (LRLTx) を施行したところ翌日には意識清明となり, 術後24日で肝機能値は正常化した. しかし, LRLTx後3カ月で汎血球減少が出現し骨髄生検にて再生不良性貧血と診断した. プレドニゾロン, cyclosporineやATGなどの投与は無効であり, 骨髄移植を施行し経過観察中である. 現在, 劇症肝炎に対する治療としてLRLTxが開始されたところであるが, 肝移植適応基準や移植後の予後・合併症などさまざまな問題が存在しており今後の症例の集積が必要と考えられた.

症例は26歳, 女性. 平成6年8月に第1子を妊娠. HBVスクリーニングではRPHA法にてHBs抗原陰性であった. 平成7年3月に第1子を出産. 平成8年1月, 母親に食欲低下が出現. AST 1, 573IU/l, ALT 2, 092IU/lと肝障害を指摘され入院となった. 入院時のウイルスマーカーはHBs抗原 (EIA法) 陽性, HBe抗原 (EIA法) 陰性, HBe抗体 (EIA法) 陽性. HBc抗体 (PHA法) は224と高値であり, HBV関連ポリメラーゼ活性 (RA法) は202cpmとHBVキャリアー状態であった. HBs抗原は4カ月間持続陽性であった. 第1子のHBVマーカーを調べたところHBs抗原 (EIA法) 陽性, HBe抗原 (EIA法) 陽性, HBe抗体 (EIA法) 陰性とキャリアー状態であった. HBs抗原陰性のキャリアーの存在が知られており, HBV母子感染防止事業においても輸血事業と同様にHBs抗原, HBc抗体測定の併用が必要と考え報告した.

The present study was undertaken to detect K‐ras oncogene point mutations at codon 12 in pure pancreatic juice (PPJ) by the hybridization protection assay (HPA) method for the diagnosis of pancreatic cancer (PC). This assay can be carried out within 30 min and can determine not only the presence of a mutation, but also the mutational type of K‐ras at codon 12. The minimal ratio of mutant DNA detectable by the HPA was 5–10% of the total DNA. PPJ was collected through a cannula under duodenal fiberscope control from 20 patients with PC and 20 patients with chronic pancreatitis (CP). Analysis of PPJ by the HPA revealed that the incidence of K‐ras point mutations at codon 12 was 55% (11/20) in patients with PC and 0% (0/20) in those with CP. Mutational types of K‐ras at codon 12 in PC were aspartic acid (Asp) in nine cases, both Asp and cysteine in one case, and arginine in one case. Analysis of K‐ras point mutations at codon 12 in PPJ using the HPA method seems promising as a new genetic test for the diagnosis of PC, because the HPA method is simple, and can easily determine the mutational type.

A 45-year-old woman was referred to us with complaint of sudden onset of continuous epigastralgia. She was alert and her blood pressure and pulse rate were in the normal range. Her symptom improved with rest. However, 2 hours later she died of hemorrhagic shock with elevation of abdominal pressure at the toilet. An autopsy revealed a rupture of splenic aneurysm-induced hemoperitoneum. The aneurysm, which was 25mm in diameter, was located in the hilum lienis. The ruptured arterial wall showed thinning of the tunica media, with disappearance of smooth muscle cells and elastic fibers.

We investigated the expressions of SLX, ST-439 and PLAP, which are regarded as having high specificity for cancer, in borderline lesions of the stomach to ascertain the significance of these potential markers in distinguishing between benign and malignant lesions. SLX, ST-439 and PLAP expressions in gastric biopsy specimens, from 73 patients with gastric lesions, were visualized using avidin-biotin-peroxidase. Although the prevalence of SLX in Group V was 90%. it was also high in intestinal metaplasia (40%) and adenoma (75%). The prevalences of ST-439 in intestinal metaplasia and adenoma grades l and 2 were 5, 23, and 17%. respectively. On the other hand, the prevalence of ST-439 was about 60% in adenoma grade 3 and in Groups IV and V. The prevalence and immunostaining range of ST-439 increased concomitantly with increasing grades of cytological and architectural atypia. The prevalence of PLAP in gastric biopsy materials was 30% overall, but was higher among the differentiated types. Moreover, PLAP was highly specific for cancer because of the negative immunostaining observed in benign lesions such as intestinal metaplasia and adenoma. These results suggest the following: 1) SLX is relatively non-specific for cancer and thus not useful in the pathological diagnosis of gastric lesions, and 2) borderline lesions with positive ST-439 mandate careful follow-up. Moreover, lesions with apparently extensive and intense ST-439 immunostaining may be gastric cancer and require urgent attention. Furthermore, 3) PLAP may provide additional diagnostic information useful for distinguishing between well-differentiated adenocarcinoma and borderline lesions including adenoma.

Biliary papillomatosis is a rare entity. A case of biliary papillomatosis associated with congenital choledochal cyst and intrahepatic gallstones is reported here. Percutaneous transhepatic cholangioscopy revealed multiple papillary lesions of the right intrahepatic duct and the common bile duct. Microscopically, the papillary mucosal lesion showed papillary proliferations of bile duct epithelial cells with mild atypia. Furthermore, a point mutation at codon 12 of the K-ras oncogene was found in the papillary lesion. To the best of our knowledge, this is the first case of biliary papillomatosis arising in congenital choledochal cyst. Although the pathogenesis of biliary papillomatosis in our case was unclear, biliary irritation associated with choledochal cyst may be related to biliary papillomatosis with point mutation at codon 12 of K-ras gene.

This study evaluated the diagnostic significance of concentrations of the cancer-associated carbohydrate antigen CA19-9 in pure pancreatic juice (PPJ) collected by endoscopic cannulation. We also attempted to elucidate the features and source of the increased CA19-9 concentration found in the pancreatic juice of patients with chronic pancreatitis (CP) by means of immunohistochemical staining. The mean output as well as the mean concentration of CA19-9 in each of the four fractions collected was highest in patients with pancreatic cancer (PC) and also was elevated significantly in patients with CP compared with controls. However, CA19-9 concentrations were not elevated in patients with cholecystolithiasis. When the cutoff value was set as the mean concentration + 2SD of the controls, significantly elevated concentrations of CA19-9 were found in the third fraction (secretory phase) in 90% of the patients with PC and 66% of the patients with CP. Immunohistochemical staining revealed that CA19-9 was expressed more widely in the ductal cells of CP tissues than in those of normal pancreatic (NP) tissues, with CP tissue showing more CA19-9-positive ductal cells per area than NP tissues. In NP tissue, CA19-9 was localized to the apical surface and supranuclear regions (apical type) in all the ductal cells stained by the antigen, while approximately 50% of cases with CP exhibited a cytoplasmic pattern showing a loss of polarity of the antigen expression. Moreover, this cellular localization pattern was more pronounced in the small ducts that had proliferated and aggregated following the destruction of lobules in CP.(ABSTRACT TRUNCATED AT 250 WORDS)

In order to elucidate the characteristics of reg-protein, which is identical to pancreatic stone protein (PSP/reg-protein), and the relationship between the generation and evolution of chronic pancreatitis and the expression of PSP/reg-protein in the pancreas, we investigated the expression of PSP/reg-protein in normal and diseased human pancreatic tissues by immunohistochemistry. The PSP/reg-protein was expressed in all cases with normal pancreas or chronic pancreatitis, and in 70.6% of cases with pancreatic cancer. This protein was present in the cytoplasm of acinar cells and, in some cases, in the intraluminal contents of ductules in nonmalignant tissues. From the view of distribution and cellular localization, PSP/reg-protein was expressed more broadly and densely in chronic pancreatitis with mild to moderate injury than in the normal pancreas. However, the protein was less expressed in severely damaged chronic pancreatitis tissue, such as calcifying pancreatitis, than in the normal pancreas. These findings suggest that mild to moderate injury to pancreatic tissue may stimulate the synthesis of PSP/reg-protein, whereas more severe injury tends to depress it.

Pancreatic cancer is detected on the basis of morphological changes delineated by means of various image-diagnostic methods. However, differentiation between chronic pancreatitis and pancreatic cancer, especially at the early stage, is not always simple when based upon the morphological changes alone. Therefore, we attempted to elucidate K-ras mutations in the sediment of pure pancreatic juice (PPJ) containing exfoliated ductal pancreatic cancer cells. PPJ was collected endoscopically from 20 patients with pancreatic cancer (PC) and 18 patients with chronic pancreatitis (CP). Polymerase chain reaction and allele specific oligonucleotide dot blot hybridization for K-ras mutations were performed with the DNA extracted from these samples. A K-ras mutation at codon 12 was identified in the PPJ of 11/20 (55%) of the patients with PC. On the other hand, the same mutation was not identified in the PPJ of any patient with CP. Moreover, K-ras mutations at codons 13 and 61 were not recognized in the PPJ of any patient with either PC or CP. These findings suggested that the presence of a K-ras mutation at codon 12 in PPJ would be useful in confirming the diagnosis of PC.

This study was undertaken to assess the diagnostic significance of the colon mucus test (CMT) by which the cancer-associated carbohydrate antigen, β-D-Gal (1 - 3)-D-GalNAc (T antigen) is measured in rectal mucus, chiefly in patients with various alimentary tract diseases. The incidence of a positive CMT was relatively high in colorectal cancer (69%) and gastric cancer (40%), and was similarly high in some benign colorectal diseases such as colonic diverticulum (42%) and colonic polyps (39%), and in gastric polyps (75%). On the other hand, the incidence of a positive CMT in other benign diseases or in healthy controls was less than 10%. A positive CMT was significantly more common in colorectal disease and in gastric tumors (cancer and polyps) than in the other diseases (p < 0.001). Of 28 colonic polyp patients, 20 (71%) had negative fecal occult blood test results (FOBT), and nine of them (45%) had positive CMT results. These results suggest that the CMT may be a useful screening test for alimentary tract disease, particularly colorectal disease and gastric tumors, although its specificity for colorectal cancer is only moderate. Furthermore, a combination assay using FOBT plus CMT may help to improve the diagnostic rate.

Serum levels of sialyl-Tn antigen (STN) were measured using a one-step radioimmunoassay kit in 257 patients with digestive cancers, 121 patients with benign digestive diseases, and in 64 healthy controls. With 45 U/ml regarded as the cutoff value, the positive rates of serum STN in digestive cancers were as follows: pancreas 40.0%, stomach 28.1, colon and rectum 27.8, biliary tract 25.0, liver 7.1, and esophagus 0%. In benign digestive diseases, the positive rate of STN was low (4.1%). In gastric and colorectal cancers, simultaneous measurements of STN and carcinoembryonic antigen (CEA) revealed that the positive rates of STN, CEA, and STN and/or CEA were 28, 42, and 55%, respectively. There was no significant correlation between STN and CEA in these cancers. STN may be a useful serum marker for digestive cancers, especially gastric and colorectal cancers.

This study was undertaken to elucidate the diagnostic significance of the measurement of a cancer-associated carbohydrate antigen, NCC-ST-439 (ST-439), in pure pancreatic juice collected by endoscopic cannulation, chiefly from patients with pancreatic diseases. The mean concentrations of ST-439 in each of the 4 fractions collected were significantly higher in patients with pancreatic cancer than in controls, but patients with chronic pancreatitis or cholecystolithiasis did not have higher levels. Similarly, a significant increase in the mean output of ST-439 was observed only in patients with pancreatic cancer. When the cut-of value was set at the mean concentration+ 2 X the standard deviations of the controls, significant concentrations of ST-439 were found, in the first fraction (washout phase) in 56% of the pancreatic cancer cases, 31% of the chronic pancreatitis cases and 0% of the cholecystolithiasis cases; in the third fraction (secretory phase) results were 50%, 7% and 0%, respectively. Furthermore, when the cut-of value was set at the highest concentration found among patients with chronic pancreatitis (to enhance the specificity for pancreatic cancer), the prevalence of significant ST-339 levels among Pancreatic cancer patients was 50% in the first fraction and 44% in the third fraction. These results indicate that the measurement of ST-439 in pancreatic juice is useful as a specific marker for pancreatic cancer, although its sensitivity is less than was initially hoped

Serum levels of tumor-associated glycoprotein (TAG-72) were measured using a two-step sandwich radioimmunoassay kit in 281 patients with digestive cancers and 135 patients with benign digestive diseases. The positive rates of TAG-72 with the cut-off values of 2.2 and 4.0 U/ml were high in pancreatobiliary (56%, 38%), gastric (49%, 37%) and colorectal (62%, 29%) cancers, while the false-positive rate in benign diseases was 11%, 0.7% respectively. Very high levels were found in patients with advanced cancer. TAG-72 was positive in 17 (greater than 2.2 U/ml) and 7 (greater than 4.0 U/ml) out of 60 CEA-negative patients, and in 7 (greater than 2.2 U/ml) and 3 (greater than 4.0 U/ml) out of 17 CA19-9-negative patients. TAG-72 might be a useful serum marker for digestive cancers, especially gastric and colorectal cancers.

We reviewed the clinical features and clinical course of patients with duct-narrowing chronic pancreatitis who were negative for immunoserologic test results (n = 16) in comparison with the findings for serological test-positive patients (n = 20) in order to determine an adequate treatment for those who had typical morphology of autoimmune pancreatitis in the absence of immunoserologic abnormality. No significant differences were found between the two groups of patients in clinical profiles including associated autoimmune-related diseases, pancreatic histology, and response to steroid therapy. Of the seronegative patients, eight who showed an improvement in narrowing of the main pancreatic duct with steroid therapy and three who did no show an improvement or who relapsed after surgical resection without this therapy had stenosis of the common bile duct with increased levels of serum hepatobiliary enzymes, except for two patients with affected sites limited to the body or tail of the gland. For the remaining five patients, who showed an improvement in pancreatic duct changes or long-term remission after surgery without steroid administration, normal biochemistry test results for liver functions were obtained, with no abnormal cholangiographic findings in the three patients examined. Duct-narrowing chronic pancreatitis without immunoserologic abnormality overlaps in clinical features with that fulfilling the immunoserologic criteria for a diagnosis of autoimmune pancreatitis. In particular, the disease with bile duct involvement should be treated clinically as autoimmune pancreatitis, for which steroid therapy is recommended, even if an autoimmune mechanism is not demonstrated serologically.

Introduction Main pancreatic duct (MPD)-narrowed chronic pancreatitis (CP) may be an autoimmune abnormality. It also has been called autoimmune pancreatitis and sclerosing pancreatitis. It is unclear whether cases with focal pancreatographic changes are part of the same clinical entity as cases with diffuse MPD changes. Aim and methodology We reviewed seven cases of chronic pancreatitis (CP) with focal narrowing of the main pancreatic duct (MPD), evidenced by endoscopic retrograde cholangiopancreatography (ERCP), and swelling of one or two segments of the pancreas, evidenced by ultrasonography (US) /computed tomography (CT), and indicated the clinicopathologic features of focal-type MPD-narrowed CP. Results The patient group comprised six men and one woman, and their age range was 28-75 years, with a mean of 63.7 years. Affected sites were in the head in two patients, the body in one patient, the tail in one patient, and the body and tail in three patients; ERP showed narrowing in six patients and obstruction in one. Stricture of the lower portion of the common bile duct (CBD) that caused obstructive jaundice was shown by ERC in two cases in which the pancreas head was affected. In all six patients, a dynamic study by CT or MRI homogeneously showed delayed enhancement of involved segments of the pancreas. Serum levels of pancreatic enzyme were elevated in five patients, but only one subject had pancreatitis-like epigastric pain. Serological evidence suggestive of autoimmune abnormality was detected in only three patients with hypergammaglobulinemia (> or =2.0 g/dL) or positive titers of antinuclear antibody (ANA; > or =80). Histological assessment was available for five patients, who characteristically had dense lymphocytic or plasmocytic infiltration with severe fibrosis that caused luminal narrowing. The clinical, serologic, and histologic findings as described above were comparable to those for 12 CP patients with diffuse narrowing of the MPD, diagnosed during the same period. Surgical resection was performed in 5 patients, in 2 of whom a similar inflammatory process recurred in the remnant head of the pancreas, whereas pancreatitis no longer developed in the other 3 patients. One patient was initially treated with steroids, with clinical remission, although there was neither hypergammaglobulinemia nor positive ANA. Conclusion These results indicate that CP with focal narrowing of the MPD is part of the same clinical spectrum as CP with diffuse narrowing of the MPD, and whether the distribution is diffuse or focal seems to be related to the stage or the extent of the disease. It is therefore important to recognize the possible existence of this focal variant to avoid unnecessary surgery.

The aim of this study was to assess the imaging findings of pathologically proven intraductal papillary-mucinous tumors of the pancreas and the natural history of follow-up cases, and to optimize the therapeutic management of patients with these tumors according to their imaging findings. All nine patients with main duct type tumors were histologically diagnosed as having adenocarcinoma or adenoma, with no hyperplastic lesion. The images failed to discriminate between the two histologic types. In 26 patients with branch duct type tumors, all but one with intraductal mural nodules or tumors ofor = 30 mm had adenocarcinoma or adenoma, regardless of the caliber of the main duct. Of the nine patients with tumors30 mm and no mural nodules. three had adenoma, and six had hyperplasia. All of four patients had hyperplasia, with the additional caliber of the main duct being6 mm. In a series of 23 cases in which the patient was followed-up, no apparent progression was found in 17 patients who had no mural nodules and tumors of30 mm. Given these results, patients with main duct type tumors, and those with branch duct type tumors showing mural nodules or a tumor diameter ofor = 30 mm, are at high risk of developing neoplasms, including adenocarcinoma, for which surgical resection should be considered, whereas those patients with tumors30 mm and no mural nodules can be followed.

The purpose of this study was to examine the correlations among enhancement of apoptosis, cell proliferation and expression of oncogenes in gastric carcinomas induced by preoperative oral administration of 5-fluorouracil (5-FU). The occurrence of spontaneous apoptotic cell death in 42 patients with gastric carcinoma was analyzed in the biopsy specimens preoperatively. p53 status was examined by polymerase chain reaction-single strand confirmation polymorphism and sequencing. Fourteen patients received oral administration of 5-FU at 300 mg/body/day for 7 days preoperatively. For detection of apoptotic cells, apoptotic incidences (AIs) were examined by the terminal deoxynucleotidyl transferase-mediated deoxy-uridine triphosphate biotin nick end labeling method, on gastric carcinoma lesions based on the endoscopic findings before administration in the biopsy and resected tissues. Expressions of p53, Bcl-2, Bax gene and proliferating cell nuclear antigen (PCNA) were also examined by immunohistochemical staining. On preoperative biopsy, p53 point mutation was observed in 14 of the 42 tumors. The immunohistochemical staining status and point mutation of p53 gene (positive or negative) were identical in 32 of the 42 tumors (76.2%). The average AIs of the biopsy specimens were 1.58+/-1.26% on p53-negative staining (n=19) and 1.14+/-1.02% on p53-positive staining (n=23), a significant association was not recognized between p53 expression and AI. In the preoperative administration group, the PCNA labeling index was significantly higher in the biopsy specimens than in the resected tissues (43. 6+/-12.8% vs. 35.3+/-8.8%, p

The present study was undertaken to detect K-ras point mutations at codon 12 in pure pancreatic juice (PPJ) for the diagnosis of pancreatic cancer (PC) using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. PPJ was collected through a cannula under a duodenal fiberscope from 26 patients with PC and 32 patients with chronic pancreatitis (CP). DNA was extracted from PPJ and was used as the template for PCR. Analysis of PPJ by PCR-RFLP with BstNI revealed that the incidence of K-ras point mutations at codon 12 was 81% (21/26) in patients with PC and 6% (2/32) in those with CP. With reference to the location of PC, the incidence of K-ras mutations was 79% (11/14) in the head, 86% (6/7) in the body, and 80% (4/5) in the tail of the pancreas. The incidence of K-ras mutants was 50% (1/2) in tumor size I (TS 1 ; ≤2.0 cm in size), 71% (5/7) in TS 2 (2.1 to ≤4.0 cm), 89% (8/9) in TS 3 (4.1 to ≤6.0 cm), and 88% (7/8) in TS 4 (>6.1 cm). These results suggested that analysis of K-ras point mutations at codon 12 in PPJ using the PCR-RFLP method is a promising new genetic test for the diagnosis of PC.

An enzyme-linked immunosorbent assay, based on two monoclonal antibodies (Hreg1-1 and Hreg101-1) specific for pancreatic stone protein (PSP)/reg-protein, was developed to determine the concentration of this protein in serum from individuals with various diseases. The serum concentration of PSP/reg-protein was significantly higher in patients with various pancreatic diseases than in normal controls, and was also significantly higher in patients with acute pancreatitis or chronic relapsing pancreatitis than in patients with chronic pancreatitis. Furthermore, the serum PSP/reg-protein concentration was also significantly increased in liver cirrhosis, choledocholithiasis, and various cancers of the digestive system, and was extremely high in all patients tested with chronic renal failure. A significant correlation was apparent between the serum concentration of PSP/reg-protein and elastase-I in 68 patients with chronic pancreatitis or pancreatic cancer. Whereas only 7 of these patients showed a normal serum PSP/reg-protein concentration and a significantly increased elastase-I concentration, 15 of these patients showed a significantly increased serum PSP/reg-protein coecentration and a normal serum elastase-1 concentration. These results indicate that the serum PSP/reg-protein concentration may reflect pancreatic damage, especially in acute pancreatitis, and may be as sensitive a marker for such damage as elastase-I, although false positivity was apparent in renal failure and in some patients with hepatic dysfunction or digestive system malignancies.

The diagnostic significance of measuring sialylated stage-specific embryonic antigen-1 (SLX) in pure pancreatic juice was evaluated in 20 patients with pancreatic cancer, 43 with chronic pancreatitis, 13 with cholecystolithiasis, and 15 control individuals. Four fractions of pure pancreatic juice were collected sequentially from the pancreatic duct by endoscopic cannulation. The SLX levels in all four fractions of pure pancreatic juice were significantly higher in patients with pancreatic cancer than in controls. On the other hand, patients with chronic pancreatitis or cholecystolithiasis did not have SLX levels that significantly differed from those of controls in any fraction. When the cut-off value was set as the mean concentration + 2 times the standard deviation of the control values, the positive rates of SLX in the first fraction (washout phase) and the third fraction (secretory phase) of pure pancreatic juice from pancreatic cancer were 55% (11/20) and 40% (8/20), respectively. Although the false positive rates in the first fraction were high in chronic pancreatitis (30%) and cholecystolithiasis (31%), such high SLX levels in the third fraction were found only in one (2%) patient with chronic pancreatitis and in one (8%) with cholecystolithiasis. The specificities of the test for pancreatic cancer in the first fraction and the third fraction were 70% (39/56) and 96% (54/56), respectively. These results indicate that the measurement of SLX in the third fraction of pure pancreatic juice is useful as a specific marker for pancreatic cancer.

Summary The expression of six sialylated carbohydrate antigens (CA19–9, CA-SO, SLEX, SLX, DU-PAN-2, ST-439) was examined in malignant and nonmalignant pancreatic tissues using an immunohistochemical method to elucidate the characteristics of these carbohydrate antigens as tumor markers. All carbohydrate antigens except for sialyl SSEA-I (SLX, 52.4%) were expressed in more than 80% of the pancreatic cancer. CA19–9 and CA-50, belonging to type I blood group antigens, and DU-PAN-2 and ST-439 were localized predominantly in the cytoplasm of cancer cells, while sialyl Lex (SLEX) and SLX, belonging to type II blood group antigens, were stained mainly on the apical membranes of malignant glands. Although type I antigens were expressed in most nonmalignant pancreatic tissues, the type II antigens and ST-439 were absent in almost all of the normal tissues and faintly expressed in few chronic pancreatitis tissues, suggesting the high tumor specificity of these antigens. Each antigen was expressed on the apical surface of ducts in normal pancreas. However, in about 30% of chronic pancreatitis cases, type I antigens and DU-PAN-2 were observed in the cytoplasm of ductal cells. All patients showing stromal stain, possibly caused by loss of antigen polar expression and shedding into the surrounding stroma adjacent to malignant glands, revealed high levels of serum antigen. This finding suggests that the stromal appearance of antigens is a significant factor in the elevation of serum antigen levels.

The authors developed monoclonal antibodies (MoAb) against human placental alkaline phosphatase (PLAP). Four specific MoAb reacting only with PLAP and two nonspecific MoAb reacting equally with isozymes of alkaline phosphatase (hepatic, intestinal, and placental) were obtained. Immunohistochemical staining with the specific MoAb showed that the cell membrane and cytoplasm of cancer cells were stained in gastric and colorectal carcinoma. The incidence of PLAP positivity was 23% (25 of 107) of all gastric carcinomas. Among gastric carcinomas, the 42% (13 of 31) positivity of highly differentiated carcinoma (papillary adenocarcinoma and well-differentiated tubular adenocarcinoma) was a significantly higher rate than that found in poorly differentiated carcinoma (poorly differentiated adenocarcinoma and signet-ring cell carcinoma, five of 41, 12%). The incidence of PLAP positivity was 11% (four of 35) in colorectal carcinoma. In contrast, gastric adenoma, intestinal metaplasia, and noncancerous tissue adjacent to cancer did not show staining. These results indicated that expression of PLAP was apt to occur in more highly differentiated gastric carcinoma and was highly specific for carcinoma in the gastrointestinal tract, although its incidence was not high.

In order to elucidate the factors affecting the serum levels of CA 19-9, we analyzed sera of 79 patients with pancreatic cancer and 169 with non-malignant diseases, chiefly consisting of hepatobiliary and pancreatic diseases. Serum CA 19-9 values in patients with pancreatic cancer had no relation to the location of the tumor or presence of jaundice. Similarly, no tendency was observed as to the location and size of tumor or to the grade of differentiation in 12 CA 19-9-negative patients with pancreatic cancer. Serum levels of CA 19-9 in patients with cholelithiasis complicated by cholangitis frequently showed markedly high values, but then rapidly normalized in parallel with the subsiding of inflammation. The behaviour of serum CA 19-9 showed little relation to renal or hepatic failures or to intrahepatic cholestasis. However, slightly elevated levels of the antigen were found in more than half of those patients with fulminant hepatitis showing massive necrosis. In chronic pancreatitis, the prevalence was only 8%; however, an increase was observed at the time of exacerbation in 2 of 5 positive patients. There was hardly any increase in serum levels of CA 19-9 after endoscopic retrograde cholangiopancreatography (ERCP), although serum levels of pancreatic enzymes rose after ERCP in almost all patients. Thus, it appears that CA 19-9 does not easily escape into the bloodstream, unlike pancreatic enzymes.