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We examined amplification of the c-met, c-erbB-2, and epidermal growth factor receptor (EGFR) gene in the patients with primary gastric cancer, and compared the data with clinical features in order to clarify the relationship between oncogenic abnormality and clinical features. Oncogene amplifications were examined by slot blot hybridization using DNAs extracted from formalin-fixed and paraffin-embedded tissues of primary gastric cancers. Seven of the seventy cancers (10.0%) had c-met gene amplification, nine (12.9%) had c-erbB-2 gene amplification, and six (8.6%) had EGFR gene amplification, respectively. Eighteen cases (25.7%) exhibited one or multiple oncogene amplification, and two cases (2.9%) exhibited simultaneous amplification of the three genes. The cases with c-met gene amplification tend to show invasive character and were related to peritoneal dissemination. The cases with c-erbB-2 gene amplification were related to lymph node metastasis. The cases with EGFR gene amplification had large tumors and were in highly advanced stage. The survival rate in patients with oncogene amplification was significantly lower than that in patients without amplification. Our data indicated that these genes were related to growth and metastasis of gastric cancer. Furthermore, this study about the three genes suggested that the type of activated gene might decide on the type of metastasis and clinical features.

Endocrine tumor of the pancreas is potentially malignant. A multicenter analysis of these tumors was conducted to clarity the present status of their surgical management and the subsequent long-term surgical results. The Japan pancreatoduodenectomy (JPD) study group carried out the study; 368 patients were enrolled and variables related to tumor characteristics, surgery, and survival were retrospectively analyzed. There were 222 patients with functioning tumor and 143 patients with nonfunctioning tumor. Malignant tumor was found in 140 of 368 (38%) of the patients, and 63/140 (45%) of these patients had metastatic lesion; the most common site of the metastasis was liver 34/136 (25%), followed by regional lymph nodes 26/136 (19%). Pancreatic resection was performed in 91% of patients with nonfunctional tumor and in 83% of those with malignant tumor, and 73% of the pancreatic resections were done with lymph node dissection. The overall 5-year actuarial survival rate was 76% in patients with malignant tumor. The actuarial 5-year survival rate was 93% in the patients without metastasis and 83% in patients who received curative resection. Multivariate analysis showed that the presence or absence of synchronous metastasis was the sole significant prognostic factor. The results suggest that: (i) malignant endocrine tumor of the pancreas is a curable malignancy when pancreatic resection with lymph node dissection is adopted and (ii) that synchronous metastasis is the dominant prognostic factor.

Background . Nodal status is one of the most important prognostic factors for carcinoma of the papilla of Vater. The pattern of lymphatic spread and mode of recurrence were analyzed by determining the frequency of nodal involvement and antemortem and postmortem examination of patients with recurrent disease. Methods . From 1974 to 1994, 36 patients with carcinoma of papilla of Vater underwent pancreatectomy at the Kanazawa University Hospital. A precise evaluation of the nodal involvement was determined by means of careful pathologic review of the extended lymphadenectomy specimen. The mode of recurrence was determined by use of autopsy and radiographic examinations. Results . Fifteen (42%) of 36 patients had nodal involvement. The lymph nodes with the highest metastatic rates were the inferior pancreaticoduodenal lymph nodes (number 13b) and the superior mesenteric lymph nodes (number 14) (13b, 31%; 14, 17%). There were no metastases in the perigastric lymph nodes. A significant relationship existed between the gross appearance of the primary tumor and nodal involvement (protruding, 22%; mixed type, 42%; ulcerative, 100%). The 5-year survival rates were 74% in the absence of nodal metastasis versus 31% with nodal metastasis. The 5-year survival rates for patients with protruding, mixed type, and ulcerative tumors were 75%, 49%, and 17%, respectively. Survival and recurrence were significantly correlated to gross appearance and nodal involvement. Retroperitoneal recurrence and liver metastasis were main modes of recurrence. Conclusions . Lymph node 13b is important in lymphatic metastasis to the superior mesenteric lymph nodes for carcinoma of papilla of Vater. Nodal dissection around the superior mesenteric artery is needed to improve the prognosis of carcinoma of papilla of Vater except in the nonexposed protruding tumor. Pylorus-preserving pancreatoduodenectomy may be indicated in patients with carcinoma of the papula of Vater.

The purpose of this study was to determine whether section of the celiac branch of the vagus nerve in man affects the insulin response to intravenous glucagon injection. Patients who received a subtotal gastrectomy with lymph node dissection for gastric carcinoma were divided into two groups: the celiac-preserved group (n = 16) and the celiac-sectioned group (n = 13). The hepatic branches of the vagus were preserved in both groups. The glucagon test was performed twice in each patient during the operation; before and after manipulation of the celiac branch. Blood samples were collected just before and 6 min after the injection. No difference in the mean increases in blood glucose, insulin and C-peptide levels were seen between the two groups before the nerve manipulation. In the celiac-preserved group, the glucagon stimulated glucose-related C-peptide ratio (x 10(-3) was 0.5 +/- 0.7 before the nerve manipulation and 3.5 +/- 3.0 after it, a significant difference (p < 0.01). In the celiac-sectioned group, this increase was not observed, the ratio was 0.7 +/- 0.6 before the nerve manipulation and 0.8 +/- 3.4 after. These results indicate that the vagal celiac branch in man may also be involved in the control of pancreatic insulin release.

Interleukin (IL) 6 is one of major mediators of inflammation, and IL-6 gene activation during hypoxia/reoxygenation has been implicated in the pathogenesis of ischemia/reperfusion injury. However, molecular events involved in IL-6 gene expression during hypoxia/reoxygenation remain to be identified. We have previously shown that NF-kappa B plays an essential and indispensable role in the transcriptional activation of the IL-6 gene induced by various stimuli, including IL-1 and tumor necrosis factor-alpha. We show here that hypoxia, but not reoxygenation, induces the activation of NF-kappa B through the degradation of a major inhibitor of NF-kappa B, I kappa B alpha. This hypoxia-induced NF-kappa B activation resulted in the kappa B-dependent transcriptional activation of the IL-6 gene. Interestingly, the time course of hypoxia-induced NF-kappa B activation was rather slow as compared with those of NF-kappa B activation induced by other stimuli, such as IL-1: a significant NF-kappa B activation was not observed before 1 hr of hypoxia treatment and persisted for up to 7 hr of hypoxia treatment. However, hypoxia-induced NF-kappa B activation was not inhibited by cycloheximide, which indicates that hypoxia directly triggers NF-kappa B activation. Furthermore, while hypoxia is unlikely to generate reactive oxygen intermediates, pretreatment of cells with antioxidants such as N-acetyl cysteine and alpha-tocopherol inhibited NF-kappa B activation induced by hypoxia. Thus, we discuss possible implications of these results for a postulated role of reactive oxygen intermediates in NF-kappa B activation.

BACKGROUND Lymph node status and neural plexus invasion are the most important prognostic factors that may be amenable to surgery for carcinoma of the body and tail of the pancreas. The pattern of lymphatic spread and neural plexus invasion were evaluated by analysis of various clinicopathologic factors. METHODS Twenty patients with carcinoma of the body and tail of the pancreas underwent pancreatectomy with systemic regional lymph node dissection at Kanazawa University Hospital. A precise evaluation of their lymph node involvement and neural plexus invasion was determined. RESULTS Sixteen of 20 patients (80%) had lymph node involvement. The lymph nodes with a high metastatic rate were those along the splenic artery (50%), the inferior body lymph nodes (35%), the lymph nodes around the common hepatic artery (25%), and the paraaortic lymph nodes (20%). There was no relationship between tumor size, histologic type, and lymph node involvement. Plexus invasion was observed in 14 patients (70%). The most frequent site was the splenic plexus, but between 15% and 20% of the patients had celiac or superior mesenteric plexus invasion. There was no relationship between tumor size, histologic type, and neural plexus invasion. CONCLUSIONS Based on these results, extended lymphadenectomy including the paraaortic lymph nodes, celiac lymph nodes, and superior mesenteric lymph nodes may improve the prognosis for patients with carcinoma of the body and tail of the pancreas. Extrapancreatic neural plexus dissection, especially of the celiac plexus and superior mesenteric plexus, also is necessary. Cancer 1996; 78:2485-91.

The diagnosis of axillary (AX) metastases remains a challenge in the management of breast cancer and is a subject of controversy. Clinical node staging clearly is limited in the assessment of AX lymph nodes. AX mammography, ultrasonography, and computed tomography (CT) do not provide histologic information. Although nuclear magnetic resonance imaging may have considerable value in the diagnosis of AX metastases, it does not detect micrometastases. The use of biologic markers in the assessment of AX metastases remains a subject of investigation. On the other hand, biopsy of selected AX nodes or tissue with examination of histology or cytology generally would not identify a significant percentage of patients with AX node involvement. Sentinel lymph node biopsy, however, might be potentially useful for assessing AX metastases, although it remains investigational. In order to simplify diagnosis and reduce morbidity and mortality, alternatives to AX dissection must be sought and imaging and staging modalities refined. We present a review of the literature pertaining to the diagnosis of AX metastases in patients with breast cancer and a discussion of some current areas of controversy.

Although breast-conserving therapy (BCT) is an accepted alternative for the treatment of breast cancer, numerous controversies surround the selection criteria and the treatment details. A review of the literature revealed that patient selection is of critical importance. However, there is disagreement over the relative importance of some of the criteria for patient selection. A wide excision is preferable to a less complete excision (tumorectomy) or a more radical excision (quadrantectomy). Accurate assessment of surgical margins is important. The risk of local recurrence may be diminished if a re-excision is performed to obtain tumor-free margins. However, the suitability and practicality of the techniques used to assess the resection margins have been questioned. Radiotherapy is an integral part of BCT. Surgery alone remains an investigational approach. Axillary dissection remains a reliable method of assessing nodal status and treating regional disease.

The diagnostic value of intraoperative histologic examination of frozen sections of axillary lymph nodes was investigated in 243 patients with operable breast cancer. One to six hard or enlarged axillary nodes were sampled from the axillary pad which was derived from a partial axillary dissection (including level 1 and 2 nodes). Half of these nodes were histologically examined using frozen sections during surgery. After a total axillary dissection, both the axillary nodes in the partial axillary dissection and the nodes dissected at level 3 were histologically examined on permanent section. A mean of four nodes were sampled (range: 1 to 6). Axillary dissection yielded a mean of 22 nodes (range: 6 to 60). Axillary sampling detected the presence of metastases in 65 of 84 (77%) patients with positive axillary lymph nodes. In the patients in whom the axillary involvement was not identified by axillary sampling, however, the extent of axillary involvement was limited to levels 1 and 2. Therefore, a partial axillary dissection may be justified for patients in whom axillary involvement is not found on frozen section of nodes from axillary sampling, whereas a total axillary dissection should be performed for patients in whom axillary involvement is found by these procedures.

金沢大学がん研究所がん分子細胞制御, FK506 is a powerful immunosuppressive drug currently in use that inhibits the activation of several transcription factors (nuclear factor (NF)-AT and NF-κB) critical for T cell activation. We show here that, contrary to the situation in T cells, FK506 activates transcription factor NF-κB in non-lymphoid cells such as fibroblasts and renal mesangial cells. We further show that FK506 induces NF-κB-regulated IL-6 production in vitro and in vivo, in particular in kidney. IL-6 has been shown previously to produce renal abnormalities in vivo, such as mesangioproliferative glomerulonephritis. Similar renal abnormalities were also observed in FK506-treated animals. These results thus suggest a causal relationship between FK506-induced NF-κB activation/IL-6 production and some of FK506-induced renal abnormalities.

Background. The most common cause of noncurative resection and recurrence in gastric cancer is peritoneal seeding. However, the results of treatment of peritoneal dissemination with chemotherapy have been poor with 5-year survival rates of 0%. Methods. A new in vitro thermochemosensitivity test was performed on gastric cancer cells obtained from 19 surgically resected specimens by using tetrazolium-based colorimetric assay (MTT assay). A novel treatment of the intraoperative chemohyperthermia was undertaken in 83 patients with gastric cancer with peritoneal dissemination. After aggressive resection of primary tumor, lymph nodes, and peritoneal metastases, warmed saline solution containing mitomycin C 30 mg, etoposide 150 mg, and cisplatin 300 mg was introduced into the peritoneal cavity via a closed circuit continuous hyperthermic peritoneal perfusion (CHPP) for 60 minutes to keep the abdominal temperature at 42° to 43° C by means of a heat exhange mechanism. Results. The in vitro thermochemosensitivity test showed that 43° C enhanced the cytotoxic effects on gastric cancer cells under clinically achievable drug concentrations. During CHPP, drug concentrations of cisplatin, mitomycin C, and etoposide in the perfusate remained statistically higher than in the peripheral venous circulation. Among 43 evaluable patients with residual peritoneal seeding, eight (19%) and nine (21%) exhibited complete response and partial response, respectively. The overall 1- and 5-year survival rates were 43% and 11%, respectively. Patients who underwent complete resection survived significantly longer than those with residual disease, and those with complete response had a significantly better prognosis than did those with partial response or nonresponders. One-year survival rates of patients with complete response, partial response, and nonresponders were 88%, 27%, and 22%, respectively. Five patients survived longer than 5 years. Conclusions. Our triple treatment combining surgery and CHPP is an effective therapy for selected patients with gastric cancer with peritoneal dissemination.

Regional lymph node metastasis is a critical prognostic factor in gastric cancer, and extended lymph node dissection and routine microscopic examination of all resected nodes could potentially provide accurate information regarding lymph node status. On the other hand, the therapeutic value of extended lymph node dissection is controversial. While retrospective and prospective nonrandomized comparative studies have shown that extended lymph node dissection significantly improves the survival rate, two prospective randomized trials have failed to demonstrate the efficacy of extended dissection, although the number of patients in these studies was limited. There is a further, ongoing, trial involving a larger series of patients; the final results of this study should help to determine whether extended lymph node dissection is of therapeutic or merely prognostic value in gastric cancer.

膵頭部領域癌133例 (膵頭部癌70例, 下部胆管癌31例, 乳頭部癌32例) の再発・浸潤様式を検索し, 上腸間膜動脈神経叢一部温存郭清の可能性について検討した. リンパ節転移は膵頭部癌の79%, 下部胆管癌の67%, 乳頭部癌の44%に, 神経叢浸潤はそれぞれ60%, 26%, 3%に認められた. 神経叢浸潤部位は膵頭部癌ではPL.phIIが, 下部胆管癌ではPL.phIが多かった. また, No.14リンパ節転移率はそれぞれ34%, 32%, 16%, No.16転移率はそれぞれ19%, 6%, 0%であった. 再発形式を膵頭部癌肉眼治癒再発確認40例でみると, リンパ節再発, 後腹膜局所再発が88%にみられた. 下部胆管癌治癒再発6例では全例に後腹膜再発がみられ, 膵臓浸潤の強いものが多かった. 以上より, 膵頭部癌では上腸間膜動脈神経叢とNo.14, No.16リンパ節郭清を行うことが重要であり, 膵臓浸潤をみない下部胆管癌や乳頭部癌では上腸間膜動脈神経叢を一部温存したNo.14リンパ節郭清が可能であると考えられた.

膵頭部癌痛における根治手術について神経浸潤を中心に述べた. 病理組織学的検索をもとに1973年より郭清範囲を広げ, 1977年にはtranslateral retroperitoneal approachによる膵頭部癌の拡大手術を開発した. 膵癌根治手術のうえで重要な神経浸潤の成立機序ならびに進展様式, 神経浸潤と臨床病理学的諸因子との関連に加え, 膵後方浸潤の詳細な検索結果について述べた. 膵後方浸潤の3次元解析によると, 浸潤様式は浸潤方向による差異がみられることが明らかになるとともに, とくに神経浸潤は上腸間膜動脈方向に強くみられることが判明した. また, 正常例における上腸間膜動脈周囲組織構造検索結果より, 神経叢温存リンパ節郭清の可能性についても述べたが, 現時点では膵癌の根治手術という点からは神経叢完全切除は不可欠な要因であることを強調した.

各種膵腸吻合法とその合併症ならびに腹腔内持続吸引ドレナージ法 (continuous intraabdominal suction drainage: CISD) の有用性について膵腸吻合143例 (膵頭部癌66例, 胆管癌40例, 乳頭部癌32例, 胆嚢癌5例) を対象に検討した. 膵嵌入 (I) 法が20例, 漿膜筋層切開膵管挿入 (II) 法が22例, 非切開膵管挿入 (III) 法が48例, 膵管空腸吻合 (IV) 法が53例であった. 膵液漏出はI, II, III, IV法でそれぞれ20%, 21%, 0%, 13%, 縫合不全は25%, 14%, 6%, 4%とIII, IV法の成績が良好であった. 膵液漏出は胆道癌で21%, 膵癌で6%, 縫合不全はそれぞれ14%, 5%と有意 (p

The supply of injectable drugs for individual patients using the prescription order entry system was started from Apr. of 1995 at Kanazawa University Hospital. The injectable drugs for individual patient are set up by pharmacists into each compartment of the kart (Ordering Kart: Sakase Corporation), and then are carried by nursing assistants to the respective clinical areas.The characteristics of this supply method are [1] it is set up by 4 pharmacists on a daily schedule (8: 30 am-3: 30 pm), [2] injectable drugs for emergency are louded in a special compartment of the carrying kart, and [3] are set up for prescription entry by the physicians within 24 hours. As a result, it is thus possible to check the prescription (dosage, route, incompatibility and stability), to reduce the stock of injectable drugs in the ward while, in addition, manpower for both the nursing and medical office personnel can be reduced.

Because selenium is seldom added to formulations for enteral nutrition (EN), postoperative patients who are supported with EN are at risk for selenium deficiency. This report describes four cases of suspected selenium deficiency in long-term EN. Two patients underwent pancreaticoduodenectomy, one underwent total gastro-pancreatectomy, and one underwent esophageal resection and reconstruction with jejunal autotransplantation. They all developed malabsorption syndrome within 2 yr after operation. Enteral nutritional support with an elemental diet was provided continuously for 7-11 yr. Over the past 1-2 yr they experienced increasing bilateral muscular pain and weakness in the legs, gait disturbance, palpitation, and shortness of breath. Investigation for possible trace element deficiency revealed very low levels of selenium in the blood. After 10-20 d of supplementation with daily intravenous administration of selenious acid 0.16 mg/d (100 micrograms/d of selenium), their blood levels of selenium rose and their symptoms resolved. They were then continued on a maintenance regimen of oral sodium selenite 0.13 mg/d (60 micrograms/d of selenium).

We have reviewed the literature regarding the chemoprevention of breast cancer. Several clinical trials using retinoid, tamoxifen, or low-fat dietary intervention for the prevention of breast cancer are ongoing. In the next few years, the implementation of these clinical chemoprevention trials will take place. Moreover, combinations of such chemopreventive agents, as well as the development of new chemopreventive compounds, will require testing in clinical settings. Even though there is probably a substantial delay before such chemopreventive approaches have a significant effect, it is clear that chemoprevention will complement other approaches in controlling breast cancer.

The diagnostic value of intraoperative histologic examination of frozen sections of surgical margins and axillary lymph nodes (AX) was investigated in 95 patients with breast cancer who underwent breast-conserving surgery. The periphery of the excised breast tissue was peeled like an orange and examined histologically by frozen section. The results were compared with examination by permanent section. Evaluation of surgical margins by frozen section resulted in a diagnostic accuracy of 87%, a sensitivity of 96%, and a specificity of 84%. Enlarged or hardened AXs were sampled from the axillary pad which was derived from a complete AX dissection. Histologic examination using frozen section was performed during surgery. After the operation, the remaining AXs were removed from the axillary pad by hand dissection and histologically examined on permanent section. A diagnostic accuracy of 97%, a sensitivity of 77%, and a specificity of 100% were achieved in the diagnosis of AX involvement on frozen section. It was therefore concluded that intraoperative histologic examination of frozen sections may be useful in the determination of involvement of the surgical margins and the AXs in patients with breast cancer.

Background. E-cadherin (ECD) is known to be an invasion suppressor gene, and urokinase-type plasminogen activator (uPA) plays a central role in infiltration of solid cancers. Methods. To elucidate the relationship between expression of these factors and metastasis in patients with gastric cancer, the authors examined immunohistochemically a combination analysis of uPA and E-cadherin expression in 98 primary tumors, and the results were correlated with several parameters related to metastasis. Results. Among 125 tumors, 42 (34%) were evaluated as having E-cadherin expression (E-cadherin-positive), and the other 83 (66%) were defined as having reduced E-cadherin expression (E-cadherin-negative). uPA immunoreactivity was observed in 82 tumors (66%). There were four subtypes of patterns of uPA and E-cadherin expression: 22 uPA-negative/E-cadherin-positive, 17 uPA-negative/E-cadherin-negative, 21 uPA-positive/E-cadherin-positive, and 65 uPA-positive/E-cadherin-negative. uPA overexpression and reduced E-cadherin expression were associated with lymph node metastasis, vessel invasion, serosal involvement, and poor prognosis. In addition, uPA-positive/E-cadherin-negative tumors were associated significantly with large tumors, positive serosal invasion, lymph node involvement, and poor prognosis. Patients with uPA-positive/E-cadherin-negative expression had the poorest prognoses, compared with the three other groups of patients. uPA-positive/E-cadherin-negative tumors had a fourfold relative risk of death when compared with uPA-negative/E-cadherin-positive tumors. A Cox proportional hazard model projected lymph node status as the strongest of the prognostic variables, followed by DNA ploidy patterns and uPA/E-cadherin tissue status. Conclusions. These results indicate that immunohistochemical combination analysis of uPA and E-cadherin expression may be a powerful aid in evaluating meta-static potential or the prognosis of patients with gastric cancer. Cancer 1995;76:941–53.

Dehiscence of the pancreaticoenterostomy is one of the most feared, yet common, postoperative complications following pancreaticoduodenectomy (PD). We report herein a new technique we developed for performing continuous intraabdominal suction drainage (CISD) following PD. This method of CISD involves positioning an 18 Fr sump tube beside the pancreaticoenterostomy, with a continuous suction pressure of about -20cmH2O. The fluid obtained from the sump tube is also useful for monitoring amylase levels and providing bacterial cultures to enable the early detection of dehiscence of pancreaticoenterostomy. A study was conducted on 150 patients who underwent PD for periampullary carcinoma over a 20-year period. The patients were divided into two groups according to whether or not CISD was performed: group 1 comprised 71 patients who had CISD, and group 2 79 patients who did not have CISD. Although the frequency of anastomotic dehiscence did not differ between the two groups (32% in group 1 and 25% in group 2), the mortality rate of the patients with anastomotic leakage in group 1 was lower than that in group 2 (P = 0.07). Thus, we believe that our new technique for performing CISD could improve the surgical outcome of patients following PD.

We evaluated the oncologic and cosmetic outcome in patients with breast cancer treated with wide excision, transposition of adipose tissue with latissimus dorsi muscle (LDM), and axillary dissection followed by radiotherapy. In this study, a wide excision of breast tissue was performed to obtain tumor-free margins. The subsequent breast deformity was not corrected in six patients in the early phase of the study (Group 1), and in 16 patients in the late phase (Group 2) in which the breast deformity was not remarkable at the time of operation. Breast deformity was corrected by transposing adipose tissue with LDM on a vascular pedicle in the remaining 51 patients (Group 3). Five year survival was 100%. Two patients developed distant metastases. None were found to have local recurrence. Fifty percent of the Group 1 patients, 69% of the Group 2 patients, and 67% of the Group 3 patients had an excellent or good cosmetic result. However, when the cosmetic results were evaluated in patients who underwent transposition and had small breasts, the results were excellent or good in 76%, compared to 38% in the patients who had reconstructions who had large breasts. The difference was statistically significant (p = 0.0309). Therefore, it was confirmed that wide excision and axillary dissection followed by breast radiation could provide adequate local control, but frequently resulted in breast deformity. However, transposition of adipose tissue may be useful to correct the breast deformity, especially in women with small breasts.

To improve the surgical results for pancreatic cancer, extended surgery has been performed at our institution since 1973. The translateral retroperitoneal approach was developed as one of these extended procedures in 1976. With this procedure, the lymph nodes around the pancreas, the superior mesenteric artery, and the abdominal, aorta are removed and a combined resection of the portal vein is performed. This approach has been employed in 54 patients with pancreatic cancer. Of these 54, 9 have survived for 5 years or more. Here we describe the technique, focusing in particular on the dissection of the retroperitoneum and the region around the superior mesenteric artery.

Epidemiologic cohort studies have established that after distal gastric resection, there is a higher risk of gastric carcinoma. It is likely that a main factor of this higher risk is the excessive duodenogastric reflux induced by surgery, because the incidence of stump carcinomas is higher in Billroth II than in Billroth I, and most of the stump carcinomas are located near the stoma. In addition, several groups of investigators have suggested that duodenogastric reflux per se induces stump carcinomas in rats. There is another human duodenogastric reflux, the primary duodenogastric reflux, through the pylorus. Experiments in animals have demonstrated that this type of duodenal reflux also induces gastric carcinomas in the antrum of the stomach that has not undergone surgery. Recent clinical attention has focused on the role of duodenogastric reflux in the pathogenesis of Barrett's esophagus and subsequent esophageal adenocarcinomas. Experimentally, reflux of duodenal contents into the esophagus can cause not only Barrett's esophagus and subsequent adenocarcinomas, but also squamous cell carcinomas. These findings suggest that duodenogastric reflux may be implicated in gastric and esophageal, that is, foregut carcinogenesis. Cancer 1995 ; 75 :1426-32.

It has been suggested that the number of argyrophilic nucleolar organizer regions (AgNORs) correlates with cellular activity and the aggressiveness of malignancy. The mean number of AgNORs per nucleus may, therefore, be a prognostic factor for hepatocellular carcinoma (HCC). The purpose of this study was to evaluate the prognostic significance of the number of AgNORs in HCC. The silver-staining technique was applied to surgically resected specimens to indicate AgNORs. Eighty-nine of the specimens were of HCC, 23 were of normal liver adjacent to HCC, and 32 were of cirrhotic liver adjacent to HCC. The number of AgNORs of HCC (mean ± SD, 3.26 ± 1.23) was significantly higher than those of normal liver (1.37 ± 0.13) and cirrhotic liver (1.49 ± 0.14). The number of AgNORs was significantly correlated with serum alpha-fetoprotein level, tumor size, portal vein invasion, and Edmondson-Steiner histological grade. In patients undergoing curative resection, the survival rate of those with a high number (>3.04) of AgNORs was significantly worse than that of those with a low number (≤3.04) of AgNORs. Multivariate analysis showed that the number of AgNORs was a significant prognostic indicator in patients without portal vein invasion, and portal vein invasion was the only significant variable when all patients undergoing curative resection were assessed together. The results of this study suggest that the number of AgNORs is useful as an indicator of the grade of malignancy and as a predictor of the prognosis of patients with HCC who do not have portal vein involvement.

Eleven patients with tracheobronchial stenosis due to a recurrent malignant tumor following resection of an esophageal cancer were treated with neodymium-ytrrium-aluminium-garnet laser (Nd-YAG laser). Intermittent irradiation of Nd-YAG laser was done for 0.5 second at 20-30 Watt through a flexible bronchoscope under local anesthesia. After the recanalization of the airway, the laser therapy was repeated 2 to 16 times for every 14 to 21 days to avoid the recurrence of airway obstruction. The average survival time from the start of the laser therapy was 138 days and the median survival time was 83 days. The direct response for tumor size detected by CT-SCAN was not recognized but dyspnea of the patients was dramatically improved by the therapy. It is concluded that the endoscopic Nd-YAG laser therapy is useful in respiratory emergency for airway obstruction by recurrent malignant tumor after resection of esophageal cancer.

胃癌手術後の残胃十二指腸間にpouchを形成した空腸を間置する再建 (JPI法) を評価した. 術後の胸やけや下痢の出現頻度は, JPI法による再建例で, 従来のBillroth法による再建と比較して低率であった. 残胃からの食物排泄を核医学的に観察すると, JPI法では食物は残胃およびpouchに貯留し, 緩徐に十二指腸へと流出するのが認められ, 残胃からの排泄時間T1/2は, Billroth I法の29±6分, Billroth II法の50±37分に対し, JPI法では104±45分と有意に延長していた. 残胃内への胆汁逆流はBillroth法では全例に認められたが, JPI法では15%にみられるのみであり, 胆汁と食物の混和異常も, Billroth法に比較してJPI法では低率であった. 以上より, JPI法は従来のBillroth法よりも術後愁訴の少ない, より生理的な状態が得られる再建法と考えられた.

We investigated the in vitro effects of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), with or without the addition of linoleic acid (LA), on cell growth and prostaglandin E (PGE) and leukotriene B (LTB) secretion by a human breast cancer cell line (MDA-MB-231). With or without the addition of LA, EPA and DHA suppressed cell growth and thymidine incorporation and reduced the secretion of PGE and LTB. In a univariate analysis, cell growth was significantly associated with both LTB and PGE concentrations when cells were treated with DHA or EPA, independent of the addition of LA. However, multivariate regression analysis showed that cell growth was more closely associated with the PGE concentration rather than the LTB concentration. These data suggest that both EPA and DHA suppress cell proliferation in the MDA-MB-231 cell line by inhibition of the cyclooxygenase rather than the lipoxygenase pathways. However, the exact mechanism underlying the antitumor activity of EPA and DHA remains unclear.

Borrmann 4型 (以下, B4と略記) 胃癌61例における手術療法, 持続温熱腹膜灌流 (continuous hyperthermic peritoneal perfusion: 以下, CHPPと略記) の治療成績について検討した. 根治度別の1, 3年生存率は根治度A 94, 60%, B 56, 11%, C 46, 0%, 非切除0, 0%とAが良好であった (p

The literature is reviewed regarding the surgical management of breast carcinoma, and controversies are discussed. Several unresolved issues remain in the surgical management of breast carcinoma. First, the optimal surgical treatment of patients who are at increased risk for having internal mammary lymph node metastases remains unknown. Second, it remains controversial whether axillary dissection is therapeutic or merely represents a staging procedure. Third, there is no consensus regarding the optimal extent of resection prior to irradiation in breast-conserving treatment. Nevertheless, breast conservation is generally accepted as a preferable therapy in patients with operable breast carcinoma, while modified radical mastectomy, with or without breast reconstruction offers an acceptable alternative for these patients.

In two patients with bile duct stones in the distal common bile duct the stones were successfully removed through the intact papilla without choledochotomy. In both patients, the stone was discovered on the intraoperative cholangiogram just after cholecystectomy. The stone was removed by intraoperative flushing with saline solution, combined with pharmacologic sphincter relaxation. This new technique employs glyceryl trinitrate and butylscopolamine bromide to relax the sphincter of Oddi, followed by intermittent flushing with saline solution to augment pressure in the the distal common bile duct. The saline flushing was initiated 3 min after the agents were administered. This technique is simple and less invasive than conventional methods of choledocholithotomy. We recommend this method as the first choice for the removal of common bile duct stones.

The risk factors for the recurrence of intrahepatic stones after an end-to-side choledochojejunostomy were investigated, along with the outcome following the treatment of such stones. Thirty-two patients with intrahepatic stones underwent an end-to-side choledochojejunostomy, and a complete lithotomy was achieved in 26 of them. The follow-up which ranged from 5-19 years after surgery revealed that eight patients developed a recurrence of intrahepatic stones, and their clinical and cholangiographic findings were thus reviewed. Recurrent stones were associated with onset of symptoms at a younger age and were predominantly located in the intrahepatic bile ducts. Recurrence was also associated with severe intrahepatic bile duct dilatation. Six of the eight patients developed recurrent stones more than 5 years after a complete lithotomy. One of these patients died of liver cirrhosis while two died of acute obstructive suppurative cholangitis. Five patients underwent cholangioscopic lithotomy through the jejunostomy for their recurrent stones, and a complete lithotomy was accomplished in three of them. These findings indicate the necessity of performing a hepatectomy in such patients whenever possible, and also emphasize the need for a long-term follow-up after a complete lithotomy with an end-to-side choledochojejunostomy. In addition, any recurrent stones should be treated promptly by a cholangioscopic lithotomy through a jejunostomy.

Presence of pancreatic alpha-amylase, trypsinogen, and lipase in normal pancreatic ducts was evaluated immunohistochemically in 10 surgically resected normal pancreatic specimens, using monoclonal antibodies against human pancreatic alpha-amylase, trypsinogen, and lipase. Immunoreactivity to all enzymes occurred patchily in some epithelial cells not only of the common bile duct and its periductal glands but also of the main and interlobular pancreatic ducts and periductal glands in the main pancreatic duct, as well as in pancreatic acinar cells. Ductal staining was fine-granular, and generally present in the supranuclear cytoplasm. Immunoreactivity was abolished by preabsorption. Centroacinar cells and intercalated and intralobular pancreatic ducts did not stain for any enzyme. These findings suggest that some epithelial cells of the large-sized pancreatic duct and its periductal glands express pancreatic alpha-amylase-, trypsinogen-, and lipase-like peptides, as do some epithelial cells of common bile duct and its periductal glands.

The anatomy and topography of tissue surrounding the superior mesenteric artery were examined histopathologically, and the structure surrounding the superior mesenteric artery (SMA) was reconstructed with data from histologic examination and three-dimensional analyses. Specimens were obtained from three autopsy cases without abnormalities, two surgically resected cases of cancer of the pancreatic head, and one autopsy case of cancer of the pancreatic head. The endothelium or basal membrane of blood and lymph vessels were identified immunohistochemically, and the distribution of lymph nodes, blood vessels, lymph vessels, and collagen fibers was determined. The superior mesenteric plexus was found to be a relatively dense structure with a thickness of about 2 mm, composed of collagen fibers and connective tissue, which concentrically enveloped the small arteries, the superior mesenteric artery, nerve bundles, and capillaries. Lymph vessels larger than a few micrometers in diameter were often found outside of the plexus, and this plexus contained no lymph nodes in any sections. The three-dimensional study of the modes of spread along the superior mesenteric artery of pancreatic cancer revealed two types of spread: the tumor extends mainly by neural invasion, and the tumor extends mainly by lymph node metastases. These morphologic features suggest that lymphatic flow in the vicinity of the superior mesenteric artery passes primarily outside of the plexus, and complete excision of lymph nodes close to the superior mesenteric artery with preservation of the superior mesenteric plexus is feasible if there is no neural invasion into retropancreatic tissues.

The effect of pancreatic resection for periampullary carcinoma in the elderly was studied by comparing the pre-and perioperative factors affecting survival in 102 patients less than 70 years of age (group A) with those in 28 patients 70 years and older (group B). Concomitant cardiac and pulmonary diseases were significantly more frequent in group B (P < 0.05), but the difference in routine laboratory data was not significant. The overall operative mortality was 7% (7/102) in group A and 18% (5/28) in group B, while the actuarial 5-year survival rates were 31%o in group A and 23% in group B, these differences not being significant. A multivariate analysis using a logistic model showed that blood loss was the greatest risk factor for early postoperative death in the elderly patients, whereas anastomotic dehiscence and postoperative bleeding were significant factors in the younger patients. Thus, we conclude that age is not a contraindication to pancreaticoduodenectomy which offers the only hope for long-term survival in patients with periampullary carcinoma; however, meticulous dissection to minimize blood loss is especially important in elderly patients.

Background/Aims: Prognostic analysis on hepatocellular carcinoma (HCC) in patients undergoing hepatectomy is necessary to determine the clinical value of hepatectomy on prognosis. Methods: Survival and disease-free survival were analyzed in 104 HCC patients undergoing hepatectomy using clinicopathologic factors by univariate and multivariate analyses. The value of the International Union Against Cancer (UICC) TNM classification on prognosis was assessed in the patients. Results: In multivariate analysis, portal vein invasion was the most influential factor. The difference between stage 1 and 2 or stage 3 and 4A using UICC's TNM classification was not significant with respect to survival or disease-free survival. The UICC's classification was modified as follows; stage 1, solitary tumor without vascular invasion; stage 2, solitary or multiple tumor(s) involving adjacent to vessel branch; stage 3, tumor(s) involving major vessel branch or with regional lymph nodal metastasis; and stage 4, tumor(s) with distant metastasis. The differences between each stage in the modified classification were significant with respect to disease-free survival. Conclusions: The UICC's TNM classification was not of prognostic significance. Further studies on survival in patients with HCC are necessary to evaluate the value of the UICC's TNM classification; some modification may be necessary.

Cell proliferation of 174 specimens obtained from the primary gastric cancers using endoscopic biopsy was investigated by immunohistochemical analysis with the monoclonal antibody PC10, which recognizes a proliferating cell nuclear antigen (PCNA) in formalin-fixed and paraffin-embedded material. All the examined samples showed nuclear staining for PCNA in cancer cells. The investigation was to test the correlation between PCNA labeling and lymph node metastasis. DNA aneuploidy was often encountered in tumors with nodal involvement and lymphatic invasion. The logistic regression analysis identified PCNA labeling rates (LRs), tumor size, and macroscopic type as independent significant factors for lymph node metastasis. When the PCNA LRs and clinicopathologic parameters were entered into the Cox regression analysis, PCNA LRs and DNA ploidy emerged as independent significant prognostic factors. In addition, combination assay of PCNA LRs and DNA ploidy yielded a powerful prognostic indication for patients with gastric cancer.

Transcatheter arterial embolization (TAE) was carried out in three patients with massive intra-abdominal bleeding caused by pancreatic fistula after radical operation for an advanced gastric cancer. Three cases had the following common features: 1) after extended lymphadenectomy, 2) with pancreatic fistula following acute pancreatitis or suture insufficiency, and 3) with bacterial infection around pancreatic fistula. Under these conditions, main arteries surrounding the stomach were exposed by activated pancreatic juice and pseudo-aneurysms developed. Postoperative sudden and massive arterial bleeding might be caused by rupture of these pseudoaneurysms. It is important that TAE should be the first choice for treatment of this complication rather than the ligation or suture of the ruptured artery, and the drainage and lavage of pancreatic fistula should be done enough to remove the infection.

The pancreatic function diagnostant (PFD test) and fecal chymotrypsin test were performed simultaneously in patients after pancreatic surgery, and findings for both tests were analyzed. The p-aminobenzoic acid recovery rate in the PFD test and the chymotrypsin activity in stools decreased after pancreatectomy, particularly after extended radical pancreaticoduodenectomy. Chymotrypsin activity in stools, measured by the fecal chymotrypsin test after extended radical pancreaticoduodenectomy, was significantly lower than the normal level. The D-xylose output in the extended radical group was significantly (p

We performed continuous hyperthermic peritoneal perfusion (CHPP) or continuous normothermic peritoneal perfusion (CNPP) combined with cisplatin (CDDP) 300 mg/kg and mitomycin C (MMC) 30 mg/kg in an attempt to prevent peritoneal recurrence after surgery for gastric cancer. Twenty-two patients were treated with perfusion using about 10 liters of saline heated to 41 degrees to 42 degrees C (CNPP group); 18 patients were treated with saline heated to 37 degrees to 38 degrees C (CNPP group); and 18 patients underwent only gastric surgery without perfusion (control group) in a randomized control study. There were two deaths (9%) due to peritoneal recurrence in the CHPP group, four (22%) in the CNPP group, and four (22%) in the control group. The 1-, 2-, and 3-year survival rates were 95%, 89%, and 68%, in the CHPP group; 81%, 75%, and 51%, in the CNPP group; and 43%, 23%, and 23%, in the control group, respectively. There was a significant difference between the three survival curves by the log-rank test (p < 0.01). This difference showed that CNPP and CHPP are both effective procedures for preventing peritoneal recurrence. The maximum concentrations in the perfusate of total and free CDDP with 300 mg administration were 12.2 and 10.1 micrograms/ml, respectively, at the end of the perfusion, and the maximum concentrations of total and free CDDP in plasma were 2.1 and 1.0 micrograms/ml, respectively. The maximum concentrations of MMC in perfusate and plasma with 30 mg administration were 1.00 and 0.05 micrograms/ml, respectively, which are intraperitoneally cytotoxic but systemically safe concentrations.

Cosmetic and psychologic morbidity was evaluated by patients self-assessment in 42 patients who underwent breast conserving therapy (BCT) and 48 patients who underwent mastectomy with immediate breast reconstruction (MIBR). Although sexual adjustment and fear of cancer recurrence were not significantly different between the two groups, body image was rated as significantly better in the BCT group. Additionally, in the MIBR group, nine patients expressed concern about abdominal or back scars and 15 related abdominal or back pain. Eighty-three percent of the BCT group indicated BCT as a future choice of treatment, whereas only 38% of the MIBR group indicated MIBR as a future choice of treatment. Therefore, body image and patients' satisfaction were thought to have been improved by BCT, but psychologic morbidity was the same in both groups. © 1993 Wiley-Liss, Inc.