Seizo Masutani

Poor prognosis associated with thrombocytosis in patients with gastric cancer

Thrombocytosis is commonly associated with malignant disease and has recently been suggested to be a poor prognostic indicator in patients with lung cancer and gynecological cancers. The prevalence of thrombocytosis in patients with gastric cancer was reviewed, and its association with poor prognosis was investigated. Platelet count (PLT) and hemoglobin concentrations (Hb) were reviewed in 369 consecutive patients with histologically verified gastric cancer from 1994 to 2000. Differences between categories were analyzed with analysis of variance, and survival was compared by using the log-rank test on the Kaplan-Meier life table. Multivariate Cox regression analysis was used to evaluate whether thrombocytosis is an independent prognostic marker. Thrombocytosis was found in 42 patients, and anemia was found in 200 patients. PLT was negatively correlated with Hb. Mean PLT was significantly increased in patients with noncurative operations. There was a positive correlation between the depth of tumor invasion and PLT. One- and 3-year survival expectancies in patients with or without thrombocytosis were 52.4% and 23.4% and 85.7% and 72.9%, respectively. PLT was identified as an independent prognostic factor after lymph node metastasis and depth of tumor invasion. Thrombocytosis is an independent prognostic indicator of survival in patients with gastric cancer.BackgroundThrombocytosis is commonly associated with malignant disease and has recently been suggested to be a poor prognostic indicator in patients with lung cancer and gynecological cancers. The prevalence of thrombocytosis in patients with gastric cancer was reviewed, and its association with poor prognosis was investigated.MethodsPlatelet count (PLT) and hemoglobin concentrations (Hb) were reviewed in 369 consecutive patients with histologically verified gastric cancer from 1994 to 2000. Differences between categories were analyzed with analysis of variance, and survival was compared by using the log-rank test on the Kaplan-Meier life table. Multivariate Cox regression analysis was used to evaluate whether thrombocytosis is an independent prognostic marker.ResultsThrombocytosis was found in 42 patients, and anemia was found in 200 patients. PLT was negatively correlated with Hb. Mean PLT was significantly increased in patients with noncurative operations. There was a positive correlation between the depth of tumor invasion and PLT. One- and 3-year survival expectancies in patients with or without thrombocytosis were 52.4% and 23.4% and 85.7% and 72.9%, respectively. PLT was identified as an independent prognostic factor after lymph node metastasis and depth of tumor invasion.ConclusionsThrombocytosis is an independent prognostic indicator of survival in patients with gastric cancer.

Total Gastrectomy With Dissection of Lymph Nodes Along the Splenic Artery: A Pancreas-Preserving Method

Background: In Japan, the tail and body of the pancreas are generally removed for dissection of lymph nodes along the splenic artery. A new pancreas-preserving method was developed to decrease the postoperative complications due to pancreatic resection.Patients and Methods: Between 1981 and 1989, 110 patients were registered in a randomized controlled trial, which included total gastrectomy plus dissection of lymph node along the splenic artery, either with (55 patients: Group A) or without (55: Group B) pancreas tail resection. In Group B, the splenic artery and spleen were removed and the pancreas was preserved. There were no significant differences between the two groups in terms of sex, age, location, microscopic classification, or disease stage. The postoperative complications and survival rates were compared between the two groups.Results: The average number of dissected nodes along the splenic artery was 4.6 and 4.1 for Groups A and B, respectively. The amounts of blood loss during the operation were 994 ml and 904 ml for groups A and B, respectively. Anastomosis failure and/or pancreatic fistula occurred in nine patients in Group A (16%) and seven in Group B (13%). One year after the operation, a glucose tolerance test showed diabetes in 6% and impaired glucose tolerance in 33% of patients in group A, while these findings were normal in group B. The 5-year survival rates were 80% and 76.7% for groups A and B, respectively.Conclusions: The pancreas-preserving method described here was superior to the more common pancreas resecting method with regard to surgical risk and postoperative glucose tolerance.

Surgery for gastric cancer increases plasma levels of vascular endothelial growth factor and von Willebrand factor

Abstract.Background: Angiogenesis and hemostatic activation are important factors in tumor progression and metastasis. Because surgical intervention induces tissue hypoxia and hemostatic activation, we analyzed the effect of gastric surgery on the plasma concentrations of vascular endothelial growth factor (VEGF), soluble P-selectin (sP-selectin), and von Willebrand factor (vWf). Methods: Plasma VEGF, sP-selectin, and vWf concentrations were measured in 14 patients with gastric cancer before operation and on postoperative day 1 (POD 1). Correlations between disease stage and the effect of surgical intervention were analyzed. Results: The plasma concentrations of these three factors did not correlate with the disease stage. Plasma levels of sP-selectin did not change after operation (before surgery, 87.6 ± 34.1 ng/ml; on POD 1, 101.1 ± 48.1 ng/ml; P = 0.123). Plasma VEGF and vWf concentrations were significantly elevated on POD 1 (VEGF, 33.3 ± 20.5 pg/ml before surgery and 61.9 ± 35.6 pg/ml on POD 1; P = 0.0013; vWf, 164 ± 31.1% before surgery and 211.1 ± 66.1% on POD 1; P = 0.027). Conclusion: Because VEGF and vWf are involved in angiogenesis, tumor-platelet adhesion, and tumor-endothelial cell adhesion, surgical intervention could influence tumor growth and metastasis.

Multiple inflammatory pseudotumors mimicking liver metastasis from colon cancer: report of a case.

A 54-year-old man underwent an operation for colon cancer histologically diagnosed as moderately differentiated adenocarcinoma with clinical staging of Dukes C. He was prescribed carmofur for adjuvant chemotherapy. A follow-up computed tomography scan done 6 months later revealed two new low-density areas in the liver. A diagnosis of metastatic adenocarcinoma from the previous colon cancer was presumed, based on the patient’s history and radiological findings, and resection of the affected area of liver was performed. Histological examination of these tumors revealed that they were inflammatory pseudotumors (IPT). The patient had an excellent postoperative course and has shown no further signs of recurrence in the 3 years since his last operation. IPT of the liver is a rare disease, for which no methods of diagnosis and treatment have been established, since it is difficult to distinguish IPT from hepatocellular carcinoma or metastatic carcinoma. We describe this case with a review of the 101 cases of IPT documented in the Japanese literature, in the hope that it will contribute to the diagnosis and treatment of this unusual disease entity.

Splenic and pulmonary metastases from renal cell carcinoma: report of a case.

Abstract We report herein the case of a patient in whom pulmonary and splenic metastases from renal cell carcinoma (RCC) were successfully treated by surgical excision. A 69-year-old man who underwent left nephrectomy for RCC 17 months before was suspected to have a pulmonary metastasis based on computed tomography (CT) findings. Partial resection of the left lower lobe was performed with thoracoscopic assistance. However, 4 months later, a splenic tumor, 6 cm in diameter, was detected by CT and ultrasonography, and a splenectomy was performed. Histologically, both resected specimens were diagnosed as metastasis from RCC. A second pulmonary metastasis of the left upper lobe was resected 4 years 8 months later. The patient was in good health when last seen 11 months after his last operation. Malignant neoplasms rarely metastasize to the spleen and most cases are found at autopsy, or feature multiple distant metastases. Only four other cases of splenic metastases from RCC have been reported. The prognosis associated with splenic metastasis is favorable when only a solitary lesion exists.

Management of hepatic arterial infusion port following prophylactic regional chemotherapy in patients who have undergone curative resection of colorectal liver metastases.

AbstractPurpose. Although hepatic arterial infusion (HAI) is widely performed as a prophylactic chemotherapy for patients who have undergone a curative resection of a metastatic liver tumor from colorectal cancer, the optimal management of implantable ports and catheters after the cessation of such adjuvant therapy remains to be elucidated. Methods. The survival and recurrence rate of 30 patients who received adjuvant regional chemotherapy following a hepatectomy were examined. The outcomes of the 15 patients who were regularly administered heparin into the port to prevent its occlusion were also analyzed. Results. With a median follow-up period of 38.1 months, local recurrence in the residual liver was observed in only 5 patients (17%), and the 3-year hepatic disease-free survival was as high as 82%. Out of the 15 patients who received heparin injection, the ports were successfully maintained in only 6 patients (40%) at from 8.8 to 24.7 months (median, 10.8 months) postoperatively, and 69% of the implantable ports were maintained without occlusion for 12 months. Furthermore, a second course of regional chemotherapy was carried out in only one patient, while a repeat hepatectomy was performed instead of chemotherapy in the other patients with hepatic recurrence. Conclusions. Because HAI remarkably reduced the degree of relapse in the residual liver, there is no benefit in maintaining the port after discontinuing the chemotherapy. Heparin administration via the same port after a cessation of the prophylactic HAI chemotherapy is not justified, and it is desirable to remove the implanted catheter when possible.

Preparation and characterization of monoclonal antibodies to an N-linked oligosaccharide.

Two monoclonal antibodies to an N-linked oligosaccharide, MT-5 and MT-9, have been prepared by immunization with a pyridylaminated, asialylated, galactosylated, fucosylated, bisected biantennary sugar. The reactivity of these antibodies was monitored by their reaction with human asialoglycophorin in a solid-phase enzyme-linked immunosorbent assay. Both antibodies reacted with the sugar chains of various human glycoproteins such as immunoglobulin G, transferrin, gamma-glutamyl transpeptidase, alpha 1-acid glycoprotein, and alpha-fetoprotein. Treatment of asialoglycophorin with beta-N-acetylhexosaminidase or alpha-mannosidase resulted in reduction of the binding to these antibodies. The reactivity of MT-5 to asialoglycophorin was slightly inhibited by D-mannose and N-acetylglucosamine, whereas that of MT-9 was inhibited by D-mannose, N-acetyl-D-glucosamine, chitobiose, and L-fucose. The epitope specificity of MT-5 appears to be a sugar chain containing biantennary N-acetyl-D-glucosamine residues, the bisected N-acetyl-D-glucosamine residue, and a trimannosyl core. The epitope to which MT-9 is directed may be a complex made up of beta-mannose, chitobiose, and L-fucose. These studies indicate that immunization with pyridylaminated sugars can produce antibodies that recognize N-linked oligosaccharides. Monoclonal/polyclonal antibodies to the N-linked sugar chains of glycopeptides would be useful in such studies of proteins.

A case of breast cancer diagnosed by inguinal lymph node metastasis.

We describe a case of a 58-year-old woman with right inguinal lymph node swelling and a Tl tumor in the right breast. She was referred with an 18-month history of the former complaint and a six-month history of the latter. Excisional biopsy of the inguinal lymph node revealed breast cancer metastasis. Radiographical examination showed no metastases to the lungs, liver or bone. Modified radical mastectomy was performed. Histological examination revealed solid tubular carcinoma, PT2, PM (axillary lymph node metastases 4/16), stage IV. Estrogen and progesterone receptors were negative. Three cycles of postoperative cyclophosphamide, adriamycin and 5-fluorouracil (CAF) chemotherapy were given, and the right inguinal area was irradiated with 40 Gy. The patient complained of swelling in both legs three years after surgery. Computed tomography revealed marked lymph node swellings in the pelvic cavity. She died six months later. Inguinal lymph node metastasis from breast cancer is very rare, although distant lymph node metastasis in the cervix occurs frequently. This case should help clarify how breast cancer metastasizes to distant lymph nodes.

The State of the Art and Perspective in Treatment of Gastric Carcinoma with Reference to Depth of Invasion.

胃癌が漿膜に露出すると, リンパ節転移陽性率が80%を超え, 腹膜播種の危険性が高まり, 肉眼型4型では後腹膜への浸潤も出現する. 大動脈周囲リンパ節転移陽性例は予後不良で, 5年生存率は17.7%であった.積極的に郭清を行った症例でも予後改善はなく, 適応例の決定が必要である. 腹膜再発の予防として漿膜露出胃癌の手術時にmitomycin C 40mgを生理食塩水1,000mlに溶解し, 60分間閉鎖腹腔内に投与した. これはinvitroではInhibition Concentration 90 (IC90) を満足する投与法であるが, 臨床的には延命効果は認めたものの, 腹膜播種を抑制することはできず, より有効な治療法の開発が必要である. 4型胃癌は, 肉眼的に他臓器に癌浸潤を認めなくても18%に組織学的癌浸潤が陽性で, 局所を十分に摘除しうる超拡大手術法が必要で, Appleby法を伴った左上腹部内臓全摘術により, 浸潤硬化型腹膜再発を抑制し, 良好な遠隔成績が得られた.

The partial characterization and clinical evaluation of pancreas cancer-associated antigen from the ascites fluid of a patient with pancreatic cancer

Monoclonal antibodies against pancreas cancer-associated antigen (PCAAp) were produced by established hybridoma cells. Two monoclonal antibodies, 3F1 and 3B6, were selected and these two monoclonal antibodies were found immunohistologically to react strongly with cancer cells and intraductal mucin-like products in well-differentiated pancreatic cancer tissues, but weakly, if at all, with gastric, colorectal and other cancers and at all not with normal adult or fetal pancreatic tissue. PCAAp is usually expressed in normal colonic mucosa (PCAAc), but the two monoclonal antibodies scarcely reacted with normal colonic mucosa. A sandwich enzyme immunoassay was developed to measure circulating PCAAp. Thirty-two normal subjects and 271 patients comprised of 210 with malignant disease and 61 with benign disease were surveyed. The cut-off value of PCAAp levels in the 32 normal subjects was 2.06 μg/ml, being the mean+2SD, while PCAAp levels of more than this were observed in 72 per cent of the patients with pancreatic cancers, 65 per cent of those with bile duct cancers, 60 per cent of those with hepatomas, 0–30 per cent of those with other malignant diseases, and 10 per cent of those with benign hepatobiliary diseases. The susceptibility of isolated PCAAp and PCAAc to various enzymes and chemical reagents were also studied. The results of this study suggest that the assay for PCAAp might be useful in the diagnosis of pancreatic cancer.