Surgical management of endocrine tumor of the pancreas in Japan

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. This study was carried out as a group project. The authors' institutions are as follows     

Usefulness of preoperative low dose cisplatin treatment for advanced esophageal cancer

In order to decrease the perioperative complications by preoperative cisplatin chemotherapy, the preoperative single administration of cisplatin (30 mg/m²) was performed weekly from one to six times in 36 consecutive patients with esophageal cancer classified as higher than Stage II. The survival curve of 17 patients in Stage III was significantly better (P<0.05) than that of patients who had been treated without preoperative cisplatin treatment. In 3 of the 12 patients who had locally invasive cancer, either the main tumors or the metastatic lymph nodes, which had invaded the trachea or the left main bronchus, sufficiently receded, so that a curative esophagectomy became possible; 2 of them have survived over 33 months while 1 died of pneumonia 33 months after surgery. The number of perioperative complications was minimal, and thus, we consider that the postoperative use of cisplatin and fluorouracil is indicated in patients in whom a histological response is noted in the resected specimens.This work was partially supported by Grant No. 02454315 from the Japanese Ministry of Education     

The significance of CA-50, SLX and ST-439 in lung cancer]

Serum levels of CA-50, SLX and ST-439 were measured in 213 patients with lung cancer (92 adenocarcinomas, 63 squamous cell carcinomas, 37 small cell carcinomas and 21 large cell carcinomas) and 87 patients with benign lung disease. The overall positive rates in patients with lung cancer were 12.8% for CA-50, 29.7% for SLX and 25.3% for ST-439. The positive rates for CA-50, SLX and ST-439 in adenocarcinoma patients were 22.8%, 42.4% and 38.0%, respectively. Of the patients with benign lung disease, 4.8% were false positive for CA-50, 15.3% for SLX and 3.6% for ST-439. In the patients with adenocarcinoma of the lung, the combination assay of CEA and ST-439 had a highly accurate rate (61.9%).     

Suppressive effect of LD78 on the proliferation of human hemopoietic progenitors.

LD78 is a cDNA newly isolated from human stimulated tonsillar lymphocytes. The expression of LD78 is related to inflammatory responses and its structure has a homology with macrophage inflammatory protein 1-alpha, which is known to have an inhibitory effect on murine CFU-S. Using a colony assay technique, we examined the effects of LD78 on human hemopoietic progenitors. The addition of doses of 100 ng/ml or more of LD78 suppressed the colony formation of KMT-2, a factor-dependent myelomonocytic cell line established from cord blood cells; this suppressive activity was neutralized by the addition of antibody against LD78. The same doses of LD78 suppressed the formation of neutrophil, macrophage, and megakaryocytic colonies which were supported by human interleukin-3 and erythropoietin; however, LD78 did not affect colony formation by either non-phagocytic mononuclear cells or sorted CD34+ cells. The conditioned medium of KMT-2 cells or peripheral blood mononuclear cells cultured with LD78 suppressed colony formation by CD34+ cells. From these findings, it is suggested that LD78 affects phagocytic cells and induces factors that are inhibitory for hemopoiesis. We consider LD78 to be a new cytokine that plays an inhibitory role in hemopoiesis.     

Preferential inhibitions of hepatic P450IA2 expression and induction by lead nitrate in the rat

Male F344 rats were treated with lead nitrate and changes inthe expression and induction of P450IA subfamily enzymes anda placental form of glutathione-S-transferase (GST-P) in theliver were assessed by means of a bacterial mutation test, immunoblottingwith a monoclonal antibody reactive to P450IA1/IA2 and anti-GST-Psera and Northern blotting with P450IA2 cDNA as a probe. Treatmentof rats with lead nitrate (20, 50 or 100 µmol/kg bodywt) decreased P450IA2 mRNA and protein in the liver in the dose-dependentfashion and also decreased the microsomal activity for P450IA2-dependentmutagenization of aromatic amines. Pretreatment of rats withlead nitrate suppressed the inductions of both P450IA2 mRNAand protein by an inducer of P450IA subfamily enzymes in theliver. In addition, amount of the induced P450IA2 was decreasedalong with increase in that of the induced GST-P.     

Dorsal skin responses to topical application with hydrogen peroxide in Mini and Wistar rats.

Mini rats (Jcl: WistarTGN(ARGHGEN) 1Nts) (MRs) are Wistar rat (WR)-derived transgenic rats in which the expression of growth hormone (GH) gene is suppressed under the presence of antisense RNA transgene. In order to evaluate the effects of GH-deficiency on the acute injury by external stimuli, the dorsal skin responses to a single topical application with 20% hydrogen peroxide (HPO), one of the environmental oxidative stressors, were histologically compared between male MRs and WRs of 8 weeks old, whose hair cycle was under the telogen phase. As a result, formation of granulation tissues, reepithelialization and regrowth of hair follicles were delayed in MRs compared with WRs. While hair follicles of MRs of this age are under a long-lasting telogen phase after their 2nd cycle, a new hair cycle started not only in the HPO-applied area but also in the solvent-applied area with a little time lag. These findings suggest that GH-deficiency may influence the skin responses to the external chemical stimuli.     

EFFECTIVENESS OF CYTODIAGNOSIS WITH PANCREATIC DUCT LAVAGE FLUID FOR PANCREATIC DUCTAL CARCINOMA: NEW SAMPLING TECHNIQUE

Background: Pancreatic carcinoma is one of the most lethal cancers. Because pancreatic carcinoma is still very difficult to diagnose in its early stage, many of these patients will be considered unsuitable for surgery. If a cytological diagnosis is obtained at initial endoscopic retrograde cholangiopancreatography (ERCP), suitable treatment will be initiated without delay. Methods: To increase the number of exfoliated cells from the pancreatic duct, we devised a new technique, pancreatic duct lavage fluid (PDLF), following bronchoalveolar lavage fluid. The present paper reports the effectiveness of cytological examination using PDLF in the diagnosis of pancreatic carcinoma. We examined 18 pancreatic carcinoma cases. After the endoscopic retrograde pancreatography (ERP), PDLF was collected from a double‐lumen catheter inserted into the main pancreatic duct. Saline injected from the lumen for the injection, and PDLF was aspirated from the other lumen for the guidewire at the same time. The cytological examination was performed using PDLF. Results: Exfoliated cells were more frequently found in PDLF from all patients. In 15 cases (83%), cytological examination of PDLF revealed positive cytological results as the diagnosis of pancreatic carcinoma. Conclusion: Cytological examination using PDLF has a high sensitivity for detection of pancreatic carcinoma. The new examination, PDLF, is simple, safe and effective, so we expect PDLF to become widely popular.     

Clinical assessment of microscopic polyangiitis in elderly patients]

OBJECTIVE: To evaluate the influence of the age at disease onset on the clinical symptoms, laboratory findings, treatment, and complications of microscopic polyangiitis (MPA). PATIENTS: From 1999 to 2001, we encountered 4 MPA patients with disease onset at age 65 or older (average 77.3, all were female: the elderly group). For comparison, 4 MPA patients with disease onset a 64 years or younger (average 44.7, two were male: the non-elderly group) were used. RESULTS: There was no statistically significant difference in clinical features between the two groups. All patients in the elderly group were referred to our hospital, because of fever of unknown origin or suspicion of connective tissue disease. The elderly group had a longer duration from the first admission to the start of treatment. Renal biopsies were done in all of the non-elderly group and one of the elderly group. The diagnosis of the other 3 patients of the elderly group was based on muscle or nerve biopsy, showing necrotizing vasculitis. At the time of diagnosis, antibodies to myeloperoidase (MPO-ANCA) were positive in 7 of 8 patients (87.5%). 2 patients of the non-elderly group were died of heart failure and hepatic failure by cyclophosphamide (CYC). The other 6 patients achieved substantial improvement. CONCLUSIONS: Muscle or nerve biopsy helped clinical management of elderly patients when renal biopsies could not be done. IVCY was relatively safe and effective treatment for MPA in elderly as well as non-elderly patients.     

Cytokine production by peripheral blood monocytes/macrophages in the patients with multiple sclerosis and its suppression by methylprednisolone]

The production of tumor necrosis factor alpha (TNF alpha), interleukin-1 alpha (IL-1 alpha), interleukin-1 beta (IL-1 beta) and interleukin-6 (IL-6) by stimulated peripheral blood monocytes/macrophages (PBM) was assessed in patients with multiple sclerosis (MS), other neurological diseases (OND) or normal controls (NC) using enzyme-linked immunosorbent assay (ELISA). PBM obtained from acute phase of MS produced significantly higher amount of all these cytokines than those from chronic stable MS, OND or NC (TNF alpha, IL-1 alpha, IL-6: p less than 0.01, IL-1 beta: p less than 0.05). Methylprednisolone (MP) inhibited the lipopolysaccharide-induced cytokine production in a dose-dependent manner. These results suggest the possible roles of activated monocytes/macrophages in the acute exacervation of MS and suppressive effect of MP on cytokine production by activated monocytes/macrophages.     

Applications of DNA Flow Cytometry and Fluorescence In situ Hybridization Using a Chromosome-specific DNA Probe on Paraffin-embedded Tissue Sections of Primary Malignant Melanomas

We have applied DNA flow cytometric analysis to paraffin-embedded tissue sections of primary malignant melanomas. Conventionally, flow cytometric analysis of paraffin-embedded tissue sections has been done by the method of Hedley et al. We added ultrasound treatment to the method of Hedley et al. and a lower value of coefficient of variation was shown. Furthermore, a new technique, fluorescence in situ hybridization with a chromosome-specific repetitive DNA probe, was used for the analysis of chromosomal numerical aberrations in the same paraffin-embedded tissue sections. The DNA flow cytometric analysis showed that in 8 cases six primary malignant melanomas were of the aneuploid pattern and two cases of lentigo maligna (melamona in situ) were of the diploid pattern. By fluorescence in situ hybridization, the two cases with the diploid pattern had spots/nucleus of 1.28 and 1.12, and those with the aneuploid pattern had spots/nucleus from 2.01 to 2.27. Only one nodular melanoma in an aneuploid case showed spots/nucleus of 1.71. These data indicate that fluorescence in situ hybridization with chromosome-specific repetitive DNA probes can serve as a cytogenetic tool for the analysis of interphase nuclei of solid human tumors and may be useful for the study of tumor cell heterogeneity.