[Multimodal treatment including intraoperative irradiation for advanced pancreatic cancer with extended metastasis].

From January 1987 to December 1999, we treated 11 advanced pancreatic cancer patients with extended metastasis with multimodal treatment. Two patients received external radiation therapy (ERT) and systemic chemotherapy, 1 received intraoperative radiation therapy (IORT) and ERT and arterial infusion chemotherapy (AIC), 2 received IORT and AIC, 4 received only IORT, 2 received only AIC, and 15 did not receive any of these treatments. There was a significant difference in the survival rate between treatment and no treatment cases (median survival of 177 days and 109 days, respectively) (p = 0.04). A significant difference in the survival rate was also observed between IORT cases and no treatment cases (median survival of 212 days and 109 days, respectively) (p = 0.02). However, there was no significant difference in the survival rate between AIC cases and no treatment cases (median survival of 177 days and 109 days, respectively) (p = 0.10). Therefore, our experience suggests that multimodal treatment including intraoperative irradiation is effective for advanced pancreatic cancer patients with extended metastasis.

[A case of peduncular hallucination after aneurysmal subarachnoid hemorrhage].

We reported a case of peduncular hallucination after aneurysmal subarachnoid hemorrhage (SAH). The patient underwent endovascular embolization of an intracranial aneurysm using the Guglielmi detachable coils (GDCs) 9 days after SAH. On the 11th day, she reported visual hallucination: a maggot was on the ceiling, or a soldier who wore green clothes was standing by a locker. The hallucination was vivid, well-formed and associated with insomnia, suggesting peduncular hallucination. A computed tomographic (CT) scan revealed small infarctions of right frontal lobe, which were not responsible for the visual hallucination. Hyperdynamic therapy relieved the visual hallucination 23 days after SAH. It was conceivable that vasospasm was the cause of the infarction and visual hallucination. Only 4 cases with peduncular hallucination after SAH were reported in conjunction with vasospasm. The symptom may be concealed by disturbance of consciousness. Visual hallucination should be considered as a sign of cerebral vasospasm, and an appropriate treatment should be done at right time.

Port site recurrence of unexpected gallbladder carcinoma after a laparoscopic cholecystectomy: report of a case.

Unexpected gallbladder carcinoma was identified in a 71-year-old woman after she underwent a laparoscopic cholecystectomy (LC) for symptomatic cholelithiasis. A subsequent laparotomy for a resection of the liver bed and a dissection of the lymph nodes around the hepatoduodenal ligament was done. Two and a half years later, the patient developed subcutaneous metastasis at the epigastric trocar site through which the gallbladder was removed. A third operation was thus performed, revealing no evidence of peritoneal dissemination, liver metastasis, or lymph node metastasis, and the abdominal wall mass was resected. The histological findings confirmed the diagnosis of metastatic carcinoma of the gallbladder. We recommend that when planning LC, the possibility of malignancy should thus be kept in mind. However, if there is any sign which does not completely exclude malignancy, such as a contracture or wall thickness of the gallbladder, LC should be performed by the abdominal wall lifting method and using a protective bag for the removal of the gallbladder.

Undifferentiated carcinoma with lymphoid infiltration of the esophagus: a case report.

This paper reports a surgically treated case of undifferentiated carcinoma with lymphoid infiltration of the esophagus. Histologically, most of the tumor consisted of undifferentiated carcinoma (non-small cell type) with lymphoid infiltration and a small portion showed features of poorly differentiated squamous cell carcinoma. Carcinoma with lymphoid infiltration in the stomach, breast or nasopharynx has a good prognosis, but in the esophagus this histological type is extremely rare and its characterization is unclear. This is only the sixth report to date of undifferentiated carcinoma with lymphoid infiltration of the esophagus.

[Histological effect of arterial embolization chemotherapy for metastatic liver tumors from colorectal cancer--report of cases of hepatectomy after arterial embolization chemotherapy].

To evaluate the histological effect of arterial embolization chemotherapy (AEC) for the metastatic liver tumors from colorectal cancer, 5 lesions were examined in 4 patients who were treated with surgery after AEC. In addition, to compare the histological changes of the metastatic liver tumors, we histologically examined 7 lesions in 5 patients who were treated with surgery alone as a historical control. For the patients with AEC, anti-cancer agents and lipiodol were administered by selected hepatic arterial infusion with fragments of sponzel. In a group of AEC, all metastatic liver tumors were detected after resection of the primary tumors. The range of tumor size in these lesions was from 2.5 to 4.2 cm in diameter. Otherwise, in a group of non-AEC, the size of tumors ranged from 2 to 5 cm in diameter. In angiography, tumor stainings were detected in 2 lesions, and in all lesions no accumulation of lipiodol was detected by CT scan. The overall response rate at the surgery was 7 to 33% (average 23%) in a group of AEC. In addition, in 2 lesions, about 60% of the lesions were necrotic tissues, and more than 90% of the tumor lesions in 3 lesions were histologically necrosis. Within these lesions, encapsulation of the metastatic tumors was observed in 3 lesions. Otherwise, in a group of non-AEC, 50-70% of the tumor lesions were histologically detected as necrosis, and in one lesion, encapsulation was observed. These evidences suggest the histological effect of AEC may be evaluated when more than 70% of tumor necrosis in lesions is observed. In conclusion, the treatment was effective in 3 cases and not effective in one case.

Correlation between expression of platelet-derived endothelial cell growth factor (thymidine phosphorylase) and microvessel density in early-stage human colon carcinomas.

Platelet-derived endothelial cell growth factor may play a role in tumor development through its angiogenic action. To clarify the relationship between expression of platelet-derived endothelial cell growth factor and microvessel density in the development of human colon carcinoma, we examined 80 early-stage colon carcinomas using microscopy and immunohistochemistry. Localization of platelet-derived endothelial cell growth factor was assessed by immunocytochemistry, while microvessel count was evaluated by either HE staining or Factor VIII immunostaining. Among the examined carcinomas, 35 were classified as m carcinomas including carcinoma in situ, whereas 45 were sm carcinomas. Fifteen (42.9%) of the 35 m and 30 (66.7%) of the 45 sm carcinomas demonstrated high vascular density, whereas 20 (57.1%) m and 15 (33.3%) sm carcinomas showed moderate or low vascular density. Vascular density was higher in sm carcinomas than in m carcinomas and there was a significant correlation between depth of invasion and vascular density. Of the 45 highly vascularized carcinomas, 44 expressed platelet-derived endothelial cell growth factor. There was a statistically significant correlation between the frequency of platelet-derived endothelial cell growth factor expression and microvessel density (P = 0.012). These data demonstrate that microvessel density may be associated with the depth of cancer invasion and that platelet-derived endothelial cell growth factor may play an important role in the early stage of colon cancer development through angiogenesis.

Total necrosis of hepatocellular carcinoma with a combination therapy of arterial infusion of chemotherapeutic lipiodol and transcatheter arterial embolization: report of 14 cases.

Combination therapy consisting of Lipiodol (Laboratoire Guerbet, Villepinte, France) containing styrene maleic acid neocarzinostatin and transcatheter arterial embolization (L-TAE) has been an important conservative therapy for hepatocellular carcinoma (HCC). We examined the clinical and pathologic characteristics of 14 HCC cases that achieved total tumor necrosis in response to L-TAE. The HCCs of all cases were resected 45 +/- 17 days after L-TAE and were confirmed to be totally necrotic. Ultrasonography showed a mean tumor size of 2.5 +/- 1.0 cm, often with a halo formation around the tumor. Angiographically, neovascularity and clear tumor stains were observed in all cases. Computed tomography portography showed nodular perfusion defects in all the cases examined. There were portal invasions in two cases. On Lipiodol-computed tomography, Lipiodol was densely and homogeneously retained within the whole tumor. The number of tumors was single in all diagnostic images. Macroscopic view of HCCs were single nodular type in nine cases and single nodular type with extra growth in four cases. Clear capsular formation was seen in each HCC nodule. Soft x-rays were taken to observe the exact distribution of Lipiodol in the operative specimens. Microscopic intrahepatic metastases were found histologically in four cases. Histologic examination showed the trabecular pattern with broad blood spaces in which Lipiodol was positive with Sudan III staining. Necrosis was seen not only in the main tumor, but also in the capsular invasions and microscopic metastases with Lipiodol deposition. The characteristics of the cases with total tumor necrosis were as follows. Deposition of Lipiodol throughout the tumor was essential, and clinically the cases showed a single HCC tumor with a diameter of more than 5 cm and arterial hypervascularity. The pathologic findings included expansive growth with capsular formation and trabecular-type HCC with abundant blood spaces. These findings are important for evaluating the radical efficacy of L-TAE.

[Granisetron versus granisetron plus methylprednisolone in the prevention of chemotherapy induced nausea and vomiting--in adjuvant chemotherapy, including CDDP against gastric cancer].

CDDP is one of the most effective drugs in chemotherapy for gastric cancer. We compared the antiemetic effect of a combination of granisetron and methylprednisolone with that of granisetron administered alone. Twenty postgastrectomy-patients who were to receive moderately emetogenic chemotherapy, including CDDP, were enrolled in randomized fashion to evaluate the efficacy and toxicity of two antiemetic regimens. The following antiemetic regimens were used: 3 mg of granisetron given intravenously before chemotherapy (11 patients) or a combination of granisetron and 250 mg of methylprednisolone in the same manner (9 patients). Granisetron combined with methylprednisolone tender to be more effective than granisetron alone. The adverse effects were very mild. Their efficacy against delayed emesis is still not entirely satisfactory.

[Chemotherapy for peritoneal dissemination in gastric cancer under ureteral catheterization].

The treatment of peritoneal dissemination of gastric cancer is mainly chemotherapy, but it use is often limited by ileus, hydronephrosis and jaundice. We employed a ureteral catheter for 6 patients with hydronephrosis due to peritoneal dissemination. Chemotherapy (CDDP + ADM + 5-FU or MTX + 5-FU) was administered in 5 patients. After ureteral catheterization, renal function was kept within normal ranges, so chemotherapy was performed safely. One of five patients became CR and the effect of the treatment was satisfactory (PR: 1, NC: 2). Thus, chemotherapy after ureteral catheterization may be effective for patients with peritoneal dissemination and hydronephrosis.

[Intrahepatic arterial infusion chemotherapy for the colon cancer patients with liver metastases--a comparison of arterial embolization chemotherapy versus continuous arterial infusion chemotherapy].

To compare the prognostic benefit between arterial embolization chemotherapy (AEC) and continuous arterial infusion chemotherapy (CAIC), we clinicopathologically examined 32 colorectal cancer patients with liver metastases. Seventy patients were treated with AEC, and 15 patients with CAIC. In the AEC regimen, either ADR or CDDP dissolved in Lipiodol was infused by the implanted reservoir every one to two months. Otherwise, for the CAIC regimen, 360 mg/m2/day of 5-FU was continuously infused by the reservoir for 14 days. Subsequently, on day 22 after the initial 5-FU infusion, 180 mg/m2/day of 5-FU was continuously infused for 7 days. After a 7-day interval without infusion, 180 mg/m2/day of 5-FU was infused for 7 days. This 7-day infusion/7-day no-infusion cycle was repeated. The efficacy of the AEC was 6% (1 PR + 7 NC + 9 PD), CAIC (6 PR + 4 NC + 5 PD), suggesting that CAIC provides the better response rate. With regard to prognosis, the 1- and 2-year survival rates of AEC were 63% and 19%, respectively. The median survival time was 415 days. Otherwise, the 1- and 2-year survival with CAIC was 54% and 40%, respectively, and the median survival time was 470 days. No significant difference between the AEC and the CAIC was observed in the colorectal cancer patients with liver metastases.

Association of epidermal growth factor-related peptides and type I receptor tyrosine kinase receptors with prognosis of human colorectal carcinomas.

The frequency of expression and localization of cripto-1 (CR-1), amphiregulin (AR), transforming growth factor alpha (TGF alpha), epidermal growth factor receptor (EGFR) and erbB-2 were examined by immunohistochemistry in 45 carcinomas and adjacent non-involved normal colon mucosa. Thirty (66.7%), 24 (53.3%), 23 (51.1%), 23 (51.1%) and 13 (28.9%) of the 45 carcinomas showed positive staining for CR-1, AR, TGF alpha, EGFR and erbB-2, respectively, whereas 7 (15.5%), 17 (37.7%), 15 (33.3%), 20 (44.4%) and 0 (0%) of the corresponding non-involved normal mucosa specimens were reactive. Among 13 carcinomas with lymph node involvement, 10 (76.9%), 8 (61.5%), 10 (76.9%), 8 (61.5%) and 7 (53.8%) exhibited positive staining for CR-1, AR, TGF-alpha, EGFR and erbB-2, respectively. There was a statistically significant association between the frequency of either TGF alpha (P < 0.05) or erbB-2 (P < 0.05) expression and lymph node metastasis. In addition, a significantly higher frequency of positive staining for TGF alpha was observed in Dukes' grade C carcinomas (P < 0.05). Finally, significant trends for coexpression of EGFR and either TGF alpha (P < 0.01) or AR (P < 0.05) were detected in carcinomas. These data suggest that AR and TGF alpha may play an important role in the development of colorectal carcinomas through an autocrine mechanism involving EGFR, and demonstrate that TGF alpha and erbB-2 may be more reliable indicators of metastasis or prognosis than CR-1, AR or EGFR in human colon cancers.

[A case of advanced gastric cancer responding to an FAP (5-FU, ADM, platinum compounds) combined chemotherapy].

An experience with an advanced gastric cancer patient with metastases to bilateral breasts, uterus, abdominal lymph nodes, bilateral axillary and supraclavicular lymph nodes, and bone marrow, responded extremely well to an FAP combined chemotherapy as reported here. The patients received four courses of 5-FU (370 mg/m2/day, for five days, continuous infusion), ADM (30 mg/m2 on day 1, i.v.) and CDDP (55 mg/m2 on day 1, i.v.) every 3 weeks in our hospital. This was followed by 7 months of outpatient therapy with 5-FU (550 mg/m2 on day 1, i.v.), ADM (30 mg/m2 on day 1, i.v.) and CBDCA (330 mg/m2 on day 1, i.v.) for every 4 weeks. The complete remission of the primary and metastatic lesions, that was confirmed by the histological examinations, was obtained after 10 months since the initial treatment started. The toxicity was generally moderate, however, the alopecia was severe. The patient has been living for 6 months without any signs of the recurrence after the complete remission obtained.

Clinicopathological study on combination therapy consisting of arterial infusion of lipiodol-dissolved SMANCS and transcatheter arterial embolization for hepatocellular carcinoma.

Combination therapy (LpTAE) consisting of arterial infusion of a lipophilic anticancer drug, SMANCS, dissolved in an oily lymphographic agent, lipiodol (LPD), and transcatheter arterial embolization (TAE) for hepatocellular carcinoma (HCC) was studied with special reference to the pathological findings. A total of 32 patients were subjected to surgical resection after LpTAE. The pattern of LPD deposition in the tumor was examined by CT scan (Lipiodol CT, LpCT) at 7 days and/or 1 month after LpTAE. The resected materials were examined radiographically with soft X-rays and histologically. LPD was deposited in tiny daughter nodules with a diameter of less than 5 mm and in tumor thrombi as well as in the main tumors, which showed necrotic change. Part of the LPD flowed out from the main tumor via the drainage vein and was deposited in the capsular invasion, resulting in necrosis. LPD accumulated almost exclusively within the blood spaces of trabecular-type HCC, creating a pattern corresponding to a cast of the tumor vessels, which showed prominent necrosis. On the other hand, LPD was not deposited in scirrhous, compact, or well-differentiated HCC, which showed little or no necrosis. It was demonstrated that LpCT images, which accurately depicted the existence and the extent of LPD deposition and necrosis in the tumor, were useful for precise evaluation of the therapeutic effect. Our findings indicate that LpTAE and LpCT are valuable for the diagnosis and treatment of HCC and should play a central role in systemic therapeutic approaches to this disease.

[Intraoperative radiation therapy of carcinoma of the pancreas].

From May 1978 to December 1989, 54 patients with pancreatic carcinoma underwent electron beam intraoperative radiotherapy (IORT). Three died of preoperative complications within a month. In 19 patients, liver metastasis and/or peritoneal dissemination became obvious at laparotomy. They therefore underwent IORT with palliative intent. Relief of pain was obtained in 12 of the 14 patients with pain (85.7%), although three of them were treated in combination with splanchnic nerve block. Thirty-two patients with localized carcinoma underwent IORT with curative intent (total tumor resection in 6, partial resection in 6, and no tumor resection in 20). With additional IORT treatment, their survival was significantly (p less than 0.05 during the 18th month) longer than that of 40 patients without IORT (total tumor resection in 13, partial resection in 9, and no tumor resection in 18). Among the patients without tumor resection, the 20 patients who underwent IORT survived significantly (p less than 0.05 during the 7th month) longer than the 18 patients who did not. Twelve patients who underwent total pancreatectomy died earlier than the 23 patients treated with IORT in combination with partial tumor resection or no tumor resection (not significant). In 26 patients with partial tumor resection or no tumor resection, either additional external irradiation or IORT using a small field within a large field significantly (p less than 0.05 during the 7th and 8th month) improved survival compared with IORT using a single field. Of the 20 patients without tumor resection, relief from pain was obtained in 18 of 19 patients with pain (94.7%), although two of them were treated in combination with splanchnic nerve block. In terms of adverse effects possibly caused by IORT in 26 patients who survived longer than 6 months, gastrointestinal problems were serious in several (gastric ulcer in 2, duodenal stenosis in 1, gastric ulcer and duodenal stenosis in 1, and duodenal perforation and duodenal ulcer in 1). In conclusion, our experience suggests that IORT can relieve patients of serious pain and improve survival in patients with localized pancreatic carcinoma.

[Clinicopathological estimation of intra-arterial infusion chemotherapy of locally advanced breast cancer].

The effect of intra-arterial infusion chemotherapy with adriamycin as a preoperating procedure was analyzed clinicopathologically in 30 cases with locally advanced breast cancer. A clinical response rate of 53.3% was obtained by the treatment and remarkable degenerative changes of tumor cells were noted histologically in the primary lesions. But there was no relationship between histological therapeutic effect and regression rate in tumors. A recurrence rate showed a higher correlation with histological therapeutic effect in comparison with clinical therapeutic effect. Especially, non-necrosis type that tumor cells were still alive mainly in the vessels showed significantly a higher recurrence rate in comparison with a central necrosis type or focal necrosis with fibrosis and hyalinization type. The local regional recurrence rate of patients receiving intra-arterial infusion chemotherapy was lower than that of patients, as the historical controls, receiving no therapy before operation. But prognostically, there was no significant difference in a survival rate between both groups. So, after operation, other alternative or multidisciplinary adjuvant chemo-endocrine therapy seems to be necessary for improving the survival rate.

Adsorption removal of benzalkonium chloride by granular activated carbon for medical waste water treatment.

The adsorption removal of benzalkonium chloride disinfectant by granular activated carbon is discussed. The adsorption isotherm of benzalkonium chloride was expressed by the Freundlich equation. A significant correlation was found between the amount of benzalkonium chloride adsorbed in less than 1000 ppm of equilibrium concentration and the micropore volume of activated carbon. As for the adsorption rate, a change in intraparticle diffusiveness was found with increasing adsorption ratio. No significant correlation between the values of intraparticle diffusiveness and the properties of activated carbon was found. It was concluded that the micropore volume of activated carbon was the dominant factor in the adsorption removal of benzalkonium chloride by granular activated carbon.

[Effect of medroxyprogesterone acetate on the cell kinetics in primary breast cancer].

Effect of medroxyprogesterone acetate (MPA) on the breast cancer cell kinetics was investigated by flow cytometry on paraffin-embedded tissues. Nuclear DNA contents were measured in 67 primary cases. MPA, 1,2000 mg/day, was administered orally for two weeks in 12 cases (MPA group) and the remaining cases (n-MPA group) served as the controls, until the day before operation. The DNA histograms were compared between both groups. The mean percentage of G0 + G1 phase was higher and that of S-phase and G2 + M phase, lower, in the MPA group than those in the n-MPA group. Especially in estrogen receptor positive and premenopausal cases, a significant difference was present between both groups. These results suggest that MPA could inhibit DNA synthesis with a delay of the cell cycle progression in human breast cancer.

[Two cases of hepatocellular carcinoma with omental mass].

Hepatocellular carcinoma rarely causes disseminated metastasis or distant metastasis. We have recently encountered two cases of hepatocellular carcinoma with omental mass. In the first case, we misdiagnosed the omental metastasis as part of the primary tumor. In the second case, omental mass was hypervascular on angiography and this was very useful for an exact diagnosis.

[Intraperitoneal administration of recombinant interferon-beta for prevention in peritoneal metastasis of gastric cancer].

Recombinant interferon-beta (IFN-beta) shows a high anti-tumor effect on cancerous ascites, has little local irritative action and can safely be administered intraperitoneally. A randomized trial was conducted to evaluate the efficacy of intraperitoneal administration of IFN-beta for the purpose of preventing peritoneal metastasis of gastric cancer. The subjects selected were patients under 75 years of age who were macroscopically positive for serosal invasion and had undergone curative operation. Comparison was made by the envelope method between the cases given IFN-beta i.v. at 6 x 10(6) units continuously for 14 days from the day of operation and from 1 week after operation. MMC, 20 mg (i.v.) on the day of operation and 5-FU, 200 mg (p.o.) for 1 year from 2 weeks after operation were administered, respectively, in the two groups. The number of cases registered from March, 1987 to September, 1988 was 33, with 17 in the administration group and 16 in the control group. No difference was noted between the two groups in 3-year survival rate and disease free survival rate. As to the recurrence involving the peritoneum, however, there was a difference between the two groups, with 1 out of 6 cases in administration group and 3 out 4 cases in control group. Intraperitoneal chemotherapy can be an effective adjuvant therapy for gastric cancer, if cases are selected.