Immunohistochemical analyses of E-cadherin, beta-catenin, CD44s, and CD44v6 expressions, and Ki-67 labeling index in intraductal papillary mucinous neoplasms of the pancreas and associated invasive carcinomas.

We examined the expressions of adhesion molecules (E-cadherin, beta-catenin, CD44s, and CD44v6) and Ki-67 labeling index (Ki-67 LI) in low- and moderate-grade dysplasia and invasive carcinoma components in ten noninvasive intraductal papillary mucinous neoplasms (IPMNs) of the pancreas and eight invasive carcinomas associated with IPMNs of the pancreas using immunohistochemical methods. There was no significant difference in regard to the proportion of components expressing either E-cadherin or beta-catenin in more than 70% of the tumor cells between the low- and moderate-grade dysplasia components. In contrast, the proportion of those in invasive carcinoma components was significantly lower than in low- or moderate-grade dysplasia components. Also, there was no significant difference in the proportion of components expressing CD44s or CD44v6 in more than 5% of tumor cells among low-grade dysplasia, moderate-grade dysplasia, and invasive carcinoma components. In contrast, the Ki-67 LI values increased in the order of low-grade dysplasia, moderate-grade dysplasia, and invasive carcinoma components, with significant differences among them. The present results indicate that carcinoma components are associated with a decrease in tumor cells expressing E-cadherin and beta-catenin and have the highest proliferative activity.

[A case of advanced rectal cancer responding to l-Leucovorin (LV)/5-fluorouracil( 5-FU) therapy as neoadjuvant chemotherapy].

We report a case in which l-Leucovorin/5-fluorouracil (l-LV/5-FU) therapy was remarkably effective for advanced rectal cancer as neoadjuvant chemotherapy (NAC). A 54-year-old man complained of bloody stool and constipation,and was diagnosed as having stage IIIB advanced rectal cancer with N2 lymphnode metastases on July 31, 2003. Two cycles of NAC by l-LV/5-FU therapy were performed. On abdominal computed tomography (micro CT), the primary lesion in the rectum decreased 82% and the metastatic lymphnodes had disappeared. As we established a diagnosis of the downstaging for stage II, a lower anterior resection with D3 lymphnode dissection was performed on December 5, 2003. The pathological examination demonstrated II, mod, 1.8 x 2.2 cm, a1, ly1,v0, ow(-), aw(-), n0, stage II. We could allow curability-A resection. The pathological effect of chemotherapy was grade 2 in which cancer cells became necrotic, suggesting apoptosis. The postoperative course was good. Postoperatively, 3 cycles of l-LV/5-FU therapy were performed. Although the patient had to be followed with internal use of 5-FU 200 mg/day as an outpatient from June 2, 2004, to date, there has been no sign of recurrence during the 12-month follow-up after the operation. Moreover, no adverse by chemotherapy was seen during the treatment. Thus, NAC by this therapy may be useful for patients with advanced rectal cancer.

[A case of advanced gastric cancer with direct invasion of the transverse colon responding to paclitaxel/5'-DFUR combined therapy].

A 50-year-old man was diagnosed with non-resectable scirrhous gastric cancer of antrum accompanied with colon ileus due to direct invasion of the transverse colon. As the ileus improved after cecostomy, chemotherapy with TS-1/cisplatin(CDDP) was performed. Because of no response, 4 cycles of paclitaxel (PTX)/doxifluridine (5'-DFUR) therapy was performed as second-line chemotherapy. Since the stenosis of transverse colon dilated completely and the tumor disappeared, we performed total gastrectomy and right hemicolectomy, and could resect completely. Though 2 cycles of PTX/5'-DFUR therapy was performed postoperatively and the patient's postoperative condition was good, he was suffering from carcinomatous peritonitis complicated by ileus and obstructive jaundice 4 months after operation. He died 1 year after the first medical examination, but his QOL was fairly good for 10 months. PTX/5'-DFUR therapy, which has only slight complications, may be useful for patients with recurrent gastric cancer who had been treated with 5-FU administration as first-line chemotherapy. But the future problem was how to control dissemination after surgery in a resectable case after chemotherapy.

[A case of cecal cancer with multiple liver metastases responding to irinotecan (CPT-11)/cisplatin (CDDP) combination therapy for elevation of CA19-9 after complete response (CR) by l-leucovorin(LV)/5-fluorouracil(5-FU) therapy].

A 62-year-old woman complained of abdominal pain and diarrhea from February 2, 2002. She was diagnosed with advanced cecal cancer with simultaneous multiple liver metastases. The serum level of CA 19-9 was 420 U/ ml. Ileoceal resection with D3 lymphnode dissection. The replacement of reservoir for hepatic arterial infusion (HAI) was performed on February 2, 2002. As the dissemination was seen near the mesocolon at laparotomy, we could resect all together. Pathological examination demonstrated II, 5.0 x 2.5 cm, mod, se, INFgamma, ly(1), v(1), n(2), stage IV. Systemic l-leucovorin/5-fluorouracil (l-LV/5-FU) + HAI of weekly high-dose 5-FU combination therapy was initiated at postoperative 14 days. The serum CA 19-9 level decreased immediately but was not within the normal range. On abdominal computed tomography (CT), liver metastatic lesions decreased 9 9% on May 27, 2002 and disappeared on August 26, 2002. Though there were no signs of recurrence, the serum CA 19-9 level elevated as of October, 2002. Since the hepatic artery was occluded, HAI was discontinued on November 28, 2002. The serum CA 19-9 level elevated inspite of the continuation of the l-LV/5-FU therapy which we increased an amount of 5- FU. Thus, we changed low-dose irinotecan (CPT-11)/cisplatin (CDDP) therapy. The serum level of CA 19-9 decreased gradually and got with in normal range on March, 2004. It did not elevate since then. Low-dose CPT-11/CDDP therapy may be useful for patients with advanced colon cancer thought to be resistant to 5-FU as second-line chemotherapy.

[A case of recurrent stomach cancer treated with 5-fluorouracil responding to weekly paclitaxel therapy].

We report a patient with unresectable stage IV stomach cancer with metastasis to the paraaortic lymph nodes who achieved an effective response to neoajuvant chemotherapy, which allowed curability-B resection, and in whom weekly paclitaxel (TXL) therapy for postoperative recurrence was very effective in improving QOL. The patient was a 65-year-old man. After preoperative PMFE therapy, CEA decreased from 68.1 ng/ml to 0.8 ng/ml, and CA19-9 from 15,000 U/ml to 190 U/ml. The paraaortic lymph nodes disappeared, and stomach wall thickening decreased. The overall response to treatment was evaluated as a partial response (PR). After surgery, the patient was given TS-1, but became unable to take oral medication because of retroperitoneal and lymph node recurrence. Since the cancer appeared to be resistant to 5-fluorouracil (5-FU), the patient was treated by weekly TXL therapy. Increased appetite and weight gain were observed from the middle of the first course of therapy, and CEA decreased from 28.2 ng/ml to 4.9 ng/ml, and CA19-9 from 15,000 U/ml to 2,000 U/ml. Abdominal CT scans demonstrated shrinkage of the tumor. Although the patient died 1 year and 8 months after the initial examination, he was able to take oral medication and maintain good QOL for 10 months after the start of TXL therapy. Only grade 1 side effects (alopecia and leukopenia) were observed throughout the course. These results suggest that TXL therapy is effective also for 5-FU-resistant stomach cancer, and exhibits effects early even in patients in a poor general condition, causing only mild side effects, with early improvements in QOL.

[A case of advanced descending colon cancer with peritoneal dissemination responding to weekly high-dose l-leucovorin/5-fluorouracil combination therapy].

We report a case in which l-leucovorin/5-fluorouracil (l-LV/5-FU) combination therapy was remarkably effective for non-resectable advanced descending colon cancer with carcinomatous peritonitis. A 65-year-old man complained of severe abdominal distension, abdominal pain and pulmonary failure, and was diagnosed as having ileus due to descending colon cancer. The patient underwent urgent open laparotomy to release the ileus condition on March 5, 2002. During the laparotomy, we established a diagnosis of nonresectable descending colon cancer accompanied by severe peritoneal dissemination and therefore performed only double-barreled transverse colostomy. The postoperative course was very good. Pathological examination of omental dissemination demonstrated moderately differentiated adenocarcinoma and cytology of ascites was class II. The levels of serum CEA and CA19-9 were within the normal ranges. l-LV/5-FU therapy was initiated postoperatively. Seven cycles of this chemotherapy regimen was performed with no apparent side effect during the treatment. There was no postoperative accumulation of carcinomatous ascites. The patient gained 15 kg compared with body weight admission. On abdominal computed tomography (CT), the primary lesion of the colon decreased 98% and there was no ascites found. To date, there has not been any sign of recurrence during the 19 months of follow-up after this therapy, and we are currently discussing closure of the transverse colostomy. This therapy may be useful for patients with advanced colon cancer accompanied by peritoneal dissemination.

[Complete response to treatment with low-dose FP therapy in a patient with stage IVB primary hepatocellular carcinoma with multiple lung and bone metastases].

We report a case in which low-dose FP (5-fluorouracil/cisplatin, 5-FU/CDDP) therapy was remarkably effective for stage IVB advanced hepatocellular carcinoma (HCC) with lung and bone metastases. 5-FU of 250 mg/body/day was continuously infused over 24 hours and CDDP of 10 mg/body/day was infused over 30 minutes from day 1 to day 5 in a week. Administration was continued for 4 weeks as 1 cycle. An 81-year-old woman was diagnosed with HCC in S3 and underwent a transcatheter hepatic arterial embolization (TAE) for the tumor in December 2000. The patient complained of lumbago and hip pain in July 2001 and was admitted for dysbasia in September 2001. On admission, the level of serum AFP and PIVKA-II elevated to a remarkable 59,300 ng/ml and 25,700 AU/ml. Chest computed tomography (CT) showed multiple bilateral lung metastases and abdominal CT showed a tumor 12 x 11 x 10 cm in diameter in the right, iliac bone. No recurrent sign was found in the liver except for the accumulation of Lipiodol. Low-dose FP therapy of 2 cycles was performed. The levels of serum AFP and PIVKA-II decreased to 374 ng/ml from 59,300 and to 35 AU/ml from 25,700, respectively, after this therapy. The CT findings revealed that a complete response (CR) was obtained for lung metastases and a partial response (PR) was obtained for bone metastases after completion of course 2, and maintained thereafter. The oral UFT of 600 mg was administered after completion of course 2 in the outpatient setting. The level of AFP and PIVKA-II decreased to 13.2 ng/ml and to 26 AU/ml, respectively, in February 2002. No sign of recurrence was seen during the 13 months of follow-up after low-dose FP therapy. Toxic events consisted of only leukopenia (grade 1). Her quality of life (QOL) was fair during this therapy. Low-dose FP therapy is possibly useful for patients with stage IVB advanced HCC.