Identification of sentinel lymph nodes by contrast-enhanced ultrasonography with Sonazoid in patients with breast cancer: a feasibility study in three hospitals.

The aim of this prospective study was to evaluate the feasibility of periareolar injection of the contrast agent Sonazoid (SNZ) followed by ultrasonography (US) for the identification of sentinel lymph node (SLN) in breast cancer patients with clinically negative node. Patients (n = 100) with T1-2N0M0 breast cancer received a periareolar injection of SNZ followed by US to identify contrast-enhanced SLN. Each contrast-enhanced SLN underwent fine needle aspiration cytology (FNAC) followed by SLN biopsy with a conventional method using blue dye and/or radiocolloid (B/R). In almost all cases, contrast-enhanced lymphatic vessels were clearly visualized by US soon after the periareolar injection of SNZ and the SLNs were easily identified with an identification rate of 98% (98/100) for SNZ and 100% (100/100) for B/R. The number of SLNs identified by SNZ (SNZ-SLN) (mean per patient, 1.52) was significantly lower than that identified by B/R (B/R-SLN) (2.19) (P < 0.0001). Twenty-five patients with positive SLNs had at least one positive SNZ-SLN. On a node-by-node basis, sensitivity, specificity, and accuracy of FNAC for SNZ-SLNs (n = 149) were 33.3%, 99.2%, and 85.9%, respectively. Identification of SLN by periareolar injection of SNZ is a technically simple method with an identification rate as high as 98%. SNZ-SLN thus seems to be a good target for FNAC, but sensitivity of FNAC for SNZ-SLNs needs to be improved.

Significance of TP53 mutations determined by next-generation "deep" sequencing in prognosis of estrogen receptor-positive breast cancer.

Next-generation "deep" sequencing (NGS) was used for the mutational analysis of TP53, and a DNA microarray was used for the determination of the TP53 mutation-associated gene expression signature (TP53 GES) in 115 estrogen receptor (ER)-positive breast cancers. NGS detected 27 TP53 mutations, of which 20 were also detected by Sanger sequencing (SS) and seven were detected only by NGS. A significantly higher number of mutant alleles (33.9%) was detected in the tumors with TP53 mutations detected by SS compared with those with TP53 mutations detected only by NGS (11.1%). The TP53 mutations detected by NGS were more significantly associated with a large tumor size, a high histological grade, progesterone receptor-negativity, and HER2-positivity compared with those detected by SS. The TP53 mutations detected by SS, but not those detected by NGS or the p53 immunohistochemistry, exhibited a significant association with poor prognosis. In addition, the TP53 GES more clearly differentiated low- from high-risk patients for relapse than the TP53 mutations detected by SS, regardless of the other conventional prognostic factors. Thus, NGS is more sensitive for the detection of TP53 mutations, but the prognostic significance of these mutations could not be demonstrated. In contrast, the TP53 GES proved to be a powerful prognostic indicator for ER-positive tumors.

Association of GSTP1 methylation with aggressive phenotype in ER-positive breast cancer.

AIM: We investigated the association of glutathione S-transferase P1 (GSTP1) expression and methylation status with clinicopathological characteristics of estrogen receptor (ER)-positive breast cancers. MATERIALS AND METHODS: Primary ER-positive breast cancer patients (n=177, stage I-III) were retrospectively analyzed. A quantitative GSTP1 methylation assay was performed using DNA micro-dissected from formalin-fixed and paraffin-embedded (FFPE) breast surgical specimens and GSTP1 expression was examined immunohistochemically. RESULTS: GSTP1 methylation index (MI) was higher for the following patient subsets: Large-size (p=0.029), high-grade (p=0.010), human epidermal growth factor receptor-2 (HER2)-positive (p=0.024) and Ki67-positive (p=0.001) patients. In addition, GSTP1 hyper-methylation was more frequently observed in the luminal-B than the luminal-A subtype (p<0.001) and there was no significant difference in GSTP1 positivity between the two subtypes (p=0.150). CONCLUSION: GSTP1 methylation may well be associated with the pathogenesis of the biologically-aggressive phenotype in ER-positive breast cancer.

[A case of gastric cancer with liver metastasis had a good reaction to S-1/CDDP chemotherapy after S-1 chemotherapy was ineffective].

A woman in her sixties underwent total gastrectomy for gastric cancer. The pathological diagnosis was pT3, pN3, sH0, pCY0, sP0, sM0, fStage IV. Chemotherapy with S-1 was used after surgical treatment. Because a CT scan after three courses chemotherapy showed the paraaortic lymph nodes swelling, combination chemotherapy with S-1 and docetaxel was used as a second-line chemotherapy. When the CT scan after 8 courses of this combination chemotherapy revealed multiple liver metastases, the chemotherapy was changed to CPT-11 monotherapy and paclitaxel monotherapy as the third-and fourth-line chemotherapy, respectively. In spite of those chemotherapies, the metastatic disease progressed, and therefore, combination chemotherapy with S-1 and CDDP was used as the fifth-line chemotherapy. After 6 courses of this treatment, serum CEA and CA19-9 levels dropped into the normal range. Multiple liver metastases were markedly reduced, and were considered as a partial response(PR). The patient is still alive, maintaining the effect of PR for 17 months without any adverse effects except appetite loss and vomiting of grade 2.

Pilot study of a combination of S-1 and paclitaxel for patients with peritoneal metastasis from gastric cancer.

BACKGROUND: This pilot study was carried out to evaluate the efficacy of chemotherapy for patients with peritoneal dissemination from gastric cancer or positive lavage cytology diagnosed by staging laparoscopy. METHODS: Sixteen patients were enrolled. Paclitaxel was administered at 120 mg/m(2) on day 1 and S-1 was administered orally at 80 mg/m(2) for 14 consecutive days, followed by a 1-week rest, as one course. After five courses of this therapy, the primary gastric tumors were evaluated and second-look laparoscopy was performed for patients showing partial response or stable disease with clinical benefit. RESULTS: Partial response or stable disease with clinical benefit was confirmed in seven and five patients, respectively, and these patients underwent second-look laparoscopy. No viable cancer cells were detected on cytopathological investigation during second-look laparoscopy in 9 patients who underwent surgical treatment. The intent-to-treat response rate for gastric tumor was 44% and the rate of disappearance of peritoneal metastasis was 38% (6 cases) at surgery. The median survival time was 555 days. Leucopenia of grade 3 and neutropenia of grade 3 were recognized in two and three patients, respectively. CONCLUSION: This chemotherapy regimen may be an acceptable option for patients with peritoneal dissemination. We plan to study this regimen further in gastric cancer patients with peritoneal dissemination.

[Case report--a long-term surviving patient who received lymph node dissection of skip metastasis from rectosigmoid cancer to bilateral lateral lymph nodes].

Skip metastasis in colorectal cancer consists of about 10% of lymph node metastases. We report a rare long-term surviving patient of skip metastasis to lateral nodes after lymph node dissection. A forty-two years old female received anterior resection for advanced rectosigmoid cancer. Because pathological stage of the patient was stage IIIa (T3N1M0), standard adjuvant chemotherapy was provided. Serum CEA increased just two years after the first operation. PET scan showed abnormal FDG uptake in lymph nodes along the aorta. Lymph nodes along the inferior mesenteric artery (IMA), bilateral common iliac artery and aorta were dissected. There were metastases to nodes along the common iliac artery but no metastasis along the IMA was observed. So we diagnosed it as skip metastasis. The patient is still alive without any metastasis after 6 years from the second operation.

[A case of epidermoid cyst in the intrapancreatic accessory spleen mimicking pancreatic malignant tumor].

We report a rare case of an epidermoid cyst in the intrapancreatic accessory spleen with producing CA19-9. A 42-year-old woman was referred to department of internal medicine of our hospital due to growing cystic lesion at the pancreatic tail. Laboratory tests on admission revealed a high serum CA19-9 (102.0 U/mL). Ultrasound sonography detected a 25-mm monolocular cystic tumor with thick capsule and septum. The capsule and septum was enhanced on computed tomography. Endoscopic examination of upper gastrointestinal tract and colon revealed normal. CA19-9 was elevated up to 147.3 U/mL after 2-month follow-up, and she was referred to department of digestive surgery. We suspected a mucinous cystic neoplasm or endocrine tumor, and distal pancreatectomy was performed. The surgical specimen showed a septate cyst surrounded by brown solid tissue resembling normal spleen. The patient was discharged on postoperative day 11. Histological diagnosis was an epidermoid cyst originated from an intrapancreatic accessory spleen. Immunohistochemical analysis of CA19-9 in the epidermoid cyst showed clear staining of the inner epithelium of the cyst. The serum CA19-9 value was confirmed to decline to normal 1 month after resection.

[Outcome of therapy for type 4 gastric cancer with peritoneal metastasis--diagnosis by laparoscopy and effect of chemotherapy].

UNLABELLED: Laparoscopy (st-lap) was performed for type 4 advanced gastric cancer cases, and chemotherapy was performed for P1 or CY1[ P(+)] cases. We present the results here. SUBJECTS: The subjects were type 4 advanced gastric cancer cases from October 2002 to December 2007 who underwent st-lap, as well as 7 P0 and CY0 [P(-)] cases (the operative group), and 18 P(+) cases which underwent chemotherapy (the chemotherapy group). The administration of S-1 (80 mg/m2: days 1-14)+PTX (120 mg/m2: day 1) every 3 weeks was the basic regimen of chemotherapy. RESULTS: After 5- course of chemotherapy, st-lap was performed in 11-PR case(61%) and 4-SD case, in which clinical symptoms had improved. An operation was performed for 11-P(-) case. Overall, there was 8-P(-) case(44%). The 1-and 3-year survival rates in the chemotherapy group in the 11 cases for which an operation was performed were 82 and 36%, respectively, and the 7 non-operative cases were 57 and 14%, respectively. Although there were no significant differences, the outcome was more favorable in the operative group. The 1-and 2-year survival rates in the operative and chemotherapy groups were 72, 39, 51 and 34%, respectively, and there was no significant difference. DISCUSSION: It was suggested that in cases of type 4 advanced gastric cancer, chemotherapy was necessary not only in P(+) but also in P(-) cases. Further investigation regarding the necessity of resection and choice of therapeutic regimen is required.

Surgical approach to left subclavian artery aneurysm in Marfan syndrome.

We present a case of left subclavian artery aneurysm in a 48-year-old man with Marfan syndrome. Aneurysmectomy and interposition with an artificial graft were successfully performed through an infraclavicular incision by dividing the clavicle at its midshaft. The clavicle bone was reconstructed with a steel plate, and the postoperative course was uneventful. Because the arterial wall is fragile in cases of connective tissue disorders such as Marfan syndrome, our surgical approach was considered to be helpful for gentle maneuvering in an adequate operative field.

[A case of metastatic pancreatic cancer after combination chemotherapy with uracil-tegafur and gemcitabine].

We report a case of pancreas head cancer with liver metastasis treated with uracil-tegafur (UFT) and gemcitabine combined chemotherapy. A 66-year-old man was referred to our hospital for obstructive jaundice. We planned to perform a pancreatoduodenectomy, but a small nodule was found at laparotomy on the liver surface. The histopathological diagnosis was adenocarcinoma, so we inserted a self-expandable metallic stent (EMS) in this inoperable pancreas head cancer. We performed 9 courses of UFT and gemcitabine (GEM) combination chemotherapy. Renewed liver metastases did not appear, and the pancreas head tumor partially responded. Pancreatoduodenectomy was performed, and EMS could not be separated from the common bile duct. After treatment with an additional 11 courses of chemotherapy, he took S-1 orally because of a tumor recurrence. He survived for 24 months from the first laparotomy. Combination chemotherapy and surgery enhanced the survival benefit in this case.

[A case of advanced sigmoid colon cancer performed resection of liver metastases after long-term control by S-1 and CPT-11 combination chemotherapy].

A 60-year-old man diagnosed as advanced sigmoid colon cancer was performed sigmoidectomy and D3 lymph node dissection. Intra-operative findings were SE, P0H1N4M (-), and Stage IV. One month after the operation, we started a combination chemotherapy using S-1 plus CPT-11 as one course for five weeks. S-1 (120 mg/body/day) was orally administered continuously for 3 weeks, and CPT-11 (80 mg/m2) was done intravenously on days 1 and 15. A Follow-up abdominal CT scan revealed a drastic reduction of liver metastasis and disappearance of para-aortic lymph node swelling (PR in). The combination chemotherapy was once finished after eight courses due to the patient's request. However, we started to administer the same regimen to him again six months later because of re-growth of liver metastasis. An additional six-course administration resulted in a reduction of liver metastasis by CT scan, and no other abnormal concentration besides two liver metastases by PET-CT examination was observed, and we performed a partial resection (two parts) of the liver and cholecystectomy 24 months after the first operation. The patient has been alive with disease free for five months since the second operation.

[Pilot study of neo-adjuvant chemotherapy involving intraperitoneal administration of paclitaxel and oral S-1 for patients with T3 gastric cancer].

The prognosis of patients with T3 gastric cancer is poor, even if a curative resection is performed. Novel combination neo-adjuvant chemotherapy has been introduced for T3 gastric cancer patients. This pilot study involving 5 patients was performed between December 2002 and March 2003. They were diagnosed with gastric cancer with serosal invasion (T3) without P1 and CY1 by staging laparoscopy. We selected a combined chemotherapy with both paclitaxel and S-1. Paclitaxel at 60 mg/m2 was administered intraperitoneally on days 1 and 8, and S-1 at 80 mg/m2 was administered orally for 14 days followed by a 7-day-rest, as one course. After one course of this therapy, surgery was performed. The plasma concentration of paclitaxel was measured in two patients. Toxicites were generally mild, and no serious adverse reactions were observed. The plasma concentration of paclitaxel was about 100 ng/mL in the period of 1-6 hours after the administration. After one course, four patients underwent a total gastrectomy and one distal gastrectomy. The final histological stagings were included one stage IB, one stage II, one stage IIIA, one stage IIIB, and one stage IV. Three patients died at 10, 11, and 16 months after the initial treatment, and two have survived for 64 and 62 months. As the intraperitoneal administration of paclitaxel and oral S-1 was well-tolerated, further studies should be conducted involving T3 gastric cancer patients.

[A long-term survival case of unresectable hepatohilar bile duct cancer treated with radiotherapy and hepatic arterial infusion chemotherapy ].

The patient, a 79-year-old woman, underwent distal gastrectomy for gastric cancer in November 2002. The lesion was judged to be T1 N0H0POM0 and fStage IA. A hepatohilar tumor was found 1 year after gastrectomy by CT scan. Radiological examinations revealed a presence of right portal vein stenosis and left portal vein obstruction due to hepatohilar bile duct cancer. Surgical treatment was considered to be difficult because of the consequence of the tumor involved in the right hepatic artery. We performed hepatic arterial infusion chemotherapy of 5-fluorouracil 1000 mg/body/week for 8 courses through the reservoir catheter. Radiation therapy was delivered concurrently with hepatic arterial infusion. The condition of the patient was good after receiving 40 Gy, Three months after the additional 20 Gy radiation, the tumor was markedly reduced in size, and was not detected 7 months thereafter. MRI showed no recurrence for three and a half years since chemo-radiation.