Hirokazu Takechi

Sentinel Lymph Node Biopsy Using Intraoperative Indocyanine Green Fluorescence Imaging Navigated with Preoperative CT Lymphography for Superficial Esophageal Cancer

BackgroundThe sentinel lymph node (SLN) concept has been gaining attention for gastrointestinal neoplasms but remains controversial for esophageal cancer. This study evaluated the feasibility of SLN identification using intraoperative indocyanine green (ICG) fluorescence imaging (IGFI) navigated by preoperative computed tomographic lymphography (CTLG) to treat superficial esophageal cancer.MethodsSubjects comprised 20 patients clinically diagnosed with superficial esophageal cancer. Five minutes after endoscopic submucosal injection of iopamidol around the primary lesion using a four-quadrant injection pattern with a 23-gauge endoscopic injection sclerotherapy needle, three-dimensional multidetector computed tomography was performed to identify SLNs and lymphatic routes. ICG solution was injected intraoperatively around the tumor. Fluorescence imaging was obtained by infrared ray electronic endoscopy. Thoracoscope-assisted standard radical esophagectomy with lymphadenectomy was performed to confirm fluorescent lymph nodes detected by CTLG.ResultsLymphatic vessels and SLNs were identified preoperatively using CTLG in all cases. Intraoperative detection rates were 100% using CTLG and 95% using IGFI. Lymph node metastases were found in four cases, including one false-negative case with SLNs occupied by bulky metastatic tumor that were not enhanced with both methods. The other 19 cases, including three cases of metastatic lymph nodes, were accurately identified by both procedures.ConclusionsPreoperative CTLG visualized the correct number and site of SLNs in surrounding anatomy during routine computed tomography to evaluate distant metastases. Referring to CTLG, SLNs were identified using IGFI, resulting in successful SLN navigation and saving time and cost. This method appears clinically applicable as a less-invasive method for treating superficial esophageal cancer.

Preoperative chemotherapy with weekly docetaxel plus low-dose cisplatin and 5-fluorouracil for stage II/III squamous cell carcinoma of the esophagus

BackgroundDocetaxel is a powerful anticancer agent for esophageal cancer. Preoperative combined chemotherapy with weekly docetaxel plus low-dose cisplatin and 5-fluorouracil (DFP) followed by surgery is expected to improve the survival of patients with resectable esophageal squamous cell carcinoma.MethodsClinical stage II/III squamous cell carcinoma patients who received DFP followed by esophagectomy (NAC group, n = 13) were compared retrospectively with patients who received surgery without preoperative DFP (Surgery group, n = 12). Not only the efficacy and toxicity of initial chemotherapy but also morbidity and survival after esophagectomy were assessed.ResultsOf 13 patients, the overall response rate was 92.3%; 30.8% (4/13) patients had CR, 61.5% (8/13) PR, 7.7% (1/13) SD, and 0 (0/13) PD. The 4 patients who achieved a pathological complete response (pCR) included 1 with cT4N1M0, 2 with cT3N1M0, and 1 with cT3N0M0. More than grade 3 toxicity of neutropenia and stomatitis occurred in 15.4% and 23.1% of patients, respectively. Leakage was 23.1% in the NAC group and 8.3% in the Surgery group. No treatment-related deaths occurred in the NAC group.ConclusionsThis regimen as preoperative chemotherapy seemed to provide a high response rate and a favorable survival benefit with acceptable toxicity and morbidity. To validate the clinical significance of this protocol, a randomized trial is essential.

Efficacy of percutaneous endoscopic gastrostomy on unplanned treatment interruption and nutritional status in patients undergoing chemoradiotherapy for advanced head and neck cancer

OBJECTIVE Efficacy of percutaneous endoscopic gastrostomy (PEG) on unplanned treatment interruption and nutritional status was examined in patients undergoing chemoradiotherapy (CRT) for advanced head and neck cancer. METHODS We retrospectively reviewed hospital charts of 44 patients with advanced head and neck cancer who were treated with CRT. RESULTS CRT-induced mucositis of grade 3 or worse and inadequate oral intake of less than one third of their usual intake developed in 33 patients who were recommended PEG placement, but not in 11 patients. Thirteen patients accepted PEG placement and then completed CRT (compliant group). However, among 20 patients who refused both PEG and nasogastoric tube (NGT) placements (non-compliant group), 10 required unplanned interruptions of CRT at a radiation dose around 30-40 Gy (UI-CRT group) while 10 others could complete CRT without interruption (C-CRT group) CRT. Total serum protein levels were significantly decreased after CRT in all patients. DISCUSSION It is suggested that therapeutic PEG placement is useful for preventing unplanned interruption of CRT in patients with advanced head and neck cancer. After severe mucositis and inadequate oral intake have developed during CRT, PEG placement should be considered before the radiation therapy dose of 30 Gy.

Thirty percent of ductal carcinoma in situ of the breast in Japan is extremely low-grade ER(+)/HER2(-) type without comedo necrosis

Background Overdiagnosis in mammography (MMG) is a problem. Combination of MMG and ultrasonography for breast cancer screening may increase overdiagnosis. Most cases of overdiagnosis are low-grade ductal carcinoma in situ (LGD), but no reports have focused on them. Materials and methods We immunostained 169 ductal carcinoma in situ (DCIS) cases for ER, PgR, HER2 and Ki67 and classified them into 4 subtypes: ER(+)/HER2(-), ER(+)/HER2(+), ER(-)/HER2(-) and ER(-)/HER2(+). The Ki67 index was used to evaluate the grade of malignancy and examined for correlations with each ER/HER2 subtype and the nuclear grade (NG), with/without comedo necrosis. Results The Ki67 index correlated significantly with NG, both with/without comedo necrosis, and reliably evaluated the grade of malignancy. The index for ER(+)/HER2(-) (n=117, 69.2%) was 7.45±7.10, which was significantly lower than for each of the other types. The index was 5.71±6.94 for ER(+)/HER2(-) without comedo necrosis (n=52, 30.8%), which was significantly lower than with comedo necrosis. This was considered LGD, characterized by absence of microcalcification in MMG and either presence of a solid mass or cystic lesion or absence of hypoechoic areas in ultrasound. Conclusion In Japan, ER(+)/HER2(-) without comedo necrosis accounts for about 30% of DCIS and is LGD. This may be being overdiagnosed. J. Med. Invest. 63: 192-198, August, 2016.

Molecular Diagnosis and Targeting Therapy for Breast Cancer

Breast cancer (BC) is a representative cancer for which molecular targeting therapy is most popular, because systemic therapy is selected according to tumor biological subtypes, luminal A, luminal B, HER2-enriched, and basal-like; those are decided by gene expression pattern or estrogen receptor (ER), HER2, and tumor proliferation measured by Ki67 expression in immunohistochemistry. Approximately 70–80% of BC is ER positive. Adjuvant therapy is selected according to the guideline based on the large-scale randomized control trials. Selective estrogen receptor modulators (SERM), like tamoxifen or toremifene, and gonadotropin-releasing hormone agonist (GnRH) are used in combination or alone for premenopausal metastatic BC (MBC) and in adjuvant setting. Aromatase inhibitor (AI) targeting the enzyme aromatase is recommended for postmenopausal BC in adjuvant and MBC both in pre- and postmenopausal.

Phase II Study of S-1 Combined With Low-Dose Docetaxel as Neoadjuvant Chemotherapy for Operable Breast Cancer Patients (N-1 Study)

Micro‐Abstract Efficacy of S‐1 (Taiho Pharmaceutical Co, Tokyo, Japan) used in combination with docetaxel (S‐1+DOC) for breast cancer was evaluated. After 4 cycles of S‐1+DOC, patients with a complete response (CR) underwent surgery, and those with partial response underwent 4 more cycles. Patients with stable disease or progressive disease received epirubicin and cyclophosphamide or trastuzumab and paclitaxel. The pathological CR rate was 29 patients [34.9%], and 8 patients [19.5%] for patients with luminal type breast cancer. S‐1+DOC was expected to be an effective chemotherapy for luminal type breast cancer. Background: To improve the pathological complete response (pCR) rate, we devised new neoadjuvant chemotherapy. Efficacy and safety of the oral fluoropyrimidine derivative S‐1 (Taiho Pharmaceutical Co, Tokyo, Japan) combined with low‐dose docetaxel (S‐1+DOC) were evaluated. Patients and Methods: Patients were treated with docetaxel (40 mg/m2 intravenously on day 1) and S‐1 (40 mg/m2 orally twice per day on days 1‐14) every 3 weeks for 4 cycles. In accord with the Response Evaluation Criteria In Solid Tumors version 1.1 criteria, the patients who showed a complete response (CR) underwent surgery, and those who achieved a partial response (PR) underwent 4 more cycles of S‐1+DOC. Patients who achieved stable disease (SD) or progressive disease (PD) received EC (epirubicin and cyclophosphamide) or HT (trastuzumab and paclitaxel) according to their HER2 status. The primary end point was the pCR rate. Results: Ninety‐four patients entered the study. After 4 cycles of S‐1+DOC, CR was noted in 5 patients, PR in 57, SD in 18, and PD in 3. Of the patients who achieved SD and PD, 12 received EC, and 9 received HT. Among the 83 assessable patients, the pCR rate was 34.9%, and the response rate was 80.7%. The pCR rates were 19.5% in the luminal type group, 53.8% in the luminal HER2 group, 46.1% in the HER2 group, and 50.0% in the triple‐negative group. Conclusion: The S‐1+DOC regimen in this study could be well tolerated and a new candidate neoadjuvant chemotherapy in operable breast cancer patients. It is also expected to be effective even in patients with luminal type disease. However, further randomized control trials are needed to ascertain whether pCR can contribute to favorable outcomes.