Jin Matsuyama

p53 genotype predicts response to chemotherapy in patients with squamous cell carcinoma of the esophagus.

BackgroundResponse to chemotherapy and anatomical spread are significant prognostic factors in patients with esophageal squamous cell carcinoma (ESCC) treated by chemotherapy then surgery. Predicting the response to chemotherapy would allow significant optimization of cancer treatment.MethodsGenomic mutation and protein expression of p53 were investigated retrospectively by polymerase chain reaction (PCR) single-strand conformation polymorphism (SSCP) and immunohistochemistry (IHC) using biopsy specimens from 77 ESCC patients before chemotherapy with 5-fluorouracil, adriamycin, and cisplatin. p53 status was correlated with various clinicopathological factors. Thereafter, we performed a prospective study of 20 consecutive patients to test our prediction model.ResultsThe retrospective study showed mutant p53 genotype and positive p53 IHC staining in 46.8 and 55.8% of patients, respectively, which was not associated with patient’s clinicopathological findings including initial tumor stage. Objective response to chemotherapy was observed in 65.9% of patients with wild genotype, but in only 16.7% of patients with mutant genotype. Patients with mutations in p53 therefore showed significantly poorer prognosis than those without mutant p53. In contrast, p53 IHC staining did not correlate with response to chemotherapy, curative resection rate or prognosis. In the prospective study, p53 mutation was seen in 50% (10/20) of patients and was again consistently associated with poorer response to chemotherapy and poorer prognosis.Conclusionsp53 genotype of pretreatment biopsy is a potentially useful predictor of response to chemotherapy and prognosis in ESCC patients. This information might be valuable to clinicians in deciding on the optimal clinical strategy in patients with ESCC.

Evaluation of clinical significance of 18F-fluorodeoxyglucose positron emission tomography in superficial squamous cell carcinomas of the thoracic esophagus

(18)F-fluorodeoxyglucose (FDG) positron emission tomography (PET) is used for pre-treatment staging and evaluation of response to pre-operative therapy in advanced thoracic esophageal cancers. To evaluate the clinical significance of PET diagnosis of superficial thoracic esophageal cancers, FDG-PET was conducted preoperatively in 41 patients with such cancers without pre-operative therapy. We compared the PET diagnosis with clinicopathological findings with respect to both the primary tumor and lymph node (LN) metastasis. Of the 41 superficial thoracic esophageal cancers, 21 (51.2%) were PET positive for primary tumors. Although tumor length and histological type did not correlate with FDG uptake by primary tumors, non-flat (elevated or depressed) tumors showed significantly stronger FDG uptake than flat ones. Of 28 tumors infiltrating the deep submucosal layer, 19 (67.9%) were PET positive, while only two (15.4%) of 13 tumors infiltrating only the mucosa or shallow submucosal layer were PET positive. Manova identified FDG uptake as the only independent risk factor for deep submucosal invasion (odds ratio, 7.407; P = 0.0279). In 13 patients with pathological LN metastasis, although no LN metastasis was detected by FDG-PET, FDG uptake by the primary tumors was the only risk factor for LN metastasis (P = 0.0318). PET-negative tumors tended to reflect longer disease-free survival than PET-positive tumors, although this was not significant. FDG-PET is useful for detecting tumors infiltrating the middle or deep submucosal layer (sm2/sm3), and for predicting LN metastasis in patients with superficial thoracic esophageal cancers. FDG-PET is helpful for decision-making regarding treatment of such patients.

Salvage lymphadenectomy of the right recurrent nerve node with tracheal involvement after definitive chemoradiation therapy for esophageal squamous cell carcinoma: report of two cases.

Thoracic esophageal cancers frequently metastasize to the right recurrent nerve nodes (RRNNs). In fact, huge RRNNs invading the trachea sometimes remain after definitive chemoradiation therapy (CRT), despite complete remission of the primary lesion. We performed salvage lymphadenectomy of a large RRNN combined with partial resection of the trachea in two patients. Using an anterior approach, we removed part of the sternum, clavicle, and the first and second costal cartilage; then, we removed the RRNNs with combined resection of the lateral quarter circumference of the trachea, the esophageal wall, and the recurrent nerve. Reconstruction was done with a musculocutaneous patch of major pectoral muscle to cover the tracheal defect. The only minor complication was venous thrombosis in one patient. Thus, combined removal of the RRNN and trachea was performed safely as a salvage operation after definitive CRT for esophageal squamous cell carcinoma.

Phase II Feasibility Study of Adjuvant S-1 plus Docetaxel for Stage III Gastric Cancer Patients after Curative D2 Gastrectomy

Objective: The aim of this prospective study was to evaluate the feasibility and safety of adjuvant S-1 plus docetaxel in patients with stage III gastric cancer. Methods: We enrolled 53 patients with pathological stage III gastric cancer who underwent D2 gastrectomy. They received oral S-1 (80 mg/m2/day) administration for 2 consecutive weeks and intravenous docetaxel (40 mg/m2) on day 1, repeated every 3 weeks (1 cycle). The treatment was started within 45 days after surgery and repeated for 4 cycles, followed by S-1 monotherapy (4 weeks on, 2 weeks off) until 1 year after surgery. The feasibility of the 4 cycles of chemotherapy, followed by S-1 administration, was evaluated. Results: A total of 42 patients (79.2%, 95% CI 65.9–82.9) tolerated the planned 4 cycles of treatment with S-1 and docetaxel, and 34 patients (64.2%, 95% CI 49.8–76.9) completed subsequent S-1 monotherapy for 1 year. Grade 4 neutropenia was observed in 28% and grade 3 febrile neutropenia in 9% of the patients, while grade 3 nonhematological toxicities were relatively low. Conclusions: Adjuvant S-1 plus docetaxel therapy is feasible and has only moderate toxicity in stage III gastric cancer patients. We believe that this regimen will be a candidate for future phase III trials seeking the optimal adjuvant chemotherapy for stage III gastric cancer patients.

Prognostic factors for cytology-positive gastric cancer

PurposePositive peritoneal lavage cytology for gastric carcinoma cells (CY1) is considered distant metastasis and is classified as Stage IV. However, patients with CY1 comprise a heterogeneous population, and their prognosis varies greatly. The prognostic factors for gastric cancer patients with CY1 were retrospectively reviewed.MethodsThe participants were 80 gastric cancer patients with CY1 in our institution encountered between 2005 and 2017. Prognostic factors were analyzed using univariate and multivariate analyses.ResultsThe operative procedure was distal gastrectomy for 30 patients, total gastrectomy for 27 patients, staging laparoscopy for 10 patients, gastrojejunostomy for 8 patients, and probe laparotomy for 5 patients. Other distant metastases were recognized in 36 patients. A multivariate analysis revealed that other distant metastases were the strongest independent risk factor for the overall survival (p < 0.0001). When the cohort was limited to CY1 patients without other distant metastases, cN2–3 (p = 0.01), the prognostic nutritional index (PNI) < 40 (p = 0.02) and Type 4 (p = 0.03) were independent risk factors according to a multivariate analysis. The survivals of patients with cN2–3 or PNI < 40 after gastrectomy were equivalent to those with other distant metastases, as assessed by log-rank analyses.ConclusionsThe prognoses of CY1 gastric cancer patients with cN2–3 or PNI < 40 were poor, even after gastrectomy.

Evaluation of the effects of postoperative oral nutrition support on body weight in gastric cancer patients by using an elemental diet: A randomized study.

110 Background: Postoperative weight loss causes deterioration in the patient’s quality of life and influences long-term prognosis in gastric cancer patients who have undergone gastrectomy. Moreover, recent retrospective studies indicated postoperative weight loss as a risk factor for premature interruption of S-1 adjuvant chemotherapy. We conducted a prospective randomized controlled study to examine whether the early institution of nutritional support comprising an oral elemental diet (ED) prepared for post-gastrectomy patients with depressed digestive/absorptive function would help prevent postoperative weight loss. Methods: After surgery, patients were randomly assigned to the ED or control groups. The groups were divided according to the surgical methods used (total/distal gastrectomy), clinical stage (≤Ia/>Ia), and patients’ body mass index ( 18.5). In patients assigned to the ED group (Elental, 300 kcal) was provided in addition to the regular diet from the day starting soft rice diet or equi...