Masao Yukawa

Trimodality therapy of esophagectomy plus neoadjuvant chemoradiotherapy improves the survival of clinical stage II/III esophageal squamous cell carcinoma patients

The prognosis of advanced esophageal cancer patients is poor. Trimodality therapy of surgical resection plus neoadjuvant chemoradiotherapy (CRT) has been developed to improve survival through locoregional control, leading to prevention of micrometastasis. We investigated whether or not neoadjuvant CRT led to survival benefits in TNM stage II/III esophageal cancer patients. We retrospectively reviewed 62 patients with stage II or III esophageal squamous cell carcinoma (ESCC) treated with neoadjuvant CRT. All patients received esophagectomy 4–7 weeks after CRT consisting of 40 Gy irradiation and chemotherapy (5-FU, 500 mg/m2/day, days 1–5 and cisplatin, 10–20 mg/body, days 1–5). Clinical response and survival rates were analyzed using Kaplan-Meier methods, with P<0.05 considered as significant. The clinical effect rate of CRT for both primary tumors and metastatic nodes was 82.3%. Operative and hospital mortality rates were 1.65 and 6.5%, respectively. The 3-year overall survival (OS) and disease-free survival (DFS) rates were 52.6 and 49.2%, respectively. A significant difference was noted between stages II and III for both OS and DFS. The 5-year OS rates were 64.2% for stage II, 33.1% for stage III (T4 and non-T4) and 46.9% for stage III (non-T4 only) patients. The depth of tumor invasion (T3 vs. T4), resectability (R0 vs. R1, R2), lymph node metastasis (positive vs. negative), and the effect of CRT were proven to be independent prognostic factors for univariate analysis, with resectability and the effect of CRT for multivariate analysis. These data suggest that CRT in stage II/III (non-T4) ESCC patient contributed to tumor shrinkage, leading to higher resectability and longer survival. Neoadjuvant CRT appears to be a promising option for these patients.

Neoadjuvant chemoradiotherapy followed by esophagectomy vs. surgery alone in the treatment of resectable esophageal squamous cell carcinoma

In order to improve the survival of esophageal cancer patients, a trimodality therapy consisting of esophagectomy in combination with neoadjuvant chemoradiotherapy (CRT) has been developed. In this study, we evaluated whether neoadjuvant CRT improved the outcomes of patients with resectable esophageal squamous cell carcinoma (ESCC) compared to surgery alone. Eighty-eight patients with resectable ESCC were treated with either neoadjuvant CRT followed by surgical resection (Group A, n=52), or surgery alone (Group B, n=36). CRT consisted of 5-fluorouracil (5-FU, 500 mg/m2 on days 1–5) and cisplatin (CDDP, 10–20 mg/kg body weight on days 1–5), repeated after 3 weeks. Survival analysis was performed using the log-rank test with the Kaplan-Meier method. The clinical response of the primary tumor and metastatic nodes was 80.8%. The postoperative complications profile was similar between the two groups, except for anastomotic leakage. The median survival time (MST) was not reached in Group A and was 27.4 months in Group B. The estimated 5-year overall survival (OS) rate was 50.3% in Group A and 39.9% in Group B (P=0.134). As regards stage II/III disease, Group A exhibited a better disease-free survival (DFS) compared to Group B (5-year DFS: 57.2% in Group A vs. 31.4% in Group B; P=0.025). Simultaneous locoregional and distant recurrences were more common in the surgery alone group (Group B, P=0.047). Neoadjuvant CRT with 5-FU and CDDP did not contribute to a better prognosis in patients with resectable ESCC. However, it may be beneficial for patients with stage II/III disease.

Management of Granulomatous Mastitis: A Series of 13 Patients Who Were Evaluated for Treatment Without Corticosteroids

Granulomatous mastitis (GM) is a rare chronic inflammatory breast condition with unknown etiology. There is still no generally accepted optimal treatment for GM. Corticosteroid treatment and/or wide excision is most commonly reported in the literature. Incision and drainage or limited excision alone has little benefit because of a strong tendency of recurrence. Corticosteroids also have a high failure rate and possible side effects. In the current series, we treated GM patients without corticosteroids, except for one patient. We also devised multidirectional deep drainage for advanced and complicated abscesses, which are characteristic of GM. This retrospective study included 13 women who met the required histologic criteria of GM. The mean age of the patients was 41 years. All of the patients were premenopausal. Six patients had breast-fed in the last 5 years. Five patients were under medication with antidepressants. A total of 11 patients developed abscesses during the clinical course, and the abscesses penetrated the retromammary space in 4 patients. We treated 2 of these 4 patients with multidirectional deep drainage and obtained complete remission in 5 and 6.5 months, respectively. These times were much shorter than those in the other 2 patients. The time to resolution in 11 patients was 4 to 28 months. This overall outcome was comparable with that of corticosteroid treatment reported in the literature. Because the natural history of GM is thought to be self-limiting, close observation and minimally required drainage of abscesses without corticosteroid administration remain the treatment modality of choice.

O6‑methylguanine‑DNA methyltransferase as a prognostic and predictive marker for basal‑like breast cancer treated with cyclophosphamide‑based chemotherapy

The O6-methylguanine-DNA methyltransferase (MGMT) protein protects cells from alkylating agents by removing alkyl groups from the O6-position of guanine. However, its effect on DNA damage induced by cyclophosphamide (CPM) is unclear. The present study investigated whether MGMT expression was correlated with prognosis in patients with breast cancer that was managed according to a common therapeutic protocol or treated with CPM-based chemotherapy. The intrinsic subtypes and MGMT protein expression levels were assessed in 635 consecutive patients with breast cancer using immunohistochemistry. In total, 425 (67%) luminal A, 95 (15%) luminal B, 47 (7%) human epidermal growth factor receptor-2+/estrogen receptor− (HER2+/ER−) and 48 (8%) basal-like subtypes were identified. Of these, MGMT positivity was identified in 398 (63%) of 635 breast cancers; 68% of luminal A, 67% of luminal B, 30% of HER2+/ER− and 46% of basal-like subtypes were positive. The overall survival (OS) and disease-free survival (DFS) rates did not significantly differ according to the MGMT status among patients with luminal A, luminal B or HER2+/ER− subtypes, and patients with MGMT-negative basal-like cancers tended to have a longer DFS, but not a significantly longer OS time. CPM-containing chemotherapy was administered to 26%, 40%, 47% and 31% of patients with luminal A, luminal B, HER2+/ER− and basal-like tumors, respectively. Although the MGMT status and clinical outcomes of patients with the luminal A, luminal B or HER2+/ER− subtypes treated with CPM were not significantly correlated, the patients with MGMT-negative basal-like tumors who received CPM exhibited significantly improved DFS and OS compared with the CPM-treated patients with MGMT-positive tumors. MGMT may be a useful prognostic and predictive marker for CPM-containing chemotherapy in basal-like breast cancer.

Self-expanding metallic stent improves histopathologic edema compared with transanal drainage tube for malignant colorectal obstruction.

To compare the usefulness of the self‐expanding metallic stent (SEMS) with that of the transanal drainage tube (TDT) and emergency surgery after failure of decompression (ESFD) in patients with malignant colonic obstruction (MCO), and to evaluate post‐decompression histopathological changes.

Effects of age on survival and morbidity in gastric cancer patients undergoing gastrectomy

AIM To evaluate clinicopathological features and surgical outcomes of gastric cancer in elderly and non-elderly patients after inverse probability of treatment weighting (IPTW) method using propensity score. METHODS We enrolled a total of 448 patients with histologically confirmed primary gastric carcinoma who received gastrectomies. Of these, 115 patients were aged > 80 years old (Group A), and 333 patients were aged < 79 years old (Group B). We compared the surgical outcomes and survival of the two groups after IPTW. RESULTS Postoperative complications, especially respiratory complications and hospital deaths, were significantly more common in Group A than in Group B (P < 0.05). Overall survival (OS) was significantly lower in Group A patients than in Group B patients. Among the subset of patients who had pathological Stage I disease, OS was significantly lower in Group A (P < 0.05) than Group B, whereas cause-specific survival was almost equal in the two groups. In multivariate analysis, pathological stage, histology, and extent of lymph node dissection were independent prognostic values for OS. CONCLUSION When the gastrectomy was performed in gastric cancer patients, we should recognized high mortality and comorbidities in that of elderly. More extensive lymph node dissection might improve prognoses of elderly gastric cancer patients.

Outcome predictors for patients with stage II/III gastric cancer who undergo gastrectomy and S‑1 adjuvant chemotherapy

Predictors of survival in patients with stage II/III gastric cancer (GC) who received tegafur/gimeracil/oteracil (S-1) adjuvant chemotherapy (ACT) subsequent to gastrectomy were examined. Additionally, the association between dose intensity of S-1 and survival rate was investigated. A total of 62 patients with stage II/III gastric cancer were retrospectively evaluated, each of whom had received a curative D2 gastrectomy and S-1 ACT. The relative performance (RP; administered/planned S-1 doses ×100%), body mass index (BMI), prognostic nutritional index (PNI) and body weight (BW) were calculated, and the association of survival with these factors and other clinicopathological parameters was examined. The 1-year treatment continuation rate for S-1 was 94.2%, excluding patients who experienced cancer recurrences during their ACT year. The initial S-1 reduction rate was 38.7%. Patients with stage II/IIIA disease exhibited significantly improved 5-year overall survival rates compared with patients with stage IIIB GC, 81.6/73.7 vs. 33.8% (P<0.01). No association between RP and survival was observed. BMI, BW and PNI were significantly decreased following surgery compared with preoperative states. In the univariate analysis, postoperative BW loss (BMI loss), pathological stage and >7 lymph node metastases were significantly associated with outcome (P<0.05); in the multivariate analysis, postoperative BW loss >10.6% and pathological stages were independent prognostic factors for survival. Continuing S-1 ACT for the full year exhibited a greater effect on survival compared with dosage. Early postoperative nutritional deterioration may decrease the survival rates in these patients.

Disseminated carcinomatosis of the bone marrow with disseminated intravascular coagulation as the first symptom of recurrent rectal cancer successfully treated with chemotherapy: A case report and review of the literature

Disseminated carcinomatosis of the bone marrow (DCBM) is a condition in which bone marrow (BM) metastases diffusely invade the BM, and is frequently accompanied by disseminated intravascular coagulation (DIC). While prostate, lung, breast and stomach malignancies, in addition to neuroblastoma, are the most prevalent non-hematological malignancies to metastasize frequently to the BM, colorectal cancer is a malignancy that rarely metastasizes to the BM. The present case describes a 65-year-old male patient treated by resection and one course adjuvant chemotherapy for stage IIIC rectal cancer who presented with nasal bleeding at 8 months post-surgery. A blood test exhibited DIC. A BM biopsy was performed and the definitive diagnosis was DCBM with DIC. Promptly, anti-DIC treatment and chemotherapy with a modified FOLFOX6 (folinic acid, leucovorin (LV), 5-fluorouracil (5-FU) and oxaplatin) regimen was started. Following 1 cycle of chemotherapy, DIC was improved and subsequent to 2 cycles of modified FOLFOX6 the patient was discharged. The patient was alive 263 days subsequent to the diagnosis of DIC, but succumbed to carcinomatous meningitis as a result of disease progression. To the best of our knowledge, this is the first report of DCBM with DIC of curatively resected rectal cancer as the first presentation of relapse that was successfully treated with aggressive therapy, including chemotherapy.

Collision tumor of choriocarcinoma and small cell carcinoma of the stomach: A case report

Graphical abstract

Thymidylate synthase expression in primary colorectal cancer as a predictive marker for the response to 5‑fluorouracil‑ and oxaliplatin‑based preoperative chemotherapy for liver metastases

In patients with colorectal liver metastases (CRLM), predictive markers for response to preoperative chemotherapy are lacking. The aim of the present study was to evaluate the expression of thymidylate synthase (TS) and excision repair cross-complementation group 1 (ERCC1) as predictive markers in CRLM. A total of 24 patients with CRLM were included in this study. Tumor response was evaluated using the tumor regression grade (TRG) and Response Evaluation Criteria in Solid Tumors (RECIST) methods. TS and ERCC1 expression in paired CRLM and primary lesions were assessed by immunohistochemistry. We analyzed correlations between i) the response to preoperative chemotherapy evaluated by TRG and RECIST, ii) TS and ERCC1 expression and the response evaluated by TRG and RESICT, and iii) TS and ERCC1 expression in matched pairs of primary tumor and CRLM. The preoperative chemotherapy response evaluated by TRG and RECIST was significantly associated (P=0.0005). The response based on RECIST criteria and TRG was significantly associated with TS expression in the primary tumor (P=0.0272, and P=0.0137, respectively). No correlations were detected between marker expression in the primary tumor and in CRLM for either TS or ERCC1 (P=0.371 and P=1.00, respectively). Our data suggested that TS expression in the primary tumor is a predictive marker of preoperative chemotherapy response in CRLM based on both TRG and RECIST methods.