Significance of Hypofractionated Radiotherapy in Postoperative Irradiation for Breast Cancer: An Asian Multi-institutional Prospective Study.

AIMS: There is a need for the adequate distribution of healthcare resources in Southeast Asia. Many countries in the region have more patients with advanced breast cancer who are eligible for postmastectomy radiotherapy (PMRT). Therefore, it is critical that hypofractionated PMRT is effective in most of these patients. This study investigated the significance of postoperative hypofractionated radiotherapy in patients with breast cancer, including advanced breast cancer, in these countries. MATERIALS AND METHODS: Eighteen facilities in 10 Asian countries participated in this prospective, interventional, single-arm study. The study included two independent regimens: hypofractionated whole-breast irradiation (WBI) for patients who had undergone breast-conserving surgery and hypofractionated PMRT for patients who had undergone total mastectomy at a dose of 43.2 Gy in 16 fractions. In the hypofractionated WBI group, patients with high-grade factors received additional 8.1 Gy boost irradiation sessions for the tumour bed in three fractions. RESULTS: Between February 2013 and October 2019, 227 and 222 patients were enrolled in the hypofractionated WBI and hypofractionated PMRT groups, respectively. The median follow-up periods in the hypofractionated WBI and hypofractionated PMRT groups were 61 and 60 months, respectively. The 5-year locoregional control rates were 98.9% (95% confidence interval 97.4-100.0) and 96.3% (95% confidence interval 93.2-99.4) in the hypofractionated WBI and hypofractionated PMRT groups, respectively. Regarding adverse events, grade 3 acute dermatitis was observed in 2.2% and 4.9% of patients in the hypofractionated WBI and hypofractionated PMRT groups, respectively. However, no other adverse events were observed. CONCLUSION: Although further follow-up is required, hypofractionated radiotherapy regimens for postoperative patients with breast cancer in East and Southeast Asian countries are effective and safe. In particular, the proven efficacy of hypofractionated PMRT indicates that more patients with advanced breast cancer can receive appropriate care in these countries. Hypofractionated WBI and hypofractionated PMRT are reasonable approaches that can contain cancer care costs in these countries. Long-term observation is required to validate our findings.

Efficacy and safety of teneligliptin, a dipeptidyl peptidase-4 inhibitor, combined with metformin in Korean patients with type 2 diabetes mellitus: a 16-week, randomized, double-blind, placebo-controlled phase III trial.

The aim of the present study was to assess the efficacy and safety of teneligliptin in combination with metformin in Korean patients with type 2 diabetes mellitus who were inadequately controlled with metformin monotherapy. Patients [glycated haemoglobin (HbA1c) 7.0-10.0%, on stable metformin ≥1000 mg/day] were randomized 2 : 1 to receive 20 mg teneligliptin plus metformin (n = 136) or placebo plus metformin (n = 68). The primary endpoint was the change in HbA1c levels from baseline to week 16. The mean baseline HbA1c was 7.9% in the teneligliptin group and 7.8% in the placebo group. The differences between the teneligliptin and placebo groups regarding changes in HbA1c and fasting plasma glucose levels were -0.78 % and -1.24 mmol/l (22.42 mg/dl), respectively, at week 16. The incidence of adverse events was similar between the groups. The addition of teneligliptin once daily to metformin was effective and generally well tolerated in Korean patients with type 2 diabetes.

A new modified cut standard straw vitrification technique reduces the apoptosis of mouse blastocysts and generates more live mouse offspring.

Effects of freezing on apoptosis and autophagy in embryos are poorly understood. This study introduces a simple and successful method (modified cut standard straw, M-CSS) for cryopreservation of mouse zygotes. Apoptosis and autophagy were investigated in cultured mouse blastocysts derived from vitrified zygotes using two vitrification containers (M-CSS vs 0.25-ml straw). The percentages of zygotes that survived and developed into blastocysts and the number of cells per blastocyst were higher in the M-CSS group than in the 0.25 ml straw group; whereas the rate of apoptosis in blastocysts was significantly lower in the M-CSS group than in the 0.25-ml straw group. The expression of the apoptosis-related gene Caspase 3 in blastocysts was higher in the 0.25-ml straw group than in the M-CSS group; however, there were no significant differences in autophagy between these two groups. Vitrified-thawed mouse zygotes were transferred into recipients. The percentage of recipients that became pregnant and the percentage of transferred zygotes that developed into live offspring were significantly lower in the 0.25-ml straw group than in the M-CSS (10.2% vs. 17.5%). In conclusion, the novel M-CSS procedure improves oocyte and embryo vitrification. The standard 0.25-ml straw vitrification procedure induces mitochondrial apoptosis in zygotes in an autophagy-independent manner.

Treatment of advanced gastric cancer by palliative gastrectomy, cytoreductive therapy and postoperative intraperitoneal chemotherapy.

BACKGROUND: The treatment options for the 10-20 per cent of patients with gastric cancer who present with peritoneal dissemination are extremely limited and no standard approach exists. METHODS: The feasibility of using intraperitoneal chemotherapy to treat gastric cancer with intra-abdominal gross residual lesions after palliative gastrectomy with maximal cytoreduction was investigated. Early postoperative intraperitoneal chemotherapy started on the day of operation with 5-fluorouracil 500 mg/m2 and cisplatin 40 mg/m2 (days 1-3) over a 4-week interval. RESULTS: Of the 53 patients enrolled between July 1994 and December 1998, 49 were eligible. The progression-free survival (PFS) was 7 months and the overall survival was 12 months. In multivariate analysis, performance status was the only significant defining factor for PFS (P = 0.009). The predominant toxicity was neutropenia and nausea/vomiting. The relative dose intensity of 5-fluorouracil and cisplatin was 89 and 63 per cent respectively. CONCLUSION: Performance status emerged as a major determining factor for prognosis and patient selection for early postoperative intraperitoneal chemotherapy in patients with advanced gastric cancer after maximally cytoreductive surgery.

Efficacy of Pre- and Postoperative Chemotherapy in Patients with Osteosarcoma of the Extremities.

PURPOSE: We evaluated the treatment efficacy including survival and recurrence, and factors associated with recurrence in osteosarcoma patients treated with preoperative chemotherapy, surgery, and adjuvant chemotherapy. MATERIALS AND METHODS: Forty nine patients with osteosarcoma were treated with preoperative chemotherapy with intra-arterial cisplatin and adriamycin infusion for 3 cycles, followed by surgery. According to the pathologic response, if tumor was necrotized more than 90%, the same adjuvant chemotherapy was reintroduced for 3 cycles, and if the response was not enough, then the salvage regimen was introduced. Plain chest film and chest CT scan were taken monthly and every 3 months, respectively. When tumor recurred, the metastasectomy was performed whenever possible. RESULTS: Forty three patients were evaluable with amedian follow up of 53 months. Five-year disease-free and overallsurvival rate was 47.0% and 66.9%, respectively. The recurrence was observed in 22 patients (51.2%) with median time of 12.5 months. Baseline alkaline phosphatase (ALP) was the only significant factor for recurrence (p=0.03) and the patients with the possibility of metastasectomy recurrence showed higher post-relapse survival compared to other treatment modalities (26 momths vs 5~12 months). CONCLUSION: These results indicates that pre- and postoperative chemotherapy with intra-arterial cisplatin and adriamycin infusion showed comparable treatment efficacy and acceptable toxicities.

The changing epidemiology of hepatitis A in children and the consideration of active immunization in Korea.

Currently, Korea is a low endemicity country for HAV, especially in children. However, recent reports of hepatitis A outbreaks show that there has been a shift of disease incidence to adolescents and young adults, with 2 cases of acute liver failure in one reported outbreak. We need to study the immune status for HAV in order to provide information for the establishment of preventive measures and possible consequences of HAV in Korea. A total of 334 infants, children and adolescents less than 20 years of age living in rural areas of Kyonggi Province, Korea were evaluated for anti-HAV immune status in 1996. Five hundred and eighty-four primary school children living in the same area were separately evaluated for the natural seroconversion rate between 1993 and follow-up samples taken in 1996. Anti-HAV IgG antibody was measured by enzyme immunoassay (HAVAB EIA kit, Abbott Laboratories, Chicago, Illinois, USA). In comparison with previous reports of seroprevalence rates, our data confirmed a dramatic drop in seroprevalence rates among children and adolescents under 20 years of age living in rural areas, from over 63.8% two decades ago to 4.6% in 1996. Natural acquisition of HAV antibody in primary school children rarely occurs, registering only 0.5% during three years. Several outbreaks in young adults during 1996-1998 suggested that immunity against HAV in this population is so low that massive outbreaks are unavoidable. Teenagers and young adults, especially soldiers, who are likely to be exposed to contaminated food or water, would also have a greater risk of hepatitis A. Immunizing children with HAV vaccine as a routine schedule should also be considered in Korea in the future, particularly if the disease burden could be estimated and the cost-effectiveness of the vaccine could be proved.

Endoscopic mucosectomy using an esophageal variceal ligation device for minute gastric cancer.

We present here a modified technique for endoscopic mucosal resection using the technique of esophageal variceal ligation for minute gastric cancer. This method of endoscopic mucosal resection requires only the commonly-used one-channel endoscope, an esophageal variceal ligation device, and some clinical experience with the ligation of esophageal varices and snare polypectomy. It can therefore be considered technically simple and safe. We treated four patients with minute gastric cancer using this endoscopic mucosal resection technique. All tumors were completely resected without major complications. Resected specimens were 1.0-1.5 cm in diameter, sufficient for histopathological evaluation, and curative resection was achieved in all patients.

Immunohistochemical detection of p53 protein, c-erbB-2 protein, epidermal growth factor receptor protein and proliferating cell nuclear antigen in gastric carcinoma.

There is increasing evidence that genes involved in normal cell growth and differentiation (oncogenes) or genes that encode for growth factors are important in determining the development and biologic aggressiveness of gastric carcinoma. This study was undertaken to define the prognostic value of the overexpression of p53 protein, c-erbB-2 protein, EGFr protein and PCNA in gastric carcinomas. Using monoclonal antibodies, immunohistochemical studies were performed on formalin-fixed, paraffin-embedded tissue sections from 84 primary gastric carcinomas. Overall, 34% of gastric carcinomas had nuclear-staining for p53 protein, 34% of carcinomas membrane staining for the c-erbB-2 and 74% of carcinomas membrane and cytoplasmic staining for EGFr, showing distribution in a heterogeneous fashion. PCNA was expressed as Grade 2 and 3 in 75% of patients with gastric carcinomas. Both c-erbB-2 and p53 staining was significantly associated with high grade expression of PCNA. p53 staining tended to be associated with positive nodal status and metastasis, and c-erbB-2 staining with positive nodal status only. Multivariate analysis using the Cox model showed that overexpression of p53 protein, c-erbB-2 protein and PCNA was not an independent prognostic variable in gastric carcinoma. These results suggest that expressions of p53 and c-erbB-2 protein are heterogeneous and that p53 and c-erbB-2 overexpressions are significantly associated with high proliferative activity in gastric carcinoma.

Metastatic involvement of the stomach secondary to lung carcinoma.

Blood-borne metastatic involvement of the stomach by cancer is a rare entity. According to the number of reports in the literature, the most common tumors that spread to the stomach through the blood stream are malignant melanoma, breast carcinoma and lung carcinoma. Recently, two cases of metastatic involvement of the stomach secondary to lung carcinoma were diagnosed by gastroscopy. The first patient was a 66-year-old man who had primary lung carcinoma with multiple bone and subcutaneous metastases. Gastroscopy showed multiple submucosal tumors with central umbilications in the fundus and in the upper body of the stomach. Pathologic examination revealed massive submucosal infiltration and conical shaped and scanty deep mucosal infiltration of undifferentiated small cell carcinoma suggestive of metastatic involvement. The second patient was a 68-year-old man who had primary lung carcinoma with brain metastasis. Gastroscopy showed a large fungating mass in the greater curvature side of the stomach. Pathologic examination revealed poorly differentiated squamous cell carcinoma. We report the two cases of metastatic gastric cancer from lung carcinoma with the literature review.

The gastric juice urea and ammonia levels in patients with Campylobacter pylori.

The authors studied gastric juice ammonia and urea nitrogen levels to determine how they are altered by gastric Campylobacter pylori (CP) infection. Patients with chronic gastritis (20), peptic ulcer (24), hepatic cirrhosis (10), chronic renal failure (13), or gastric remnant (20) were included. Endoscopic biopsy specimens stained with the Warthin-Starry stain were evaluated for the presence of CP. Blood and gastric juice analysis was performed for 11 of the patients with chronic renal failure and 37 patients from the remaining groups. CP was identified in gastric biopsies from 50 of 87 (57.5%) patients, including 87.5% with peptic ulcer and 40-50% of those with chronic gastritis, cirrhosis, chronic renal failure, or gastric remnant. CP infection had no effect on blood urea nitrogen or blood ammonia levels in any group of patients. The urea nitrogen level of gastric juice was higher in patients with chronic renal failure than in other groups but was not related to CP infection. CP infection was associated with a significant increase in gastric juice ammonia levels, both in patients with chronic renal failure (23.3 mmol/L vs. 2.90 mmol/L; [P less than 0.05]) and in other groups (5.48 mmol/L vs. 1.26 mmol/L [P less than 0.0001]). The authors conclude that elevation of gastric juice ammonia level is an indicator of gastric CP infection.

Hepatoma presenting as extrahepatic biliary obstruction due to hemobilia.

A case of hepatoma presenting as extrahepatic biliary obstruction due to hemobilia is reported. The patient, a 49-year-old woman, developed jaundice of the obstructive type after a history of B-viral hepatitis. On laparotomy, the liver revealed macronodular cirrhosis without any noticeable mass. A 4-cm sized friable tissue and blood clots were identified within the distended left hepatic duct. Pathologic examination of this tissue confirmed the diagnosis of hepatocellular carcinoma extended in the hepatic duct.

Intussusception into the enteroanastomosis after Billroth II gastric resection; diagnosed by gastroscopy.

A case of retrograde intussusception (acute type) of efferent limb into Braun side-to-side jejuno-jejunal anastomosis is presented. Intussusception, though infrequent, is well recognized complication after gastric surgery. Patient was 50 year old man who was admitted with epigastric pain and abdominal mass for 6 hours. Patient had a history of total gastrectomy 2 years before admission due to stage II gastric cancer. Seven hours after admission, hematemesis developed. Emergency fiberopticgastroscopy revealed type 4 jejunogastric intussusception. Segmental resection with end-to-end reanastomosis was performed.