Masayuki Okido

Role of surgery for gallbladder carcinoma with special reference to lymph node metastasis and stage using western and Japanese classification systems.

Abstract. The role of radical resection in the treatment of gallbladder carcinoma was examined with special reference to lymph node metastasis using two classifications: one proposed by the American Joint Committee on Cancer (AJCC) and the other by the Japanese Society of Biliary Surgery (JSBS). Histologic evaluations for the depth of tumor invasion (T), lymph node metastasis (N), stage, and follow-up for a mean period of 38 months (range 4–185 months) were completed in 52 patients with gallbladder carcinoma who underwent surgical resection from 1982 to 1997. The definition of T was similar in the two classifications. The extent of nodal involvement (N, AJCC; n, JSBS), stage, and survival were examined. In the absence of lymph node metastasis, the 5-year survival rate reached 71%. The 5-year survival rate in patients with involved nodes confined to the hepatoduodenal ligament, posterosuperior pancreaticoduodenal region, or along the common hepatic artery (N1 and part of N2 by AJCC; n1 and n2 by JSBS) approximated 28%. In contrast, postoperative survival was poor in the presence of more extensive nodal involvement (rest of N2 by AJCC; n3 and n4 by JSBS), with no 2-year survivors. The definition of stage I was the same in both classifications, and all patients in this stage are alive. The 5-year survival rates in stages II and III by the AJCC were 70.7% and 22.4%, respectively, and those by JSBS 61.9% and 23.1%, respectively. Thus the survival rates in stages I to III were essentially similar irrespective of the staging system. Stage IV showed significantly worse survival than stage III by the JSBS classification. In contrast, the differentiation of stage IV from III by the AJCC was not significant because of the better survival in stage IV that contained any T with nodal involvement in the posterosuperior pancreaticoduodenal region and along the common hepatic artery. Radical resection should be considered for patients with stage I to III disease defined by either classification and applied to the tumor invasion up to T3 with nodal involvement confined to the hepatoduodenal ligament, posterosuperior pancreaticoduodenal region, and along the common hepatic artery. The role of radical surgery seems to be limited in patients with more extensive tumor invasion or lymph node metastasis.

Infrasternal mediastinoscopic thymectomy in myasthenia gravis: surgical results in 23 patients

BACKGROUND Infrasternal mediastinoscopic surgery is a new approach to resection of the anterior mediastinal mass. METHODS We evaluated this new approach in 23 patients with myasthenia gravis who underwent total thymectomy assisted by infrasternal mediastinoscopy between 1998 and 2000. The results were analyzed with special reference to morbidity and short-term improvement of the disease severity determined according to quantitative myasthenia gravis (QMG) scores. RESULTS Complete removal of the thymic gland with the pericardial adipose tissue was accomplished through an infrasternal mediastinoscopic approach in 21 of the 23 (91.3%) patients. The remaining 2 patients required conversion to sternotomy, the one for insufficient sternal lifting with vascular tape and the other for invasion of a thymoma to the innominate vein. There was no related mortality and only one complication, a phrenic nerve injury in 1 patient (4.3%). Significant clinical improvement of disease was achieved in the short term and several advantages were apparent. CONCLUSIONS Infrasternal mediastinoscopic thymectomy is safe and feasible for patients with myasthenia gravis.

Inhibition of the proliferation of acquired aromatase inhibitor-resistant breast cancer cells by histone deacetylase inhibitor LBH589 (panobinostat)

Aromatase inhibitors (AIs) are important drugs for treating postmenopausal patients with hormone receptor-positive breast cancer. However, acquired resistance to AI therapies is a significant problem. Our study has revealed that the histone deacetylase inhibitor LBH589 treatment abrogated growth of AI-resistant cells in vitro and in vivo, causing cell cycle G2/M arrest and induced apoptosis. LBH589 treatment also reduced the level of NF-κB1 which is overexpressed when AI resistance develops. Analyzing paired tumor specimens from 12 patients, we found that NF-κB1 expression was increased in recurrent AI-resistant tumors as compared to the paired primary tumors before AI treatment. This finding was consistent with up-regulated NF-κB1 expression seen in a collection of well-established AI-resistant cell lines. Furthermore, knockdown of NF-κB1 expression significantly suppressed the proliferation of AI-resistant cells. Treatment of AI-resistant cell lines with LBH589 suppressed NF-κB1 mRNA and protein expression. In addition, LBH589 treatment abrogated growth of AI-resistant tumors in mice, and was associated with significantly decreased levels of NF-κB1 in tumors. In all, our findings strongly support further investigation of LBH589 as a novel therapeutic strategy for patients with AI-resistant breast cancer, in part by suppressing the NF-κB1 pathway.

The Impact of Visceral Fat Accumulation on Laparoscopy- Assisted Distal Gastrectomy for Early Gastric Cancer

BACKGROUND Laparoscopy-assisted distal gastrectomy (LADG) has been widely accepted for the treatment for early gastric cancer. Obesity is a rapidly growing epidemic, and the number of obese patients with gastric cancer is increasing, but the impact of visceral fat (VF) accumulation on laparoscopic gastric surgery remains unknown. The aim of the present study was to determine the impact of VF accumulation on LADG. MATERIALS AND METHODS The medical charts of 30 patients who underwent LADG for early gastric cancer in our hospital between November 2000 and November 2006 were analyzed retrospectively. The patients were divided into two groups on the basis of VF accumulation measured on cross-sectional computed tomography at the level of the umbilicus. Twelve patients had high VF accumulation (> or =100 cm2) and 18 had low VF accumulation (<100 cm2). RESULTS Although subcutaneous fat accumulation was not correlated with operation time or operative blood loss, VF accumulation was strongly, and significantly, correlated with both operation time and operative blood loss. The high-VF-accumulation group had a significantly longer operation time and significantly more operative blood loss than the low-VF-accumulation group. There was no significant difference in the rate of postoperative complications or conversion to open laparotomy between the two groups. There were no operative deaths or requirements for blood transfusion in either group. CONCLUSIONS VF accumulation was significantly correlated with operative difficulties during LADG. Although LADG was as safe for patients with high VF accumulation as for patients with low VF accumulation, a longer operative time and more operative blood loss were observed in patients with high VF accumulation. VF accumulation appears to be a possible risk factor in LADG and should be considered when making a decision about treating early gastric cancer with LADG.

The combination of PD-L1 expression and decreased tumor-infiltrating lymphocytes is associated with a poor prognosis in triple-negative breast cancer

This study included patients with primary triple-negative breast cancer (TNBC) who underwent resection without neoadjuvant chemotherapy between January 2004 and December 2014. Among the 248 TNBCs studied, programmed cell death ligand-1 (PD-L1) expression was detected in 103 (41.5%) tumors, and high levels of tumor-infiltrating lymphocytes (TILs) were present in 118 (47.6%) tumors. PD-L1 expression correlated with high levels of TILs, but was not a prognostic factor. Patients with TILs-high tumors had better overall survival than those with TILs-low tumors (P = 0.016). There was a strong interaction between PD-L1 expression and TILs that was associated with both recurrence-free survival (P = 0.0018) and overall survival (P = 0.015). Multivariate Cox proportional hazards model analysis showed that PD-L1-positive/TILs-low was an independent negative prognostic factor for both recurrence-free survival and overall survival. Our findings suggest that PD-L1-positive/TILs-low tumors are associated with a poor prognosis in patients with TNBC, and that it is important to focus on the combination of PD-L1 expression on tumor cells and TILs present in the tumor microenvironment. These biomarkers may be useful for stratification of TNBCs and for predicting prognosis and developing novel cancer immunotherapies.

Metastatic Breast Carcinoma Simulating Linitis Plastica of the Colon : Report of a Case

A 48-year-old woman developed a mobile abdominal mass in the course of treatment for recurrent breast cancer. Imaging studies indicated linitis plastica of the colon. She underwent surgery because of the stenosis of the transverse colon. An examination of the resected specimen revealed a segmental stricture, thickening of the entire wall, and a granular mucosa resembling cobblestones. Microscopic findings of the colon lesion were very similar to those of her primary, invasive lobular carcinoma of the breast. Atypical cells showed immunoreactivity for cytokeratin-7, but not for cytokeratin-20. These findings suggested that the lesion of the colon was a colonic metastasis of breast cancer. Metastatic gastrointestinal diseases originating from breast carcinoma are unusual, and colonic metastases are especially rare. Although colon cancer may occur in patients with a history of breast cancer, metastatic colon cancer should be suspected if linitis plastica is detected.

Video-assisted parathyroidectomy for primary hyperparathyroidism

Background: Recent advances have allowed the performance of parathyroidectomy as an endoscopic procedure. Carbon dioxide (CO2) insufflation can be used to create a working space in the anterior neck, but it has been associated with a number of complications. We have devised a skin-lifting method to overcome these problems. Methods: Eleven consecutive patients underwent video-assisted parathyroidectomy. Preoperative imaging revealed a solitary adenoma in all 11 cases. A 3-cm oblique incision was made below the clavicle, and a 5-mm incision was made on the lateral neck. After the skin was lifted, video-assisted parathyroidectomy was performed. Results: Surgery required 186 ± 50 min. No conversions to conventional cervicotomy were needed. Levels of serum calcium and intact parathormone decreased significantly in all patients on postoperative day 1. Laryngeal recurrent nerve paresis and seroma were noted in one patient each. Conclusions: Our procedure eliminates any potential CO2 problems and offers the advantages of direct manipulation and improved cosmesis. Endoscopic parathyroidectomy should be considered a viable option for the surgical treatment of a solitary adenoma.

Unusual multiple gastric carcinoids with hypergastrinemia: report of a case.

We report the case of a patient demonstrating multiple gastric carcinoids with hypergastrinemia. A 50-year-old Japanese woman was admitted to our hospital for the further examination of multiple carcinoids of the stomach with hypergastrinemia, although she was asymptomatic. However, based on our clinical examination, this case seemed to be neither type I nor II carcinoid. We performed a total gastrectomy with D1 lymph node dissection. A pathological examination showed numerous endocrine micronests, hyperplasia of the parietal cells extending to the foveolar neck region, and numerous dilated oxyntic glands filled with eosinophilic secretions. Many parietal cells exhibited vacuolated cytoplasms and apical snouts. Furthermore, the dilated glands at the base of the mucosa had hyperchromatic nuclei and ciliated surfaces. The postoperative serum gastrin level was soon normalized to 47 pg/ml. This is only the third reported case of multiple gastric carcinoids with hypergastrinemia due to an intrinsic abnormality in the acid secretion of the parietal cells.

A Poor Prognostic Case of Mucoepidermoid Carcinoma of the Thyroid: A Case Report

Mucoepidermoid carcinoma (MEC) of the thyroid is very rare and low-grade indolent neoplasm. In past reports of the thyroid MEC, only seven cases were described as poor prognosis. A 91-year-old woman presented with a rapidly growing mass of the left upper neck. She was followed thyroid papillary carcinoma (PC) without operation for two years. Fine needle aspiration cytology (FNAC) showed undifferentiated cells. Total thyroidectomy and bilateral neck dissection were performed. In pathological findings, the tumor had two areas of MEC and PC. The boundary of them was mixed. She died of multiple lung metastases only after four months from the operation. We report a rare case of thyroid MEC which had an aggressive behavior and poor prognosis. This case is a precious in that thyroid MEC occurred during observation of PC and suggests a possibility of the transformation from PC to MEC.

Pseudo-Meigs' syndrome associated with breast cancer metastasis to both ovaries: Report of a case.

A 50-year-old woman was admitted because of abdominal fullness due to bilateral ovarian tumors, pleural effusion, and ascites associated with breast cancer. Although chemotherapy and the removal of ascites were performed periodically, the ascites did not disappear. The cytology of the ascites did not indicate malignancy. Pseudo-Meigs’ syndrome caused by metastasis to both ovarian tumors was suspected. The patient underwent a bilateral salpingo-oophorectomy, and the pathological diagnosis was bilateral metastatic ovarian tumors from breast cancer. The ascites and pleural effusion resolved after the surgery, with the consequent improvement of the patient’s quality of life; however, she unfortunately died 4 months later due to hepatic failure caused by multiple metastases.