Characterization of an inhibitor for luteinizing hormone receptor site binding.

An inhibitor for luteinizing hormone (LH) receptor site binding has been partially purified from aqueous extracts of ovaries from pseudo-pregnant or pregnant rats. The LH receptor binding inhibitor (LH-RBI) was heat-resistant, partially inactivated by trypsin or pronase digestion, and had a molecular weight of approximately 3800 daltons. The LH-RBI was not found in the ovary of mature non-pregnant rats or immature rats, nor was it found in testis or liver extracts. The LH-RBI strongly inhibited the in vitro binding of 125I-labeled ovine LH to ovarian LH receptors but did not inhibit 125I-labeled ovine prolactin binding to ovarian PRL receptors.     

Primary Malignant Melanoma of the Esophagus in a Young Adult

A 31-year-old white man presented with a 30-day history of dysphagia without weight loss. Esophagogram revealed a lobulated mass at the junction of the middle and lower third of the esophagus. Esophagoscopy showed the presence of a pigmented tumor at that level. Histological examination indicated that the tumor was a primary malignant melanoma. Partial esophagectomy was performed through a right thoracotomy incision, revealing hilar lymph nodes invaded by tumor. One month postoperatively, the patient died from extensive brain metastases.     

Liver cell adenoma presenting as acute abdomen

A 31-year-old female presented with a sudden onset of acute abdominal pain in the right hypochondrium. Two days later, the patient was in shock and suffering from severe intra-abdominal bleeding. Investigations showed that the bleeding originated in the right lobe of the liver. The patient had been taking oral contraceptives for seven years. She underwent a laparotomy and right lobectomy of the liver which was performed successfully for bleeding cell adenoma. The patient made a full recovery.     

Human parathyroid autotransplantation: proved function by radioimmunoassay of plasma parathyroid hormone.

The possibility of transplanting parathyroid gland fragments into accessible muscle as functioning autografts in the human being has been supported but unproved. During operations in the thyrocervical area, the parathyroid glands frequently are removed, either intentionally or inadvertently. We have had occasion to transplant slices of parathyroid glands in five instances; four parathyroid glands were proved to be normal, and a benign adenoma appeared in the fifth. The parathyroid gland was positioned in a muscular bed in the patient's forearm. Plasma parathyroid hormone (PTH) measurements by radioimmunoassay were made from the implant venous effluent. The venous outflow from the contralateral arm was used for control. We have concluded that parathyroid tissue can be transplanted, does function, and might be capable of providing calcium homeostasis.     

Clinical and endocrinological evaluation of 16 acromegalic patients treated by transsphenoidal surgery.

Sixteen patients with acromegaly treated with transsphenoidal pituitary surgery were evaluated with the measurement of serum human growth hormone (HGH) before and after intravenous stimulation with thyrotropin-releasing hormone (TRH). Fourteen of these patients showed a significant rise of serum HGH after TRH stimulation before surgery. After surgery, 12 patients with Grade 2 noninvasive adenomas had normal fasting serum HGH levels which did not stimulate with TRH. Two of these patients showed high serum HGH levels both at fasting and after TRH stimulation and required a second operation to remove residual adenoma within the sella before adequate lowering of HGH was achieved. Evidence of recurrent adenoma has not occurred clinically or biochemically in this group of 12 patients followed for an average of 24 months (2 to 60 months). The results were unsatisfactory in four of these 16 patients. One patient who has a postoperative HGH of 9 ng/ml which still stimulates with TRH has made clinical improvement, but must have residual adenoma in the sella or invasive adenoma in the dura and tumor capsule. Additional treatment with irradiation has been given. Failure to achieve satisfactory results in the other three patients was attributed to the presence of locally invasive adenoma; one in the sphenoid sinus, and the other two possibly as a consequence of previous operative procedures.     

Acute cardiac toxicity of antineoplastic agents as the first manifestation of pheochromocytoma.

A 47-year-old male with histiocytic lymphoma and no previous history of heart disease developed significant fluctuations of blood pressure, electrocardiographic evidence of myocardial ischemia, and life-threatening arrhythmia after the first dose of BACOP (bleomycin, adriamycin, cyclophosphamide, Oncovin, and prednisone) chemotherapy. The presence of pheochromocytoma was suspected, and it was demonstrated by elevated urinary metanephrines, catecholamines, and vanillylmandelic acid, and finally confirmed on autopsy. The possible role of chemotherapeutic agents in stimulating excessive catecholamine release, thus causing transient cardiac injury, is suggested.     

The efficacy and safety of S-1-based regimens in the first-line treatment of advanced gastric cancer: a systematic review and meta-analysis

Background

S-1 is first-line therapy for advanced gastric cancer in Asia and is used with increased frequency in Western counties. We conducted a meta-analysis to investigate the efficacy and toxicity of S-1-based therapy compared with 5-fluorouracil (5-FU)/capecitabine-based therapy and S-1-based combination therapy compared with S-1 monotherapy.

Methods

MEDLINE, Embase, the Cochrane Central Register of Controlled Trials, American Society of Clinical Oncology meeting abstracts, European Society for Medical Oncology meeting abstracts and ClinicalTrials.gov were searched for randomized clinical trials until May 2015. Data were extracted for overall survival (OS), progression-free-survival (PFS), objective response rate (ORR) and grade 1–2 and grade 3–4 adverse events. Stratified OS data for subgroups were extracted.

Results

S-1 was not different from 5-FU (eight studies, n = 2788) in terms of OS [hazard ratio (HR) 0.93, 95 % confidence interval (CI) 0.85–1.01] and PFS (HR 0.87, 95 % CI 0.73–1.04), whereas ORR was higher (risk ratio 1.43, 95 % CI 1.05–1.96). There was no subgroup difference in efficacy among Asian and Western patients, but in Western patients S-1 was associated with a lower rate of febrile neutropenia, toxicity-related deaths and grade 3–4 stomatitis and mucositis compared with 5-FU. S-1 showed no difference in efficacy compared with capecitabine (three studies, n = 329), but was associated with a lower rate of grade 3–4 neutropenia and grade 1–2 hand–foot syndrome. S-1-combination therapy was superior to S-1 monotherapy (eight studies, n = 1808) in terms of OS (HR 0.76, 95 % CI 0.65–0.90), PFS (HR 0.68, 95 % CI 0.56–0.82) and ORR (risk ratio 1.20, 95 % CI 1.04–1.38) but was more toxic. Survival benefit of S-1 combination therapy over S-1 monotherapy was most pronounced in patients with non-measurable disease, diffuse-type histological features and peritoneal metastasis.

Conclusions

S-1 is effective and tolerable as first-line therapy for advanced gastric cancer in both Asian and Western countries.