Combinations of cytogenetics and international scoring system can predict poor prognosis in multiple myeloma after high‐dose chemotherapy and autologous stem cell transplantation

High‐dose chemotherapy followed by autologous stem cell transplantation (ASCT) is a standard therapy for newly diagnosed multiple myeloma. Combinations of recently proposed prognostic factors such as cytogenetics and international scoring system (ISS) may be useful to predict prognosis after ASCT. This study evaluated 60 consecutive patients who underwent ASCT in four institutes. The median age of patients was 57 years old. Cytogenetic analyses of bone marrow at diagnosis detected metaphase abnormalities in 9 of 51 patients and interphase abnormalities in six of 35 patients (17p13 deletion, t(4;14) and t(14;16)). Seventeen patients had ISS stage 3 at diagnosis. Twenty‐five patients who had any of these risk factors were defined as high risk. All patients were conditioned with high‐dose melphalan. With a median follow‐up of 3.4 years, overall survival and event‐free survival at 3 years were significantly worse in high‐risk patients (48% vs. 97%; P = 0.0005 and 16% vs. 37%; P = 0.038, respectively) despite the higher CR plus VGPR rate among high‐risk patients. In addition, survival at 1 year after progression was significantly worse in high‐risk patients despite salvage chemotherapy containing thalidomide (32% vs. 100%, P = 0.0001). Combinations of cytogenetics and ISS could readily predict prognosis. Quality of response is a poor surrogate marker for ultimate outcome. High‐risk patients may need more effective treatment. Am. J. Hematol. 2009. © 2009 Wiley‐Liss, Inc.     

Ultrasound findings of diffuse metastasis of gastric signet-ring-cell carcinoma to the thyroid gland

It has been shown that metastases to the thyroid from extrathyroidal malignancies occur as solitary or multiple nodules, or may involve the whole thyroid gland diffusely. However, diffuse metastasis of gastric cancer to the thyroid is extremely rare. Here, we report a case of a 74-year-old woman with diffuse infiltration of gastric adenocarcinoma (signet-ring-cell carcinoma/poorly differentiated adenocarcinoma) cells in the thyroid. The pathological diagnosis was made based on upper gastrointestinal endoscopy with biopsy and fine-needle aspiration cytology of the thyroid. An 18F-FDG PET/CT revealed multiple lesions with increased uptake, including the bilateral thyroid gland. On thyroid ultrasound examination, diffuse enlargement with internal heterogeneity and hypoechoic reticular lines was observed. On color Doppler imaging, a blood-flow signal was not detected in these hypoechoic lines. These findings were similar to those of diffuse metastases caused by other primary cancers, such as lung cancer, as reported earlier. Therefore, the presence of hypoechoic reticular lines without blood-flow signals is probably common to diffuse thyroid metastasis from any origin and an important diagnostic finding. This is the first report to show detailed ultrasound findings of diffuse gastric cancer metastasis to the thyroid gland using color Doppler.     

Prognostic significance of in vitro thymidine uptake in patients with colorectal carcinoma

In 127 patients with colorectal carcinoma, we measured thymidine uptake by tumor cells cultured in a semisolid medium and compared the influence of various parameters on survival by univariate and multivariate analysis. Fifty-four of the 127 carcinomas (42.5%) incorporated >1,000 cpm of tritiated thymidine per culture dish and were designated as the high-uptake group, while the other tumors (57.5%, 73/127) were designated as the low-uptake group. There was no significant correlation between high or low thymidine uptake and most of the clinicopathological characteristics of the patients. Patients in the high-uptake had a poor prognosis and a 7-year survival rate of 32.6%, which was significantly different from the rate of 69.3% in the low-uptake group (P < 0.0005). Multivariate analysis showed that thymidine uptake was one of the variables strongly associated with survival in our study population. Thus, it is concluded that thymidine uptake by tumor cells has a high capacity of predicting prognosis, independent of its relationship to other variables. Furthermore, it seems to us that thymidine uptake can help in selecting those patients with colorectal carcinoma who are most likely to benefit from perioperative adjuvant therapy. © Wiley-Liss, Inc.     

Combination chemotherapy of carboplatin and cytosine arabinoside for high-risk leukemia: A pilot study

Fourteen patients with high-risk leukemia (six with relapsed AML, three with relapsed ALL, one with AML-M0, four with CML in myeloid blastic crisis) were treated with a combination chemotherapy of carboplatin (200–300 mg/m²/day) and cytosine arabinoside (100 mg/m²/day) by 24 h continuous infusion for 5–7 days. Five patients (35.7%) achieved complete remission including two patients complicated with myelofibrosis (one with AML-M0 and one with CML in myelo-megakaryocytic crisis). Thirteen patients had nausea and vomiting, five patients had severe, prolonged neutropenia for which it was necessary to administer granulocyte colony-stimulating factor and six patients had severe thrombocytopenia. We concluded that this regimen is effective for the treatment of high-risk leukemia.     

Precursor-product relationship between oval cells and hepatocytes: comparison between tritiated thymidine and bromodeoxyuridine as tracers

The expansion and differentiation of oval cells in the acetylaminofluorene(AAF)/partial hepatectomy (PH) model was studied utilizing pulse-chaselabeling with both tritiated thymidine ([³H]TdR) and bromodeoxyuridine(BUdR). Animals in which a significant decrease in serum albuminand increase in alanine aminotransferase and bilirubin wereobserved demonstrated the most prominent differentiation ofoval cells into hepatocytes. Administration of [³H]TdR or BUdR,either individually or together, to the animals on day 6 afterpartial hepatectomy resulted in labeling of the majority ofthe oval cells by days 7 and 9 after PH. A striking differencein the distribution of [³H]TdR- and BUdR-labeled cells in thedouble labeling experiments was observed on day 11, at whichtime the number of [³H]TdR-labeled cells increased 6-fold andthat of double labeled cells decreased 2-fold. Furthermore,on day 11 the basophilic foci were weakly positive for BUdRand negative at later time points in animals receiving BUdRalone or together with [³H]TdR. In contrast, the cells in basophilicfoci as well as transitional cells were positive for [³H]TdR.Cells heavily labeled with both [³H]TdR and BUdR were presentat all time points, indicating an inhibition of the proliferativeactivity. Pulse labeling of rat liver epithelial cells withBUdR in vitro demonstrated that immunodetection of BUdR waslost after three or more cell divisions. We conclude that theBUdR tagging method is particularly sensitive to label dilutionduring cell cycling and may not be suitable for establishmentof a precursor-product relationship between cell lineages whenthe progenitor population proliferates more than three times.     

Thrombolytic therapy with tissue plasminogen activator for the treatment of nonstructural malfunction of bileaflet cardiac valve prostheses

This study was conducted to determine the effect of thrombolytic therapy with tissue plasminogen activator (t-PA) for nonstructural malfunction of bileaflet cardiac valve prostheses. Twenty-seven patients with bileaflet prosthetic valve malfunction diagnosed by a combination of cineradiography and transthoracic echocardiography were treated with the administration of intravenous t-PA. The treatment resulted in complete success in 55.6% (15 of 27), partial success in 22.2% (6 of 27), and no change in 22.2% (6 of 27). In the complete success and partial success groups, the condition of the patients in 85.7% (18 of 21) of the cases improved within 24 h after the administration of t-PA. Six cases in whom thrombolytic therapy was instituted more than 1 month (ranged from 1 to 38 months, mean 14.7 months) after the diagnosis of prosthetic valve malfunction showed significantly less effectiveness of thrombolytic therapy with t-PA. Only one patient (3.7%) had a major complication (thromboembolism) after t-PA treatment. The results suggest that thrombolytic therapy with t-PA in patients with nonstructural malfunction of bileaflet cardiac valve prostheses is effective with low incidence of complication when the treatment is instituted early after the diagnosis.     

Laparoscopic biliary surgery

Laparoscopic cholecystectomy has become the standard treatment for patients with symptomatic gallbladder disease. However, there is a substantial proportion of patients in whom laparoscopic cholecystectomy cannot be successfully performed, and conversion to open surgery is required because of technical difficulties or complications. The incidence of bile duct injury has increased in laparoscopic cholecystectomy. Meticulous dissection and intraoperative cholangiography could significantly reduce the rate of that injury. Laparoscopic cholecystectomy for acute cholecystitis is still controversial because of surgical difficulty. In our experience, early laparoscopic cholecystectomy is a beneficial option for patients with acute cholecystitis, and it may even be safe in the acute stage. A better alternative for high-risk early operation and septic cases is percutaneous transhepatic gallbladder drainage. The coexistence of gallbladder cancer should be ruled out and preoperative diagnosis should be done carefully. Laparoscopic management of common bile duct (CBD) stones has many advantages. However it has been reported to be demanding and time-consuming to perform, which limits its widespread adoption. In our experience with 258 patients, laparoscopic CBD exploration was feasible for almost all CBD stones. The technical difficulties associated with laparoscopic CBD exploration could be overcome with the development of suitable equipment and increased expertise.     

Development of hyperthyroidism in a patient with idiopathic nephrotic syndrome

We present a 13-year-old boy who developed hyperthyroidism during the clinical course of idiopathic nephrotic syndrome treated with glucocorticoid. He had a second relapse of minimal change nephrotic syndrome, and complete remission of nephrotic syndrome was achieved immediately with oral glucocorticoid. However, when the steroid dosage was reduced, signs of hyperthyroidism such as systolic hypertension and tachycardia were observed. Laboratory findings revealed thyroid-stimulating hormone (TSH) below 0.05 μU/ml, free tri-iodothyronine of 16.1 pg/ml, free thyroxine of 5.6 ng/dl, and anti-TSH receptor antibody of 90%. Thus, a diagnosis of hyperthyroidism was made and treatment with thiamazol was started. Massive proteinuria may decrease the activity of hyperthyroidism due to urinary loss of thyroid hormones. A decrease in glucocorticoid dosage may also be involved in the development of hyperthyroidism due to a reduced immunosuppressive effect. Received: 11 July 2001 / Revised: 22 October 2001 / Accepted: 27 November 2001