Association of Loss of Heterozygosity at the p53 Locus with Chemoresistance in Osteosarcomas

Although the osteosarcoma is considered to be among the most chemosensitive malignancies and preoperative chemotherapy is commonly applied, an appreciable proportion of cases are in fact quite insensitive. Predictive markers for chemosensitivity are therefore desirable in order to develop effective treatment strategies. Thirty-two cases of conventional osteosarcomas treated at the Cancer Institute Hospital, Tokyo, were analyzed. The sensitivity to preoperative chemotherapy was investigated with reference to loss of heterozygosity (LOH) at the 17p13 ( p 53) and 13q14 ( Rb ) loci and expression of the cell-cycle associated proteins, p53, Rb, p21/Waf-1, mdm-2 and Ki-67, as detected immunohistochemically. LOH was detected by analyzing polymerase chain reaction products at marker microsatellite loci. The efficacy of chemotherapy was evaluated both radiologically and histologically. LOH at p 53 or Rb loci was seen in 54% (13/24) and 58% (14/24) of cases, respectively. Only 15% of osteosarcomas with LOH at the p 53 locus were sensitive to preoperative chemotherapy, as compared to 64% of tumors without such loss ( P <0.05). A similar but much less distinct tendency was observed with LOH at the Rb locus. No relationship was evident between chemosensitivity and immunohistochemical staining patterns for p53, Rb, p21/Waf-1, mdm-2 or Ki-67. The results suggest that p 53 gene deletion, but not the other parameters investigated, may be useful for predicting chemoresistance of osteosarcomas.     

Histogenesis and clinicopathological characteristics of superficially spreading carcinoma of the esophagus

To explore the possible histogenesis of superficially spreading carcinoma of the esophagus, the clinicopathological features of these tumors (n = 44) were compared with those of ordinary superficial carcinoma (n = 163). Tumors of a heterogeneous histological type and having in situ carcinoma components were significantly more common (P < .05), and the number of residual squamous islands was significantly greater (P < 0.05) in the former group than the latter. Furthermore, the tumor size was not different among in situ, intramucosal, and submucosal carcinomas of the former, whereas the tumors became larger according to the depth of invasion in the latter group. These results indicate that the collision of multiple simultaneously developing superficial tumors is a plausible histogenesis of superficially spreading carcinoma of the esophagus.     

An estimate of the secondary spindle receptor afferent contribution to the stretch reflex in extensor muscles of the decerebrate cat.

1. Vibration or stretch of the medial gastrocnemius muscle in the decerebrate cat each caused a significant increase in the tension of a synergist, the lateral gastrocenmius. 2. Simultaneous vibration and stretch of the medial gastrocnemius resulted in a substantial increase of lateral gastrocnemius tension which was greater that that produced by medial gastrocnemius vibration alone. The size of this force increase was proportional to the amplitude of medial gastrocnemius stretch, for the limited range of amplitudes examined. 3. Since the discharge of the medial gastrocnemius I a afferent fibres was held constant by vibration, the additional tension in lateral gastrocnemius provoked by medial gastrocnemius stretch must have resulted from the activation of an excitatory pathway separate from the I a afferent system. The secondary spindle afferent pathway was considered to be the most likely candidate. 4. The contributions of the Ia afferents and the additional stretch induced excitation to the stretch reflex were compared. The Ia potency was calculated from the ration of tonic vibration reflex force and the vibration frequency. The total Ia contribution to the stretch reflex, which was estimated from the product of this ratio and the primary ending stretch sensitivity, seemed modest, and was consistently smaller than the proposed secondary contribution. 5. The medial gastrocnemius nerve was subjected to anodal blockade at a strength sufficient to eliminate Ia transmission. Under these conditions, the lateral gastrocnemius excitation produced by medial gastrocnemius stretch or vibration was largely eliminated. When lateral gastrocnemius vibration was superimposed, the excitatory effect of medial gastrocnemius stretch was partly restored suggesting that some central facilitation by group Ia afferents may be necessary for group II pexcitatory effects to be manifested. 6. Although the additional excitatory actions of medial gastrocnemius stretch were examined exclusively in a synergist, it is suggested that similar effects are likely to occur in the homonymous stretch reflex.     

Fibronectin Glomerulopathy Confused with Glomerular Endothelial Injury in a Patient with Takotsubo Cardiomyopathy

A 46-year-old woman developed takotsubo cardiomyopathy and nephrotic syndrome. The first kidney biopsy suggested non-immune-complex-mediated membranoproliferative glomerulonephritis (MPGN), and she was diagnosed with glomerular endothelial injury associated with takotsubo cardiomyopathy. A second biopsy was performed two years later because of persistent proteinuria despite renin-angiotensin system inhibition. This biopsy indicated non-immune-complex-mediated MPGN, but a mesangial and subendothelial substance of a higher electron density than that in the first biopsy was detected, suggesting the possibility of glomerular disease with non-immune deposits rather than endothelial injury. Finally, she was diagnosed with fibronectin nephropathy. Although rare, fibronectin glomerulopathy should be considered in non-immune-complex-mediated MPGN.     

Risk Factors for Complications Associated with Peripherally Inserted Central Catheters During Induction Chemotherapy for Acute Myeloid Leukemia

Objective Peripherally inserted central catheters (PICCs) are widely used in patients with hematologic malignancies. However, the risks of PICC-related complications during chemotherapy for acute myeloid leukemia (AML) are not fully understood. Methods We conducted a retrospective review of 128 adult patients with AML who received induction therapy by way of PICC insertion between 2012 and 2019. Results The median duration of PICC insertion was 30 days. The incidence rate of catheter-related bloodstream infection (CRBSI) was 2.4% at 30 days, and women were more likely to suffer from CRBSI than men. Local reactions at the insertion site were observed in 56 patients; however, these events did not predict CRBSI. The incidence rates of catheter-related thrombosis (CRT) were 1.6% at 30 days. Obesity put patients at an increased risk for CRT. Unexpected PICC removal occurred in 59 patients, and women were at a higher risk of catheter removal than men. Conclusion Low PICC-related complication rates, possibly associated with high rates of catheter removal, were observed during intensive chemotherapy for AML. Women and obese patients require careful monitoring of their PICC. Procedures to achieve appropriate PICC removal without increasing the complication rate need to be considered.     

Long-term results of elective hepatectomy for the treatment of ruptured hepatocellular carcinoma

Background/Purpose According to the General rules for the clinical and pathological study of primary liver cancer, compiled by the Liver Cancer Study Group of Japan, ruptured hepatocellular carcinoma (HCC) is classified as stage 4, even if the tumor is small and solitary. We examined the long-term results of elective hepatectomy for the treatment of ruptured HCC. Methods A first hepatectomy was performed without operative death in 193 patients with HCC. Ten patients had ruptured HCC (ruptured group) and 183 patients had nonruptured HCC (nonruptured group). The extension of HCC was macroscopically classified as stage 1 in 23 patients, stage 2 in 71, stage 3 in 53, and stage 4 in 46. Results Cumulative survival rates in the ruptured group at 1, 5, and 10 years were 90.0%, 67.5%, and 20.3%, respectively. The cumulative survival rate was lower in patients with stage 4 disease in the nonruptured group than that in patients in the ruptured group (P < 0.05). Cumulative survival rates did not differ significantly between patients in the ruptured group and those with stage 2 or stage 3 disease. Conclusions Survival rates after elective hepatectomy in patients with ruptured HCC are good, even if the disease is classified as stage 4.     

Subacute bulbar palsy as the initial sign of follicular thyroid cancer

We report a 64-year-old woman with follicular thyroid cancer found by subacute bulbar palsy. Progressive bulbar palsy (PBP) was considered the most likely diagnosis, because no abnormal finding was detected on brain CT and blood test except for the decrease of free T4. An echogram of the thyroid revealed a small nodule which was shown to be class IIb by fine needle biopsy. However, 201Tl scintillation examination showed skull base metastasis. Follicular thyroid cancer sometimes seems to manifest as a distant metastasis with no clinically evident thyroid lesion. This case suggested the importance of a detailed survey for malignancy, when subacute bulbar palsy is seen.     

A case of coexisting malignant carcinoid tumor and adenocarcinoma in the papilla of Vater

A 47-year-old Japanese woman in whom obstructive jaundice had already been diagnosed, was found to have a dome-shaped elevated tumor approximately 3 cm in diameter located in the area very close to the papilla of Vater on endoscopical and radiographical investigations. Histopathologically, the resected tumor was composed mainly of solid nests of atypical argyrophilic cells, and partially of an area of well differentiated tubular adenocarcinoma, showing mutual transition in the mucosal layer. Both immunohistochemical and ultrastructural analyses confirmed the difference in character of tumor cells between these two areas: neuroendocrine cell carcinoma and tubular adenocarcinoma of common type in the intestine. To the best of our knowledge, this is only the third case reported to be a coexisting malignant carcinoid tumor and adenocarcinoma arising in the periampullary region.     

A pseudohypoparathyroidism type Ia patient with normocalcemia

Pseudohypoparathyroidism type Ia (PHP-Ia), one of 4 types of PHP, is a genetic disease characterized by clinical hypoparathyroidism caused by parathyroid hormone (PTH) resistance. In addition, patients with PHP-Ia show resistance to other hormones as well as Albright's hereditary osteodystrophy (AHO), a constellation of features including short stature, obesity, brachydactyly, ectopic ossifications, and/or mental retardation. Hypocalcemia is one of the hallmarks of PHP-Ia, but several PHP-Ia patients have been described to have normocalcemia. We encountered a 10-year-old girl with typical Albright's hereditary osteodystrophy with round face, short stature, brachydactyly, and obesity. Biochemical examination showed normocalcemia and increased PTH levels. Ellsworth-Howard test did not show any responses of urinary cAMP and phosphate. Based on these findings, she was diagnosed as having PHP-Ia with normocalcemia. Sequencing analysis of the GNAS gene identified a heterozygous missense mutation in exon 13 (R385H), which was previously reported in a PHP-Ia patient. The exact reason for her normocalcemia is not determined, but we must recognize heterogeneous biochemical findings even in PHP-Ia.     

Herpes simplex encephalitis and subsequent cytomegalovirus encephalitis after chemoradiotherapy for central nervous system lymphoma: a case report and literature review

Neurological complications during the treatment of hematological malignancies have a wide range of causes. Treatment-related leukoencephalopathy has been recognized as a major complication of combined chemotherapy and radiotherapy for central nervous system (CNS) lymphoma, and can complicate the diagnosis of CNS infection. Herein, we present a patient with diffuse large B-cell lymphoma who developed herpes simplex encephalitis (HSE) and subsequent cytomegalovirus encephalitis after chemoradiotherapy for CNS relapse. Although cerebrospinal fluid examination (CSF) showed no significant pleocytosis, brain magnetic resonance imaging and polymerase chain reaction analysis of the CSF were useful in the diagnosis. With a review of the literature on the association between HSE and radiotherapy for CNS malignancies, our case suggests that an awareness of viral encephalitis is important in the differential diagnosis of acute neurologic disturbance during chemoradiotherapy for CNS lymphoma.