Plasma trough concentration of imatinib and its effect on therapeutic efficacy and adverse events in Japanese patients with GIST

International Journal of Clinical Oncology - Imatinib mesylate (IM) is the standard chemotherapy for patients with gastrointestinal stromal tumors (GISTs) and has a favorable safety profile....     

Angioimmunoblastic T-cell lymphoma with hyperplastic germinal centers: a clinicopathological and immunohistochemical study of 10 cases

An absence of germinal centers is one of the histological characteristics of angioimmunoblastic T-cell lymphoma (AITL). We report here 10 unusual cases of AITL with hyperplastic germinal centers. The clinical presentation of each patient was characterized by generalized lymphadenopathy, constitutional symptoms and polyclonal hypergammaglobulinemia. The initial biopsy findings of each patient were similar and were characterized by hyperplastic germinal centers with ill-defined borders and a proliferation of high endothelial venules (HEV). In the paracortical area there was a mixed infiltrate including irregularly shaped clusters or small nests of clear cells in all cases. Moreover, the clear cells invaded the lymphoid follicles, resulting in expansion of the germinal centers, except for one case. Immunohistochemistry revealed that the tumor cells, including clear cells, were CD4-expressing T cells. Some of the atypical lymphocytes were also Bcl-6-positive. A majority of the follicular dendritic cell networks showed a normal/reactive or an expanded/disrupted pattern in all cases. Moreover, three lesions possessed a few large irregularly shaped proliferations of follicular dendritic cells around the HEV Four cases progressed to AITL within a few years. The present 10 cases probably represent an early stage of AITL preceding follicular dendritic cell hyperplasia. Detection of clear cells, Bcl-6-positive atypical T lymphocytes, and foci of irregularly shaped proliferation of follicular dendritic cells appears to be critical for early diagnosis and treatment of AITL with hyperplastic follicles.     

Nodal cytotoxic lymphoma spectrum: a clinicopathologic study of 66 patients.

The expression of cytotoxic granule-associated proteins has been reported in some T-cell or natural killer (NK)-cell lymphomas of mostly extranodal origin, but rarely of nodal origin except for anaplastic large cell lymphoma (ALCL) and Hodgkin's disease (HD). This study analyzed 66 nodal lymphomas expressing T-cell intracellular antigen-1 (TIA-1) and/or granzyme B to characterize the clinicopathologic spectrum of these neoplasms. Four main groups could be delineated. The first group consisted of p80/anaplastic lymphoma kinase (ALK)-positive ALCL (n = 35). The patients were 2 to 62 years of age (median age, 16 years), and the lymphomas pursued a relatively indolent clinical course. The tumors were phenotypically of either T- or null-cell type with constant expression of CD30, epithelial membrane antigen (EMA), and p80/ALK, but not CD15 or BCL2. None harbored Epstein-Barr virus (EBV). The second group consisted of peripheral T/NK-cell lymphoma, the nodal high-grade cytotoxic type (n = 13). The patients were 29 to 72 years in age (median age, 55 years), and the tumors pursued an aggressive clinical course. The tumors often showed pleomorphic, anaplastic, or centroblastoid morphology, and were featured by either EBV association or CD56 expression. The third group consisted of peripheral T-cell lymphoma, of the nodal low-grade cytotoxic type (n = 8). The patients, three men and five women, were 31 to 75 years old (median age, 61 years). Notably, six of them exhibited lymphoepithelioid (Lennert's) lymphoma. The fourth group consisted of cytotoxic Hodgkin's-like ALCL/HD (n = 10), included seven cases of Hodgkin's-like ALCL and three cases of HD, and was characterized by the presence of Reed-Sternberg cells and often the CD15+ phenotype. The patients were all men except for one woman, and they ranged in age from 24 to 84 years (median age, 62 years). The link among these four groups was reinforced by the presence of a highly characteristic large cell with horseshoelike or reniform nuclei-the frequent expression of CD30 and EMA-and the often lack of T-cell receptor-alphabeta. In this series, the expression of p80/ALK and CD56 was also associated with favorable and poor prognoses respectively (p<0.001, log-rank test).     

Comparison Between Radical Esophagectomy and Definitive Chemoradiotherapy in Patients with Clinical T1bN0M0 Esophageal Cancer

Background

Esophagectomy remains the mainstay treatment for clinical T1bN0M0 esophageal cancer because pathologic lymph node metastases in these patients are not negligible. Recently, chemoradiotherapy (CRT), which can preserve the esophagus, has been reported to be a promising therapeutic alternative to esophagectomy. However, to our knowledge, no comparative studies of esophagectomy and CRT have been reported in clinical T1bN0M0 esophageal cancer.

Methods

A total of 173 patients with clinical T1bN0M0 squamous cell carcinoma of the thoracic esophagus were enrolled in this study, 102 of whom were treated with radical esophagectomy (S group) and 71 with definitive CRT (CRT group). Treatment results of both groups were retrospectively compared.

Results

No statistically significant difference was found in overall survival, but the S group displayed significantly better progression-free survival than the CRT group. Disease recurrence was observed in 12 S group patients and 20 CRT group patients. The incidence of distant recurrence was similar, while local recurrence and lymph node recurrence were significantly more frequent in the CRT group. In the S group, 20 patients had pathologic lymph node metastasis. The progression-free survival of patients with pathologic lymph node metastasis did not differ from those without nodal metastasis. In the CRT group, local recurrence could be controlled by salvage esophagectomy, but treatment results of lymph node recurrence were poor; only 4 of 12 patients with lymph node recurrences were cured.

Conclusions

Selection of patients at high risk of pathologic lymph node metastasis is essential when formulating treatment decisions for clinical T1bN0M0 esophageal cancers.     

Laparoscopic distal gastrectomy for gastric cancer with simultaneous resection of para‐aortic schwannoma

An asymptomatic 74‐year‐old man was diagnosed with early gastric cancer during screening. Preoperative CT revealed a 25‐mm tumor surrounded by the abdominal aorta, inferior vena cava, and left renal vein. Based on the primary tumor stage, para‐aortic lymph node metastasis was considered to be unlikely but could not be ruled out. For this reason, we planned a concurrent diagnostic and therapeutic laparoscopic resection with gastrectomy. The gastric cancer and para‐aortic tumor were successfully resected laparoscopically. The tumor was diagnosed as a schwannoma. With care and skill, we were able to resect the para‐aortic schwannoma and gastric cancer simultaneously and safely by using laparoscopic techniques.     

Clinical significance of muscle layer interruption in T3 esophageal cancer

Background

Patients with adventitia-invading (T3) tumors, which account for the majority of esophageal cancers, are indicated for surgery but still have a poor prognosis. Subclassifying T3 tumors based on clinical outcome would be useful for selecting adequate adjuvant therapies.

Methods

Using 268 esophageal cancer specimens from patients without preoperative treatment, the length of the vertical and longitudinal tumor invasion, entire esophageal wall thickness, and interruption of the outer muscle layer were measured. These morphological parameters correlated with clinico-pathological factors and outcome.

Results

Patients were classified as T1 (38.4 %), T2 (11.9 %), T3 (38.4 %), and T4 (11.2 %) and T stage correlated well with the four morphological parameters (p < 0.0001). Each of the four morphological parameters was a significant prognostic factor. A cutoff at 20 mm of muscle layer interruption (MLI) yielded the highest prognostic significance (5-year survival 36.7 vs. 59.1 %, p = 0.009). T3 tumors with <20 mm MLI showed survival rates equivalent to T2 tumors (5-year survival 59.5 %), whereas those with ≥20 mm MLI had survival rates similar to T4 tumors (5-year survival 26.7 %). Although lymphatic and hematogenic recurrence was not significantly different, local recurrences occurred more frequently in patients with T3 tumors with ≥20 mm MLI than in those with <20 mm MLI (4.3 vs. 21.4 %, p = 0.019).

Conclusions

T3 esophageal cancer can be classified into subgroups according to the length of MLI. Additional local treatment would be indicated for T3 tumors with >20 mm MLI.     

Hepatic metastasis from gastric GIST radically resected after imatinib mesylate therapy-a case report

We report a case of hepatic metastasis from gastric gastrointestinal stromal tumor (GIST), which was safely resected with preoperative imatinib therapy. A 60-year-old woman was hospitalized and underwent a treatment for hepatic SOL at another hospital prior to gastric GIST resection. Computed tomography revealed a tumor compressing the right and middle hepatic vein. The tumor volume decreased after an initiation of imatinib therapy aimed at preserving the middle hepatic vein. Although tumor volume was further decreased over the course of twelve months, a new lesion appeared, suggesting a progressive disease. Our findings suggest that a radical resection of gastric GIST to preserve the middle hepatic vein is possible.