Rapid progression of gastric cancer with liver metastasis after discontinuation of lenalidomide in a patient with concurrent multiple myeloma: A case report.

INTRODUCTION: The synchronous incidence of multiple myeloma (MM) and other primary malignant solid tumor is rare. No detailed studies have been published regarding the perioperative management of patients with concurrent MM and malignant solid tumor. We report a patient with concurrent MM and gastric cancer who experienced rapid progression of liver metastasis after lenalidomide was discontinued. PRESENTATION OF CASE: An 82-year-old woman with MM was diagnosed with clinical T3N2M0 gastric cancer, and MM had been maintained in remission with lenalidomide. Preoperatively, pancytopenia was found, and lenalidomide was discontinued and lenograstim was administered. Blood transfusions were also administered preoperatively due to anemia caused by tumor bleeding. Surgery was performed after her pancytopenia improved. Intraoperatively, several nodules were found on the liver, which were diagnosed as adenocarcinoma metastases. On postoperative day 13, a low density mass in the liver that was not observed before surgery was shown. The patient received best supportive care because she did not desire adjuvant chemotherapy for gastric cancer or resumption of treatment for MM. She died of progressive gastric cancer on postoperative day 80. DISCUSSION: Discontinuation of lenalidomide in our case may have promoted tumor angiogenesis and lowered antitumor immunity, causing rapid tumor growth and liver metastasis. Continuation of the MM agent may be preferable in patients who do not have marked myelosuppression. CONCLUSION: Surgeons should be familiar with the risks associated with discontinuation of MM drugs when operating on patients with MM and concurrent malignant solid tumor.

Immune microenvironment in Barrett's esophagus adjacent to esophageal adenocarcinoma: possible influence of adjacent mucosa on cancer development and progression.

The immune microenvironment plays a pivotal role in cancer development and progression. Therefore, we studied the status of immune cells in esophageal adenocarcinoma (EAC) and adjacent Barrett's esophagus (BE) and their association with the clinical course of patients. We included 87 patients with EAC who underwent surgical resection or endoscopic submucosal dissection. CD3, CD8, Foxp3, p53, and Ki-67 were immunolocalized in EAC and adjacent BE (N = 87) and BE without EAC (N = 13). BE adjacent to EAC exhibited higher CD3+ lamina propria lymphocyte (LPL) numbers than BE without EAC. Abundant Foxp3+ LPLs in BE were associated with dysplasia and increased Ki-67 labeling index (LI) in BE glandular cells and tended to link to aberrant p53 expression. Abundant CD8+ LPLs in adjacent BE were associated with worse prognosis of EAC patients (P = 0.019). Results of our present study firstly revealed the potential influence of the tissue immune microenvironment of BE adjacent to EAC on cancer development and eventual clinical outcome of EAC patients. T cell infiltration could play pivotal roles in facilitating the dysplasia-adenocarcinoma sequence in BE. The number of Foxp3+ T cells is increased at the early stage of carcinogenesis and could help identify patients harboring dysplastic and highly proliferating cells. CD8+ T cells could reflect unfavorable inflammatory response in adjacent tissue microenvironment and help predict worse prognosis of EAC patients.

CD7-Positive Diffuse Large B-Cell Lymphoma Presenting as an Intranasal Tumor.

We report a case of a 74-year-old man with a cluster of differentiation (CD) 7-positive diffuse large B-cell lymphoma (DLBCL) in the right nasal cavity. Flow cytometry analyses showed CD7 and CD20 positivity in tumor cells. The patient received 6 cycles of R-CHOP plus local radiation therapy because positron emission tomography-computed tomography after R-CHOP revealed an intranasal lesion. The patient achieved complete remission (CR) after radiation therapy. The frequency of CD7-positive DLBCL is rare, and only 11 cases with follow-up of clinical course have been reported thus far. CR or partial response was noted in 8 of 11 cases after receiving rituximab combined with chemotherapy. In total, 9 of 12 cases involved the development of extranodal lesions, which occurred as an intranasal tumor in 3 cases. It is important to examine the clinical features by accumulation of further cases.

Glucocorticoid receptor and serum- and glucocorticoid-induced kinase-1 in esophageal adenocarcinoma and adjacent Barrett's esophagus.

Barrett's esophagus (BE) is a consequence of gastroesophageal reflux disease and is predisposed to esophageal adenocarcinoma (EAC). EAC is an exemplar model of inflammation-associated cancer. Glucocorticoids suppress inflammation through glucocorticoid receptor (GR) and serum- and glucocorticoid-induced kinase-1 (Sgk1) expressions. Therefore, we immunolocalized GR and Sgk1 in EAC and the adjacent BE tissues and studied their association with clinical disease course in 87 patients with EAC who underwent surgical resection (N = 58) or endoscopic submucosal dissection (N = 29). Low GR and Sgk1 expressions in adjacent BE tissues were associated with adverse clinical outcomes (P = 0.0008 and 0.034, respectively). Patients with low Sgk1 expression in EAC cells exhibited worse overall survival (P = 0.0018). In multivariate Cox regression analysis, low GR expression in the adjacent nonmalignant BE tissues was significantly associated with worse overall survival (P = 0.023). The present study indicated that evaluation of GR and Sgk1 expressions in both the EAC cells and adjacent nonmalignant BE tissues could help to predict clinical outcomes following endoscopic and surgical treatments. In particular, the GR status in BE tissues adjacent to EAC was an independent prognostic factor.

Clinically diagnosed primary transitional cell carcinoma of the colon: A case report.

INTRODUCTION: Most transitional cell carcinomas (TCCs) occur in the urinary tract. There are no reports of TCC originating in the colon. This report presents a very rare case of TCC that primarily occurred in the colon. PRESENTATION OF CASE: A 78-year-old female presented with adenocarcinoma of the rectum and TCC of the ascending colon. She was screened for urologic and gynecologic carcinomas because the TCC was considered a metastatic lesion; however, cytodiagnosis of urine, the cervix and corpus uteri revealed no abnormal findings. An operation was performed, and histological examination revealed adenocarcinoma of the rectum and TCC of the ascending colon. Immunohistochemical stained specimens of the ascending colon revealed tumor cells of cytokeratin (CK) 7-/CK20+ pattern. Eleven months post-operation, a metastatic TCC was found in the liver. The patient was treated with chemotherapy; however, she died 19 months after the operation. DISCUSSION: Our case was clinically considered that the TCC primarily occurred in the colon after analyzing the results of several examinations. Immunohistochemical staining of CK7 and CK20 expression pattern also suggested that the TCC of the ascending colon originated in the colon. CONCLUSION: To the best of our knowledge, this is the first literature report of TCC that originated in the colon. TCC that primarily occurs in the colon may rapidly progress, as in the case presented. Therefore, it is necessary to establish more appropriate treatment for similar cases.

Non-Hodgkin lymphoma diagnosed by a percutaneous trans-hepatic needle biopsy of portal vein tumor emboli.

A 58-year-old woman was admitted to our hospital for evaluation of left flank pain. Abdominal computed tomography showed a greatly enlarged splenic tumor with a massive portal vein tumor thrombosis (PVTT). We suspected non-Hodgkin lymphoma (NHL) based on the high values of serum soluble interleukin-2 receptor and lactate dehydrogenase. Because there was no superficial lymph node enlargement, ultrasound-guided percutaneous trans-hepatic needle biopsy was performed to obtain a pathological diagnosis of PVTT, instead of a splenectomy, after the patient had provided informed consent. This procedure was thought to be less invasive than splenectomy. Histologic examination revealed CD20-positive NHL. A complete response was achieved after six courses of R-CHOP and it was confirmed by splenectomy. A PVTT due to NHL is extremely rare as compared with that due to hepatocellular carcinoma, gastric cancer, and colon cancer. However, NHL should be considered in the differential diagnosis for a patient with a PVTT, because B cell-NHL tends to have a good prognosis when rituximab combined chemotherapy is administered. We suggest that a percutaneous trans-hepatic needle biopsy may be useful for diagnosing PVTT due to NHL.

Comparison of short-term outcomes between prone and lateral decubitus positions for thoracoscopic esophagectomy.

BACKGROUND: Prone thoracoscopic esophagectomy was introduced at our institution from 2012. This study describes our experiences of the main differences between thoracoscopic esophagectomy in the prone and traditional left lateral decubitus positions together with an analysis of the short-term surgical outcomes. METHOD: In total, 87 patients undergoing thoracoscopic esophagectomy between January 2012 and October 2013 at Tohoku University Hospital were enrolled; of these, 54 and 33 patients were operated in the prone (Group P) and lateral decubitus (Group L) positions, respectively. RESULTS: The background of the patients was similar, and there was no in-hospital mortality. There were no significant differences between the groups in terms of whole surgical duration, thoracic duration, and number of dissected lymph nodes. Total blood loss and thoracic estimated blood loss were significantly lower in Group P than Group L. Furthermore, postoperative pulmonary complications, intensive care unit stay, and hospital stay were significantly lower in Group P. CONCLUSION: Thoracoscopic esophagectomy in the prone position is feasible and safe. The prone position technique may be superior to conventional lateral decubitus position esophagectomy.

Murine double minute 2 and its association with chemoradioresistance of esophageal squamous cell carcinoma.

BACKGROUND: Definitive chemoradiotherapy (dCRT) has been established as the standard treatment for esophageal squamous cell carcinoma (ESCC). However, many patients develop persistent or recurrent disease following dCRT. We investigated factors related to chemoradioresistance and treatment outcomes in patients with ESCC who underwent salvage esophagectomy after dCRT. PATIENTS AND METHODS: We selected 38 patients with persistent disease and 24 with recurrent disease who underwent salvage esophagectomy after dCRT, immunolocalized p53, p16, p27, murine double minute 2 (MDM2), cyclin D1, Ki-67, and epidermal growth factor receptor, and correlated the findings with clinicopathological features. RESULTS: MDM2 positivity was significantly higher among patients with persistent disease than among those with recurrent disease (p<0.0001). In addition, negative p16 expression was a predictor of poor prognosis among patients with persistent disease. CONCLUSION: MDM2 overexpression plays an important role in chemoradioresistance of ESCC; furthermore, negative p16 expression can predict poor prognosis of patients with persistent disease.

Significance of CD133 expression in esophageal squamous cell carcinoma.

BACKGROUND: CD133 was recently reported to be a cancer stem cell marker and a prognostic marker for several tumors. However, few studies have investigated CD133 expression in esophageal squamous cell carcinoma (ESCC). Therefore, we examined whether CD133 could serve as a prognostic marker of ESCC and investigated the correlation between CD133 expression and the clinicopathological findings of ESCC patients and several markers. METHODS: We studied 86 ESCC patients who underwent curative surgery without neoadjuvant treatment at Tohoku University Hospital (Sendai, Japan) between January 2000 and December 2005. We analyzed tissue specimens by immunohistochemical staining for CD133, p53, p16, p27, murine double minute 2 (MDM2), Ki-67, and epidermal growth factor receptor (EGFR). RESULTS: Pathological tumor depth and tumor stage were significantly more advanced among CD133-negative patients than among CD133-positive patients. A log-rank test showed that CD133 immunoreactivity was significantly correlated with the overall survival of the patients (P = 0.049). However, multivariate analysis showed that it was not significantly correlated (P = 0.078). Moreover, CD133 was significantly positively correlated with p27 immunoreactivity (P = 0.0013) and tended to be positively correlated with p16 immunoreactivity (P = 0.057). In addition, p16 immunoreactivity was correlated with smoking history (P = 0.018), pathological lymph node status (P = 0.033), and lymphatic invasion (P = 0.018). CONCLUSIONS: This study indicated that CD133 immunoreactivity is a good predictor of prognosis in ESCC patients. In addition, CD133 may play a role in the regulation of tumor cell cycle through p27 and p16 in ESCC. At present, it thus remains controversial whether CD133 expression is a valid prognostic marker for ESCC. To elucidate this relationship, further investigations are required.

Estrogen receptor α and ß in esophageal squamous cell carcinoma.

A gender difference has been reported in the morbidity of esophageal squamous cell carcinoma (ESCC). Estrogens have been proposed to play a role in this difference but the details have not yet been clarified. Therefore, in the present study, we examined the status of estrogen receptor (ER)α and ERß in 90 Japanese ESCC patients. ERα and ERß immunoreactivity was detected in the nuclei of ESCC cells (41.1 and 97.8%, respectively). There was a significant positive association between the ERß H score and histological differentiation (P = 0.0403), TNM-pM (LYM) (P = 0.00164) and Ki67/MIB1 LI of carcinoma cells (P = 0.0497, r = 0.207). In addition, the ERß status of carcinoma cells was significantly correlated with unfavorable clinical outcome of the patients. Multivariate analysis further revealed the ERß status in carcinoma cells as an independent unfavorable prognostic factor of these patients. We further examined the effects of estrogen treatment on ESCC cell line (ECGI-10) transfected with ERα or ERß in vitro. The number of ECGI-10 transfected with ERß was increased by estradiol or ERß specific agonist but estradiol did not exert any effect upon the cell number of ECGI-10 transfected with ERα. In summary, the results of the present study clearly demonstrate that the status of ERß in ESCC was closely associated with the unfavorable prognosis, possibly through altering cell proliferation of carcinoma cells.