Tomoya Sudo

Optimal Lymphadenectomy for Squamous Cell Carcinoma in the Thoracic Esophagus: Comparing the Short- and Long-term Outcome among the Four Types of Lymphadenectomy

Controversy continues over the optimal extent of lymphadenectomy (regional versus three-field) for a potentially resectable squamous cell carcinoma in the thoracic esophagus. In the Consensus Conference of the International Society for Diseases of the Esophagus (ISDE), held in Munich in 1994, the types of lymphadenectomy were classified as standard, extended, total, or three-field lymphadenectomy. The objective of the present study was to determine the optimal procedure among these four types of lymphadenectomy. The mortality and morbidity rates, postoperative course, and survival rates were compared among 302 patients who underwent curative (R0) transthoracic esophagectomy with one of these four types of lymphadenectomy at Kurume University Hospital, Fukuoka, Japan, from 1986 to 1998. Three-field lymphadenectomy resulted in better survival than any other type of lymphadenectomy for patients with positive lymph node metastasis from a cancer in the upper or middle thoracic esophagus. A postoperative complication, such as recurrent laryngeal nerve paralysis, anastomotic leakage, and tracheal ischemic lesion, was significantly more common after three-field lymphadenectomy. However, the mortality rate was the same among the four procedures. Three-field lymphadenectomy was optimal for an upper or middle thoracic esophageal cancer with metastasis in the lymph node(s) based on improved long-term survival, whereas there was not a large difference in short-term and long-term outcomes after the four types of lymphadenectomy for a lower thoracic esophageal cancer.

Adjuvant Chemotherapy after Radical Resection of Squamous Cell Carcinoma in the Thoracic Esophagus: Who Benefits?

Background: A definitive combined modality therapy superior to surgery alone has not yet been found for esophageal cancer. This retrospective study investigated the impact of postoperative adjuvant chemotherapy in patients who underwent curative (R0) esophagectomy with radical lymphadenectomy. Study Design: Two hundred and eleven patients with a squamous cell carcinoma in the thoracic esophagus who underwent transthoracic curative (R0) esophagectomy with radical lymphadenectomy, such as 3-field lymphadenectomy or total 2-field lymphadenectomy, between 1988 and 2000, were retrospectively reviewed. Ninety-four patients received postoperative chemotherapy – 2 courses of cisplatin (CDDP) plus fluorouracil (5-FU) or vindesine (VDS) – while the other 117 patients received surgery alone. The overall survival rate was compared between the two groups after being stratified by the numbers of the metastasis- positive lymph nodes. Results: Only in the subgroup of patients with 8 or more lymph nodes metastasis- positive, the surgery-with-postoperative-chemotherapy group had a significantly better survival than the surgery-alone group. No significant difference was found in survival between the two groups in any other stratified subgroup. Conclusions: Postoperative adjuvant chemotherapy following curative (R0) esophagectomy with radical lymphadenectomy such as 3-field lymphadenectomy or total 2-field lymphadenectomy provided a benefit only in patients having metastasis in a large number – 8 or more – lymph nodes.

Locoregional adoptive immunotherapy resulted in regression in distant metastases of a recurrent esophageal cancer

Abstract. Esophageal cancer is one of the most common malignant diseases. However, postoperative recurrences are still resistant to currently available radiochemotherapy. We recently reported a study on the initial clinical efficacy of locoregional adoptive immunotherapy for advanced esophageal cancer. We report here our clinical experience of remarked responses in distant metastatic lesions in a patient with recurrent cancer after receiving this immunotherapy. A male patient underwent curative surgery, and presented with multiple recurrent metastases in the supraclavicular lymph nodes (LNs), liver, and abdominal aortic LNs. Autologous tumor-activated lymphocytes (AuTLs) generated ex vivo were regionally injected into supraclavicular LNs every 2 weeks 13 times. Mean numbers of the administrated cells were 0.8 × 109 cells/injection. AuTLs established from peripheral blood lymphocytes stimulated by autologous tumor cells with interleukin-2 were tested for their cytotoxicity before every treatment. During immunotherapy, Grade 2 diarrhea and fever were observed. The clinical partial responses were obtained in all lesions and were sustained for 11 months. Because clinical toxicity was tolerable, this immunotherapy might be useful for patients with far-advanced esophageal cancers.

Clinical Impact of Tumor-Infiltrating Lymphocytes in Esophageal Squamous Cell Carcinoma

BackgroundRecently, several immune checkpoint inhibitors have been developed and are being used to treat malignant melanoma, lung cancer, and other cancers. Several reports have indicated that tumor-infiltrating lymphocytes (TILs) are associated with clinical and histopathologic risk factors in various cancers. However, the role of TILs in esophageal squamous cell carcinoma (ESCC) has not been well studied. This study aimed to investigate the perilesional status of TILs in ESCC and to show associations between TILs and clinical variables.MethodsThe study enrolled 277 ESCC patients. Evaluation of TILs was performed according to the criteria of the International TILs Working Group 2014, and associations between TIL and clinicopathologic variables were examined.ResultsMost of the clinicopathologic factors were not statistically associated with TIL status. The number of patients who received adjuvant therapy was significantly larger in the TIL-negative group. Cancer-specific survival (CSS) of patients in the TIL-positive group was significantly better than in the TIL-negative group. Among the patients who received adjuvant therapy, CSS was significantly better in the TIL-positive group than in the TIL-negative group. Uni- and multivariate analyses identified tumor depth and TIL status as independent prognostic factors for CSS. Among the other clinicopathologic variables, TIL status was the strongest CSS indicator.ConclusionTumor-infiltrating lymphocyte status is a strong predictor of good prognosis for ESCC patients.

Significance of CD47 expression in gastric cancer

Integrin-associated protein (CD47) is ubiquitously expressed on the surface of cells and functions as an identifier of self. In blood cancer, tumor cells expressing CD47 evade phagocytosis by macrophages, leading to a poor patient prognosis. However, the status of CD47 expression in solid tumors, particularly in gastric cancer, is not well understood. The purpose of the present study was to examine the level of CD47 in the primary tumor, peripheral blood (PB) and bone marrow (BM) of patients with gastric cancer, and to determine its effect. Reverse transcription-quantitative polymerase chain reaction analysis was performed to determine the level of CD47 mRNA expression in primary tumor, PB and BM samples collected from 168 patients with gastric cancer. Cell sorting was performed to investigate CD47 protein expression in PB and BM fractions, and to identify the source of CD47 expression. In primary tumors, the expression of CD47 was not associated with any clinicopathological factors or prognosis. By contrast, in PB, the low CD47 expression group demonstrated a significantly increased tumor size, and frequency of lymphatic invasion and lymph node metastasis, compared with the high CD47 expression group. In addition, the clinical tumor stage of the low CD47 expression group was significantly increased compared with that of the high CD47 expression group. Conversely, in PB, the high CD47 expression group had a significantly higher frequency of lymphatic invasion and lymph node metastasis compared with the low CD47 expression group. The lymphocyte fraction exhibited the highest CD47 expression compared with the other fractions in PB and BM samples. Low expression of CD47 was associated with the advancement of gastric cancer, in contrast to other cancers, and it may be associated with a decrease in lymphocytes during later stages. These results indicate that CD47 expression in the PB and BM may serve as a marker to analyze the immunological function of patients with gastric cancer; however, the significance of CD47 in gastric cancer requires further study.

PD-L1 expression in pancreatic adenosquamous carcinoma: PD-L1 expression is limited to the squamous component

AIM We examined the programmed death-ligand 1 (PD-L1) expression in surgically resected pancreatic adenosquamous carcinoma (PASC) samples. Furthermore, the detection rate was also assessed using biopsy cases obtained from endoscopic ultrasound-guided fine needle aspiration (EUS-FNA). METHODS Fifteen cases of PASC (six resected and nine EUS-FNA biopsied) from the Kurume University Hospital between 2009 and 2016 were used for the evaluation of PD-L1 expression. As a control group, 34 cases of pancreatic ductal adenocarcinomas (PDACs) were selected. To compare　the positivity and intensity of PD-L1, two types of clones (SP263, E1L3N) were examined for immunostaining. Only the membrane expression of PD-L1 was regarded as positive. The PD-L1 expressions in the squamous cell carcinoma component (SCc), adenocarcinoma component (ACc), and immune cells were assessed separately. The ratio of PD-L1 expression was calculated by counting the positive tumor cells, and tumor proportion score (TPS) was applied (TPS; Null < 1%, low expression; 1 ≤ TPS ≤ 49% and high expression; ≥ 50%). RESULTS PD-L1 expression was observed in five surgical PASC samples (83%). This shows that SCc presented a high expression in these cases. However, the overall TPS indicated a low expression. In contrast, only one case (3%) was positive for PD-L1 in PDACs, and the TPS indicated a low expression. No differences in PD-L1 expression were observed between the two clones, SP263 and E1L3N. High PD-L1 expression in the EUS-FNA sample was found in only one case (11%). DISCUSSION Although assessment using the tumor cells of PASC samples obtained from EUS-FNA was difficult, this study suggests the selective expression of PD-L1 in the SCc of PASC. Furthermore, it was considered that immune checkpoint inhibitors could provide therapeutic effects selectively on the SCc for the entire range of TPSs, though the PD-L1 expression was low.