Yoshiyuki Yamamura

The immunological impact of neoadjuvant chemotherapy on the tumor microenvironment of esophageal squamous cell carcinoma.

BackgroundEsophageal cancer is an aggressive cancer with poor prognosis. However, little is known about the immune response in the tumor microenvironment after neoadjuvant chemotherapy.PurposeTo investigate the immunological impact of neoadjuvant chemotherapy in the tumor microenvironment of esophageal squamous cell carcinoma.MethodsEighteen patients with esophageal squamous cell carcinoma with and without neoadjuvant chemotherapy were analyzed using immunohistochemical methods for human leukocyte antigen (HLA) class I heavy chain, CD4-, CD8-, and Foxp3-positive cell infiltration.ResultsThe number of CD4 T cells in the stroma and within the cancer nest was significantly higher in the neoadjuvant chemotherapy group. The number of CD8 T cells in the stroma was significantly higher in the neoadjuvant chemotherapy group. HLA class I expression was more downregulated in the control group compared with the neoadjuvant chemotherapy group.ConclusionNeoadjuvant chemotherapy utilizing 5-fluorouracil and cisplatin in esophageal squamous cell carcinoma is useful to induce CD4 and CD8 T lymphocytes in the tumor microenvironment and to maintain HLA class I expression levels in combination with its direct cytotoxic effects.

Simultaneous Resection of Bilateral Intralobar and Extralobar Pulmonary Sequestrations With Video-Assisted Thoracoscopic Surgery

The term pulmonary sequestration is applied to a pulmonary lobe or portion of a lobe that is supplied by an anomalous systemic artery and drain either into the systemic or pulmonary veins. The conditions are divided into intralobar pulmonary sequestration, in which the sequestration is situated inside the visceral pleura of a normal lobe, and extralobar sequestration, in which the sequestration is surrounded by its own pleura. Most sequestrations are unilateral; bilateral sequestrations are rare. We report the case of a synchronous bilateral intralobar and extralobar pulmonary sequestrations resected simultaneously with video-assisted thoracoscopic surgery.

Differential detection of cytoplasmic Wilms tumor 1 expression by immunohistochemistry, western blotting and mRNA quantification

Wilms tumor 1 (WT1) is considered to be a promising target of cancer treatment because it has been reported to be frequently expressed at high levels in various malignancies. Although WT1-targeted cancer treatment has been initiated, conclusive detection methods for WT1 are not established. The present study aimed to consolidate immunohistochemistry for WT1 with statistical basis. Transfected cells with forced WT1 expression yielded specific western blot bands and nuclear immunostaining; cytoplasmic immunostaining was not specifically recognized. Immunohistochemistry, western blotting, and quantitative reverse transcriptase-polymerase chain reaction were performed in 35 human cell lines using multiple WT1 antibodies and their results were quantified. Relationships among the quantified results were statistically analyzed; the nuclear immunostaining positively correlated with western blot bands and mRNA expression levels, whereas cytoplasmic immunostaining did not. These results indicate that nuclear immunostaining reflects WT1 expression but cytoplasmic immunostaining does not. The nuclear immunostaining was barely (3/541) observed in primary cancer of esophagus, bile duct, pancreas and lung. Although the present study has some limitations, the results indicate that the cytoplasmic immunostaining does not correlate with actual WT1 expression and prompts researchers to carefully evaluate target molecule expression in treatment of cancer.

Surgical resection of colorectal recurrence of gastric cancer more than 5 years after primary resection.

INTRODUCTION Intestinal metastasis from gastric cancer is rare, although the most common cause of secondary neoplastic infiltration of the colon is gastric cancer. However, little data is available on recurrence or death in patients with gastric cancer surviving >5 years post-gastrectomy. Here we report two cases of lower intestinal metastasis from gastric cancer >5 years after primary resection and discuss with reference to the literature. PRESENTATION OF CASE Case 1: A 61-year-old man with a history of total gastrectomy for gastric cancer 9 years earlier was referred to our hospital with constipation and abdominal distention. We diagnosed primary colon cancer and subsequently performed extended left hemicolectomy. Histological examination revealed poorly differentiated adenocarcinoma resembling the gastric tumor he had 9 years earlier. The patient refused postoperative adjuvant chemotherapy and remained alive with cancerous peritonitis and skin metastases as of 17 months later. Case 2: A 46-year-old woman with a history of total gastrectomy for gastric cancer 9 years earlier presented with constipation. She also had a history of Krukenberg tumor 3 years earlier. We diagnosed metastatic rectal cancer and subsequently performed low anterior resection and hysterectomy. Pathological examination revealed poorly differentiated tubular adenocarcinoma, resembling the gastric tumor. The patient remained alive without recurrence as of 17 months later. DISCUSSION We found 19 reported cases of patients with resection of colon metastases from gastric cancer. Median disease-free interval was 74 months. CONCLUSION Resection of late-onset colorectal recurrence from gastric cancer appears worthwhile for selected patients.

Laparoscopic segmental duodenectomy for a gastrointestinal stromal tumor located in the second portion of the duodenum: A case report

Gastrointestinal stromal tumors of the duodenum are rare. For benign tumors, premalignant lesions, or malignant potential tumors located in the second portion of the duodenum close to the papilla of Vater, pancreaticoduodenectomy is sometimes performed. A case of laparoscopic segmental duodenectomy for a gastrointestinal stromal tumor at the second portion of the duodenum is reported. The surgical procedure was performed as follows: first, the second portion of the duodenum was separated from the pancreatic head; second, the duodenum was cut off with the linear stapler after having confirmed preservation of the papilla by intraoperative endoscopy; and third, reconstruction was carried out by a side‐to‐side duodenojejunostomy. Laparoscopic segmental duodenectomy for duodenal gastrointestinal stromal tumors is thought to be advantageous compared with pancreaticoduodenectomy in terms of low burden and organ function preservation. The present procedure is feasible for benign or low‐malignant tumors that do not infiltrate outside of the duodenal walls.

Time-dependent transition of the immunoglobulin G subclass and immunoglobulin E response in cancer patients vaccinated with cholesteryl pullulan-melanoma antigen gene-A4 nanogel

A phase I+II clinical trial of vaccination with MAGE-A4 protein complexed with cholesteryl pullulan melanoma antigen gene-A4 nanogel (CHP-MAGE-A4) is currently underway in patients with MAGE-A4-expressing cancer. In the present study, the primary phase I endpoint was to test the safety of the administration of 300 µg CHP-MAGE-A4 with and without OK-432. Another aim of the study was to clarify the details of the specific humoral immune response to vaccination. The 9 patients enrolled for phase I were vaccinated 6 times, once every 2 weeks: 3 patients with 100 µg and 3 patients with 300 µg CHP-MAGE-A4, and 3 patients with 300 µg CHP-MAGE-A4 plus 0.5 clinical units of OK-432. Toxicities were assessed using Common Terminology Criteria for Adverse Events v3.0. Clinical response was evaluated by modified Response Evaluation Criteria in Solid Tumours. Immunological monitoring of anti-MAGE-A4-specific antibodies was performed by ELISA of pre- and post-vaccination patient sera. The 6 vaccinations produced no severe adverse events. Stable disease was assessed in 4/9 patients. Anti-MAGE-A4 total immunoglobulin (Ig)G titers increased in 7/9 patients. Efficacious anti-MAGE-A4 IgG1, 2 and 3 antibody responses were observed in 7/9 patients. Among them, positive conversions to T helper 2 (Th2)-type antibody responses (IgG4 and IgE) were observed after frequent vaccination in 4/7 patients. The Th2 conversion was possibly associated with undesirable clinical observations, including progressive disease and the appearance of a new relapse lesion. The present study suggested that frequent vaccinations activated a Th2-dominant status in the cancer patients. The identification of a time-dependent IgG subclass and IgE antibody production during vaccination protocols may be a useful surrogate marker indicating a potentially undesirable change of the immunological environment for an effective antitumor immune response in cancer patients.

Minimally invasive surgery for esophageal cancer after esophageal perforation: Esophageal cancer after perforation

Both esophageal rupture and esophageal cancer are life‐threatening diseases. We report a case of esophageal cancer that occurred after esophageal rupture was treated with thoracoscopic and laparoscopic surgery. A 76‐year‐old man presented with vomiting followed by epigastric pain and was diagnosed with spontaneous esophageal rupture. Laparoscopic and thoracoscopic surgery were performed. Primary closure was completed with a fundic patch, and thoracic lavage was performed. Ten months later, his condition was diagnosed as squamous cell carcinoma of the abdominal esophagus. He underwent thoracoscopic esophageal resection in the prone position, and a gastric conduit was created laparoscopically. The pathological finding was superficial esophageal carcinoma without lymph node metastasis. The patients postoperative course was uneventful, and there was no recurrence at 21 months of follow‐up.