Production of NY-ESO-1 peptide/DRB1*08:03 tetramers and ex vivo detection of CD4 T-cell responses in vaccinated cancer patients

We established CD4 T-cell clones, Mz-1B7, and Ue-21, which recognized the NY-ESO-1 121–138 peptide from peripheral blood mononuclear cells (PBMCs) of an esophageal cancer patient, E-2, immunized with an NY-ESO-1 protein and determined the NY-ESO-1 minimal epitopes. Minimal peptides recognized by Mz-1B7 and Ue-21 were NY-ESO-1 125–134 and 124–134, respectively, both in restriction to DRB1*08:03. Using a longer peptide, 122–135, and five other related peptides, including either of the minimal epitopes recognized by the CD4 T-cell clones, we investigated the free peptide/DR recognition on autologous EBV-B cells as APC and peptide/DR tetramer binding. The results showed a discrepancy between them. The tetramers with several peptides recognized by either Mz-1B7 or the Ue-21 CD4 T-cell clone did not bind to the respective clone. On the other hand, unexpected binding of the tetramer with the peptide not recognized by CD4 T-cells was observed. The clone Mz-1B7 did not recognize the free peptide 122–135 on APC, but the peptide 122–135/DRB1*08:03 tetramer bound to the TCR on those cells. The failure of tetramer production and the unexpected tetramer binding could be due to a subtly modified structure of the peptide/DR tetramer from the structure of the free peptide/DR molecule. We also demonstrated that the NY-ESO-1 123–135/DRB1*08:03 tetramer detected ex vivo CD4 T-cell responses in PBMCs from patients after NY-ESO-1 vaccination in immunomonitoring.     

Thoracoscopic hepatectomy for malignant liver tumor

Background

Anatomical position of the liver poses a difficulty in approaching the lesions using a laparoscopic approach.

Methods

The patient was a 79-year-old man with a surgical history of laparoscopic sigmoidectomy for colon cancer and posterior segmentectomy of the liver for metastatic liver tumor. On admission, he presented with another liver tumor (diameter, 1.5 cm) in the dome of segment VIII. Because of the high possibility of severe adhesion around the liver and difficulty of approaching the lesion from the abdomen, we selected the transthoracic approach rather than the abdominal approach; the patient consented to this procedure. The patient was placed in the left-lateral position under general anesthesia with single-lung ventilation. We placed three trocars into the right thoracic space. The intrathoracic space was observed using a flexible-tip rigid scope (Olympus, Tokyo, Japan). The tumor was detected by inserting a flexible laparoscopic ultrasound probe (Hitachi Aloka, Ltd., Tokyo, Japan) through the diaphragm; the diaphragm was dissected immediately above the tumor using a harmonic scalpel (Ethicon Endo-Surgery, Inc., Cornelia, GA). The liver surface was precoagulated using a low-voltage monopolar coagulator with a ball-shaped tip (Amco Inc., Tokyo, Japan) with the electrosurgical unit VIO300D (Erbe Elektromedizin, Tuebingen, Germany). The parenchyma was first sealed using BiClamp LAP forceps (Erbe Elektromedizin) and divided using the harmonic scalpel. The specimen was extracted using a retrieval bag. After complete hemostasis was achieved, the diaphragm was closed by continuous suturing.

Results

The operation lasted for 310 min and estimated blood loss was 10 mL. The patient was discharged on postoperative day 4.

Conclusions

Although the duration of TH was long because of the narrow thoracic cavity space, TH was performed without any problems. As a rule, we should select TH for lesions located in the dorsal segment VII/VIII, with severe adhesion around the liver.     

A Modification of Radical Antegrade Modular Pancreatosplenectomy for Adenocarcinoma of the Left Pancreas: Significance of En Bloc Resection Including the Anterior Renal Fascia

Background

Radical antegrade modular pancreatosplenectomy (RAMPS) has theoretical advantages for curative resection of adenocarcinomas of the left pancreas. The anterior renal fascia is a key structure, and resection planes should run posterior to this fascia. However, it is difficult to delineate this fascia and set a precise dissection plane. We modified RAMPS to achieve such a precise dissection plane with ease.

Methods

After clamping the splenic artery, the third duodenal portion was mobilized from the left to the right to locate the inferior vena cava, which was covered by the anterior renal fascia. Here, the anterior renal fascia was incised while approaching the dissection plane. Dissection then continued cephalad, with this plane along the inferior vena cava, and then turned along the left renal vein at the confluence of the left renal vein toward the renal hilum. At this point, dissection continued along the coronal plane to the superior edge of the pancreas.

Results

Between July 2007 and December 2012, a total of 24 pancreatic adenocarcinoma patients underwent modified RAMPS. Tumor extension beyond the pancreatic parenchyma (T3) and lymph node metastases was confirmed in 17 and 13 cases, respectively. Histologically clear surgical margins were achieved (R0 resection) in 21 patients (88 %). The 5-year overall survival rate was 53 %. Six patients survived for over 5 years without recurrence.

Conclusions

This modification of RAMPS is advantageous for en bloc resection while actually including removal of the anterior renal fascia. It is associated with satisfactory survival rates for patients with distal pancreatic carcinomas.     

Functional Plasticity of Language Confirmed with Intraoperative Electrical Stimulations and Updated Neuronavigation: Case Report of Low-Grade Glioma of the Left Inferior Frontal Gyrus

Removal of glioma from the dominant side of the inferior frontal gyrus (IFG) is associated with a risk of permanent language dysfunction. While intraoperative cortical and subcortical electrical stimulations can be used for functional language mapping in an effort to reduce the risk of postoperative neurological impairment, the extent of resection is limited by the functional boundaries. Recent reports proposed that a two-stage surgical approach for low-grade glioma in eloquent areas could avoid permanent deficits via the functional plasticity that occurs between the two operations. The report describes a patient with World Health Organization (WHO) grade II oligoastrocytoma in the left IFG, in functional plasticity of language occurred in the interval between two consecutive surgeries. Intraoperative electrical stimulations suggested that a language area and related subcortical fiber crossed the pre-central sulcus during tumor progression owing to functional plasticity. In the present case, we integrated neurophysiological data into the intraoperative neuronavigation system. We also confirmed the peri-lesional shift of language area and related subcortical fiber on image findings. Consequently, the tumor was sub-totally removed with two separate resections. Permanent language disturbance did not occur, and this favorable outcome was attributed to functional plasticity. The present experience sustains the multistage approach for low-grade gliomas in the language area. A combination of intraoperative electrical stimulations and updated neuronavigation may facilitate the characterization of brain functional plasticity.     

Prediabetes,Diabetes, and the Risk of All-Cause and Cause-Specific Mortality in a Japanese Working Population: Japan Epidemiology Collaboration on Occupational Health Study

OBJECTIVEPrediabetes has been suggested to increase risk for death; however, the definitions of prediabetes that can predict death remain elusive. We prospectively investigated the association of multiple definitions of prediabetes with the risk of death from all causes, cardiovascular disease (CVD), and cancer in Japanese workers.RESEARCH DESIGN AND METHODSThe study included 62,785 workers who underwent a health checkup in 2010 or 2011 and were followed up for death from 2012 to March 2019. Prediabetes was defined according to fasting plasma glucose (FPG) or glycated hemoglobin (HbA_1c) values or a combination of both using the American Diabetes Association (ADA) or World Health Organization (WHO)/International Expert Committee (IEC) criteria. The Cox proportional hazards regression model was used to investigate the associations.RESULTSOver a 7-year follow-up, 229 deaths were documented. Compared with normoglycemia, prediabetes defined according to ADA criteria was associated with a higher risk of all-cause mortality (hazard ratio [HR] 1.53; 95% CI 1.12–2.09) and death due to cancer (HR 2.37; 95% CI 1.45–3.89) but not with death due to CVD. The results were materially unchanged when prediabetes was defined according to ADA FPG, ADA HbA_1c, WHO FPG, or combined WHO/IEC criteria. Diabetes was associated with the risk of all-cause, CVD, and cancer deaths.CONCLUSIONSIn a cohort of Japanese workers, FPG- and HbA_1c-defined prediabetes, according to ADA or WHO/IEC, were associated with a significantly increased risk of death from all causes and cancer but not CVD.     

Emergence of a carbapenem-resistant and colistin-heteroresistant Enterobacter cloacae clinical isolate in Japan

A carbapenem-resistant and colistin-heteroresistant clinical isolate of Enterobacter cloacae was obtained from an inpatient in Okinawa, Japan. The minimum inhibitory concentrations of both imipenem and meropenem were 32 μg/mL. The isolate showed heteroresistance to colistin using the Etest method and resistance to colistin using the broth microdilution method. It had a disrupted ompC and a mutation in the promoter region of bla_ACT-2, but did not harbor any genes encoding carbapenemase. The disruption of ompC and the mutation in bla_ACT-2 was associated with the carbapenem resistance of this isolate. This isolate also had mutations in pmrAB and phoPQ encoding two-component regulatory systems, which may be associated with colistin heteroresistance.     

Repeating regional acute pancreatitis in the head of the pancreas caused by intraductal papillary mucinous neoplasms in the tail: report of a case

Intraductal papillary mucinous neoplasm (IPMN) of the pancreas is a distinct entity characterized by papillary proliferations of mucin-producing epithelial cells with excessive mucin production and cystic dilatation of the pancreatic ducts. The clinical presentation often involves recurrent episodes of pancreatitis associated with the temporal obstruction of the main pancreatic duct caused by the hypersecretion of mucin. We herein describe a case in which the patient repeatedly experienced the occurrence of idiopathic acute pancreatitis in the head of the pancreas over a 9-year period, and who was ultimately was cured by distal pancreatectomy for IPMNs in the pancreatic tail. This case illustrates the potential pitfalls in the diagnosis of IPMNs owing to a discrepancy between the site of pancreatitis and that of the IPMN. The possible mechanisms linking acute pancreatitis with the formation of IPMNs are also reviewed.