[A case of R0 resection in conversion surgery after duodenal stent placement for locally advanced unresectable pancreatic cancer with duodenal stenosis].

A 67-year-old man presented to our hospital with vomiting. Esophagogastroduodenoscopy revealed duodenal stenosis and atypical epithelium. A tumor in the pancreatic head, about 30mm in size, involving the superior mesenteric artery and a superior mesenteric vein was identified using abdominal contrast computed tomography (CT). Locally advanced pancreatic cancer was diagnosed in the patient through an endoscopic biopsy. Due to the duodenal stenosis complication, duodenal stent placement was conducted. After stent placement, oral intake was resumed, and improvement of the systemic condition led to chemotherapy (modified FOLFIRINOX). After chemotherapy, CT revealed decreased carcinoma progression and vascular invasion. Conversion surgery was improved, and R0 resection was achieved. Our study showed that duodenal stent placement could enhance prognosis;as a result, it was regarded as a good choice for multidisciplinary therapy.

Outcomes of adolescents and young adults with chronic-phase chronic myeloid leukaemia treated with tyrosine kinase inhibitors.

INTRODUCTION: Few studies have reported the outcomes of adolescents and young adults (AYAs) with chronic-phase chronic myeloid leukaemia (CML-CP) on tyrosine kinase inhibitors (TKIs). MATERIALS AND METHODS: We retrospectively analysed the clinical features, treatment response, and long-term outcomes of 42 AYA patients, in comparison to older patients. The initial therapies of AYA patients between 2001 and 2016 included imatinib (n = 24), dasatinib (n = 13) and nilotinib (n = 5). RESULTS: In AYA patients, the peripheral blood (PB) white blood cell count and percentage of blasts at the diagnosis were significantly higher, haemoglobin levels were lower and the spleen size was larger. The major molecular response (MMR), event-free survival (EFS) and overall survival (OS) rates were comparable. A sub-analysis comparing imatinib to second-generation TKIs as the initial therapy also showed that their prognosis was comparable. DISCUSSION: In conclusion, the tumour burden at the diagnosis of CML-CP is higher in AYA patients; however, their prognosis was not worse in comparison to older patients treated with TKIs. KEY MESSAGESFew studies have reported the outcomes of adolescents and young adults (AYAs) with chronic-phase chronic myeloid leukaemia (CML-CP) on tyrosine kinase inhibitors (TKIs). This study showed the tumour burden at the diagnosis of CML-CP is higher in AYA pa tients; however, their prognosis was not worse in comparison to older patients treated with TKIs. Understanding the biological and non-biological features of AYA patients with CML-CP on TKI therapy is essential for better management and to improve the outcomes.

[3 + 2] Coupling of Quinone Monoacetals with Vinyl Ethers Effected by Tetrabutylammonium Triflate: Regiocontrolled Synthesis of 2-Oxygenated Dihydrobenzofurans.

The synthesis of 2-oxygenated dihydrobenzofurans involving the [3 + 2] coupling of quinone monoacetals with vinyl ethers has been realized by tetrabutylammonium triflate catalysis. The reaction involves a new activation method of the acetal moiety in quinone monoacetals under acid-free conditions affording the highly oxygenated dihydrobenzofurans. This new activation mode was achieved by using the triflate anion catalyst for stabilization of the highly reactive cationic intermediate.

The prognostic value of the Fibrinogen-Albumin Ratio Index in patients with myelodysplastic syndrome and acute myeloid leukemia with myelodysplasia-related changes treated with azacitidine.

Inflammation is a major hallmark of several cancers. The present study evaluated the prognostic value of the Fibrinogen-Albumin Ratio Index (FARI) at the diagnosis in patients with myelodysplastic syndrome (MDS) and acute myeloid leukemia with myelodysplasia-related changes (AML-MRC) treated with azacitidine (AZA). A retrospective study was conducted in a single cohort of 99 patients with de novo MDS and AML-MRC who were treated with AZA between May 2011 and June 2019 in our hospital. Plasma fibrinogen and serum albumin levels were measured before the start of AZA treatment. A total of 99 patients were included in the analysis. The optimal cut-off value of FARI for predicting the 1-year overall survival (OS) was determined by a receiver operating characteristic (ROC) analysis to be 0.079. A total of 59 (60%) and 40 (40%) patients had an FARI ≥0.079 (high-FARI group) and < 0.079 (low-FARI group), respectively. The high-FARI patients had a significantly shorter OS than low-FARI patients (1-year OS, 35.6% vs. 77.5%, p < 0.001). In a multivariate analysis, parameters with independent adverse significance for the OS were a high FARI (≥0.079) (hazard ratio (HR) 2.41, 95% confidence interval (CI), 1.36-4.29; p = 0.006), and Revised-International Prognostic Scoring System (IPSS-R) very high (HR 1.483, 95% CI, 1.12-1.963, p = 0.006). A high FARI was found to be associated with a poor outcome in MDS and AML-MRC patients treated with AZA, and FARI was an independent prognostic factor for the OS in these patients. Further internal and external validations are needed to clarify the prognostic role of the FARI for MDS and AML-MRC patients.

The prognostic value of the controlling nutritional status score in patients with multiple myeloma.

The Controlling Nutritional Status (CONUT) score predicts the prognosis in several tumors. However, its prognostic significance in multiple myeloma (MM) remains unclear. The present study investigated the correlation between the CONUT score and the survival outcomes of MM patients. A total of 178 patients newly diagnosed with MM were retrospectively enrolled. Patients with a high CONUT score (≥5) had a significantly shorter median overall survival (OS) than those with a low CONUT score (≤4) (33 vs. 57 months, p < .001). In a multivariate analysis among patients with International Staging System (ISS) score of ≤2, a high CONUT score was an independent prognostic covariate for the OS after adjusting for other significant factors (hazard ratio 2.364; 95% confidence interval 1.324-4.220, p = .004). Our results suggest that the CONUT score is a predictor of a poor outcome in patients with MM, particularly in low-ISS-score cases.

Prognostic Impact of ABO Blood Group on Survival in Patients With Malignant Lymphoma.

BACKGROUND: The ABO blood group is reported to be associated with survival for several types of malignancy. We conducted a retrospective study to evaluate the prognostic significance of the ABO blood group in patients with malignant lymphoma. PATIENTS AND METHODS: A total of 523 patients with malignant lymphoma were included in this study. The primary outcome measured was the association between the ABO blood group and survival. RESULTS: Patients with blood group B had shorter 5-year overall survival (OS) than patients with non-B blood groups (40.9% vs. 57.3%; P < .01). Among 240 patients with diffuse large B-cell lymphoma (DLBCL), patients with blood group B had shorter 5-year OS in comparison with patients with non-B blood groups (36.3% vs. 56.9%; P < .01). Among male patients with DLBCL, those with blood group B had significantly shorter 5-year OS than those with non-B blood groups (27.5% vs. 55.8%; P = .003). On the other hand, there was no significant difference in the survival between female patients with blood group B and those with non-B blood groups (5-year OS: 49.2% vs. 58.2%; P = .67). A multivariate analysis demonstrated that blood group B (hazard ratio, 1.83; 95% confidence interval, 1.21-2.78; P = .04) was an independent predictor of shorter OS in male patients with DLBCL. CONCLUSION: The ABO blood group is associated with survival in patients with lymphoma. Interestingly, only male patients with DLBCL with blood group B had significantly shorter OS than those male patients with DLBCL with non-B blood groups.

Generation of multivirus-specific T cells by a single stimulation of peripheral blood mononuclear cells with a peptide mixture using serum-free medium.

BACKGROUND: Restoration of virus-specific immunity by virus specific T cells (VSTs) offers an attractive alternative to conventional drugs, and can be highly effective in immunocompromised patients, including hematopoietic stem cell transplant (HSCT) recipients. However, conventional VSTs manufacture requires preparation of specialized antigen-presenting cells (APCs), prolonged ex vivo culture in serum-containing medium and antigen re-stimulation with viruses or viral vectors to provide viral antigens for presentation on APCs. METHODS: To simplify this complex process, we developed a method to generate multiple VSTs by direct stimulation of peripheral blood mononuclear cells (PBMCs) with overlapping peptide libraries in serum-free medium. RESULTS: We generated VSTs that targeted seven viruses (cytomegalovirus [CMV], Epstein-Barr virus [EBV], adenovirus [AdV], human herpesvirus 6 [HHV-6], BK virus [BKV], JC virus [JCV] and Varicella Zoster virus [VZV]) in a single line. The phenotype, growth and specificity of multiple VSTs produced in serum-free medium were equivalent to those generated in conventional serum-containing medium. DISCUSSION: The use of serum-free medium allows this approach to be readily introduced to clinical practice with lower cost, greater reproducibility due to the absence of batch-to-batch variability in serum and without concerns for infectious agents in the serum used. This simplified approach will now be tested in recipients of Human Leukocyte Antigen (HLA)-matched sibling HSCT.

[Immunotherapy for refractory viral infections].

Various antiviral agents have been developed, which are sometimes associated with toxicity, development of virus-resistant strain, and high cost. Virus-specific T-cell (VST) therapy provides an alternative curative therapy that can be effective for a prolonged time without eliciting drug resistance. VSTs can be directly separated using several types of capture devices and can be obtained by stimulating peripheral blood mononuclear cells with viral antigens (virus, protein, or peptide) loaded on antigen-presenting cells (APC). APC can be transduced with virus-antigen coding plasmid or pulsed with overlapping peptides. VST therapy has been studied in drug non-responsive viral infections after hematopoietic cell transplantation (HCT). Several previous studies have demonstrated the efficacy of VST therapy without significant severe GVHD. In addition, VSTs from a third-party donor have been prepared and administered for post-HCT viral infection. Although target viruses of VSTs include herpes virus species and polyomavirus species, a wide variety of pathogens, such as papillomavirus, intracellular bacteria, and fungi, can be treated by pathogen-specific T-cells. Perhaps, these specific T-cells could be used for opportunistic infections in other immunocompromised hosts in the near future.

Characterization of In Vitro Expanded Virus-Specific T cells for Adoptive Immunotherapy against Virus Infection.

Adoptive transfer of virus-specific T cells has emerged as a promising therapeutic approach for treatment of virus infections in immunocompromised hosts. Characterization of virus-specific T cells provides essential information about the curative mechanism of the treatment. In this study, we developed a T cell epitope mapping system for 718 overlapping peptides spanning 6 proteins of 3 viruses (pp65 and IE1 from cytomegalovirus; LMP1, EBNA1, and BZLF1 from Epstein-Barr virus; Penton from adenovirus). Peripheral blood mononuclear cells (PBMCs) from 33 healthy Japanese donors were stimulated with these peptides and virus-specific CD4+ and CD8+ T cells were expanded in vitro in the presence of interleukin (IL) 4 and IL7. A median of 13 (minimum-maximum, 2-46) peptides was recognized in the cohort. Both fresh and cryopreserved PBMCs were used for in vitro expansion. The expansion and breadth of T cell responses were not significantly different between the 2 PBMC sets. We assessed viral regions frequently recognized by T cells in a Japanese cohort that could become pivotal T cell targets for immunotherapy in Japan. We tested epitope prediction for CD8+ T cell responses against a common target region using a freely available online tool. Some epitopes were considered to be predictive.

Bleeding due to acquired hemophilia A in acute pancreatitis: a case report.

Acquired hemophilia A leads to severe bleeding and is known to be related to many underlying diseases; however, it has not been reported to occur as a complication of pancreatitis. We present a case of acquired hemophilia A secondary to severe acute pancreatitis. A 76-year-old female developed a hematoma in the lower leg muscle while being treated for severe acute pancreatitis. Blood tests revealed prolonged activated partial thromboplastin time (APTT) and the presence of an autoantibody to factor VIII. The bleeding diathesis was successfully controlled by immunosuppressive therapy. This case highlights the need for careful differential diagnosis for successful management of bleeding disorders as complications of pancreatitis.

Effectiveness and clinical results of endoscopic management of sigmoid volvulus using unsedated water-immersion colonoscopy.

BACKGROUND AND AIM: Although intestinal obstruction as a result of sigmoid volvulus (SV) may be successfully resolved using endoscopic detorsion, surgical treatment remains the main therapeutic strategy. We evaluated the endoscopic detorsion procedure using unsedated water-immersion colonoscopy for the treatment of SV. METHODS: A retrospective chart review was conducted on the clinical background and prognosis of 21 SV patients who underwent 71 endoscopic detorsion procedures using unsedated, water-immersion colonoscopy. RESULTS: In all, 14 (67%) male and seven (33%) female patients, with a mean age of 73 years (range, 54-95 years) were enrolled; 86% were >70 years of age. Among these patients, 90% had a background of key predisposing factors. In the 21 patients, endoscopic detorsion was successfully done using unsedated water-immersion colonoscopy. SV recurred in 10 patients at a median of 180 days. Endoscopic detorsion for recurrent SV was successfully achieved in all cases, and none of the secondary cases became severe. Only male patients were observed to experience three or more recurrent episodes of SV. CONCLUSIONS: SV occurred most commonly in elderly patients with a surgical risk. Our experience suggests that conservative endoscopic treatment using unsedated water-immersion colonoscopy is a safe, reasonable, conservative endoscopic approach for elderly patients in the absence of necrotic findings. We currently use this procedure in most of our cases.