Congenital choanal atresia where the atretic wall thickened while waiting for an elective surgery.

INTRODUCTION AND IMPORTANCE: Although bilateral congenital choanal atresia (CCA) requires early intervention to open closure walls for safe breathing, it is desirable to be withheld until an infant acquires surgical and anesthetic tolerance. Here we introduce an infant of CCA whose closure wall had thickened during a waiting period for an elective surgery. CASE PRESENTATION: The choana of the patient could not be identified by intranasal fiberscopy and the bilateral CCA was found by CT scan on day 17 after birth. Since he could breathe orally without distress, surgery was withheld until he acquires the tolerance. At nine weeks old, however, CT image detected thickening of the closure wall. At 10 weeks old, he underwent scheduled surgery in which the bilateral closure walls were removed together with attached posterior part of the nasal septum under endoscopic endonasal approach. The patient became able to breath nasally and the choana remained open without restenosis at 3 years after surgery. CLINICAL DISCUSSION: This is the first CCA case reporting closure walls thickened during a waiting period for an elective surgery. Although waiting for surgery was systemically safer by growth, the surgery became more invasive to prevention from restenosis. CONCLUSIONS: This case suggests that we must decide appropriate timing of surgery in an infant, considering dilemma between systemic safety ensuring and lesion aggravation by waiting for surgery.

Delayed immune-related adverse events in long-responders of immunotherapy: a single-center experience.

BACKGROUND: Immune-checkpoint inhibitors (ICIs) often cause immune-related adverse events (irAEs). The spectrum of irAEs and their managements has been partially clarified, however the knowledge on time-course of irAEs is not well understood. METHODS: A retrospective study based on the medical record was performed. The study subjects were consisting of patients with various types of solid tumors for whom ICIs (nivolumab, pembrolizumab, durvalumab, atezolizumab, nivolumab plus ipilimumab) were used between April 2016 and October 2021. We focused on irAEs developed more than 1-year after commencement ICIs (delayed irAE group) and compared with irAEs developed within 1-year (non-delayed irAE group) in terms of types and severity of irAEs. RESULTS: A total of 336 patients were enrolled in the study. Eighty-eight patients (26.2%) developed irAEs and 248 did not. Most of the patients developing irAEs were treated using PD-L1/PD-1 inhibitors. Eighty-one patients (24.1%) in non-delayed irAE group and 7 patients (2.1%) in delayed irAE group developed irAEs. The median onset of irAEs in the delayed irAE group was 18.6 months (range: 13.5-24.3). The types of irAEs observed in delayed irAE group were dermatitis (2 cases), pneumonitis (2 cases), nephritis (1 case), arthritis (1 case), and gastritis (1 case). The severity of irAEs was almost mild (≤G2), but one patient (.3%) developed G3 nephritis. CONCLUSION: PD-L1/PD-1 inhibitors frequently caused various irAEs but their severities were mostly tolerable. Few patients developed delayed irAE with mild toxities.

Usefulness of endoscopic endonasal underwater surgery using a combination of coblation and a lens-cleaning system for hemostasis in hereditary hemorrhagic telangiectasia.

Hemostatic procedures for controlling nasal bleeding in refractory diseases such as hereditary hemorrhagic telangiectasia (HHT) can be challenging. In this report, we present a novel technique for underwater endoscopic endonasal hemostatic surgery, which was performed on a 69-year-old man with HHT. The patient had been experiencing frequent episodes of nasal bleeding and had many telangiectasias in the nasal cavity, which were the cause of the bleeding. These telangiectasias were effectively treated using a coblation device in combination with an endoscope lens-cleaning system that supplied saline to create stable underwater conditions. There are several advantages to this technique, including provision of a stable and clear endoscopic field of view, allowing for better visualization of the surgical site. This makes it easier to identify bleeding points and ensure accurate hemostasis. Additionally, the hydrostatic pressure created by the underwater environment helps to reduce bleeding during the procedure. However, it is important to take careful precautions to prevent water from entering the lower airway. With this precautionary measure, this technique is particularly useful in managing bleeding in patients with HHT.

A comparison of the incidence of ≥ grade 2 radiation pneumonitis between intensity-modulated radiotherapy and three-dimensional conformal radiotherapy in patients with unresectable non-small cell lung cancer treated with durvalumab after concurrent chemoradiotherapy.

BACKGROUND: Intensity-modulated radiation therapy (IMRT) has been increasingly used as a new radiation modality for unresectable non-small cell lung cancer (NSCLC). The risk factors for radiation pneumonitis (RP) during consolidation durvalumab following concurrent chemoradiotherapy (CCRT) using IMRT have not been thoroughly investigated. METHODS: This retrospective study analyzed medical record data from consecutive patients diagnosed with NSCLC who underwent CCRT and consolidation durvalumab at our institution between April 2018 and September 2022. Since we adopted IMRT for the treatment of NSCLC in April 2020, these patients were categorized into two groups: those treated with IMRT after April 2020 and those treated with three-dimensional conformal radiotherapy (3D-CRT) before April 2020. RESULTS: A total of 31 patients underwent IMRT (the IMRT group), while 25 patients underwent 3D-CRT (the 3D-CRT group). In both groups, the total dose was 60 Gy in 30 fractions. The cumulative incidence of ≥ grade 2 RP at 12 months was significantly lower in the IMRT group than in the 3D-CRT group (27.0% vs. 64.0%, hazard ratio [HR]: 0.338, 95% confidence interval [CI]: 0.144-0.793, p = 0.013). In the multivariable analysis, V20 (≥ 25.6%, HR: 2.706, 95% CI: 1.168-6.269, p = 0.020) and radiotherapy technique (IMRT, HR: 0.414, 95% CI: 0.172-0.994, p = 0.048) were identified as significant risk factors for ≥ grade 2 RP. CONCLUSIONS: IMRT is associated with a lower rate of ≥ grade 2 RP in patients with NSCLC who received CCRT followed by durvalumab.

Pathogenesis of chronic rhinosinusitis with nasal polyp and a prominent T2 endotype.

Chronic rhinosinusitis is a heterogenous and multifactorial disease, characterized by persistent inflammation of the nose and paranasal sinuses, which causes nasal obstruction, nasal discharge, facial pain, and smell disturbance. Chronic rhinosinusitis is divided into two phenotypes: chronic rhinosinusitis with nasal polyp and chronic rhinosinusitis without nasal polyp. Nasal polyps can be associated with many inflammatory cells including eosinophil cells, neutrophil cells, plasma cells, and lymphocytes. T2 endotype is characterized by the type-2 immune response and nasal polyps are associated with eosinophilic dominant infiltration. In contrast, in the T1 and T3 endotypes, chronic rhinosinusitis can be associated with neutrophilic dominant infiltration. In addition, there are mixed types of inflammation with different proportions of eosinophils-neutrophils in chronic rhinosinusitis. In the T2 endotype, there is an increase in the production of Th2 cytokines, including interleukin-4, interleukin-5, and interleukin-13, high levels of immunoglobulin-E in polyp tissue, and eosinophilia. Stimulation of Th2 cells, type-2 innate lymphoid cells, epithelial cell damage, Staphylococcus aureus enterotoxins, and autoimmune antibodies have important roles in the enhancement of Th2 cytokines and pathogenesis of chronic rhinosinusitis with nasal polyp. Monoclonal antibodies target type-2 inflammation, decrease nasal polyp size, and improve the clinical symptoms of CRSwNP patients. The present review will focus on factors involved in the pathogenesis of chronic rhinosinusitis and its treatment.

Predictors and prognosis of respiratory epithelial adenomatoid hamartoma in sinonasal cavities.

Objective: Respiratory epithelial adenomatoid hamartoma (REAH) is classified as a histopathologic diagnosis and often identified in sinus surgery for chronic rhinosinusitis (CRS). The purpose of this study was to clarify the frequency and predictors of REAH and prognosis of CRS with REAH in CRS cases. Methods: In the first study, we histologically reviewed sinonasal polyps and mucosal tissue specimens obtained from patients who underwent endoscopic sinus surgery (ESS) for CRS to reveal how many REAH were involved in ESS cases. We compared REAH and non-REAH groups in terms of preoperative symptoms and endoscopic, imaging and blood examination findings to elucidate predictors of REAH genesis. In the second study, we compared the data 3 months after surgery such as endoscopic and imaging findings and olfactory test to evaluate prognosis of CRS with REAH. Results: The prevalence of REAH was 15.5% of all 304 cases in the first and second studies combined. Higher polyp score in the middle meatus was an independent predictor of the presence of REAH (p = .02). Presence of REAH was significantly associated with the enlargement of olfactory cleft polyps (p < .01), increasing postoperative scores of standard olfactory tests (p = .03), and decline of ratio of improvement (p < .01) measured using T&T olfactometry. Conclusions: Higher polyp score in the middle meatus is an independent predictor of REAH. Olfactory function is difficult to recover after surgery in REAH patients because it is associated with recurrent polyps in the olfactory cleft.

Transplantation of Human Induced Pluripotent Stem Cell-Derived Airway Cells on Vitrigel Membrane into Rat Nasal Cavity.

The nasal mucosa functions as a frontline biological defense against various foreign substances and pathogens. Maintaining homeostasis of the nasal epithelium is necessary to promote good health. Nasal epithelia are constantly replaced under normal conditions. However, hereditary diseases, including primary ciliary dyskinesia and cystic fibrosis, can result in intractable dysfunction of the nasal mucosa. Since there is no treatment for this underlying condition, extrinsic manipulation is necessary to recover and maintain nasal epithelia in cases of hereditary diseases. In this study, we explored the use of airway epithelial cells (AECs), including multiciliated airway cells, derived from human induced pluripotent stem cells (iPSCs) on porcine atelocollagen vitrigel membranes, as a candidate of a therapeutic method for irreversible nasal epithelial disorders. To confirm the regenerative capacity of iPSC-derived AECs, we transplanted them into nasal cavities of nude rats. Although the transplanted cells were found within cysts isolated from the recipient nasal respiratory epithelia, they survived in some rats. Furthermore, the surviving cells were composed of multiple cell types similar to the human airway epithelia. The results could contribute to the development of novel transplantation-related technologies for the treatment of severe irreversible nasal epithelial disorders. Impact Statement Nasal respiratory epithelia are important for the functions of nasal cavity, including humidifying the air and filtering various toxic substances. However, hereditary diseases, including primary ciliary dyskinesia and cystic fibrosis, can result in intractable dysfunction of the nasal mucosa. Our novel method to transplant airway epithelial cells derived from human induced pluripotent stem cells will be a candidate method to replace malfunctioned nasal respiratory epithelia in such a situation. To secure our method's safety, we used porcine atelocollagen vitrigel membranes, which prevent the immune response and bovine spongiform encephalopathy, as a scaffold.

Catheter-Directed Thrombolysis for Persistent Sciatic Artery Presenting with Acute Limb Ischemia.

Persistent sciatic artery (PSA) is a rare congenital peripheral artery disorder that is usually detected incidentally on computed tomographic examination. PSA can also cause iliac aneurysm and acute thromboembolism, which are potentially associated with rest pain, claudication, and limb-threatening ischemia. Patients with PSA and leg ischemia should be treated with revascularization and appropriate management of PSA aneurysm. The authors often choose emergent bypass surgery or endovascular intervention for aneurysmal rupture and acute lower-extremity arterial occlusion. This report describes an emergency procedure using catheter-based thrombolysis for acute limb ischemia in a patient with PSA.

Oncological and functional outcomes of supratotal resection of IDH1 wild-type glioblastoma based on 11C-methionine PET: a retrospective, single-center study.

The oncological and functional outcomes in glioblastoma (GBM) patients following supratotal resection (SupTR), involving complete resection of contrast-enhancing enhanced (CE) tumors and areas of methionine (Met) uptake on 11C-met positron emission tomography (Met-PET), are unknown. We conducted a retrospective review in newly diagnosed, IDH1 wild-type GBM patients, comparing SupTR with gross total resection (GTR), in which only CE tumor tissue was resected. All patients underwent standard radiotherapy and temozolomide treatment, and were followed for tumor recurrence and overall survival (OS). Among the 30 patients included in this study, 7 underwent SupTR and 23 underwent GTR. Awake craniotomy with cortical and subcortical mapping was more frequently performed in the SupTR group than in the GTR group. During the follow-up period, significantly different patterns of disease progression were observed between groups. Although more than 80% of recurrences were local in the GTR group, all recurrences in the SupTR group were distant. Median OS in the GTR and SupTR groups was 18.5 months (95% confidence interval [CI] 14.2-35.1) and not reached (95% CI 30.5-not estimable), respectively; this difference was statistically significant (p = 0.03 by log-rank test). No postoperative neurocognitive decline was evident in patients who underwent SupTR. Compared to GTR alone, aggressive resection of both CE tumors and areas with Met uptake (SupTR) under awake craniotomy with functional mapping results in a survival benefit associated with better local control and neurocognitive preservation.

Open Repair of a Giant Popliteal Artery Aneurysm Presenting with Nerve Compression Symptoms.

Popliteal artery aneurysm (PAA) is a rare vascular disease, especially in women, and presents with various symptoms, ranging from being asymptomatic to rupture or acute life-threatening ischemia. We have presented a case of PAA in an 81-yearold woman complaining of tingling sensations in her leg. Computed tomography revealed a large 10-cm sized PAA. Because of the compression related symptoms, an open repair approach was selected and performed successfully via a posterior approach, including partial aneurysm resection and interposition graft with a reversed saphenous vein.

Non-inferior clinical outcomes of immune checkpoint inhibitors in non-small cell lung cancer patients with interstitial lung disease.

OBJECTIVES: The efficacy of immune checkpoint inhibitors (ICIs) in non-small-cell lung cancer (NSCLC) patients with pre-existing interstitial lung disease (ILD) is unclear. MATERIALS AND METHODS: Retrospective medical data from advanced or recurrent NSCLC patients who were treated with nivolumab or pembrolizumab at ten institutions in Japan between January 2016 and September 2018 were analyzed. Eligible patients were divided into two groups according to the presence of pre-existing ILD. RESULTS: A total of 461 NSCLC patients were enrolled, 412 without ILD (Non-ILD group) and 49 with ILD (ILD group). The response rate (RR) and disease control rate (DCR) of the ILD group were not inferior to those of the Non-ILD group [RR: 49.0 % (24/49) vs. 30.1 % (124/412), P < 0.01 and DCR: 69.4 % (34/49) vs. 51.2 % (211/412), P = 0.016, respectively]. Non-inferior outcomes were also observed with respect to progression-free survival (PFS) and overall survival (OS) (median PFS: 5.9 months vs. 3.5 months, P = 0.14 and median OS: 27.8 months vs. 25.2 months, P = 0.74 in the ILD and Non-ILD groups, respectively). Among immune-related adverse effects (irAEs), checkpoint inhibitor pneumonitis (CIP) was more frequently observed among NSCLC patients in the ILD group [30.6 % (15/49) vs. 9.5 % (39/412), P < 0.01]. The frequency of irAEs other than CIP and infusion reactions was not significantly different between the ILD group and the Non-ILD group. CONCLUSION: These results suggest that the clinical outcomes of ICIs are not significantly affected by pre-existing ILD despite the increased frequency of CIP. NSCLC patients with ILD are therefore probable candidates for ICIs.

A Phase II, Multicenter, Randomized, Placebo-Controlled Study of Benralizumab, a Humanized Anti-IL-5R Alpha Monoclonal Antibody, in Patients With Eosinophilic Chronic Rhinosinusitis.

BACKGROUND: Strong eosinophil infiltration in chronic rhinosinusitis with nasal polyp (CRSwNP) is highly associated with recalcitrance and higher nasal polyp recurrence rate after surgery. The prevalence of eosinophilic CRSwNP (ECRS) is increasing in Asian countries including Japan. Benralizumab is a humanized anti-IL-5R alpha monoclonal antibody that depletes eosinophils by antibody-dependent cell-mediated cytotoxicity. OBJECTIVE: To assess the efficacy and safety of benralizumab in patients with ECRS. METHODS: This phase II, randomized, double-blind, placebo-controlled study was conducted in Japan. Patients were randomized 1:2:2 to placebo, a single administration of benralizumab 30 mg, or benralizumab 30 mg every 4 weeks (q4w) for a total of three doses. The primary endpoint was the change in nasal polyp score from baseline at Week 12. RESULTS: Overall, 56 patients were enrolled (placebo, n = 11; benralizumab single dose, n = 22; benralizumab q4w, n = 23). Although the mean total nasal polyp score began to decrease after the initiation of benralizumab treatment, there were no statistically significant differences in change in nasal polyp score from baseline at Week 12 between benralizumab and placebo (placebo, -0.5 ± 0.8; benralizumab single, -0.3 ± 0.8; benralizumab q4w, -0.5 ± 1.5). Post-hoc analysis showed that the administration of benralizumab decreased nasal polyp scores ≥2 points in 42.2% of ECRS patients and that patients with high blood eosinophil levels had a greater tendency to respond to benralizumab treatment. The safety profile was similar to that in previous studies and no unexpected adverse events were noted. CONCLUSION: Although benralizumab did not meet the primary efficacy endpoint, reductions of nasal polyp scores were seen in the benralizumab group compared with the placebo group over the whole study period, especially in patients with high levels of blood eosinophils.

CD1d expression in glioblastoma is a promising target for NKT cell-based cancer immunotherapy.

Glioblastoma is the most common and aggressive type of brain tumor with high recurrence and fatality rates. Although various therapeutic strategies have been explored, there is currently no effective treatment for glioblastoma. Recently, the number of immunotherapeutic strategies has been tested for malignant brain tumors. Invariant natural killer T (iNKT) cells play an important role in anti-tumor immunity. To address if iNKT cells can target glioblastoma to exert anti-tumor activity, we assessed the expression of CD1d, an antigen-presenting molecule for iNKT cells, on glioblastoma cells. Glioblastoma cells from 10 of 15 patients expressed CD1d, and CD1d-positive glioblastoma cells pulsed with glycolipid ligand induced iNKT cell-mediated cytotoxicity in vitro. Although CD1d expression was low on glioblastoma stem-like cells, retinoic acid, which is the most common differentiating agent, upregulated CD1d expression in these cells and induced iNKT cell-mediated cytotoxicity. Moreover, intracranial administration of human iNKT cells induced tumor regression of CD1d-positive glioblastoma in orthotopic xenografts in NOD/Shi-scid IL-2RγKO (NOG) mice. Thus, CD1d expression represents a novel target for NKT cell-based immunotherapy for glioblastoma patients.

Hypermethylation of Corticotropin Releasing Hormone Receptor-2 Gene in Ulcerative Colitis Associated Colorectal Cancer.

BACKGROUND/AIM: The difficulty of early diagnosis of colitis associated colorectal cancer (CACRC) due to colonic mucosal changes in long-standing ulcerative colitis (UC) patients is often experienced in daily clinical practice. Noninvasive objective monitoring for cancer development is advantageous for optimizing treatment strategies in UC patients. We aimed to examine the epigenetic alterations occurring in CACRC, focusing on DNA hypermethylation of CpG islands. MATERIALS AND METHODS: The level of DNA methylation in CpG cites was compared between CACRC and the counterpart non-tumorous mucosa using Infinium HumanMethylation 450K BeadChip. RESULTS: Our subjects included 3 males and 3 females (median age, 49.5 years). The 450K CpG site DNA methylation microarray revealed that the difference in ß value (level of hypermethylation) was the highest for corcicotropin releasing hormone receptor 2 (CRHR2) between CACRC and counterpart non-tumorous mucosa. CONCLUSION: Detection of hypermethylation of CRHR2 may be promising for cancer screening in UC patients.

Electrical properties of cells from human olfactory epithelium.

OBJECTIVE: The electrical properties of olfactory cells (OCs) are typically examined using animals such as newts, mice, and frogs, with few studies on human OCs. This study investigated the electrical properties of human cells from olfactory epithelium (hCOEs) obtained from subjects of olfactory epithelium showing no clinical symptoms during endoscopic sinus surgery. METHODS: hCOEs were isolated by collagenase treatment for whole-cell patch clamp recording. The identity of the cells was confirmed by immunohistochemistry with an antibody against olfactory maker protein. Under the voltage clamp with the whole-cell recording configuration, the voltage-gated currents of isolated hCOEs were recorded when the membrane potential was depolarized from a holding potential of -100 mV in a stepwise manner between -90 mV and + 40 mV. RESULTS: Only one of 14 hCOE samples expressed a transient inward current at the depolarizing voltage step that was activated by depolarization beyond -40 mV and reached a peak at -30 mV. Delayed and sustained outward currents (444 ± 106 pA at + 40 mV pulse; n = 20) were suppressed by tetraethyl ammonium (n = 3), which is consistent with the properties of newt OCs. CONCLUSIONS: Most hCOEs did not exhibit the transient inward current observed in animal models. These findings provide insight into the physiological basis of the unique aspects of human olfactory signal transduction.

Endovenous Laser Ablation Combined with Stripping Technique for Large Saphenous Varicose Veins: The Selection of Operation Technique.

Objective: Saphenous varicose veins can be accomplished by various operative techniques that result in stripping, ablation, or ligation of the venous reflux section. Great saphenous vein (GSV) stripping is one of the standard operations for varicose veins to eliminate reflux of the sapheno-femoral junction. The goal of any treatment regimen is to eliminate the junctional varicose reflux to control congestive dysfunction. Endovenous laser ablation (EVLA) is safe and effective with less postoperative pain, bleeding, and peripheral nerve damage than open surgery. In this study, a patient with severe progression of primary saphenous varicose veins is presented. We report the outcome of combined surgical strategy and perioperative treatment for extremely swollen varicose veins of the lower limbs to improve leg symptoms and congestion and/or promote skin ulcer healing. Materials and Methods: The subjects included 42 patients (51 limbs) who underwent EVLA with stripping. The patients comprised 24 males and 18 females, who presented a maximum GSV diameter >15 mm. The Clinical-Etiological-Anatomic-Pathophysiologic classification identified 9, 20, 9, 2, 6, and 5 limbs with C2, C3, C4a, C4b, C5, and C6, respectively, among the 42 patients. Results: EVLA was used to treat GSV with a mean length of 16.1±2.8 cm. The mean of the maximum GSV diameter was 16.8±3.2 mm (14.6-21.8 mm). The preoperative visual analog scale (VAS) score was 82.1±12.1. After operation, the VAS gradually deteriorated to 31.3±17.9 (p<0.0001), 2.8±3.6 (p<0.0001), and 1.2±1.8 (p<0.0001) in 7 days, 1 month, and 3 months, respectively. Conclusion: We obtained a satisfactory outcome from our combined strategy and perioperative treatment for extremely swollen saphenous varicose veins. This approach may show the possibility that lower saphenous varicose veins can induce cosmetic and minimally invasive ameliorated intervention to avoid late-phase incompetent perforating veins.

Endoscopic endonasal transmaxillary ligation of a feeding artery and coblation plasma technology enables en bloc resection of advanced juvenile nasopharyngeal angiofibroma without preoperative embolization.

Juvenile nasopharyngeal angiofibroma (JNA) is a hypervascular tumor and uncontrolled hemorrhage makes its removal very difficult. Although preoperative intravascular embolization of a feeding artery is recommended, serious complications such as iatrogenic thrombosis in the brain and insufficient decrease in blood flow to the tumor are concerns. Recently, coblation plasma technology has been reported to be useful for tumor removal with minimum hemorrhage under a clear surgical field. Here we report successful removal of advanced JNA without preoperative embolization, using intraoperative ligation of the maxillary artery and coblation plasma technology. The left nasal cavity of a 23-years-old man was closed by a JNA tumor at Radkowski stage IIC, which was 65mm in size and extended from the nasal cavity to the infratemporal fossa. MRA imaging showed the maxillary artery running along the posterior wall of the maxillary sinus. Therefore, the maxillary artery was first clipped using an endoscopic modified medial maxillectomy (EMMM) approach and endoscopic endonasal en bloc resection of the tumor was then completed using coblation technology with no need for blood transfusion. This case illustrates that preoperative embolization is dispensable in JNA surgery even at Stage IIC if the maxillary artery can be ligated during surgery and a coblation device can be utilized.

Eighty percent survival rate at 15 years for 1p/19q co-deleted oligodendroglioma treated with upfront chemotherapy irrespective of tumor grade.

INTRODUCTION: Chromosomes 1p/19q co-deletion is a robust molecular marker for the diagnosis of oligodendroglial tumors, and has been included in the 2016 WHO modified classification. Although treatment for oligodendroglioma is controversial, upfront chemotherapy is regarded as one of the treatment option for low-grade tumor. We have treated all the 1p/19q co-deleted oligodendrogliomas, both grades II and III, with upfront chemotherapy without conventional radiotherapy for 20 years. The clinical experience from this trial may be suggestive for understanding of the biological features of oligodendroglioma with 1p/19q co-deletion toward precision medicine. METHODS: This is a long-term retrospective data of the non-selected patients with 1p/19q co-deleted oligodendrogliomas uniformly treated with up-front chemotherapy. Seventy consecutive patients (48 with grade II and 22 with grade III tumors) were included. RESULTS: The median follow-up period was 13 years. The 5-, 10-, and 15-year progression-free survival (PFS) rates were 85.7%, 54.8%, and 31.5%, respectively, and the median PFS was 146 months. In most cases, tumor recurrence was remained local and could be controlled by salvage surgery and/or chemotherapy. The 5-, 10-, and 15-year overall survival (OS) rates were 96.8%, 88.7%, and 80.0%, respectively, and the median OS was not reached. These survival data compared favorably with previous large clinical studies employing radiotherapy. Tumor grades based on World Health Organization classification, extent of surgery, and age affected neither PFS nor OS. Most patients were able to return to their premorbid social life. CONCLUSIONS: The long-term results drawn from 20-years of single institution experience show that the patients with 1p/19q co-deleted oligodendrogliomas can be successfully treated with up-front chemotherapy alone without compromising OS.

UGT1A1 polymorphisms in rectal cancer associated with the efficacy and toxicity of preoperative chemoradiotherapy using irinotecan.

The purpose of the present study was to assess the efficacy and toxicity of preoperative chemoradiotherapy using irinotecan against locally advanced lower rectal cancer according to UDP-glucuronosyltransferase 1A1 (UGT1A1) polymorphisms. Between 2009 and 2016, 46 patients with resectable rectal cancer (T3-T4, N0-N2, M0) received preoperative chemoradiotherapy consisting of 80 mg/m2 per day tegafur/gimeracil/oteracil (S-1; days 1-5, 8-12, 22-26, and 29-33), 60 mg/m2 per day irinotecan (days 1, 8, 22, and 29), and 45 Gy radiation (1.8 Gy/day, 5 days per week for 5 weeks). Six to eight weeks after completing chemoradiotherapy, total mesorectal excision was carried out. Patients with UGT1A1 polymorphisms were divided into WT (n = 26), heterozygous (n = 15), and homozygous (n = 5) groups, the latter including double heterozygosities. We evaluated associations between clinical characteristics, including UGT1A1 polymorphisms, and chemoradiotherapy efficacy and toxicity. Incidence rates of grade 3+ neutropenia and diarrhea were 17.0% and 30.4%, respectively. Relative dose intensity was 89.3%. Pathological complete response rate (grade 3) was 26.1%, and the good response (grade 2/3) rate was 84.8%. UGT1A1 polymorphisms were significantly associated with neutropenia and pathological good responses, but not with diarrhea. UGT1A1 polymorphism was the only predictive factor for pathological good responses. Our results indicate that UGT1A1 polymorphism is a predictive factor to determine the clinical efficacy of preoperative chemoradiotherapy and hematological toxicity induced by chemoradiotherapy using irinotecan in locally advanced rectal cancer patients.

Evaluation of appropriate follow-up after curative surgery for patients with colorectal cancer using time to recurrence and survival after recurrence: a retrospective multicenter study.

INTRODUCTION: The follow-up schedule for colorectal cancer patients after curative surgery is inconsistent among the guidelines. Evaluation of time to recurrence (TTR) and survival after recurrence (SAR) may provide evidence for appropriate follow-up. METHODS: We assessed 3039 colon cancer (CC) and 1953 rectal cancer (RC) patients who underwent curative surgery between 2007 and 2008. We evaluated the pre- and post-recurrent clinicopathological factors associated with TTR and SAR in each stage of CC and RC. RESULTS: The recurrence rates of stages I, II, and III were 1.2%, 13.1%, and 26.3%, respectively, for CC, and 8.4%, 20.0%, and 30.4%, respectively, for RC. In CC patients, high carcinoembryonic antigen (CEA) level and lymphovascular invasion were independent predictors of short TTR. In RC patients, metastatic factors (liver metastasis in stage III) and venous invasion (stage III) were independent predictors of short TTR. The prognostic factors of SAR were age (stage II CC and stage III RC), female gender (stage III RC), high CEA level (stage II RC), histological type (stage III CRC), nodal status (stage III CC), recurrence within 1 year (stage III RC), M1b recurrence (stage II CRC), local recurrence (stage II CC), and no surgical resection after recurrence (stage II and III CRC). CONCLUSIONS: The follow-up schedule for stage I should be different from that for the other stages. We recommend that intensive follow-up is appropriate in stage III CC patients with undifferentiated adenocarcinoma or N2 nodal status, stage II RC patients with high preoperative CEA level, and stage III RC patients.