Impact of intraoperative fluid management on postoperative complications in patients undergoing minimally invasive esophagectomy for esophageal cancer: a retrospective single-center study.

BACKGROUND: Esophagectomy is a high-risk procedure that can involve serious postoperative complications. There has been an increase in the number of minimally invasive esophagectomies (MIEs) being performed. However, the relationship between intraoperative management and postoperative complications in MIE remains unclear. METHODS: After the institutional review board approval, we enrolled 300 patients who underwent MIE at Tohoku University Hospital between April 2016 and March 2021. The relationships among patient characteristics, intraoperative and perioperative factors, and postoperative complications were retrospectively analyzed. The primary outcome was the relationship between intraoperative fluid volume and anastomotic leakage, and the secondary outcomes included the associations between other perioperative factors and postoperative complications. RESULTS: Among 300 patients, 28 were excluded because of missing data; accordingly, 272 patients were included in the final analysis. The median [interquartile range] operative duration was 599 [545-682] minutes; total intraoperative infusion volume was 3,747 [3,038-4,399] mL; total infusion volume per body weight per hour was 5.48 [4.42-6.73] mL/kg/h; and fluid balance was + 2,648 [2,015-3,263] mL. The postoperative complications included anastomotic leakage in 68 (25%) patients, recurrent nerve palsy in 91 (33%) patients, pneumonia in 62 (23%) patients, cardiac arrhythmia in 13 (5%) patients, acute kidney injury in 5 (2%) patients, and heart failure in 5 (2%) patients. The Cochrane-Armitage trend test indicated significantly increased anastomotic leakage among patients with a relatively high total infusion volume (P = 0.0085). Moreover, anastomotic leakage was associated with male sex but not with peak serum lactate levels. Patients with a longer anesthesia duration or recurrent nerve palsy had a significantly higher incidence of postoperative pneumonia than those without. Further, the incidence of postoperative pneumonia was not associated with the operative duration, total infusion volume, or fluid balance. The operative duration and blood loss were related to the total infusion volume. Acute kidney injury was not associated with the total infusion volume or serum lactate levels. CONCLUSIONS: Among patients who underwent MIE, the total infusion volume was positively correlated with the incidence of anastomotic leakage. Further, postoperative pneumonia was associated with recurrent nerve palsy but not total infusion volume or fluid balance.

A preliminary report on retrospective dose assessment by FISH translocation assay in FDNPP Nuclear Emergency Worker Study (NEWS).

In Japan, a national project of longitudinal health care and epidemiological research (NEWS) was developed in 2014 to analyse the effects of radiation on human health for workers who responded to the Fukushima Dai-ichi nuclear emergency in 2011. In 2018, peripheral blood for chromosome translocation analysis was collected from 62 workers. Retrospective dose assessment was performed with fluorescence in situ hybridisation translocation (FISH-Tr) assay. The range of estimated doses by FISH-Tr assay was 0-635 mGy, in which 22 workers had estimated doses of more than 189 mGy. Biological dose estimates were five times higher in workers with physically measured total exposure recordings above 70 mGy. It is likely that smoking and medical exposure caused the discrepancy between estimated biological and physical total exposure doses. Thus, there is a possibility that retrospective biodosimetry assessment might over-estimate occupational exposures to workers exposed to chronic radiation during nuclear emergency work.

No increase in translocated chromosomal aberrations, an indicator of ionizing radiation exposure, in childhood thyroid cancer in Fukushima Prefecture.

To investigate the effects of radiation exposure due to the Fukushima nuclear power plant accident, following the disaster Fukushima Prefecture launched thyroid ultrasound examinations of residents who were generally younger than 18 years at the time of the earthquake. As the rate of pediatric thyroid cancer was higher than expected, we conducted biological dose assessment based on the frequency of translocated chromosome (Tr) aberrations using peripheral blood lymphocytes. Tr formation frequency was compared among the thyroid cancer (n = 38, median age 18 years, age range 12-26 years), thyroid-related disease (n = 30, median age 21 years, age range 15-28 years), and healthy controls (n = 31, median age 22 years, age range 20-23 years) groups. Tr aberration frequency was initially significantly higher in the thyroid cancer than in the other two groups; however, differences among the groups disappeared after adjusting for history of CT scan, as 92%, 67%, and 28% of those in the thyroid cancer, thyroid-related disease, and control groups, respectively, had undergone CT previously. Therefore, the significant difference in the initial number of Tr formations is presumably due to radiation exposure from CT. Accordingly, the effects of medical exposure on the chromosomes of children and adolescents should be noted.

ΔNp63α transcriptionally represses p53 target genes involved in the radiation-induced DNA damage response : ΔNp63α may cause genomic instability in epithelial stem cells.

BACKGROUND: The DNA damage response (DDR) is a mechanism that protects cells against radiation-induced oxidative DNA damage by causing cell cycle arrest and apoptosis. TP63 is a member of the tumour suppressor TP53 gene family, and ΔNp63α, a TP63 splicing variant, is constitutively expressed in the stem cell-containing basal layer of stratified epithelial tissues, including the mammary gland, where it plays a critical role in stemness and tissue development. ΔNp63α has been reported to transcriptionally inhibit the tumour suppression protein p53. This p53-repressive activity may cause genomic instability in epithelial stem cells exposed to radiation. In this study, we analysed the inhibitory effect of ΔNp63α on radiation-induced DDR. METHODS: To elucidate the role of the p53-repressive effect of ΔNp63α in radiation response, we performed a p63-siRNA knockdown experiment using human mammary epithelial cells (HMECs) expressing ΔNp63α and then performed ectopic and entopic expression experiments using human induced pluripotent stem cells (hiPSCs). After irradiation, the expression of DDR-related genes and proteins in ΔNp63α-expressing and control cells was analysed by RT-qPCR, Western blotting, and flow cytometry. RESULTS: The mRNA/protein expression levels of BAX and p21 were significantly increased in p63-siRNA-treated HMECs (sip63) after X-ray irradiation (4 Gy, 0.7 Gy/min) but not in scramble-siRNA treated HMECs (scr). Transcriptomic analysis showed decreased RNA expression of cell cycle-related genes and increased expression of programmed cell death-related genes in sip63 cells compared to scr cells. Furthermore, flow cytometric analysis revealed an increase in apoptotic cells and a decrease in 5-ethynyl-2´-deoxyuridine uptake in sip63 cells compared to scr cells. On the other hand, both the ectopic and entopic expression of ΔNp63α in apoptosis-sensitive hiPSCs reduced the expression levels of BAX after irradiation and significantly decreased the number of apoptotic cells induced by radiation. CONCLUSION: Taken together, these results indicate that ΔNp63α represses p53-related radiation-induced DDR, thereby potentially causing genomic instability in epithelial stem cells.

[Effectiveness of Nivolumab in a Case of Inoperable Advanced Gastric Cancer with Lung Metastasis].

A 66-year-old man was diagnosed with inoperable advanced gastric cancer with liver and peritoneal metastases. The patient underwent SOX therapy as primary chemotherapy; subsequently, liver and peritoneal metastases disappeared. However, lung metastasis was detected later, and weekly paclitaxel(PTX)combined with ramucirumab(RAM)chemotherapy was initiated; subsequently, lung metastasis and advanced gastric cancer disappeared. During remission, lung metastasis was detected again. Although weekly PTX combined with RAM chemotherapy was reinitiated, a progressive disease status was achieved. As tertiary chemotherapy, nivolumab therapy(240 mg/body, every 2 weeks)was initiated for 20 courses over 11 months. This therapy was significantly effective, which aid the patient to achieve a complete response. The patient survived and is healthy for 5 years due to chemotherapy administration alone.

[A Case of Non-Resectable Advanced Gastric Cancer for Which Nivolumab Was Markedly Effective].

A 74-year-old man presented to our hospital because of anorexia. Upper gastrointestinal endoscopy revealed type 3 gastric cancer. Further examination disclosed metastasis to the perigastric lymph nodes and to the liver, and a diagnosis of non- resectable advanced gastric cancer(cT4N2H1P0M0)in cStage Ⅳ was made. A total of 4 courses of S-1 plus oxaliplatin therapy(80 mg/body/day and 100 mg/m2/cycle, respectively, for 2 weeks followed by a 1-week rest)were administered as the primary chemotherapy. Then, another metastasis to the abdominal lymph nodes and increased liver metastasis were found; thus, the patient's condition was rated as progressive disease(PD). Secondary chemotherapy comprising 10 courses of weekly nab-paclitaxel(nab-PTX)plus ramucirumab(RAM)therapy(100 mg/m2 on days 1, 8, and 15 and 8 mg/kg on days 1 and 15, respectively, every 4 weeks)were administered. Although temporary reductions in the perigastric lymph node metastasis and liver metastasis as compared with the baseline were observed, another metastasis to the abdominal lymph nodes occurred subsequently, resulting in PD. As tertiary chemotherapy, nivolumab therapy(240 mg/body, every 3 weeks) was repeated up to a total of 30 courses over 13 months. This therapy was markedly effective, achieving a near complete response. The patient is currently being followed up as an outpatient.

Chromosomal translocation t(11;14) and p53 deletion induced by the CRISPR/Cas9 system in normal B cell-derived iPS cells.

Multiple myeloma (MM) cells are derived from mature B cells based on immunoglobulin heavy chain (IgH) gene analysis. The onset of MM is often caused by a reciprocal chromosomal translocation (cTr) between chr 14 with IgH and chr 11 with CCND1. We propose that mature B cells gain potential to transform by reprograming, and then chromosomal aberrations cause the development of abnormal B cells as a myeloma-initiating cell during B cell redifferentiation. To study myeloma-initiating cells, we have already established normal B cell-derived induced pluripotent stem cells (BiPSCs). Here we established two BiPSCs with reciprocal cTr t(11;14) using the CRISPR/Cas9 system; the cleavage site were located in the IgH Eµ region of either the VDJ rearranged allele or non-rearranged allele of IgH and the 5'-upsteam region of the CCND1 (two types of BiPSC13 with t(11;14) and MIB2-6 with t(11;14)). Furthermore, p53 was deleted using the CRISPR/Cas9 system in BiPSC13 with t(11;14). These BiPSCs differentiated into hematopoietic progenitor cells (HPCs). However, unlike cord blood, those HPCs did not differentiated into B lymphocytes by co-culture with BM stromal cell. Therefore, further ingenuity is required to differentiate those BiPSCs-derived HPCs into B lymphocytes.

[Transverse Colon Cancer with Peritoneal Metastasis Successfully Treated with mFOLFOX6 plus Bevacizumab-A Case Report].

A male patient in his 80s, diagnosed with rectal cancer, underwent transverse colon resection(pT3, pN0, cM0, and pStage Ⅱa, RAS wild-type, BRAF-mutant). However, 19 months later, intraperitoneal metastasis was detected and the patient received 8 courses of mFOLFOX6 plus bevacizumab. Following the observation of an allergic reaction that was attributable to oxaliplatin, the regimen was changed to a total of 7 courses of sLV5FU2 plus bevacizumab. Subsequently, a marked decrease was observed in intraperitoneal metastasis. The patient completed sLV5FU2 plus bevacizumab chemotherapy. At 1 year after the marked decrease, the metastatic recurrence was not exacerbated.

Quantum Yield Enhancement in Graphene Quantum Dots via Esterification with Benzyl Alcohol.

The quantum yield of graphene quantum dots was enhanced by restriction of the rotation and vibration of surface functional groups on the edges of the graphene quantum dots via esterification with benzyl alcohol; this enhancement is crucial for the widespread application of graphene quantum dots in light-harvesting devices and optoelectronics. The obtained graphene quantum dots with highly graphene-stacked structures are understood to participate in π-π interactions with adjacent aromatic rings of the benzylic ester on the edges of the graphene quantum dots, thus impeding the nonradiative recombination process in graphene quantum dots. Furthermore, the crude graphene quantum dots were in a gel-like solid form and showed white luminescence under blue light illumination. Our results show the potential for improving the photophysical properties of nanomaterials, such as the quantum yield and band-gap energy for emission, by controlling the functional groups on the surface of graphene quantum dots through an organic modification approach.

[A Case Report of Inoperable Gastric Cancer with Peritoneal Dissemination, Liver Metastasis, and Lung Metastasis Successfully Treated with Weekly Paclitaxel and Ramucirumab].

A 63-year-old man diagnosed with a perforated gastric ulcer and generalized peritonitis underwent surgical intervention. However, computed tomography(CT), esophagogastroduodenoscopy(EGD), and positron emission tomography-CT(PETCT) revealed an inoperable gastric cancer with liver and peritoneal metastases(cT4NxH1P1M0, cStage Ⅳ, for which he received S-1 and oxaliplatin chemotherapy[SOX therapy]). The patient underwent 10 SOX therapy cycles. Following the initial chemotherapy course, the peritoneal and liver metastases disappeared on radiographic images. However, lung metastasis was detected, and the patient initiated weekly paclitaxel(PTX)and ramucirumab(RAM)chemotherapy. After 4 treatment cycles, lung metastasis and gastric cancer disappeared.

Progressive Cerebral Ischemia and Intracerebral Hemorrhage after Indirect Revascularization for a Patient with Cerebral Proliferative Angiopathy.

We previously reported a patient with cerebral proliferative angiopathy (CPA) who showed cerebral ischemia in resting and acetazolamide-stressed N-isopropyl-p-[123I] iodoamphetamine single-photon emission computed tomography (123I-IMP-SPECT). At onset, the patient was treated conservatively. However, during the 2 years following initial onset, his hemiparesis and aphasia had gradually aggravated and his IQ scores were markedly decreased. MRI revealed progressive vascular proliferation and brain atrophy. 123I-IMP-SPECT showed more severely impaired cerebral blood flow (CBF) and cerebrovascular reactivity over the affected hemisphere. We performed an indirect revascularization to augment CBF; however, his neurological deficits were not improved and new arteriovenous shunts via extracranial-intracranial bypass were developed, followed by an asymptomatic small intracerebral hemorrhage. There are no reports on CPA patients who have shown cerebral hemorrhage after indirect revascularization. Treatments for CPA are still challenging and controversial. Cases with severe stenosis of the proximal arteries may benefit from indirect revascularization. But indirect bypass should not be indicated for such patients without main arterial stenosis, even if they have persistent ischemia.

Clinical significance of neutrophil gelatinase-associated lipocalin and galectin-7 in tape-stripped stratum corneum of acne vulgaris.

The usefulness of stratum corneum neutrophil gelatinase-associated lipocalin and stratum corneum galectin-7 as biomarkers of acne vulgaris was studied. A comparison of neutrophil gelatinase-associated lipocalin levels on the cheeks of patients with acne vulgaris at the start of the study and at the time of symptom improvement showed a significant decrease. On the other hand, the galectin-7 levels at the time of symptom improvement were significantly higher than those at the start of the study. Therefore, because the inflammation in the epidermis and hair follicles was reduced after therapy, as a result of the solution of the inflammatory eruptions caused by acne vulgaris, the neutrophil gelatinase-associated lipocalin level also showed a significant decrease after therapy. These results suggest that stratum corneum neutrophil gelatinase-associated lipocalin may be useful as an objective biomarker of changes in acne vulgaris symptoms.

[A Case Report of Sigmoid Colon Cancer with Multiple Lung Metastases Successfully Treated with S-1].

A patient in his 70s was diagnosed with sigmoid colon cancer[pT3pN1cM1(PUL1), pStage IV ]for which he underwent sigmoid colectomy and received S-1 adjuvant therapy for the lung metastases. The patient received a total of 10 courses of S- 1, administered orally on days 1-14 of a 21-day cycle. The lung metastases showed a complete response, and the patient completed the S-1 chemotherapy. No recurrence of lung metastases was detected up to 6 months later.

Isomethoxyneihumicin, a new cytotoxic agent produced by marine Nocardiopsis alba KM6-1.

A new cytotoxic agent designated isomethoxyneihumicin (1 and 2), a mixture of lactam-lactim tautomers, was isolated along with methoxyneihumicin (3) from the culture broth of the marine Nocardiopsis alba KM6-1. The structures of 1 and 2 were elucidated in spectroscopic analyses (1D and 2D NMR data, and ROESY correlations). Isomethoxyneihumicin (15.0 µM) and 3 (15.0 µM) arrested the cell cycle of Jurkat cells at the G2/M phase (66 and 67%) in 12 h. Isomethoxyneihumicin and 3 exhibited cytotoxicity against Jurkat cells with IC50 values of 6.98 and 30.5 µM in 20 h, respectively. These results strongly suggest that isomethoxyneihumicin and 3 exhibit cytotoxicity against Jurkat cells by inhibiting the cell cycle at the G2/M phase.