Global Forum of Cancer Surgeons: Cancer Surgery During the COVID-19 Pandemic: Impact and Lessons Learned.

BACKGROUND: The purpose of this article is to summarize the opinions of the surgical oncology leaders from the Global Forum of Cancer Surgeons (GFCS) about the global impact of COVID-19 pandemic on cancer surgery. METHODS: A panel session (virtual) was held at the annual Society of Surgical Oncology 2021 International Conference on Surgical Cancer Care to address the impact of COVID-19 on cancer surgery globally. Following the virtual meeting, a questionnaire was sent to all the leaders to gather additional opinions. The input obtained from all the leaders was collated and analyzed to understand how cancer surgeons from across the world adapted in real-time to the impact of COVID-19 pandemic. RESULTS: The surgical oncology leaders noted that the COVID-19 pandemic led to severe disruptions in surgical cancer care across all domains of clinical care, education, and research. Several new changes/protocols associated with increased costs were implemented to deliver safe care. Leaders also noted that preexisting disparities in care were exacerbated, and the pandemic had a detrimental effect on well-being and financial status. CONCLUSIONS: The COVID-19 pandemic has led to severe disruptions in surgical cancer care globally. Leaders of the GFCS opined that new strategies need to be implemented to prepare for any future catastrophic events based on the lessons learned from the current events. The GFCS will embark on developing such a roadmap to ensure that surgical cancer care is preserved in the future regardless of any catastrophic global events.

Neurological outcomes of out-of-hospital cardiac arrest occurring in Tokyo train and subway stations.

OBJECTIVES: The purpose of this study was to identify a relationship between the background environment, bystander and emergency medical services intervention, and favourable neurological outcomes (CPC1-2) one-month after out-of-hospital cardiac arrest (OHCA) occurred at Tokyo train and subway stations. METHODS: This retrospective observational study used OHCA data between 2014 and 2018 that occurred at train stations in Tokyo. The eligible 954 patients were analysed for correlation between background, time frame, and location. Multivariable logistic regression models were used to estimate factors associated with CPC1-2 in patients with cardiogenic OHCA. RESULTS: A total of 886 OHCA cases, cardiogenic (n=562) and non-cardiogenic (n=324), met the inclusion criteria. Of the cardiogenic cases, 71.9% occurred at the platform and on-a-train. One-month CPC1-2 was achieved in 32.0% of cardiogenic OHCAs, which included 47.3% during morning rush hour, 24.7% during daytime hours, 40.2% during evening rush hour, and 20.5% during night-time/early morning hours. CPC1-2 had significant correlation with morning rush hour (adjusted odds ratio [AOR],4.52; 95% confidence interval [CI], 1.09-18.78), evening rush hour (AOR, 6.85; 95% CI, 1.51-31.15), public access defibrillation (AOR, 5.19; 95% CI, 1.38-19.51), and ventricular fibrillation or pulseless ventricular tachycardia (AOR, 7.56; 95% CI, 1.35-42.43). CONCLUSION: A total of 71.9% of cardiogenic OHCAs occurred at platforms and on trains. To improve neurological outcomes of OHCAs at stations, AED installations on train platforms are necessary. Additionally, using artificial intelligence-based platform monitoring for early detection of OHCAs and offering CPR training are required.

Pre-operative endovascular coil embolisation for chronic pulmonary aspergillosis.

OBJECTIVE: To retrospectively evaluate the clinical outcomes of pre-operative endovascular coil embolisation (ECE) for chronic pulmonary aspergillosis (CPA).METHODS: We evaluated surgical patients with CPA between November 2016 and April 2020. Pre-operative ECE for CPA with severe adhesions was selectively performed to reduce intra-operative blood loss. ECE procedures, operative procedures, intra-operative blood loss and complications were evaluated.RESULTS: Twenty-eight patients (21 males and 7 females; median age: 55 years) were included in the study. Of the 28 patients, 8 (28.6%) underwent pre-operative ECE. Technical success rate in pre-operative ECE was 100%. The median time required for ECE procedures was 123 min. The median number of vessels embolised per procedure was 2.5. The median period between embolisation and surgery was 5 days. Major complications were observed in three patients (10.7%). There were no significant differences between patients with and without pre-operative ECE in operative time (284 vs. 365 min, respectively, P = 0.7602) and intra-operative blood loss (294 vs. 228 mL, respectively, P = 0.8987).CONCLUSIONS: Pre-operative ECE for CPA appears to be feasible and safe; however, its role in reducing intra-operative blood loss needs further investigation.

Time-to-onset of diabetes with everolimus use: analysis of a spontaneous reporting system database.

The incidence of hyperglycemia and diabetes induced by everolimus has been shown in previous studies. Our study analyzed diabetes time-to-onset profiles after everolimus use in patients who underwent transplantation and patients with cancer. Using data from April 2007 to December 2018 in the Japanese Adverse Drug Event Report database, the reports with everolimus were classified according to its use as an immunosuppressant or anticancer drug. The median (25%-75%) days of diabetes time-to-onset in patients who underwent transplantation and patients with cancer were 172 (56-315) and 32 (18.5-57), respectively. There were no significant variations among patients with breast cancer, neuroendocrine tumor, and renal cell carcinoma. By conducting a Weibull shape parameter test, the lower limits of the 95% confidence intervals of the shape parameter ß values for the indications of the cancer types were >1, indicating the wear out failure type profile, whereas those for transplantation data indicated a random failure type profile. The diabetes time-to-onset profiles after everolimus use differed between usage as an anticancer drug and immunosuppressant and there were no significant variations among the type of cancer. It was suggested that the incidence of diabetes should be monitored for 1-2 months in patients with cancer, whereas continuous monitoring is needed in patients who undergo transplantation.

Effects of an elemental diet to reduce adverse events in patients with esophageal cancer receiving docetaxel/cisplatin/5-fluorouracil: a phase III randomized controlled trial-EPOC 2 (JFMC49-1601-C5).

BACKGROUND: Oral mucositis (OM) is an unpleasant adverse event in patients receiving chemotherapy. A prospective feasibility study showed that elemental diet (ED), an oral supplement that does not require digestion, may prevent OM. Based on this, we established a central review system for oral cavity assessment by dental oncology specialists blinded to background data. We used this system to elucidate the preventive effect of an ED against OM in patients with esophageal cancer receiving docetaxel, cisplatin, and 5-fluorouracil (DCF) therapy. PATIENTS AND METHODS: In this phase III, multicenter, parallel-group, controlled trial, patients consuming a normal diet orally were randomly assigned (1 : 1) to receive two cycles of DCF with (group A) or without (group B) an ED (Elental® 160 g/day). We assessed the incidence of grade ≥2 OM evaluated by two reviewers, changes in body weight, prealbumin, C-reactive protein, and DCF completion rate based on ED compliance. RESULTS: Of the 117 patients randomly assigned to treatment, four failed to start treatment and were excluded from the primary analysis; thus, groups A and B comprised 55 and 58 patients, respectively. There were no significant differences in background characteristics. Grade ≥2 OM was observed in eight (15%) and 20 (34%) patients in groups A and B, respectively (P = 0.0141). Changes in body weight and prealbumin during the two DCF cycles were significantly higher in group A than B (P = 0.0022 and 0.0203, respectively). During the first cycle, changes in C-reactive protein were significantly lower in group A than B (P = 0.0338). In group A (receiving ED), the DCF completion rate was 100% in patients with 100% ED compliance and 70% in patients failing ED completion (P = 0.0046). CONCLUSIONS: The study findings demonstrate that an ED can prevent OM in patients with esophageal cancer receiving chemotherapy.

Evaluation of pharyngeal swallowing pressure using high-resolution manometry during transoral surgery for oropharyngeal cancer.

BACKGROUND: Transoral robotic surgery is frequently described, driven by the desire to offer a less morbid alternative to chemoradiation. However, the objective evaluation of post-operative function has rarely been reported. Therefore, high-resolution manometry was used in this study to evaluate the impact of changes in peri-operative swallowing function on pharyngeal pressure events. METHODS: Ten patients with various stages of oropharyngeal cancer underwent transoral surgery. High-resolution manometry and videofluoroscopic swallow studies were performed before surgery and two months afterwards. The following parameters were obtained: velopharyngeal and mesopharyngeal post-deglutitive upper oesophageal sphincter pressures, velo-meso-hypopharyngeal contractile integral, upper oesophageal sphincter relaxation pressure, and pharyngeal velocity. RESULTS: There was no significant difference in pharyngeal pressure or contractile integral pre- versus post-operatively. However, pharyngeal velocity was significantly higher post-operatively than pre-operatively. CONCLUSION: High-resolution manometry showed that transoral surgery in patients without pre-operative dysphagia preserved pharyngeal constriction. However, transoral surgery might produce scar formation in the pharynx, which could lead to narrowing of the pharynx.

A case of hypereosinophilia with digital ischaemia successfully treated with intravenous prostaglandin E1.

In the therapeutic management of eosinophilic disorder, it is important to prevent hypereosinophilia (HE)-related organ damage even in the process of diagnosis. We describe here a unique clinical and histopathological findings of the patient with HE accompanied with digital ischaemia. Treatment with intravenous prostaglandin E1 was essential for digital ischaemia in our case while benralizumab, humanized monoclonal antibody against interleukin-5 receptorα, did not affect. Our case suggests an earlier intervention for digital ischaemia in the therapeutic management of eosiniphilic disorder.

Prescription patterns of psychotropics in patients receiving synthetic glucocorticoids.

OBJECTIVE: Synthetic glucocorticoids cause various psychiatric symptoms. Prescription of psychotropic drugs could be considered to be a proxy for manifestation of psychiatric symptoms. The aim of this study was to investigate the prescriptions of psychotropics in outpatients receiving synthetic glucocorticoids. METHODS: We used the claims sampling data during January 2015 from the National Database of Health Insurance Claims and Specific Health Checkups of Japan made by the Ministry of Health, Labor, and Welfare in Japan. We compared the prescription rates of psychotropics between outpatients receiving oral synthetic glucocorticoids and age- and sex-matched controls and the prescription rates of psychotropics among the eight dosage groups of synthetic glucocorticoids by chi-squared test, and chlorpromazine/imipramine/diazepam equivalent doses (or daily defined doses) of respective psychotropics among these groups using Welch's t-test. RESULTS: Synthetic glucocorticoids were prescribed to 3.1% (n = 18 122) of 581 990 patients. The prescription rates of psychotropics were significantly higher among the synthetic glucocorticoid recipients than among the non-recipients: antipsychotics, 1.8% (n = 321) vs. 1.1% (n = 201) (P = 1.4 × 10-7 ); antidepressants, 4.0% (n = 724) vs. 2.0% (n = 359) (P = 8.7 × 10-30 ); anxiolytics/hypnotics, 16.7% (n = 3029) vs. 10.2% (n = 1841) (P = 2.7 × 10-75 ); and mood stabilizers, 1.3% (n = 238) vs. 0.7% (n = 120) (P = 3.6 × 10-10 ) respectively. There was no significant difference in the prescription rates of any psychotropic drugs, other than anxiolytics/hypnotics, among the eight synthetic glucocorticoid dosage groups. CONCLUSION: Prescriptions of oral synthetic glucocorticoids were found to be associated with the use of any of the types of psychotropic drugs, other than anxiolytics/hypnotics, although a causal relationship could not be confirmed due to the retrospective and cross-sectional nature of this study.

Adherence to clozapine vs. other antipsychotics in schizophrenia.

BACKGROUND: To date, there have been no studies evaluating adherence to clozapine with electronic adherence monitoring (EAM) such as the Medication Event Monitoring System (MEMS® ). METHODS: In outpatients with schizophrenia, we conducted a 3-month prospective study investigating antipsychotic adherence with EAM (eCAP® ). Participants were treated with different oral antipsychotics, including clozapine, and blind to EAM monitoring; all were on antipsychotic monotherapy administered once daily. Outcome measures included adherence rate, missed dose, and medication gap. Adherence trajectory patterns were also analyzed for clozapine vs. other antipsychotics collectively. RESULTS: A total of 111 patients were included in the study; 33 and 78 patients received clozapine or other antipsychotics, respectively. Adherence rates, defined as proportion of days that the subject took the medication at the prescribed time ± 3 h and proportion of subjects with ≥80% adherence, were numerically higher in patients receiving clozapine vs. other antipsychotics (72.0% vs. 65.1%, P = 0.10; 49.5% vs. 35.7%, P = 0.11, respectively). Along similar lines, some of the missed dose and medication gap outcomes were significantly better in patients receiving clozapine vs. other antipsychotics. Three adherence trajectory patterns were identified for both clozapine and other antipsychotics, with two shared by both groups (i.e., low adherence with a slight decrease over time; high and stable adherence). CONCLUSION: Findings suggest that in patients with schizophrenia clozapine adherence is at least comparable, if not slightly better, compared with other antipsychotics.

An artificial impact on the asteroid (162173) Ryugu formed a crater in the gravity-dominated regime.

The Hayabusa2 spacecraft investigated the small asteroid Ryugu, which has a rubble-pile structure. We describe an impact experiment on Ryugu using Hayabusa2's Small Carry-on Impactor. The impact produced an artificial crater with a diameter >10 meters, which has a semicircular shape, an elevated rim, and a central pit. Images of the impact and resulting ejecta were recorded by the Deployable CAMera 3 for >8 minutes, showing the growth of an ejecta curtain (the outer edge of the ejecta) and deposition of ejecta onto the surface. The ejecta curtain was asymmetric and heterogeneous and it never fully detached from the surface. The crater formed in the gravity-dominated regime; in other words, crater growth was limited by gravity not surface strength. We discuss implications for Ryugu's surface age.

Minimally invasive oesophagectomy with extended lymph node dissection and thoracic duct resection for early-stage oesophageal squamous cell carcinoma.

BACKGROUND: Oesophageal squamous cell carcinoma is an aggressive disease owing to early and widespread lymph node metastases. Multimodal therapy and radical surgery may improve prognosis. Few studies have investigated the efficacy of radical lymph node and thoracic duct resection. METHODS: Patients with oesophageal squamous cell carcinoma who underwent transthoracic minimally invasive oesophagectomy (TMIE) for cancer at Keio University Hospital between January 2004 and December 2016 were selected. Between 2004 and 2008, TMIE was performed in the lateral decubitus position without thoracic duct resection (standard TMIE). From 2009 onwards, TMIE with extended lymph node and thoracic duct resection was introduced (extended TMIE). Demographics, co-morbidity, number of retrieved lymph nodes, pathology, postoperative complications and recurrence-free survival (RFS) were compared between groups. RESULTS: Forty-four patients underwent standard TMIE and 191 extended TMIE. There were no significant differences in clinical and pathological tumour stage or postoperative complications. The extended-TMIE group had more lymph nodes removed at nodal stations 106recL and 112. Among patients with cT1 N0 disease, RFS was better in the extended-TMIE group (P < 0·001), whereas there was no difference in RFS between groups in patients with advanced disease. CONCLUSION: Extended TMIE including thoracic duct resection increased the number of lymph nodes retrieved and was associated with improved survival in patients with cT1 N0 oesophageal squamous cell carcinoma.

POGLUT1 biallelic mutations cause myopathy with reduced satellite cells, α-dystroglycan hypoglycosylation and a distinctive radiological pattern.

Protein O-glucosyltransferase 1 (POGLUT1) activity is critical for the Notch signaling pathway, being one of the main enzymes responsible for the glycosylation of the extracellular domain of Notch receptors. A biallelic mutation in the POGLUT1 gene has been reported in one family as the cause of an adult-onset limb-girdle muscular dystrophy (LGMD R21; OMIM# 617232). As the result of a collaborative international effort, we have identified the first cohort of 15 patients with LGMD R21, from nine unrelated families coming from different countries, providing a reliable phenotype-genotype and mechanistic insight. Patients carrying novel mutations in POGLUT1 all displayed a clinical picture of limb-girdle muscle weakness. However, the age at onset was broadened from adult to congenital and infantile onset. Moreover, we now report that the unique muscle imaging pattern of "inside-to-outside" fatty degeneration observed in the original cases is indeed a defining feature of POGLUT1 muscular dystrophy. Experiments on muscle biopsies from patients revealed a remarkable and consistent decrease in the level of the NOTCH1 intracellular domain, reduction of the pool of satellite cells (SC), and evidence of α-dystroglycan hypoglycosylation. In vitro biochemical and cell-based assays suggested a pathogenic role of the novel POGLUT1 mutations, leading to reduced enzymatic activity and/or protein stability. The association between the POGLUT1 variants and the muscular phenotype was established by in vivo experiments analyzing the indirect flight muscle development in transgenic Drosophila, showing that the human POGLUT1 mutations reduced its myogenic activity. In line with the well-known role of the Notch pathway in the homeostasis of SC and muscle regeneration, SC-derived myoblasts from patients' muscle samples showed decreased proliferation and facilitated differentiation. Together, these observations suggest that alterations in SC biology caused by reduced Notch1 signaling result in muscular dystrophy in LGMD R21 patients, likely with additional contribution from α-dystroglycan hypoglycosylation. This study settles the muscular clinical phenotype linked to POGLUT1 mutations and establishes the pathogenic mechanism underlying this muscle disorder. The description of a specific imaging pattern of fatty degeneration and muscle pathology with a decrease of α-dystroglycan glycosylation provides excellent tools which will help diagnose and follow up LGMD R21 patients.

Hayabusa2 arrives at the carbonaceous asteroid 162173 Ryugu-A spinning top-shaped rubble pile.

The Hayabusa2 spacecraft arrived at the near-Earth carbonaceous asteroid 162173 Ryugu in 2018. We present Hayabusa2 observations of Ryugu's shape, mass, and geomorphology. Ryugu has an oblate "spinning top" shape, with a prominent circular equatorial ridge. Its bulk density, 1.19 ± 0.02 grams per cubic centimeter, indicates a high-porosity (>50%) interior. Large surface boulders suggest a rubble-pile structure. Surface slope analysis shows Ryugu's shape may have been produced from having once spun at twice the current rate. Coupled with the observed global material homogeneity, this suggests that Ryugu was reshaped by centrifugally induced deformation during a period of rapid rotation. From these remote-sensing investigations, we identified a suitable sample collection site on the equatorial ridge.

Early Outcomes of Living-Donor Kidney Transplantation With Immunosuppression Therapy Induction With Tacrolimus Extended-Release: A Comparison With Cyclosporine.

BACKGROUND: Extended-release tacrolimus (TacER), administered once daily, offers improved adherence with reduced side effects while still maintaining an immunosuppressive potency equivalent to that of conventional tacrolimus preparations. METHODS: The study included 83 patients who received consecutive living-donor kidney transplants at our facility from June 2013 to December 2016. Comparisons were made between 48 cases of induction with TacER and 35 cases of induction with cyclosporine (CyA). The observation period was 3 months after transplantation. Transplanted kidney function, rejection, infectious disease, lipid abnormalities, and glucose tolerance were compared. RESULTS: The 2 groups showed no significant difference in donor background or transplanted kidney function. Within the 3-month observation period, an acute rejection response was observed in 2 cases in the TacER group and in 8 cases in the CyA group. After transplantation, hyperlipidemia requiring medication was observed more frequently in the CyA group. The 2 groups did not show a marked difference in systemic infection or renal calcineurin inhibitor toxicity in histopathologic examination of the transplanted kidneys 3 months after surgery. DISCUSSION: Proactive use of TacER leads to improved adherence while yielding immunosuppressive potency equivalent to that of conventional tacrolimus preparations; however, tacrolimus has a potent blood sugar-elevating effect; thus, direct comparison with the CyA group is important for assessing the side effects. CONCLUSION: TacER has the potential to also reduce side effects in the early stages after surgery, suggesting its potential as a drug of first choice.

Meta-analysis of the impact of postoperative complications on survival after oesophagectomy for cancer.

BACKGROUND: Oesophagectomy has a high risk of postoperative morbidity. The impact of postoperative complications on overall survival of oesophageal cancer remains unclear. This meta-analysis addressed the impact of complications on long-term survival following oesophagectomy. METHODS: A search of PubMed and Cochrane Library databases was undertaken for systematic review of papers published between January 1995 and August 2016 that analysed the relation between postoperative complications and long-term survival. In the meta-analysis, data were pooled. The main outcome was overall survival (OS). Secondary endpoints included disease-free (DFS) and cancer-specific (CSS) survival. RESULTS: A total of 357 citations was reviewed; 21 studies comprising 11 368 patients were included in the analyses. Overall, postoperative complications were associated with significantly decreased 5-year OS (hazard ratio (HR) 1·16, 95 per cent c.i. 1·06 to 1·26; P = 0·001) and 5-year CSS (HR 1·27, 1·09 to 1·47; P = 0·002). Pulmonary complications were associated with decreased 5-year OS (HR 1·37, 1·16 to 1·62; P < 0·001), CSS (HR 1·60, 1·35 to 1·89; P < 0·001) and 5-year DFS (HR 1·16, 1·00 to 1·33; P = 0·05). Patients with anastomotic leakage had significantly decreased 5-year OS (HR 1·20, 1·10 to 1·30; P < 0·001), 5-year CSS (HR 1·81, 1·11 to 2·95; P = 0·02) and 5-year DFS (HR 1·13, 1·02 to 1·25; P = 0·01). CONCLUSION: Postoperative complications after oesophagectomy, including pulmonary complications and anastomotic leakage, decreased long-term survival.

Size of recurrent laryngeal nerve as a new risk factor for postoperative vocal cord paralysis.

Recurrent laryngeal nerve paralysis (RLNP) is a frequent and serious complication following esophageal cancer surgery. Therefore, this study aims to evaluate the correlation between recurrent laryngeal nerve (RLN) size and RLNP. This was a retrospective study of esophageal cancer patients who underwent thoracoscopic esophagectomy from January 2012 to December 2014. Eighty-four patients were included in the primary analysis. Diameter of the RLN was measured using the digital video recording of surgical procedures by the ratio between scissor and RLN. For evaluation of vocal cord paralysis or paresis, indirect laryngoscopy was performed. Because RLNP more frequently occurs on the left side than the right, we evaluated the correlation between size of the left RLN and left RLNP. The median size of the left RLN was 1.51 mm. We found that the incidence of postoperative left RLNP (Clavien-Dindo classification ≥1) was significantly higher (71% vs. 24%; P < 0.001) in thin RLNs (≤1.5 mm) than in thick RLNs (>1.5 mm). Thin RLN (P < 0.001), female sex (P = 0.025), and being overweight (P = 0.034) were identified as significant independent risk factors for postoperative RLNP. RLNP more easily occurred when the RLN was thin. It is difficult to confirm occurrence of postoperative RLNP before and at extubation. Therefore, it is helpful to know its risk factors including size of RLN.

Genetic analysis of adult leukoencephalopathy patients using a custom-designed gene panel.

Leukoencephalopathies encompass all clinical syndromes that predominantly affect brain white matter. Genetic diagnosis informs clinical management of these patients, but a large part of the genetic contribution to adult leukoencephalopathy remains unresolved. To examine this genetic contribution, we analyzed genomic DNA from 60 Japanese patients with adult leukoencephalopathy of unknown cause by next generation sequencing using a custom-designed gene panel. We selected 55 leukoencephalopathy-related genes for the gene panel. We identified pathogenic mutations in 8 of the 60 adult leukoencephalopathy patients (13.3%): NOTCH3 mutations were detected in 5 patients, and EIF2B2, CSF1R, and POLR3A mutations were found independently in 1 patient each. These results indicate that cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) caused by NOTCH3 mutations is the most frequent adult leukoencephalopathy in our cohort. Moreover, brain imaging analysis indicates that CADASIL patients who do not present typical phenotypes may be underdiagnosed if not examined genetically.

Efficacy of fluoroscopy-guided endoscopic cricopharyngeal myotomy.

BACKGROUND: In endoscopic cricopharyngeal myotomy, surgeons sometimes have concerns about performing an adequate incision with only a narrow intra-cavital view from one direction. In order to overcome these issues, fluoroscopic radiography was used during endoscopic cricopharyngeal myotomy. METHODS: Peri-operative fluoroscopic radiography was utilised to check the position of the diverticuloscope, and to confirm the extent of the incision during surgery. A balloon catheter was used to determine whether the cricopharyngeal muscle was sufficiently resected. Blood loss, peri-operative complications, and functional oral swallowing scale and penetration aspiration scale scores were evaluated. RESULTS: In 12 out of 15 patients, intra-operative fluoroscopic radiography showed the diverticuloscope positioned in the post-cricoid area, and the cricopharyngeal muscle was raised and the surgery completed without adverse effect. Swallowing functions improved following surgery. CONCLUSION: Intra-operative fluoroscopy might improve endoscopic cricopharyngeal myotomy by allowing surgeons to confirm the extent of resection, and by reducing peri-operative morbidity and complication rates.