Blood flow assessment of gastric tube with indocyanine green fluorescence angiography and postoperative endoscopy during esophagectomy: indocyanine green enhancement time indicated congestion.

BACKGROUND: During esophagectomy, evaluation of blood supply to the gastric tube is critically important to estimate and avoid anastomotic complications. This retrospective study investigated the relationship between indocyanine green (ICG) fluorescence angiography during esophagectomy and postoperative endoscopy findings, especially mucosal color change. METHODS: This study retrospectively collected data from 86 patients who underwent subtotal esophagectomy and reconstruction using a gastric tube for esophageal cancer at the Tokyo Medical and Dental University between 2017 and 2020. The flow speed of ICG fluorescence in the gastric tube was evaluated during the operation. Additionally, the main root of ICG enhancement and pattern of ICG distribution in the gastric tube were evaluated. On postoperative day 1 (POD1), the change in the mucosal color to white, thought to reflect ischemia, or black, thought to reflect congestion of the proximal gastric tube, was evaluated. The correlations between these factors, clinical parameters, and surgical outcomes were evaluated. Univariate and multivariate analyses used logistic regression to identify the risk factors affecting mucosal color change. RESULTS: Multivariate analyses revealed that the only independent significant predictor of mucosal congestion on POD1 was the ICG enhancement time of the right gastric tube tip (odds ratio, 14.49; 95% confidential interval, 2.41-87.24; P = 0.004). CONCLUSIONS: This study indicated that the ICG enhancement time is related to venous malperfusion and congestion rather than arterial malperfusion and ischemia.

Insulin-like growth factor II-producing colonic carcinoma presenting with non-islet cell tumor hypoglycemia: An autopsy report revealing neuroendocrine differentiation in the metastatic foci and literature review.

Non-islet cell tumor hypoglycemia (NICTH) is a very rare symptom of severe hypoglycemia associated with extrapancreatic tumors. It is considered to be caused by insulin-like growth factor (IGF)-II. There have been no autopsy cases of colorectal carcinoma with NICTH confirmed with both serum high molecular weight and tumoral IGF-II. We report the case of a 46-year-old woman with advanced sigmoid colon cancer and liver metastases. She underwent open sigmoidectomy, and histologically, the lesion was a differentiated-type tubular adenocarcinoma. Postoperative chemotherapy was initiated. However, she experienced repeated hypoglycemia attacks 10 months after the operation, while the liver metastases increased. We examined the cause of hypoglycemia, and finally diagnosed her with NICTH associated with high molecular weight IGF-II production, which was proven by Western immunoblot of the serum. She died 12 months after surgery and was examined by autopsy. Liver metastases showed a transition from adenocarcinoma to carcinoma with neuroendocrine differentiation. Immunohistochemistry showed that both metastatic carcinoma of the liver and primary colonic adenocarcinoma were positive for IGF-II. Neuroendocrine differentiation in liver metastases proven by an autopsy may have contributed to tumor growth, which may have exacerbated the symptoms.

Uncertainty among families of patients with cerebrovascular diseases in Japan: association with quality of life and background characteristics.

PURPOSE: To determine the relationship between family uncertainty and family quality of life (QOL) during the recovery period of patients with cerebrovascular disease in Japan, and the factors that influence family uncertainty. METHODS: Data were collected from copies of patient medical files and interviews with family members of 85 patients admitted to two rehabilitation wards in Japan. Family uncertainty was measured using the Japanese version of the Managing Uncertainty in Illness Scale-Family Member form (MUIS-FM) and family QOL using the World Health Organization Five Well-Being Index (WHO-5). Multiple linear regression analysis was applied to investigate associated factors. RESULTS: WHO-5 score was significantly negatively associated with MUIS-FM score (ß = - 0.236, p = 0.03); other factors associated with MUIS-FM score were the Care Shared Decision-Making Questionnaire for care providers score (ß = - 0.384, p < 0.001), Short Intolerance of Uncertainty Scale score (ß = 0.296, p = 0.001), and history of surgical treatment (ß = 0.199, p = 0.032). CONCLUSIONS: Family QOL could be improved by reducing family uncertainty. It is also suggested that promoting shared decision-making between healthcare providers and patients' families may help reduce family uncertainty. It is necessary to take into account not only family intolerance of uncertainty but also uncertainty that varies by type of acute care provided.

Real-world treatment patterns and outcomes in Japanese patients with cervical esophageal cancer.

BACKGROUND: Cervical esophageal cancer (CEC) carries a poor prognosis; however, due to its low incidence, optimal treatment for CEC remains to be established. The purpose of this study was to clarify the current status of treatment of CEC in Japan and obtain evidence for establishing the appropriate treatment method. PATIENTS AND METHODS: We asked specialist training facilities accredited by the Japanese Broncho-Esophageal Society to register data on CEC cases that received curative treatment from January 2009 to December 2014, and conducted a retrospective review of the clinical data of 302 cases registered from 27 facilities. RESULTS: In regard to the initial therapy, of the 302 patients, 33 had undergone endoscopic resection, 41 had undergone surgery, 67 had received induction chemotherapy (IC), and 143 had received chemoradiotherapy (CRT). There were no significant differences in the 5-year overall survival rates among the patient groups that had received surgery, IC or CRT as the initial treatment; advanced stage and recurrent nerve invasion were identified as independent poor prognostic factors. Among the patients who had received IC or CRT as laryngeal-preserving surgery was not indicated at the time of the initial diagnosis, the functional laryngeal preservation rate at the end of the observation period was 34.8%. CONCLUSION: Even in patients with advanced CEC, there is the possibility of preserving the larynx by adopting IC or CRT. However, if the laryngeal function cannot be preserved, there is a risk of complications from aspiration pneumonia, so that the choice of treatment should be made carefully.

A novel needle electrode for intraoperative fourth cranial nerve neurophysiological mapping.

OBJECTIVES: Trochlear nerve (CN-IV) mapping method has not been confirmed to date. The compound muscle action potential (CMAP) of CN-IV cannot be recorded because of the low mapping sensitivity and anatomical characteristics of the superior oblique muscle (SOM). The aim of this study was to evaluate the effectiveness of a novel needle electrode (NNE), for the intraoperative mapping of CN-IV. MATERIALS AND METHODS: The NNEs were inserted in the target extraocular muscles in 19 patients. We compared the CMAP amplitude of the NNE with that of the conventional needle electrode (CNE). Furthermore, we investigated the dissimilarity between the CMAP of the CN-IV and other extraocular cranial nerves (ECNs) and the correlation between the readings of the CN-IV mapping and its postoperative functional outcome. RESULTS: The CMAP of CN-IV has been measured in nine patients (47.4%). The CMAP of CN-IV was distinguishable from other ECNs. The CMAP of the NNE was found to be three times higher than that of the CNE. Although the NNE has shown the potential to record the CN-IV's CMAP, 4 cases ended up having a CN-IV postoperative dysfunction. CONCLUSIONS: For the first time, we confirmed the possibility of intraoperative mapping the CN-IV using an NNE inserted into the SOM. The NNE can also be useful for other neurophysiological monitoring methods.

[Ependymoma of the Sella Turcica and Suprasellar Region].

An ependymoma of the sella turcica and the suprasellar region has been described by only 10 reports in the available literature. We describe similar pathology in a 70-year-old woman who presented with dementia and visual disturbance. Magnetic resonance imaging with gadolinium revealed a mixed contrast-enhanced lesion(maximum diameter 3.5 cm)in the sella turcica and suprasellar area associated with a noncommunicating hydrocephalus. The patient was preoperatively presumptively diagnosed with a craniopharyngioma. The lesion was adherent to the hypothalamus, and the third ventricular floor was completely resected via an endoscopic endonasal transsphenoidal approach. Histopathological findings confirmed an ependymoma. Although her visual disturbance improved, the patient developed postoperative panhypopituitarism. She has had no recurrence for 7 years postoperatively. An ependymoma of the sella turcica and the suprasellar region is extremely rare; establishing the preoperative diagnosis is challenging in such patients. Maximum tumor resection and long-term follow-up are essential for good prognosis.

Identification of six novel susceptibility loci for dyslipidemia using longitudinal exome-wide association studies in a Japanese population.

Recent genome-wide association studies have identified various dyslipidemia-related genetic variants. However, most studies were conducted in a cross-sectional manner. We thus performed longitudinal exome-wide association studies of dyslipidemia in a Japanese population. We used ~244,000 genetic variants and clinical data of 6022 Japanese individuals who had undergone annual health checkups for several years. After quality control, the association of dyslipidemia-related phenotypes with 24,691 single nucleotide polymorphisms (SNPs) was tested using the generalized estimating equation model. In total, 82 SNPs were significantly (P < 2.03 × 10-6) associated with dyslipidemia phenotypes. Of these SNPs, four (rs74416240 of TCHP, rs925368 of GIT2, rs7969300 of ATXN2, and rs12231744 of NAA25) and two (rs34902660 of SLC17A3 and rs1042127 of CDSN) were identified as novel genetic determinants of hypo-HDL- and hyper-LDL-cholesterolemia, respectively. A replication study using the cross-sectional data of 8310 Japanese individuals showed the association of the six identified SNPs with dyslipidemia-related traits.

Two novel susceptibility loci for type 2 diabetes mellitus identified by longitudinal exome-wide association studies in a Japanese population.

Recent genome-wide association studies identified genetic variants that confer susceptibility to type 2 diabetes mellitus (T2DM). However, few longitudinal genome-wide association studies of this metabolic disorder have been reported to date. Therefore, we performed a longitudinal exome-wide association study of T2DM, using 24,579 single nucleotide polymorphisms (SNPs) and repeated measurements from 6022 Japanese individuals. The generalized estimating equation model was applied to test relations of SNPs to three T2DM-related parameters: prevalence of T2DM, fasting plasma glucose level, and blood glycosylated hemoglobin content. Three SNPs that passed quality control were significantly (P<2.26×10-7) associated with two of the three T2DM-related parameters in additive and recessive models. Of the three SNPs, rs6414624 in EVC and rs78338345 in GGA3 were novel susceptibility loci for T2DM. In the present study, the SNP of GGA3 was predicted to be a genetic variant whose minor allele frequency has recently increased in East Asia.

[Repair of Spontaneous Cerebrospinal Fluid Leakage due to Multiple Defects in the Skull Base:A Case Report].

Spontaneous cerebrospinal fluid(CSF)rhinorrhea may have multiple leakage sites, and occasionally, may become difficult to manage. A 46-year-old man was admitted to our hospital presenting with bacterial meningitis that occurred after CSF rhinorrhea. The CSF leak had stopped following conservative medical treatment;however, it recurred immediately. The leakage was assumed to be in the left lateral recess of the sphenoid sinus based on the location of fluid accumulation on the CT and MR images and the nasal endoscopic findings. First, we performed an endoscopic endonasal repair of the CSF leakage sites. There were multiple defects in the roof of the sphenoid sinus, including the left lateral sphenoid recess. These bone defects were repaired with abdominal fat;however, this did not stop the CSF leak. Therefore, he underwent a craniotomy and nasal endoscopy, which were performed simultaneously using a galeal flap. The galeal flap was inserted from the middle of the skull base to the sphenoid sinus to cover the bone defects, and the position was adjusted under the guidance of nasal endoscopy. Moreover, intraoperatively, another meningocele with CSF leak was discovered in the cribriform plate and was repaired using abdominal fat. The CSF leak stopped after the second surgery. It is important to be mindful of possible multiple leakage sites when treating cases of idiopathic CSF leakage;moreover, the determination of the leakage sites can be difficult. A repair surgery using a galeal flap is preferable in cases of multiple CSF leakage sites, such as in this case, because it allows for all defects to be covered and repaired simultaneously.

[Coexisting Symptomatic Adrenocorticotropic Hormone- and Growth Hormone-producing Double Pituitary Adenomas with Difficulty in Tumor Localization:A Case Report].

Double functional pituitary adenomas are rare, and only a few cases of excessive clinical symptoms of both adrenocorticotropic hormone(ACTH)and growth hormone(GH)have been reported. We herein report a case of symptomatic ACTH-and GH-producing double pituitary adenomas, which were discretely located within the same pituitary gland. A 38-year-old woman presented with general malaise, facial and lower limb edema, unexplained weight gain, facial redness, acne, and nasal enlargement. Endocrinological findings matched with the diagnostic criteria for both acromegaly and Cushing's disease. Preoperative magnetic resonance imaging showed a 15-mm cyst-like lesion on the right side of the sellae surrounded by what was thought to be the normal contrast-enhancing pituitary gland. We assumed that the cyst-like lesion was an adenoma and performed endoscopic endonasal transsphenoidal surgery. However, the cyst-like lesion was a parenchymal tumor. Furthermore, the region we considered to be a normal pituitary gland was also found to be an adenoma. Both adenomas were completely resected. The postoperative blood analysis showed ACTH<1.0pg/dL, cortisol 1.8µg/dL, and insulin-like growth factor-1 60ng/mL, all of which were below reference levels. The histopathological examination confirmed the coexistence of two adenomas, a GH-producing adenoma and an ACTH-producing adenoma. We concluded that these adenomas were endocrinologically active within the pituitary gland. Thus, a diagnosis of double pituitary adenomas was made. When treating a patient with symptoms caused by hypersecretion of multiple anterior pituitary hormones, the possibility of coexisting multiple pituitary adenomas should be considered.

[A Surgical Case of Desmoid Tumor in the Transverse Mesocolon with Pancreatic Invasion].

A 40-year-old man with no previous history of abdominal surgery or noteworthy family history presented to our hospital because of a palpable abdominal mass. Abdominal CT revealed a 9 cm diameter mass in the mesocolon. The differential diagnosis included desmoid tumor, and right hemicolectomy with partial resection of the pancreas head and duodenum was performed. Pathologically, the tumor cells were negative for S-100, c-kit, CD34, and desmin but partially positive for a-SMA and slightly for b-catenin. From these findings, desmoid tumor of the mesocolon was diagnosed. Invasion of the pancreas was also found. Desmoid tumor is pathologically benign, but because of its malignant-like characteristics, such as direct invasion and local recurrence, it is treated as a malignant tumor. Desmoid tumors are associated with familial adenomatous polyposis coli and Gardner syndrome, or they arise in patients who have a history of laparotomy or antecedent trauma. In this paper, we report a rare case of resected sporadic desmoid tumor in the mesocolon with pancreatic invasion, together with a review of the literature.

Secondary brain tumors after cranial radiation therapy: A single-institution study.

AIM: To study the probability of developing secondary brain tumors after cranial radiotherapy.Background Patients treated with cranial radiotherapy are at risk for developing secondary brain tumors. PATIENTS AND METHODS: We planned an institutional survey for secondary brain tumors in survivors after cranial irradiation and reviewed the 30-year duration data. Event analysis and cumulative proportion curves were performed to generally estimate the cumulative proportion of developing secondary brain tumors, cavernoma and meningioma at different periods of time. RESULTS: Secondary brain tumors occurred in 21% of cases: 10% were cavernomas, 6% were meningiomas, 3% were skull osteomas, and 1% were anaplastic astrocytoma. The cumulative proportion of developing secondary brain tumor was 6% at 10 years and 20% at 20 years, while the cumulative proportion for developing cavernomas and meningiomas was 16% and 7% at 20 years, respectively. CONCLUSION: Our study shows that patients who received cranial irradiation were at risk of secondary brain tumors such as cavernomas and meningiomas. Thus, a meticulous follow-up of cancer survivors with history of cranial irradiation by an annual MRI scan is justifiable. This will help clinicians to detect secondary brain tumors early and make its management much easier.

[Corticospinal Tract Mapping by Calculating the Ratio of Subcortical to Cortical Stimulation Intensity:A Technical Note].

OBJECTIVE: Motor evoked potentials(MEPs)have been developed and utilized as safe surgical procedures. A correlation between the threshold intensity of direct stimulation MEPs and the distance of the corticospinal tract(CST)has been already established. However, MEPs are affected by anesthesia and patient-related conditions. Here, we describe a unique technique to avoid these effects. METHOD: When tumors developed in proximity to the CST, the transcortical MEP monitoring was done by placing grid electrodes on the primary motor cortex continuously while direct subcortical MEP mapping was conducted with a monopolar probe. The ratios of the subcortical to the transcortical stimulation intensity were calculated. The point at which the ratios reached 50% was defined as the surgical excision limit. DISCUSSION: MEPs are affected by anesthesia, paralysis, body temperature, and other factors. By measuring the ratio of the cortical stimulation intensity instead of the absolute value of the white matter stimulation intensity, various affecting factors can be avoided, and more accurate monitoring can become possible. CONCLUSION: By calculating the ratio of subcortical to cortical stimulation intensity, the corticospinal tract mapping is less likely to be influenced by the stimulation condition or facility setup, and this warrants further investigation.

Identification of nine novel loci related to hematological traits in a Japanese population.

Recent genome-wide association studies have identified various genetic variants associated with hematological traits. Although it is possible that quantitative data of hematological traits are varied among the years examined, conventional genome-wide association studies have been conducted in a cross-sectional manner that measures traits at a single point in time. To address this issue, we have traced blood profiles in 4,884 Japanese individuals who underwent annual health check-ups for several years. In the present study, longitudinal exome-wide association studies were conducted to identify genetic variants related to 13 hematological phenotypes. The generalized estimating equation model showed that a total of 67 single nucleotide polymorphisms (SNPs) were significantly [false discovery rate (FDR) of <0.01] associated with hematological phenotypes. Of the 67 SNPs, nine SNPs were identified as novel hematological markers: rs4686683 of SENP2 for red blood cell count (FDR = 0.008, P = 5.5 × 10-6); rs3917688 of SELP for mean corpuscular volume (FDR = 0.005, P = 2.4 × 10-6); rs3133745 of C8orf37-AS1 for white blood cell count (FDR = 0.003, P = 1.3 × 10-6); rs13121954 at 4q31.2 for basophil count (FDR = 0.007, P = 3.1 × 10-5); rs7584099 at 2q22.3 (FDR = 2.6 × 10-5, P = 8.8 × 10-8), rs1579219 of HCG17 (FDR = 0.003, P = 2.0 × 10-5), and rs10757049 of DENND4C (FDR = 0.008, P = 5.6 × 10-5) for eosinophil count; rs12338 of CTSB for neutrophil count (FDR = 0.007, P = 2.9 × 10-5); and rs395967 of OSMR-AS1 for monocyte count (FDR = 0.008, P = 3.2 × 10-5).

Identification of three genetic variants as novel susceptibility loci for body mass index in a Japanese population.

Recent genome-wide association studies have identified various obesity or metabolic syndrome (MetS) susceptibility loci. However, most studies were conducted in a cross-sectional manner. To address this gap, we performed a longitudinal exome-wide association study to identify susceptibility loci for obesity and MetS in a Japanese population. We traced clinical data of 6,022 Japanese subjects who had annual health check-ups for several years (mean follow-up period, 5 yr) and genotyped ~244,000 genetic variants. The association of single nucleotide polymorphisms (SNPs) with body mass index (BMI) or the prevalence of obesity and MetS was examined in a generalized estimating equation model. Our longitudinal exome-wide association studies detected 21 BMI- and five MetS-associated SNPs (false discovery rate, FDR <0.01). Among these SNPs, 16 have not been previously implicated as determinants of BMI or MetS. Cross-sectional data for obesity- and MetS-related phenotypes in 7,285 Japanese subjects were examined in a replication study. Among the 16 SNPs, three ( rs9491140 , rs145848316 , and rs7863248 ) were related to BMI in the replication cohort ( P < 0.05). In conclusion, three SNPs [ rs9491140 of NKAIN2 (FDR = 0.003, P = 1.9 × 10-5), rs145848316 of KMT2C (FDR = 0.007, P = 4.5 × 10-5), and rs7863248 of AGTPBP1 (FDR = 0.006, P = 4.2 × 10-5)] were newly identified as susceptibility loci for BMI.

Identification of CDC42BPG as a novel susceptibility locus for hyperuricemia in a Japanese population.

Chronic kidney disease and hyperuricemia are serious global health problems. Recent genome-wide association studies have identified various genetic variants related to these disorders. However, most studies have been conducted in a cross-sectional manner. To identify novel susceptibility loci for chronic kidney disease or hyperuricemia, we performed longitudinal exome-wide association studies (EWASs), using ~ 244,000 genetic variants and clinical data of Japanese individuals who had undergone annual health checkups for several years. After establishing quality controls, the association of renal function-related traits in 5648 subjects (excluding patients with dialysis and population outliers) with 24,579 single nucleotide variants (SNVs) for three genetic models (P < 3.39 × 10- 7) was tested using generalized estimating equation models. The longitudinal EWASs revealed novel relations of five SNVs to renal function-related traits. Cross-sectional data for renal function-related traits in 7699 Japanese subjects were examined in a replication study. Among the five SNVs, rs55975541 in CDC42BPG was significantly (P < 4.90 × 10- 4) related to the serum concentration of uric acid in the replication cohort. We also examined the SNVs detected in our longitudinal EWASs with the information on P values in GKDGEN meta-analysis data. Four SNVs in SLC15A2 were significantly associated with the estimated glomerular filtration rate in European ancestry populations, although these SNVs were related to the serum concentration of uric acid with borderline significance in our longitudinal EWASs. Our findings indicate that CDC42BPG may be a novel susceptibility locus for hyperuricemia.

Privacy-preserving search for chemical compound databases.

BACKGROUND: Searching for similar compounds in a database is the most important process for in-silico drug screening. Since a query compound is an important starting point for the new drug, a query holder, who is afraid of the query being monitored by the database server, usually downloads all the records in the database and uses them in a closed network. However, a serious dilemma arises when the database holder also wants to output no information except for the search results, and such a dilemma prevents the use of many important data resources. RESULTS: In order to overcome this dilemma, we developed a novel cryptographic protocol that enables database searching while keeping both the query holder's privacy and database holder's privacy. Generally, the application of cryptographic techniques to practical problems is difficult because versatile techniques are computationally expensive while computationally inexpensive techniques can perform only trivial computation tasks. In this study, our protocol is successfully built only from an additive-homomorphic cryptosystem, which allows only addition performed on encrypted values but is computationally efficient compared with versatile techniques such as general purpose multi-party computation. In an experiment searching ChEMBL, which consists of more than 1,200,000 compounds, the proposed method was 36,900 times faster in CPU time and 12,000 times as efficient in communication size compared with general purpose multi-party computation. CONCLUSION: We proposed a novel privacy-preserving protocol for searching chemical compound databases. The proposed method, easily scaling for large-scale databases, may help to accelerate drug discovery research by making full use of unused but valuable data that includes sensitive information.

Continuous-wave 193.4 nm laser with 120 mW output power.

This Letter describes an all-solid-state continuous-wave, deep-ultraviolet coherent source that generates more than 100 mW of output power at 193.4 nm. The source is based on nonlinear frequency conversion of three single-frequency infrared fiber laser master-oscillator power-amplifier (MOPA) light sources.

Development of a new high-resolution intraoperative imaging system (dual-image videoangiography, DIVA) to simultaneously visualize light and near-infrared fluorescence images of indocyanine green angiography.

BACKGROUND: Intraoperative indocyanine green videoangiography (ICG-VA) has been widely used in vascular surgery, where vessels are clearly shown as white on a black background. However, other structures cannot be observed during ICG-VA. We have developed a new, high-resolution intraoperative imaging system (dual-image VA [DIVA]) to simultaneously visualize both light and near-infrared (NIR) fluorescence images from ICG-VA, allowing observation of other structures. METHODS: The operative field was illuminated via an operating microscope by halogen and xenon lamps with a filter to eliminate wavelengths over 780 nm. In the camera unit, visible light was filtered to 400-700 nm and NIR fluorescence emission light was filtered to 800-900 nm using a special sensor unit with an optical filter. Light and NIR fluorescence images were simultaneously visualized on a single monitor. RESULTS: Our system clearly visualized the operative field together with fluorescence-enhanced blood flow. In aneurysm surgeries, we could confirm incomplete clipping with the neck remnant or with remnant flow into the aneurysm. In cases of arteriovenous malformation or arteriovenous fistula, feeding arteries and draining veins were easily distinguished. CONCLUSIONS: This system allows observation of the operative field and enhanced blood flow by ICG together in real time and may facilitate various types of neurovascular surgery.