Long-term outcomes of treatment for achalasia: Laparoscopic Heller myotomy versus POEM.

Achalasia is a rare esophageal motility disorder characterized by nonrelaxation of the lower esophageal sphincter. Laparoscopic Heller myotomy (LHM) is the gold standard treatment for achalasia. Peroral endoscopic myotomy (POEM), a less invasive treatment, is performed extensively, and the selection of the intervention method remains debatable to date. In addition to the availability of extensive studies on short-term outcomes, recent studies on the long-term outcomes of LHM and POEM have shown similar clinical success after 5 y of follow-up. However, gastroesophageal reflux disease (GERD) was more common in patients who had undergone POEM than in those who had undergone LHM. Moreover, existing studies have compared treatment outcomes in various disease states. Some studies have suggested that POEM is superior to LHM for patients with type III achalasia because POEM allows for a longer myotomy. Research on treatment for sigmoid types is currently in progress. However, the long-term results comparing LHD and POEM are insufficient, and the best treatment remains controversial. Further research is needed, and treatment options should be discussed with patients and tailored to their individual needs and pathologies.

Association of changes in appendicular skeletal muscle mass with weight loss and visceral fat reduction after laparoscopic sleeve gastrectomy.

PURPOSE: Laparoscopic sleeve gastrectomy (LSG) drastically affects body composition. However, studies focusing on the association between the changes in the pre-and postoperative muscle mass and postoperative results are limited. We evaluated the association between changes in the muscle mass and weight loss and fat reduction. METHODS: This retrospective study included 29 consecutive patients who underwent both LSG and a bioelectrical impedance analysis (BIA) consecutively. We investigated changes in the body composition on the BIA and visceral fat area (VFA) on computed tomography and correlational changes in muscle mass with weight loss and fat reduction. RESULTS: The total weight loss (%TWL) 12 months after surgery was 30.9%. The VFAs pre- and postoperatively were 224 and 71.0 cm2, respectively. The fat mass (FM), percentage of FM, appendicular skeletal muscle mass (ASM), and skeletal muscle mass index (SMI) decreased from pre- to postoperatively (54.8 vs. 32.2 kg; 49.0 vs. 41.2%, 26.7 vs. 23.9 kg, 9.24 vs. 8.27, respectively), whereas the percentage of ASM (%ASM) increased (22.1 vs. 28.0%). The rate of change in %ASM positively correlated with weight loss and fat reduction (%TWL, rs = 0.65; %VFA loss, rs = 0.62). CONCLUSION: The rate of change in %ASM was positively correlated with weight loss and fat reduction.

Redefining the ontogeny of hyalocytes as yolk sac-derived tissue-resident macrophages of the vitreous body.

BACKGROUND: The eye is a highly specialized sensory organ which encompasses the retina as a part of the central nervous system, but also non-neural compartments such as the transparent vitreous body ensuring stability of the eye globe and a clear optical axis. Hyalocytes are the tissue-resident macrophages of the vitreous body and are considered to play pivotal roles in health and diseases of the vitreoretinal interface, such as proliferative vitreoretinopathy or diabetic retinopathy. However, in contrast to other ocular macrophages, their embryonic origin as well as the extent to which these myeloid cells might be replenished by circulating monocytes remains elusive. RESULTS: In this study, we combine transgenic reporter mice, embryonic and adult fate mapping approaches as well as parabiosis experiments with multicolor immunofluorescence labeling and confocal laser-scanning microscopy to comprehensively characterize the murine hyalocyte population throughout development and in adulthood. We found that murine hyalocytes express numerous well-known myeloid cell markers, but concomitantly display a distinct immunophenotype that sets them apart from retinal microglia. Embryonic pulse labeling revealed a yolk sac-derived origin of murine hyalocytes, whose precursors seed the developing eye prenatally. Finally, postnatal labeling and parabiosis established the longevity of hyalocytes which rely on Colony Stimulating Factor 1 Receptor (CSF1R) signaling for their maintenance, independent of blood-derived monocytes. CONCLUSION: Our study identifies hyalocytes as long-living progeny of the yolk sac hematopoiesis and highlights their role as integral members of the innate immune system of the eye. As a consequence of their longevity, immunosenescence processes may culminate in hyalocyte dysfunction, thereby contributing to the development of vitreoretinal diseases. Therefore, myeloid cell-targeted therapies that convey their effects through the modification of hyalocyte properties may represent an interesting approach to alleviate the burden imposed by diseases of the vitreoretinal interface.

The impact on obesity-related quality of life and eating satisfaction in the early period after laparoscopic sleeve gastrectomy.

INTRODUCTION: Obesity impairs patients' quality of life (QoL). Laparoscopic sleeve gastrectomy (LSG) is a common procedure for patients with severe obesity; however, studies reporting changes in obesity-related QoL are limited. The aim of this study was to assess changes in obesity-related QoL and food tolerance in the early postoperative period. METHODS: We included 20 consecutive patients who underwent LSG between May 2021 and July 2023. We evaluated changes in obesity-related QoL 6 months after surgery using an obesity and weight loss QoL questionnaire (OWLQOL) and a weight related symptom measure (WRSM). Additionally, we assessed eating satisfaction and food tolerance after surgery. RESULTS: The percentages of total weight loss and excess weight loss were 28.5% and 79.1%, respectively. OWLQOL scores and WRSM changed from 36.5 to 73.0 points and from 44.0 to 15.0 points (p = .007, .007), respectively. The food tolerance score decreased from 25 to 21.2 points (p < .001), while eating satisfaction showed no significant change (p = .25). CONCLUSION: Obesity-related QoL is enhanced even in the early postoperative period, without sacrificing eating satisfaction. The findings of this study may provide valuable insights for patients when considering LSG.

IRF8 and MAFB drive distinct transcriptional machineries in different resident macrophages of the central nervous system.

The central nervous system (CNS) includes anatomically distinct macrophage populations including parenchyma microglia and CNS-associated macrophages (CAMs) localized at the interfaces like meninges and perivascular space, which play specialized roles for the maintenance of the CNS homeostasis with the help of precisely controlled gene expressions. However, the transcriptional machinery that determines their cell-type specific states of microglia and CAMs remains poorly understood. Here we show, by myeloid cell-specific deletion of transcription factors, IRF8 and MAFB, that both adult microglia and CAMs utilize IRF8 to maintain their core gene signatures, although the genes altered by IRF8 deletion are different in the two macrophage populations. By contrast, MAFB deficiency robustly affected the gene expression profile of adult microglia, whereas CAMs are almost independent of MAFB. Our data suggest that distinct transcriptional machineries regulate different macrophages in the CNS.

Prognostic significance of preoperative osteosarcopenia on patient' outcomes after emergency surgery for gastrointestinal perforation.

PURPOSE: Sarcopenia is a prognostic predictor in emergency surgery. However, there are no reports on the relationship between osteopenia and in-hospital mortality. This study clarified the effect of preoperative osteosarcopenia on patients with gastrointestinal perforation after emergency surgery. METHODS: We included 216 patients with gastrointestinal perforations who underwent emergency surgery between January 2013 and December 2022. Osteopenia was evaluated by measuring the pixel density in the mid-vertebral core of the 11th thoracic vertebra. Sarcopenia was evaluated by measuring the area of the psoas muscle at the level of the third lumbar vertebra. Osteosarcopenia is defined as the combination of osteopenia and sarcopenia. RESULTS: Osteosarcomas were identified in 42 patients. Among patients with osteosarcopenia, older and female patients and those with an American Society of Anesthesiologists Physical Status of ≥ 3 were significantly more common, and the body mass index, hemoglobin value, and albumin level were significantly lower in these patients than in patients without osteosarcopenia. Furthermore, the osteosarcopenia group presented with more postoperative complications than patients without osteosarcopenia (P < 0.01). In the multivariate analysis, age ≥ 74 years old (P = 0.04) and osteosarcopenia (P = 0.04) were independent and significant predictors of in-hospital mortality. CONCLUSION: Preoperative osteosarcopenia is a risk factor of in-hospital mortality in patients with gastrointestinal perforation after emergency surgery.

Role of modified Glasgow Prognostic Score in patients with achalasia who underwent laparoscopic Heller-myotomy with Dor-fundoplication.

BACKGROUND: Systemic inflammatory response is significant prognostic indicator in patients with various diseases. The relationship between prognostic scoring systems based on the modified Glasgow Prognostic Score (mGPS) and achalasia in patients treated with laparoscopic Heller­myotomy with Dor­fundoplication (LHD) remains uninvestigated. This study aimed to examine the role of mGPS in patients with achalasia. METHODS: 457 patients with achalasia who underwent LHD as the primary surgery between September 2005 and December 2020 were included. We divided patients into the mGPS 0 and mGPS 1 or 2 groups and compared the patients' background, pathophysiology, symptoms, surgical outcomes, and postoperative course. RESULTS: mGPS was 0 in 379 patients and 1 or 2 in 78 patients. Preoperative vomiting and pneumonia were more common in patients with mGPS of 1 or 2. There were no differences in surgical outcomes. Postoperative upper gastrointestinal endoscopy revealed that severe esophagitis was more frequently observed in patients with mGPS of 1 or 2 (P < 0.01). The clinical success was 91% and 99% in the mGPS 0 and mGPS 1 or 2 groups, respectively (P < 0.01). CONCLUSIONS: Although severe reflux esophagitis was more common in patients with achalasia with a high mGPS, good clinical success was obtained regardless of the preoperative mGPS.

Prognostic significance of the preoperative C-reactive protein-albumin-lymphocyte (CALLY) index on outcomes after gastrectomy for gastric cancer.

PURPOSE: Systemic inflammatory response markers are reported to be prognostic for patients with cancer. The C-reactive protein (CRP)-albumin-lymphocyte (CALLY) index has been established as an immuno-nutritional scoring system. The aim of this study was to clarify the impact of the preoperative CALLY index on the outcome of patients undergoing gastrectomy for gastric cancer. METHODS: We analyzed the data of 826 patients who underwent gastrectomy for stage I, II, or III gastric cancer between 2010 and 2017. The CALLY index was defined as (albumin × lymphocyte)/(CRP × 104). RESULTS: The cut-off of the CALLY index was 2. The 147 patients with a preoperative CALLY index < 2 had significantly worse overall survival (OS) and relapse-free survival (RFS) than those with a CALLY index ≥ 2 (P < 0.01, P < 0.01, respectively). Multivariate analysis identified that a CALLY index < 2 (P = 0.02), intraoperative blood loss (P < 0.01), and stage II or III disease (P < 0.01) were independent and significant predictors of worse RFS. A CALLY index < 2 (P = 0.01), intraoperative blood loss (P < 0.01), postoperative complications (P = 0.02), and stage II or III disease (P < 0.01) were independent and significant predictors of worse OS. CONCLUSION: The preoperative CALLY index was independently associated with a poor prognosis for patients after gastrectomy for gastric cancer.

Severe acute interstitial nephritis induced by α-glucosidase inhibitor miglitol in an elderly patient with type 2 diabetic nephropathy.

A 79-year-old male patient with type 2 diabetic nephropathy and hypertension was admitted to our hospital because of acute kidney injury with significantly elevated serum creatinine (8.12 mg/dL) and urinary ß2-microglobulin (ß2MG, 31,748 µg/L) levels. α-Glucosidase inhibitor (α-GI) miglitol, started two weeks prior to presentation, was discontinued because drug-induced acute interstitial nephritis (AIN) was suspected. Renal biopsy revealed AIN and diabetic nephropathy. The drug-induced lymphocyte stimulation test for miglitol was also positive. After the discontinuation of miglitol, the urinary ß2MG levels decreased to the normal range. This case raises the possibility that α-GI miglitol can worsen the renal function in patients with underlying renal dysfunction.

A unique case of bilateral ventricular infiltration by lung adenocarcinoma with paraneoplastic hypereosinophilia.

Existence of poorly differentiated tumour cells or paraneoplastic hypereosinophilia indicates extensive disease progression and poor prognosis in patients with malignancy. When these conditions are present, it is necessary to consider the possibility of intracardiac metastasis even in cases of lung adenocarcinoma.

Laparoscopic sleeve gastrectomy combined with Toupet fundoplication (T-sleeve): A short report of a Japanese obesity patient with gastroesophageal reflux disease.

Laparoscopic sleeve gastrectomy (LSG) is the most frequently performed procedure in bariatric-metabolic surgery (BMS) worldwide, accounting for approximately 90% of BMS procedures in Japan. While numerous studies have reported on the safety and efficacy of LSG, gastroesophageal reflux disease (GERD) remains a major postoperative complication. Although Roux-en-Y gastric bypass (RYGB) is preferred for severe obesity with GERD, it is less suitable for Japanese patients who have a higher risk of gastric cancer due to the remnant stomach which is difficult to observe with esophago-gastro-duodenoscopy. To address de novo and exacerbation GERD after LSG, we conducted LSG with Toupet fundoplication (T-sleeve) for Japanese patients with severe obesity. In our first T-sleeve case, the patient demonstrated sufficient weight loss and improved GERD following surgery. Hence, we suggest that T-sleeve is a feasible option for Japanese patients with obesity and concurrent GERD.

Is it meaningful to add mesh reinforcement to laparoscopic fundoplication for esophageal hiatal hernias in the patients with high risk of hiatal hernia recurrence?

BACKGROUND: While laparoscopic fundoplication is a standard surgical procedure for patients with esophageal hiatal hernias, the postoperative recurrence of esophageal hiatal hernias is a problem for patients with giant hernias, elderly patients, or obese patients. Although there are some reports indicating that reinforcement with mesh is effective, there are differing opinions regarding the use thereof. The aim of this study is to investigate whether mesh reinforcement is effective for laparoscopic fundoplication in patients with esophageal hiatus hernias. METHODS: The subjects included 280 patients who underwent laparoscopic fundoplication as the initial surgery for giant esophageal hiatal hernias, elderly patients aged 75 years or older, and obese patients with a BMI of 28 or higher, who were considered at risk of recurrent hiatal hernias based on the previous reports. Of the subject patients, 91 cases without mesh and 86 cases following the stabilization of mesh use were extracted to compare the postoperative course including the pathology, symptom scores, surgical outcome, and recurrence of esophageal hiatus hernias. RESULTS: The preoperative conditions indicated that the degree of esophageal hiatal hernias was high in the mesh group (p = 0.0001), while the preoperative symptoms indicated that the score of heartburn was high in the non-mesh group (p = 0.0287). Although the surgical results indicated that the mesh group underwent a longer operation time (p < 0.0001) and a higher frequency of intraoperative complications (p = 0.037), the rate of recurrence of esophageal hiatal hernia was significantly low (p = 0.049), with the rate of postoperative reflux esophagitis also tending to be low (p = 0.083). CONCLUSIONS: Mesh reinforcement in laparoscopic fundoplication for esophageal hiatal hernias contributes to preventing the recurrence of esophageal hiatal hernias when it comes to patient options based on these criteria.

Direct neuronal conversion of microglia/macrophages reinstates neurological function after stroke.

Although generating new neurons in the ischemic injured brain would be an ideal approach to replenish the lost neurons for repairing the damage, the adult mammalian brain retains only limited neurogenic capability. Here, we show that direct conversion of microglia/macrophages into neurons in the brain has great potential as a therapeutic strategy for ischemic brain injury. After transient middle cerebral artery occlusion in adult mice, microglia/macrophages converge at the lesion core of the striatum, where neuronal loss is prominent. Targeted expression of a neurogenic transcription factor, NeuroD1, in microglia/macrophages in the injured striatum enables their conversion into induced neuronal cells that functionally integrate into the existing neuronal circuits. Furthermore, NeuroD1-mediated induced neuronal cell generation significantly improves neurological function in the mouse stroke model, and ablation of these cells abolishes the gained functional recovery. Our findings thus demonstrate that neuronal conversion contributes directly to functional recovery after stroke.

[Cellular and molecular heterogeneity of CNS macrophages in health and disease].

The central nervous system (CNS) is a highly complex collection of various cell-types, such as neurons, glial cells, vascular cells, and immune cells, and their complex and dynamic interactions enable to achieve highly sophisticated functions of the CNS. Among such CNS cells are microglia, which are well-known primary CNS macrophages localized in the CNS parenchyma and play a pivotal role in the maintenance of tissue homeostasis. Besides microglia, there are anatomically distinct macrophage populations at the border of the CNS, such as meninge, and perivascular space, called CNS-associated macrophages (CAMs). Recent studies have given novel insights into the nature of CAMs. In this review, I will discuss our current knowledge of the origins, the cellular properties of CNS macrophages.

Postoperative inflammatory markers predict survival in patients after McKeown esophagectomy for esophageal cancer.

BACKGROUND: Preoperative C-reactive protein-to-albumin ratio (CAR) and neutrophil-to-lymphocyte ratio (NLR) are correlated with a poor prognosis of various cancers. The significance of postoperative systemic inflammation markers for prognostic stratification of patients with esophageal cancer (EC) has not been established. Therefore, this study aimed to elucidate the impact of postoperative CAR and NLR on survival in patients with EC for prognostic stratification. METHODS: A total of 235 patients who received curative esophagectomy were analyzed. A Cox proportional hazard model was performed to detect prognostic factors. RESULTS: Multivariate analysis revealed that postoperative CAR ≥ 0.05 (hazard ratio [HR], 1.62; 95% confidence interval [CI], 1.01-2.57) and NLR ≥ 3.0 (HR, 2.81; 95% CI, 1.79-4.40) were independent prognostic factors for overall survival. Meanwhile, postoperative CAR ≥ 0.05 (HR, 1.61; 95% CI, 1.07-2.41) and NLR ≥ 3.0 (HR, 1.92; 95% CI, 1.29-2.85) were also significant prognostic factors for relapse-free survival. In addition, the patient group with postoperative CAR ≥ 0.05 and NLR ≥ 3.0 had the worst survival. CONCLUSIONS: Postoperative CAR ≥ 0.05 and NLR ≥ 3.0 can predict the poor survival of patients who received curative esophagectomy for EC.

Thoracoscopic repair of iatrogenic diaphragmatic hernia following multiple abdominal surgeries: a case report.

Iatrogenic diaphragmatic hernia (IDH) is a rare complication that has been reported after various interventions, including liver transplantation, liver resection and nephrectomy. A surgical procedure for IDH has not been optimized. A 56-year-old man presented to our hospital with a 1-week history of abdominal pain and nausea. His medical history included an open nephrectomy for renal cancer 8 years ago and open distal pancreatectomy for its recurrence 1.5 years ago. Enhanced computed tomography showed IDH with the fornix of the stomach herniating to the left pleural cavity, without radiographic signs of strangulation. His symptoms improved after gastric decompression with nasogastric tube placement, and he underwent elective surgery. The incarcerated stomach was repositioned, and the hernia orifice was closed and reinforced with expanded polytetrafluoroethylene mesh using a thoracoscopic procedure. The patient had an uneventful postoperative course. The operative procedure for IDH should be tailored depending on anatomical alternations after previous surgeries.

Microglial Cytokines Mediate Plasticity Induced by 10 Hz Repetitive Magnetic Stimulation.

Microglia, the resident immune cells of the CNS, sense the activity of neurons and regulate physiological brain functions. They have been implicated in the pathology of brain diseases associated with alterations in neural excitability and plasticity. However, experimental and therapeutic approaches that modulate microglia function in a brain region-specific manner have not been established. In this study, we tested for the effects of repetitive transcranial magnetic stimulation (rTMS), a clinically used noninvasive brain stimulation technique, on microglia-mediated synaptic plasticity; 10 Hz electromagnetic stimulation triggered a release of plasticity-promoting cytokines from microglia in mouse organotypic brain tissue cultures of both sexes, while no significant changes in microglial morphology or microglia dynamics were observed. Indeed, substitution of tumor necrosis factor α (TNFα) and interleukin 6 (IL6) preserved synaptic plasticity induced by 10 Hz stimulation in the absence of microglia. Consistent with these findings, in vivo depletion of microglia abolished rTMS-induced changes in neurotransmission in the mPFC of anesthetized mice of both sexes. We conclude that rTMS affects neural excitability and plasticity by modulating the release of cytokines from microglia.SIGNIFICANCE STATEMENT Repetitive transcranial magnetic stimulation (rTMS) is a noninvasive brain stimulation technique that induces cortical plasticity. Despite its wide use in neuroscience and clinical practice (e.g., depression treatment), the cellular and molecular mechanisms of rTMS-mediated plasticity remain not well understood. Herein, we report an important role of microglia and plasticity-promoting cytokines in synaptic plasticity induced by 10 Hz rTMS in organotypic slice cultures and anesthetized mice, thereby identifying microglia-mediated synaptic adaptation as a target of rTMS-based interventions.

Prognostic significance of preoperative osteopenia on outcomes after gastrectomy for gastric cancer.

Aim: Osteopenia, characterized by low bone mineral density, is a potential prognostic factor for patients with cancer. The aim of this study was to clarify the impact of preoperative osteopenia in patients with gastric cancer (GC) after gastrectomy. Methods: We included 224 patients with GC who underwent gastrectomy between August 2013 and May 2022. Osteopenia was evaluated by measuring the pixel density in the mid-vertebral core of the 11th thoracic vertebra using computed tomography. Results: Osteopenia was identified in 68 patients (30%). The osteopenia group had significantly worse overall survival (OS) and disease-free survival (DFS) than the non-osteopenia group (P < .01, P < .01, respectively). The postoperative hospital stay was significantly longer, and the occurrence of postoperative complications (Clavien-Dindo grade ≥ III) was significantly higher in the osteopenia group (P = .04, P < .01, respectively). In multivariate analysis, osteopenia (P < .01), stage ≥II (P < .01), and R1 or R2 curability (P < .01) were independent and significant predictors of DFS. Additionally, osteopenia (P < .01), intraoperative blood loss (P = .04), stage ≥II (P < .01), and R1 or R2 curability (P < .01) were independent and significant predictors of OS. Conclusion: Preoperative osteopenia was independently associated with a poor prognosis and recurrence in patients who underwent gastrectomy for GC.