Association between fibrosis around the tumor and postoperative infectious complication in patients with esophageal cancer who underwent preoperative therapy.

BACKGROUND: Multidisciplinary treatment combining chemotherapy, chemo radiation therapy (CRT), and surgery has been utilized for advanced esophageal cancer. However, preoperative treatment could cause postoperative inflammation and complications. We hypothesized that fibrosis surrounding tumor tissue caused by preoperative treatment could induce postoperative systemic inflammation and influence postoperative complications. METHODS: Surgical specimens from patients with thoracic esophageal cancer who underwent preoperative CRT (38 cases) or chemotherapy (77 cases) and those who received no preoperative treatment (49 cases) were evaluated to measure the fibrotic area adjacent to the tumor (10 mm from the tumor edge) by applying Azan staining. Pleural effusion and peripheral blood serum interleukin-6 levels were analyzed to evaluate local and systemic postoperative inflammation in 37 patients. RESULTS: The fibrotic areas around the tumors were significantly larger in patients who underwent preoperative CRT than in patients who underwent chemotherapy (p < 0.001) or who had received no preoperative therapy (p < 0.001). Infectious complications were higher in patients who underwent preoperative CRT than chemotherapy (p = 0.047) or surgery alone (p < 0.001). The patients with larger fibrotic areas had more infectious complications (p = 0.028). Multivariate analysis showed that both a large fibrotic area and preoperative CRT were correlated with infectious complications, but not significantly. Pleural effusion interleukin-6 was significantly higher in patients who underwent preoperative CRT than in patients who received no preoperative therapy (p = 0.013). CONCLUSIONS: A large fibrotic peritumoral esophageal tissue area after preoperative treatment could cause postoperative inflammatory response and infectious complications.

Phase II study of S-1 plus docetaxel as first-line treatment for older patients with advanced gastric cancer (OGSG 0902).

BACKGROUND: Although there is insufficient evidence for the treatment of older patients with advanced gastric cancer, fluorouracil combined with platinum chemotherapy has been recognized as a standard first-line treatment for such populations in Japan despite the lack of efficacy and toxicity data. METHODS: Patients aged 75 years or older with advanced gastric cancer were enrolled. S-1 plus docetaxel (docetaxel: 40 mg/m2, day 1; S-1: 80 mg/m2, days 1-14; q21 days) was repeated every 3 weeks. The primary endpoint was overall response rate. Secondary endpoints were safety, progression-free survival, time to treatment failure, and overall survival. The sample size was calculated as 30 under the hypothesis of an expected response rate of 40% and a threshold response rate of 20%, at a power of 90% and a two-sided alpha value of 5%. RESULTS: From February 2010 to January 2015, 31 patients were enrolled and assessed for efficacy and toxicity. The response rate was 45.2% (95% CI 27.3%-64.0%; p = 0.001) and it exceeded the expected response rate set at 40%. Median progression-free survival was 5.8 months, the 1-year survival rate was 58.1%, and the median survival time was 16.1 months. The major grade 3/4 adverse events were neutropenia (58%), febrile neutropenia (13%), anemia (10%), anorexia (10%), and fatigue (6%). CONCLUSIONS: These findings indicate that S-1 plus docetaxel as first-line treatment for older patients is feasible and that it has promising efficacy against advanced gastric cancer.

Indications for neoadjuvant chemotherapy in older patients undergoing esophagectomy for esophageal cancer.

PURPOSE: To investigate the indications for neoadjuvant chemotherapy (NAC) in esophageal cancer patients aged 75 years or older. METHODS: We analyzed data, retrospectively, from 155 patients over 75 years old, who underwent esophagectomy for esophageal cancer between 2010 and 2020. Forty-one patients underwent upfront surgery (US group) and 114 were treated with NAC followed by surgery (NAC group). We compared the patient backgrounds and perioperative outcomes including prognosis, between the two groups. RESULTS: The NAC group patients were significantly younger and had significantly more advanced clinical stage disease than the US group patients. The incidence of postoperative complications was similar in the two groups. Patients with a good pathological response to NAC had a significantly better prognosis than those with a poor response and those in the US group. Among patients with a performance status (PS) of 0, the 5-year OS rate was 56.5% in the NAC group and 38.1% in the US group (HR = 0.63, 95% CI 0.35-1.12). Among those with a PS of 1-2, the 5-year OS rates were 28.1% and 57.1%, respectively (HR = 1.69, 95% CI 0.99-2.89; P = 0.037 for interaction). CONCLUSIONS: NAC did not improve the postoperative prognosis of older esophageal cancer patients with a PS of 1 or higher.

The role of anterior gastropexy in elderly Japanese hiatal hernia patients.

PURPOSE: As Japanese society ages, the number of surgeries performed in elderly patients with hiatal hernia (HH) is increasing. In this study, we examined the feasibility, safety, and potential effectiveness of the addition of anterior gastropexy to hiatoplasty with or without mesh repair and/or fundoplication in elderly Japanese HH patients. METHODS: We retrospectively evaluated 39 patients who underwent laparoscopic HH repair between 2010 and 2021. We divided them into 2 groups according to age: the "younger" group (< 75 years old, n = 21), and the "older" group (≥ 75 years old, n = 18). The patient characteristics, intraoperative data, and postoperative results were collected. RESULTS: The median ages were 68 and 82 years old in the younger and older groups, respectively, and the female ratio was similar between the groups (younger vs. older: 67% vs. 78%, p = 0.44). The older group had more type III/IV HH cases than the younger group (19% vs. 83%, p < 0.001). The operation time was longer in the older group than in the younger group, but there was no significant difference in blood loss, perioperative complications, or postoperative length of stay between the groups. The older group had significantly more cases of anterior gastropexy (0% vs. 78%, p < 0.001) and less fundoplication (100% vs. 67%, p = 0.004) than the younger group. There was no significant difference in HH recurrence between the groups (5% vs. 11%, p = 0.46). CONCLUSIONS: The addition of anterior gastropexy to other procedures is feasible, safe, and potentially effective in elderly Japanese patients with HH.

Prognostic factors and significance of postoperative adjuvant chemotherapy in patients with advanced gastric cancer undergoing neoadjuvant chemotherapy followed by gastrectomy.

PURPOSE: In Japan, gastrectomy with D2 lymph node dissection and postoperative adjuvant chemotherapy are the standard treatments for locally advanced gastric cancer. Neoadjuvant chemotherapy (NAC) is not affected by postgastrectomy syndromes or postoperative complications. This multicenter retrospective study investigated the prognostic factors and significance of postoperative adjuvant chemotherapy in patients with advanced gastric cancer who underwent NAC followed by gastrectomy. METHODS: Consecutive patients (n = 221) with advanced gastric cancer who underwent NAC followed by curative surgery were enrolled in this study. Prognostic factors including postoperative adjuvant chemotherapy were investigated using univariate and multivariate analyses. RESULTS: A multivariate analysis revealed that pathological lymph node metastasis (ypN) status and postoperative adjuvant chemotherapy were independent prognostic factors for the overall and relapse-free survival. Forty-five patients (20.4%) did not receive postoperative adjuvant chemotherapy. There were no significant differences between patients with and without adjuvant chemotherapy for all factors, except age. The most common reason for not undergoing postoperative adjuvant chemotherapy was a poor condition (n = 23). CONCLUSIONS: ypN status and postoperative adjuvant chemotherapy were independent prognostic factors in gastric cancer patients who underwent NAC followed by curative gastrectomy. It is important to maintain the patient's condition during NAC and the perioperative period so that they can receive postoperative adjuvant chemotherapy.

Innovative device for surgical wound irrigation: a preclinical testing and pilot clinical validation study.

INTRODUCTION: Surgical site infection (SSI) poses a substantial postoperative challenge, affecting patient recovery and healthcare costs. While surgical wound irrigation is pivotal in SSI reduction, consensus on the optimal method remains elusive. We developed a novel device for surgical wound irrigation and conducted preclinical and clinical evaluations to evaluate its efficacy and safety. METHODS: Two preclinical experiments using swine were performed. In the washability test, two contaminated wound model were established, and the cleansing rate between the device and the conventional method were compared. In the contamination test, the irrigation procedure with a fluorescent solution assessed the surrounding contamination of drapes. Subsequently, a clinical trial involving patients undergoing abdominal surgery was conducted. RESULTS: The washability test demonstrated significantly higher cleansing rates with the device method (86.4% and 82.5%) compared to the conventional method (65.2% and 65.1%) in two contamination models. The contamination test revealed a smaller contaminated region with the device method than the conventional method. In the clinical trial involving 17 abdominal surgery cases, no superficial SSIs or adverse events related to device use were observed. CONCLUSIONS: Our newly developed device exhibits potential for achieving more effective and safe SSI control compared to conventional wound irrigation.

Combination of pimitespib (TAS-116) with sunitinib is an effective therapy for imatinib-resistant gastrointestinal stromal tumors.

Despite the effectiveness of imatinib, most gastrointestinal stromal tumors (GISTs) develop resistance to the treatment, mainly due to the reactivation of KIT tyrosine kinase activity. Sunitinib, which inhibits the phosphorylation of KIT and vascular endothelial growth factor (VEGF) receptor, has been established as second-line therapy for GISTs. The recently-developed heat shock protein 90 (HSP90) inhibitor pimitespib (PIM; TAS-116) demonstrated clinical benefits in some clinical trials; however, the effects were limited. The aim of our study was therefore to clarify the effectiveness and mechanism of the combination of PIM with sunitinib for imatinib-resistant GISTs. We evaluated the efficacy and mechanism of the combination of PIM with sunitinib against imatinib-resistant GIST using imatinib-resistant GIST cell lines and murine xenograft models. In vitro analysis demonstrated that PIM and sunitinib combination therapy strongly inhibited growth and induced apoptosis in imatinib-resistant GIST cell lines by inhibiting KIT signaling and decreasing auto-phosphorylated KIT in the Golgi apparatus. In addition, PIM and sunitinib combination therapy enhanced antitumor responses in the murine xenograft models compared to individual therapies. Further analysis of the xenograft models showed that the combination therapy not only downregulated the KIT signaling pathway but also decreased the tumor microvessel density. Furthermore, we found that PIM suppressed VEGF expression in GIST cells by suppressing protein kinase D2 and hypoxia-inducible factor-1 alpha, which are both HSP90 client proteins. In conclusion, the combination of PIM and sunitinib is effective against imatinib-resistant GIST via the downregulation of KIT signaling and angiogenic signaling pathways.

Risk stratification of oesophageal squamous cell carcinoma using change in total lesion glycolysis and number of PET-positive lymph nodes.

BACKGROUND: The efficacy of neoadjuvant chemotherapy (NACT) correlates with patient survival in oesophageal squamous cell carcinoma (OSCC), but optimal evaluation of the treatment response based on PET-CT parameters has not been established. METHODS: We analysed 226 OSCC patients who underwent PET-CT before and after NACT followed by surgery. We assessed SUVmax, metabolic tumour volume (MTV), and total lesion glycolysis (TLG) for the primary tumour and the number of PET-positive lymph nodes before and after NACT to predict patient survival. RESULTS: In a stepwise analysis, we defined 60%, 80%, and 80% as the optimal cut-off values for SUVmax, MTV, and TLG reduction, respectively, to distinguish responders and non-responders to NACT. In the ROC analysis, the TLG reduction rate was the best predictor of recurrence among PET-CT parameters. The TLG responders achieved significantly more favourable prognoses than non-responders (2-year progression-free survival [PFS] rate: 64.1% vs. 38.5%; P = 0.0001). TLG reduction rate (HR 2.58; 95% CI 1.16-5.73) and the number of PET-positive lymph nodes after NACT (HR 1.79; 95% CI 1.04-3.08) were significant independent prognostic factors. CONCLUSIONS: TLG reduction is the best predictor of prognosis. Preoperative PET-CT evaluation of both the primary tumour and lymph nodes could accurately stratify risk in OSCC patients.

Density and maturity of peritumoral tertiary lymphoid structures in oesophageal squamous cell carcinoma predicts patient survival and response to immune checkpoint inhibitors.

BACKGROUND: Tertiary lymphoid structures (TLSs) are ectopic lymphoid aggregates in non-lymphoid tissues, which are associated with improved prognosis in some cancer types. This study aimed to investigate the clinical significance of TLSs in oesophageal cancer (EC). METHODS: In a series of 316 EC surgical specimens from two different institutes, we evaluated the density and maturity of peritumoral TLSs using haematoxylin/eosin, immunohistochemistry, and multiplex immunofluorescence staining. We analysed the association between TLSs and clinicopathological parameters. The clinical significance of TLSs was further evaluated in a different cohort of 34 patients with recurrent EC treated with anti-PD-1 antibody. RESULTS: Tumours with high TLS density predominantly consisted of matured TLSs. High TLS density was significantly associated with less advanced tumour stage, absence of lymphatic/vascular invasion, better serum nutrition parameters (neutrophils count, albumin, neutrophil-to-lymphocyte ratio, and prognostic nutritional index), and prolonged survival. This survival trend was more remarkable in cases with matured TLSs, which represented an increased population of CD138+ plasma cells. In the second EC cohort, TLS density predicted the clinical response to anti-PD-1 antibody and patient survival. CONCLUSION: The density and maturity of peritumoral TLSs are useful parameters for predicting long-term survival and response to anti-PD-1 antibody treatment in EC patients.

Immunoscore Signatures in Surgical Specimens and Tumor-Infiltrating Lymphocytes in Pretreatment Biopsy Predict Treatment Efficacy and Survival in Esophageal Cancer.

OBJECTIVES: Tumor-infiltrating lymphocytes (TILs) have long been recognized as playing an important role in tumor immune microenvironment. Lately, the Immunoscore (IS) has been proposed as a new method of quantifying the number of TILs in association with patient survival in several cancer types. METHODS: In 300 preoperatively untreated esophageal cancer (EC) patients who underwent curative resection at two different institutes, immunohistochemical staining using CD3 and CD8 antibodies was performed to evaluate IS, as objectively scored by auto-counted TILs in the tumor core and invasive margin. In addition, in pre-neoadjuvant chemotherapy (pre-NAC) endoscopic biopsies of a different cohort of 146 EC patients who received NAC, CD3, and CD8 were immunostained to evaluate TIL density. RESULTS: In all cases, the IS-high (score 3-4) group tended to have better survival [5-year overall survival (OS) of the IS-high vs low group: 77.6 vs 65.8%, P = 0.0722] than the IS-low (score 1-2) group. This trend was more remarkable in cStage II-IV patients (70.2 vs 54.5%, P = 0.0208) and multivariate analysis of OS further identified IS (hazard ratio 2.07, P = 0.0043) to be an independent prognostic variable. In preNAC biopsies, NAC-responders had higher densities than non-responders of both CD3 + ( P = 0.0106) and CD8 + cells ( P = 0.0729) and, particularly CD3 + cell density was found to be an independent prognostic factor (hazard ratio 1.75, P = 0.0169). CONCLUSIONS: The IS signature in surgical specimens and TIL density in preNAC- biopsies could be predictive markers of clinical outcomes in EC patients.

The tissue-resident marker CD103 on peripheral blood T cells predicts responses to anti-PD-1 therapy in gastric cancer.

BACKGROUND: Immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment. Since clinical benefits are limited to a subset of patients, we aimed to identify peripheral blood biomarkers that predict the efficacy of the anti-programmed cell death protein 1 (PD-1) antibody (nivolumab) in patients with gastric cancer. METHODS: We collected peripheral blood samples from gastric cancer patients (n = 29) before and after treatment with nivolumab and investigated the relationship between the frequency of surface or intracellular markers among nivolumab-binding PD-1+CD8+ T cells and treatment responses using multicolor flow cytometry. The tumors, lymph nodes, and peripheral blood of gastric cancer patients who underwent gastrectomy following nivolumab treatment were collected, and nivolumab-binding PD-1+CD8+ T cells in these tissue samples were characterized. RESULTS: Patients with a high frequency of CD103 among PD-1+CD8+ T cells in peripheral blood 2 weeks after the start of treatment had significantly better progression-free survival than the low group (P = 0.032). This CD103+PD-1+CD8+ T cell population mainly consisted of central memory T cells, showing the high expression of Ki-67 and few cytotoxic granules. In contrast, effector memory T cells were more frequently observed among CD103+PD-1+CD8+ T cells in tumors, which implied a change in the differentiated status of central memory T cells in lymph nodes and peripheral blood to effector memory T cells in tumors during the treatment with ICIs. CONCLUSIONS: A high frequency of CD103 among PD-1+CD8+ T cells 2 weeks after nivolumab treatment in patients with advanced gastric cancer may be a useful biomarker for predicting the efficacy of anti-PD-1 therapy.

Clinical Significance of Intramural Metastasis as an Independent Prognostic Factor in Esophageal Squamous Cell Carcinoma.

BACKGROUND: Although intramural metastasis (IM) in esophageal cancer is considered a poor prognostic factor, there are only limited reports detailing its clinicopathologic characteristics and prognostic impact. PATIENTS AND METHODS: We retrospectively included patients with esophageal squamous cell carcinoma (ESCC) with esophagectomy at our institution between 2010 and 2016. We compared patients with intramural metastases (IMs) (IM group) versus those without IMs (non-IM group) to clarify the clinical significance of intramural metastasis in ESCC. RESULTS: A total of 23 (3.9%) out of all 597 patients were identified to have IM. The IMs were located on the cranial side in 13 (56.5%) and caudal side in 10 (43.5%) of the primary tumor, with two multiple cases. The IM group, compared with the non-IM group, was associated with higher percentage of cN-positive (91.3 versus 67.9%, P = 0.02), pN-positive (82.6 versus 55.9%, P = 0.04), and pM(lym)-positive (30.4 versus 12.5%, P = 0.02) cases. Five-year recurrence-free survival (RFS) was significantly worse in the IM group than the non-IM group (14.9 versus 55.0 %, P < 0.001). Multivariable analysis of recurrence-free survival identified pT (HR 1.74, 95% CI 1.36-2.23, P < 0.001), pN (HR 2.11, 95% CI 1.60-2.78, P < 0.001), histological classification (HR 1.68, 95% CI 1.21-2.35, P = 0.002), and pM(LYM) (HR 1.64, 95% CI 1.64-2.95, P < 0.001), along with presence of IM (HR 2.24, 95% CI 1.37-3.64, P < 0.001) to be independent prognostic factors. Lymphatic (65.2 versus 24.9%, P < 0.001) and hepatic (26.1 versus 6.8%, P = 0.005) recurrences were significantly more common in the IM group than in the non-IM group. CONCLUSIONS: IM was shown to be associated with dismal survival after surgery. A treatment strategy emphasizing more intensive systemic control should be considered for patients with ESCC with IM.

Preoperative Comprehensive Geriatric Assessment Predicts Postoperative Risk in Older Patients with Esophageal Cancer.

BACKGROUND: Preoperative risk assessment is important in older patients because they often have comorbidities and impaired organ function. We performed preoperative comprehensive geriatric assessment (CGA) for older patients with esophageal cancer. PATIENTS AND METHODS: A total of 217 patients over 75 years old who underwent esophagectomy for thoracic esophageal cancer were analyzed. The CGA was performed preoperatively and included the Mini-Mental State Examination (MMSE), Geriatric Depression Score (GDS), vitality index, Barthel index, and instrumental activities of daily living (IADL). We defined the robust group as patients with normal function on every instrument, and the pre-frail and frail groups as those with functional impairment on one instrument or two or more instruments, respectively. We assessed how the CGA correlated with postoperative complications and prognosis. RESULTS: Of the 217 patients, 86 (39.6%) were in the robust group, 68 (31.3%) in the pre-frail group, and 63 (29.0%) in the frail group. Postoperative pneumonia (P = 0.026) and anastomotic leakage (P = 0.032) were significantly more common in the frail group. The frail group had a significantly longer postoperative hospitalization period (P = 0.016) and significantly lower rate of discharge to home (P = 0.016). Overall survival (OS) was significantly worse in the frail group (5-year overall survival rate, frail group versus others, 37.8% versus 52.0%, P = 0.046), but it was not significant on multivariate analysis. CONCLUSIONS: The preoperative CGA in older patients with esophageal cancer was associated with risk of postoperative complications.

Gas leakages from gastrointestinal endoscopy system-its visualization and semi-quantification utilizing schlieren optical system in the swine models.

BACKGROUND AND AIMS: With the global epidemic of SARS-CoV-2, there has been a growing concern regarding the risk of aerosol exposure to healthcare workers and patients during medical/surgical interventions. The Schlieren device is capable of visualizing fine gas-flows by using refractive index differences in the medium. We aimed to reveal the existence of gas leakage from gastro-intestinal endoscopy system by utilizing Schlieren device and to clarify the factors which relates to the amount of gas leakage. METHODS: The experiments were performed on the excised swine stomach while maintaining a constant pressure environment in the stomach. The System Schlieren (SS100,KatoKoken) was used to visualize possible gas leakages from forceps plugs of endoscopy. We attempted to semi-quantify the leakage by referring to the image of the gas from the forceps plug and by measuring the initial velocity and diffusion area of the leakage. RESULTS: Regardless of the type of forceps plugs, a certain amount of leakage was detected during both insertion and removal of forceps. The initial velocity and the diffusion area of the leakage increased with the increase in intragastric pressure. Semi-quantitative comparison showed that there was a difference in the amount of gas leakage among various forceps plugs. Furthermore, the amount of gas leakage was significantly greater in the forceps plugs that were used repeatedly. CONCLUSION: It was possible to visualize gas leakages from the gastrointestinal endoscope system using the Schlieren optical device. Avoiding too high intragastric pressure and not using deteriorated plugs may reduce the risk of aerosol exposure.

Miliary tuberculosis-associated hemophagocytic lymphohistiocytosis with a high level of soluble interleukin-2 receptor successfully treated with concomitant recombinant thrombomodulin: A case report.

Hemophagocytic lymphohistiocytosis (HLH) is a fatal disease characterized by a highly inflammatory state due to the abnormal activation of T lymphocytes and macrophages. Miliary tuberculosis (MTB) is a rare cause of HLH and its clinical appearances occasionally resembles that of intravascular lymphoma (IVL). A 76-year-old woman presented with persistent fever and fatigue. Abnormal laboratory findings showing thrombocytopenia (13,000/µL), hypofibrinogenemia (101 mg/dL), hyperferritinemia (2,312 ng/mL), and markedly elevated soluble interleukin-2 receptor (sIL-2R) level (32,200 U/mL), in addition, hemophagocytosis in the bone marrow (BM) smear, were suggestive of IVL-associated HLH. The pathology of the BM biopsy specimen showed granuloma with non-caseous necrosis, and culture tests using sputum, gastric fluid, urine, and peripheral and bone marrow blood revealed the presence of Mycobacterium tuberculosis, leading to the final diagnosis of MTB-associated HLH. Anti-TB medications and corticosteroids were administered, but thrombocytopenia, hypofibrinogenemia, and hyperferritinemia persisted. Concomitant use of recombinant thrombomodulin (rTM) enabled regression of clinical status. In this case, BM biopsy served as the diagnosis of MTB-associated HLH, although IVL-associated HLH is initially suspected by an extremely high level of sIL-2R. Furthermore, this case report informs that using rTM could improve the outcomes of MTB-associated HLH.

Plasma trough concentration of imatinib and its effect on therapeutic efficacy and adverse events in Japanese patients with GIST.

BACKGROUND: Imatinib mesylate (IM) is the standard chemotherapy for patients with gastrointestinal stromal tumors (GISTs) and has a favorable safety profile. Pharmacokinetics (PK), such as plasma trough concentration (Cmin), varies among patients, requiring the need for therapeutic drug monitoring (TDM) during IM administration. Despite some reports from overseas, the relationship between Cmin, adverse events (AEs), and treatment efficacy in Japanese patients with GIST has still been lacking. This study aimed to investigate the relationship between IM plasma concentration and AEs in Japanese patients with GISTs. METHODS: This retrospective study analyzed the data of 83 patients who underwent IM treatment for GISTs at our institution between May 2002 and September 2021. RESULTS: The IM Cmin was associated with any grade of AEs (with AEs vs. without AEs = 1294 (260-4075) vs. 857 (163-1886) ng/mL, P < 0.001), edema (with edema vs. without edema = 1278 (634-4075) vs. 1036 (163-4069) ng/mL, P = 0.017), and fatigue (with fatigue vs. without fatigue = 1373 (634-4069) vs. 1046 (163-4075) ng/mL, P = 0.044). Moreover, a Cmin ≥ 1283 ng/mL was a risk factor for severe AEs. The median progression-free survival (PFS) was 3.04 years in the lowest Cmin tertile (T1, < 917 ng/mL) compared with 5.90 years for T2 and T3 (P = 0.010). CONCLUSION: Edema and fatigue are potentially associated with IM plasma trough concentrations of ≥ 1283 ng/mL in Japanese patients with GISTs. Further, maintaining an IM plasma trough concentration above 917 ng/mL may improve PFS.

Oral frailty is a risk factor for body weight loss after gastrectomy: a single-center, retrospective study.

BACKGROUND: Body weight loss (BWL) is a serious complication of gastrectomy in patients with gastric cancer (GC). Nutritional intervention alone is inadequate for preventing BWL, and a new approach is needed. Oral frailty among older adults has recently attracted attention. This study aimed to investigate masticatory ability and BWL after gastrectomy. METHODS: This was a single-center, retrospective study. Functional tooth units (FTU) were used to measure masticatory ability. Patients with FTU < 4 were defined as low FTU group and FTU ≥ 4 as high FTU group. The BWL was compared between the two groups. RESULTS: Sixty patients who underwent distal gastrectomy for GC from March 2022 to January 2023 were enrolled in this study. The median FTU was 3 (range 0-12). The low-FTU group (FTU < 4) included 29 patients, while the high-FTU group (FTU ≥ 4) included 31 patients. The %BWL in the low FTU group was significantly higher than that in the high-FTU group at 1 and 3 months (p = 0.003 and p = 0.017, respectively). The risk factors associated with a %BWL > 5 at 1 and 3 months after gastrectomy were analyzed using logistic regression analysis. Only FTU < 4 was an independent risk factor after gastrectomy for GC in univariate and multivariate analyses (p = 0.028 and p = 0.006, respectively). CONCLUSIONS: Low FTU in patients with preoperative GC was a risk factor for %BWL 1 and 3 months postoperatively. Appropriate oral interventions may be useful in improving the postoperative nutritional status after gastrectomy.

The impact of postoperative blood glucose levels on complications and prognosis after esophagectomy in patients with esophageal cancer.

PURPOSE: This study aimed to characterize postoperative blood glucose fluctuation in patients who underwent esophagectomy for esophageal cancer, and to define its impact on complications and prognosis. METHODS: The subjects of this retrospective study were 284 patients who underwent esophagectomy at Osaka University Hospital between 2015 and 2017. Data analyzed included clinicopathological background, the immediate postoperative blood glucose level (IPBG), postoperative blood glucose variability (PBGV), insulin dosage, postoperative complications, and prognosis. RESULTS: The median IPBG and PBGV were 170 (64-260) mg/dl and 64.5 (11-217) mg/dl, respectively. Postoperative pneumonia was more common in patients with PBGV > 100 mg/dl (P = 0.015). Patients with IPBG < 170 mg/dl had significantly worse 5-year overall survival (OS) and 5-year recurrence-free survival (RFS) than those with IPBG > 170 mg/dl (54.5% vs. 80.4%, respectively, [P < 0.001] and 44.3% vs. 69.3%, respectively, [P = 0.001]). The 5-year OS rates were 43.5%, 68.3%, 80.6%, and 79.0% for patients with IPBG < 154, 154-170, 170-190, and ≥ 190 mg/dl, respectively. The corresponding 5-year RFS rates were 38.1%, 52.4%, 77.0%, and 61.3%, respectively. Multivariate analysis revealed that IPBG < 154 mg/dl and pathological stage were independent poor prognostic factors for OS. CONCLUSION: PBGV was associated with postoperative pneumonia, and low IPBG was an independent poor prognostic factor for patients with esophageal cancer.

Management of abdominal gas leakage from surgical trocars in laparoscopic surgery: a preclinical study.

Introduction: There is an ongoing concern about the potential infectious risk due to pneumoperitoneal gas leakage from surgical trocars in laparoscopic surgery. We aimed to visually confirm the presence of leakage from trocars and investigate the changes in the leakage scale according to intra-abdominal pressures and trocar types. Material and methods: We established a porcine pneumoperitoneum model and performed experimental forceps manipulation using 5-mm grasping forceps with 12-mm trocars. The gas leakage, if any, was imaged using a Schlieren optical system, which can visualize minute gas flow invisible to the naked eye. For measuring the scale, we calculated the gas leakage velocity and area using image analysis software. Four types of unused and exhausted disposable trocars were compared. Results: Gas leakage was observed from trocars during forceps insertion and removal. Both the gas leakage velocity and area increased as the intra-abdominal pressure increased. Every type of trocar we handled was associated with gas leakage, and exhausted disposable trocars had the largest scale gas leakage. Conclusions: We confirmed gas leakage from trocars during device traffic. The scale of leakage increased with high intra-abdominal pressure and with the use of exhausted trocars. Current protection against gas leakage may not be sufficient and new surgical safety measures and device development may be needed in the future.

Safety and efficacy of double-tract reconstruction with remnant stomach conservation in esophagectomy for patients with a history of distal gastrectomy.

BACKGROUND: Total gastrectomy with jejunum or colon reconstruction after esophagectomy is commonly performed in patients with esophageal cancer who have a history of distal gastrectomy. In this study, we examined the safety and effectiveness of double-tract reconstruction (DTR) with preservation of the remnant stomach for said patient population. METHODS: Twenty-seven esophageal cancer patients with a history of distal gastrectomy who underwent transthoracic esophagectomy between 2010 and 2020 in our institution were retrospectively analyzed; 15 of these patients underwent DTR, whereas 12 underwent completion gastrectomy with jejunal Roux-en-Y reconstruction (RYR). Short-term outcomes, postoperative nutritional indexes, and ghrelin levels were evaluated. Moreover, abdominal lymph-node metastasis and recurrence, which were removed by total residual gastrectomy, were examined to determine the oncological validity of residual stomach preservation. RESULTS: There was no metastasis and recurrence in abdominal lymph nodes, such as #4sa or #11d, which were removed by total residual gastrectomy. Total operation time did not differ between the groups (P = 0.4247). The blood loss for the DTR group was 495 ± 446 mL, whereas that for the RYR group was 844 ± 575 mL (P = 0.0168). Clavien-Dindo grade III or higher complications were not significantly different between the groups (P = 0.7063). The rates of serum total protein values at 6 months in the DTR and RYR groups were 112% ± 12.2% and 102.6% ± 10.7% (P = 0.0403), respectively. The prognostic nutritional indexes at 6 months in the DTR and RYR groups were 108.6% ± 14.5% and 83.2% ± 42.6% (P = 0.0376), respectively. CONCLUSIONS: DTR in esophagectomy is safe and effective for patients with a history of distal gastrectomy.