Fibroblastic reticular cells regulate intestinal inflammation via IL-15-mediated control of group 1 ILCs.

Fibroblastic reticular cells (FRCs) of secondary lymphoid organs form distinct niches for interaction with hematopoietic cells. We found here that production of the cytokine IL-15 by FRCs was essential for the maintenance of group 1 innate lymphoid cells (ILCs) in Peyer's patches and mesenteric lymph nodes. Moreover, FRC-specific ablation of the innate immunological sensing adaptor MyD88 unleashed IL-15 production by FRCs during infection with an enteropathogenic virus, which led to hyperactivation of group 1 ILCs and substantially altered the differentiation of helper T cells. Accelerated clearance of virus by group 1 ILCs precipitated severe intestinal inflammatory disease with commensal dysbiosis, loss of intestinal barrier function and diminished resistance to colonization. In sum, FRCs act as an 'on-demand' immunological 'rheostat' by restraining activation of group 1 ILCs and thereby preventing immunopathological damage in the intestine.

Glucocorticoids Drive Diurnal Oscillations in T Cell Distribution and Responses by Inducing Interleukin-7 Receptor and CXCR4.

Glucocorticoids are steroid hormones with strong anti-inflammatory and immunosuppressive effects that are produced in a diurnal fashion. Although glucocorticoids have the potential to induce interleukin-7 receptor (IL-7R) expression in T cells, whether they control T cell homeostasis and responses at physiological concentrations remains unclear. We found that glucocorticoid receptor signaling induces IL-7R expression in mouse T cells by binding to an enhancer of the IL-7Rα locus, with a peak at midnight and a trough at midday. This diurnal induction of IL-7R supported the survival of T cells and their redistribution between lymph nodes, spleen, and blood by controlling expression of the chemokine receptor CXCR4. In mice, T cell accumulation in the spleen at night enhanced immune responses against soluble antigens and systemic bacterial infection. Our results reveal the immunoenhancing role of glucocorticoids in adaptive immunity and provide insight into how immune function is regulated by the diurnal rhythm.

A Chimeric IL-7Rα/IL-2Rß Receptor Promotes the Differentiation of T Cell Progenitors into B Cells and Type 2 Innate Lymphoid Cells.

IL-7 and IL-2 are evolutionarily related cytokines that play critical roles in the development and expansion of immune cells. Although both IL-7R and IL-2R activate similar signaling molecules, whether their signals have specific or overlapping functions during lymphocyte differentiation remains unclear. To address this question, we generated IL-7R α-chain (IL-7Rα)/IL-2R ß-chain (IL-24ß) (72R) knock-in mice expressing a chimeric receptor consisting of the extracellular domain of IL-7Rα and the intracellular domain of IL-2Rß under the control of the endogenous IL-7Rα promoter. Notably, this 72R receptor induced higher levels of STAT5 and Akt phosphorylation in T cells. In the periphery of 72R mice, the number of T cells, B cells, and type 2 innate lymphoid cells (ILC2s) was increased, whereas early T cell progenitors and double-negative 2 thymocytes were reduced in the thymus. In addition, cell proliferation and Notch signaling were impaired in the early thymocytes of 72R mice, leading to their differentiation into thymic B cells. Interestingly, ILC2s were increased in the thymus of 72R mice. Early T cell progenitors from 72R mice, but not from wild-type mice, differentiated into NK cells and ILC2-like cells when cocultured with a thymic stromal cell line. Thus, this study indicates that the chimeric 72R receptor transduces more robust signals than the authentic IL-7Rα, thereby inducing the alternative differentiation of T cell progenitors into other cell lineages. This suggests that cytokine receptors may provide instructive signals for cell fate decisions.

A RORE-dependent Intronic Enhancer in the IL-7 Receptor-α Locus Controls Glucose Metabolism via Vγ4+ γδT17 Cells.

The IL-7R regulates the homeostasis, activation, and distribution of T cells in peripheral tissues. Although several transcriptional enhancers that regulate IL-7Rα expression in αß T cells have been identified, enhancers active in γδ T cells remain unknown. In this article, we discovered an evolutionarily conserved noncoding sequence (CNS) in intron 2 of the IL-7Rα-chain (IL-7Rα) locus and named this region CNS9. CNS9 contained a conserved retinoic acid receptor-related orphan receptor (ROR)-responsive element (RORE) and exerted RORγt-dependent enhancer activity in vitro. Mice harboring point mutations in the RORE in CNS9 (CNS9-RORmut) showed reduced IL-7Rα expression in IL-17-producing Vγ4+ γδ T cells. In addition, the cell number and IL-17A production of Vγ4+ γδ T cells were reduced in the adipose tissue of CNS9-RORmut mice. Consistent with the reduction in IL-17A, CNS9-RORmut mice exhibited decreased IL-33 expression in the adipose tissue, resulting in fewer regulatory T cells and glucose intolerance. The CNS9-ROR motif was partially responsible for IL-7Rα expression in RORγt+ regulatory T cells, whereas IL-7Rα expression was unaffected in RORγt-expressing Vγ2+ γδ T cells, Th17 cells, type 3 innate lymphoid cells, and invariant NKT cells. Our results indicate that CNS9 is a RORΕ-dependent, Vγ4+ γδ T cell-specific IL-7Rα enhancer that plays a critical role in adipose tissue homeostasis via regulatory T cells, suggesting that the evolutionarily conserved RORΕ in IL-7Rα intron 2 may influence the incidence of type 2 diabetes.

CD45 alleviates airway inflammation and lung fibrosis by limiting expansion and activation of ILC2s.

Group 2 innate lymphoid cells (ILC2s) are critical for the immune response against parasite infection and tissue homeostasis and involved in the pathogenesis of allergy and inflammatory diseases. Although multiple molecules positively regulating ILC2 development and activation have been extensively investigated, the factors limiting their population size and response remain poorly studied. Here, we found that CD45, a membrane-bound tyrosine phosphatase essential for T cell development, negatively regulated ILC2s in a cell-intrinsic manner. ILC2s in CD45-deficient mice exhibited enhanced proliferation and maturation in the bone marrow and hyperactivated phenotypes in the lung with high glycolytic capacity. Furthermore, CD45 signaling suppressed the type 2 inflammatory response by lung ILC2s and alleviated airway inflammation and pulmonary fibrosis. Finally, the interaction with galectin-9 influenced CD45 signaling in ILC2s. These results demonstrate that CD45 is a cell-intrinsic negative regulator of ILC2s and prevents lung inflammation and fibrosis via ILC2s.

Retinoic acid receptor activity is required for the maintenance of type 1 innate lymphoid cells.

Group 1 innate lymphoid cells (G1-ILCs) are innate immune effectors critical for the response to intracellular pathogens and tumors. G1-ILCs comprise circulating natural killer (NK) cells and tissue-resident type 1 ILCs (ILC1s). ILC1s mainly reside in barrier tissues and provide the initial sources of interferon-γ (IFN-γ) to prime the protecting responses against infections, which are followed by the response of recruited NK cells. Despite such distribution differences, whether local environmental factors influence the behavior of NK cells and ILC1s is unclear. Here, we show that the signaling of retinoic acid (RA), active metabolites of vitamin A, is essential for the maintenance of ILC1s in the periphery. Mice expressing RARα403, a truncated form of retinoic acid receptor α (RARα) that exerts dominant negative activity, in a lymphoid cell- or G1-ILC-specific manner showed remarkable reductions of peripheral ILC1s while NK cells were unaffected. Lymphoid cell-specific inhibition of RAR activity resulted in the reduction of PD-1+ ILC progenitors (ILCPs), but not of common lymphoid progenitors (CLPs), suggesting the impaired commitment and differentiation of ILC1s. Transcriptome analysis revealed that RARα403-expressing ILC1s exhibited impaired proliferative states and declined expression of effector molecules. Thus, our findings demonstrate that cell-intrinsic RA signaling is required for the homeostasis and the functionality of ILC1s, which may present RA as critical environmental cue targeting local type 1 immunity against infection and cancer.

Lung group 2 innate lymphoid cells differentially depend on local IL-7 for their distribution, activation, and maintenance in innate and adaptive immunity-mediated airway inflammation.

Interleukin-7 (IL-7) is a cytokine critical for the development and maintenance of group 2 innate lymphoid cells (ILC2s). ILC2s are resident in peripheral tissues such as the intestine and lung. However, whether IL-7 produced in the lung plays a role in the maintenance and function of lung ILC2s during airway inflammation remains unknown. IL-7 was expressed in bronchoalveolar epithelial cells and lymphatic endothelial cells (LECs). To investigate the role of local IL-7 in lung ILC2s, we generated two types of IL-7 conditional knockout (IL-7cKO) mice: Sftpc-Cre (SPC-Cre) IL-7cKO mice specific for bronchial epithelial cells and type 2 alveolar epithelial cells and Lyve1-Cre IL-7cKO mice specific for LECs. In steady state, ILC2s were located near airway epithelia, although lung ILC2s were unchanged in the two lines of IL-7cKO mice. In papain-induced airway inflammation dependent on innate immunity, lung ILC2s localized near bronchia via CCR4 expression, and eosinophil infiltration and type 2 cytokine production were reduced in SPC-Cre IL-7cKO mice. In contrast, in house dust mite (HDM)-induced airway inflammation dependent on adaptive immunity, lung ILC2s localized near lymphatic vessels via their CCR2 expression 2 weeks after the last challenge. Furthermore, lung ILC2s were decreased in Lyve1-Cre IL-7cKO mice in the HDM-induced inflammation because of decreased cell survival and proliferation. Finally, administration of anti-IL-7 antibody attenuated papain-induced inflammation by suppressing the activation of ILC2s. Thus, this study demonstrates that IL-7 produced by bronchoalveolar epithelial cells and LECs differentially controls the activation and maintenance of lung ILC2s, where they are localized in airway inflammation.

Androgens Alleviate Allergic Airway Inflammation by Suppressing Cytokine Production in Th2 Cells.

Asthma is more common in females than males after adolescence. However, the mechanism of the sex bias in the prevalence of asthma remains unknown. To test whether sex steroid hormones have some roles in T cells during development of asthma, we analyzed airway inflammation in T cell-specific androgen receptor (AR)- and estrogen receptor (ER)-deficient mice. T cell-specific AR-deficient male mice developed severer house dust mite-induced allergic airway inflammation than did control male mice, whereas T cell-specific ERα- and ERß-deficient female mice exhibited a similar degree of inflammation as for control female mice. Furthermore, administration of dihydrotestosterone reduced cytokine production of Th2 cells from control, but not AR-deficient, naive T cells. Transfer of OT-II transgenic AR-deficient Th2 cells into wild-type mice induced severer allergic airway inflammation by OVA than transfer of control Th2 cells. Gene expression profiling suggested that the expression of genes related with cell cycle and Th2 differentiation was elevated in AR-deficient Th2 cells, whereas expression of dual specificity phosphatase (DUSP)-2, a negative regulator of p38, was downregulated. In addition, a chromatin immunoprecipitation assay suggested that AR bound to an AR motif in the 5' untranslated region of the Dusp2 gene in Th2 cells. Furthermore, the Dusp2 promoter with a wild-type AR motif, but not a mutated motif, was transactivated by dihydrotestosterone in a reporter assay. Finally, forced expression of DUSP-2 by retrovirus vector reduced IL-4 expression in Th2 cells. Thus, these results suggest that androgen signaling suppresses cytokine production of Th2 cells by inducing DUSP-2, explaining, in part, the sex bias of asthma after adolescence.

Evaluation of anorectal function using real-time tissue elastography before and after preoperative chemoradiotherapy.

PURPOSE: This study aimed to clarify the relationship between changes in elasticity and anorectal function before and after chemoradiotherapy. METHODS: This is a single-center prospective cohort study (Department of Surgical Oncology, The University of Tokyo). We established a technique to quantify internal anal sphincter hardness as elasticity using transanal ultrasonography with real-time tissue elastography. Twenty-seven patients with post-chemoradiotherapy rectal cancer during 2019-2022 were included. Real-time tissue elastography with transanal ultrasonography was performed before and after chemoradiotherapy to measure internal anal sphincter hardness as "elasticity" (hardest (0) to softest (255); decreased elasticity indicated sclerotic changes). The relationship between the increase or decrease in elasticity pre- and post-chemoradiotherapy and the maximum resting pressure, maximum squeeze pressure, and Wexner score were the outcome measures. RESULTS: A decrease in elasticity was observed in 16/27 (59.3%) patients after chemoradiotherapy. Patients with and without elasticity decrease after chemoradiotherapy comprised the internal anal sphincter sclerosis and non-sclerosis groups, respectively. The maximum resting pressure post-chemoradiotherapy was significantly high in the internal anal sphincter sclerosis group (63.0 mmHg vs. 47.0 mmHg), and a majority had a worsening Wexner score (60.0% vs. 18.2%) compared with that of the non-sclerosis group. Decreasing elasticity (internal anal sphincter sclerosis) correlated with a higher maximum resting pressure (r = 0.36); no correlation was observed between the degree of elasticity change and maximum squeeze pressure. CONCLUSION: Internal anal sphincter sclerosis due to chemoradiotherapy may correlate to anorectal dysfunction.

Nutritional Status Indicators Predict Tolerability to Adjuvant Chemotherapy in Patients with Stage II/III Rectal Cancer Undergoing Neoadjuvant Chemoradiotherapy.

INTRODUCTION: Adjuvant chemotherapy (AC) after radical surgery following preoperative chemoradiotherapy (CRT) for locally advanced rectal cancer (LARC) is now the standard of care. The identification of risk factors for the discontinuation of AC is important for further improvements in survival. We herein examined the prognostic impact of chemotherapy compliance and its relationship with the prognostic nutritional index (PNI) before surgery. METHODS: A total of 335 stage II-III LARC patients who underwent preoperative CRT between 2003 and 2022 at the University of Tokyo Hospital were retrospectively reviewed. We excluded patients with recurrence during AC and those who had not received AC. The relationship between AC and long-term outcomes and that between PNI values and the duration of AC were examined. RESULTS: Thirty-one patients discontinued AC and 62 continued AC. Recurrence-free survival (RFS) was significantly shorter in patients who discontinued AC (p = 0.0056). The discontinuation of AC was identified as an independent risk factor for RFS (hazard ratio [HR]: 2.24, p = 0.0233). Twenty-one patients were classified as having low PNI (less than 40), which correlated with an older age, low body mass index, and incomplete AC. Low PNI was an independent risk factor for a shorter duration of AC (HR: 2.53, p = 0.0123). CONCLUSION: The discontinuation of AC was related to poor RFS in patients with LARC undergoing preoperative CRT. Furthermore, a low PNI value was identified as a risk factor for a shorter duration of AC.

Minimally invasive versus open multivisceral resection for rectal cancer clinically invading adjacent organs: a propensity score-matched analysis.

BACKGROUND: Minimally invasive surgery (MIS), such as laparoscopic and robotic surgery for rectal cancer, is performed worldwide. However, limited information is available on the advantages of MIS over open surgery for multivisceral resection for cases clinically invading adjacent organs. PATIENTS AND METHODS: This was a retrospective propensity score-matching study of consecutive clinical T4b rectal cancer patients who underwent curative intent surgery between 2006 and 2021 at the University of Tokyo Hospital. RESULTS: Sixty-nine patients who underwent multivisceral resection were analyzed. Thirty-three patients underwent MIS (the MIS group), while 36 underwent open surgery (the open group). Twenty-three patients were matched to each group. Conversion was required in 2 patients who underwent MIS (8.7%). R0 resection was achieved in 87.0% and 91.3% of patients in the MIS and open groups, respectively. The MIS group had significantly less blood loss (170 vs. 1130 mL; p < 0.0001), fewer Clavien-Dindo grade ≥ 2 postoperative complications (30.4% vs. 65.2%; p = 0.0170), and a shorter postoperative hospital stay (20 vs. 26 days; p = 0.0269) than the open group. The 3-year cancer-specific survival rate, relapse-free survival rate, and cumulative incidence of local recurrence were 75.7, 35.9, and 13.9%, respectively, in the MIS group and 84.5, 45.4, and 27.1%, respectively, in the open group, which were not significantly different (p = 0.8462, 0.4344, and 0.2976, respectively). CONCLUSION: MIS had several short-term advantages over open surgery, such as lower complication rates, faster recovery, and a shorter hospital stay, in rectal cancer patients who underwent multivisceral resection.

Local excision versus radical surgery for anal squamous cell carcinoma: a multicenter study in Japan.

BACKGROUND: The standard treatment for anal squamous cell carcinoma is chemoradiation therapy (CRT), but there is a possibility of over-treatment for early-stage disease. cTisN0 and cT1N0 disease is currently indicated for local excision, but it is unclear whether the indication of local excision can be expanded to cT2N0 disease. METHODS: 126 patients with cTis-T2N0 anal cancer treated at 47 centers in Japan between 1991 and 2015 were included. Patients were first classified into the CRT group and surgical therapy group according to the initial therapy, and the latter was further divided into local excision (LE) and radical surgery (RS) groups. We compared prognoses among the groups, and analyzed risk factors for recurrence after local excision. RESULTS: The CRT group (n = 87) and surgical therapy group (n = 39) showed no difference in relapse-free survival (p = 0.29) and overall survival (p = 0.94). Relapse-free survival curves in the LE (n = 23) and RS groups (n = 16) overlapped for the initial 3 years, but the curve for the LE group went lower beyond (p = 0.33). By contrast, there was no difference in overall survival between the two groups (p = 0.98). In the LE group, the majority of recurrences distributed in locoregional areas, which could be managed by salvage treatments. Muscular invasion was associated with recurrence after local excision (hazard ratio: 22.91, p = 0.011). CONCLUSION: LE may be applied to selected patients with anal cancer of cTis-T2N0 stage. Given the high risk of recurrence in cases with muscular invasion, it may be important to consider close surveillance and additional treatment in such patients.

Control of the Development, Distribution, and Function of Innate-Like Lymphocytes and Innate Lymphoid Cells by the Tissue Microenvironment.

Recently, considerable attention has been directed toward innate-like T cells (ITCs) and innate lymphoid cells (ILCs) owing to their indispensable contributions to immune responses, tissue homeostasis, and inflammation. Innate-like T cells include NKT cells, MAIT cells, and γδ T cells, whereas ILCs include NK cells, type 1 ILCs (ILC1s), type 2 ILCs (ILC2s), and type 3 ILCs (ILC3s). Many of these ITCs and ILCs are distributed to specific tissues and remain tissue-resident, while others, such as NK cells and some γδ T cells, circulate through the bloodstream. Nevertheless, recent research has shed light on novel subsets of innate immune cells that exhibit characteristics intermediate between tissue-resident and circulating states under normal and pathological conditions. The local microenvironment frequently influences the development, distribution, and function of these innate immune cells. This review aims to consolidate the current knowledge on the functional heterogeneity of ITCs and ILCs, shaped by local environmental cues, with particular emphasis on IL-15, which governs the activities of the innate immune cells involved in type 1 immune responses.

Enhancement of radiation therapy by indoleamine 2,3 dioxygenase 1 inhibition through multimodal mechanisms.

BACKGROUND: Indoleamine 2,3-dioxygenase 1 (IDO1) is an enzyme that converts tryptophan to kynurenine. IDO1 expression is found not only in tumor cells but also in immune cells and is associated with tumor proliferation and immune responses. IDO1 inhibitors and radiation may cooperatively suppress tumor proliferation through the alterations in the Wnt/ß-catenin pathway, cell cycle, and immune response. We investigated the antitumor effects of combination therapy of an IDO1 inhibitor, 1-methyl tryptophan (1-MT), and radiation on colorectal cancer. METHODS: In vitro experiments were conducted using human and murine colon cancer cell lines (HCT116, HT-29, and Colon26). Cell growth inhibition was assessed using a MTS assay and Clonogenic assay. Cells were cultured for 48 h with or without 500 µM 1-MT after exposure to radiation (4 Gy). Cell cycle effects and modulation of Wnt/ß-catenin pathway were evaluated using western blot analysis, flow cytometry, RT-PCR. Subcutaneous Colon26 tumors in BALB/c mice were treated by oral 1-MT (6 mg/mL) for 2 weeks and/or local radiation (10 Gy/10 fr). Bromodeoxyuridine (BrdU) incorporation in tumor cells and expression of differentiation markers of immune cells were evaluated using immunohistochemistry. RESULTS: 1-MT and a small interfering RNA against IDO1 suppressed proliferation of all cell lines, which was rescued by kynurenine. Clonogenic assay showed that administration of 1-MT improved radiosensitivity by suppressing the Wnt/ß-catenin pathway activated by radiation and enhancing cell cycle arrest induced by radiation. Combination therapy showed a further reduction in tumor burden compared with monotherapies or untreated control, inducing the highest numbers of intratumoral CD3 + and CD8 + T cells and the lowest numbers of Foxp3 + and BrdU-positive tumor cells. CONCLUSIONS: The combination of 1-MT and radiation suppressed colon cancer cells in vitro and in vivo via multiple mechanisms.

Preoperative chemoradiotherapy using tegafur/uracil, oral leucovorin, and irinotecan (TEGAFIRI) followed by oxaliplatin-based chemotherapy as total neoadjuvant therapy for locally advanced rectal cancer: the study protocol for a phase II trial.

BACKGROUND: Total neoadjuvant therapy (TNT) is a novel treatment strategy that is an alternative to preoperative chemoradiotherapy (CRT) for locally advanced rectal cancer (LARC). However, an optimal protocol for TNT has not yet been established. The present study will be an open-label, single-arm, single-center trial to develop a new protocol. METHODS: Thirty LARC patients at high risk of distant metastasis will receive CRT consisting of long-course radiation, concurrent with tegafur/uracil, oral leucovorin, irinotecan (TEGAFIRI), followed by mFOLFOX-6 or CAPOX before undergoing surgery. DISCUSSION: Since previous findings showed a high percentage of grade 3-4 adverse events with the TEGAFIRI regimen for CRT and TNT, the primary outcome of this study will be safety and feasibility. Our regimen for CRT consists of the biweekly administration of irinotecan for good patient compliance. The novel combination approach of this treatment may improve the long-term outcomes of LARC. TRIAL REGISTRATION: Japan Registry of Clinical Trials jRCTs031210660.

Clinicopathological Characteristics of Anastomotic Recurrence After Curative Resection for Colorectal Cancer: Comparison With Nonanastomotic Local Recurrences.

BACKGROUND: Anastomotic recurrence is thought to be caused by implantation of tumor cells to the anastomotic line; however, its risk factors and prognostic significance remain unclear. OBJECTIVE: This study aimed to clarify the risk factors for anastomotic recurrence in colorectal cancer and assess the prognosis in comparison to nonanastomotic local recurrence. DESIGN: A single-center retrospective observational study. SETTINGS: The medical records of the study participants were retrospectively collected from the Department of Surgical Oncology at the University of Tokyo Hospital database. PATIENTS: This study included 1584 patients with colorectal cancer who underwent surgical resection between January 2005 and December 2017. We focused on 15 patients who had an anastomotic recurrence. MAIN OUTCOME MEASURES: The main outcome measures were the risk factors of anastomotic recurrence at the primary resection and prognosis data in comparison to that of nonanastomotic local recurrence. RESULTS: There were 15 patients (0.95%) with anastomotic recurrence and 35 (2.21%) with nonanastomotic local recurrence. Univariate analysis revealed that lymph node metastasis and advanced T stage are the risk factors for anastomotic recurrence. The prognosis of patients with anastomotic recurrence was similar to that of those with nonanastomotic local recurrence who underwent resection. LIMITATIONS: The small number of patients with anastomotic recurrence is a major limitation of this study. Additionally, the retrospective study design may have increased the risk of selection bias. CONCLUSIONS: Lymph node metastasis and advanced T stage were associated with anastomotic recurrence. The prognosis of patients with anastomotic recurrence was similar to that with resected nonanastomotic local recurrence. Thus, surveillance should be carefully continued while considering the poor prognosis of patients with anastomotic recurrence. See Video Abstract at http://links.lww.com/DCR/C92 . CARACTERSTICAS CLINICOPATOLGICAS DE LA RECURRENCIA ANASTOMTICA DESPUS DE LA RESECCIN CURATIVA DEL CNCER COLORRECTAL COMPARACIN CON LAS RECURRENCIAS LOCALES NO ANASTOMTICAS: ANTECEDENTES:Se cree que la recurrencia anastomótica es causada por la implantación de células tumorales en la línea anastomótica; sin embargo, los factores de riesgo asociados y el significado en cuanto a pronóstico siguen sin estar claros.OBJETIVO:Este estudio tuvo como objetivo aclarar los factores de riesgo para la recurrencia anastomótica en el cáncer colorrectal y evaluar el pronóstico en comparación con la recurrencia local no anastomótica.DISEÑO:Un estudio observacional retrospectivo de un solo centro.ESCENARIO:Los registros médicos de los participantes del estudio se recopilaron retrospectivamente de la base de datos del Departamento de Cirugía Oncológica del Hospital de la Universidad de Tokio.PACIENTES:Este estudio incluyó a 1584 pacientes con cáncer colorrectal que se sometieron a resección quirúrgica entre enero de 2005 y diciembre de 2017. Nos enfocamos en 15 pacientes que tuvieron recurrencia anastomótica.PRINCIPALES MEDIDAS DE RESULTADO:Las principales medidas de resultado fueron los factores de riesgo de recurrencia anastomótica en la resección primaria y los datos de pronóstico en comparación con la recurrencia local no anastomótica.RESULTADOS:Hubo 15 pacientes (0.95%) con recurrencia anastomótica y 35 (2.21%) con recurrencia local no anastomótica. El análisis univariable reveló que la metástasis en los ganglios linfáticos y el estadio T avanzado son los factores de riesgo para la recurrencia anastomótica. El pronóstico de los pacientes con recidiva anastomótica fue similar al de aquellos con recidiva local no anastomótica sometidos a resección.LIMITACIONES:El pequeño número de pacientes con recurrencia anastomótica es una limitación importante de este estudio. Además, el diseño retrospectivo del estudio puede haber aumentado el riesgo de sesgo de selección.CONCLUSIONES:La metástasis en los ganglios linfáticos y el estadio T avanzado se asociaron con recurrencia anastomótica. El pronóstico de los pacientes con recidiva anastomótica fue similar al de la recidiva local no anastomótica resecada. Por lo tanto, la vigilancia debe continuarse cuidadosamente considerando el mal pronóstico de los pacientes con recurrencia anastomótica. Consulte Video Resumen en http://links.lww.com/DCR/C92 . (Traducción-Dr. Jorge Silva Velazco ).

Prediction of lymph node metastasis of well-differentiated rectal neuroendocrine tumours using multiple diagnostic modalities.

AIM: The preoperative prediction of lymph node metastasis of well-differentiated rectal neuroendocrine tumours is highly desirable and useful in defining surgical indication more accurately. We aimed to evaluate lymph node metastasis in rectal neuroendocrine neoplasms using multiple imaging modalities. METHODS: The clinical records and radiological images of 70 patients with well-differentiated rectal neuroendocrine tumours who received treatment at the University of Tokyo Hospital between 2010 and 2022 were retrospectively analysed. The relationship between evaluation by multiple imaging modalities and pathological lymph node metastasis was analysed. RESULTS: The receiver operating characteristic curves showed that a maximum lymph node diameter ≥4 mm on computed tomography and ≥8 mm on magnetic resonance imaging were the optimal predictive factors for lymph node metastasis. Accumulation in the lymph nodes on somatostatin receptor scintigraphy (P = 0.058) and Delle's findings on colonoscopy (P = 0.014) were also significant predictors of pathological lymph node positivity, and combination of multiple modalities was useful. Pathologically, lymphatic (P = 0.0030)/venous (P = 0.0007) invasion were risk factors for lymph node metastasis. CONCLUSIONS: In addition to pathological risk factors, a combination of multiple radiological imaging modalities is useful for predicting lymph node metastasis in well-differentiated rectal neuroendocrine tumours.

Determination of the positional relationship of the second Houston valve and peritoneal reflection using computed tomographic colonography and magnetic resonance imaging.

PURPOSE: The second Houston valve is used as a surrogate for estimating the position of the peritoneal reflection; however, the concordance between the positions of the valve and peritoneal reflection has not been investigated. This study aimed to clarify this positional relationship. METHODS: The second Houston valve and peritoneal reflection positions were assessed using tomographic colonography and magnetic resonance imaging. In total, 117 patients were enrolled in this study. RESULTS: The positions of the second Houston valve and peritoneal reflection were nearly concordant, although the space between them ranged from - 20.7 to 33.9 mm. A peritoneal reflection located further from the anal verge than the second Houston valve was defined as a shallow peritoneal reflection. Male sex, high body weight, and a high body mass index were significantly correlated with a shallower peritoneal reflection, as determined by a univariate analysis (sex: P = 0.0138, weight: P = 0.0097, body mass index: P = 0.0311). A multivariate analysis revealed a significantly shallower peritoneal reflection in males than in females (odds ratio: 2.75, 95% confidence interval: 1.15-6.56, P = 0.023). CONCLUSIONS: The second Houston valve located near the peritoneal reflection can be a useful surrogate marker for estimating its position. In relatively heavy males, the peritoneal reflection is located more cranially than the second Houston valve.

Surgical outcomes of robotic, laparoscopic, and open low anterior resection after preoperative chemoradiotherapy for patients with advanced lower rectal cancer.

PURPOSE: We investigated the surgical outcomes of robotic low anterior resection (LAR) for lower rectal cancer after preoperative chemoradiotherapy (pCRT). METHODS: A total of 175 patients with lower rectal cancer who underwent LAR after pCRT between 2005 and 2020 were stratified into open (OS, n = 65), laparoscopic (LS, n = 64), and robotic surgery (RS, n = 46) groups. We compared the clinical, surgical, and pathological results among the three groups. RESULTS: The RS and LS groups had less blood loss than the OS group (p < 0.0001). The operating time in the RS group was longer than in the LS and OS groups (p < 0.0001). The RS group had a significantly longer mean distal margin than the LS and OS groups (25.4 mm vs. 20.7 mm and 20.3 mm, respectively; p = 0.026). There was no significant difference in the postoperative complication rate among the groups. The local recurrence rate in the RS group was comparable to those in the LS and OS groups. CONCLUSION: Robotic LAR after pCRT was performed safely for patients with advanced lower rectal cancer. It provided a longer distal margin and equivalent local control rates.

Benefits of a laparoscopic approach for second colorectal resection after colectomy or proctectomy -a retrospective study.

BACKGROUND: A laparoscopic approach generally provides several benefits in patients who undergo colon or rectal surgery without jeopardizing oncological outcomes. However, there is a paucity of studies on comparative outcomes of laparoscopic versus open approaches for second primary colorectal lesions after colectomy or proctectomy. METHODS: From patients with colorectal disease who underwent surgery between 2008 and 2022 at our hospital, we collected 69 consecutive patients who had previous colorectal surgery for this retrospective study. Based on the second surgery approach (laparoscopic or open), patients were classified into the Lap (n = 37) or Op group (n = 32). Patients' baseline data and perioperative and postoperative outcomes were compared between the two groups. RESULTS: Four patients (11%) of the Lap group needed conversion to laparotomy. The intraoperative blood loss was lower in the Lap group than the Op group (median: 45 ml vs. 205 ml, p = 0.001). The time to first bowel movement was shorter in the Lap group than the Op group (median: 2.8 days vs. 3.6 days, p = 0.007). The operative time, frequencies of postoperative morbidities, and overall survival did not differ between the two groups. CONCLUSION: Laparoscopic surgery appeared feasible and beneficial for selected patients undergoing second colorectal resection after colectomy or proctectomy regarding blood loss and bowel function recovery without affecting other outcomes.