Analyses of a Mutant Foxp3 Allele Reveal BATF as a Critical Transcription Factor in the Differentiation and Accumulation of Tissue Regulatory T Cells.

Foxp3 controls the development and function of regulatory T (Treg) cells, but it remains elusive how Foxp3 functions in vivo. Here, we established mouse models harboring three unique missense Foxp3 mutations that were identified in patients with the autoimmune disease IPEX. The I363V and R397W mutations were loss-of-function mutations, causing multi-organ inflammation by globally compromising Treg cell physiology. By contrast, the A384T mutation induced a distinctive tissue-restricted inflammation by specifically impairing the ability of Treg cells to compete with pathogenic T cells in certain non-lymphoid tissues. Mechanistically, repressed BATF expression contributed to these A384T effects. At the molecular level, the A384T mutation altered Foxp3 interactions with its specific target genes including Batf by broadening its DNA-binding specificity. Our findings identify BATF as a critical regulator of tissue Treg cells and suggest that sequence-specific perturbations of Foxp3-DNA interactions can influence specific facets of Treg cell physiology and the immunopathologies they regulate.

Single Crystals of Mixed-Cation Copper-Based Perovskite with Trimodal Bandgap Behavior.

Two-dimensional (2D) hybrid perovskites with novel functionalities and structural diversity are a perfect platform for emerging optoelectronic devices such as photodetectors, light-emitting diodes, and solar cells. Here, we demonstrate that excess concentration of Cesium bromide (CsBr) is key to the formation of easily exfoliated 2D Cs2 Cu(Cl/Br)4 perovskite crystal. Furthermore, by employing this trick to 2D perovskite MA2 Cu(Cl/Br)4 (MA=methylammonium), we achieve a phase-pure easily exfoliated 2D mixed-cation (MA/Cs)2 Cu(Cl/Br)4 perovskite crystal, which exhibits reduced bandgap (1.53 eV) with ferromagnetic behavior and photovoltaic property. The resultant mixed-cation structured device reveals enhanced efficiency compared to all MA and all Cs counterparts. These findings demonstrate the importance of cation-engineering in developing innovative materials with novel properties.

Enhancement of the mechanical and thermal transport properties of carbon nanotube yarns by boundary structure modulation.

Carbon nanotubes (CNTs) exhibit extremely high nanoscopic thermal/electrical transport and mechanical properties. However, the macroscopic properties of assembled CNTs are significantly lower than those of CNTs because of the boundary structure between the CNTs. Therefore, it is crucial to understand the relationship between the nanoscopic boundary structure in CNTs and the macroscopic properties of the assembled CNTs. Previous studies have shown that the nanoscopic phonon transport and macroscopic thermal transport in CNTs are improved by Joule annealing because of the improved boundary Van-der-Waals interactions between CNTs via the graphitization of amorphous carbon. In this study, we investigate the mechanical strength and thermal/electrical transport properties of CNT yarns with and without Joule annealing at various temperatures, analyzing the phenomena occurring at the boundaries of CNTs. The obtained experimental and theoretical results connect the nanoscopic boundary interaction of CNTs in CNT yarns and the macroscopic mechanical and transport properties of CNT yarns.

Paraganglioma of the urinary bladder initially diagnosed as gastrointestinal stromal tumor requiring combined resection of the rectum: a case report.

BACKGROUND: Paraganglioma of the urinary bladder (Pub) is rare and presents with clinical symptoms caused by catecholamine production and release. The typical symptoms of Pub are hypertension, macroscopic hematuria, and a hypertensive crisis during micturition. The average size of detected Pubs is approximately 3 cm. Herein, we report a case of a large Pub in which the symptoms were masked by oral medication, precise preoperative diagnosis was difficult, and intraoperative confirmation of tumoral adhesion to the rectum resulted in hypertensive attacks during surgery. CASE PRESENTATION: A 64-year-old Japanese male with a history of hypertension and arrhythmia controlled with oral medication presented with a large tumor in the pelvic region, detected on examination for weight loss, with no clinical symptoms. Computed tomography and magnetic resonance imaging revealed a tumor measuring 77 mm in diameter in the posterior wall of the urinary bladder. The border with the rectum was unclear, and the tumor showed heterogeneous enhancement in the solid part with an enhancing hypodense lesion. Cystoscopy revealed compression of the bladder trigone by external masses; however, no tumor was visible in the lumen. Endoscopic ultrasonography-guided fine-needle aspiration revealed CD34-positive spindle-shaped cells in the fibrous tissue, suggestive of a mesenchymal neoplasm. The tumor was suspected to be a gastrointestinal stromal tumor, and surgery was performed. After laparotomy, we suspected that the tumor had invaded the rectum, and total cystectomy and anterior resection of the rectum were performed. Histologically, the tumor cells had granular or clear amphophilic cytoplasm with an oval nucleus and nests of cells delimited by connective tissue and vascular septations. Immunohistochemically, the tumor was positive for chromogranin A, CD56, and synaptophysin, and a diagnosis of paraganglioma of the urinary bladder was confirmed. There was no tumor recurrence at the 7-month follow-up. CONCLUSION: This case highlights the importance of careful examination of pelvic tumors, including endocrine testing, for detecting paraganglioma of the urinary bladder in patients with a history of hypertension or arrhythmia.

A study on preserving endometrial glandular architecture during preparation using BD SurePath™ liquid-based cytology reagents: Cellular fixation with preservative fluid requires at least 18 h.

INTRODUCTION: This study aimed to determine the causes of disruption of the three-dimensional architecture of endometrial glands prepared using BD SurePath™ liquid-based cytology (SP-LBC) reagents. One sample preparation method for endometrial cytology is presented in which this three-dimensional architecture can be retained. METHODS: SP-LBC specimens were prepared by the following three methods: (1) using the BD PrepMateTM (PrepMate) System after cellular fixation for 1-6 h (method A); (2) without using the PrepMate System after cellular fixation for 1-6 h (method B); and (3) using the PrepMate System after cellular fixation for at least 18 h (method C). Size and numbers of endometrial cell clusters and numbers of solitary scattered cells were then evaluated. RESULTS: Significantly higher numbers of cell clusters with a major axis of 200 µm or more were yielded by method C (71.3 ± 57.2) than methods A (9.3 ± 5.9, P < 0.001) or B (44.3 ± 28.8, P < 0.05). Method B yielded significantly higher numbers of cell clusters than method A (P < 0.001). Method A (132.2 ± 107.7, p < 0.001) yielded significantly higher numbers of solitary scattered cells than methods B (29.1 ± 14.8) and C (35.7 ± 23.3). No significant difference in solitary cell numbers was found between methods B and C. CONCLUSIONS: Retention of endometrial glandular architecture is rendered possible by allowing sample fixation times of 18 h or more when preparing specimens using the PrepMate System.

The expression pattern of CD10 and CD31 identifies fine fibrovascular stroma of grade 1-endometrial endometrioid carcinomas in cytology.

INTRODUCTION: The objective of this study was to assess the diagnostic utility of CD10 in the differential diagnosis of grade 1-endometrial endometrioid carcinoma (G1-EEC) and the metaplastic changes associated with the endometrial glandular and stromal breakdown (EGBD) on liquid-based cytological (LBC) samples. METHODS: (1) The type and distribution of CD10-positive cells in EGBD and G1-EEC patients were evaluated. (2) Based on the results from (1), histological and cytological specimens were double-immunostained with CD31 and CD10 to confirm whether CD10-positive tubular-canalicular material found in (1) was represented by fine threads of endometrial-type fibrovascular stroma. (3) Based on the results from (2), additional immunostaining of histological specimens was performed for CD146 and αSMA as markers of perivascular cells. RESULTS: (1) CD10 positive cells showed two main patterns of expression: cytoplasmic immunoreactivity in the form of dense brown granules in EGBD and tubular-canalicular branching patterns in G1-EEC. (2) The tubular-canalicular material observed in cytological specimens of G1-EEC samples co-expressed CD10 and CD31, and was interpreted as representing fine threads of endometrial fibrovascular stroma in the corresponding histological samples. Conversely, metaplastic changes in EGBD cases, only a few CD31-positive signals were found inside the condensed stromal clusters with CD10-positive. (3) Cells surrounding the CD31-positive vascular endothelial cells expressed CD146 and αSMA; moreover, some of the thin CD10-positive fibrous stromal strands also co-expressed αSMA. CONCLUSIONS: CD10 is a very useful immunomarker for distinguishing between G1-EEC and the metaplastic changes of EGBD in LBC samples.

Optimal Size Criteria for Lateral Lymph Node Dissection After Neoadjuvant Chemoradiotherapy for Rectal Cancer.

BACKGROUND: Although chemoradiotherapy followed by radical surgery without lateral lymph node dissection is the current standard treatment in patients with rectal cancer, recent studies have demonstrated the benefits of adding lateral lymph node dissection to total mesorectal excision in patients with suspected lateral lymph node metastasis. However, the optimal indication for lateral lymph node dissection after chemoradiotherapy has not been determined. OBJECTIVE: This study aimed to establish the optimal indication for lateral lymph node dissection after chemoradiotherapy in patients with rectal cancer. DESIGN: This is a retrospective study. SETTINGS: This study was conducted at a single referral hospital. PATIENTS: A total of 279 patients with rectal cancer who underwent chemoradiotherapy followed by radical surgery between 2007 and 2018 were retrospectively enrolled. MAIN OUTCOME MEASURES: The largest lateral lymph nodes on CT were retrospectively assessed and compared with the pathologic results of dissected lateral lymph nodes and recurrences in lateral lymph node areas. RESULTS: The incidence of lateral lymph node metastasis after chemoradiotherapy was estimated to be 9.3%. Although patients with lateral lymph node metastasis frequently developed distant recurrence, 40.4% survived for >5 years without recurrence. An analysis of the lateral lymph node sizes showed that lateral lymph node size ≥8 mm before chemoradiotherapy was the optimal criterion for lateral lymph node dissection, with a sensitivity and specificity of 92.3% and 78.7%. Using this criterion, 72.0% of the patients could be spared lateral lymph node dissection. LIMITATIONS: Because of the retrospective nature of the present study, the selection of patients who underwent lateral lymph node dissection was biased. CONCLUSIONS: The optimal indication for lateral lymph node dissection was lateral lymph node size ≥8 mm before chemoradiotherapy. Cancer could be eradicated in >30% of patients with lateral lymph node metastasis by dissecting metastatic lateral lymph nodes. See Video Abstract at http://links.lww.com/DCR/B428. CRITERIOS DE TAMAO PTIMO PARA LA DISECCIN DE GANGLIOS LINFTICOS LATERALES DESPUS DE LA QUIMIORRADIOTERAPIA NEOADYUVANTE PARA EL CNCER DE RECTO: ANTECEDENTES:Aunque la quimiorradioterapia seguida por cirugía radical sin disección de ganglios linfáticos laterales es el tratamiento estándar actual en pacientes con cáncer de recto, estudios recientes han demostrado beneficios de agregar disección de ganglios linfáticos laterales a la escisión mesorrectal total en pacientes con sospecha de metástasis de ganglios linfáticos laterales. Sin embargo, no se ha determinado la indicación óptima para la disección de los ganglios linfáticos laterales después de la quimiorradioterapia.OBJETIVO:Este estudio tuvo como objetivo establecer la indicación óptima para la disección de los ganglios linfáticos laterales después de la quimiorradioterapia en pacientes con cáncer de recto.DISEÑO:Estudio retrospectivo.ENTORNO CLINICO:Este estudio se realizó en un solo hospital de referencia.PACIENTES:Se inscribieron retrospectivamente un total de 279 pacientes con cáncer de recto que se sometieron a quimiorradioterapia seguida por cirugía radical entre 2007 y 2018.PRINCIPALES MEDIDAS DE VALORACION:Los ganglios linfáticos laterales más grandes en la tomografía computarizada se evaluaron retrospectivamente y se compararon con los resultados patológicos de los ganglios linfáticos laterales disecados y recidivas en las áreas de los ganglios linfáticos laterales.RESULTADOS:Se estimó que la incidencia de metástasis en los ganglios linfáticos laterales después de la quimiorradioterapia fue del 9,3%. Aunque los pacientes con metástasis en los ganglios linfáticos laterales con frecuencia desarrollaron recurrencia a distancia, el 40,4% sobrevivió durante más de 5 años sin recurrencia. Un análisis de los tamaños de los ganglios linfáticos laterales mostró que la mayor dimensión de los ganglios linfáticos laterales ≥ 8 mm antes de la quimiorradioterapia eran el criterio óptimo para la disección de los ganglios linfáticos laterales, con una sensibilidad y especificidad del 92,3% y 78,7%, respectivamente. Utilizando este criterio, el 72,0% de los pacientes podría evitarse la disección de los ganglios linfáticos laterales.LIMITACIONES:Debido a la naturaleza retrospectiva del presente estudio, la selección de pacientes que fueron sometidos a disección de ganglios linfáticos laterales fue sesgada.CONCLUSIÓN:La indicación óptima para la disección de los ganglios linfáticos laterales fue la dimensión mayor de los ganglios linfáticos laterales ≥ 8 mm antes de la quimiorradioterapia. El cáncer se podría erradicar en más del 30% de los pacientes con metástasis en los ganglios linfáticos laterales disecando los ganglios linfáticos laterales metastásicos. Consulte Video Resumen en http://links.lww.com/DCR/B428.

Low preoperative maximum squeezing pressure evaluated by anorectal manometry is a risk factor for non-reversal of diverting stoma.

PURPOSE: A diverting stoma is created to prevent anastomotic leakage and related complications impairing sphincteric function in rectal surgery. However, diverting stoma may be left unclosed. This study is aimed to analyze preoperative factors including anorectal manometric data associated with diverting stoma non-reversal before rectal surgery. We also addressed complications related to diverting stoma in patients undergoing surgery for rectal malignant tumor. METHODS: A total of 203 patients with rectal malignant tumor who underwent sphincter-preserving surgery with diverting stoma were retrospectively evaluated. The risk factors for non-reversal of diverting stoma were identified by univariate and multivariate analyses. For these analyses, anorectal manometric data were measured before rectal surgery. The association between stoma-related complications and other clinicopathological features was also analyzed. RESULTS: During the median follow-up of 46.4 months, 24% (49 patients) did not undergo stoma reversal. Among parameters that were available before rectal surgery, age ≥ 75 years, albumin < 3.5 g/dl, tumor size ≥ 30 mm, tumor distance from the anal verge < 4 cm, and maximum squeezing pressure (MSP) < 130 mmHg measured by anorectal manometry (ARM) were independent factors associated with stoma non-reversal. The most common stoma-related complication was peristomal skin irritation (25%). Ileostomy was the only factor associated with peristomal skin irritation. CONCLUSION: The current study demonstrated that low preoperative MSP evaluated by ARM, old age, hypoalbuminemia, and a large tumor close to the anus were predictive of diverting stoma non-reversal. Stoma site should be well deliberated when patients have the aforementioned risk factors for diverting stoma non-reversal.

Metastatic role of mammalian target of rapamycin signaling activation by chemoradiotherapy in advanced rectal cancer.

Postoperative distant metastasis dramatically affects rectal cancer patients who have undergone neoadjuvant chemoradiotherapy (NACRT). Here, we clarified the association between NACRT-mediated mammalian target of rapamycin (mTOR) signaling pathway activation and rectal cancer metastatic potential. We performed immunohistochemistry for phosphorylated mTOR (p-mTOR) and phosphorylated S6 (p-S6) on surgical specimen blocks from 98 rectal cancer patients after NACRT (cohort 1) and 80 colorectal cancer patients without NACRT (cohort 2). In addition, we investigated the association between mTOR pathway activity, affected by irradiation, and the migration ability of colorectal cancer cells in vitro. Based on the results of the clinical study, p-mTOR was significantly overexpressed in cohort 1 (with NACRT) as compared to levels in cohort 2 (without NACRT) (P < .001). High p-mTOR and p-S6 levels correlated with the development of distant metastasis only in cohort 1. Specifically, high p-S6 expression (HR 4.51, P = .002) and high pathological T-stage (HR 3.73, P = .020) after NACRT were independent predictors of the development of distant metastasis. In vitro, p-S6 levels and migration ability increased after irradiation in SW480 cells (TP53 mutation-type) but decreased in LoVo cells (TP53 wild-type), suggesting that irradiation modulates mTOR signaling and migration through cell type-dependent mechanisms. We next assessed the expression level of p53 by immunostaining in cohort 1 and demonstrated that p-S6 was overexpressed in samples with high p53 expression as compared to levels in samples with low p53 expression (P = .008). In conclusion, p-S6 levels after NACRT correlate with postoperative distant metastasis in rectal cancer patients, suggesting that chemoradiotherapy might modulate the mTOR signaling pathway, promoting metastasis.

Postoperative chemotherapy is associated with prognosis of stage IV colorectal cancer treated with preoperative chemotherapy/chemoradiotherapy and curative resection.

PURPOSE: Advances in systemic chemotherapy have increased the resectability in colorectal cancer (CRC) associated with metastases even if it was initially unresectable. However, what determines the prognosis of stage IV CRC patients treated by preoperative therapy and surgery remains unclear. We attempted to identify prognostic factors in such CRC patients. METHODS: We reviewed stage IV CRC patients who underwent curative resection between December 2007 and May 2019. The patients who underwent conversion chemotherapy for initially unresectable disease and those who received neoadjuvant chemotherapy (NAC) for resectable synchronous metastases or neoadjuvant chemoradiotherapy (NACRT) for advanced lower rectal cancer with resectable metastases were included. Recurrence-free survival (RFS) and overall survival (OS) were examined by multivariate analyses using Cox proportional hazard models. The RFS and OS curves were analyzed according to postoperative adjuvant chemotherapy (AC). RESULTS: Among 70 patients who underwent curative surgery (34 men, mean age: 60 years old), 33 had initially unresectable disease, 23 received NAC, and 14 NACRT. By multivariate analyses, AC was an independent predictor for improved RFS and OS (hazard ratio = 0.29, p = 0.0002, and hazard ratio = 0.37, p = 0.025). Patients treated with AC showed improved RFS and OS than those without AC (2-year RFS rate = 30% vs 19%, p = 0.031, and 3-year OS rate = 87% vs 67%, p = 0.045). CONCLUSION: Because of its association with improved prognosis, AC should be considered for stage IV CRC patients after curative resection regardless of initial resectability status and preoperative therapy.

Loss of RUNX3 Immunoreactivity in Non-Neoplastic Rectal Mucosa May Predict the Occurrence of Ulcerative Colitis-Associated Colorectal Cancer.

BACKGROUND/AIMS: Runt-related transcription factor (RUNX) 3 is a tumor suppressor whose expression is reduced in non-neoplastic rectal mucosa of patients with ulcerative colitis (UC) with coexisting colitis-associated cancer (CAC). We aimed to evaluate RUNX3 utility as a predictive marker for CAC using immunohistochemistry (IHC) for non-neoplastic UC mucosa. METHODS: We retrospectively compared the RUNX3 expression detected by IHC between non-neoplastic rectal biopsy specimens from 20 cases with invasive cancer (CAC group) and 20 cases selected from 138 patients without CAC (non-CAC group) that were treated during the same period (2006-2017) and were matched for sex, duration, extension, and age. We validated the results using tissue microarrays (TMA) of 44 operated cases with CAC. The RUNX3 expression level was determined by calculating the percentage of RUNX3-positive-cells. RESULTS: The RUNX3 expression was lower in the CAC than that in the non-CAC group (35.6 vs. 70.7%, p = 0.03). For a cutoff value of 58%, the sensitivity and specificity for predicting CAC were 75.0 and 70.0% respectively. The immunostaining results for the TMA showed the same trend; 74% of cases with CAC were negative for the RUNX3 expression. CONCLUSION: RUNX3 immunostaining of non-neoplastic mucosa is useful for identifying UC patients at a high risk of developing CAC.

Liquid-like dielectric response is an origin of long polaron lifetime exceeding 10 µs in lead bromide perovskites.

Lead halide perovskites are promising materials for optoelectronic applications because of their exceptional performances in carrier lifetime and diffusion length; however, the microscopic origins of their unique characteristics remain elusive. The organic-inorganic hybrid perovskites show unique dielectric functions, i.e., ferroelectric-like phonon responses in the 0.1-10 THz region and liquid-like rotational relaxation in the 1-100 GHz range. To reveal the role of the dielectric responses is of primal importance because the dielectric screening is a key to understanding the optoelectronic properties governed by polarons in the perovskites. Here, we conducted comparative studies of broadband dielectric spectroscopy on both all-inorganic CsPbBr3 and organic-inorganic hybrid (CH3NH3)PbBr3 single crystals to uncover the origin of the liquid-like dielectric relaxation in the 1-100 GHz range. We confirmed the absence of the dielectric response in the range of 106-1010 Hz in CsPbBr3, which was clearly present in the hybrid (CH3NH3)PbBr3. This suggests that the response is almost purely due to the rotational motions of the organic dipoles in the hybrid perovskites. We evaluated the lifetimes of the polarons using surface-free transient photoluminescence. The lifetime in CsPbBr3 was up to 1.6 µs, while the lifetime in (CH3NH3)PbBr3 was 18 µs. The lifetime in the hybrid (CH3NH3)PbBr3 was significantly longer than in CsPbBr3, also confirmed by transient infrared spectroscopy. We concluded that the liquid-like dielectric response inhibits polaron recombination due to the efficient separation of opposite charges by the additional dynamic disorder.

Anastomotic bleeding following ileocolic end-to-side anastomosis using a circular stapler: incidence and risk factors.

PURPOSE: To identify the incidence of and risk factors for postoperative bleeding after ileocolic end-to-side anastomosis using a circular stapler. METHODS: We analyzed, retrospectively, the risk factors for postoperative anastomotic bleeding in patients who underwent right-sided colectomy with end-to-side anastomosis done using a circular stapler during colon tumor surgery at our institute between January 2015 and March 2019. RESULTS: Anastomotic bleeding developed in 10 (3.6%) of the total 279 patients. Univariate analysis revealed that age ≥ 80 years (8.8% vs. 1.9%; P = 0.008) and Eastern Cooperative Oncology Group performance status (ECOG PS) ≥ 1 (12.5% vs. 2.8%; P = 0.014) were significant risk factors for anastomotic bleeding. Postoperative anticoagulation therapy was not a risk factor for anastomotic bleeding. Multivariate analysis revealed that only age ≥ 80 years was an independent risk factor (odds ratio 4.12, 95% confidence interval 1.02-16.68, P = 0.047). Six of the ten patients with anastomotic bleeding were treated conservatively, three were treated by colonoscopic clipping, and one required surgery. CONCLUSION: End-to-side anastomosis is safe and feasible, but must be performed carefully in the elderly, who are at higher risk of anastomotic bleeding.

Management of isolated para-aortic lymph node recurrence of colorectal cancer.

Isolated para-aortic lymph node recurrence (PALNR) after curative surgery for colorectal cancer (CRC) is rare and its optimal management is not defined clearly. This review investigates the best outcomes among published studies on the management of PALNR in the field of CRC. We searched the PubMed database for studies reporting on the management of isolated PALNR in CRC, published in English or Japanese from January, 2000 to December, 2018. Studies including patients with other metastases were excluded. A total of 24 retrospective studies including 227 patients with PALNR were evaluated. The 3-year overall survival (OS) ranged from 60 to 100%, with a median OS of 34-80 months for patients who underwent PALNR dissection, and 14-42 months for patients who received non-surgical treatment. No surgery-related mortality was reported and the incidence of surgical, mainly low-grade, complications ranged from 33 to 52%. The predictors of improved survival outcome included R0 resection margins. Dissection for PALNR from CRC is considered a feasible treatment option that may yield a better prognosis than non-surgical treatment alone. Preoperative chemotherapy or CRT should be considered for their potential benefits, including a reduction in cancer volume and improved R0 resection rates.

Laparoscopic surgery in rectal cancer patients taking anti-thrombotic therapy.

Background: Several previous studies have shown that laparoscopic resection of rectal cancer is a feasible option. However, its safety and efficacy in patients receiving long-term anti-thrombotic therapy (AT) remain unclear.Material and methods: We retrospectively reviewed 364 patients who underwent elective resection for rectal cancer via a laparoscopic approach between 2007 and 2018 in our institute. Patients were classified according to the long-term use of AT. AT was interrupted perioperatively with or without heparin bridging therapy in all anti-thrombotic users. Clinicopathological factors and surgical outcomes were analyzed between patient groups.Results: Thirty-two patients (9%) receiving AT were older and had lower albumin and hemoglobin levels than those not receiving AT (the non-AT group), and were predominantly male. Estimated blood loss and operative time in the AT group (median: 50 mL and 294 min) did not differ from those in the non-AT group (median: 20 mL and 295 min). There were no intergroup differences in the frequencies of other postoperative complications and oncological outcomes.Conclusions: Our results at the very least can support that laparoscopic surgery for rectal cancer is a safe and feasible option for patients taking long-term AT discontinued perioperatively.

The component changes of lysophospholipid mediators in colorectal cancer.

Although lysophospholipids are known to play an important role in the development and progression of several kinds of cancers, their role in human colorectal cancer is as yet unclear. In this study, we aim to investigate lysophospholipid levels in colorectal cancer tissues to identify lysophospholipids, the levels of which change specifically in colorectal cancers. We used liquid chromatography-tandem mass spectrometry to measure lysophospholipid levels in cancerous and normal tissues from 11 surgical specimens of sigmoid colon cancers, since recent advances in this field have improved detection sensitivities for lysophospholipids. Our results indicate that, in colon cancer tissues, levels of lysophosphatidylinositol and lysophosphatidylserine were significantly higher ( p = 0.025 and p = 0.01, respectively), whereas levels of lysophosphatidic acid were significantly lower ( p = 0.0019) than in normal tissues. Although levels of lysophosphatidylglycerol were higher in colon cancer tissues than in normal tissues, this difference was not found to be significant ( p = 0.11). Fatty acid analysis further showed that 18:0 lysophosphatidylinositol and 18:0 lysophosphatidylserine were the predominant species of lysophospholipids in colon cancer tissues. These components may be potentially involved in colorectal carcinogenesis.

Correlations between the Recurrence Patterns and Sizes of Lateral Pelvic Lymph Nodes before and after Chemoradiotherapy in Patients with Lower Rectal Cancer.

OBJECTIVE: Factors that predict rectal cancer metastasis to the lungs remain undefined. We investigated whether the lateral pelvic lymph node (LPN) sizes before and after chemoradiotherapy (CRT) correlate with lung metastasis after surgery for lower rectal cancer. METHODS: Two hundred and forty patients with lower rectal cancer who received preoperative CRT and curative surgery between 2003 and 2017 were examined. Computed tomography-measured LPN sizes before and after CRT were retrospectively determined by 1 colorectal surgeon who was blinded to the patients' clinical and pathological outcomes. RESULTS: The 5-year cumulative lung metastasis rates were 15.2%. The mean LPN sizes in patients who developed lung metastasis were larger than those in patients who did not (pre-CRT: 8.7 vs. 6.3 mm, p = 0.003; post-CRT: 6.8 vs. 4.5 mm, p = 0.001). The cumulative lung metastasis rate in patients with large LPNs was higher than in those with small LPNs both before and after CRT. On multivariate analysis, lung metastasis was independently correlated with the LPN size only after CRT (hazard ratio [HR]: 5.58), together with the ypT stage (HR: 2.96) and the tumor location (HR: 0.38). CONCLUSIONS: LPN size after CRT is strongly predictive of postoperative lung metastasis in patients with lower rectal cancer.

Pine-cone and villi patterns are endoscopic signs suggestive of ulcerative colitis-associated colorectal cancer and dysplasia.

BACKGROUND AND AIMS: The appropriate site for targeted biopsy during surveillance colonoscopy for ulcerative colitis (UC) is still unclear. We aimed to clarify key endoscopic findings suggestive of neoplastic lesions for targeted biopsy in UC. METHODS: First, we created 769 stereomicroscopic pictures (509 neoplastic, 260 non-neoplastic) mimicking magnifying colonoscopic images from surgically resected specimens, including areas surrounding 25 neoplastic lesions in 15 patients with colitis-associated cancer at a single referral center. Second, we validated the results by using 113 magnifying endoscopic images (64 neoplastic, 49 non-neoplastic) from 39 lesions in 26 patients. Two evaluators, blinded to the pathologic diagnosis, independently classified them according to Kudo's pit pattern and surface morphology, such as pine-cone/villi patterns. The correlation between stereomicroscopic and pathologic findings (neoplastic vs non-neoplastic) for each image was investigated. The interobserver agreement was assessed using kappa statistics. RESULTS: In the stereomicroscopic analysis, neoplastic pit patterns (types III-V) were significantly correlated with the presence of neoplasia (sensitivity 77.4%, specificity 89.5%, kappa value 0.677). Pine-cone/villi patterns also showed high specificity (96.8%) but low sensitivity (21.4%, kappa value 0.625) for neoplasia. Endoscopic validation showed similar trends. A revision of the endoscopic findings of flat dysplasia with non-neoplastic pit patterns revealed that a reddish area may facilitate the identification of such lesions. CONCLUSIONS: Targeted biopsies are recommended, especially for lesions showing pine-cone/villi patterns in addition to neoplastic pit patterns. For flat "non-neoplastic pit patterns," a reddish area may be an indication for a biopsy.

Short- and Long-term Outcomes of Minimally Invasive Versus Open Multivisceral Resection for Locally Advanced Colorectal Cancer.

BACKGROUND: Colorectal cancer invading the adjacent organs/structures is detected in 5% to 20% of all surgical interventions performed for the management of colorectal cancer. OBJECTIVE: Our purpose is to verify the safety and feasibility of laparoscopic surgery for the treatment of locally advanced colorectal cancer invading the adjacent organs. DESIGN: This is a retrospective study. SETTINGS: The study was conducted at a single institution in Japan. PATIENTS: We compared the morbidity, appropriate oncological resection, and disease-free survival of laparoscopic and open multivisceral resection in patients with colorectal carcinoma in the period between 2007 and 2015. MAIN OUTCOME MEASURES: The primary outcome measures were curative resection rate, morbidity rate, and recurrence of laparoscopic and open multivisceral resection in patients with colorectal cancer. RESULTS: Thirty-one patients received laparoscopic surgery, and 50 received open surgery. The amount of blood loss was smaller in the laparoscopic group than in the open group (60 vs 595 mL, p < 0.01). Curative surgery was performed in 46 patients of the open group (92.0%) and in 30 patients of the laparoscopic group (96.8%). Days until oral intake (5 vs 7 days, p < 0.01) and postoperative hospital stay (14 vs 19 days, p < 0.01) were shorter in the laparoscopic group. Overall morbidity was not different between the groups (22.5% vs 40.0%). Three-year disease-free survival rates were 62.7% in the open group and 56.7% in the laparoscopic group (p = 0.5776). LIMITATION: This study was a retrospective small study conducted at a single institute. CONCLUSION: Laparoscopic multivisceral resection may be a safe, less invasive alternative to open surgery, with less blood loss and shorter hospital stay, and was not inferior to open surgery based on long-term oncological end points. See Video Abstract at http://links.lww.com/DCR/A785.

Prognostic significance of doubling time in patients undergoing radical surgery for metachronous peritoneal metastases of colorectal cancer.

PURPOSE: The doubling times of tumor volume and tumor markers are associated with the prognosis of liver or lung metastases from colorectal cancer (CRC). However, no studies have assessed peritoneal metastases. Therefore, we aimed to elucidate the association between doubling time and the prognosis of patients who underwent radical surgery for metachronous peritoneal metastases of CRC. METHODS: We calculated the tumor doubling times (TDT) of peritoneal metastases and serum carcinoembryonic antigen-doubling times (CEA-DT) in 33 consecutive patients who underwent radical surgery for metachronous peritoneal metastases between January 2006 and April 2017. The impact of short TDT and CEA-DT on overall survival (OS) and relapse-free survival (RFS) was retrospectively reviewed. RESULTS: In long TDT (> 137 days) group, the 5-year OS rate was 74.1% and median OS time was 6.6 years. In long CEA-DT (> 102 days) group, the 5-year OS rate was 50.0% and median OS time was 5.6 years. Conversely, in short TDT (≤ 137 days) and CEA-DT (≤ 102 days) group, the 5-year OS rates and median OS times were both 0.0% and 3.2 years, respectively. In the multivariate analysis, short TDT was an independent risk factor for poor RFS (P = 0.006) and OS (P = 0.010). Similarly, short CEA-DT was also a poor risk factor for RFS (P < 0.001) and OS (P = 0.012). CONCLUSIONS: Short TDT and CEA-DT are independent risk factors for poor OS and RFS after surgery for metachronous peritoneal metastases of CRC. TDT and CEA-DT should be considered when selecting candidates for surgical resection.