AQP5 enriches for stem cells and cancer origins in the distal stomach.

LGR5 marks resident adult epithelial stem cells at the gland base in the mouse pyloric stomach1, but the identity of the equivalent human stem cell population remains unknown owing to a lack of surface markers that facilitate its prospective isolation and validation. In mouse models of intestinal cancer, LGR5+ intestinal stem cells are major sources of cancer following hyperactivation of the WNT pathway2. However, the contribution of pyloric LGR5+ stem cells to gastric cancer following dysregulation of the WNT pathway-a frequent event in gastric cancer in humans3-is unknown. Here we use comparative profiling of LGR5+ stem cell populations along the mouse gastrointestinal tract to identify, and then functionally validate, the membrane protein AQP5 as a marker that enriches for mouse and human adult pyloric stem cells. We show that stem cells within the AQP5+ compartment are a source of WNT-driven, invasive gastric cancer in vivo, using newly generated Aqp5-creERT2 mouse models. Additionally, tumour-resident AQP5+ cells can selectively initiate organoid growth in vitro, which indicates that this population contains potential cancer stem cells. In humans, AQP5 is frequently expressed in primary intestinal and diffuse subtypes of gastric cancer (and in metastases of these subtypes), and often displays altered cellular localization compared with healthy tissue. These newly identified markers and mouse models will be an invaluable resource for deciphering the early formation of gastric cancer, and for isolating and characterizing human-stomach stem cells as a prerequisite for harnessing the regenerative-medicine potential of these cells in the clinic.

High-Sensitive Spatiotemporal Distribution Imaging of Compression Stresses Based on Time-Evolutional Responsiveness.

Mechanoresponsive materials have been studied to visualize and measure stresses in various fields. However, the high-sensitive and spatiotemporal imaging remain a challenging issue. In particular, the time evolutional responsiveness is not easily integrated in mechanoresponsive materials. In the present study, high-sensitive spatiotemporal imaging of weak compression stresses is achieved by time-evolutional controlled diffusion processes using conjugated polymer, capsule, and sponge. Stimuli-responsive polydiacetylene (PDA) is coated inside a sponge. A mechanoresponsive capsule is set on the top face of the sponge. When compression stresses in the range of 6.67-533 kPa are applied to the device, the blue color of PDA is changed to red by the diffusion of the interior liquid containing a guest polymer flowed out of the disrupted capsule. The applied strength (F/N), time (t/s), and impulse (F·t/N s) are visualized and quantified by the red-color intensity. When a guest metal ion is intercalated in the layered structure of PDA to tune the responsivity, the device visualizes the elapsed time (τ/min) after unloading the stresses. PDA, capsule, and sponge play the important roles to achieve the time evolutional responsiveness for the high-sensitive spatiotemporal distribution imaging through the controlled diffusion processes.

Combined Comprehensive Risk Score of the Estimation of Physiologic Ability and Surgical Stress and C-Reactive Protein-to-Albumin Ratio Is a Strong Prognostic Indicator of Long-term Outcomes in Colorectal Cancer.

BACKGROUND: In patients with colorectal cancer, both C-reactive protein-to-albumin ratio and comprehensive risk score of the estimation of physiologic ability and surgical stress have demonstrated prognostic significance. OBJECTIVE: To assess the clinical value of the combined use of C-reactive protein-to-albumin ratio and comprehensive risk score for predicting prognosis in patients with colorectal cancer. DESIGN: Multicenter retrospective study. SETTINGS: The cohort was divided into 3 groups based on a combined score derived from the value of C-reactive protein-to-albumin ratio and comprehensive risk score (low/mid /high). PATIENTS: Patients who underwent curative resection between 2010 and 2019 at multiple institutions were enrolled in this study. MAIN OUTCOME MEASURES: Overall and recurrence-free survival. RESULTS: A total of 2207 patients (801 in low cohort, 817 in mid cohort, and 589 in high cohort) were included in this study. Multivariate analysis revealed that combined score was an independent prognostic factor for both overall and recurrence-free survival, irrespective of disease stage (p < 0.05). Furthermore, Harrell's C-Index indicated that the predictive power of combined score was significantly superior to that of C-reactive protein-to-albumin ratio or comprehensive risk score (p < 0.001). LIMITATIONS: This study had a retrospective design, and data on genetic markers were not included. CONCLUSION: The synergistic combination of C-reactive protein-to-albumin ratio and comprehensive risk score contributes to the robust definition of combined score, a potent prognostic factor, regardless of disease stage. This finding has the potential to provide novel insights into the management of patients with CRC who have undergone curative resection. See Video Abstract.

Impact of the COVID-19 pandemic on the number and short-term outcomes in hepatectomy for hepatocellular carcinoma: Results from the Japanese National Clinical Database, 2018-2021.

AIM: The coronavirus disease 2019 (COVID-19) pandemic has significantly impacted the allocation of medical resources, including cancer screening, diagnosis, and treatment. We aimed to investigate the effects of the pandemic on morbidity and mortality following hepatectomy for hepatocellular carcinoma (HCC). METHODS: We identified patients who underwent hepatectomy for HCC between 2018 and 2021 from the Japanese National Clinical Database (NCD). The number of surgical cases, the use of intensive care units, and the incidence of morbidity were assessed. The standardized morbidity / mortality ratio (SMR) was used to evaluate the rates of morbidity (bile leakage and pneumonia) and mortality in each month, which compares the observed incidence to the expected incidence calculated by the NCD's risk calculator. RESULTS: The study included a total of 10 647 cases. The number of patients undergoing hepatectomy for HCC gradually decreased. The proportion of patients aged 80 years or older increased and that of cases with T1 stage decreased. The proportion of patients who were admitted to the intensive care unit did not change between the pre- and postpandemic period. The mean actual incidence rates of bile leakage, pneumonia, 30-day mortality, and surgical mortality were 9.2%, 2.3%, 1.4%, and 2.1%, respectively. The SMR for the mortalities and morbidities in each month did not increase mostly throughout the COVID-19 pandemic. CONCLUSIONS: The present study showed the decreasing number of resected cases for HCC, while the surgical safety for hepatectomy was enough to be maintained by managing medical resources in Japan.

Efficacy of transanal drainage tube placement in preventing anastomotic leakage after ileal pouch-anal anastomosis in patients with ulcerative colitis.

BACKGROUND: Transanal drainage tube (TDT) is used to prevent anastomotic leakage after surgery for rectal cancer. However, it remains unclear whether intraoperative TDT placement is also useful in preventing anastomotic leakage after ileal pouch-anal or ileal pouch-anal canal anastomosis (IPAA) in patients with ulcerative colitis (UC). This study aimed to evaluate the efficacy of intraoperative TDT placement in preventing anastomotic leakage after IPAA in patients with UC. METHODS: Patients with UC who underwent proctectomy with IPAA in the study institution between January 2000 and December 2021 were enrolled in this retrospective cohort study. The relationship between TDT placement and anastomotic leakage was evaluated by logistic regression analysis. RESULTS: The study population included 168 patients. TDT was placed intraoperatively in 103 of the 168 patients (61.3%). The rate of anastomotic leakage was significantly lower in the TDT group than in the non-TDT group (7.8% vs 18.5%, p = 0.037). Reoperation was not needed in any patient in the TDT group whereas two reoperations were necessary in the non-TDT group (3.1%). By logistic regression analysis, intraoperative TDT placement was an independent protective factor for anastomotic leakage. CONCLUSIONS: TDT placement was significantly associated with anastomotic leakage of IPAA in patients with UC undergoing surgery. Although two-stage surgery with ileostomy is usually preferred in UC surgery, our findings suggest that TDT placement might contribute to the improvement of postoperative outcomes after UC surgery.

POFUT1 and PLAGL2 are characteristic markers of mucinous colorectal cancer associated with MUC2 expression.

Colorectal mucinous adenocarcinoma (MAC) is one of the most lethal histological types of colorectal cancer, and its mechanism of development is not well understood. In this study, we aimed to clarify the molecular characteristics of MAC via in silico analysis using The Cancer Genome Atlas database. The expression of genes on chromosome 20q (Chr20q) was negatively associated with the expression of MUC2, which is a key molecule that can be used to distinguish between MAC and nonmucinous adenocarcinoma (NMAC). This was consistent with a significant difference in copy number alteration of Chr20q between the two histological types. We further identified 475 differentially expressed genes (DEGs) between MAC and NMAC, and some of the Chr20q genes among the DEGs are considered to be pivotal genes used to define MAC. Both in vitro and in vivo analysis showed that simultaneous knockdown of POFUT1 and PLAGL2, both of which are located on Chr20q, promoted MUC2 expression. Moreover, these genes were highly expressed in NMAC but not in MAC according to the results of immunohistological studies using human samples. In conclusion, POFUT1 and PLAGL2 are considered to be important for defining MAC, and these genes are associated with MUC2 expression.

Stratification of Stage II Colon Cancer Using Recurrence Prediction Value: A Multi-institutional International Retrospective Study.

OBJECTIVE: To create a recurrence prediction value (RPV) of high-risk factor and identify the patients with high risk of cancer recurrence. SUMMARY BACKGROUND DATA: There are several high-risk factors known to lead to poor outcomes. Weighting each high-risk factor based on their association with increased risk of cancer recurrence can provide a more precise understanding of risk of recurrence. METHODS: We performed a multi-institutional international retrospective analysis of patients with Stage II colon cancer patients who underwent surgery from 2010 to 2020. Patient data from a multi-institutional database were used as the Training data, and data from a completely separate international database from two countries were used as the Validation data. The primary endpoint was recurrence-free survival (RFS). RESULTS: A total of 739 patients were included from Training data. To validate the feasibility of RPV, 467 patients were included from Validation data. Training data patients were divided into RPV low (n = 564) and RPV high (n = 175). Multivariate analysis revealed that risk of recurrence was significantly higher in the RPV high than the RPV low (Hazard ratio (HR) 2.628; 95% confidence interval (CI) 1.887-3.660; P < 0.001). Validation data patients were divided into two groups (RPV low, n = 420) and RPV high (n = 47). Multivariate analysis revealed that risk of recurrence was significantly higher in the RPV high than the RPV low (HR 3.053; 95% CI 1.962-4.750; P < 0.001). CONCLUSIONS: RPV can identify Stage II colon cancer patients with high risk of cancer recurrence world-wide.

Effect of Biologics on the Risk of Advanced-Stage Inflammatory Bowel Disease-Associated Intestinal Cancer: A Nationwide Study.

INTRODUCTION: The aim of this study was to evaluate the effect of biologics on the risk of advanced-stage inflammatory bowel disease (IBD)-associated intestinal cancer from a nationwide multicenter data set. METHODS: The medical records of patients with Crohn's disease (CD) and ulcerative colitis (UC) diagnosed with IBD-associated intestinal neoplasia (dysplasia or cancer) from 1983 to 2020 were included in this study. Therapeutic agents were classified into 3 types: biologics, 5-aminosalicylic acid, and immunomodulators. The pathological cancer stage was compared based on the drug used in both patients with CD and UC. RESULTS: In total, 1,042 patients (214 CD and 828 UC patients) were included. None of the drugs were significantly associated with cancer stage in the patients with CD. In the patients with UC, an advanced cancer stage was significantly associated with less use of biologics (early stage: 7.7% vs advanced stage: 2.0%, P < 0.001), 5-aminosalicylic acid, and immunomodulators. Biologic use was associated with a lower incidence of advanced-stage cancer in patients diagnosed by regular surveillance (biologics [-] 24.5% vs [+] 9.1%, P = 0.043), but this was not the case for the other drugs. Multivariate analysis showed that biologic use was significantly associated with a lower risk of advanced-stage disease (odds ratio = 0.111 [95% confidence interval, 0.034-0.356], P < 0.001). DISCUSSION: Biologic use was associated with a lower risk of advanced IBD-associated cancer in patients with UC but not with CD. The mechanism of cancer progression between UC and CD may be different and needs to be further investigated.

The Prognostic Impact of Preoperative Osteopenia in Patients With Colorectal Cancer.

BACKGROUND: Osteopenia, a condition in which bone mineral density is lower than normal, is a noted risk factor that leads to a shortened healthy life expectancy. OBJECTIVE: To investigate the prognostic impact of preoperative osteopenia in patients with colorectal cancer. DESIGN: This was a retrospective study. SETTING: This study was conducted at a university hospital. PATIENTS: A total of 1086 patients with stage I to III colorectal cancer who underwent curative resection. MAIN OUTCOME MEASURES: Osteopenia was evaluated with CT. Overall survival, disease-specific survival, and recurrence-free survival were the primary end points. RESULTS: Osteopenia was identified in 300 patients (27.6%). Compared with the no osteopenia group, the 5-year overall survival (74.0% vs 93.4%, p < 0.001), disease-specific survival (81.6% vs 97.2%, p < 0.001), and recurrence-free survival rates (57.1% vs 88.3%, p < 0.001) were significantly lower in the osteopenia group. Multivariate analyses showed that preoperative osteopenia was significantly associated with worse overall survival (HR: 4.135; 95% CI, 2.963-5.770; p < 0.001), disease-specific survival (HR: 7.673; 95% CI, 4.646-12.675; p < 0.001), and recurrence-free survival (HR: 5.039; 95% CI, 3.811-6.662; p < 0.001). The prognosis of the osteopenia group was poorer than that of the no osteopenia group in every stage: 5-year overall survival (stage I: 89.4% vs 96.9%, p = 0.028; stage II: 76.5% vs 91.9%, p < 0.001; stage III: 56.4% vs 90.8%, p < 0.001) and 5-year recurrence-free survival (stage I: 85.4% vs 96.6%, p = 0.002; stage II: 62.0% vs 86.5%, p < 0.001; stage III: 26.4% vs 80.0%, p < 0.001). LIMITATIONS: The main limitations are retrospective single-institutional features and races of the study population. CONCLUSIONS: Preoperative osteopenia could be a strong predictive marker for long-term prognosis in colorectal cancer regardless of stage. EL IMPACTO PRONSTICO DE LA OSTEOPENIA PREOPERATORIA EN PACIENTES CON CNCER COLORRECTAL: ANTECEDENTES:La osteopenia, una afección en la que la densidad mineral ósea es más baja de lo normal, es un relevante factor de riesgo que conduce a una expectativa menor de vida saludable.OBJETIVO:Investigar el impacto pronóstico de la osteopenia preoperatoria en pacientes con cáncer colorrectal (CCR).DISEÑO:Un estudio retrospectivo.AJUSTE:Estudio realizado en un hospital universitario.PACIENTES:Un total de 1.086 pacientes con CCR en estadio I-III sometidos a una resección curativa.PRINCIPALES MEDIDAS DE RESULTADO:La osteopenia se evaluó con imágenes de tomografía computarizada. La supervivencia global la supervivencia específica de la enfermedad y la supervivencia libre de recurrencia fueron los criterios de valoración primaria.RESULTADOS:Se identificó osteopenia en 300 pacientes (27,6%). En comparación con el grupo sin osteopenia, las tasas de supervivencia global a 5 años (74,0% frente a 93,4%, p < 0,001), supervivencia especifica de la enfermedad (81,6 % frente a 97,2%, p < 0,001) tasas de supervivencia libre de recurrencia (57,1% frente a 88,3%, p < 0,001) fueron significativamente más bajas en el grupo de osteopenia. Los análisis multivariados mostraron que la osteopenia preoperatoria se asoció significativamente con una peor supervivencia global (HR 4,135; IC 95% 2,963-5,770; p < 0,001), supervivencia especifica de la enfermedad (HR 7,673; IC 95% 4,646-12,675; p < 0,001) y tasas de supervivencia libre de recurrencia (HR 5,039; IC 95% 3,811-6,662; p < 0,001). El pronóstico del grupo con osteopenia fue peor que el del grupo sin osteopenia en todos los estadios: supervivencia global a 5 años (estadio I: 89,4% frente a 96,9%, p = 0,028; estadio II: 76,5% frente a 91,9%, p < 0,001; estadio III: 56,4% frente a 90,8%, p < 0,001) y tasas de supervivencia libre de recurrencia a 5 años (estadio I: 85,4% frente a 96,6%, p < 0,002; estadio II: 62,0% frente a 86,5%, p < 0,001; estadio III: 26,4% frente a 80,0%, p < 0,001).LIMITACIONES:Las principales limitaciones son las características retrospectivas de una sola institución y las razas de la población de estudio.CONCLUSIONES:La osteopenia preoperatoria puede ser un fuerte marcador predictivo para el pronóstico a largo plazo en CCR independientemente de la etapa. (Traducción-Dr. Fidel Ruiz Healy ).

Drainage pattern of the splenic flexure vein and its accompanying arteries using three-dimensional computed tomography angiography: a single-centre study of 600 patients.

AIM: The splenic flexure has variable vascular anatomy, and the details of the venous forms are not known. In this study, we report the flow pattern of the splenic flexure vein (SFV) and the positional relationship between the SFV and arteries such as the accessory middle colic artery (AMCA). METHODS: This was a single-centre study using preoperative enhanced CT colonography images of 600 colorectal surgery patients. CT images were reconstructed into 3D angiography. SFV was defined as a vein flowing centrally from the marginal vein of the splenic flexure visible on CT. AMCA was defined as the artery feeding the left side of the transverse colon, separate from the left branch of the middle colic artery. RESULTS: The SFV returned to the inferior mesenteric vein (IMV) in 494 cases (82.3%), the superior mesenteric vein in 51 cases (8.5%) and the splenic vein in seven cases (1.2%). The AMCA was present in 244 cases (40.7%). The AMCA branched from the superior mesenteric artery or its branches in 227 cases (93.0% of cases with existing AMCA). In the 552 cases in which the SFV returned to the IMV, superior mesenteric vein or splenic vein, the left colic artery was the most frequent artery accompanying the SFV (42.2%), followed by the AMCA (38.1%) and the left branch of the middle colic artery (14.3%). CONCLUSIONS: The most common flow pattern of the vein in the splenic flexure is from the SFV to IMV. The SFV is frequently accompanied by the left colic artery or AMCA.

The Prognostic Nutritional Index is a Predictive Marker for Postoperative Complications in Patients with Late-Onset Ulcerative Colitis.

PURPOSE: The number of patients with late-onset ulcerative colitis (UC) requiring surgery has increased in recent years. The risk of postoperative complications is higher in the elderly, so preoperative assessment is important. We aimed to explore the performance of preoperative assessment of nutritional markers for predicting postoperative complications in patients with late-onset UC. METHODS: We retrospectively analysed 140 medically refractory UC patients who underwent surgery. The association between age at UC onset and risk of postoperative complications was explored using a fractional polynomial model. Uni- and multi-variate logistic regression analyses were performed to identify nutritional markers associated with postoperative complications. RESULTS: The polynomial model showed patients with UC onset after 50 years of age had an increased risk of postoperative complications. Late-onset (LO) UC, an onset occurring after 50 years old, was associated with a higher risk of incisional surgical site infection (SSI) and intra-abdominal abscess than early-onset (EO) UC. Compared with the EO group, the LO group had fewer nutritional markers that were significantly associated with postoperative complications. The prognostic nutritional index (PNI) was calculated using the albumin level and the total lymphocyte count, and it was the only index that was significant in the LO group (odds ratio 0.872 95% CI 0.77-0.99, P = 0.03). CONCLUSIONS: It was more difficult to use nutritional status to predict the risk of postoperative complications in patients with late-onset UC than in patients with early-onset ulcerative colitis. PNI may be a useful nutritional marker for patients with both late- and early-onset UC.

Prognostic Impact of Main Lymph Node Metastasis in Patients with Colon Cancer.

BACKGROUND: Although extended lymph node dissection during colon cancer surgery is recommended in both Western and Eastern countries, the perception and clinical significance of main lymph node metastasis (MLNM) remains controversial. METHODS: In total, 1557 patients with colon cancer who underwent curative resection with D3 dissection were retrospectively analyzed. Clinicopathological factors associated with MLNM were analyzed. Kaplan-Meier survival analysis and log-rank tests were used to compare the prognosis between the MLNM and non-MLNM groups. RESULTS: Multivariate analysis showed that overall survival (OS) [hazard ratio, 2.117 (0.939-4.774), p = 0.071] and recurrence-free survival (RFS) [hazard ratio, 2.183 (1.182-4.031), p = 0.013] were affected by the MLNM status independent of the TNM stage. Survival analysis demonstrated that among patients with stage III disease, the OS and RFS rates were significantly different between patients with and without MLNM (OS: p = 0.0147, RFS: p = 0.0001). However, the OS and RFS rates were not significantly different between patients who had stage III disease with MLNM and patients who had stage IV disease (OS: p = 0.5901, RFS: p = 0.9610). CONCLUSIONS: MLNM is an independent prognostic factor for patients with colon cancer. The addition of the MLNM status to the current TNM classification may enhance the prognostic value of the TNM staging system and the clinical efficacy of adjuvant therapy in patients with colon cancer.

Analysis of the short-term outcomes after esophagectomy for esophageal cancer during the COVID-19 pandemic using data from a nationwide Japanese database.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic had adversely impacted cancer screening, diagnosis, and treatment. We investigated the change in medical resource, such as the intensive care unit use, and short-term outcomes after esophagectomy during the pandemic. METHODS: Data of patients who underwent esophagectomy for esophageal cancer registered in the National Clinical Database (NCD) in Japan from January 2018 to December 2021 were analyzed. The time series change in the number of surgical cases; usage of intensive care unit; incidence of morbidity and mortality; standardized mortality and morbidity ratio (SMR) for 30-days mortality; surgical mortality; and morbidities for pneumonia, sepsis, unplanned intubation, and anastomotic leakage were evaluated. RESULTS: The annual number of patients undergoing esophagectomy remained similar from 2018 to 2021. The negative impact of the pandemic on medical resources was strongly identified in the patients from an epidemic area where there is a higher cumulative number of infections per population as compared to all prefectures. The proportions of patients admitted to the intensive care unit were 91.4%, 93.0%, 91.6%, and 90.5% in 2018, 2019, 2020, and 2021, respectively. Moreover, 93.3%, 94.0%, 92.0%, and 90.9% patients who underwent surgery in an epidemic area were admitted to the intensive care unit in 2018, 2019, 2020, and 2021, respectively. However, the morbidity and mortality rates during the pandemic did not worsen according to the SMR values. CONCLUSIONS: Esophagectomy was performed during the pandemic despite limited medical resources by a systematic endeavor of the entire surgical department in Japan, without increasing the incidence rate of worse outcome.

Real-world application of next-generation sequencing-based test for surgically resectable colorectal cancer in clinical practice.

Aim: To evaluate the significance of next-generation sequencing-based gene panel testing in surgically resectable colorectal cancer by analyzing real-world data. Materials & methods: A total of 107 colorectal cancer patients who underwent curative surgery were included, and correlations between next-generation sequencing data and clinicopathological findings were evaluated. Results: More combination patterns in gene alteration were identified in advanced-stage tumors than in early-stage tumors. The copy number alteration count was significantly lower in right-sided colon tumors and early-stage tumors. Homologous recombination deficiency was more often identified in advanced-stage tumors, and high homologous recombination deficiency status was useful for identifying high-risk stage II tumors. Conclusion: Homologous recombination deficiency was identified as a useful result of gene panel testing with novel utility in clinical practice.

The prognostic impact of preoperative mean corpuscular volume in colorectal cancer.

OBJECTIVE: The relationship between preoperative mean corpuscular volume and postoperative prognosis has been reported in some cancers recently, but no certain consensus has been reached, especially for colorectal cancer. We evaluated the usefulness of mean corpuscular volume as a prognostic factor in colorectal cancer patients. METHODS: This study included 1003 patients with colorectal cancer who underwent curative surgery in a single institution. The relationship between mean corpuscular volume values and postoperative recurrence was evaluated by fractional polynomial model. Based on the result, patients were divided into groups according to mean corpuscular volume values. Clinicopathological factors and long-term outcomes were compared between the groups. RESULTS: The risk of postoperative recurrence according to mean corpuscular volume value showed a J-shaped curve, suggesting that both low and high mean corpuscular volume have high risk. Low mean corpuscular volume (≤84 fl) group was oncologically advanced in terms of pathological tumor stage, histological grade and lymphatic invasion with higher inflammation markers. High mean corpuscular volume (>95 fl) group had higher frequency of drinking habit with higher values of aspartate aminotransferase, alanine aminotransferase and γ-glutamyl transpeptidase. Abnormal mean corpuscular volume group including these two groups showed significantly worse disease-free survival than the other (P < 0.001). Multivariate analysis suggested that abnormal mean corpuscular volume was an independent risk factor for postoperative recurrence (hazard ratio, 1.344; 95% confidence interval, 1.005-1.796; P = 0.046). Furthermore, its prognostic impact was more significant in pStage III than in other stages. CONCLUSION: Preoperative low and high mean corpuscular volume is a poor prognostic factor in colorectal cancer patients. It could be a predictive marker to estimate worse survival outcome after surgery.

Evaluation of abdominal aortic calcification by plain CT predicts anastomotic leakage in laparoscopic surgery for colorectal cancer.

BACKGROUND: Anastomotic leakage is one of the most severe and critical complications of laparoscopic surgery for colorectal cancer. However, definitive preoperative predictors of anastomotic leakage remain elusive. With the ageing of society, the number of colorectal cancer patients with arteriosclerotic disease in Japan is increasing. This study was performed to evaluate the correlation between preoperative arteriosclerosis and anastomotic leakage. METHODS: In total, 98 patients undergoing laparoscopic surgery for colorectal cancer with reconstruction using the double-stapling technique without diversion of the stoma were enrolled in the study. Preoperative assessment of arteriosclerotic disease was performed by abdominal computed tomography. The calcification volume percentage of the aorta between the level of the celiac artery root and aortic bifurcation was calculated using ZIOstation2 software, and the relationship between arteriosclerosis and anastomotic leakage was analysed. RESULTS: Among 98 cases, anastomotic leakage was observed in 16 (16.3%). The median calcification volume percentage (range) was 2.35% (0-40.3%). Age, male sex, hypertension, dissection number, estimated glomerular filtration rate and tumour location were correlated with anastomotic leakage on statistical analysis. Statistical analysis showed that calcification volume percentage was one of the robust risk factors for anastomotic leakage (odds ratio: 1.09, 95% confidence interval: 1.03-1.17, P < 0.01). CONCLUSIONS: Calcification of the abdominal aorta may be a promising predictor of AL after laparoscopic surgery for colorectal cancer reconstruction using the double-stapling technique.

Surgical glove perforation during laparoscopic colorectal procedures.

BACKGROUND: It has been reported that in conventional open surgery, approximately 10% of surgical gloves are perforated during surgery without being noticed. To protect both the patient and medical staff from harm, double gloving or changing gloves routinely at certain intervals during surgery is recommended. However, whether these protective measures are also necessary for laparoscopic colorectal surgery is unknown because the actual perforation rate during laparoscopic procedures is unclear. METHODS: Seventy-seven laparoscopic colorectal surgeries were evaluated, and a total of 616 surgical gloves used in the surgeries were collected for analysis. The presence of glove perforation was tested by the standard water-leak test method (EN455-1). RESULTS: Seven perforations were detected (1.1%). The duration of the laparoscopic procedure was not a statistically significant risk factor for glove perforation (p = 0.41). Postoperative surgical site infections (SSIs) were observed in 12 cases (15.6%), but there was no significant correlation between the presence of glove perforation and SSI (p = 0.92). According to the bacterial cultivation results, the majority of causative agents of SSI were enterobacteria, which belong to the major gut flora. CONCLUSION: Although the perforation rate was considerably lower than that in open surgery, surgical glove perforation occurred during laparoscopic procedures. Double gloving in laparoscopic colorectal surgery is recommended not to prevent SSI but to protect medical workers from harmful infections after direct contact with the patient.

Impact of intraoperative hypocapnia on postoperative complications in laparoscopic surgery for colorectal cancer.

PURPOSE: In laparoscopic surgery (LS) for colorectal cancer (CRC), the relationship between intraoperative end-tidal carbon dioxide concentration (EtCO2) and surgery-related complications remains unexplored. This study assessed the impact of intraoperative EtCO2 on postoperative complications in LS for CRC. METHODS: In total, 909 patients who underwent LS for CRC were enrolled. Hypocapnia and hypercapnia were defined as EtCO2 < 35 mmHg and > 40 mmHg, respectively, and the relationships between hypocapnia or hypercapnia duration and postoperative complications were analyzed. RESULTS: The median (range) durations of hypocapnia and hypercapnia were 2.0 (0-8.3) h and 0.3 (0-5.8) h, respectively. Complications were observed in 208 cases (23.0%), which included 37 (4.1%) instances of anastomotic leakage and 86 (9.5%) of superficial surgical site infection (SSI). While the hypercapnia duration was not associated with the short-term outcomes, prolonged hypocapnia was significantly correlated with complications (p = 0.02), specifically superficial SSI (p = 0.005). Multivariate analyses adjusted for confounding factors confirmed that hypocapnia prolongation was an independent risk factor for postoperative superficial SSI [OR 1.19; 95% confidence interval (Cl) 1.03-1.36, p = 0.01]. CONCLUSION: Intraoperative hypocapnia may be a risk factor for postoperative complications, in particular superficial SSI, in LS for CRC.

Horizontal spread of pericolic lymph node metastasis as a prognostic factor for recurrence in Stage III colorectal cancer.

AIM: Main lymph node (LN) metastasis dissected with a high vascular tie at the root of the feeding artery is a poor prognostic factor in colorectal cancer (CRC). However, the effects of horizontal spread on recurrence after curative resection remain unclear. The purpose of this study is to evaluate the relationship between the horizontal spread of LN metastasis and recurrence in CRC. METHOD: In this retrospective study, 189 CRC patients (98 men, 91 women) who underwent curative resection at our hospital from 2003 to 2018 and had only pericolic LN metastasis were divided into two groups: patients with LN metastasis beside the tumour only (T group, n = 121) and those with LN metastasis with horizontal spread (S group, n = 68) (mean follow-up period 50.9 ± 34.1 months). The primary outcome was recurrence-free survival (RFS). We investigated the correlation between clinicopathological background factors and recurrence using Cox regression analysis. RESULTS: Fewer than three LN metastases (N1) were found in 157 patients (107 T group, 50 S group), and four or more metastases (N2a) were found in 32 patients (14 T group, 18 S group). Univariate analyses revealed significantly shorter RFS in the S group [hazard ratio (HR) 1.95, 95% CI 1.07-3.55; p = 0.03). Multivariate analyses revealed that horizontal spread is an independent risk factor for recurrence (HR 1.95, 95% CI 1.05-3.68; p = 0.03). CONCLUSION: Although further investigation is needed, horizontal spread of LN metastasis is a prognostic factor for recurrence in Stage III CRC.

A contemporary snapshot of intestinal stem cells and their regulation.

Intestinal stem cells (ISCs) marked by Lgr5 are located at the bottom of the epithelial crypt compartment. Canonical Wnt signaling, activated by Wnt/Rspo ligands, determines the stem cell identity of Lgr5 + ISCs and is strictly regulated by the ISC niche. Emerging evidence indicates that both epithelial and stromal compartments provide the requisite Wnt/Rspo ligands, confining the ISC niche to the lower crypt regions of the intestine. Recent studies have also shown that the ISC niche can reprogram differentiated cells to replenish lost ISCs following tissue injury, accounting for the epithelial cell plasticity within the crypt compartment. Here we review these recent advances and discuss the role of canonical Wnt signaling in maintaining homeostasis and effecting cell plasticity following tissue injury in the intestine, which could reveal potential novel therapeutic opportunities in the clinic.