Venous Thromboembolism Following Lateral Lymph Node Dissection for Rectal Cancer.

BACKGROUND/AIM: Postoperative venous thromboembolism (VTE) is a well-recognized complication that leads to morbidity and mortality. Lateral lymph node dissection (LLND) for rectal cancer is thought to potentially increase the risk of VTE due to its technical complexity. However, the relationship between LLND and VTE remains inadequately understood. The aim of this study was to elucidate the impact of LLND on the incidence of postoperative VTE. PATIENTS AND METHODS: This is a retrospective analysis of patients who underwent rectal cancer resection between 2010 and 2018 to identify the risk factors associated with postoperative VTE. Patients were divided into two groups: those who underwent surgery with LLND (LLND+ group) and those who underwent surgery without LLND (LLND- group). RESULTS: A total of 543 patients were enrolled in this study, and 113 patients underwent surgery for rectal cancer with LLND. VTE developed in 8 patients (1.47%), with the incidence rates being 4.42% in the LLND+ group and 0.69% in the LLND- group, respectively (p=0.012). Three of 8 patients had developed severe postoperative complications, and the other two patients needed intraoperative repair of the iliac vein during LLND procedure. Multivariate analysis identified the incidence of postoperative complications and LLND as the independent risk factors of VTE. CONCLUSION: Patients undergoing rectal cancer surgery with LLND should be closely monitored for signs of VTE.

High Level Sacral Bone Resection for Locally Recurrent Rectal Cancer.

BACKGROUND/AIM: Locally recurrent rectal cancer (LRRC) involving the upper sacrum is generally considered a contraindication for curative surgery. In the surgical management of LRRC, sacrectomy is frequently performed to secure clear resection margins. Nonetheless, the indications for high sacrectomy remain controversial due to potential postoperative complications, questions about radicality, and the increased complexity of the operation. Furthermore, comprehensive studies addressing this issue are notably absent. This study aimed to assess the feasibility, safety, and surgical prognosis in high sacrectomy for LRRC. PATIENTS AND METHODS: All patients with LRRC who required concomitant sacrectomy, but did not include the inferior margin of the second sacral vertebra, between 2003 and 2014, were reviewed retrospectively. RESULTS: Eight patients with a median age of 59 years were included in this study. The proximal resection line for sacral bone resection was the central part of the S1 vertebra in one patient, lower edge of the S1 vertebra in six patients, and central part of the S2 vertebra in one patient. Negative margin resection was achieved in five out of the eight patients. The median operative time was 922 min, and the median operative blood loss volume was 6,370 ml. Major complications included pelvic abscess (n=5), ileus (n=1), and pulmonary vein embolism (n=1), none of which proved fatal during the postoperative period. Both the 5-year local re-recurrence-free survival rate and the 5-year distant metastasis-free survival rate were 50% (4/8). CONCLUSION: High sacrectomy is safe and feasible to achieve negative margins in patients with LRRC.

Clinical Significance of Preoperative and Postoperative Serum CEA and Carbohydrate Antigen 19-9 Levels in Patients Undergoing Curative Resection of Locally Recurrent Rectal Cancer.

BACKGROUND: Local recurrence is common after curative resection for rectal cancer. Although one expects radical resection of locally recurrent rectal cancer to be curative, the postoperative re-recurrence rate is relatively high. Therefore, identifying risk factors for recurrence may improve the prognosis of locally recurrent rectal cancer with early therapeutic intervention. OBJECTIVE: This study aimed to evaluate the relationship between perioperative serum CEA/carbohydrate antigen 19-9 levels and prognosis in locally recurrent rectal cancer to validate their usefulness for postoperative surveillance in locally recurrent rectal cancer. DESIGN: This was a single-center retrospective cohort study. SETTING: The study is based on data obtained from procedures at the Osaka University Hospital. PATIENTS: Ninety patients underwent radical resection for locally recurrent rectal cancer between January 2000 and January 2015. MAIN OUTCOME MEASURES: We evaluated the correlation between perioperative serum CEA/carbohydrate antigen 19-9 levels and prognosis after complete resection of locally recurrent rectal cancer and the serum CEA and carbohydrate antigen 19-9 levels at the diagnosis of postoperative re-recurrence. RESULTS: The median preoperative serum CEA level was 4 ng/mL and carbohydrate antigen 19-9 level was 12 U/mL. Of the 90 patients, 43.3% had serum CEA ≥5 ng/mL, and 15.6% had serum carbohydrate antigen 19-9 ≥37 U/mL. Preoperatively, this serum carbohydrate antigen 19-9 level strongly correlated with poorer prognoses regarding cancer-specific survival. Postoperatively, serum CEA ≥5 ng/mL significantly correlated with a worse prognosis. At the time of diagnosis of re-recurrence after resection of locally recurrent rectal cancer, 53.2% of patients had serum CEA ≥5 ng/mL, and 23.4% of patients had serum carbohydrate antigen 19-9 ≥37 U/mL. LIMITATIONS: The study was limited by its single-center retrospective design, an insufficient sample size, and a relatively long study period. CONCLUSIONS: High serum levels of carbohydrate antigen 19-9 preoperatively and CEA postoperatively are associated with poor prognosis after locally recurrent rectal cancer. Furthermore, we found a high rate of serum CEA elevation in the diagnosis of postoperative re-recurrence. See Video Abstract at http://links.lww.com/DCR/C106 . IMPORTANCIA CLNICA DE LOS NIVELES SRICOS PREOPERATORIOS Y POSOPERATORIOS DE CEA Y CA EN PACIENTES SOMETIDOS A RESECCIN CURATIVA DE CNCER DE RECTO LOCALMENTE RECURRENTE: ANTECEDENTES:La recurrencia local es común después de la resección curativa del cáncer de recto. Aunque se espera que la resección radical del cáncer rectal localmente recurrente sea curativa, la tasa de recurrencia posoperatoria es relativamente alta. Por lo tanto, la identificación de los factores de riesgo de recurrencia puede mejorar el pronóstico del cáncer de recto localmente recurrente con una intervención terapéutica temprana.OBJETIVO:Evaluamos la relación entre los niveles séricos perioperatorios de CEA/CA19-9 y el pronóstico en el cáncer de recto localmente recurrente para validar su utilidad para la vigilancia posoperatoria en el cáncer de recto localmente recurrente.DISEÑO:Este fue un estudio de cohorte retrospectivo de un solo centro.AJUSTE:El estudio se basa en datos obtenidos de procedimientos en el Hospital Universitario de Osaka.PACIENTES:Noventa pacientes fueron sometidos a resección radical por cáncer de recto localmente recurrente entre Enero de 2000 y Enero de 2015.PRINCIPALES MEDIDAS DE RESULTADOS:Evaluamos la correlación entre los niveles séricos perioperatorios de CEA/CA19-9 y el pronóstico después de la resección completa del cáncer de recto localmente recurrente y los niveles séricos de CEA y CA19-9 en el diagnóstico de recurrencia posoperatoria.RESULTADOS:La mediana de los niveles séricos preoperatorios de CEA y CA19-9 fueron de 4 ng/mL y 12 U/mL, respectivamente. De los 90 pacientes, el 43,3 % tenía CEA sérico ≥5 ng/mL y el 15,6 % tenía CA19-9 sérico ≥37 U/mL. Antes de la operación, este nivel sérico de CA19-9 se correlacionó fuertemente con peores pronósticos con respecto a la supervivencia específica del cáncer. Después de la operación, el CEA sérico ≥5 ng/mL se correlacionó significativamente con un peor pronóstico. En el momento del diagnóstico de recurrencia después de la resección del cáncer de recto localmente recurrente, el 53,2 % de los pacientes tenían CEA sérico ≥5 ng/mL y el 23,4 % de los pacientes tenían CA19-9 sérico ≥37 U/mL.LIMITACIONES:El estudio estuvo limitado por su diseño retrospectivo de un solo centro, un tamaño de muestra insuficiente y un período de estudio relativamente largo.CONCLUSIONES:Los niveles séricos altos de CA19-9 antes de la operación y de CEA después de la operación están asociados con un mal pronóstico después del cáncer de recto localmente recurrente. Además, encontramos una alta tasa de elevación del CEA sérico en el diagnóstico de recurrencia posoperatoria. Consulte el Video Resumen en http://links.lww.com/DCR/C106 . (Traducción-Dr. Yesenia Rojas-Khalil ).

Postoperative pain management after concomitant sacrectomy for locally recurrent rectal cancer.

PURPOSE: To assess pain management in patients post-sacrectomy, focusing on opioid use, and to identify the factors associated with postoperative pain. METHODS: Patients who underwent resection of locally recurrent rectal cancer (LRRC) with concomitant sacrectomy at one of two hospitals between 2007 and 2020 were reviewed retrospectively. We examined the use of opioids preoperatively and postoperatively. Patients were classified into high and low sacrectomy groups based on the sacral bone resection level passing through the S3 vertebra. RESULTS: Sixty-four patients were enrolled. Opioid use was significantly higher in the high sacrectomy group than in the low sacrectomy group at all times assessed: on postoperative days 7, 14, 30, 90, 180, and 365. Opioid use 3 months after locally recurrent rectal cancer surgery was significantly higher in patients with local re-recurrence of the tumor than in those without re-recurrence (p < 0.05), and the median morphine-equivalent opioid use 3 months postoperatively was significantly higher in the high sacrectomy group (30 vs. 0 mg/day; p < 0.05). CONCLUSIONS: Opioid use after concomitant sacrectomy for LRRC was higher in the high sacrectomy group. Prolonged postoperative pain or increasing pain was associated with local recurrence.

Development and evaluation of a Japanese prediction model for low anterior resection syndrome after rectal cancer surgery.

BACKGROUND: Low anterior resection syndrome (LARS) is the most common complication after rectal cancer resection. We aimed to identify LARS' predictive factors and construct and evaluate a predictive model for LARS. METHODS: This retrospective study included patients with rectal cancer more than 1 year after laparoscopic or robotic-assisted surgery. We administered a questionnaire to evaluate the degree of LARS. In addition, we examined clinical characteristics with univariate and multivariate analysis to identify predictive factors for major LARS. Finally, we divided the obtained data into a learning set and a validation set. We constructed a predictive model for major LARS using the learning set and assessed the predictive accuracy of the validation set. RESULTS: We reviewed 160 patients with rectal cancer and divided them into a learning set (n = 115) and a validation set (n = 45). Univariate and multivariate analyses in the learning set showed that male (odds ratio [OR]: 2.88, 95% confidence interval [95%CI] 1.11-8.09, p = 0.03), age < 75 years (OR: 5.87, 95%CI 1.14-47.25, p = 0.03) and tumors located < 8.5 cm from the AV (OR: 7.20, 95%CI 2.86-19.49, p < 0.01) were significantly related to major LARS. A prediction model based on the patients in the learning set was well-calibrated. CONCLUSIONS: We found that sex, age, and tumor location were independent predictors of major LARS in Japanese patients that underwent rectal cancer surgery. Our predictive model for major LARS could aid medical staff in educating and treating patients with rectal cancer before and after surgery.

[Capecitabine and Oxaliplatin(CAPOX)plus Bevacizumab as Second-Line Chemotherapy for Metastatic Colorectal Cancer].

OBJECTIVE: To evaluate the efficacy and safety of CAPOX plus bevacizumab as second-line chemotherapy for metastatic colorectal cancer. METHODS: In this multicenter phase Ⅱ study, the planned number of patients was 48, but owing to poor case accumulation, registration was discontinued for 20 patients. The primary endpoint was the response rate(RR). Secondary endpoints were progression-free survival(PFS), overall survival(OS), disease control rate(DCR), and safety. RESULTS: First-line treatment was combined with irinotecan in 14 cases and bevacizumab in 12 cases. The median number of second- line treatment courses was 7, and the median treatment period was 203 days. The reason for discontinuation of treatment was disease progression in 13 cases, adverse events in 4 cases, and other reasons in 3 cases. The best response was PR in 5 cases, SD in 8 cases, and NE in 4 cases. The RR was 25%, and the DCR was 65%. The median PFS was 7.2 months, and the median OS was 18.6 months. Grade≥3 adverse events were neutropenia in 3 cases and diarrhea and peripheral neuropathy in 2 cases each. There were no treatment-related deaths. CONCLUSION: CAPOX plus bevacizumab was a safe and effective second-line treatment option for metastatic colorectal cancer.

Impact of the preoperative prognostic nutritional index as a predictor for postoperative complications after resection of locally recurrent rectal cancer.

BACKGROUND: Local recurrence is common after curative resections for rectal cancer. Surgical intervention is among the best treatment choices. However, achieving a negative resection margin often requires extensive pelvic organ resections; thus, the postoperative complication rate is quite high. Recent studies have reported that the inflammatory index could predict postoperative complications. This study aimed to validate the correlation between clinical factors, including inflammatory markers, and severe complications after surgery for local recurrent rectal cancer. METHODS: This retrospective study included 99 patients that underwent radical resections for local recurrences of rectal cancer. Postoperative complications were graded according to the Clavien-Dindo classification. Grades ≥3 were defined as severe complications. Risk factors for severe complications were identified with univariate and multivariate logistic regression models and assessed with receiver-operating characteristic curves. RESULTS: Severe postoperative complications occurred in 38 patients (38.4%). Analyses of correlations between inflammatory markers and severe postoperative complications revealed that the strongest correlation was found between the prognostic nutrition index and severe postoperative complications. The receiver-operating characteristic analysis showed that the optimal prognostic nutrition index cut-off value was 42.2 (sensitivity: 0.790, specificity: 0.508). In univariate and multivariate analyses, a prognostic nutrition index ≤44.2 (Odds ratio: 3.007, 95%CI:1.171-8.255, p = 0.02) and a blood loss ≥2850 mL (Odds ratio: 2.545, 95%CI: 1.044-6.367, p = 0.04) were associated with a significantly higher incidence of severe postoperative complications. CONCLUSIONS: We found that a low preoperative prognostic nutrition index and excessive intraoperative blood loss were risk factors for severe complications after surgery for local recurrent rectal cancer.

SIRT3-Mediated SOD2 and PGC-1α Contribute to Chemoresistance in Colorectal Cancer Cells.

BACKGROUND: Anticancer drugs generate excessive reactive oxygen species (ROS), which can cause cell death. Cancer cells can resist this oxidative stress, but the mechanism of resistance and associations with chemoresistance are unclear. Here, we focused on Sirtuin 3 (SIRT3), a deacetylating mitochondrial enzyme, in oxidative stress resistance in colorectal cancer (CRC). METHODS: To evaluate SIRT3-related changes in mitochondrial function, ROS (mtROS) induction, and apoptosis, we used the human CRC cell lines HT29 and HCT116 transfected with short-hairpin RNA targeting SIRT3 and small interfering RNAs targeting superoxide dismutase 2 mitochondrial (SOD2) and peroxisome proliferator-activated receptor γ coactivator-1 (PGC-1α). In 142 clinical specimens from patients with CRC, we also assessed the association of SIRT3 protein levels (high/low) and prognosis. RESULTS: SIRT3 expression correlated with mtROS generation and apoptosis induction in cells treated with anticancer agents. Suppressing SIRT3 increased mtROS levels and cell sensitivity to anticancer agents. SIRT3 knockdown decreased SOD2 expression and activity, and suppressing SOD2 also improved sensitivity to anticancer drugs. In addition, SIRT3 was recruited with PGC-1α under oxidative stress, and suppressing SIRT3 decreased PGC-1α expression and mitochondrial function. PGC-1α knockdown decreased mitochondrial activity and increased apoptosis in cells treated with anticancer drugs. In resected CRC specimens, high vs low SIRT3 protein levels were associated with significantly reduced cancer-specific survival. CONCLUSIONS: SIRT3 expression affected CRC cell chemoresistance through SOD2 and PGC-1α regulation and was an independent prognostic factor in CRC. SIRT3 may be a novel target for CRC therapies and a predictive marker of sensitivity to chemotherapy.

[Laparoscopic Left Hemicolectomy for Advanced Descending Colon Cancer in Patient with Idiopathic Pulmonary Arterial Hypertension-Report of a Case].

We experienced a case of laparoscopic left hemicolectomy for advanced descending colon cancer in patient with idiopathic pulmonary arterial hypertension(IPAH). The patient was a 39-year-old woman. She visited her family doctor in November 201X because of bowel movement disturbance and melena. She was diagnosed as advanced descending colon cancer. Although intraoperative management for hemodynamic stability was expected to be difficult due to IPAH, hemodynamic stability was achieved under 10 mmHg pneumoperitoneum. During the operation noradrenaline and phenylephrine were used for hemodynamic management. Laparoscopic left hemicolectomy was performed safely. Postoperative histopathological findings were as follows; Type 2, tub1>tub2, pT4a(SE), pN1a(1/65), int, INF b, ly1, v1, Pn1b, pPM0, pDM0, pStage Ⅲb(the Japanese Classification of Colorectal, Appendiceal, and Anal Carcinoma, 9th edition). The patient was discharged from the hospital on the 18th day after surgery without any complications except for Grade 2 diarrhea, which was considered a side effect of PGI2 preparation.