TLK1 Inhibition Enhances the Anticancer Effect of Deep UV Irradiation Through CHK1 Activation.

BACKGROUND/AIM: A deep ultraviolet (DUV) light-emitting diode (LED) is a device that can irradiate electromagnetic waves from 250 nm to 350 nm. Tousled-like kinase 1 (TLK1) encodes a nuclear serine/threonine kinase, which is thought to influence the effects of DUV irradiation in cancer. The aim of this study was to clarify the interaction of TLK1 with DUV irradiation-induced DNA damage in cancer cells. MATERIALS AND METHODS: Pancreatic cancer cell lines were treated with or without DUV. TLK1 expression and phosphorylation in the two groups were examined. Then, these cancer cell lines were treated with thioridazine (THD), DUV or both. Thereafter, cytomorphology and apoptosis were assessed. Several proteins related to DNA damage, were analyzed in cancer cells treated with DUV and THD. Tumors in a subcutaneous xenograft model were treated with THD, DUV, or both for six weeks. RESULTS: DUV irradiation induced the phosphorylation of TLK1 in pancreatic cancer cell lines. Cytomorphology was significantly changed in pancreatic cancer cells treated with DUV and THD. TLK1 inhibition enhanced DUV irradiation-induced apoptosis in cancer cells. Interestingly, CHK1 and pCHK1 expression was suppressed after TLK1 inhibition. In addition, inhibition of MRE11 led to a decrease in the expression of CHK1 and pCHK1, accompanied by a notable increase in apoptosis. In the subcutaneous xenograft models, the tumor volume in the DUV and THD groups was lower than that in the other groups. CONCLUSION: TLK1 phosphorylation is an important event in DUV irradiation. DUV irradiation combined with TLK1 inhibition has therapeutic potential in pancreatic cancer cells.

Short- and long-term outcomes of surgical treatment for inguinal lymph node metastasis in rectal and anal canal adenocarcinoma.

AIM: The significance of lymphadenectomy and its indications in patients with inguinal lymph node metastasis (ILNM) of anorectal adenocarcinoma is unclear. This study aimed to clarify the surgical outcomes and prognostic factors of inguinal lymphadenectomy for ILNM. METHOD: This study included patients who underwent surgical resection for ILNM of rectal or anal canal adenocarcinoma with pathologically positive metastases between 1997 and 2011 at 20 participating centres in the Study Group for Inguinal Lymph Node Metastasis from Colorectal Cancer organized by the Japanese Society for Cancer of the Colon and Rectum. Clinicopathological characteristics and short- and long-term postoperative outcomes were retrospectively analysed. RESULTS: In total, 107 patients were included. The primary tumour was in the rectum in 57 patients (53.3%) and in the anal canal in 50 (46.7%). The median number of ILNMs was 2.34. Postoperative complications of Clavien-Dindo Grade III or higher were observed in five patients. The 5-year overall survival rate was 38.8%. Multivariate analysis identified undifferentiated histological type (P < 0.001), pathological venous invasion (P = 0.01) and pathological primary tumour depth T0-2 (P = 0.01) as independent prognostic factors for poor overall survival. CONCLUSION: The 5-year overall survival after inguinal lymph node dissection was acceptable, and it warrants consideration in more patients. Further larger-scale studies are needed in order to clarify the surgical indications.

Significance of Adjuvant Chemotherapy for Obstructive Colorectal Cancer After Stent Placement: A Multicenter Retrospective Study.

BACKGROUND/AIM: To explore the survival benefit of adjuvant chemotherapy for obstructive colorectal cancer (OCRC) managed by self-expandable metallic stent (SEMS) placement as a bridge to surgery (BTS). PATIENTS AND METHODS: One hundred twenty-nine patients with pathological stage II/III OCRC who underwent BTS using a SEMS were included in this multicenter retrospective study. Patients were divided into the no-adjuvant chemotherapy group (No-Adj group) (n=52) and adjuvant chemotherapy group (Adj group) (n=77), and relapse-free survival (RFS) was compared. RESULTS: The No-Adj group had more fragile patient background factors, such as higher age, higher American Society of Anesthesiologists score, and lower preoperative albumin compared with the Adj group. The 3-year RFS rates for the overall cohort were significantly different between the No-Adj and Adj groups (56.4% and 78.5%, respectively; p=0.003). Significant RFS benefits of adjuvant chemotherapy were observed in both pathological stage II and III cancer. Characteristics of more advanced cancer, such as high carcinoembryonic antigen (CEA), pathological T4, and lymphovascular invasion, were associated with survival improvement by adjuvant chemotherapy. T4 and adjuvant chemotherapy were significantly associated with RFS in the multivariate Cox proportional analysis. CONCLUSION: To our knowledge, this is the first study to show a survival benefit of adjuvant chemotherapy in patients with OCRC undergoing BTS using a SEMS. Adjuvant chemotherapy is basically recommended regardless of the cancer stage and is strongly recommended with more advanced characteristics, such as high CEA, T4, and lymphovascular invasion.

The benefits of interval appendectomy and risk factors for nonoperative management failure in the therapeutic strategy for complicated appendicitis.

PURPOSE: Emergency surgery (ES) for complicated appendicitis (CA) is associated with high morbidity. Interval appendectomy (IA) decreases this rate; however, nonoperative management (NOM) is not always successful. Some patients require unplanned ES due to NOM failure (IA failure: IA-F). This study aimed to verify the benefits of IA and to evaluate the risk factors for NOM failure. METHODS: Patients diagnosed with CA who underwent surgery between January 2012 and December 2021 were included in this study. We compared the surgical outcomes of the ES group with those of the IA success (IA-S) and IA-F groups. We also analyzed 14 factors that predicted NOM failure. RESULTS: Among 302 patients, the rate of severe complications (Clavien-Dindo grade ≥ III) was significantly higher in the ES group (N = 165) than in the IA-S group (N = 102). The rates were equal between the ES (N = 165) and IA-F (N = 35) groups. NOM was successful in 110 patients and failed in 27. Lack of abscesses, comorbidities, high WBC count, and free air were independent risk factors for NOM failure. CONCLUSIONS: Considering the benefits of IA and the non-inferior surgical outcomes of IA-F compared to ES, IA is a good therapeutic strategy for CA. However, in patients exhibiting four independent risk factors for NOM failure, careful monitoring of unplanned ES is necessary.

Prediction model of the risk for lateral local recurrence in locally advanced rectal cancer without enlarged lateral lymph nodes: Lessons from a Japanese multicenter pooled analysis of 812 patients.

Aim: Although the oncological impact of lateral lymph node dissection on enlarged lateral lymph nodes has been gradually accepted over the last decade, that on lateral lymph nodes without swelling remains doubtful. This study aimed to develop a prediction model for the future risk of lateral local recurrence and to clarify the value of adding lateral lymph node dissection in locally advanced rectal cancer without enlarged lateral lymph nodes. Methods: This retrospective, multi-institutional study recruited 812 patients with cStage II/III low rectal cancer without enlarged lateral lymph nodes <7 mm. Total lateral local recurrence was a hypothetical value of future risk of lateral local recurrence when lateral lymph node dissection was never performed. Results: Overall, total lateral local recurrences were observed in 67 patients (8.3%). In the multivariate analyses, the strongest risk factor for total local recurrences was no preoperative chemoradiotherapy (odds ratio [OR][95%Cl]: 33.2 [4.56-241.7], P < 0.001), followed by tumor distance ≤40 mm (OR [95%Cl]: 2.71 [1.51-4.86], P < 0.001) and lateral lymph node 5-7 mm (OR[95%Cl]: 2.38 [1.26-4.48], P = 0.007). In patients with lateral lymph nodes of 5-7 mm, the total lateral recurrence rate was 4.8% after preoperative chemoradiotherapy. Lateral lymph node dissection could reduce from a total lateral local recurrence of 21.6% to an actual lateral local recurrence of 8.0% in patients without preoperative treatment. Conclusion: We introduce a novel prediction model of future risk of lateral local recurrences, which has the potential to enable us to indicate lateral lymph node dissection selectively according to the patients' risks.

Impact of resection for ovarian metastases from colorectal cancer and clinicopathologic analysis: A multicenter retrospective study in Japan.

Aim: The aim of this study was to clarify the significance of resection of ovarian metastases from colorectal cancer and to identify the clinicopathologic characteristics. Methods: In this multicenter retrospective study, we evaluated data on ovarian metastases from colorectal cancer obtained from patients at 20 centers in Japan between 2000 and 2014. We examined the impact of resection on the prognosis of patients with ovarian metastases and examined prognostic factors. Results: The study included 296 patients with ovarian metastasis. The 3-y overall survival rate was 68.6% for solitary ovarian metastases. In all cases of this cohort, the 3-y overall survival rates after curative resection, noncurative resection, and nonresection were 65.9%, 31.8%, and 6.1%, respectively (curative resection vs noncurative resection [P < 0.01] and noncurative resection vs nonresection [P < 0.01]). In the multivariate analysis of prognostic factors, tumor size of ovarian metastasis (P < 0.01), bilateral ovarian metastasis (P = 0.01), peritoneal metastasis (P < 0.01), pulmonary metastasis (P = 0.04), liver metastasis (P < 0.01), and remnant of ovarian metastasis (P < 0.01) were statistically significantly different. Conclusion: The prognosis after curative resection for solitary ovarian metastases was shown to be relatively favorable as Stage IV colorectal cancer. Resection of ovarian metastases, not only curative resection but also noncurative resection, confers a survival benefit. Prognostic factors were large ovarian metastases, bilateral ovarian metastases, the presence of extraovarian metastases, and remnant ovarian metastases.

Oncologic investigation of the interval from stent placement to surgery in patients with obstructive colorectal cancer.

PURPOSE: Self-expandable metallic stent (SEMS) placement is widely used as a bridge to surgery (BTS) procedure for obstructive colorectal cancer. However, evidence regarding the optimal interval between SEMS placement and elective surgery is lacking. METHODS: We retrospectively collected data from patients with BTS between January 2013 and October 2021. Inverse probability treatment-weighted propensity score analyses were used to compare short- and long-term outcomes between the short-interval (SI) and long-interval (LI) groups, using a cutoff of 20 days. RESULTS: In total, 138 patients were enrolled in this study (SI group, n = 63; LI group, n = 75). In the matched cohort, the patients' backgrounds were well balanced. The incidence of Clavien-Dindo grade ≥ II postoperative complications was not significantly different between the SI and LI groups (19.0% vs. 14.0%, P = 0.47). There were no significant differences between the SI and LI groups in the 3-year recurrence-free survival (68.0% vs. 76.4%, P = 0.73) or 3-year overall survival rates (86.0% vs. 90.6%, P = 0.72). CONCLUSIONS: A longer interval did not deteriorate the oncological outcomes. Individual perioperative management with an appropriate interval to improve the patient's condition is required to ensure safe surgery.

Pks-positive Escherichia coli in tumor tissue and surrounding normal mucosal tissue of colorectal cancer patients.

A significant association exists between the gut microbiome and colorectal carcinogenesis, as well as cancer progression. It has been reported that Escherichia coli (E. coli) containing polyketide synthetase (pks) island contribute to colorectal carcinogenesis by producing colibactin, a polyketide-peptide genotoxin. However, the functions of pks+ E. coli in initiation, proliferation, and metastasis of colorectal cancer (CRC) remain unclear. We investigated the clinical significance of pks+ E. coli to clarify its functions in CRC. This study included 413 patients with CRC. Pks+ E. coli of tumor tissue and normal mucosal tissue were quantified using droplet digital PCR. Pks+ E. coli was more abundant in Stages 0-I tumor tissue than in normal mucosal tissue or in Stages II-IV tumor tissue. High abundance of pks+ E. coli in tumor tissue was significantly associated with shallower tumor depth (hazard ratio [HR] = 5.0, 95% confidence interval [CI] = 2.3-11.3, p < 0.001) and absence of lymph node metastasis (HR = 3.0, 95% CI = 1.8-5.1, p < 0.001) in multivariable logistic analyses. Pks+ E. coli-low and -negative groups were significantly associated with shorter CRC-specific survival (HR = 6.4, 95% CI = 1.7-25.6, p = 0.005) and shorter relapse-free survival (HR = 3.1, 95% CI = 1.3-7.3, p = 0.01) compared to the pks+ E. coli-high group. Pks+ E. coli was abundant in Stages 0-I CRC and associated with CRC prognosis. These results suggest that pks+ E. coli might contribute to carcinogenesis of CRC but might not be associated with tumor progression.

Successful management of malignant colovesical fistula using covered colonic self-expanding metallic stent: a case report.

BACKGROUND: A colovesical fistula (CVF) is commonly treated by resection of the intestine containing the fistula or creation of a defunctioning stoma. We herein report a case of successful fistula closure and avoidance of colostomy after placement of a covered colonic self-expanding metallic stent (SEMS) as a palliative treatment for a malignant CVF. CASE PRESENTATION: A 75-year-old man undergoing infusional 5-fluorouracil and irinotecan chemotherapy plus bevacizumab for recurrent peritoneal dissemination of rectal cancer was admitted to our hospital because of fecaluria with a high-grade fever. Blood tests showed a moderate inflammatory reaction (white blood cell count, 9200/mm3; C-reactive protein, 11.03 mg/dL; procalcitonin, 1.33 ng/mL). Urinary sediment examination showed severe bacteriuria. Abdominal contrast-enhanced computed tomography showed intravesical gas, thickening of the posterior wall of the bladder, and irregular thickening of the sigmoid colon wall contiguous with the posterior bladder wall. Magnetic resonance imaging (MRI) clearly showed a fistula between the bladder and sigmoid colon. Colonoscopy revealed a circumferential malignant stricture 15 cm from the anal verge, and a fistula to the bladder was identified by water-soluble contrast medium. We diagnosed a complicated urinary tract infection (UTI) associated with a CVF due to peritoneal dissemination and started empirical treatment with sulbactam/ampicillin. Given the absence of active inflammatory findings around the fistula on MRI and the patient's physical frailty, we decided to place a covered SEMS to close the fistula. Under fluoroscopic and endoscopic guidance, a covered colonic SEMS of 80-mm length and 20-mm diameter was successfully deployed, and the fistula was sealed immediately after placement. Urine culture on day 3 after stenting was negative for bacteria, and a contrast study on day 5 showed no fistula. The patient was discharged home on day 6 with no complications. The UTI did not recur for 4 months after discharge. CONCLUSIONS: A covered colonic SEMS was useful for sealing a malignant CVF in a patient unfit for surgery, and MRI was valuable to determine the status of the fistula. A covered colonic SEMS could be an alternative to surgical treatment for CVFs in patients who require palliative care.

Renal Dysfunction after Rectal Cancer Surgery: A Long-term Observational Study.

Objectives: Despite the high incidence of urinary dysfunction (UD) after rectal surgery, it remains questionable whether UD causes future chronic kidney disease (CKD). This study aimed to clarify the long-term trends in renal function and risk factors for future CKD after rectal resection. Methods: For comparison, patients who underwent rectal resection (n = 129) and colectomy (n = 127) between 2006 and 2017 were identified. The estimated glomerular filtration rate (eGFR) ratio was calculated as the ratio to the baseline. "eGFR ratio < 0.75 at 3-year" was adopted as a surrogate indicator of future CKD. Results: eGFR ratio significantly decreased in the rectal cohort compared with the colon cohort at 1.5 years (0.9 vs. 0.95, p = 0.008) and at 3 years (0.85 vs. 0.94, p < 0.001). Although the preoperative prevalence of CKD was lower in the rectal than the colon cohort (13.9% vs. 23.6%, p = 0.055), it was similar at 3 years (29.5% vs. 30.7%). In multivariate analysis, females, and cT4 were independent risk factors for future CKD, but UD itself was not. Conclusions: Postoperative eGFR significantly decreased after rectal cancer surgery compared to colectomy. The prevalence of CKD more than doubled at 3 years after rectal resection. The female sex and cT4 tumor, instead of the UD, were independent risk factors for future CKD.

Robot-assisted surgery for rectal cancer with solitary sacrococcygeal metastasis after neoadjuvant chemoradiotherapy: A case report.

An 81-year-old man was referred to our hospital for anal bleeding. Colonoscopy revealed a type 3 tumor at the upper rectum and biopsy showed adenocarcinoma. An enhanced circumferential lesion at the upper rectum and a solitary soft-tissue shadow at the fifth sacral vertebra to the coccyx were detected on abdominal magnetic resonance imaging. Fluorodeoxyglucose uptake was observed at the same sites on positron emission tomography. The patient was diagnosed with rectal cancer with isolated sacrococcygeal metastasis and was treated with neoadjuvant chemoradiotherapy followed by robotic surgery. Hartmann's operation was performed in the lithotomy position. The left internal iliac artery and vein were then divided. The internal pudendal artery and vein, the piriformis muscle, and sacrospinous ligament were also divided while preserving the lumbosacral trunk. The scheduled transection line of the sacral surface was fully exposed to prevent massive bleeding during sacrectomy. The dorsal surface of the sacrum was then exposed in the prone position and communicated with the pelvic space. The sacrum was transected at the superior margin of S3 and a specimen was extracted. Pathological findings revealed the infiltration of cancer cells in the sacrococcygeal specimen. The postoperative course was uneventful and the patient was discharged on postoperative day 13.

Crohn's Disease-Associated Anorectal Cancer Has a Poor Prognosis With High Local Recurrence: A Subanalysis of the Nationwide Japanese Study.

INTRODUCTION: Colorectal cancer (CRC) is one of the major life-threatening complications in patients with Crohn's disease (CD). Previous studies of CD-associated CRC (CD-CRC) have involved only small numbers of patients, and no large series have been reported from Asia. The aim of this study was to clarify the prognosis and clinicopathological features of CD-CRC compared with sporadic CRC. METHODS: A large nationwide database was used to identify patients with CD-CRC (n = 233) and sporadic CRC (n = 129,783) over a 40-year period, from 1980 to 2020. Five-year overall survival (OS), recurrence-free survival (RFS), and clinicopathological characteristics were investigated. The prognosis of CD-CRC was further evaluated in groups divided by colon cancer and anorectal cancer (RC). Multivariable Cox regression analysis was used to adjust for confounding by unbalanced covariables. RESULTS: Compared with sporadic cases, patients with CD-CRC were younger; more often had RC, multiple lesions, and mucinous adenocarcinoma; and had lower R0 resection rates. Five-year OS was worse for CD-CRC than for sporadic CRC (53.99% vs 71.17%, P < 0.001). Multivariable Cox regression analysis revealed that CD was associated with significantly poorer survival (hazard ratio 2.36, 95% confidence interval: 1.54-3.62, P < 0.0001). Evaluation by tumor location showed significantly worse 5-year OS and RFS of CD-RC compared with sporadic RC. Recurrence was identified in 39.57% of CD-RC cases and was mostly local. DISCUSSION: Poor prognosis of CD-CRC is attributable primarily to RC and high local recurrence. Local control is indispensable to improving prognosis.

Cyclodextrin Conjugated α-Bisabolol Suppresses FAK Phosphorylation and Induces Apoptosis in Pancreatic Cancer.

BACKGROUND/AIM: α-Bisabolol is an essential oil component extracted from plants, such as chamomile. We have previously reported that α-bisabolol suppressed proliferation, invasion, and motility of pancreas cancer. Cyclodextrin improved the solubility of α-bisabolol, therefore it enabled to administer intravenously. The aim of this study was to clarify the effect of cyclodextrin conjugated α-bisabolol (CD-BSB) and the signals pathways associated with α-bisabolol for pancreatic cancer. MATERIALS AND METHODS: Human pancreatic cancer cell lines were treated with or without CD-BSB. Cytomorphology and apoptosis were assessed in these treated groups. In addition, several phosphorylated proteins were analyzed to clarify the signal pathway concerning CD-BSB. In subcutaneous xenograft model, tumor volume and Ki-67 expression were evaluated among Control (untreated), CD-BSB, or Gemcitabine (GEM). RESULTS: CD-BSB significantly changed cytomorphology and induced apoptosis in pancreatic cancer cells. CD-BSB suppressed phosphorylation of focal adhesion kinase (FAK). In addition, pFAK 397 was inhibited by CD-BSB in a concentration-dependent manner in cancer cells. In the subcutaneous xenograft models, the tumor volume in the CD-BSB groups was lower than Control groups. Ki67-positive cells in CD-BSB treated group were lower than the GEM-treated groups. CONCLUSION: We clarified the efficiency of CD-BSB in xenograft tumor using intravenous administration. α-Bisabolol suppresses phosphorylation of FAK 397 and impairs cytoskeletal polymerization in a pancreatic cancer cell line. Further investigations are required to reveal the precise mechanisms of the antitumor effects of solubilized α-bisabolol to facilitate its clinical application. Our data indicate that solubilized α-bisabolol has therapeutic potential and could improve the prognosis of cancer patients.

Antitumor Effects of Deep Ultraviolet Irradiation for Pancreatic Cancer.

BACKGROUND/AIM: Deep ultraviolet (DUV) light spans within the 250 nm to 350 nm invisible wavelength range. Although it strongly damages various cells, the efficacy of DUV irradiation on pancreatic cancer cells has never been clarified. The purpose of this study was to reveal the antitumor effects of DUV irradiation on pancreatic cancer cells. MATERIALS AND METHODS: Human pancreatic cancer cell lines were eradicated with DUV or ultraviolet A (UVA) for 5 s. Several angiogenesis-related proteins were studied in cancer cells after DUV irradiation using a protein antibody array. A subcutaneous xenograft model was established by inoculation of pancreatic cancer cells into mice. Tumors in this model were irradiated with DUV or UVA once or twice for two weeks. Tumor volumes in these groups (DUV×1: one irradiation, DUV×2: two irradiations, and untreated) were analyzed one week after the second irradiation. RESULTS: DUV irradiation significantly changed the cytomorphology of pancreatic cancer cells. In addition, DUV irradiation induced apoptosis on pancreatic cancer cells more strongly than UVA irradiation and no irradiation. Interestingly, lower expression of thrombospondin 1 (TSP1) and tissue inhibitor of metalloproteinase 1 (TIMP1) was identified after DUV treatment. The tumor volume in the DUV-treated groups (DUV×1 and DUV×2) was smaller than that in the untreated group. CONCLUSION: Further investigations are required to reveal the precise mechanisms of the antitumor effects of DUV irradiation and to facilitate its clinical application as a new therapy for pancreatic cancer. Overall, DUV irradiation can be potentially used as a therapeutic option of pancreatic malignancy.

Early Prediction of a Serious Postoperative Course in Perihilar Cholangiocarcinoma: Trajectory Analysis of the Comprehensive Complication Index.

OBJECTIVE: The aim of this study was to visualize the postoperative clinical course using the comprehensive complication index (CCI) and to propose an early alarming sign for subsequent serious outcomes in perihilar cholangiocarcinoma. BACKGROUND: Surgery for this disease carries a high risk of morbidity and mortality. The developmental course of the overall morbidity burden and its clinical utility are unknown. METHODS: Patients who underwent major hepatectomy for perihilar cholan-giocarcinoma between 2010 and 2019 were reviewed retrospectively. All postoperative complications were evaluated according to the Clavien-Dindo classification (CDC), and the CCI was calculated on a daily basis until postoperative day 14 to construct an accumulating graph as a trajectory. Group-based trajectory modeling was conducted to categorize the trajectory into clinically distinct patterns and the predictive power of early CCI for a subsequent serious course was assessed. RESULTS: A total of 4230 complications occurred in the 484 study patients (CDC grade I, n = 27; II, n = 132; IlIa, n = 290; IIIb, n = 4; IVa, n = 21; IVb, n = 1; and V, n = 9). The trajectory was categorized into 3 patterns: mild (n = 209), moderate (n = 235), and severe (n = 40) morbidity courses. The 90-day mortality rate significantly differed among the courses: 0%, 0.9%, and 17.5%, respectively (P<0.001). The cutoff values of the CCI on postoperative days 1, 4, and 7 for predicting a severe morbidity course were 15.0, 28.5, and 40.6 with areas under the curves of 0.780, 0.924, and 0.984, respectively. CONCLUSIONS: The CCI could depict the chronological increase in the overall morbidity burden, categorized into 3 patterns. Early CCI potentially predicted sequential progression to serious outcomes.

Efficacy of Extended Modification in Left Hemihepatectomy for Advanced Perihilar Cholangiocarcinoma: Comparison Between H12345'8'-B-MHV and H1234-B.

OBJECTIVE: The aim of this study was to verify the prognostic impact of the tumor exposure at the liver transection margin (LTM) in left-sided perihilar cholangiocarcinoma and the impact of middle hepatic vein (MHV) resection on this exposure. BACKGROUND: In perihilar cholangiocarcinoma, tumors are unexpectedly exposed at the LTM during left hemihepatectomy (LH). METHODS: Patients who underwent LH for perihilar cholangiocarcinoma during 2002 to 2018 were retrospectively evaluated. LH was classified into conventional and extended types, which preserved and resected the MHVs, respectively. Positive LTM was defined as the involvement of invasive carcinoma at the liver transection plane and/or the adjacent Glissonean pedicle exposed. The clinicopathologic features and survival outcomes were compared between procedures. RESULTS: Among 236 patients, conventional and extended LHs were performed in 198 and 38 patients, respectively. The LTM was positive in 31 (13%) patients, with an incidence of 14% versus 8% ( P = 0.432) and 24% versus 0% in advanced tumors ( P = 0.011). Tumor size ≥ 18 mm ( P = 0.041), portal vein invasion ( P = 0.009), and conventional LH ( P = 0.028) independently predicted positive LTM. In patients with negative LTM, the survival was comparable between the two groups: 60.4% versus 59.2% at 3 years ( P = 0.206), which surpassed 17.7% for those with positive LTM in the conventional group ( P < 0.001). Multivariable analysis demonstrated that LTM status was an independent prognostic factor ( P = 0.009) along with ductal margin status ( P = 0.030). CONCLUSIONS: The LTM status is an important prognostic factor in perihilar cholangiocarcinoma. Extended LH reduced the risk of tumor exposure at the LTM with a subsequent improvement in the survival, particularly in advanced tumors.

Impact of preoperative muscle mass and quality on surgical outcomes in patients undergoing major hepatectomy for perihilar cholangiocarcinoma.

PURPOSES: This study sought to define the impact of skeletal muscle mass and quality on postoperative outcomes in patients with perihilar cholangiocarcinoma. METHODS: Patients who underwent major hepatectomy for perihilar cholangiocarcinoma were included. The normalized total psoas area (TPA) (psoas muscle index [PMI]) and average Hounsfield units of the TPA (psoas muscle density [PMD]) were measured using preoperative computed tomography images. The cohort was dichotomized using the following indices: sex-specific lowest tertile (low PMI and low PMD) and other (normal PMI and normal PMD). Intraoperative and postoperative outcomes were compared, focusing on PMI and PMD. RESULTS: A total of 456 patients were analyzed. The intraoperative blood loss (IBL) was 21.3 ml/kg in the low PMI group and 17.2 ml/kg in the normal PMI group (P = .008). Patients in the low PMI or PMD group experienced postoperative infectious complications more frequently than those in the other groups. The median survival time was 37.8 months in the low PMI group and 54.2 months in the normal PMI group (P = .027). CONCLUSIONS: PMI and PMD were closely associated with IBL and postoperative infectious complications. Additionally, PMI impacted long-term survival. These results suggest an importance of improving muscle mass and quality before surgery.