Increased mitochondria are responsible for the acquisition of gemcitabine resistance in pancreatic cancer cell lines.

Pancreatic ductal adenocarcinoma has a particularly poor prognosis as it is often detected at an advanced stage and acquires resistance to chemotherapy early during its course. Stress adaptations by mitochondria, such as metabolic plasticity and regulation of apoptosis, promote cancer cell survival; however, the relationship between mitochondrial dynamics and chemoresistance in pancreatic ductal adenocarcinoma remains unclear. We here established human pancreatic cancer cell lines resistant to gemcitabine from MIA PaCa-2 and Panc1 cells. We compared the cells before and after the acquisition of gemcitabine resistance to investigate the mitochondrial dynamics and protein expression that contribute to this resistance. The mitochondrial number increased in gemcitabine-resistant cells after resistance acquisition, accompanied by a decrease in mitochondrial fission 1 protein, which induces peripheral mitosis, leading to mitophagy. An increase in the number of mitochondria promoted oxidative phosphorylation and increased anti-apoptotic protein expression. Additionally, enhanced oxidative phosphorylation decreased the AMP/ATP ratio and suppressed AMPK activity, resulting in the activation of the HSF1-heat shock protein pathway, which is required for environmental stress tolerance. Synergistic effects observed with BCL2 family or HSF1 inhibition in combination with gemcitabine suggested that the upregulated expression of apoptosis-related proteins caused by the mitochondrial increase may contribute to gemcitabine resistance. The combination of gemcitabine with BCL2 or HSF1 inhibitors may represent a new therapeutic strategy for the treatment of acquired gemcitabine resistance in pancreatic ductal adenocarcinoma.

Impact of Early Enteral Nutrition on Delayed Gastric Emptying and Nutritional Status After Pancreaticoduodenectomy.

BACKGROUND: Although early enteral nutrition (EEN) is an accepted practice after pancreaticoduodenectomy (PD), the impact of EEN on postoperative complications or nutritional status remains unclear. We aimed to investigate the impact of EEN on delayed gastric emptying (DGE) and nutritional status after PD. METHODS: A total of 143 patients underwent PD between January 2012 and September 2020. We excluded patients who underwent a two-stage pancreatojejunostomy, in whom the enteral tube was accidentally pulled out, or with insufficient information in their medical records. The incidence of postoperative complications was compared between patients who received EEN (EEN group, n = 21) and those who did not (control group, n = 21) after propensity score matching. Univariate and multivariate analyses were performed to identify the risk factors affecting the incidence of these complications. Nutritional status was assessed at postoperative months 1, 3, and 6. RESULTS: The incidence of grade B/C DGE in the EEN group was significantly lower than that in the control group (4.8% vs. 28.6%, p = 0.03). There was no significant difference in overall morbidity, incidence of any other postoperative complications, or all-grade DGE. In multivariate analysis, EEN was associated with a reduction in the incidence of grade B/C DGE (p < 0.01). In the analysis of nutritional status, EEN was significantly associated with better nutritional status at postoperative month 1. CONCLUSION: EEN can lead to a lower clinically relevant DGE rate and better nutritional status in the early postoperative period in patients undergoing PD.

Preoperative Peripheral Blood Lymphocyte-to-Monocyte Ratio Predicts Long-Term Outcome for Patients with Pancreatic Ductal Adenocarcinoma.

BACKGROUND: Although various biomarkers are useful in predicting cancer prognosis, the most effective preoperative systemic biomarkers for pancreatic ductal adenocarcinoma (PDAC) have not been established. This study aimed to evaluate whether the lymphocyte-to-monocyte ratio (LMR) can predict the long-term outcomes for patients who were to undergo surgical resection of PDAC. METHODS: The study involved 170 patients with PDAC who underwent resection. Multivariate analysis was performed to identify the independent prognostic factors for overall survival (OS) and disease-free survival (DFS) among clinicopathologic, surgical, and seven systemic biomarker-related factors including LMR. Subgroup analysis of PDAC located in the body and tail of the pancreas (B/T PDAC) was performed (n = 60) to eliminate the influence of preoperative cholangitis and surgical procedure. Furthermore, OS according to the postoperative course of the LMR value group was investigated. RESULTS: A low LMR (<3.3) was the only independent predictive factor for OS (hazard ratio [HR], 3.52; p < 0.001) and DFS (HR, 3.31; p < 0.001) among the systemic biomarkers. Subgroup analysis of the B/T PDAC also showed that low the LMR was the independent predictive factor for OS (HR, 3.24; p = 0.002) and DFS (HR, 4.42; p = 0.003). The PDAC that maintained a high LMR from before surgery to 1 year after surgery showed good long-term outcomes (median OS, 8.5 years; 5-year survival rate, 61.8 %). CONCLUSIONS: Preoperative LMR was an independent predictor of OS and DFS after surgery for PDAC. Maintaining a high LMR through the pre- and postoperative courses might improve the prognosis for patients with PDAC.

Clinical study of a new skin antiseptic olanexidine gluconate in gastrointestinal cancer surgery.

BACKGROUND: Surgical site infection (SSI) is a common complication of gastrointestinal surgery. Olanexidine gluconate (OLG) is a novel skin antiseptic that is effective against a wide range of bacteria. The purpose of this study was to evaluate the bactericidal efficacy of OLG in gastrointestinal cancer surgery. METHODS: This retrospective study included a total of 281 patients who underwent gastrointestinal cancer surgery (stomach or colon). The patients were divided into two groups: 223 patients were treated with OLG (OLG group), and 58 patients were treated with povidone-iodine (PVP-I) (control group). The efficacy and safety outcomes were measured as the rate of SSI within 30 days after surgery. In addition, we conducted subgroup analyses according to the surgical approach (open or laparoscopic) or primary lesion (stomach or colon). RESULTS: There was a significant difference in the rate of SSI between the control group and OLG group (10.3% vs. 2.7%; p = 0.02). There was a significant difference in the SSI rate in terms of superficial infection (8.6% vs. 2.2%; p = 0.0345) but not in deep infection (1.7% vs. 0.5%; p = 0.371). There was no significant difference between the control group and OLG group in the overall rate of adverse skin reactions (5.2% vs. 1.8%; p = 0.157). CONCLUSION: This retrospective study demonstrates that OLG is more effective than PVP-I in preventing SSI during gastrointestinal cancer surgery.

Survival Benefits of Surgical Resection in Patients with Recurrent Biliary Tract Carcinoma.

BACKGROUND: Whether surgical resection for recurrent biliary tract carcinoma (BTC) prolongs survival and the patients who are most likely to benefit from such treatment remain unclear. METHODS: Among 251 patients with recurrences after the initial resection of BTC, a total of 21 patients (8.4%) underwent surgical resection for the recurrence, with a zero mortality rate. The clinicopathological features of these patients were compared with those of patients who did not undergo surgery. RESULTS: The median survival time (MST) after the first recurrence and the 5-year post-recurrent survival (PRS) rate were 19.8 months and 32.8%, respectively, for patients who underwent re-resection. Fourteen patients (66.7%) experienced second recurrences; however, none of these patients underwent further surgical resection. Surgical resection for recurrence was identified as an independent prognostic factor for survival after recurrence (hazard ratio of 0.33, 95% CI of 0.17-0.58, p < 0.001). Patients with less than three liver metastases had a significantly better PRS after surgical resection than after chemotherapy (p = 0.015). Among the patients with an isolated solitary liver metastasis, patients who underwent resection had a significantly longer MST after the first recurrence than patients receiving chemotherapy (22.8 vs. 10.9 months, p = 0.025), whereas the PRS was similar between the two groups among patients with two liver lesions. CONCLUSIONS: Surgical resection for recurrent BTC may prolong survival in highly selected patients. A hepatectomy might offer a survival benefit for patients with a solitary liver metastasis.

Contrast-enhancement ratio on multiphase enhanced computed tomography predicts recurrence of pancreatic neuroendocrine tumor after curative resection.

BACKGROUND/OBJECTIVE: No previous study has quantitatively investigated the degree of enhancement of pancreatic neuroendocrine tumors (pNETs) using a routine preoperative modality. The aim of this study was to evaluate the contrast-enhancement ratio (CER) of pNETs using multiphase enhanced CT and to assess the impact of the CER on disease recurrence after surgery. METHODS: A retrospective study was performed using data from 47 consecutive patients with pNETs who had undergone curative surgery. The CER of the tumor was calculated by dividing the CT attenuation value obtained during the maximum-enhanced phase by that obtained during the pre-enhanced phase. A region of interest was placed in the largest tumor dimension plane so as to cover as much surface of the tumor as possible while avoiding adjacent normal structures, calcification, and necrotic areas of the tumor. RESULTS: During a median follow-up period of 51 months (range, 1-132 months), a total of 4 patients (8.5%) developed disease recurrence. The median CER value was significantly lower for the patients with recurrence than for the patients without recurrence (2.9 vs. 4.3, P = 0.013). Univariate analyses showed that a CER ≤3.2 was significantly associated with disease recurrence (P < 0.001). All the patients with disease recurrence had tumors that were both large (>20 mm) and weakly enhanced (CER ≤ 3.2), whereas no recurrences were observed even in patients with tumors >20 mm when the CER was greater than 3.2. CONCLUSIONS: CER might be a useful predictor of disease recurrence in patients with pNETs.

Utilization of muscle area in an accurate prediction formula for renal function for patients with hepatocellular carcinoma.

OBJECTIVE: Accurate assessment of renal function prior to surgery for hepatocellular carcinoma is important for patient outcome, but current methods such as the estimated glomerular filtration rate (eGFR) are inadequate. We developed a new prediction formula that incorporates preoperative computed tomography (CT) imaging data to determine renal function. METHODS: We retrospectively analyzed 400 patients who underwent hepatectomy for hepatocellular carcinoma between January 2010 and December 2021. Predictors associated with renal function were identified by multivariate analysis. RESULTS: Age, sex, body height, body weight, body surface area, body mass index, serum creatinine, and muscle areas including third lumbar vertebra total muscle area (L3 TMA) determined by preoperative CT were identified as independent predictors likely to be associated with renal function. These were used to construct a new prediction formula using multiple regression analysis performed with a stepwise method: 232.2 + (-1.17 × age) + (-89.0 × serum creatinine) + (0.28 × L3 TMA). The median difference between conventional eGFR and CCr was 47.6 ml/min (range, 1.7-137.9 ml/min), while that between the new eGFR and CCr was 14.3 ml/min (range, 0.02-64.7 ml/min). Spearman rank correlation analysis revealed that the new eGFR was more positively correlated with CCr than conventional eGFR (ρ = 0.623, P < 0.05; ρ = 0.700, P < 0.05, respectively), and hence more accurately reflected renal function. CONCLUSION: A new prediction formula based on L3 TMA determined by CT is more accurate than conventional eGFR for evaluating renal function.

Long-term remnant liver volume dynamics after major hepatectomy for perihilar cholangiocarcinoma following portal vein embolization.

BACKGROUND: Portal vein embolization (PVE) followed by major hepatectomy is a common treatment strategy for patients with perihilar cholangiocarcinoma (PHCC); however, the long-term dynamics of the liver remnant volume (LRV) remain unclear. Here, we report the dynamics of the LRV in patients who underwent hepatectomy following PVE. METHODS: A total of 39 patients with PHCC who underwent right hemihepatectomy or left trisectionectomy with extrahepatic bile duct resection between 2004 and 2021 were enrolled in this study [PVE (n = 27) and non-PVE (n = 12]). Long-term remnant liver dynamics were analyzed in propensity score-matched pairs (n = 10/group). RESULTS: The LRV/future liver remnant volume (FLRV) at 1 week to 1 month after hepatectomy were smaller in the PVE group than in the non-PVE group (1.53 vs. 1.69, p = .044 and 1.52 vs 1.99, p = .003, respectively). In the non-PVE group, the LRV/FLRV ratio plateaued 1-3 months postoperatively, whereas progressive hypertrophy occurred in the PVE group, and the LRV/FLRV ratio became equal in both groups at 1 year after hepatectomy (1.96 vs. 1.97; p = .799). Multivariate analysis revealed that FLRV/total liver volume (TLV) ≤ 0.43 was the only independent predictor of LRV/FLRV ≥1.9 at 1 year after hepatectomy (odds ratio:5.345, 95% confidence interval:1.210-23.615; p = .027). CONCLUSION: Although the long-term LRV was nearly equal in both groups, short-term LRV hypertrophy was lower in the PVE group than in the non-PVE group.

Impact of anatomical liver resection for hepatocellular carcinoma in preventing early-phase local recurrence after surgery.

BACKGROUND: The superiority of anatomical liver resection (AR) for localized hepatocellular carcinoma (HCC) over nonanatomical liver resection (NR) remains controversial. This study aimed to investigate the impact of AR in preventing local and early HCC recurrence. METHODS: A total of 280 patients who underwent initial liver resection for solitary HCC ≤5 cm in diameter were categorized into the AR and NR groups and compared using propensity score matching analysis. RESULTS: Between the matched pairs (n = 87 in each group), the incidence rates of local and early (recurrence within 2 years after surgery) recurrences in the AR group were significantly lower than those in the NR group (13.8% vs. 28.7%, p = .025; 20.7% vs. 35.6%, p = .028, respectively). The overall survival in the AR group was better than that in the NR group (median: 13.4 vs. 7.6 years, p = .003). NR was among independent risk factors for early recurrence (odds ratio: 1.98, 95% CI: 1.1-3.6, p = .023) and prognostic factors for local recurrence (hazard ratio: 2.44, 95% CI: 1.4-4.4, p = .003). CONCLUSION: AR is superior in controlling local and early recurrence postoperatively for solitary HCC ≤5 cm in diameter compared with NR.

An Immunohistochemical Analysis of Osteopontin and S100 Calcium-binding Protein P is Useful for Subclassifying Large- and Small-duct Type Intrahepatic Cholangiocarcinomas.

Intrahepatic cholangiocarcinoma (iCCA) has been newly subclassified into two different subtypes: large-duct (LD) type and small-duct (SD) type. However, many cases are difficult to subclassify, and there is no consensus regarding subclassification criteria. LD type expresses the highly sensitive diagnostic marker S100 calcium-binding protein P (S100P), while SD type lacks sensitive markers. We identified osteopontin (OPN) as a highly sensitive marker for SD type. This study aimed to develop new subclassification criteria for LD-type and SD-type iCCA. We retrospectively investigated 74 patients with iCCA and subclassified them based on whole-section immunostaining of S100P and OPN. Of the 74 cases, 41 were subclassified as LD type, 32 as SD type, and one was indeterminate. Notably, all S100P-negative cases had OPN positivity. Seventy-three of the 74 cases (98.6%) were clearly and easily subclassified as LD or SD type using only these 2 markers. We also determined the value of immunohistochemistry in cases that were difficult to diagnose based on hematoxylin-eosin and Alcian blue-periodic acid-Schiff staining. Furthermore, we analyzed the clinicopathological characteristics and prognoses of these 2 subtypes. LD type was a poor prognostic factor on univariate analysis; it had significantly worse overall survival ( P = 0.007) and recurrence-free survival ( P < 0.001) than the SD type. In conclusion, we propose new subclassification criteria for iCCA based on immunostaining of S100P and OPN. These criteria may help pathologists to diagnose subtypes of iCCA, supporting future clinical trials and the development of medications for these 2 subtypes as distinct cancers.

A new fistula risk score using sarcopenic obesity and subcutaneous fat area for predicting postoperative pancreatic fistula after pancreaticoduodenectomy.

BACKGROUND/PURPOSE: Postoperative pancreatic fistula (POPF) is a serious complication of pancreaticoduodenectomy and current predictors of POPF are inadequate. We developed a new fistula score to more accurately predict POPF. METHODS: We retrospectively reviewed 169 patients who underwent pancreaticoduodenectomy between January 2010 and August 2021 at our institution and examined patients' risk factors according to the occurrence of grade B/C POPF. Muscle and fat were assessed on preoperative computed tomography images and cutoff values were determined by receiver operating characteristic curve analysis. RESULTS: Grade B/C POPF occurred in 38 (22.5%) patients. Multivariate analysis of patients' risk factors revealed that sarcopenic obesity (odds ratio [OR] 2.94; p = .033), L3 subcutaneous fat area (SFA) ≥ 98.0 cm2 (OR 2.69; p = .049), and soft pancreatic texture (OR 27.5; p = .002) were independent risk factors of grade B/C POPF occurrence. In addition, a new fistula risk score based on these factors revealed that 63.6% of patients with high scores developed grade B/C POPF, while those with negligible or low scores did not. CONCLUSIONS: A new fistula risk scoring system based on sarcopenic obesity, SFA, and pancreatic texture may accurately predict POFP.

Safety and oncological benefits of hepatectomy for hepatocellular carcinoma in octogenarians.

BACKGROUND: The number of octogenarians requiring surgery for hepatocellular carcinoma (HCC) is increasing. However, the safety of hepatectomy in octogenarians remains controversial. The aim of this retrospective study was to determine the effect of age on the short- and long-term outcomes of hepatectomy for HCC to evaluate the safety of hepatectomy for octogenarians. METHODS: Data from a total of 845 patients who underwent initial hepatectomy for HCC between April 1990 and March 2021 were retrospectively reviewed. Patients were categorized based on the age at the time of surgery (<80 years, n = 790; ≥80 years, n = 55), and the short- and long-term postoperative outcomes of the two groups were compared to evaluate whether hepatectomy is appropriate for octogenarian patients. RESULTS: The proportion of octogenarian patients undergoing hepatectomy increased from 2.6% in 1990-1995 to 16.8% in 2016-2020 (P < 0.001), and the overall incidences of anatomical and major hepatectomy have increased. There was no significant difference in the morbidity rate between the octogenarians and the group of patients <80 years old (60.0% vs. 54.4%, P = 0.420), and the 90-day mortality rate was 0% in the octogenarian group. Furthermore, the two groups had similar overall survival and recurrence-free survival rates (P = 0.173 and 0.671, respectively). CONCLUSION: Favorable postoperative outcomes following initial hepatectomy for HCC are achieved in appropriately selected octogenarians.

Combination of sarcopenia and prognostic nutritional index to predict long-term outcomes in patients undergoing initial hepatectomy for hepatocellular carcinoma.

OBJECTIVE: To determine if preoperative sarcopenia and prognostic nutritional index (PNI) could accurately predict the postoperative outcomes of patients with hepatocellular carcinoma (HCC) undergoing initial hepatectomy. METHODS: Three hundred three patients who underwent curative hepatectomy for HCC between January 2010 and August 2021 were enrolled and their data were retrospectively analyzed. Sarcopenia was determined from computed tomography images obtained 3 weeks prior to surgery, and PNI was calculated from preoperative albumin and whole lymphocyte count data in receiver operating characteristic (ROC) curve analysis, with a cutoff value of 46.2 to categorize high and low groups. RESULTS: One hundred six (35%) patients had sarcopenia prior to surgery. Kaplan-Meier analysis revealed that sarcopenia and low PNI were associated with significantly worse overall survival (OS) compared with no sarcopenia and high PNI, respectively (P = 0.023 and P = 0.035, respectively). In addition, patients with sarcopenia had worse OS than those without sarcopenia in the high and low PNI groups (P = 0.058 and P = 0.038, respectively). Sarcopenia (hazard ratio [HR] 1.66; 95% confidence interval [CI] 1.00-2.76; P = 0.048) and PNI ≤46.2 (HR 1.96; 95% CI 1.17-3.27; P = 0.011) were independent prognostic factors on multivariate analysis, and combined sarcopenia and PNI had a higher AUC value (AUC = 0.722, P < 0.001) than either one alone in ROC analysis. CONCLUSION: Combined sarcopenia and PNI as a prognostic marker can better predict the postoperative prognostic outcomes of HCC patients following hepatectomy than either sarcopenia or PNI alone.

Accuracy and limitations of preoperative assessment of longitudinal spread of perihilar cholangiocarcinoma.

OBJECTIVE: Although surgical resection offers the only chance of cure of perihilar cholangiocarcinoma and R1 resection has a poor prognosis, there is no consensus on optimal preoperative assessment of its longitudinal spread. We aimed to establish the optimal means of achieving this goal. METHODS: This was a retrospective, single-center study of 61 patients who had undergone multi-detector row computed tomography, endoscopic retrograde cholangiography, intraductal ultrasonography, and mapping biopsy prior to resection of perihilar cholangiocarcinomas in our institute from January 2010 and December 2021. RESULTS: The most accurate single methods for assessing longitudinal spread were intraductal ultrasonography and mapping biopsy (both 72.1%). A combination of all four assessment methods was accurate in 51 (83.6%) of our patients. Independent risk factors for inaccuracy were Bismuth-Corlette Type IV and high histologic-grade tumors. The R0 resection rate was higher with accurate than inaccurate assessments (90.2% vs. 30.0%, P < 0.001). R0 resection was associated with significantly better relapse-free survival than R1 resection (P = 0.006). However, overall survival did not differ between these groups. CONCLUSION: Preoperative assessment of longitudinal spread of perihilar cholangiocarcinomas by four different modalities is optimal, achieving 83.6% accuracy and a 90.2% R0 resection rate.

Impact of endothelial nitric oxide synthase activation on accelerated liver regeneration in a rat ALPPS model.

BACKGROUND: Although the associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) induces more rapid liver regeneration than portal vein embolization, the mechanism remains unclear. AIM: To assess the influence of inflammatory cytokines and endothelial nitric oxide synthase (eNOS) activation on liver regeneration in ALPPS. METHODS: The future liver remnant/body weight (FLR/BW) ratio, hepatocyte proliferation, inflammatory cytokine expression, and activation of the Akt-eNOS pathway were evaluated in rat ALPPS and portal vein ligation (PVL) models. Hepatocyte proliferation was assessed based on Ki-67 expression, which was confirmed using immunohistochemistry. The serum concentrations of inflammatory cytokines were measured using enzyme linked immune-solvent assays. The Akt-eNOS pathway was assessed using western blotting. To explore the role of inflammatory cytokines and NO, Kupffer cell inhibitor gadolinium chloride (GdCl3), NOS inhibitor N-nitro-arginine methyl ester (L-NAME), and NO enhancer molsidomine were administered intraperitoneally. RESULTS: The ALPPS group showed significant FLR regeneration (FLR/BW: 1.60% ± 0.08%, P < 0.05) compared with that observed in the PVL group (1.33% ± 0.11%) 48 h after surgery. In the ALPPS group, serum interleukin-6 expression was suppressed using GdCl3 to the same extent as that in the PVL group. However, the FLR/BW ratio and Ki-67 labeling index were significantly higher in the ALPPS group administered GdCl3 (1.72% ± 0.19%, P < 0.05; 22.25% ± 1.30%, P < 0.05) than in the PVL group (1.33% ± 0.11% and 12.78% ± 1.55%, respectively). Phospho-Akt Ser473 and phospho-eNOS Ser1177 levels were enhanced in the ALPPS group compared with those in the PVL group. There was no difference between the ALPPS group treated with L-NAME and the PVL group in the FLR/BW ratio and Ki-67 labeling index. In the PVL group treated with molsidomine, the FLR/BW ratio and Ki-67 labeling index increased to the same level as in the ALPPS group. CONCLUSION: Early induction of inflammatory cytokines may not be pivotal for accelerated FLR regeneration after ALPPS, whereas Akt-eNOS pathway activation may contribute to accelerated regeneration of the FLR.

Risk factors for postoperative cholangitis after pancreaticoduodenectomy and evaluation of internal stenting on hepaticojejunostomy: A single-center propensity score-based analysis.

BACKGROUND/PURPOSE: This retrospective study aimed to investigate the risk factors for postoperative cholangitis (POC) after pancreaticoduodenectomy (PD) and the efficacy of stenting on hepaticojejunostomy (HJ). METHODS: We investigated 162 patients. Postoperative cholangitis occurring before and after discharge was defined as early-onset POC (E-POC) and late-onset POC (L-POC), respectively. Risk factors for E-POC and L-POC were identified using univariate and multivariate logistic regression analyses. Propensity score matching (PSM) between the stenting group (group S) and the non-stenting group (group NS), and subgroup analysis in patients with risk factors were performed to evaluate the efficacy of stenting on HJ in preventing POC. RESULTS: Body mass index (BMI) ≥ 25 kg/m2 and preoperative non-biliary drainage (BD) were risk factors for E-POC and L-POC, respectively. PSM analysis revealed that E-POC occurrence was significantly higher in group S than in group NS (P = .045). In the preoperative non-BD group (n = 69), E-POC occurrence was significantly higher in group S than in group NS (P = .025). CONCLUSIONS: BMI ≥ 25 kg/m2 and preoperative non-BD status were risk factors for E-POC and L-POC, respectively. Stenting on HJ implants did not prevent POC after PD.

Impact of sarcopenic obesity on post-hepatectomy bile leakage for hepatocellular carcinoma.

BACKGROUND: Post-hepatectomy bile leakage (PHBL) is a potentially fatal complication that can arise after hepatectomy. Previous studies have identified obesity as a risk factor for PHBL. In this study, we investigated the impact of sarcopenic obesity on PHBL in hepatocellular carcinoma (HCC) patients. METHODS: In total, we enrolled 409 patients who underwent hepatectomy without bilioenteric anastomosis for HCC between January 2010 and August 2021. Patients were grouped according to the presence or absence of PHBL. Patient characteristics, including body mass index and sarcopenic obesity, were then analyzed for predictive factors for PHBL. RESULTS: Among the 409 HCC patients included in the study, 39 developed PHBL. Male sex, hypertension, cardiac disease, white blood cell counts, the psoas muscle area, and visceral fat area, and intraoperative blood loss were significantly increased in the PHBL (+) group compared with the PHBL (-) group. Multivariate analysis showed that the independent risk factors for the occurrence of PHBL were intraoperative blood loss ≥370 mL and sarcopenic obesity. CONCLUSIONS: Our results show that it is important to understand whether a patient is at high risk for PHBL prior to surgery and to focus on reducing intraoperative blood loss during surgery for patients with risk factors for PHBL.

Urgent versus elective laparoscopic cholecystectomy following percutaneous transhepatic gallbladder drainage for high-risk grade II acute cholecystitis.

BACKGROUND: The aim of this study was to evaluate the safety of urgent laparoscopic cholecystectomy (Lap-C) for grade II acute cholecystitis (AC) in high-risk patients who were defined by Tokyo Guideline 18 as having age-adjusted Charlson comorbidity index ≥6 or American Society of Anesthesiologists physical status classification (ASA-PS) ≥ 3, compared with elective Lap-C following percutaneous transhepatic gallbladder drainage (PTGBD). METHODS: In 73 grade II AC patients who underwent Lap-C from January 2012 to March 2021, 35 were identified as high-risk; 22 underwent urgent Lap-C (urgent group) and 13 PTGBD followed by elective Lap-C (elective group). Surgical and perioperative outcomes were analyzed. RESULTS: There was no significant difference in operation time (median: 101 min vs 125 min; P = 0.371), blood loss (25 ml vs 7 ml; P = 0.853), morbidity rate (31.8% vs 38.5%; P = 0.726), or the incidence of total perioperative major complications (13.6% vs 15.4%; P = 1.000) between the two groups. The total duration of treatment was significantly shorter in the urgent group than the elective group (11 days vs 71 days; P < 0.001). Multivariate analysis revealed that blood loss ≥45 ml [odds ratio (OS): 12.14, 95% confidence interval (CI): 2.03-72.42, P = 0.006], and age ≥75 years with ASA-PS ≥ 3 (OS: 9.85, 95%CI: 1.26-77.26, P = 0.03) were the independent risk factors for total perioperative major complications. CONCLUSION: In well-selected high-risk patients with grade II AC, urgent Lap-C can be performed with comparable safety to elective Lap-C following PTGBD.

IgG4 expression and IgG4/IgG ratio in the tumour invasion front predict long-term outcomes for patients with intrahepatic cholangiocarcinoma.

IgG4-positive plasma cells are reportedly increased in the tumour microenvironment, and a high number of these cells in tumours is a poor prognostic factor in several cancers. However, there are no reported analyses of IgG4 expression in intrahepatic cholangiocarcinoma (ICC). This study aimed to analyse the correlations between prognosis-related clinicopathological features of patients with ICC and IgG4 expression. We identified 37 ICC patients who underwent surgical resection between January 2010 and December 2020. The number of IgG-positive and IgG4-positive plasma cells in the tumour, invasion front, and stroma near the tumour was analysed by immunostaining. Furthermore, we examined the association of prognosis-related clinicopathological data with the number of IgG4-positive plasma cells and IgG4/IgG ratio in ICC patients. The IgG4-positive plasma cell percentages for the intra-tumour area, invasion front, and non-cancerous area (NCA) near the tumour were 91.9%, 56.8%, and 81.1%, respectively. IgG-positive plasma cells were observed in each region for all cases, except for NCA tissue in one case. A high IgG4 expression level and IgG4/IgG ratio in the invasion front were significantly associated with poor overall survival (OS) (log-rank test p=0.0438 and p=0.0338, respectively). Multivariate analysis for OS revealed that high IgG4 expression (p=0.0140), lymph node metastasis (p=0.0205), and positive surgical margin (p=0.0009) or a high IgG4/IgG ratio (p=0.0051), lymph node metastasis (p=0.0280), and positive surgical margin (p=0.0009) were independent poor prognostic factors. In conclusion, a high IgG4 expression level and IgG4/IgG ratio in the invasion front are independent poor prognostic factors for ICC. Targeted therapy for IgG4 may improve the prognosis for patients with ICC.

Usefulness of frailty to predict short- and long-term outcomes in patients who have undergone major hepatectomy for perihilar cholangiocarcinoma.

Aim: The influence of frailty on outcomes after hepatectomy for perihilar cholangiocarcinoma (PHCC) remains unclear. This study aimed to investigate the impact of frailty on the incidence of postoperative complications and survival after major hepatectomy for PHCC. Methods: A total of 87 patients who had undergone surgery for PHCC between 2007 and 2020 were enrolled in this study. Frailty was scored retrospectively using the Clinical Frailty Scale (CFS). The survival and incidence of postoperative complications were compared based on the degree of frailty, and their risk factors were analyzed. Results: The overall survival of the CFS score 1-2 group was significantly higher than that of the CFS score 3-7 group (P = .01). The survival benefit was especially observed in stage I or II PHCC. Furthermore, there were significant differences between the CFS score 1-3 group and the CFS score 4-7 group in the incidence of Clavien-Dindo classification grade ≥ IIIa (39.4% vs 70.6%; P = .03). Frailty was an independent risk factor for severe postoperative complications (odds ratio, 4.11; 95% confidence interval, 1.18-15.20; P = .03) and the incidence of systemic complications (P < .01). Conclusion: Frailty is a predictive factor for short- and long-term outcomes in patients who have undergone major hepatectomy for PHCC.