High Subcutaneous Fat Area Is an Independent Risk Factor for Parastomal Hernia after Transperitoneal Colostomy for Colorectal Cancer.

Objectives: Parastomal hernia (PSH) is a common complication of colostomy; however, its risk factors remain poorly investigated. In this study, we examined the associations between sarcopenia, visceral and subcutaneous fat, and PSH in patients who underwent transperitoneal colostomy for colorectal cancer. Methods: This retrospective, single-center, cohort study included 60 patients who underwent laparoscopic or robot-assisted abdominoperineal resection or Hartmann's procedure for colorectal cancer between November 2010 and February 2022. Stoma creation was uniformly performed using the transperitoneal approach, and PSH was diagnosed via abdominal computed tomography (CT) at 1 year postoperatively. Visceral fat areas (VFAs) and subcutaneous fat areas (SFAs) were measured through preoperative CT images using an image analysis system. Risk factors for PSH were retrospectively analyzed. Results: PSH was diagnosed in 13 (21.7%) patients. In the univariate analysis, PSH was significantly associated with body mass index >22.3 kg/m2 (p=0.002), operation time >319 min (p=0.027), estimated blood loss >230 mL (p=0.008), postoperative complications (p=0.028), stoma diameter >18.6 mm (p=0.015), VFA >89.2 cm2 (p=0.005), and SFA >173.2 cm2 (p=0.001). Multivariate analyses confirmed that SFA >173.2 cm2 (odds ratio: 16.7, 95% confidence interval 1.29-217.2, p=0.031) was an independent risk factor for PSH. Conclusions: Subcutaneous fat area is significantly associated with the development of PSH after transperitoneal colostomy. Applying these insights could help to prevent PSH.

Novel tumor marker index using carcinoembryonic antigen and carbohydrate antigen 19-9 is a significant prognostic factor for resectable colorectal cancer.

We evaluated the usefulness of a newly devised tumor marker index (TMI), namely, the geometric mean of normalized carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9), in determining colorectal cancer (CRC) prognosis. This retrospective cohort study included 306 patients with stages I-III CRC who underwent elective laparoscopic resection between April 2010 and March 2020. Survival rates and risk factors of relapse-free survival (RFS) and cancer-specific survival (CSS) were analyzed using Kaplan-Meier curves and Cox proportional hazards model. High-TMI group (122 patients) had significantly lower rates (95% confidence interval [95% CI]) for 5-year RFS (89.7%, 83.9-93.5 vs. 65.8%, 56.3-73.8, p < 0.001) and CSS (94.9%, 89.4-97.6 vs. 77.3%, 67.7-84.4, p < 0.001) than low-TMI group. Multivariate analysis (hazard ratio [95% CI]) indicated ≥ T3 disease (RFS: 2.69, 1.12-6.45, p = 0.026; CSS: 7.64, 1.02-57.3, p = 0.048), stage III CRC (RFS: 3.30, 1.74-6.28, p < 0.001; CSS: 6.23, 2.04-19.0, p = 0.001), and high TMI (RFS: 2.50, 1.43-4.38, p = 0.001; CSS: 3.80, 1.63-8.87, p = 0.002) as significant RFS and CSS predictors. Area under the curve (AUC) of 5-year cancer deaths (0.739, p < 0.001) was significantly higher for TMI than for CEA or CA19-9 alone. Preoperative TMI is a useful prognostic indicator for patients with resectable CRC.

Effect of low visceral fat area on long-term survival of stage I-III colorectal cancer.

OBJECTIVE: The prognostic significance of a low visceral fat area (VFA) in colorectal cancer (CRC) remains unclear. The aim of this study was to evaluate the prognostic effects of a low VFA on the long-term outcomes of patients with CRC after laparoscopic surgery. METHODS: This retrospective study included 306 patients with stages I-III CRC who underwent R0 resection. VFA was preoperatively measured via computed tomography using image processing software. Relapse-free survival (RFS) and overall survival (OS) rates were analyzed using the Cox proportional hazards model and Kaplan-Meier curves. RESULTS: Low VFA was identified in 153 patients. The low VFA group had significantly lower RFS and OS rates than did the high VFA group (5-y RFS rates: 72 versus 89%, P = 0.0002; 5-y OS rates: 72 versus 92%, P = 0.0001). The independent significant predictors of RFS were T3 or T4 disease (hazard ratio [HR], 2.75; 95% confidence interval [CI], 1.12-6.76; P = 0.027), stage III CRC (HR, 3.49; 95% CI, 1.82-6.69; P < 0.001), low psoas muscle index (PMI; HR, 2.12; 95% CI, 1.19-3.79; P = 0.011), and low VFA (HR, 2.12; 95% CI, 1.16-3.86; P = 0.014). The independent significant predictors of OS were age ≥65 y (HR, 2.59; 95% CI, 1.13-5.92, P = 0.024), carbohydrate antigen 19-9 levels ≥37 ng/mL (HR, 2.32; 95% CI, 1.18-4.58; P = 0.015), stage III CRC (HR, 2.66; 95% CI, 1.37-5.17; P = 0.004), low PMI (HR, 2.00; 95% CI, 1.06-3.77; P = 0.031), and low VFA (HR, 2.42; 95% CI, 1.24-4.70; P = 0.009). CONCLUSION: A low preoperative VFA was significantly associated with worse RFS and OS rates in patients who underwent CRC resection.

Biliary Parasitic Diseases Associated with Hepatobiliary Carcinoma.

Background: Despite long-term preventative efforts by local public health authorities, the prevalence of fluke infection remains high in specific areas in eastern and southeastern Asia. Recently increasing travel or migration activities have led to the transfer and spread of such infections from endemic areas to other regions. Summary: The epidemiology, clinical signs, and symptoms for three common blood and liver flukes, namely Schistosoma japonicum, Clonorchis sinensis, and Opisthorchis viverrini, are described in this review, and their current diagnosis and management strategy are reviewed. These flukes are considered clinically important because of the increased risk of liver or biliary cancer. Key Messages: Early treatment and prevention of disease spread can reduce the incidence of related hepatobiliary cancer. Recognition of these fluke infection is essential for a correct diagnosis and early treatment to prevent the development of deadly cancers.

Dysbiosis of the Fecal and Biliary Microbiota in Biliary Tract Cancer.

Characteristic bile duct and gut microbiota have been identified in patients with chronic biliary tract disease. This study aimed to characterize the fecal and bile microbiota in biliary tract cancer (BTC) patients and their relationship. Patients with BTC (n = 30) and benign biliary disease (BBD) without cholangitis (n = 11) were included. Ten healthy, age-matched subjects were also recruited for fecal microbiota comparison. The fecal and bile duct microbiotas were analyzed by sequencing the 16S rRNA gene V3-V4 region. Live bacteria were obtained in the bile from three BTC patients by culture, and metagenomics-based identification was performed. Linear discriminant analysis effect size showed a higher Enterobacteriaceae abundance and a lower Clostridia abundance, including that of Faecalibacterium and Coprococcus, in the BTC patients than in the other subjects. Ten of 17 operational taxonomic units (OTUs) assigned to Enterobacteriaceae in the bile were matched with the OTUs found in the BTC subject fecal samples. Furthermore, a bile-isolated strain possessed the carcinogenic bacterial colipolyketide synthase-encoding gene. Enterobacteriaceae was enriched in the BTC feces, and more than half of Enterobacteriaceae in the bile matched that in the feces at the OTU level. Our data suggests that fecal microbiota dysbiosis may contribute to BTC onset.

Application of a novel surgical difficulty grading system during laparoscopic cholecystectomy.

BACKGROUND: Prevention of bile duct injury and vasculo-biliary injury while performing laparoscopic cholecystectomy (LC) is an unsolved problem. Clarifying the surgical difficulty using intraoperative findings can greatly contribute to the pursuit of best practices for acute cholecystitis. In this study, multiple evaluators assessed surgical difficulty items in unedited videos and then constructed a proposed surgical difficulty grading. METHODS: We previously assembled a library of typical video clips of the intraoperative findings for all LC surgical difficulty items in acute cholecystitis. Fifty-one experts on LC assessed unedited surgical videos. Inter-rater agreement was assessed by Fleiss's κ and Gwet's agreement coefficient (AC). RESULTS: Except for one item ("edematous change"), κ or AC exceeded 0.5, so the typical videos were judged to be applicable. The conceivable surgical difficulty gradings were analyzed. According to the assessment of difficulty factors, we created a surgical difficulty grading system (agreement probability = 0.923, κ = 0.712, 90% CI: 0.587-0.837; AC2  = 0.870, 90% CI: 0.768-0.972). CONCLUSION: The previously published video clip library and our novel surgical difficulty grading system should serve as a universal objective tool to assess surgical difficulty in LC.

Prognostic value of immune factors in the tumor microenvironment of patients with pancreatic ductal adenocarcinoma.

BACKGROUND: Both activated tumor-infiltrating lymphocytes (TILs) and immune-suppressive cells, such as regulatory T cells (Tregs), in the tumor microenvironment (TME) play an important role in the prognosis of patients with pancreatic ductal adenocarcinoma (PDAC). METHODS: The densities of TILs, programmed death receptor 1 (PD-1) + T cells, and forkhead box P3 (Foxp3) + T cells were analyzed by immunohistochemical staining. The associations of the immunological status of the PDAC microenvironment with overall survival (OS) time and disease-free survival (DFS) time were evaluated. RESULTS: PDAC patients with a high density of TILs in the TME or PD-1-positive T cells in tertiary lymphoid aggregates (TLAs) demonstrated a significantly better prognosis than those with a low density of TILs or PD-1-negativity, respectively. Moreover, PDAC patients with high levels of Foxp3-expressing T cells showed a worse prognosis than those with low levels of Foxp3-expressing T cells. Importantly, even with a high density of the TILs in TME or PD-1-positive T cells in TLAs, PDAC patients with high levels of Foxp3-expressing T cells showed a worse prognosis than patients with low levels of Foxp3-expressing T cells. A PDAC TME with a high density of TILs/high PD-1 positivity/low Foxp3 expression was an independent predictive marker associated with superior prognosis. CONCLUSION: Combined assessment of TILs, PD-1+ cells, and Foxp3+ T cells in the TME may predict the prognosis of PDAC patients following surgical resection.

The segment IV approach: a useful method for achieving the critical view of safety during laparoscopic cholecystectomy in patients with anomalous bile duct.

BACKGROUND: The critical view of safety (CVS) method can be achieved by avoiding vasculo-biliary injury resulting from misidentification during laparoscopic cholecystectomy (LC). Although achieving the CVS has become popular worldwide, there is no established standardized technique to achieve the CVS in patients with an anomalous bile duct (ABD). We recently reported our original approach for securing the CVS using a new landmark, the diagonal line of the segment IV of the liver (D-line). The D-line is an imaginary line that lies on the right border of the hilar plate. The cystic structure can be securely isolated along the D-line without any misidentification, regardless of the existence of an ABD. We named this approach the segment IV approach in LC. METHODS: In this study, we adopted the segment IV approach in patients with an ABD. RESULTS: From October 2015 to June 2020, 209 patients underwent LC using the segment IV approach. Among them, three (1.4%) were preoperatively diagnosed with an ABD. The branching point of the cystic duct was the posterior sectional duct, anterior sectional duct, or left hepatic duct in each patient. The CVS was achieved in all cases without any complications. CONCLUSION: It is a promising technique, especially even for patients with an ABD during LC.

Multidisciplinary treatment for colorectal liver metastases in elderly patients.

BACKGROUND: Limited data describe the therapeutic practice and outcomes of colorectal liver metastases (CRLMs) in elderly patients. We aimed to evaluate the impact of age on multidisciplinary treatment for CRLMs. METHODS: We reviewed treatment and outcomes for patients in different age groups who underwent initial hepatectomy for CRLMs from 2004 through 2012. RESULTS: We studied 462 patients who were divided into three groups by age: ≤ 64 years (n = 265), 65-74 years (n = 151), and ≥ 75 years (n = 46). The rate of major hepatectomy and incidence of postoperative complications did not differ between groups. Adjuvant chemotherapy was used less in the ≥ 75-year group (19.6%) than that in the ≤ 64 (54.3%) or 65-74 age group (43.5%). Repeat hepatectomy for liver recurrence was performed less in the ≥ 75-year group (35%) than in the ≤ 64 (57%) or 65-74 (66%) age group. The 5-year disease-specific survival (DSS) rate of 44.2% in the ≥ 75-year group was lower than in the ≤ 64 (59.0%) or 65-74 (64.7%) age group. Multivariate analysis revealed age ≥ 75 years was an independent predictor of poor DSS. CONCLUSIONS: Liver resection for CRLMs can be performed safely in elderly patients. However, repeat resection for recurrence are performed less frequently in the elderly, which may lead to the poorer disease-specific prognosis.

Segment IV approach for difficult laparoscopic cholecystectomy.

Although achieving the critical view of safety (CVS) is useful for avoiding vasculobiliary injury during laparoscopic cholecystectomy (LC), the CVS cannot always be achieved in cases of severe cholecystitis because of technical difficulties. Herein, we focused on segment IV of the liver and its diagonal line (D-line) as a feasible landmark for carrying out difficult LC. The D-line connects the right dorsal and left ventral corners of segment IV and is used as the vectoral landmark, which is where the gallbladder is first dissected to achieve CVS without misidentification. Conversion to subtotal cholecystectomy along the D-line is also feasible when gallbladder wall scarring is severe. We named this procedure the segment IV approach for LC. Sixty-two consecutive difficult LC (including 27 scheduled LC after percutaneous transhepatic gallbladder drainage [PTGBD] and 35 conservatively treated cases of Tokyo Guidelines [TG] grade II cholecystitis) were managed by the segment IV approach. Successful gallbladder extraction along the D-line was achieved in 44 (71%) cases; all of these cases also achieved CVS following total cholecystectomy. The other 18 (29%) cases were converted to subtotal cholecystectomy because gallbladder extraction along the D-line failed as a result of severe cholecystitis with inflammatory adhesion with surrounding structures. Median operative time and intraoperative blood loss were 135 (range, 54-290) min and 10 (range, 0-100) mL, respectively. No intra- or postoperative complications were observed. The segment IV approach is feasible for achieving CVS and for considering subtotal cholecystectomy in difficult LC cases where scarring of the gallbladder wall is present.

Impact of Bile Exposure Time on Organ/space Surgical Site Infections After Pancreaticoduodenectomy.

BACKGROUND/AIM: Organ/space surgical site infections (SSIs) are critical complications of pancreaticoduodenectomy. We investigated the impact of the time between division of the common hepatic duct and completion of biliary reconstruction [bile exposure (BE) time] on the occurrence of post-pancreaticoduodenectomy organ/space SSI. PATIENTS AND METHODS: Sixty-one patients who underwent pancreaticoduodenectomy were retrospectively studied. The impact of perioperative variables and BE time on organ/space SSI occurrence was analyzed. RESULTS: Organ/space SSIs occurred in 17 patients (28%). Patients were divided into two groups according to BE time. The incidence of organ/space SSIs was significantly higher in the long BE time group than in the short BE time group (42% versus 13%, p=0.0127). Multivariate analysis revealed that long BE times [odds ratio (OR)=4.8; p=0.0240] and soft pancreatic texture (OR=16.5; p=0.0106) were independent risk factors for organ/space SSIs. CONCLUSION: Long BE time is a risk factor for post-pancreaticoduodenectomy organ/space SSIs. Shortening BE time may reduce organ/space SSI occurrence.

Renal Infarction during Anticoagulant Therapy after Living Donor Liver Transplantation.

INTRODUCTION: Liver transplant recipients are at risk for complications of vascular thrombosis. The reconstructed hepatic artery and portal vein thrombosis potentially result in hepatic failure and graft loss. Renal infarction is a rare clinical condition, but in severe cases, it may lead to renal failure. We herein report a case of renal infarction after living donor liver transplantation (LDLT) during anticoagulant therapy. CASE PRESENTATION: A 60-year-old woman with end-stage liver disease due to primary biliary cholangitis underwent LDLT with splenectomy. Postoperatively, tacrolimus, mycophenolate mofetil, and steroid were used for initial immunosuppression therapy. On postoperative day (POD) 5, enhanced computed tomography (CT) revealed splenic vein thrombosis, and anticoagulant therapy with heparin followed by warfarin was given. Follow-up enhanced CT on POD 20 incidentally demonstrated right renal infarction. The patient's renal function was unchanged and the arterial flow was good, and the splenic vein thrombosis resolved. At 4 months postoperatively, warfarin was discontinued, but she developed recurrent splenic vein thrombosis 11 months later, and warfarin was resumed. As of 40 months after transplantation, she discontinued warfarin and remains well without recurrence of splenic vein thrombosis or renal infarction. CONCLUSION: Renal infarction is a rare complication of LDLT. In this case, renal infarction was incidentally diagnosed during anticoagulant therapy and was successfully treated.

Use of intercostal trocars for laparoscopic resection of subphrenic hepatic tumors.

BACKGROUND: The aim of this study was to demonstrate the detailed surgical techniques of laparoscopic hepatectomy using intercostal transthoracic trocars for subcapsular tumors located in segment VII or VIII. METHODS: Intercostal transthoracic trocars were used in patients undergoing laparoscopic hepatectomy for tumors located in segment VII or VIII. Following establishment of pneumoperitoneum and placement of abdominal trocars, balloon-tipped trocars were inserted into the abdominal cavity from the intercostal space and through the pleural space and diaphragm. Upon placement of the intercostal trocars, the lung edge was confirmed by ultrasonography and laparoscopic examination. Following minimal mobilization of the right liver, hemispherical wedge resection of segment VII or VIII was performed using the intercostal trocars as a camera port or for the forceps of the surgeon's left hand. After the hepatectomy, the holes in the diaphragm were sutured closed. RESULTS: Among the 79 patients who underwent laparoscopic hepatectomy, intercostal trocars were used in 14 patients for resection of tumors located in segment VII (4 nodules) or VIII (10 nodules). The median (range) operation time and amount of blood loss for hepatectomy were 225 (109-477) min and 60 (20-310) mL, respectively. No postoperative complications associated with hepatectomy or the use of intercostal trocars occurred. CONCLUSIONS: Use of intercostal transthoracic trocars is safe and effective not only for complicated laparoscopic hepatectomy but also for hemispherical wedge resections of subcapsular hepatic tumors located in segment VII or VIII.

Donor screening algorithm for exclusion of thrombophilia during evaluation of living donor liver transplantation.

Living donor liver transplantation (LDLT) has evolved based on the premise that donor safety is most important. In 2005, we encountered a donor who developed a pulmonary embolism during the early post-operative period. As it is important for donors to be healthy, most risk factors related to perioperative thrombosis, such as obesity, age, and malignancy are used as exclusion criteria during the evaluation process. We speculated that thrombophilia not detected by conventional laboratory examinations may cause post-operative thrombotic complications and should be investigated by application of additional parameters, including protein S, protein C, antithrombin III, anti-ß2-glycoprotein I antibodies (anti-ß2GPI), and lupus anticoagulant. From July 2005 to June 2007, we evaluated 44 donor candidates for LDLT using our novel algorithm for screening of thrombophilia, which revealed two suspected candidates (one with low protein S, one with low protein C, and positive anti-ß2GPI findings), who were subsequently excluded from the donor pool. Thereafter, all donor hepatectomies, which included two borderline donors given anticoagulants perioperatively, were performed without complications. Four donors (two suspected, two borderline) would not have been recognized without additional screening. In conclusion, we were able to detect thrombophilia and avoid donor thrombosis using additional screening criteria and our novel algorithm.

Two cases of central venous catheter-related thrombosis in living liver donors: how can the risk be minimized?

A central venous catheter (CVC) is commonly used for intraoperative management by anesthetists and surgeons during major operations, including donor operations for living donor liver transplantation (LDLT), in which donor safety is of utmost importance. Reasons for use of CVC for donors include measurement of central venous pressure and drug infusion when necessary. A potentially serious complication of a major operation is pulmonary thromboembolism. We report two cases of LDLT donors complicated by catheter related thrombosis (CRT) of the jugular vein, who were eventually discharged without long-term complications. To the best of our knowledge, there has been no report of CRT among LDLT donor population. In this report, in order to minimize the risks related to CRT in LDLT donors, we propose thorough screening for thrombophilic disorders, use of a silicone or polyurethane double-lumen CVC as thin as possible, placement of the tip of the CVC at the superior vena cava via the right jugular vein using ultrasonography as a guide for puncture, and removal of the catheter at the end of the operation based on our experience of CRT among LDLT donors.