Immunotherapy Using Activated Natural Killer Cells Improves Postoperative Neutrophil-to-Lymphocyte Ratio and Long-Term Prognosis of Living Donor Liver Transplant Recipients With Hepatocellular Carcinoma.

OBJECTIVE: Preoperative neutrophil-to-lymphocyte ratio (NLR) is a well-known prognostic indicator in various malignancies; however, the impact of postoperative NLR on living donor liver transplant (LDLT) recipients is unknown. Immunotherapy with donor liver-derived activated natural killer (NK) cells may improve postoperative NLR by coactivating immune cells or suppressing activated neutrophils. This study aims to clarify the clinical significance of postoperative NLR in recipients after LDLT with HCC and assess whether immunotherapy improves postoperative NLR. METHODS: We conducted a retrospective study of LDLT recipients between 2001 and 2022 to evaluate the clinical significance of postoperative NLR. Furthermore, the correlation between postoperative NLR and the activation marker of infused NK cells was also evaluated. The postoperative NLR was examined 4 weeks after LDLT. RESULTS: The postoperative high NLR group (N = 78) had preoperative lower NLR and higher model for end-stage liver disease and a higher rate of postoperative infection within 30 days after LDLT than the postoperative low NLR group (N = 41). Postoperative high NLR (hazard ratio [HR], 2.62; 95% confidence interval [CI], 1.01-6.79; P = .047) and nontreatment of immunotherapy (HR, 3.10; 95% CI, 1.33-7.22; P < .01) were independent risk factors for poor overall survival in multivariate analysis. Furthermore, the activation marker of infused NK cells is inversely correlated with decreased postoperative NLR. CONCLUSIONS: The higher level of postoperative NLR was independently associated with poor prognosis in patients after LDLT with HCC. Immunotherapy using activated NK cells may improve postoperative NLR and long-term prognosis.

Effect of Abdominal Aortic Calcification on Recurrence Following Initial Hepatectomy for Colorectal Liver Metastases.

BACKGROUND/AIM: The aim of the study was to analyze the association between abdominal aortic calcification (AAC) and patient prognosis following resection of colorectal liver metastases (CRLM). AAC potentially reflects intrahepatic immunity and is involved in tumor development and progression. However, the clinical effects of AAC on colorectal cancer (CRC) prognosis after curative-intent liver resection for CRLM remain unclear. PATIENTS AND METHODS: We evaluated the effect of AAC on the clinical prognosis and metastatic patterns in 99 patients who underwent hepatectomy for CRLM between 2010 and 2019. RESULTS: The high-AAC group had significantly worse overall survival (OS) and remnant liver recurrence rate (RR) after propensity score matching to adjust for differences in baseline characteristics of patients and tumors. In multivariate Cox regression analyses, high AAC volume was an independent risk factor for poor OS and liver RR, but not poor lung RR. The expression of tumor necrosis factor-related apoptosis-inducing ligand, known as an anti-tumor marker, in liver natural killer (NK) cells was lower in the high-AAC group than in the low-AAC group. CONCLUSION: High AAC volume showed a strong relationship with remnant liver RR after curative resection of CRLM. High AAC volume may be responsible for the suppression of anti-tumor activity of liver NK cells, which results in an increased risk of liver recurrence and poor prognosis.

Weekday Surgery Associated With Short-Term Outcomes in Patients With Colorectal Cancers.

INTRODUCTION: The "weekday effect" on elective surgery remains controversial. We aimed to examine the association between the day of surgery and short-term outcomes after elective surgery for stage I-III colorectal cancer (CRC). METHODS: We performed a multicenter retrospective analysis of 2574 patients who underwent primary colorectal resection for CRC between January 2017 and December 2019 at 15 institutions belonging to the Hiroshima Surgical Study Group of Clinical Oncology. Patients were divided into two groups according to the day of surgery: Friday and non-Friday (Monday to Thursday). After propensity score matching (PSM), we compared 30-day mortality and postoperative outcomes. RESULTS: Out of the total, 368 patients underwent surgery on Fridays, and the remaining 2206 underwent surgery on non-Fridays. The overall mortality rate was 0.04% (n = 1). In 1685 patients with colon cancer, the proportion of American Society of Anesthesiologists scores was significantly lower in the Friday group than in the non-Friday group before PSM. After PSM of patient, tumor, and operative characteristics, operative time was slightly more prolonged and blood loss was slightly greater in the Friday group; however, these differences were not clinically meaningful. In the 889 patients with rectal cancer, the proportion of patients with abnormal respiratory patterns was significantly lower in the Friday group than in the non-Friday group before PSM. After PSM, the Friday group had a higher incidence of morbidity (≥ Clavien-Dindo 3a), higher incidence of digestive complications, and prolonged postoperative hospital stay. CONCLUSIONS: The results may be useful in determining the day of the week for CRC surgery, which requires more advanced techniques and higher skills.

C-Reactive Protein/Albumin Ratio Is an Independent Risk Factor for Recurrence and Survival Following Curative Resection of Stage I-III Colorectal Cancer in Older Patients.

BACKGROUND: The number of older patients with cancer has increased, and colorectal cancer is expected to be affected by this trend. This study aimed to compare prognostic factors, including nutritional and inflammation-based indices, between patients aged ≥ 70 and < 70 years following curative resection of stage I-III colorectal cancer. PATIENTS AND METHODS: This study included 560 patients with stage I-III colorectal cancer who underwent curative resection between May 2010 and June 2018. A retrospective analysis was performed to identify prognosis-associated variables in patients aged ≥ 70 and < 70 years. RESULTS: Preoperative low body mass index, high C-reactive protein/albumin ratio, and comorbidities were mainly associated with poor prognosis in patients aged ≥ 70 years. Tumor factors were associated with a poor prognosis in patients aged < 70 years. The C-reactive protein/albumin ratio was independently associated with poor overall survival and recurrence-free survival in those aged ≥ 70 years. The time-dependent area under the curve for the C-reactive protein/albumin ratio was superior to those of other nutritional and inflammation-based indices in most postoperative observation periods in patients aged ≥ 70 years. CONCLUSIONS: Tumor factors were associated with a poor prognosis in patients aged < 70 years. In addition to lymph node metastasis, preoperative statuses were associated with poor prognosis in patients aged ≥ 70 years. Specifically, the preoperative C-reactive protein/albumin ratio was independently associated with long-term prognosis in patients aged ≥ 70 years with stage I-III colorectal cancer after curative resection.

Conscientiousness Counts: How Personality Traits Impact Laparoscopic Surgical Skill Improvement in Medical Students.

OBJECTIVE: Studies have shown that personality traits affect cognitive performance; however, little is known about their influence on surgical performance. This study aimed to assess the impact of the Big Five personality traits on medical students' laparoscopic surgical skills. DESIGN: In this prospective study, medical students' laparoscopic surgical skills were assessed using the Hiroshima University Laparoscopic Surgical Assessment Device (HUESAD). The participants performed the HUESAD tasks 10 times before they underwent training. After completing the simulator training, they performed the tasks 10 times. Thereafter, they answered Big Five personality trait questionnaires (Extraversion, Neuroticism, Openness to experience, Conscientiousness, and Agreeableness). SETTING: Academic medical centers. PARTICIPANTS: Forty medical students (10 women) were recruited. The selection criterion was a lack of simulations or clinical experience in laparoscopic procedures. RESULTS: No significant correlations were found between personality traits and HUESAD assessment scores before training. Laparoscopic surgical skills improved significantly after the training (p < 0.001). The Big Five personality traits were correlated with improved laparoscopic surgical performance after training (r = -0.44, p < 0.05). Moreover, statistically significant positive correlations were observed between Conscientiousness and improvement rates (r = 0.36, p < 0.05). CONCLUSIONS: The results suggest that medical students scoring high on Conscientiousness were more likely to have improved laparoscopic surgical skills, regardless of their initial skills. The ability to predict laparoscopic surgical skills would be useful in designing tailor-made training programs for safe and high-quality operations.

Predictive factors associated with anastomotic leakage after resection of rectal cancer: a multicenter study with the Hiroshima Surgical study group of Clinical Oncology.

PURPOSE: Several factors have been reported as risk factors for anastomotic leakage after resection of rectal cancer. This study aimed to evaluate the risk factors for anastomotic leakage, including nutritional and immunological indices, following rectal cancer resection. METHODS: This study used a multicenter database of 803 patients from the Hiroshima Surgical study group of Clinical Oncology who underwent rectal resection with stapled anastomosis for rectal cancer between October 2016 and April 2020. RESULTS: In total, 64 patients (8.0%) developed postoperative anastomotic leakage. Five factors were significantly associated with the development of anastomotic leakage after rectal cancer resection with stapled anastomosis: male sex, diabetes mellitus, C-reactive protein/albumin ratio ≥ 0.07, prognostic nutritional index < 40, and low anastomosis under peritoneal reflection. The incidence of anastomotic leakage was correlated with the number of risk factors. The novel predictive formula based on odds ratios in the multivariate analysis was useful for identifying patients at high risk for anastomotic leakage. Diverting ileostomy reduced the ratio of anastomotic leakage ≥ grade III after rectal cancer resection. CONCLUSIONS: Male sex, diabetes mellitus, C-reactive protein/albumin ratio ≥ 0.07, prognostic nutritional index < 40, and low anastomosis under peritoneal reflection are possible risk factors for developing anastomotic leakage after rectal cancer resection with the stapled anastomosis. Patients at high risk of anastomotic leakage should be assessed for the potential benefits of diverting stoma.

Clinical efficacy of Daikenchuto (DKT: TJ-100) for gastrointestinal symptoms in patients with a history of colon and rectosigmoid cancer surgery: a randomized crossover study.

PURPOSE: This randomized crossover trial investigated the effects of Daikenchuto (DKT: TJ-100) on gastrointestinal symptoms of patients after colon and rectosigmoid cancer surgery. METHODS: Among patients who had completed surgery for colon cancer, including rectosigmoid cancer, over 6 months ago, 20 who complained of gastrointestinal symptoms were enrolled. Subjects were randomly assigned to two sequences: sequences: A and B. In period 1, sequence A subjects were orally administered DKT, whereas sequence B subjects were untreated for 28 days. After a 5-day interval, in period 2, sequences A and B were reversed. Quality-of-life markers (GSRS and VAS), the Sitzmark transit study, the orocecal transit time (lactulose hydrogen breath test) and Gas volume score were evaluated before and after each period with findings compared between the presence of absence of DKT administration. RESULTS: Between sequences, there were no significant differences in clinicopathological characters or any evaluations before randomization. There was no carryover effect in this crossover trial. The administration of DKT significantly ameliorated the GSRS in total, indigestion, and diarrhea, although the planned number of subjects for inclusion in this trial was not reached. CONCLUSIONS: DKT may ameliorate subjective symptoms for postoperative patients who complain of gastrointestinal symptoms.

Effect of abdominal aortic calcification on the prognosis and recurrence of colorectal cancer stages II-III: A retrospective cohort study.

PURPOSE: Abdominal aortic calcification (AAC) is a well-known risk marker for cardiovascular disease. However, its clinical effect on patients who underwent radical surgery for colorectal cancer (CRC) stages II-III is unclear. This study aimed to analyze the associations between AAC and prognosis of patients with stage II-III CRC. METHODS: To evaluate the effect of AAC on clinical outcomes, prognosis, and metastatic patterns of CRC, we analyzed 362 patients who underwent radical surgery for stage II-III CRC between 2010 and 2018. RESULTS: The high AAC group had significantly worse overall survival (OS), cancer-specific survival (CSS), and recurrence-free survival (RFS) after propensity score matching to adjust for differences in baseline characteristics of patients and tumors. In the multivariate Cox regression analyses, a high AAC was an independent risk factor for poor OS (hazard ratio [HR], 2.38; 95% confidence interval [CI], 1.23-4.59; p = 0.01), poor CSS (HR, 5.22; 95% CI, 1.74-15.6; p < 0.01), and poor RFS (HR, 1.83; 95% CI, 1.19-2.83; p < 0.01). A high AAC was not associated with a risk of lung metastasis or local or peritoneal recurrence, but a risk for liver metastasis of CRC. CONCLUSION: A high AAC showed a strong relationship with poor OS, CSS, and RFS after curative resection for stage II-III CRC. A high AAC was also associated with a risk for liver metastasis, which may worsen the prognosis in stage II-III CRC. AAC could be a new clinical tool for predicting the prognosis for patients in stage II-III CRC.

Determining Invasion Depth in Superficial Pharyngeal Carcinoma by Transoral Ultrasonography.

OBJECTIVES: To examine the clinical usefulness of transoral ultrasonography (US) in determining the invasion depth of superficial pharyngeal carcinoma (SPC). Determining the invasion depth of SPC is crucial for transoral surgery including determining treatment strategy. This study aimed to examine the usefulness of transoral US in determining the invasion depth of SPC. METHODS: Forty-six patients with 51 lesions who underwent both magnifying endoscopy with narrow-band imaging (ME-NBI) and transoral US were included. The primary outcomes were the sensitivity, specificity, positive (PPV), and negative predictive values (NPV) of ME-NBI and transoral US findings for pathological tumor depth in SPCs. RESULTS: The accuracy (82.4%), sensitivity (85.2%), PPV (82.1%), and NPV (82.6%) rates of US for subepithelial propria (SEP) were higher than those of ME-NBI and macroscopic classification, indicating that transoral US is superior to ME-NBI in determining the invasion depth. All cases where the SEP was clearly invaded (SEP deep) could be diagnosed as SEP by transoral US. CONCLUSIONS: Transoral US may be useful in determining the invasion depth of SPCs. LEVEL OF EVIDENCE: 3 Laryngoscope, 133:2192-2197, 2023.

Efficacy of bailout surgery for preventing intraoperative biliary injury in acute cholecystitis.

BACKGROUND: Bailout surgery (BOS; partial cholecystectomy, open conversion, and fundus-first approach) has been recommended for difficult cases to ensure safe performance of cholecystectomy. However, the efficacy of BOS for preventing intraoperative massive bleeding and bile duct injury (BDI) remains unclear, especially in the context of acute cholecystitis (AC). This study aimed to retrospectively validate the feasibility of BOS for AC. METHODS: We enrolled 479 patients who underwent emergency cholecystectomies for AC between 2011 and 2021. Univariate and multivariate analyses were performed to detect the risk factors for BOS in patients with AC. Perioperative variables were compared between patients who underwent total cholecystectomy (TC) and those who underwent BOS. Propensity score matching analysis was performed to compare the two groups. RESULTS: Significant differences in American Society of Anesthesiologists physical status and Charlson Comorbidity Index scores, TG18 severity grading, white blood cell count, and albumin and C-reactive protein (CRP) levels were found between the TC and BOS groups. Preoperative CT imaging demonstrated severe inflammation evidenced by gallbladder wall thickness, enhancement of the liver bed, and duodenal edema in the BOS group compared to the TC group. Postoperative complications were significantly higher in the BOS group than in the TC group. Further, BDI was completely prevented by BOS. Multivariate analysis identified TG18 grade ≥ II, CRP ≥ 7.7, and duodenal edema as independent risk factors for BOS. After PSM analysis, postoperative complications were not worse in patients who underwent BOS rather than TC. Among BOS procedures, laparoscopic BOS (lap-BOS) was the most efficacious in preventing intraoperative blood loss and postoperative bile leakage. CONCLUSION: Severity grading > II, elevated CRP levels, or duodenum edema revealed by CT were determined to be risk factors impeding total cholecystectomy. BOS is a safe, feasible, and efficacious procedure for preventing BDI. Among BOS procedures, lap-BOS showed better postoperative outcomes.

Swallowing function after transoral surgery for laryngopharyngeal cancer.

Transoral surgery (TOS) has been widely used to treat laryngopharyngeal cancers. Although TOS is a minimally invasive procedure, postoperative complications, such as postoperative dysphagia, may occur, which can lead to a poor quality of life for patients undergoing TOS. This study aimed to investigate factors that may affect swallowing function in patients who underwent TOS for laryngopharyngeal cancers. Swallowing function of 84 patients who underwent endoscopic resection for oropharyngeal, hypopharyngeal, and supraglottic lesions was evaluated by the Functional Outcome Swallowing Scale, and predictors for postoperative dysphagia were identified. Multivariate analysis identified the following factors as independent predictors for postoperative dysphagia: Eastern Cooperative Oncology Group Performance Status (ECOG PS, p = 0.008), prior neck radiation therapy (p = 0.008), and operative time (p = 0.021). This study suggests that patients with poor ECOG PS or those who received prior neck radiation therapy should be fully assessed for preoperative swallowing function. In the future, we would like to clarify the criteria for preoperative swallowing evaluation to create a system that can identify patients suitable for TOS.

Distal Gastrectomy for Symptomatic Stage IV Gastric Cancer Contributes to Prognosis with Acceptable Safety Compared to Gastrojejunostomy.

BACKGROUND: The prognostic prolongation effect of reduction surgery for asymptomatic stage IV gastric cancer (GC) is unfavorable; however, its prognostic effect for symptomatic stage IV GC remains unclear. We aimed to compare the prognosis of gastrectomy and gastrojejunostomy for symptomatic stage IV GC. METHODS: This multicenter retrospective study analyzed record-based data of patients undergoing palliative surgery for symptomatic stage IV GC in the middle or lower-third regions between January 2015 and December 2019. Patients were divided into distal gastrectomy and gastrojejunostomy groups. We compared clinicopathological features and outcomes after propensity score matching (PSM). RESULTS: Among the 126 patients studied, 46 and 80 underwent distal gastrectomy and gastrojejunostomy, respectively. There was no difference in postoperative complications between the groups. Regarding prognostic factors, surgical procedures and postoperative chemotherapy were significantly different in multivariate analysis. Each group was further subdivided into groups with and without postoperative chemotherapy. After PSM, the data of 21 well-matched patients with postoperative chemotherapy and 8 without postoperative chemotherapy were evaluated. Overall survival was significantly longer in the distal gastrectomy group (p = 0.007 [group with postoperative chemotherapy], p = 0.02 [group without postoperative chemotherapy]). CONCLUSIONS: Distal gastrectomy for symptomatic stage IV GC contributes to prognosis with acceptable safety compared to gastrojejunostomy.

Prediction of anastomotic leakage after left-sided colorectal cancer surgery: a pilot study utilizing quantitative near-infrared spectroscopy.

BACKGROUND: Anastomotic leakage (AL) occurs with some frequency in all types of colorectal cancer surgery and is associated with increased morbidity, mortality and recurrence rates. Complications might be prevented by monitoring intra-operative bowel perfusion at the anastomotic site. A pilot study concerning the objective and quantitative measurement of tissue perfusion by monitoring regional tissue saturation of oxygen (rSO2) was conducted, using the In Vivo Optical Spectroscopy (INVOS™) system (Medtronic, Minneapolis, MN, USA). METHODS: This study evaluated the ability of the INVOS™ system to predict AL after left-sided colorectal cancer surgery. rSO2 measurements of the oral side of the site of bowel anastomosis were taken before anastomosis in 73 patients. Clinical factors, including rSO2, were analyzed to identify risk factors for AL. RESULTS: Among 73 patients, 6 (8.2%) experienced AL. The rSO2 values of the oral anastomotic site were significantly lower in AL patients than in non-AL patients. In the multivariate analysis, the rSO2 value of the oral anastomotic site was an independent risk factor for AL. CONCLUSION: Monitoring the rSO2 at the anastomotic site enabled the prediction of AL. A prospective study to evaluate the efficacy of the INVOS™ system for monitoring intestinal rSO2 is in progress.

Omnidirectional camera and head-mount display contribute to the safety of laparoscopic surgery.

BACKGROUND: We focused on the availability of an omnidirectional camera and head-mount display (HMD). If the laparoscope is an omnidirectional camera, captured images are sent to the HMD worn by the operator in real time. The operator can thus view the image as they like without moving the camera and obtain a 360° view intuitively. However, the surgical system that can be used for actual laparoscopic operations has not yet been developed. In this study, we aimed to show that an omnidirectional camera and HMD would be useful in laparoscopic surgery. MATERIAL AND METHODS: Eleven medical students and twelve surgical residents (Surgeons group) participated in this study. We created an experimental box with five marks randomly attached inside the box, and the inside cannot be seen from the outside. We measured the time it took to identify all marks between conventional laparoscope and substitute system in each group. RESULTS: In the substitute system, the time required for the task was significantly shorter than with conventional laparoscopy in each group. CONCLUSION: An omnidirectional camera and HMD may be a useful new device for laparoscopic surgery. This system may help improve the safety of laparoscopic surgery.

The arrival time of indocyanine green in tissues can be a quantitative index because of its correlation with tissue oxygen saturation: A clinical pilot study.

Indocyanine green (ICG) fluorescence angiography has recently been reported useful as a method for predicting intestinal blood flow and may reduce anastomotic leakage. However, the quantification method for ICG fluorescence angiography has not been established. We usually measure the tissue oxygen saturation (StO2 ) in the intestinal tract via near-infrared spectroscopy, as it is able to measure the oxygen concentration accurately and immediately shows objective data. In this study, we propose that the time to reach the anastomotic site after intravenous ICG injection is an effective parameter for quantifying ICG fluorescence angiography from the comparison to the data of StO2 in the intestinal tract.

The characteristics of residual pneumoperitoneum after laparoscopic colorectal surgery.

INTRODUCTION: Despite the popularity of laparoscopic surgery, it remains unclear whether residual pneumoperitoneum influences the patient's postoperative course. This study aimed to evaluate the characteristics of residual pneumoperitoneum. METHODS: This retrospective study included 201 Japanese patients who had undergone elective laparoscopic colorectal surgery. The patients were divided into groups, with and without anastomotic failure; the non-anastomotic failure group was further divided into subgroups, with and without residual pneumoperitoneum. Patient characteristics were compared between the various groups. RESULTS: The group with residual pneumoperitoneum included 57 patients (30.3%). Percutaneous drainage was required for one patient with residual pneumoperitoneum. Univariate analyses revealed that residual pneumoperitoneum was associated with low values for body mass index (BMI) and subcutaneous fat area (SFA). Furthermore, relative to the group with anastomotic failure, the group without anastomotic failure but with residual pneumoperitoneum had lower values for inflammatory markers. CONCLUSION: Low BMI and SFA values were identified as risk factors for residual pneumoperitoneum. Inflammatory markers may be useful as indicators for avoiding emergent surgery when it is difficult to differentiate between asymptomatic residual pneumoperitoneum and free air related to anastomotic failure.

Tumor budding as a predictive marker for 5-fluorouracil response in adjuvant-treated stage III colorectal cancer.

BACKGROUND: Tumor budding (TB) has been described as an adverse prognostic marker for operable colorectal cancer (CRC); however, a limited number of studies have demonstrated the prognostic significance of TB in patients with drug therapy. This study was conducted to determine the predictive power of TB in stage III CRC patients who received adjuvant chemotherapy. METHODS: We retrospectively collected clinicopathological data including TB of 237 stage III colorectal cancer patients at Hiroshima University Hospital between July 1, 2006 and June 31, 2019. Differential disease-free survival (DFS) was investigated according to TB status. RESULTS: This study included 237 patients with a median age of 67 years, comprising patients who underwent surgery alone (n = 65), 5-fluorouracil (5-FU) monotherapy (n = 129), and oxaliplatin-based chemotherapy (n = 43). Overall, 81 patients developed disease recurrence, and 33 patients died of cancer-related causes. The TB status was categorized into two groups: 99 with low budding (< 5 buds) and 138 with high budding (≥ 5 buds). Overall, the low budding cases demonstrated significantly better DFS. In the 5-FU monotherapy group, low-risk patients (T1, T2, or T3 and N1) with low budding showed a remarkably higher 3-year DFS (91%) compared to high budding (55%). CONCLUSION: Our results indicate that TB could play a subsidiary role in selecting patients who could maintain a favorable prognosis with 5-FU monotherapy in stage III CRC.