Clinical utility of BRCA and ATM mutation status in circulating tumour DNA for treatment selection in advanced pancreatic cancer.

BACKGROUND: Identification of homologous recombination deficiency (HRD) remains a challenge in advanced pancreatic cancer (APC). We investigated the utility of circulating tumour DNA (ctDNA) profiling in the assessment of BRCA1/2 and ATM mutation status and treatment selection in APC. METHODS: We analysed clinical and ctDNA data of 702 patients with APC enroled in GOZILA, a ctDNA profiling study using Guardant360. RESULTS: Inactivating BRCA1/2 and ATM mutations were detected in 4.8% (putative germline, 3.7%) and 4.4% (putative germline, 0.9%) of patients, respectively. Objective response (63.2% vs. 16.2%) and PFS (HR 0.55, 95% CI 0.32-0.93) on platinum-containing chemotherapy were significantly better in patients with putative germline BRCA1/2 (gBRCA) mutation than those without. In contrast, putative gBRCA mutation had no impact on the efficacy of gemcitabine plus nab-paclitaxel. In 2 patients treated with platinum-containing therapy, putative BRCA2 reversion mutations were detected. Three of seven patients with somatic BRCA mutations responded to platinum-containing therapy, while only one of four with putative germline ATM mutations did. One-third of somatic ATM mutations were in genomic loci associated with clonal haematopoiesis. CONCLUSION: Comprehensive ctDNA profiling provides clinically relevant information regarding HRD status. It can be a practical, convenient option for HRD screening in APC.

Long-term survival and functional outcomes of laparoscopic surgery for clinical stage I ultra-low rectal cancers located within 5 cm of the anal verge: A prospective phase II trial (Ultimate trial).

OBJECTIVE: To clarify the long-term oncological outcomes and postoperative anal, urinary, and sexual functions after laparoscopic surgery for clinical stage I very low rectal carcinoma located near the anal canal. SUMMARY BACKGROUND DATA: Laparoscopic surgery is widely applied for rectal cancer; however, concerns remain, with some studies showing poorer outcomes compared to open surgery. METHODS: This single-arm, phase II trial included patients registered preoperatively from 47 institutions in Japan. The planned sample size was 300. The primary endpoint was the 3-year local recurrence rate. Anal, urinary, and sexual functions were evaluated using a prospective questionnaire. RESULTS: Three-hundred patients were registered between January 2014 and March 2017. Anus-preserving surgery was performed in 278 (93%), including 172 who underwent intersphincteric resection (58%) and 106 (36%) who underwent low anterior resection. The 3-year cumulative local recurrence rate was 6.3%. At 3 years postoperatively, 87% of patients used their own anus, and the median incontinence score improved from 12 at 3 months to 8 at 3 years. Only 5% of patients had severe incontinence (incontinence score of 16 points). Postoperative urinary function evaluation showed that International Prostate Symptom Score and Overactive Bladder Symptom Score decreased 1 week after surgery, but recovered to preoperative level 1 month after surgery. International Consultation on Incontinence Questionnaire-Sort Form remained almost stable after surgery. Sexual function evaluation using the International Index of Erectile Function-5 and International Index of Erectile Function-15 revealed that the patients had deteriorated 3 months after surgery but had recovered only slightly by 6 months. CONCLUSIONS: Laparoscopic surgery achieves feasible long-term oncological outcomes and a high rate of anus preservation with moderate anal function, and an acceptable incontinence score. While urinary function recovered rapidly, sexual function showed poor recovery.

Clinical impact of intraoperative pancreatic transection margin analysis and additional resection during pancreaticoduodenectomy for pancreatic ductal adenocarcinoma.

BACKGROUND: The prognostic impact of additional resection based on intraoperative frozen section analysis (FSA) of the pancreatic transection margin in patients with pancreatic ductal adenocarcinoma (PDAC) is controversial. The purpose of this study was to evaluate the prognosis based on the results of the first FSA of the pancreatic transection margin (1st FSA) and the clinical significance of additional resection. METHODS: Patients who underwent pancreaticoduodenectomy for PDAC from 2000 to 2020 at a single center were included. Patients were divided into 3 groups based on the 1stFSA. Survival and prognostic factors were analyzed according to the 1stFSA. RESULTS: A total of 311 patients were included in this study. The 1stFSA was negative in 272 patients (1stFSA-R0) and positive in 39 patients [carcinoma in situ (1stFSA-CIS), 21 patients; invasive carcinoma (1stFSA-IC), 18 patients]. Additional resections were performed on 37 patients [1stFSA-CIS, 20 patients; 1stFSA-IC, 17 patients], and R0 resection was achieved in 34 patients intraoperatively. Comparing median survival time to 1stFSA-R0 (36.4 months), 1stFSA-CIS was comparable (27.8 months, p = 0.276), although 1stFSA-IC was significantly worse (18.8 months, p = 0.001). On multivariate analysis, 1stFSA-IC was an independent prognostic factor (hazard ratio 2.68, 95 % confidence interval 1.16-6.17, p = 0.020). CONCLUSIONS: 1stFSA-CIS and 1stFSA-R0 had similar OS, implying that additional resection may be acceptable for 1stFSA-CIS. 1stFSA-IC was still an independent prognostic factor based on additional resection, and the prognostic significance of additional resection is uncertain for 1stFSA-IC.

The emerging emetogenicity of trifluridine/tipiracil (TAS­102) from patient self-reporting: a multicenter, prospective, observational study.

BACKGROUND: Trifluridine/tipiracil (TAS-102) is an oral anticancer drug with adequate efficacy in unresectable colorectal cancer, but frequently also induces chemotherapy-induced nausea and vomiting (CINV). To investigate the occurrence of CINV and antiemetic therapy in patients with colorectal cancer treated with TAS-102 (JASCC-CINV 2001). METHODS: We conducted a multicenter, prospective, observational study in patients with colorectal cancer who received TAS-102 without dose reduction for the first time. Primary endpoint was the incidence of vomiting during the overall period. Secondary endpoints were the incidence of nausea, significant nausea, anorexia, other adverse events (constipation, diarrhea, insomnia, fatigue, dysgeusia) and patient satisfaction. Patient diaries were used for primary and secondary endpoints. All adverse events were subjectively assessed using PRO-CTCAE ver 1.0. and CTCAE ver 5.0. RESULTS: Data from 100 of the 119 enrolled patients were analyzed. The incidence of vomiting, nausea, and significant nausea was 13%, 67%, and 36%, respectively. The incidence of vomiting in patients with and without prophylactic antiemetic therapy were 20.8% and 10.5%, respectively. Prophylactic antiemetics were given to 24% of patients, of whom 70% received D2 antagonists. Multivariate Cox proportional hazards analysis showed that experience of CINV in previous treatment tended to be associated with vomiting (hazard ratio [HR]: 7.13, 95% confidence interval [CI]: 0.87-58.5, P = 0.07), whereas prophylactic antiemetic administration was not (HR: 1.61, 95 CI: 0.50-5.21, P = 0.43). With regard to patient satisfaction, the proportion of patients who were "very satisfied," "satisfied," "slightly satisfied" or "somewhat satisfied" was 81.8%. CONCLUSIONS: The low incidence of vomiting and high patient satisfaction suggest that TAS-102 does not require the use of uniform prophylactic antiemetic treatments. However, patients with the experience of CINV in previous treatment might require prophylactic antiemetic treatment.

Application of an artificial intelligence-based system in the diagnosis of breast ultrasound images obtained using a smartphone.

BACKGROUND: Breast ultrasound (US) is useful for dense breasts, and the introduction of artificial intelligence (AI)-assisted diagnoses of breast US images should be considered. However, the implementation of AI-based technologies in clinical practice is problematic because of the costs of introducing such approaches to hospital information systems (HISs) and the security risk of connecting HIS to the Internet to access AI services. To solve these problems, we developed a system that applies AI to the analysis of breast US images captured using a smartphone. METHODS: Training data were prepared using 115 images of benign lesions and 201 images of malignant lesions acquired at the Division of Breast Surgery, Gifu University Hospital. YOLOv3 (object detection models) was used to detect lesions on US images. A graphical user interface (GUI) was developed to predict an AI server. A smartphone application was also developed for capturing US images displayed on the HIS monitor with its camera and displaying the prediction results received from the AI server. The sensitivity and specificity of the prediction performed on the AI server and via the smartphone were calculated using 60 images spared from the training. RESULTS: The established AI showed 100% sensitivity and 75% specificity for malignant lesions and took 0.2 s per prediction with the AI sever. Prediction using a smartphone required 2 s per prediction and showed 100% sensitivity and 97.5% specificity for malignant lesions. CONCLUSIONS: Good-quality predictions were obtained using the AI server. Moreover, the quality of the prediction via the smartphone was slightly better than that on the AI server, which can be safely and inexpensively introduced into HISs.

Successful multidisciplinary treatment for synchronous advanced esophageal and cecal cancers after total gastrectomy with reconstruction by jejunal interposition.

BACKGROUND: Esophageal squamous cell carcinoma is characterized by field cancerization, wherein multiple cancers occur in the esophagus, head and neck, and stomach. Synchronous esophageal and colorectal cancers are also encountered with a certain frequency. A good prognosis can be expected if the tumors in both locations can be safely and completely removed. For patients with multiple cancers that occur simultaneously with esophageal cancer, it is necessary to perform a staged operation, taking into consideration the associated surgical invasiveness. It is also necessary to select multidisciplinary treatment depending on the degree of progression of the multiple lesions. We report our rare experience with a staged operation for a patient with synchronous advanced cancers of the esophagus and cecum who had previously undergone total gastrectomy with reconstruction by jejunal interposition for gastric cancer. CASE PRESENTATION: A 71-year-old man with a history of reconstruction by jejunal interposition after total gastrectomy was diagnosed as having multiple synchronous esophageal and cecal cancers. After neoadjuvant chemotherapy, we performed a planned two-stage operation, with esophagectomy and jejunostomy in the first stage and ileocecal resection and jejunal reconstruction with vascular anastomosis in the second. Postoperatively, the patient was relieved without major complications, and both tumors were amenable to curative pathologic resection. CONCLUSIONS: Our procedure reported here may be recommended as an option for staged resection and reconstruction in patients with simultaneous advanced esophageal and cecal cancer after total gastrectomy.

Technical outcomes of robotic-assisted surgery versus laparoscopic surgery for rectal tumors: a single-center safety and feasibility study.

PURPOSE: Robot-assisted surgery has a multi-joint function, which improves manipulation of the deep pelvic region and contributes significantly to perioperative safety. However, the superiority of robot-assisted surgery to laparoscopic surgery remains controversial. This study compared the short-term outcomes of laparoscopic and robot-assisted surgery for rectal tumors. METHODS: This single-center, retrospective study included 273 patients with rectal tumors who underwent surgery with anastomosis between 2017 and 2021. In total, 169 patients underwent laparoscopic surgery (Lap group), and 104 underwent robot-assisted surgery (Robot group). Postoperative complications were compared via propensity score matching based on inverse probability of treatment weighting (IPTW). RESULTS: The postoperative complication rates based on the Clavien-Dindo classification (Lap vs. Robot group) were as follows: grade ≥ II, 29.0% vs. 19.2%; grade ≥ III, 10.7% vs. 5.8%; anastomotic leakage (AL), 6.5% vs. 4.8%; and urinary dysfunction (UD), 12.1% vs. 3.8%. After adjusting for the IPTW method, although AL rates did not differ significantly between groups, postoperative complications of both grade ≥ II (odds ratio [OR] 0.66, 95% confidence interval [CI] 0.50-0.87, p < 0.01) and grade ≥ III (OR 0.29, 95% CI 0.16-0.53, p < 0.01) were significantly less frequent in the Robot group than in the Lap group. Furthermore, urinary dysfunction also tended to be less frequent in the Robot group than in the Lap group (OR 0.62, 95% CI 0.38-1.00; p = 0.05). CONCLUSION: Robot-assisted surgery for rectal tumors provides better short-term outcomes than laparoscopic surgery, supporting its use as a safer approach.

Clinical significance of circulating-tumour DNA analysis by metastatic sites in pancreatic cancer.

BACKGROUND: Liquid biopsy is an alternative to tissue specimens for tumour genotyping. However, the frequency of genomic alterations with low circulating-tumour DNA (ctDNA) shedding is shown in pancreatic ductal adenocarcinoma (PDAC). We, therefore, investigated the prevalence of KRAS mutations and ctDNA fraction by the metastatic site in patients with PDAC. METHODS: This study enrolled previously treated PDAC patients from a plasma genomic profiling study; ctDNA analysis was performed using Guardant360 at disease progression before initiating subsequent treatment. RESULTS: In 512 patients with PDAC, KRAS mutations were detected in 57%. The frequency of KRAS mutation in ctDNA differed depending on the metastatic organ; among patients with single-organ metastasis (n = 296), KRAS mutation detection rate was significantly higher in patients with metastasis to the liver (78%). In addition, the median maximum variant allele frequency (VAF) was higher with metastasis to the liver (1.9%) than with metastasis to the lungs, lymph nodes, peritoneum or with locally advanced disease (0.2%, 0.4%, 0.2% and 0.3%, respectively). CONCLUSION: The prevalence of KRAS mutations and maximum VAF were higher in patients with metastasis to the liver than in those with metastasis to other sites. This study indicated the clinical utility of ctDNA analysis, especially in PDAC with liver metastases.

Prognostic impact of severe neutropenia in colorectal cancer patients treated with TAS-102 and bevacizumab, addressing immortal-time bias.

BACKGROUND: Several studies have reported an association between severe neutropenia and long-term survival in patients treated with trifluridine-tipiracil (TAS-102). Because some of these studies failed to address immortality time bias, however, their findings should be interpreted with caution. Additionally, the association between severe neutropenia and survival in patients receiving TAS-102 in combination with bevacizumab (Bmab) remains unclear. PATIENTS AND METHODS: We conducted a single-center retrospective cohort study in patients with colorectal cancer who received Bmab + TAS-102. We compared overall survival (OS) between patients who developed grade ≥ 3 neutropenia during the treatment period and those who did not. To account for immortal time bias, we used two approaches, time-varying Cox regression and landmark analysis. RESULTS: Median OS was 15.3 months [95% CI: 14.1-NA] in patients with grade ≥ 3 neutropenia and 10.0 months [95% CI: 8.1-NA] in those without. In time-varying Cox regression, onset grade ≥ 3 neutropenia was significantly related to longer survival after adjustment for age and modified Glasgow Prognostic Score. Additionally, 30-, 60-, 90-, and 120-day landmark analysis showed that grade ≥ 3 neutropenia was associated with longer survival after adjustment for age and modified Glasgow Prognostic Score, with respective HRs of 0.30 [0.10-0.90], 0.65 [0.30-1.42], 0.39 [0.17-0.90], and 0.41 [0.18-0.95]. CONCLUSION: We identified an association between long-term survival and the development of severe neutropenia during the early cycle of Bmab + TAS-102 using an approach that addressed immortality time bias.

NEXUS trial: a multicenter phase II clinical study evaluating the efficacy and safety of the perioperative use of encorafenib, binimetinib, and cetuximab in patients with previously untreated surgically resectable BRAF V600E mutant colorectal oligometastases.

BACKGROUND: The optimal treatment strategy for resectable BRAF V600E mutant colorectal oligometastases (CRM) has not been established due to the rarity and rapid progression of the disease. Since the unresectable recurrence rate is high, development of novel perioperative therapies are warranted. On December 2020, the BEACON CRC triplet regimen of encorafenib, binimetinib, and cetuximab was approved for unresectable metastatic colorectal cancer in Japan. METHODS: The NEXUS trial is a multicenter phase II clinical study evaluating the efficacy and safety of the perioperative use of encorafenib, binimetinib, and cetuximab in patients with previously untreated surgically resectable BRAF V600E mutant CRM. The key inclusion criteria are as follows: histologically diagnosed with colorectal adeno/adenosquamous carcinoma; RAS wild-type and BRAF V600E mutation by tissue or blood; and previously untreated resectable distant metastases. The triplet regimen (encorafenib: 300 mg daily; binimetinib: 45 mg twice daily; cetuximab: 400 mg/m2, then 250 mg/m2 weekly, 28 days/cycle) is administered for 3 cycles each before and after curative resection. The primary endpoint of the study is the 1-year progression-free survival (PFS) rate and the secondary end points are the PFS, disease-free survival, overall survival, and objective response rate. The sample size is 32 patients. Endpoints in the NEXUS trial as well as integrated analysis with the nationwide registry data will be considered for seeking regulatory approval for the perioperative use of the triplet regimen. DISCUSSION: The use of the triplet regimen in the perioperative period is expected to be safe and effective in patients with resectable BRAF V600E mutant CRM. TRIAL REGISTRATION: jRCT2031220025, April. 16, 2022.

Perioperative predictive factors of failure to rescue following highly advanced hepatobiliary-pancreatic surgery: a single-institution retrospective study.

BACKGROUND: Failure to rescue (FTR), defined as a postoperative complication leading to death, is a recently described outcome metric used to evaluate treatment quality. However, the predictive factors for FTR, particularly following highly advanced hepatobiliary-pancreatic surgery (HBPS), have not been adequately investigated. This study aimed to identify perioperative predictive factors for FTR following highly advanced HBPS. METHODS: This single-institution retrospective study involved 177 patients at Gifu University Hospital, Japan, who developed severe postoperative complications (Clavien-Dindo classification grades ≥ III) between 2010 and 2022 following highly advanced HBPS. Univariate analysis was used to identify pre-, intra-, and postoperative risks of FTR. RESULTS: Nine postoperative mortalities occurred during the study period (overall mortality rate, 1.3% [9/686]; FTR rate, 5.1% [9/177]). Univariate analysis indicated that comorbid liver disease, intraoperative blood loss, intraoperative blood transfusion, postoperative liver failure, postoperative respiratory failure, and postoperative bleeding significantly correlated with FTR. CONCLUSIONS: FTR was found to be associated with perioperative factors. Well-coordinated surgical procedures to avoid intra- and postoperative bleeding and unnecessary blood transfusions, as well as postoperative team management with attention to the occurrence of organ failure, may decrease FTR rates.

Drain fluid and serum amylase concentration ratio is the most reliable indicator for predicting postoperative pancreatic fistula after distal pancreatectomy.

BACKGROUND: Postoperative pancreatic fistula (POPF) is a major complication of pancreatic surgery. Drain fluid amylase concentration (DAC) is considered a predictive indicator of POPF. However, other indicators related to postoperative drain fluid amylase status exist, and the most reliable indicator for predicting POPF remains unclear. The object of this study is to identify the single most accurate indicator related to drain fluid amylase status of POPF after distal pancreatectomy (DP). METHODS: This single-institution retrospective study included 122 patients who underwent DP. The study was conducted between 2010 and 2022 at Gifu University Hospital. We statistically analyzed DAC, drain fluid amylase amount (DAA) calculated by multiplying DAC and daily drainage volume, and drain and serum amylase concentration ratio (DSACR) to assess the correlation with POPF. RESULTS: Based on the definition and grading of the International Study Group of Pancreatic Fistula, 24.6 (%) of the 122 patients had Grades B and C POPF. The result of the receiver operating characteristic (ROC) curve for predicting POPF after DP, DSACR had the highest area under curve(AUC) value among DAC, DAA, and DSACR both POD1 and POD3. The cutoff value of DSACR on POD1 was 17 (AUC 0.69, sensitivity 80.0%, specificity 58.2%, and accuracy 63.6%). The cutoff value of DSACR on POD3 was 22 (AUC 0.77, sensitivity 77.7%, specificity 73.3%, and accuracy 73.6%). Overall, DSACR on POD3 had the highest AUC value. Furthermore, a multivariate logistic regression analysis revealed that pancreatic texture (soft; odds ratio [OR] 9.22; 95% confidence interval [CI] 2.22-44.19; p < 0.01) and DSACR on POD3 (> 22; OR 8.76; 95% CI 2.78-31.59; p < 0.001) were independently associated with POPF after DP. CONCLUSIONS: DSACR is the most reliable indicator of drain fluid amylase status for predicting POPF after DP.

Short-term outcomes associated with the use of a new powered circular stapler for rectal reconstructions: a retrospective study comparing it to manual circular staplers using inverse probability of treatment weight analysis.

BACKGROUND: The most common postoperative complication in malignant rectal surgery is anastomotic leakage (AL). AL after anterior or low anterior resection in rectal tumors is a fatal postoperative complication. Recently, the first automated suture circular stapler, which is expected to reduce the incidence of AL, (J&J). MATERIALS AND METHODS: This study included a total of 248 rectal tumor patients who underwent double stapler technique (DST) anastomotic procedures in the department of gastroenterological surgery /pediatric surgery at Gifu University School of Medicine from January 2017 to December 2021. The experience of a single institution utilizing the The Echelon circular™ stapler (ECP stapler:Manual VS Automatic) in rectal surgery cases was evaluated retrospectively from maintained database. RESULT: One hundred thirty-nine patients (58.4%) were performed by manual circular stapling, 99 patients (41.6%) by powerd circular stapling. Diverting stoma was performed in 45 cases (32.4%) by manual circular stapling, 42 patients (42.4%) by powerd circular stapling Postoperative complications were occurred clavien-dindo grade II or higher in 57 cases (23.9%) and grade III or higher in 20 cases (8.4%). Anastomotic leakage occurred in 14 patients (5.9%) within all grades. After IPTW, the variables of patient characteristics was SMD ≤ 0.2 (Table.3), and there was a significant difference in anastomotic leakage (Odds Ratio (OR), 0.57; 95% Confidence Interval(CI), 0.34-0.98; p = 0.041). In addition, there was no significant difference in postoperative complications in grade II or higher (OR, 0.88; 95%CI, 0.65-1.19; p = 0.417) and grade III or higher (OR, 0.46; 95%CI, 0.29-0.74; p = 0.001) were significantly remarkable lower in powered circular stapling group. CONCLUSION: In this IPTW comparison of patients undergoing rectal reconstructions, the ECP trial cohort had lower risks of several surgical complications AL and statistically signifcant lower rates of ileus/bowel obstruction, infection, and bleeding as Clavien-Dindo ≥ grade II and III as compared with for whom manual circular staplers were used.

Gastric carcinosarcoma with FGFR2 amplification under long-term control with pazopanib: a case report and literature review.

BACKGROUND: Gastric carcinosarcoma is most frequently diagnosed at an advanced stage when the tumor is generally large with invasion into other organs, lymph node metastasis, and distant metastasis. Standard chemotherapy has not been established, and surgery is the only curative treatment. Here, we present a case of postoperative recurrence of gastric carcinosarcoma under long-term tumor control with pazopanib. CASE PRESENTATION: A 77-year-old man was referred to our hospital because of nausea and vomiting. Computed tomography and upper gastrointestinal endoscopy revealed a type 1 tumor arising from the gastric antrum and extending into the duodenal bulb. He underwent distal gastrectomy (D2) with Roux-en-Y reconstruction. Histopathologically, the tumor had mixed adenocarcinoma and sarcoma components. According to the tumor-node-metastasis classification, the diagnosis was primary gastric carcinosarcoma pT1bN1M0 stage IB. Liver metastasis was detected 2 months after surgery; multiple lung metastases were detected 17 month after surgery. A genomic profiling test was performed using liver specimens as the patient became refractory to chemotherapy commonly used for gastric cancer, and the test revealed FGFR2 amplification along with TP53 R209*, AKT3 N127D, NOTCH1 A2036T, and POLD1 M161I. The patient was treated with pazopanib (800 mg/daily), and the tumor growth was controlled for 11 months. CONCLUSIONS: We report a case of postoperative recurrence of gastric carcinosarcoma under long-term tumor control with pazopanib. This case suggested that pazopanib may be effective in treating gastric carcinosarcoma.

Serum diamine oxidase activity derived from response to chemotherapy affects adverse events and serum amino acid levels.

PURPOSE: The relationship between activity of the small intestinal villi and the effectiveness of chemotherapy remains unclear. This study aimed to investigate how serum diamine oxidase (DAO) activity affects antitumor effects, adverse events, and amino acid absorption. METHODS: We performed a single-center prospective cohort study that enrolled 50 patients with esophageal cancer (EC) receiving docetaxel, cisplatin, and 5-fluorouracil therapy. We determined the cut-off value of serum DAO activity contributing to a response to chemotherapy using a generalized additive model. Additionally, we compared adverse events, inflammatory markers, blood amino acid levels, and quality of life between the high and low DAO activity groups during chemotherapy. RESULTS: The cut-off value of serum DAO activity at the first visit that contributed to a chemotherapy response was 6.5 units/L. Leukopenia and neutropenia of grade ≥ 3 were significantly higher in the DAO low (< 6.5 units/L) group (p = 0.044, 0.017, respectively). Interleukin-6 was significantly lower in the DAO high (≥ 6.5 units/L) group at the first visit and at 4 weeks after the end of chemotherapy (p = 0.039, 0.011, respectively). Glutamine was higher in the DAO high group at all measurement points during chemotherapy. Fatigue was significantly lower in the DAO high group (p = 0.001). CONCLUSION: Serum DAO activity may be a predictor of the response to chemotherapy in patients with EC. The absorption capacity of amino acids was maintained in the group with high DAO activity, which may have contributed to the anti-inflammatory effect and provided a background for reducing adverse events.

A randomized controlled trial of surgery and postoperative modified FOLFOX6 versus surgery and perioperative modified FOLFOX6 plus cetuximab in patients with KRAS wild-type resectable colorectal liver metastases: EXPERT study.

PURPOSE: To clarify the efficacy of perioperative chemotherapy for the patients with resectable colorectal liver metastases (CLM), we conducted a multicenter randomized phase III trial to compare surgery followed by postoperative FOLFOX regimen with perioperative FOLFOX regimen plus cetuximab in patients with KRAS wild-type resectable CLM. METHODS: Patients who had KRAS wild-type resectable CLM having one to eight liver nodules without extrahepatic disease were randomly assigned to the postoperative chemotherapy group, wherein up-front hepatectomy was performed followed by 12 cycles of postoperative modified FOLFOX6, and the perioperative chemotherapy group (experimental), wherein six cycles of preoperative modified FOLFOX6 plus cetuximab were performed followed by hepatectomy and six cycles of postoperative modified FOLFOX6 plus cetuximab. The primary endpoint was progression-free survival (PFS). RESULTS: There were 37 patients in postoperative chemotherapy group and 40 patients in the perioperative chemotherapy group who were analyzed. Baseline characteristics were well-balanced between groups. The PFS and overall survival (OS) showed no significant difference (PFS, hazard ratio 1.18 [95% confidence interval 0.69-2.01], P = 0.539: OS, 1.03 [0.46-2.29], P = 0.950). In the postoperative chemotherapy group, 35.1% had a 3-year PFS, and 86.5% had a 3-year OS. Meanwhile, in the perioperative chemotherapy group, 30.0% had a 3-year PFS, and 74.4% had a 3-year OS. CONCLUSION: There was no difference in survival found between the group of the perioperative chemotherapy plus cetuximab and that of the postoperative chemotherapy in the cohort of our study. The study was registered in the University Hospital Medical Information Network (UMIN000007787).

Right top pulmonary vein is a venous anomaly of which surgeons should be aware in subcarinal dissection for thoracoscopic esophagectomy: a case report and literature review.

BACKGROUND: A right top pulmonary vein (RTPV) that crosses behind the right main or intermediate bronchus is a variation of the superior posterior pulmonary vein in the right upper lobe. Damage or ligation of this abnormal vessel can lead to massive intraoperative bleeding and serious complications, such as congestion of the posterior segment of the right upper lobe and cardiac tamponade. Subcarinal lymph node dissection is mandatory in radical thoracoscopic esophagectomy for esophageal cancer, and the RTPV is an anomalous vessel of which thoracic surgeons should be aware. CASE PRESENTATION: A 70-year-old man underwent thoracoscopic esophagectomy for esophageal cancer (T3N1M0). An anomaly of the superior posterior pulmonary vein in the right lobe was recognized on preoperative computed tomography imaging. With simulation and intraoperative navigation using three-dimensional imaging of the same view as that observed during the operation, radical subcarinal dissection could be performed with preservation of the RTPV. CONCLUSION: In our review of the relevant literature, the incidence of RTPV ranged from 0.28 to 9.3%, and its mean vascular diameter was 7.0 mm at the maximum and 2.2 ± 0.72 mm at the minimum, with the right superior pulmonary vein being a relatively common inflow site. Our case in which the RTPV ran dorsal to the right main bronchus is very rare. In radical subcarinal dissection of thoracoscopic esophagectomy, it is important to recognize the posterior pericardial plane and release the ventral fixation of these lymph nodes to free space for the back side. This is also true in the case of RTPV, which should be noted to avoid injury. In cases involving an RTPV larger than 4.5 mm, ligation should be avoided, and preoperative recognition of the exact run of this abnormal vessel using three-dimensional imaging can be very useful.

Total laparoscopic resection by medial-retroperitoneal approach using virtual navigation: two case reports of primary retroperitoneal schwannoma.

BACKGROUND: We report two rare cases of retroperitoneal schwannoma completely resected by a laparoscopic medial-retroperitoneal approach aided by virtual navigation. Three-dimensional images have been used in liver and lung surgery, but there are few prior reports on retroperitoneal surgery. CASE PRESENTATION: These two case reports are of a 60-year-old man and a 40-year-old man with asymptomatic retroperitoneal schwannoma. In both cases, the tumors were located in the right renal hilum and were close to the duodenum, right ureter, and inferior vena cava. Simulation using three-dimensional images was performed before surgery, and a medial-retroperitoneal approach was performed to secure a wide surgical field. During the operation, we confirmed the location of the main feeder and the relationship between the tumor and organs with those shown on the three-dimensional images and performed total laparoscopic resection. CONCLUSION: The medial-retroperitoneal approach provides operative safety. Preoperative simulation and intraoperative navigation with three-dimensional images, which can be freely rotated and interactively visualized from any angle, are useful methods to enhance the surgeon's understanding of a patient's specific anatomy and are especially effective when resecting a retroperitoneal tumor that is located in an anatomically deep and complex location.

The pancreas-to-muscle signal intensity ratio on T1-weighted MRI as a predictive biomarker for postoperative pancreatic fistula after distal pancreatectomy: a single-center retrospective study.

BACKGROUND: Postoperative pancreatic fistula (POPF) is one of the serious complications of pancreatic surgery. When POPF occurs and becomes severe, it causes secondary complications and a longer treatment period. We previously reported a correlation between pancreatic fibrosis and magnetic resonance imaging (MRI) findings, and MRI may have the potential to predict POPF. This study aimed to assess the predictive ability of the pancreas-to-muscle signal intensity ratio on T1-weighted MRI (SIR on T1-w MRI) for POPF after distal pancreatectomy (DP). METHODS: This single-institution retrospective study comprised 117 patients who underwent DP. It was conducted between 2010 and 2021 at the Gifu University Hospital. We statistically analyzed pre-, intra-, and postoperative factors to assess the correlation with POPF. RESULTS: According to the definition and grading of the International Study Group of Pancreatic Fistula (ISGPF), 29 (24.8%) of the 117 patients had POPF grades B and C. In the univariate analysis, POPF was significantly associated with the pancreas-to-muscle SIR on T1-w MRI, the drainage fluid amylase concentration (D-Amy) levels on postoperative day (POD) 1 and 3, white blood cell count on POD 1 and 3, C-reactive protein level on POD 3, and heart rate on POD 3. In multivariate analysis, only the pancreas-to-muscle SIR on T1-w MRI (>1.37; odds ratio [OR] 23.25; 95% confidence interval [CI] 3.93-454.03; p < 0.01) and D-Amy level on POD 3 (>737 U/l; OR 3.91; 95% CI 1.02-16.36; p = 0.046) were identified as independent predictive factors. CONCLUSIONS: The pancreas-to-muscle SIR on T1-w MRI and postoperative D-Amy levels were able to predict the development of POPF after DP. The pancreas-to-muscle SIR on T1-w MRI may be a potential objective biomarker reflecting pancreatic status.

Evaluation of the SYNAPSE VINCENT for lateral lymph node dissection in rectal cancer with robotic surgery: a preliminary report.

BACKGROUND: Even if 3D angiographic images of preoperative contrast-enhanced computed tomography (CT) are created, the coronal and axial sections can be unclear, and thus, it is difficult to achieve projection awareness similar to that of actual laparoscopic images. In recent years, the technology of analyzing and applying medical images has advanced, and surgical simulation and navigation have been widely used to improve the safety of surgical operations. It is important to understand pelvic anatomy in the area of rectal cancer, and use of the SYNAPSE VINCENT makes it possible to simulate the anatomy before surgery, which is very useful in educating surgeons and their assistants. MATERIALS AND METHODS: An important objective in surgery is to understand the anatomy of the external/internal iliac arteries and lymph nodes in lateral lymph node dissection (LLD) for rectal cancer. In this study, we explored the accuracy and usefulness of SYNAPSE VINCENT images of pelvic anatomy (especially vascular anatomy) analyzed preoperatively in two cases of LLD for rectal cancer in our department. RESULTS: The patients were two men aged 73 and 57 years, respectively. Both patients underwent robotic abdominal perineal resection and LLD with neoadjuvant chemoradiotherapy. The operating times for LLD were 138 and 106 min, estimated blood loss was less than 10 mL and 20 mL, and the harvested lymph nodes were nos. 21 and 22, respectively. The SYNAPSE VINCENT could be used for simulation and navigation before and during surgery. For experienced surgeons, the system helped them carry out operations more accurately. CONCLUSION: In the future, surgical support using virtual reality, augmented reality, and mixed reality based on medical images will be useful and is expected to improve the safety, accuracy, and efficiency of surgery, which is extremely useful for both young and skilled surgeons preparing for difficult operations.