Monitoring ctDNA RAS Mutational Status in Metastatic Colorectal Cancer: A Trial Protocol of RAS-trace and RAS-trace-2 Studies.

Background: Spatial and temporal heterogeneities of RAS and other molecular genes should be considered in the treatment of metastatic colorectal cancer (mCRC) treated with anti-epidermal growth factor receptor (EGFR) monoclonal antibodies (mAbs); acquired RAS mutation is sometimes observed at disease progression of treatment with the anti-EGFR mAb. At the same time, discrepancy of RAS status from tissues and circulating tumor DNA (ctDNA) in the same patient is sometimes observed. Based on this, we commenced two observational studies to clarify these heterogeneities of RAS and BRAF in mCRC, using next generation sequencing from liquid biopsy. Methods/Design: RAS-trace study is an observational study to monitor ctDNA RAS/BRAF/PIK3CA status every 4-12 weeks using the Plasma-SeqSensei™ CRC RUO Kit (Sysmex Inostics GmbH) in mCRC with RAS/BRAF wild-type (wt) on tumor tissue. The primary endpoint was the time to the acquired RAS mutations. A total of 42 patients has been accrued. RAS-trace-2 study is also an observational study aimed at comparing the efficacy of the anti-EGFR mAb in ctDNA RAS/BRAF wt with ctDNA RAS or BRAF mutant mCRC patients, whose RAS/BRAF are wt in tumor tissue. The primary endpoint was progression-free survival in patients with ctDNA RAS/BRAF wt and RAS or BRAF mutant. A total of 240 patients will be accrued over 2 years. Discussion: These trials will help us understanding the clinical significance of spatial and temporal heterogeneities of RAS, BRAF and other genes, while optimizing the anti-EGFR mAb treatment strategies in mCRC.

Low prognostic nutrition index as a prognostic biomarker in elderly patients with early gastric cancer after gastrectomy.

Purpose Non-invasive biomarkers including systemic inflammatory or nutrition-based index including neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR) lymphocyte to monocyte ratio (LMR), and prognostic nutritional index (PNI) can be useful in determining treatment strategies for elderly patients with early gastric cancer (EGC). The aim of this study was to investigate the significance of these index for predicting the long-term survival of EGC patients aged 80 years over. Methods This study included 80 elderly EGC patients with pStageIA after gastrectomy. Optimal cutoff value for PNI, NLR, PLR and LMR were set by using receiver operating curve analysis. The long-term outcomes after gastrectomy were analyzed by univariate and multivariate Cox regression analyses. Results Cut-off value for PNI, NLR, PLR and LMR was set at 46.5, 2.8, 210 and 4.6, respectively. By univariate analyses, low PNI, high NLR, high PLR and low LMR were significantly associated with worse prognosis. By multivariate analysis, low PNI was confirmed as an independent prognostic factor after gastrectomy (HR 0.17 ; 95% CI 0.03-0.91 ; P = 0.04). 5-year overall survival rate of patients with low PNI (≤ 46.5) were 52.4%. Conclusion Low PNI might be useful biomarker to predict worse prognosis of elderly EGC patients after gastrectomy. J. Med. Invest. 71 : 113-120, February, 2024.

Intrathoracic anastomosis using handsewn purse-string suturing by the double-ligation method in laparo-thoracoscopic esophagectomy.

Purpose: In minimally invasive esophagectomy (MIE), it is important to reduce the rate of anastomotic leakage to ensure its safety. At our institute, the double-ligation method (DLM) has been introduced to insert and fix the anvil of the circular stapler for intracorporeal circular esophagojejunostomy in gastric surgery. We adopted this method for intrathoracic anastomosis (IA) in MIE. The aim of this study was to investigate the safety of IA with DLM in MIE. Methods: In this study, 48 patients diagnosed with primary middle or lower third segment thoracic esophageal carcinoma with clinical stage I, II, III or IV disease were retrospectively evaluated. Postoperative outcomes were assessed. Results: Among the 48 patients, 42 patients underwent laparo-thoracoscopic esophagectomy and IA using a circular stapler with the DLM. The average total operation time and thoracoscopic operation time were 433 and 229 minutes, respectively. The average purse-string suturing time was 4.7 minutes. The rates of anastomotic leakage and stenosis were 2.4% and 14.3%, respectively. The overall incidence of postoperative complications (Clavien-Dindo grade of ≥III) was 16.7%. The average postoperative stay was 16 days. Conclusion: The procedure of IA using a circular stapler with the DLM in MIE was safe and provided a low rate of anastomotic leakage.

Laparoscopic pancreaticoduodenectomy in patients with a history of right hemicolectomy : A report of three cases.

Laparoscopic pancreaticoduodenectomy (LPD) has been widely adopted in institutions with sufficiently skilled practitioners. This technique requires attentive dissection around the superior mesenteric vein (SMV) and artery. Dissection around the SMV and Henle's trunk is one of the key aspects of right hemicolectomy (RHC) ; adhesions and fibrosis around these vessels may impede LPD in patients with a history of RHC. We encountered three cases of periampullary tumors in patients with a history of RHC who were successfully treated with LPD. Cases 1, 2, and 3 were of 60-, 73-, and 74-year-old men with periampullary tumors. The operative durations in cases 1, 2, and 3 were 316, 267, and 265 min, respectively. The estimated blood loss volumes in cases 1, 2, and 3 were 20, 50, and 720 mL, respectively. The postoperative hospital stay durations in cases 1, 2, and 3 were of 13, 35, and 15 days, respectively. In conclusion, LPD following RHC may be safely completed with laparoscopy. J. Med. Invest. 70 : 285-289, February, 2023.

Tranexamic acid and blood loss in pancreaticoduodenectomy: TAC-PD randomized clinical trial.

BACKGROUND: Tranexamic acid (TXA) may reduce intraoperative blood loss, but it has not been investigated in pancreaticoduodenectomy (PD). METHODS: A pragmatic, multicentre, randomized, blinded, placebo-controlled trial was conducted. Adult patients undergoing planned PD for biliary, duodenal, or pancreatic diseases were randomly assigned to TXA or placebo groups. Patients in the TXA group were administered 1 g TXA before incision, followed by a maintenance infusion of 125 mg/h TXA. Patients in the placebo group were administered the same volume of saline as those in the placebo group. The primary outcome was blood loss during PD. The secondary outcomes included perioperative blood transfusions, operating time, morbidity, and mortality. RESULTS: Between September 2019 and May 2021, 218 patients were randomly assigned and underwent surgery (108 in the TXA group and 110 in the placebo group). Mean intraoperative blood loss was 659 ml in the TXA group and 701 ml in the placebo group (mean difference -42 ml, 95 per cent c.i. -191 to 106). Of the 218 patients, 202 received the intervention and underwent PD, and the mean blood loss during PD was 667 ml in the TXA group and 744 ml in the placebo group (mean difference -77 ml, 95 per cent c.i. -226 to 72). The secondary outcomes were comparable between the two groups. CONCLUSION: Perioperative TXA use did not reduce blood loss during PD. REGISTRATION NUMBER: jRCTs041190062 (https://jrct.niph.go.jp).

Removing part of the pancreas is an operation with a risk of major blood loss. Tranexamic acid is a drug thought to reduce blood loss. This study asked the question, 'Does tranexamic acid reduce blood loss during surgery on the pancreas?' Half of patients received tranexamic acid during surgery. The other half received only standard care. This study showed that tranexamic acid did not decrease the blood loss during the surgery and may have little effect in patients having a pancreaticoduodenectomy.

Correlation between the complex of small heat shock proteins (HSPBs) and the progression in patients with hepatocellular carcinoma.

Small heat shock proteins (HSPBs) regulate various cell functions. We previously reported that HSPB1, HSPB6, and HSPB8 each suppress the progression of hepatocellular carcinoma (HCC). The heterooligomerization of HSPs is speculated to be crucial for functional activities. Here, we investigated the relationship between the complex of HSPBs and the progression of HCC. HSPB1/HSPB6 complex and HSPB1/HSPB8 complex, but not HSPB6/HSPB8 complex, were observed in both HSPB6-overexpressing human HCC-derived HuH-7 cells and resected human HCC tumor tissue. Differentiation, stage, tumor size, and vein invasion of HCC were inversely related to the presence of HSPB complexes in the HCC tissue. Our results strongly suggest that the HSPB complex formation plays a suppressive role in the HCC progression.

Comparison of surgical outcomes of emergent laparoscopic cholecystectomy for acute cholecystitis between attending surgeons and senior residents: A propensity-matched analysis.

INTRODUCTION: Emergent laparoscopic cholecystectomy (LC) is routinely performed for acute cholecystitis (AC) at our institution. This study was conducted to investigate the feasibility and safety of emergent LC for AC performed by senior residents. MATERIALS AND METHODS: Data from 362 patients with AC who underwent emergent LC between January 2012 and June 2020 were retrospectively reviewed. Of these patients, 328 were operated on by senior residents (SR), and 34 were operated on by the attending surgeon (AS). Clinical characteristics and surgical and postoperative outcomes were compared between the SR and AS groups. Propensity score matching was used to minimize selection bias. When the operator was an SR, the LC was assisted by the AS. RESULTS: Before matching, in the SR group, more patients had a history of abdominal surgery, and C-reactive protein and white blood cell counts were significantly higher. In the image findings, the minor axis of the gallbladder (GB) was longer, and the wall of the GB was thicker in the SR group. After propensity score matching, 28 pairs were identified. There were no significant differences in operative time (83 vs 88 minutes, P = .92), the amount of blood loss (25 vs 10 mL, P = .13), conversion to open surgery (3.6% vs 3.6%, P = 1), postoperative complications (7.2% vs 0%, P = .74), and postoperative hospital stay (4 vs 4 days, P = .87). CONCLUSION: Emergent LC for AC performed by SR under supervision appears to be feasible and safe.

Identification of the suitable candidates for EOB-MRI with the high risk of the presence of non-hypervascular hypointense nodules in patients with HCV infection.

OBJECTIVES: Non-hypervascular hypointense nodules (NHHNs) depicted by gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid-enhanced magnetic resonance imaging (EOB-MRI) have a high likelihood of progressing to hepatocellular carcinoma (HCC). The presence of NHHNs is a strong risk factor for HCC development in patients with chronic hepatitis C virus (HCV) infection after the achievement of sustained virologic response (SVR). However, it is difficult for all patients with HCV infection to undergo EOB-MRI for NHHN detection. We therefore explored serum markers that potentially indicate the presence of NHHNs. METHODS: Three serum markers, alpha-fetoprotein (AFP), FIB-4 index, and Wisteria floribunda agglutinin-positive Mac-2 binding protein glycan isomer (M2BPGi), were measured in 481 patients with HCV infection and no history of HCC who underwent EOB-MRI. The associations between these serum marker levels and the presence of NHHNs were investigated. RESULTS: All three markers were associated with the presence of NHHNs. M2BPGi predicted the presence of NHHNs more accurately than AFP and FBB-4 index; M2BPGi had the highest area under the receiver operating characteristic curve. Multivariate analysis identified male gender and high M2BPGi as factors associated with the presence of NHHNs. When patients were stratified by the degree of liver fibrosis, M2BPGi increased with the progression of fibrosis. In addition, NHHNs were more prevalently detected in patients with higher M2BPGi (COI > 3.46) in patients with similar fibrosis degree. CONCLUSIONS: M2BPGi is a serum marker that potentially identifies HCV patients with high risk of the presence of NHHNs, for whom EOB-MRI should be considered. KEY POINTS: • Non-hypervascular hypointense nodule on EOB-DTPA-enhanced MRI is pre-HCC nodule with high likelihood of progressing to HCC, which is a strong predictor for HCC that develops after the eradication of HCV in patients with HCV infection. • It is difficult for all patients with HCV infection to undergo EOB-MRI for NHHN detection due to limited access, limited availability of MRI equipment, and high costs. • Serum Wisteria floribunda agglutinin-positive Mac-2 binding protein glycan isomer (M2BPGi) levels effectively indicate the presence of NHHNs and can be used to identify patients with high risk of their presence, for whom EOB-DTPA-enhanced MRI should be considered.

Neoadjuvant chemotherapy with S-1 plus cisplatin for esophageal squamous cell carcinoma.

S-1 shows good efficacy for esophageal squamous cell carcinoma (ESCC) under single use or combined with cisplatin or radiotherapy. The S-1 plus cisplatin (SP) regimen is one of the chemotherapy candidates for ESCC. However, the efficacy of the SP regimen for neoadjuvant chemotherapy (NAC) has not been verified. The aim of this study was to investigate the feasibility and efficacy of NAC with SP for advanced ESCC. In this study, patients with clinical stage II/III/IV ESCC received NAC with SP regimen from June 2016 to July 2020 in Ogaki Municipal Hospital were retrospectively evaluated. In the SP regimen, S-1 80 mg/m2 was administered on days 1-14, and cisplatin was administered 70 mg/m2 on day 1, repeated every 4 weeks, for two cycles. The completion rate, clinical and pathological response rate, adverse events, and long-term outcomes were analyzed. 43 ESCC patients were diagnosed clinical stage II/III/IV ESCC. Among the 43 patients, 31 patients underwent NAC with SP regimen. The completion rate was 93.5%. The clinical response and pathological response rates (grade 2 or 3) were 83.9% and 32.3%, respectively. Seven patients (22.6%) had a pathological complete response (grade 3). Grade 3 neutropenia was observed in 33.7% of cases. No other grade 3 cases or higher toxicity was observed. The 3-year relapse-free and overall survival rates were 52.6% and 65.6%, respectively. NAC with SP is a feasible and effective treatment strategy for advanced. ESCC. The antitumor response could be higher than that under the cisplatin plus 5-fluorouracil regimen.

Concordance of human equilibrative nucleoside transporter-1 expressions between murine (10D7G2) and rabbit (SP120) antibodies and association with clinical outcomes of adjuvant chemotherapy for pancreatic cancer: A collaborative study from the JASPAC 01 trial.

BACKGROUND: Expression of human equilibrative nucleoside transporter-1 (hENT1) is reported to predict survival of gemcitabine (GEM)-treated patients. However, predictive values of immunohistochemical hENT1 expression may differ according to the antibodies, 10D7G2 and SP120. AIM: We aimed to investigate the concordance of immunohistochemical hENT1 expression between the two antibodies and prognosis. METHODS: The subjects of this study were totally 332 whose formalin-fixed paraffin-embedded specimens and/or unstained sections were obtained. The individual H-scores and four classifications according to the staining intensity were applied for the evaluation of hENT1 expression by 10D7G2 and SP120, respectively. RESULTS: The highest concordance rate (79.8%) was obtained when the cut-off between high and low hENT1 expression using SP120 was set between moderate and strong. There were no correlations of hENT1 mRNA level with H-score (p = .258). Although the hENT1 mRNA level was significantly different among four classifications using SP120 (p = .011), there was no linear relationship among them. Multivariate analyses showed that adjuvant GEM was a significant predictor of the patients with low hENT1 expression using either 10D7G2 (Hazard ratio [HR] 2.39, p = .001) or SP120 (HR 1.84, p < .001). In contrast, agent for adjuvant chemotherapy was not significant predictor for the patients with high hENT1 expression regardless of the kind of antibody. CONCLUSION: The present study suggests that the two antibodies for evaluating hENT1 expression are equivalent depending on the cut-off point and suggests that S-1 is the first choice of adjuvant chemotherapy for pancreatic cancer with low hENT1 expression, whereas either S-1 or GEM can be introduced for the pancreatic cancer with high hENT1 expression, no matter which antibody is used.

Preoperative risk factors for technical difficulty in emergent laparoscopic cholecystectomy for acute cholecystitis.

AIM: We have routinely performed emergent laparoscopic cholecystectomy (LC) as soon as we diagnosed acute cholecystitis (AC), if patients could tolerate surgery. This study was conducted to identify the preoperative risk factors that predict the technical difficulty of emergent LC for AC. METHODS: A retrospective review of patients with AC who underwent emergent LC between 2012 and 2019 was conducted. Technical difficulty was defined as the presence of the following conditions: open conversion, operative time ≥120 min, or blood loss ≥500 ml. RESULTS: In all, 327 patients were included and divided into difficult LC (DLC, n = 61) and nondifficult LC (non-DLC, n = 266). Multivariate logistic analysis revealed that symptom duration ≥72 h was the only independent risk factor for DLC. Comparison of late LC (beyond 72 h, LLC) and early LC (within 72 h, ELC) showed a lower rate of creation of the critical view of safety and a longer hospital stay, as well as a longer operative time, a larger amount of bleeding, and a higher open conversion rate in LLC. However, the postoperative complication rates were equivalent. CONCLUSION: LC for AC with symptom duration ≥72 h tends to be technically difficult. However, it is acceptable regarding operative outcomes.

Assessment of Perioperative Symptoms of Patients with Gastric Cancer Using The Edmonton Symptom Assessment System Revised Japanese version (ESAS-r-J).

Purpose To evaluate the perioperative symptoms of gastric cancer patients undergoing gastrectomy using the Edmonton Symptom Assessment System Revised Japanese version (ESAS-r-J), which is a nine-item visual analogue scale to rate patient symptoms. Methods Between February 2015 and March 2017, 246 patients completed the ESAS-r-J before and after gastrectomy. We evaluated the changes in the prevalence and score of each ESAS-r-J item before and after gastrectomy. In addition, we compared them after gastrectomy between patients who underwent the different approaches. Results Before gastrectomy, anxiety and well-being were the most prevalent items (80%), followed by depression (45%). After gastrectomy, well-being was the most prevalent item (87%), followed by pain (68%). The prevalence of anxiety decreased from 80% to 59% (P = 0.002). The depression and anxiety scores decreased from 1.6 to 1.1 (P < 0.001) and from 2.6 to 1.7 (P = 0.002), respectively. The total score was higher in patients who underwent open surgery than in patients who underwent laparoscopic surgery (16.9 vs 12.9 ; P = 0.031). Conclusions After gastrectomy, psychological symptoms such as depression and anxiety improved despite more physical complaints than before gastrectomy. The laparoscopy was less invasive. It is very important to take care of psychological aspects before gastrectomy. J. Med. Invest. 68 : 90-95, February, 2021.

The impact of standardized methods of hepatic vein reconstruction with an external iliac vein graft.

BACKGROUND: Liver tumors that invade the hepatic vein are surgically challenging, especially in patients with liver dysfunction. Preservation of as much of the parenchyma as possible is important; thus, when feasible, we perform hepatectomy with hepatic vein reconstruction (HVR) using an external iliac vein (EIV) graft. We conducted a retrospective study to investigate the benefit of HVR and to evaluate our procedure. METHODS: The study included patients treated by hepatectomy with HVR using EIV grafts and vascular clips. We reviewed the surgical outcomes, including total operation and HVR times, postoperative complications, and postoperative liver function. RESULTS: The surgeries included right HVR (n=13), left HVR (n=3), and middle HVR (n=1). The total operation time was 277±72 minutes (155-400 minutes), and the HVR time was 27±5 minutes (19-40 minutes). Graft patency was confirmed in 14 (82%) of the patients. One patient who underwent HVR with running sutures required emergency surgery due to graft thrombosis. Clavien-Dindo > grade IIIa postoperative complications occurred in 4 (23.5%) patients, but there were no treatment-related deaths. CONCLUSIONS: In conclusion, our hepatic resections with HVR using the same techniques and graft materials showed acceptable surgical outcomes. From our experience, we believe that preparatory hepatic resection with HVR is an effective treatment, especially for patients with decreased liver function or with a small residual liver parenchyma.

Pretreatment non-hypervascular hypointense nodules on Gd-EOB-DTPA-enhanced MRI as a predictor of hepatocellular carcinoma development after sustained virologic response in HCV infection.

BACKGROUND: Identification of risk factors for the development of hepatocellular carcinoma (HCC) after a sustained virologic response (SVR) in patients with chronic hepatitis C virus (HCV) infection is urgently needed for HCC surveillance. AIMS: To evaluate whether the presence of non-hypervascular hypointense nodules (NHHNs) depicted by gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid-enhanced magnetic resonance imaging (EOB-MRI) before direct-acting antivirals (DAAs) therapy is a risk factor for de novo HCC development after SVR. METHODS: The presence of NHHNs was examined with EOB-MRI before the start of DAA therapy in 383 patients with HCV infection who achieved SVR. The incidence of de novo HCC after SVR was compared between patients with versus without NHHNs. RESULTS: NHHNs were detected before DAA therapy in 32 patients (8.4%). The incidence of de novo HCC after SVR was significantly higher in patients with NHHNs than in those without (1-, 3-, 5-year incidence, 9.8%, 24.2% and 41.6% vs. 0%, 1.2% and 4.4%, P < 0.0001). The presence of NHHNs before DAA therapy (adjusted HR, 10.86; 95% CI, 4.03-31.64) and cirrhosis (adjusted HR, 7.23; 95% CI, 1.88-35.85) were independently associated with a higher incidence of HCC after SVR. A higher incidence of de novo HCC after SVR remained after adjustment for age, gender, regular alcohol intake, diabetes, cirrhosis, FIB-4 index and serum alpha-foetoprotein with inverse probability of treatment weighting. CONCLUSIONS: This study confirmed that the presence of NHHNs before DAA therapy is a strong risk factor for the development of de novo HCC after SVR.

Short- and Long-Term Outcomes of Transabdominal Preperitoneal, Open Mesh Plug and Open Tissue Inguinal Hernia Repair.

BACKGROUND: There have been few comparisons of the postoperative outcomes of transabdominal preperitoneal (TAPP), open mesh plug (mesh plug) and open tissue (tissue) hernia repair. The objectives of this study were to compare these repair methods. METHODS: This was a retrospective study of 1813 inguinal hernia patients between January 2008 and December 2016. Of these patients, 474 underwent TAPP repair, 1293 underwent mesh plug repair, and 46 underwent tissue repair. The short-term and long-term outcomes determined by questionnaire were compared among the three groups. In addition, risk factors for patient dissatisfaction were assessed. RESULTS: In the TAPP group, the postoperative complications rate was the lowest at 4.6% (7.4% and 6.5% in the mesh plug and the tissue groups, respectively, P = 0.07), and recurrence rate was lower compared to the mesh plug group (0.8% vs. 3.3%, P = 0.002). As long-term outcomes, 92%, 88% and 75% of patients were satisfied in the TAPP, mesh plug and tissue groups, respectively (P = 0.03). The rate of patients with numbness was 3.1% in the TAPP group, 5.2% in the mesh plug group and 14% in the tissue group (P = 0.04). Predictive independent risk factors for patient dissatisfaction were complications (OR: 3.99, 95% CI: 1.35-11.8, P = 0.012) and infection (OR: 16.9, 95% CI: 1.25-229, P = 0.003). CONCLUSIONS: TAPP repair is superior to mesh plug and tissue repairs in terms of complications, satisfaction and numbness, as determined by questionnaire. Complications and infection were independently associated with the patient dissatisfaction.

Prediction of early recurrence of hepatocellular carcinoma after resection using digital pathology images assessed by machine learning.

Hepatocellular carcinoma (HCC) is a representative primary liver cancer caused by long-term and repetitive liver injury. Surgical resection is generally selected as the radical cure treatment. Because the early recurrence of HCC after resection is associated with low overall survival, the prediction of recurrence after resection is clinically important. However, the pathological characteristics of the early recurrence of HCC have not yet been elucidated. We attempted to predict the early recurrence of HCC after resection based on digital pathologic images of hematoxylin and eosin-stained specimens and machine learning applying a support vector machine (SVM). The 158 HCC patients meeting the Milan criteria who underwent surgical resection were included in this study. The patients were categorized into three groups: Group I, patients with HCC recurrence within 1 year after resection (16 for training and 23 for test); Group II, patients with HCC recurrence between 1 and 2 years after resection (22 and 28); and Group III, patients with no HCC recurrence within 4 years after resection (31 and 38). The SVM-based prediction method separated the three groups with 89.9% (80/89) accuracy. Prediction of Groups I was consistent for all cases, while Group II was predicted to be Group III in one case, and Group III was predicted to be Group II in 8 cases. The use of digital pathology and machine learning could be used for highly accurate prediction of HCC recurrence after surgical resection, especially that for early recurrence. Currently, in most cases after HCC resection, regular blood tests and diagnostic imaging are used for follow-up observation; however, the use of digital pathology coupled with machine learning offers potential as a method for objective postoprative follow-up observation.

Outcome of Hepatocellular Carcinoma Detected During Surveillance: Comparing USA and Japan.

BACKGROUND & AIMS: Differences in outcomes of hepatocellular carcinoma (HCC) between countries have been largely attributed to variation in the conduct of surveillance and subsequent HCC treatment eligibility. However, differences in outcomes among those detected under surveillance have not been well described. We compared characteristics and prognosis between patients with surveillance-detected HCC from the United States (US) and Japan. METHODS: Patients in whom initial HCC was detected under surveillance between January 2006 and December 2015 from two centers in the US and two from Japan were included. Survival was compared between patients from the US and Japan using multivariable Cox regression analysis and propensity-score matched analysis. We performed subgroup analyses by liver disease etiology, tumor stage, and type of HCC treatment. RESULTS: Of 3788 HCC patients, 1797 (47.4%) were diagnosed under surveillance, 715 from the US and 1082 from Japan. Patients from the US diagnosed under surveillance had worse liver dysfunction and larger tumor burden than those from Japan. In multivariate analysis, US patients with surveillance-detected HCC had significantly worse survival than those from Japan (HR 1.17, 95% CI 1.00-1.35), which was also observed in propensity-score matched analysis. However, this difference was no longer significant after adjusting for treatment type (HR 1.07, 95% CI 0.92-1.25). When stratified by treatment type, survival was comparable between the two countries except lower survival among patients who underwent resection in the US versus Japan. CONCLUSIONS: Prognosis of patients with surveillance-detected HCC is poorer in the US than Japan, primarily driven by differences in treatment delivery. Studies are necessary to elucidate reasons for these differences.

Laparoscopic liver resection after laparoscopic pancreatoduodenectomy for liver metastases of ampulla of Vater adenocarcinoma.

BACKGROUND: Repeat laparoscopic surgery has become increasingly common. However, reports of liver resection after pancreatoduodenectomy are scarce, and we report the first successful case of a patient who underwent laparoscopic liver resection after laparoscopic pancreatoduodenectomy. CASE PRESENTATION: A 65-year-old man underwent laparoscopic pancreatoduodenectomy for ampulla of Vater adenocarcinoma. According to the American Joint Committee on Cancer (8th edition) staging guidelines, the tumour was labelled as stage IIIB (fT2N2M0). Twelve months later, a computed tomography (CT) scan revealed liver masses (in segments 3 and 5) and swollen para-aortic lymph nodes. After six chemotherapy courses of gemcitabine with cisplatin, the CT scan showed the disappearance of the para-aortic lymph nodes and progression of liver metastases. Nineteen months after the initial surgery, the patient underwent laparoscopic partial liver resection of segment 5 and left lateral sectionectomy. First, we performed the operation in the left half lateral decubitus position. In this position, the portal vein was isolated safely without hindering the hepato-jejunal anastomosis, although the adhesions around the hepato-jejunal anastomosis were dense. Therefore, we were able to perform liver transection safely with vascular inflow control. The operation duration was 235 min, and the volume of blood loss was 100 g. Macroscopically, the resected margins were negative. The patient was uneventfully discharged 12 days after the second operation. Afterwards, drainage was needed because of an intra-abdominal abscess. Currently, he has been alive for 8 months postoperatively, receives chemotherapy to suppress para-aortic lymph node metastases, and has not had another recurrence. CONCLUSIONS: Liver resection after pancreatoduodenectomy can be performed safely with an innovative body position to isolate the portal vein, which is a key point of the surgery. A laparoscopic approach for liver resection after pancreatoduodenectomy is a feasible option.

Optimal Criteria for G3 (Poorly Differentiated) Stage II Colon Cancer: Prospective Validation in a Randomized Controlled Study (SACURA Trial).

Grade 3 (G3, poorly differentiated) is an important treatment-decision factor in stage II colon cancer, but no unified diagnostic criteria are established. According to previous studies, an intratumoural poorly differentiated area with no glandular formation (POR) that fills the microscopic field of a ×40 objective lens was an essential factor that defined G3. We aimed to prospectively validate this in a randomized controlled study of adjuvant chemotherapy (SACURA trial). We enrolled 991 patients with stage II colon cancer. POR was graded according to the ×40 objective lens rule and the intensity of poorly differentiated clusters (Grade), and its prognostic power was compared with that of the conventional tumor grade on the basis of predominant histology rule (Grade). According to Grade, 313, 526, and 152 tumors were classified as G1, G2, and G3, respectively, and the 5-year relapse-free survival (RFS) rates were 91.1%, 82.9%, and 74.7%, respectively (P<0.0001). When G3 and G3 were alternatively added to the prognostic model consisting of 8 conventional factors, only G3 was a significant factor for RFS (P=0.040, Wald test). The adverse impact of G3 on RFS was greater in the microsatellite stable/microsatellite instability-low subset than that in the full analysis set. In the microsatellite stable/microsatellite instability-low subset, the 5-year RFS rate of patients with G3 tumors in the chemotherapy group achieved greater improvement (9.1%) than the surgery-alone group. The least differentiation policy with the ×40 objective lens rule may be highlighted as the diagnostic criterion for G3 because of its validated prognostic value.