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Due to the overwhelming spread of SARS-CoV-2 and its disruption of the healthcare system, delays and reduced numbers were reported for colorectal cancer screening, colonoscopies, and surgery during the COVID-19 pandemic. This multicenter retrospective study investigated the still poorly understood impact of the COVID-19 pandemic on colorectal cancer treatment in Japan.This study was organized by the Clinical Study Group of Osaka University, which comprised 32 major institutions in Osaka. We retrospectively analyzed the number of surgeries and colonoscopies performed and the characteristics of patients who underwent surgery for colorectal cancer between March 2019 and February 2021. We compared data collected before and during the COVID-19 pandemic. We also assessed the methods used for detecting colorectal cancer, including fecal occult blood test, abdominal symptoms, and anemia.The COVID-19 pandemic caused reductions in the annual numbers of surgeries (3569 vs 3198) and colonoscopies (67 622 vs 58 183) performed in the 2020 fiscal year, compared to the 2019 fiscal year. During the COVID-19 pandemic, a significantly lower proportion of patients were treated for clinical stages ≤I (24.2% vs 26.9%;The COVID-19 pandemic reduced the number of colonoscopies and surgeries performed for colorectal cancer and hindered the detection of asymptomatic early-stage cancers, and its impact varied by hospital size.

PDF - 135K, qRT-PCR for miR-340 and miR-542-3p in BM4 in patients with and without liver metastasis.

PDF - 89K, Legends for Supplementary Figures 1 and 2.

PDF - 150K, Over expression of miR-340 suppressed c-Met expression in HCT116 and SW480 in vitro.

PDF - 63K, miR-340 expression and clinicopathologic factors.

PDF - 364K, List of microRNA array results.

Studies have shown the prognostic significance of disseminated tumor cells (DTC) in bone marrow of patients with colorectal cancer. However, the molecular characteristics of DTCs, including their miRNA expression profiles, remain mostly unknown. In this study, we analyzed the miRNA expression of DTCs in bone marrow. EpCAM+ bone marrow cells were collected using immunomagnetic beads after exclusion of CD14+ and CD45+ cells, then subjected to miRNA microarray analysis. Cluster analysis (7 colorectal cancer patients with liver metastasis and 12 colorectal cancer patients without liver metastasis) indicated that miR-340 and miR-542-3p expressions were significantly decreased in EpCAM+ bone marrow cells of patients with liver metastasis (P = 0.019 and 0.037, respectively). We demonstrated that pre-miR-340 administration inhibited growth of colon cancer cells and suppressed c-Met expression in vitro. In clinical samples of colorectal cancer, miR-340 was expressed at significantly lower levels in tumor tissues compared with normal mucosa. Survival analysis in 136 patients with colorectal cancer indicated that low miR-340 expression was correlated with shorter 5-year disease-free survival (P = 0.023) and poor 5-year overall survival (P = 0.046). It was of note that the colorectal cancer group with low miR-340 and high c-Met expression had the worst prognosis. We further demonstrated that systemic pre-miR-340 administration suppressed growth of pre-established HCT116 tumors in animal therapeutic models. These findings indicate that miR-340 may be useful as a novel prognostic factor and as a therapeutic tool against colorectal cancer. Our data suggest that miR-340 in bone marrow may play an important role in regulating the metastasis cascade of colorectal cancer. Mol Cancer Ther; 13(4); 976–85. ©2014 AACR.

PDF - 60K, Clinicopathologic factors of patients analyzed by miRNA array.

Non-LPACs were observed after each treatment, 5-FU, L-OHP and radiation (8Gy), at 0 hour, 24 hours, 48 hours and 72 hours. Non-LPACs never changed to LPACs in each assay. Bar: 100μm.

Purpose: We reported in a retrospective study that the presence of micrometastasis in lymph nodes, when assessed by carcinoembryonic antigen (CEA)-specific RT-PCR, is a significant prognostic factor in stage II colorectal cancer. The aim of this study was to clarify the clinical value of micrometastasis in a prospective multicenter trial.Experimental Design: From November 2001 to December 2005, a total of 419 colorectal cancer cases were preoperatively registered at a central data center. Of them, 315 node-negative stage II colorectal cancer cases were enrolled. After RNA quality check, 304 colorectal cancer cases were analyzed for CEA mRNA in lymph nodes by both conventional RT-PCR (a band method) and quantitative RT-PCR. Long-term prognosis of the patients was determined by each method.Results: A positive band for CEA mRNA was detected in 73 (24.0%) of 304 patients. Postoperative adjuvant chemotherapy was applied in 31 CEA band-positive cases with an oral 5-fluorouracil derivative HCFU (1-hexylcarbamoyl-5-fluorouracil) for 1 year, whereas chemotherapy was not administered to CEA band-negative group. Multivariate Cox regression analyses revealed that a high micrometastasis volume (high MMV, n = 95) was an independent poor prognostic factor for 5-year disease-free survival (DFS; P = 0.001) and 5-year overall survival (OS; P = 0.016).Conclusions: This prospective clinical trial demonstrates that micrometastasis volume is a useful marker in identifying patients who are at high or low risk for recurrence of stage II colorectal cancer. Clin Cancer Res; 22(13); 3201–8. ©2016 AACR.

No significant differences were found between the two groups regarding clinicopathological factors, such as age, gender, tumor location, depth of tumor invasion, lymph node metastasis, histological grade, Dukes' stage, and vessel invasion.

Several cancer-related gene candidates were identified using microarray data from the four cell lines (HCT116, SW480, DLD1, KM12SM)

LNs were collected within 3 hours after resection of the specimens with a disposable LN sampling kit that was prepared in a RNase-free state. In addition to routine pathological examination of LNs, representative five pericolic nodes adjacent to the tumor were cut into halves and stored in RNA laterTM at -20{degree sign}C. Immediately after pathological tests reported node-negative stage II CRC, RNA was extracted from LNs, checked for RNA quality, and then subjected to conventional RT-PCR for the CEA band and qRT-PCR for CEA mRNA value by the Light CyclerTM. Among seven CRC cases tested, Case No. 3, 4, and 6 were judged positive (Lower panel). Positivity of the CEA band was judged consistently by reference of the simultaneously produced control panel. One microgram of RNA from gastric cancer MKN45 cells and colon cancer LoVo cells was subjected to the RT reaction. Each cDNA was serially diluted at 1x10-1 to 1x10-5. PCR was performed using CEA primers and PBGD primers. A positive CEA band was visible at a 1x10-4 dilution in the MKN45 cells and at a 1x10-3 dilution in the LoVo cells (Upper panel).

Purpose: One of the main reasons for cancer treatment resistance is the existence of cancer stem-like cells (CSCs). Here, we elucidated the relationship between low proteasome activity cells (LPACs) and CSCs.Experimental Design: The human colorectal cancer cell lines HCT116, SW480, DLD1, and KM12SM were engineered to stably express a green fluorescent molecule fused to the degron of ornithine decarboxylase, resulting in an accumulation of the fluorescence in LPACs. LPACs were isolated by flow cytometry. Treatment resistance (radio- and chemotherapy) and the capacity of LPACs to act as CSCs were analyzed. Microarray analysis was performed to reveal genes related to treatment resistance. The prognostic impact of potent genes was examined in 190 patients with colorectal cancer.Results: LPACs had a significantly increased capacity for radioresistance and chemoresistance (5-fluorouracil and oxaliplatin), significantly lower reactive oxygen species activity, and significantly increased sphere formation capacity compared with non-LPACs. The number of cells in the G0–G1 phase was significantly higher among LPACs. Subcutaneous injection of as few as 20 LPACs led to tumor formation in immunologically incompetent mice. Microarray analysis revealed that the expression of EP300-interacting inhibitor of differentiation 3 (EID3) was significantly increased in LPACs. In vitro assay revealed that EID3 positively controlled cell proliferation and treatment resistance. The high expression of EID3 was an adverse prognostic indicator in patients with colorectal cancer (P = 0.0400).Conclusions: LPACs have characteristic treatment resistance and act as CSCs in colorectal cancer. In addition, EID3 is one of the potential regulators of treatment resistance in colorectal cancer and may be a potential therapeutic target. Clin Cancer Res; 22(21); 5277–86. ©2016 AACR.

The standard curves were plotted using the serial dilution of cDNA from MKN45. We confirmed that the CEA value was reproducibly measured in the range of 1.0x10-1 to 1.0x10-4 with standard deviation < 10% in each dilution.

Of 55 node-negative CRCs (9 stage I and 46 stage II), Micrometastais was positive in 59 of 373 LNs (15.8%) at level 1, 16 of 193 LNs (8.3%) at level 2 and 4 of 86 LNs (4.7%) at level 3 through 5 slides inspection by immunostaining using pan-cytokeratin AE1/AE3 antibody (Dako). As results, 27 CRC cases were positive for micrometastasis in LNs. Micromstastasis was found at pericolic nodes adjacent to the tumor (level 1) in 26 cases of 27 CRCs (96.3%). On the other hand, micrometastasis stayed at intermediate nodes along the course of the main blood vessel, e.g., inferior mesenteric artery (level 2) and at central nodes around the root of the main blood vessel (level 3) in 37.0% and 14.8%, respectively. Level 1, pericolic nodes adjacent to the tumor; Level 2, intermediate nodes along the course of the main blood vessel; Level 3, central nodes around the root of the main blood vessel. Level 1, pericolic nodes adjacent to the tumor; Level 2, intermediate nodes along the course of the main blood vessel; Level 3, central nodes around the root of the main blood vessel.

Figure S5: Impact of chemotherapy in High-MMV group. Post-operative chemotherapy was performed in 29 of 95 High-MMV cases and 2 of 201 Low-MMV cases. Irrespective of chemotherapy applied to High-MMV cases, High-MMV group consistently showed significantly worse 5-year DFS as compared to the Low-MMV group with no treatment (P= 0.009, 0.007). Similar results were observed in analyses for OS (P=0.003, 0.026).; Figure S6:Disease recurrence mode in stage II CRC. Among 296 patients, 51 developed disease recurrence after surgery. The recurrent organ site was 60 in all and are listed here. Like more advanced-stage patients, stage II patients had often hematogenous metastasis to liver and lung.

Described markers expression, CD133, CD166, Lgr5 (Alexa Fluor® 647 channel, BD Biosciences) and EpHB2 (PE channel, R&D systems, Minneapolis, MN, USA), were compared between LPACs and non-LPACs. The LPACs clearly showed up-regulation of several CSC markers including CD133, CD166, Lgr5 and EpHB2. Especially, Lgr5 was enriched in all cell lines (HCT116; 0.7% (non-LPACs) vs 18.1% (LPACs), SW480; 0.2% vs 28.1% and DLD1; 2.3% vs 45.2%).

EID3 was identified by microarray analysis. The expression of EID3 was confirmed by PCR and western blotting. (A) The mRNA expression of EID3 was significantly enriched in LPACs of HCT116, KM12SM and DLD1 compared to non-LPACs, except SW480 which just missed statistical significance (p=0.0555). (B) Western blotting was also performed for checking the expression of EID3 protein in LPACs and non-LPACs using EID3 antibody (Abcam, Cambridge, UK, ab124447), but the evaluation was difficult, because expression of EID3 is low in humans as per previous report (31, 32). * p

Figure S8: Survival analyses of the entire CEA　band-positive group.　 Of the entire CEA band-positive cases, 31 cases eventually received post-operative chemotherapy using HCFU for one year, whereas 41 cases had no treatment. There was no significant difference in 5-year DFS and 5-year OS between the two groups.; Figure S9. Survival curves stratified by High CK19 expression and Low CK19 expression. Survival analyses indicated that the High CK19 group (n=96) had a significantly (A) worse 5-year DFS (P= 0.001), (B) 5-year OS (P= 0.020), and (C) OS (P= 0.014) as compared to the Low CK19 group (n=193). A total of 289 cases with residual preserved RNA were analyzed.

(A) The efficiency of over-expression was validated by expression of mRNA. The expression of EID3 was significantly higher in cells with EID3 　expression vector than cells with control vector. (B) The efficiency of down-regulation was confirmed by mRNA. The expression of EID3 was significantly lower in cells with double-stranded RNA duplexes targeting human EID3 than cells with negative control siRNA. * p

MM-free CRC group (group a, n=90) had a considerably favorable prognosis. (A) 5-year DFS: 5-year DSF was 93.3, 86.5, and 74.7% in group a, group b and group c+d (High-MMV), respectively. (B) 5-year OS: 5-year OS was 97.8, 95.5, and 89.5 % in group a, group b, and group c+d (High-MMV), respectively. (C) Final OS: final OS was 97.8, 93.7, and 86.3% in group a, group b, and group c+d (High-MMV), respectively.

Supplementary Figure 4 from Activation of Insulin-like Growth Factor Signaling Induces Apoptotic Cell Death Under Prolonged Hypoxia by Enhancing Endoplasmic Reticulum Stress Response

Supplementary Table 1 from Activation of Insulin-like Growth Factor Signaling Induces Apoptotic Cell Death Under Prolonged Hypoxia by Enhancing Endoplasmic Reticulum Stress Response

Supplementary Figure 1 from Activation of Insulin-like Growth Factor Signaling Induces Apoptotic Cell Death Under Prolonged Hypoxia by Enhancing Endoplasmic Reticulum Stress Response

Supplementary Figure 2 from Activation of Insulin-like Growth Factor Signaling Induces Apoptotic Cell Death Under Prolonged Hypoxia by Enhancing Endoplasmic Reticulum Stress Response

Supplementary Figure 3 from Activation of Insulin-like Growth Factor Signaling Induces Apoptotic Cell Death Under Prolonged Hypoxia by Enhancing Endoplasmic Reticulum Stress Response

We have proposed a new compressive combustion principle leading to the auto-ignition of fuel by focusing compression due to the collision of the pulsed supermulti-jets. This principle has the potential of nearly-complete air insulation due to encasing burned gas around the center of the combustion chamber and a high compression ratio around the chamber center while suppressing vibration and noise levels. We have developed the first prototype engine having a very small combustion chamber of a diameter of 18 mm and also 14 side passages for the supermulti-jets colliding at the chamber center. Combustion experimental results indicating air insulation effect and high thrust over 100 N were obtained as basic data for various types of applications, including automobiles and aerospace usage such as for rockets. However, it was found that higher compression due to more jets is necessary to get stabler combustion. Therefore, by using a metal 3D printer, we have developed the second engine with 24 side passages of gas jets colliding, while performing direct injection of liquid fuel at injection pressure over 5 MPa into the combustion chamber. In our previous report, the experiment without combustion and its computational simulation show that the second engine enables a higher compression ratio than that of the first prototype engine. In this research, we conduct fundamental combustion experiments using the second engine with a direct injection system, purposing to achieve stable multi-cycle combustion with auto-ignition of the fuel by focusing compression due to the collision of supermulti-jets. As a result, a stabler occurrence of combustion is confirmed for the second engine. Experimental data of wall pressure obtained also indicate that auto-ignition occurs due to collision of the supermulti-jets while showing a possibility of higher thrust over 300 N. Furthermore, we qualitatively perform computations of reacting flows for the second engine, while showing liquid fuel spray atomized strongly by the gas jets.

Background Successful achievement of randomized controlled trials (RCTs) is dependent on the acquisition of informed consent (IC) from patients. The aim of this study was to prospectively calculate the proportion of participation in a surgical RCT and to identify the reasons for failed acquisition of IC. Methods A 50-insitution RCT was conducted to evaluate oncological outcomes of open and laparoscopic surgery for stage IV colon cancer (JCOG1107: UMIN-CTR 000000105). The success rate of obtaining IC was evaluated in eight periods between January 2013 and January 2021. In addition, reasons for failed acquisition of IC were identified from questionnaires. Results In total, 391 patients were informed of their eligibility for the trial, and 168 (42%) were randomly assigned to either the laparoscopic surgery group (n = 84) or open surgery group (n = 84). The success rate of IC acquisition ranged from 33 to 58% in three periods. The most common reasons for failed IC acquisition were the patients’ preference for one approach of surgery based on recommendations from referring doctors and family members, and anxiety/unhappiness about randomization. Conclusions The success rate of acquiring IC from patients for an RCT of laparoscopic versus open surgery for stage IV colon cancer was lower than the expected rate planned in the protocol. To obtain the planned rate, investigators should make efforts to inform patients and their families about the medical contributions a surgical RCT can make and recognize that the period in equipoise may be limited.

Advanced gastric cancer with liver metastasis is classified as stage IV disease and is generally treated with systemic chemotherapy. Despite recent advances in chemotherapy regimens, the prognosis for gastric cancer with liver metastasis is poor. Recent studies reported the effectiveness of upfront chemotherapy followed by conversion surgery for gastric cancer with liver metastasis. Here, we report a case of an advanced stage IV gastric cancer with liver metastasis treated with upfront systemic chemotherapy followed by conversion surgery, which resulted in pathological complete response and good prognosis.A 79-year-old man diagnosed with human epidermal growth factor receptor type 2 (HER2)-positive gastric cancer with multiple liver metastases. He underwent systemic chemotherapy with capecitabine, cisplatin, and trastuzumab. After 14 courses of chemotherapy, the primary tumor and liver metastases shrank, suggesting a partial response. We performed distal gastrectomy with D2 dissection plus lateral hepatic segment resection. Pathological examination revealed no residual tumor cells in the primary or metastatic sites, which indicated a pathological complete response. The postoperative course was uneventful. The patient was discharged on postoperative day 8. Adjuvant S-1 chemotherapy was started on postoperative day 46 and given for 1 year. The patient has been alive and recurrence-free for approximately 5 years after surgery.This case shows the possibility of conversion surgery after systemic chemotherapy for stage IV advanced gastric cancer with liver metastasis.

The patient was a 75-year-old woman who was referred to our department because she had type 3 advanced gastric cancer on the posterior wall of the gastric body. Following a thorough examination, she was diagnosed as cT4aN3M1 (#16a1 int, #16b2 lat), cStage Ⅳ, an unresectable advanced gastric cancer with multiple extranodal lymph node metastases. As radical resection was not possible, chemotherapy(SOX therapy)was started. After the start of chemotherapy, the main lesion and metastatic lymph nodes shrank markedly. At the time of 7 courses, it was judged that R0 resection by conversion surgery was possible, and surgical treatment was performed. The patient underwent sub-total gastrectomy with D2 dissection and para-aortic lymph node dissection. The specimen was submitted for pathological examination and showed no residual tumor component including the main lesion and dissected lymph nodes, indicating a complete pathological response. She was started on S-1 as adjuvant chemotherapy on postoperative day 51 and has been recurrence-free for approximately 5 months after surgery.

We report a case of sphenoid bone metastasis from breast cancer detected with diplopia, as first site of recurrence. Forty- year-old woman with left breast cancer underwent breast-conserving surgery and sentinel lymph node biopsy. The diagnosis was papillotubular carcinoma, pT1pN0, ER(+), PgR(+), HER2(-). Tweleb years later, the examination of diplopia revealed left abducens nerve palsy for sphenoid bone metastasis from breast cancer. Radiation therapy(a total dose of 36 Gy with VMAT)was administrated as topical treatment, but diplopia did not improve. After that, systemic treatment was performed, and 2 years and 6 months have passed since the recurrence was found, she is still alive. We need to be careful of orbital metastasis as a symptom of metastasis from breast cancer.

We report a case of non-exposed endoscopic wall-inversion surgery(NEWS)performed by TANKO technique for gastric GIST. A 52-year-old man was diagnosed as having gastric GIST. A 2 cm-sized tumor was found in the lesser curvature of the middle body of the stomach, and an endoscopic biopsy revealed GIST. A 2.5 cm umbilical incision was made and TANKO surgery was performed. After seromyotomy around the tumor, the outer serosal muscularis was sutured closed to invert the tumor into the stomach. The inverted tumor was resected from the stomach wall and recovered using endoscopic techniques. NEWS is an operation developed to resect a tumor without exposing it into the abdominal cavity and is expected to avoid the risk of postoperative abdominal abscess and peritoneal dissemination. On the other hand, the TANKO is a procedure with excellent plastic technique and can be performed in this operation.

This phase II study (MCSGO-1202) aimed to evaluate the initial dose reduction of oxaliplatin in XELOX plus bevacizumab therapy.This was a phase II, multicenter, open-label, single-arm, prospective, study conducted at 14 Japanese institutions. The study included patients with metastatic colorectal cancer (mCRC) with performance status (PS) of 1 or 2 who had not undergone chemotherapy. Patients received oxaliplatin (100 mg/mBetween April 2012 and March 2016, 56 patients were enrolled. The median age was 71 years (range=44-85 years), and the majority (90.6%) had a PS of 1. A complete response was observed in three patients (5.7%), partial response in 24 (45.3%), stable disease in 22 (43.4%), and progressive disease in one (1.9%). The median progression-free survival and overall survival were 11.4 and 26.5 months, respectively. The most common grade 3-4 adverse events were leucopenia (15.1%), neutropenia (9.4%), neuropathy (9.4%).The dose-reduction strategy of oxaliplatin was effective for elderly or vulnerable patients with mCRC.

A woman in her 30s visited our hospital complaining primarily of melena. Colonoscopy revealed the presence of a type 1 tumor in 2 cm from anal verge. Contrast-enhanced CT showed an unresectable massive liver metastasis in the left lobe of the liver and another metastasis in the right lobe. The patient received front-line chemotherapy with Leucovorin, fluorouracil, oxaliplatin, and irinotecan(FOLFOXIRI)plus bevacizumab(BEV). A year later, a marked reduction of liver metastases and primary lesions was confirmed by CT scan imaging. A multidisciplinary team recommended resection of the liver metastases followed by laparoscopic intersphincteric resection for primary lesions. However, after 1 year, a recurrence was diagnosed in the liver; hence, FOLFOXIRI plus BEV was reintroduced for volume reduction. The patient underwent a repeat hepatectomy since enough volume reduction was confirmed. One year later, she experienced a re-relapse of the metastasis in the liver. Currently, she is still undergoing chemotherapy following 7 years since the first visit. Long-term survival can be expected following surgical treatment during chemotherapy.

The patient is an 85-year-old female who had previously undergone a mastectomy for right breast cancer at the age of 42 years. In September 2020, she visited our hospital with a chief complaint of a chest wall tumor. Physical examination revealed a 3×3 cm ulcerative lesion on the right side of the center chest wall. She underwent a skin biopsy of the tumor under local anesthesia and was diagnosed with a recurrence of right breast cancer(ER positive, PR positive, HER2 negative). PET-CT revealed localized skin thickening on the right side of the sternum and FDG accumulation in the same area, with no other findings suggestive of distant metastasis. Treatment was started with anastrozole and is still ongoing. In this article, we report a very rare case of recurrence 43 years after surgery.

Laparoscopic surgery is a safe, minimally invasive, and effective approach in managing abdominal malignancies. Laparoscopic anatomical resection has been covered by insurance in Japan since 2016. Here, we have reported the short-term outcomes of gallbladder cancer in laparoscopic cholecystectomy, gallbladder bed resection, or S4a/S5 liver resection with lymph node dissection.Between May 2012 and December 2020, 28 patients underwent laparoscopic cholecystectomy for gallbladder cancer at Kansai Rosai Hospital. Two patients underwent laparoscopic choledochotomy with lymph node dissection, 6 patients underwent gallbladder bed resection, and 7 patients underwent S4a/S5 liver resection. The control group included 13 patients who received open surgery between July 2010 and November 2019. The patient age was 74.2 and 74.4 years, while the male to female ratio was 19/24 and 8/5 in the laparoscopic and open surgery groups, respectively. According to the Japanese Society of Hepato-Biliary-Pancreatic Surgery, the pathological stage was 0/Ⅰ/Ⅱ/Ⅲ A/ⅢB/ⅣA/ⅣB in 4/17/13/4/2/1/2 and 0/1/2/3/1/1/5 patients(p=0.0100)in the laparoscopic and open surgery groups, respectively. This study was approved by the Human Ethics Review Committee of Kansai Rosai Hospital(Certificate Number: 2101001).The laparoscopic surgery group had an average operation time of 223.3 minutes, an estimated blood loss of 18.7 g, and a hospital stay of 8.5 days. The open surgery group had an average operation time of 514.5 minutes, an estimated blood loss of 1,274.3 g, and a hospital stay of 33.9 days. There was no postoperative bleeding or bile leakage in both groups. After laparoscopic cholecystectomy, the 5-year disease-free survival rate was 100% among Stage 0 or Ⅰ patients, 64.8% among Stage Ⅱ patients, and 0% in Stage Ⅲ or Ⅳ patients. The 5-year overall survival rate was 100% among Stage 0 or Ⅰ patient and 66.7% among Stage Ⅱ patients. The 1-year overall survival rate was 50% among Stage Ⅲ or Ⅳ patients. After laparoscopic liver resection with lymph node dissection, the 5-year disease-free survival rate was 100% among Stage Ⅰ or Ⅱ patients and 66.7% among Stage Ⅲ or Ⅳ patients. The 5-year overall survival rate was 100% among Stage Ⅰ or Ⅱ patients and 62.5% among Stage Ⅲ or Ⅳ patients.Laparoscopic cholecystectomy in Stage 0 or Ⅰ patients and laparoscopic gallbladder bed resection or S4a/S5 liver resection with lymph node dissection were safe and effective approaches to gallbladder cancer management.

Atezolizumab plus bevacizumab combination therapy is the first cancer immunotherapy that has shown efficacy in the treatment of hepatocellular carcinoma(HCC). We report a case of HCC with recurrent peritoneal dissemination for which atezolizumab plus bevacizumab combination therapy was effective. The patient, a 63-year-old man, underwent transarterial embolization(TAE)for ruptured HCC, and a mass with dissemination on the caudal side of liver S3 was observed. Laparoscopic lateral hepatic resection plus resection of the dissemination plus cholecystectomy was thus performed in September 2019. However, in November 2019, multiple peritoneal dissemination recurrence was observed, and lenvatinib therapy was initiated. In May 2020, PD was observed, and we had switched to sorafenib therapy. However, in October 2020, further tumor growth and rapid increase in tumor markers(AFP 25,668 ng/mL, PIVKA-Ⅱ 64,960 mAU/mL)were observed, and the patient was judged to have PD. Atezolizumab plus bevacizumab combination therapy was initiated in the same month. Subsequently, a CT scan in January 2021 showed a marked decrease in tumor size, indicating PR. The tumor markers have since normalized(AFP 5 ng/mL, PIVKA-Ⅱ 28 mAU/mL). The patient has been treated with atezolizumab plus bevacizumab combination therapy again and is maintaining PR as an outpatient.