Hybrid robot-assisted abdominoperineal resection supported by simultaneous trans-perineal approach for anal gland adenocarcinoma with vaginal invasion: a case report.

Hybrid surgery (abdominal robotic approach with a trans-anal approach) has been reported to improve oncological outcomes in cases involving advanced cancer or technical difficulties. A 74-year-old woman presented with anal pain and stenosis. Examination revealed palpable sclerosis on the anterior wall at the anal verge with possible vaginal invasion. A biopsy revealed an adenocarcinoma. We performed a two-team robot-assisted abdominoperineal resection combined with resection of the vagina supported by a simultaneous trans-perineal approach. After rendezvous at the posterior side, the abdominal team cut the posterior wall of the vaginal vault while the perineal team confirmed the surgical margin. Histopathological findings identified the tumour as an anal gland adenocarcinoma (pT4b [vagina] N0M0 pathological stage IIC) with a negative circumferential resection margin. Hybrid surgery combined with resection of the posterior wall of the vagina may be performed safely and is a valuable surgical option for multimodal treatment of anal adenocarcinomas.

Chemical Bowel Preparation Exerts an Independent Preventive Effect Against Surgical Site Infection Following Elective Laparoscopic Colorectal Surgery.

BACKGROUND: We investigated the independent clinical value of mechanical bowel preparations (MBP) and chemical bowel preparations (CBP) for preventing surgical site infection (SSI) in patients undergoing elective laparoscopic colorectal surgery. MATERIALS AND METHODS: This retrospective cohort study included 475 patients who underwent elective laparoscopic colorectal surgery between January 2018 and March 2022. CBP was introduced in January 2021 and included kanamycin (1 g) and metronidazole (1 g) 2 times a day, the day before surgery. In some cases, MBP was omitted in patients who planned to undergo right-sided colectomy, those with tumor obstruction, and those with poor general conditions, depending on the judgment of the physician. The primary endpoint was the overall SSI incidence, while the secondary endpoints were the incidences of incisional SSI and organ-space SSI, culture from the surgical site, and length of postoperative hospital stay. RESULTS: In total, 136 patients underwent CBP. MBP was omitted in 53 patients. Overall, SSI occurred in 80 patients (16.8%), including 61 cases of incisional SSI (12.8%) and 36 cases of organ-space SSI (7.6%). Multivariate logistic regression revealed that CBP exerted an independent preventive effect on overall and incisional SSI, whereas MBP did not. However, CBP was not associated with a decreased risk of overall SSI in patients who had undergone preoperative therapy, those with benign disease, and those with stoma formation in the subgroup analysis. Levels of Bacteroides species at the surgical site were significantly lower in the CBP group than in the non-CBP group. Postoperative hospital stay was significantly longer in the incisional SSI group than in the non-SSI group and was significantly longer in the organ-space SSI group than in the other groups. CONCLUSIONS: CBP, but not MBP, exerts an independent preventive effect on SSI, especially incisional SSI, in patients undergoing elective laparoscopic colorectal surgery.

Visualization of Anorectal Lymphatic Flow Using Indocyanine Green Fluorescence Imaging: An Observational Study.

BACKGROUND/AIM: Currently, only a small part of functional lymphatic flow around the anorectal region has been anatomically analyzed. Despite the fact that local recurrence is often experienced in the pelvic floor, the functional lymphatic network in this region has rarely been studied due to difficulties in observation. This prospective observational study aimed to observe anorectal lymphatic flow around the pelvic floor using intraoperative indocyanine green fluorescence imaging during laparoscopic or robot-assisted rectal surgery. PATIENTS AND METHODS: Fourteen patients who underwent laparoscopic (n=7) or robot-assisted (n=7) surgery without any preoperative therapy between April and December 2022 were enrolled. Indocyanine green solution (0.25 mg) was injected into the submucosa at the dentate line of the anterior, posterior, and bilateral walls prior to surgery. During and after total mesorectal excision, lymphatic flow was observed using a near-infrared camera system. RESULTS: Lymphatic flow visualized by indocyanine green was detected not only in the already-known route from the low rectum to the lateral pelvic lymph nodes via the lateral ligament, but also in the novel route from the low rectum to the surface of the levator ani muscle and hiatal ligament. Fluorescence was widely spread in the pelvic floor between the longitudinal muscle of the low rectum and the surface of the levator ani muscle. CONCLUSION: Even though the results are preliminary since histological analyses were not performed, a novel widespread lymphatic network on the surface of the levator ani muscle originating from the longitudinal muscle fibers of the low rectum was revealed.

Short- and long-term outcomes of preservation versus ligation of the inferior mesenteric artery in laparoscopic D3 lymph node dissection for descending colon cancer: a propensity score-matched analysis.

PURPOSE: This study aimed to compare the short- and long-term outcomes of laparoscopic D3 lymph node (LN) dissection between ligation of the inferior mesenteric artery (IMA) (LIMA) and preservation of the IMA (PIMA) for descending colon cancer using propensity score-matched analysis. METHODS: This retrospective study included 101 patients with stage I-III descending colon cancer who underwent laparoscopic D3 LN dissection with LIMA (n = 60) or PIMA (n = 41) at a single center between January 2005 and March 2022. After propensity score matching, 64 patients (LIMA, n = 32; PIMA, n = 32) were included in the analysis. The primary endpoint was the long-term outcomes, and the secondary endpoint was the surgical outcomes. RESULTS: In the matched cohort, no significant difference was noted in the surgical outcomes, including the operative time, estimated blood loss, number of harvested LNs, number of harvested LN 253, and complication rate. The long-term outcomes were also not significantly different between the LIMA and PIMA groups (3-year recurrence-free survival, 72.2% vs. 75.6%, P = 0.862; 5-year overall survival, 69.8% vs. 63.4%, P = 0.888; 5-year cancer-specific survival, 84.2% vs. 82.8%, P = 0.607). No recurrence of LN metastasis was observed around the IMA root. CONCLUSION: Laparoscopic D3 dissection in PIMA was comparable to that in LIMA regarding both short- and long-term outcomes. The optimal LN dissection for descending colon cancer should be investigated in future large-scale studies.

Comparison of Short-term Outcomes of a Self-expandable Metallic Stent as a Bridge to Laparoscopic Surgery between Right- and Left-sided Obstructive Colorectal Cancers: A Retrospective Observational Study.

Objectives: Few studies have compared the tumor-site-based postoperative short-term outcomes of a bridge to surgery using self-expandable metallic stents. This study compared the perioperative outcomes following stent placement between right- and left-sided obstructive colorectal cancers, focusing on patients undergoing laparoscopic surgery. Methods: This study included 127 patients with stage I-IV obstructive colorectal cancer (right-sided, n = 25 [19.7%]; left-sided, n = 102 [80.3%]) who underwent laparoscopic-assisted surgery following stent placement between May 2012 and September 2021. We compared the postoperative complication rates and the success rates of stent placement. Results: The clinical success rate was not significantly different (92% vs. 97.1%, P = 0.254). The rates of all-grade complications (36% vs. 16.7%, P = 0.05) and postoperative ileus or small-bowel obstruction (20% vs. 2%, P = 0.003) were significantly higher in the right-sided group. The rates of the Clavien-Dindo classification ≥ III complications (8% vs. 6.9%, P = 1) and the median durations of postoperative hospital stay (8 days vs. 8 days, P = 1) were not significantly different. On multivariate analysis, right-sided colon cancer was an independent risk factor for postoperative ileus or small-bowel obstruction (odds ratio [OR]: 16.5, 95% confidence interval [CI]: 2.42-112, P = 0.004) but not for all grades of complications (OR: 2.63, 95% CI: 0.976-7.09, P = 0.056). Conclusions: Although the rates of clinical success, postoperative Clavien-Dindo classification ≥ III severe complications, and postoperative hospital stay were comparable, the bridge to surgery following stent placement for right-sided obstructive colon cancer raises concerns about ileus or small-bowel obstruction.

Postoperative colon perforation due to the tip of the transanal decompression tube after laparoscopic low anterior resection: A case report.

A 66-year-old man underwent laparoscopic low anterior resection for rectal cancer. A transanal decompression tube (24Fr Nelaton catheter) was placed laparoscopically during the surgery. Contrast enema on postoperative day 5 showed perforation of the sigmoid colon around the tip of the tube, and emergency laparotomy was performed. Perforation of the posterior sigmoid colon located on the proximal side of the colorectal anastomosis at the level of the promontorium was identified. Closure of the perforation site, lavage drainage, and a diverting loop ileostomy were performed. Although a transanal decompression tube is useful in preventing anastomotic leakage, tube-related colon perforation should be noted, and controversies about the safety of laparoscopically transanal decompression tube placement should be resolved. Adequate management for tube placement should be discussed.

Safety of Insertion of Percutaneous Totally Implantable Central Venous Access Devices by Surgical Residents.

BACKGROUND/AIM: To compare the outcomes of totally implantable central venous access device (TIVAD) insertions by surgical residents (SRs) with those by experienced surgeons (ESs) and establish the safety of percutaneous TIVAD insertion by SRs. PATIENTS AND METHODS: A total of 700 insertions were successfully performed between January 2015 and December 2019 in our Department. The puncture site conversion and complication rates were compared, and risk factors related to complications were analysed. RESULTS: In total, 84 and 616 insertions were performed in the SR and ES groups, respectively. SRs mainly punctured the internal jugular vein (IJV), and ESs punctured the subclavian vein (SV). The conversion rate from the IJV to SV was similar, whereas that from the SV to IJV was higher by SRs than ESs. Overall, early, and delayed complications were similar between the two groups. CONCLUSION: Percutaneous TIVAD inserted into the IJV by an SR was demonstrated to be safe.

Short-term outcomes of extracorporeal colo-colonic triangular anastomosis versus functional end-to-end anastomosis in laparoscopic-assisted surgery for left-sided colon cancer: a propensity score matching analysis.

PURPOSE: To the best of our knowledge, no studies have compared the short-term outcomes between colo-colonic extracorporeal triangular anastomosis (TA) and functional end-to-end anastomosis (FEEA), with a focus on laparoscopic-assisted surgery for left-sided colon cancer. Therefore, this study compared the short-term outcomes of these anastomoses using propensity score matching analysis. METHODS: This retrospective study included 129 patients with stage I-IV left-sided colon cancer who underwent laparoscopic-assisted surgery with colo-colonic extracorporeal TA (n = 75) or FEEA (n = 54) between May 2009 and March 2021. After propensity score matching, 84 patients (TA, n = 42; FEEA, n = 42) were included in the analysis. The primary endpoint was the complication rate for all grades, and the secondary endpoints were the rates of Clavien - Dindo grade ≥ 3 complications and anastomotic leakage. RESULTS: In the matched cohort, there were no significant differences in the complication rates for all grades (35.7% vs. 26.2%, p = 0.479), Clavien - Dindo grade ≥ 3 complications (11.9% vs. 11.9%, p = 1), and anastomotic leakage (0% vs. 4.8%, p = 0.494) between the TA and FEEA groups. In the univariate logistic regression analysis, TA did not increase the frequency of complications for any grades compared with FEEA (odds ratio: 1.570, 95% confidence interval: 0.616-3.980, p = 0.347). CONCLUSION: Extracorporeal TA demonstrated equivalent short-term outcomes compared with FEEA in cases of laparoscopic-assisted surgery for left-sided colon cancer. TA can be an alternative anastomosis technique in cases wherein FEEA is difficult to perform.

Short- and long-term outcomes of a self-expandable metallic stent versus a transanal decompression tube for pathological stage II and III left-sided obstructive colorectal cancer: a retrospective observational study.

PURPOSE: Few studies have investigated the long-term oncological outcomes of the self-expandable metallic stent (SEMS) as a bridge to surgery (BTS) for obstructive colorectal cancer (OCRC). We conducted this study to compare the short- and long-term outcomes of the SEMS with those of the traditional transanal decompression tube (TDT) in patients with stage II and III left-sided OCRC. METHODS: The subjects of this retrospective study were 78 patients with pathological stage II and III left-sided OCRC who underwent radical surgery after SEMS or TDT placement, between April, 2005 and September, 2019. We compared perioperative data, including decompression success rates and 3-year relapse-free survival (RFS), between the SEMS and TDT groups. RESULTS: A SEMS was placed in 60 (76.9%) patients and a TDT was placed in 18 (23.1%) patients, achieving a clinical success rate of decompression of 98.3% in the SEMS group and 77.8% in the TDT group (P = 0.009). The 3-year RFS of the overall cohort was better in the SEMS group than in the TDT group (74.9% vs. 40.9%, respectively; P = 0.003). CONCLUSIONS: Decompression using a SEMS as the BTS may improve oncological outcomes over those achieved by a TDT in patients with left-sided stage II and III OCRC.

Comparison of outcomes between laparoscopic and open Hartmann's reversal: A single-center retrospective study in Japan.

INTRODUCTION: Laparoscopic Hartmann's reversal (LHR) has recently been reported to be safer and more feasible than open Hartmann's reversal (OHR); however, there is limited data on the outcomes of LHR compared with those of OHR from Asian countries. Therefore, we aimed to clarify the postoperative outcomes of LHR compared with OHR, and additionally compare the patient outcomes post-LHR according to the previous Hartmann's procedure (HP) approach. METHODS: Patients who underwent OHR and LHR between January 2006 and September 2020 in a single center in Japan, were retrospectively evaluated. Patient characteristics and perioperative data were collected from the medical and surgical records and assessed. RESULTS: Overall, 15 and 19 patients underwent OHR and LHR, respectively, between January 2006 and September 2020. LHR was associated with less blood loss (median: 15 mL vs 185 mL; P < .001) and shorter hospital stays (9 days vs 14 days; P = .023) than OHR. There was no significant difference in postoperative complications between LHR and OHR (26.3% vs 40.0%, P = .475). However, two severe anastomotic complications in LHR were observed in patients with the stump below the peritoneal reflection. No significant difference in outcomes was observed between LHR patients who underwent open and laparoscopic HP. CONCLUSION: LHR resulted in positive outcomes regarding estimated blood loss and postoperative hospitalization, compared with OHR. Although the postoperative complications between LHR and OHR were not significant, patients with the stump below the peritoneal reflection may be at a high risk of anastomotic complications.

Comparison of prognostic impact between positive intraoperative peritoneal and lavage cytologies in colorectal cancer.

BACKGROUND: The prognostic value of positive intraoperative peritoneal cytology and lavage cytology, including the differences in their prognostic impact, in colorectal cancer is controversial. We aimed to investigate the prognostic values of positive peritoneal cytology and lavage cytology findings for colorectal cancer and compare their prognostic impact. METHODS: We retrospectively evaluated 592 clinical stage II-IV colorectal cancer patients who underwent peritoneal cytology (n = 225) or lavage cytology (n = 367) between November 1993 and December 2018. The prognostic factors for cancer-specific survival were identified, and the differences in cancer-specific survival were examined between the patients. RESULTS: The cytology-positive rate was 10.8% (64/592), 17.8% (40/225), and 6.5% (24/367) in the overall, peritoneal cytology, and lavage cytology groups, respectively. Both positive peritoneal cytology (hazard ratio: 2.196) and lavage cytology (hazard ratio: 2.319) were independent prognostic factors. The peritoneal cytology-positive group showed significantly poorer cancer-specific survival than the cytology-negative group (5-year: 3.5% vs. 59.5%; 10-year: 3.5% vs. 46.1%, p < 0.001). Similar results were obtained for lavage cytology (5-year: 14.1% vs. 73.9%; 10-year: 4.7% vs. 63.5%, p < 0.001). The cancer-specific survival was not significantly different between the peritoneal cytology-positive and lavage cytology-positive groups (p = 0.058). Both positive peritoneal and lavage cytology were associated with poorer cancer-specific survival across all colorectal cancer stages. CONCLUSIONS: Positive peritoneal and lavage cytology are associated with worse cancer-specific survival in colorectal cancer. The prognostic impact was comparable between positive lavage and peritoneal cytology. Thus, cytology should be a standard assessment modality for colorectal cancer.

[A case of pneumatosis cystoides intestinalis after neoadjuvant chemotherapy for esophageal cancer].

A man in his 60s was diagnosed with esophageal cancer (T3, N0, StageII) and treated with 5-fluorouracil and cisplatin as neoadjuvant chemotherapy (NAC). On day 18 of the second NAC course, the patient developed febrile neutropenia, and a computed tomography (CT) scan showed pneumatosis cystoides intestinalis (PCI) of the ascending and transverse colon, free air around the ascending colon, thickening of the gallbladder wall, pleural effusion, and ascites. Because there were no signs of peritoneal irritation and intestinal perforation was ruled out, conservative treatment was selected. Seven days after PCI was diagnosed, CT showed improvement in PCI and the free air had disappeared, and 26 days after the diagnosis, a subtotal esophagectomy was performed. Observation of the abdomen did not show a thickened wall or stenosis of the ascending or transverse colon. PCI could be treated conservatively, even with free air in the abdominal cavity, by comprehensively assessing not only the imaging but also the physical findings. We were able to perform radical resection of the esophageal cancer without excessive treatment for PCI.

[A case of malignant peritoneal mesothelioma without deletion of p16].

The patient was a man in his 60s with a history of 2 operations for the treatment of malignant neurogenic tumors. Partial resection of the stomach and liver was performed in December 2006, followed by chemotherapy with adriamycin and interferon; resection of a recurrent tumor in the left subphrenic space was performed in December 2007. In June 2011, recurrent tumors were detected in the lesser curvature of the stomach body and left inferior quadrant of the abdomen (12 mm [SUVmax 7.9] and 23 mm [SUVmax 10.5], respectively)by using 18F-fluorodeoxyglucose-positron emission tomography (FDG-PET). The tumors resected in August 2011 were diagnosed as malignant peritoneal mesothelioma on immunohistochemical analysis. In February 2013, FDG-PETrevealed a 20-mm tumor of in the mesentery with a SUVmax of 7.6, and the tumor was resected. This secondary tumor had the same features of the previously resected malignant mesothelioma. Fluorescence in situ hybridization revealed no deletion of the p16 gene, and the patient had had no other recurrence during follow-up. Malignant peritoneal mesothelioma is a rare disease, accounting for 10% of all malignant mesothelioma cases, with low rates of p16 gene deletion compared with malignant pleural mesothelioma. Previous studies have reported that the lack of p16 deletion is associated with better prognosis in malignant pleural mesothelioma. Herein, we report of a patient diagnosed with malignant peritoneal mesothelioma, without deletion of the p16 gene, who survived for over 2 years and 10 months after initial diagnosis of malignant mesothelioma.

Lectin-like receptor Ly49s3 on dendritic cells contributes to the differentiation of regulatory T cells in the rat thymus.

Naturally occurring regulatory T cells (nTregs), important for immune regulation and the maintenance of self-tolerance, develop in the thymus. The Hirosaki hairless rat (HHR), derived from the Sprague-Dawley rat (SDR), was shown to have decreased peripheral lymphocyte number, small thymus, and leukocyte infiltration in its dermis. In the HHR thymus, the medulla was underdeveloped and nTreg number was decreased. Array comparative genome hybridization revealed the deletion of an NK cell lectin-like receptor gene, Ly49s3, detecting MHC class I molecules on target cells, in the chromosome 4q42 region in HHRs. The gene was expressed in thymic conventional dendritic cells (cDCs) in SDRs, but not in HHRs. When CD4-single-positive or CD4(+)CD8(-)CD25(-) thymocytes were cultured with thymic cDCs, the expression of nTreg marker genes was lower when these cells were from HHRs than from SDRs, suggesting that HHR cDCs are deficient in the ability to induce and maintain nTreg differentiation. Expression of the genes was recovered when Ly49s3 was expressed on HHR thymic cDCs. Expression levels of MHC class II genes, presumably from cDCs, were parallel to those of nTreg marker genes in mixed-cell cultures. However, in the presence of an anti-MHC class I Ab, blocking interaction between Ly49s3 and MHC class I molecules, the expression of the former genes was upregulated, whereas the latter was downregulated. These results suggest that Ly49s3 contributes to nTreg regulation along with MHC class II molecules, whose effects alone are insufficient, and loss of Ly49s3 from thymic cDCs is the reason for the nTreg deficiency in HHRs.

[A case of malignant lymphoma of the gallbladder after chemotherapy for malignant lymphoma of the skin and right intraocular].

A case is a 65-year-old female. She was diagnosed as T-cell malignant lymphoma (skin and right intraocular). Chemotherapy( THP-COP) was performed for 6 months and she was in remission. A gallbladder tumor was pointed out in August 2010, and she was admitted to our department for the purpose of excision biopsy of the gallbladder tumor. In abdominal US, we confirmed an iso-hypoechoic tumor. The tumor size was 24 × 14 mm. We considered the invasion depth was subserosa. We observed the tumor which had the imaging effectiveness in the body of gallbladder by abdominal CT. The invasion was suspected in the liver bed side. In PET-CT, We observed an accumulation of SUVmax 8 . 5 in the body of gallbladder. The protruded lesion of 33 .5 mm in diameter was detected by MRI to the body of gallbladder, and an invasion was also suspected. Cholecystectomy was performed to this case. By operative US, the gallbladder tumor was SMT and existed in the symmetric side of liver bed. Pathological diagnosises were malignant lymphoma and peripheral T-cell lymphoma.

Decrease of hepatic stellate cells in rats with enhanced sensitivity to clofibrate-induced hepatocarcinogenesis.

To examine the possible involvement of nonparenchymal cells in the development of preneoplastic hepatic lesions induced by clofibrate (CF), alterations of these cells were investigated immunohistochemically in glutathione S-transferase M1 gene polymorphic rats (KS and NC types) with different cancer susceptibilities. After CF administration for 8 weeks, α-smooth muscle actin (α-SMA)-positive hepatic stellate cells (HSC) were markedly decreased in sensitive KS-type rats, but not in the NC-type rats. Kupffer cells were decreased with similar extents between them. The sinusoidal endothelial cells were not changed in either type. The other markers for HSC, vimentin and CRBP1, also confirmed the decrease of HSC in the KS type. The decrease of HSC was not observed at 4 weeks of CF administration. Preneoplastic peroxisomal bifunctional enzyme-negative foci were detected in the KS-type rats at 8 weeks of CF administration, but not at 4 weeks. Human HSC were cultured in the presence of clofibric acid and expression of most HSC marker genes, such as vimentin and α-SMA (ACTA2), evaluated by a microarray, was not altered by the treatment, suggesting that HSC loss in the KS-type rats was not due to the direct toxic effect of CF. The expression levels of most HSC marker genes were low in both control and CF-treated rat livers. A possible link between HSC loss and the development of preneoplastic hepatic foci is discussed.

Effects of S-1 as a second-line chemotherapy for patients with relapsed pancreatic cancer.

Adjuvant chemotherapy with gemcitabine is the standard treatment in Japan for patients who have undergone resection of pancreatic cancer. However, few reports have described suitable regimens for patients who present cancer relapse following adjuvant chemotherapy. In the present study, we retrospectively evaluated the efficacy and safety of S-1, an oral fluoropyrimidine derivative, as a second-line chemotherapy for patients who had suffered relapse of pancreatic cancer following adjuvant chemotherapy with gemcitabine. A total of 51 patients with pancreatic cancer suffered relapse after curative resection and subsequent adjuvant chemotherapy with gemcitabine at our institution. A group of 26 of these patients were administered S-1 orally twice daily after meals at a dose of 80 mg/m(2) for body surface areas for 14 consecutive days, followed by a 7-day rest (S-1 group). The remaining 25 patients received no additional anticancer drugs other than continuation of gemcitabine (GEM/BSC group). During a median follow-up period of 35 months, a significant difference was observed in overall survival (OAS) between the S-1 group and the control group (median OAS, 20.9 vs. 13.7 months; p=0.0157, log-rank test). Furthermore, there was a significant inter-group difference in survival after relapse (SAR) (median SAR, 11.4 vs. 6.20 months; p=0.0025, log-rank test). No increase in grade 3/4 hematological and non-hematological toxicity was observed in the S-1 group. In conclusion, second-line chemotherapy using a combination of S-1 and adjuvant chemotherapy with gemcitabine may be an efficient and beneficial strategy for patients with relapsed pancreatic cancer.

Sustained repression and translocation of Ntcp and expression of Mrp4 for cholestasis after rat 90% partial hepatectomy.

BACKGROUND & AIMS: To clarify the mechanism of persistent cholestasis after massive hepatectomy, the relationship between such cholestasis and the expression and localization of organic anion transporters for bile acids was examined in a rat model. METHODS: Male Sprague-Dawley rats were subjected to 90% hepatectomy, and tissues were harvested at 0, 1, 3, and 7 days for microarray analysis, quantitative real-time polymerase chain reaction (RT-PCR), Western blotting, and immunohistochemistry to examine the expression of multidrug resistance protein 4 (Mrp4), bile salt export pump (Bsep), and sodium-dependent taurocholate cotransporting polypeptide (Ntcp). RESULTS: Persistently elevated levels of serum bile acids were observed at days 3 and 7. RT-PCR and Western blotting indicated that the expression of Mrp4, a bile acid export pump located in the basolateral membrane, was increased at day 3. The expression of Ntcp, a transporter used to uptake bile acids from the sinusoids, was significantly decreased throughout the period. The levels of Bsep, an export pump localized to the canalicular membrane, were unchanged. Immunohistochemistry revealed the localization of Mrp4 and Bsep in the basolateral and canalicular membranes, respectively. On the other hand, at days 3 and 7, Ntcp was localized in the cytoplasm and was hardly detected in the basolateral membrane. CONCLUSIONS: These results suggested that the sustained repression and translocation of Ntcp and the expression of Mrp4 at the basolateral membrane seem to be responsible for the high blood bile acids levels after massive hepatectomy.