Myelodysplasia after clonal hematopoiesis with APOBEC3-mediated CYBB inactivation in retroviral gene therapy for X-CGD.

Stem cell gene therapy using the MFGS-gp91phox retroviral vector was performed on a 27-year-old patient with X-linked chronic granulomatous disease (X-CGD) in 2014. The patient's refractory infections were resolved, whereas the oxidase-positive neutrophils disappeared within 6 months. Thirty-two months after gene therapy, the patient developed myelodysplastic syndrome (MDS), and vector integration into the MECOM locus was identified in blast cells. The vector integration into MECOM was detectable in most myeloid cells at 12 months after gene therapy. However, the patient exhibited normal hematopoiesis until the onset of MDS, suggesting that MECOM transactivation contributed to clonal hematopoiesis, and the blast transformation likely arose after the acquisition of additional genetic lesions. In whole-genome sequencing, the biallelic loss of the WT1 tumor suppressor gene, which occurred immediately before tumorigenesis, was identified as a potential candidate genetic alteration. The provirus CYBB cDNA in the blasts contained 108 G-to-A mutations exclusively in the coding strand, suggesting the occurrence of APOBEC3-mediated hypermutations during the transduction of CD34-positive cells. A hypermutation-mediated loss of oxidase activity may have facilitated the survival and proliferation of the clone with MECOM transactivation. Our data provide valuable insights into the complex mechanisms underlying the development of leukemia in X-CGD gene therapy.

A clinical assessment of three-dimensional-printed liver model navigation for thrice or more repeated hepatectomy based on a conversation analysis.

PURPOSES: We performed a conversation analysis of the speech conducted among the surgical team during three-dimensional (3D)-printed liver model navigation for thrice or more repeated hepatectomy (TMRH). METHODS: Seventeen patients underwent 3D-printed liver navigation surgery for TMRH. After transcription of the utterances recorded during surgery, the transcribed utterances were coded by the utterer, utterance object, utterance content, sensor, and surgical process during conversation. We then analyzed the utterances and clarified the association between the surgical process and conversation through the intraoperative reference of the 3D-printed liver. RESULTS: In total, 130 conversations including 1648 segments were recorded. Utterance coding showed that the operator/assistant, 3D-printed liver/real liver, fact check (F)/plan check (Pc), visual check/tactile check, and confirmation of planned resection or preservation target (T)/confirmation of planned or ongoing resection line (L) accounted for 791/857, 885/763, 1148/500, 1208/440, and 1304/344 segments, respectively. The utterance's proportions of assistants, F, F of T on 3D-printed liver, F of T on real liver, and Pc of L on 3D-printed liver were significantly higher during non-expert surgeries than during expert surgeries. Confirming the surgical process with both 3D-printed liver and real liver and performing planning using a 3D-printed liver facilitates the safe implementation of TMRH, regardless of the surgeon's experience. CONCLUSIONS: The present study, using a unique conversation analysis, provided the first evidence for the clinical value of 3D-printed liver for TMRH for anatomical guidance of non-expert surgeons.

Utility of modified pancreaticoduodenectomy (Hi-cut PD) for middle-third cholangiocarcinoma: an alternative to hepatopancreaticoduodenectomy.

BACKGROUND: The standard procedure for middle-third cholangiocarcinoma (MCC) is pancreaticoduodenectomy (PD); hepatopancreaticoduodenectomy (HPD) is often performed despite its high risk. There is no clear selection guidance for these procedures. METHODS: Patients with MCC who underwent HPD or PD were retrospectively evaluated. The conventional PD was modified (mPD) to transect the bile duct beyond or close to the cranial level of the portal bifurcation. RESULTS: The mPD group (n = 55) was characterized by older age, shorter operation time, less blood loss, and less frequent complications than were observed in the HPD group (n = 34). The median grossly tumor-free margin of the proximal bile duct (GM) was 13 mm vs 20 mm (P = 0.006). Overall survival did not differ significantly between groups (48% vs 53% at 5 years, P = 0.399). Multivariate analysis identified positive surgical margin as a sole independent prognostic factor (hazard ratio, 1.89; P = 0.043), which was statistically associated with GM length. Five-year survival for mPD patients with GM ≥15 mm was significantly better than that for those who had GM <15 mm (69% vs 33%, P = 0.011) and comparable to that of HPD patients (53%, P = 0.450). CONCLUSION: The mPD may be recommended in patients with MCC, provided that GM ≥15 mm is expected from the preoperative radiological imaging. Otherwise, HPD should be considered.

Early Prediction of a Serious Postoperative Course in Perihilar Cholangiocarcinoma: Trajectory Analysis of the Comprehensive Complication Index.

OBJECTIVE: The aim of this study was to visualize the postoperative clinical course using the comprehensive complication index (CCI) and to propose an early alarming sign for subsequent serious outcomes in perihilar cholangiocarcinoma. BACKGROUND: Surgery for this disease carries a high risk of morbidity and mortality. The developmental course of the overall morbidity burden and its clinical utility are unknown. METHODS: Patients who underwent major hepatectomy for perihilar cholan-giocarcinoma between 2010 and 2019 were reviewed retrospectively. All postoperative complications were evaluated according to the Clavien-Dindo classification (CDC), and the CCI was calculated on a daily basis until postoperative day 14 to construct an accumulating graph as a trajectory. Group-based trajectory modeling was conducted to categorize the trajectory into clinically distinct patterns and the predictive power of early CCI for a subsequent serious course was assessed. RESULTS: A total of 4230 complications occurred in the 484 study patients (CDC grade I, n = 27; II, n = 132; IlIa, n = 290; IIIb, n = 4; IVa, n = 21; IVb, n = 1; and V, n = 9). The trajectory was categorized into 3 patterns: mild (n = 209), moderate (n = 235), and severe (n = 40) morbidity courses. The 90-day mortality rate significantly differed among the courses: 0%, 0.9%, and 17.5%, respectively (P<0.001). The cutoff values of the CCI on postoperative days 1, 4, and 7 for predicting a severe morbidity course were 15.0, 28.5, and 40.6 with areas under the curves of 0.780, 0.924, and 0.984, respectively. CONCLUSIONS: The CCI could depict the chronological increase in the overall morbidity burden, categorized into 3 patterns. Early CCI potentially predicted sequential progression to serious outcomes.

Efficacy of Extended Modification in Left Hemihepatectomy for Advanced Perihilar Cholangiocarcinoma: Comparison Between H12345'8'-B-MHV and H1234-B.

OBJECTIVE: The aim of this study was to verify the prognostic impact of the tumor exposure at the liver transection margin (LTM) in left-sided perihilar cholangiocarcinoma and the impact of middle hepatic vein (MHV) resection on this exposure. BACKGROUND: In perihilar cholangiocarcinoma, tumors are unexpectedly exposed at the LTM during left hemihepatectomy (LH). METHODS: Patients who underwent LH for perihilar cholangiocarcinoma during 2002 to 2018 were retrospectively evaluated. LH was classified into conventional and extended types, which preserved and resected the MHVs, respectively. Positive LTM was defined as the involvement of invasive carcinoma at the liver transection plane and/or the adjacent Glissonean pedicle exposed. The clinicopathologic features and survival outcomes were compared between procedures. RESULTS: Among 236 patients, conventional and extended LHs were performed in 198 and 38 patients, respectively. The LTM was positive in 31 (13%) patients, with an incidence of 14% versus 8% ( P = 0.432) and 24% versus 0% in advanced tumors ( P = 0.011). Tumor size ≥ 18 mm ( P = 0.041), portal vein invasion ( P = 0.009), and conventional LH ( P = 0.028) independently predicted positive LTM. In patients with negative LTM, the survival was comparable between the two groups: 60.4% versus 59.2% at 3 years ( P = 0.206), which surpassed 17.7% for those with positive LTM in the conventional group ( P < 0.001). Multivariable analysis demonstrated that LTM status was an independent prognostic factor ( P = 0.009) along with ductal margin status ( P = 0.030). CONCLUSIONS: The LTM status is an important prognostic factor in perihilar cholangiocarcinoma. Extended LH reduced the risk of tumor exposure at the LTM with a subsequent improvement in the survival, particularly in advanced tumors.

The Goal of Intraoperative Blood Loss in Major Hepatobiliary Resection for Perihilar Cholangiocarcinoma: Saving Patients From a Heavy Complication Burden.

OBJECTIVE: To determine the goal of intraoperative blood loss in hepatectomy for perihilar cholangiocarcinoma. BACKGROUND: Although massive bleeding can negatively affect the postoperative course, the target value of intraoperative bleeding to reduce its adverse impact is unknown. METHODS: Patients who underwent major hepatectomy for perihilar cholangiocarcinoma between 2010 and 2019 were included. Intraoperative blood loss was adjusted for body weight [adjusted blood loss (aBL)], and the overall postoperative complications were evaluated by the comprehensive complication index (CCI). The impact of aBL on CCI was assessed by the restricted cubic spline regression. RESULTS: A total of 425 patients were included. The median aBL was 17.8 (interquartile range, 11.8-26.3) mL/kg, and the CCI was 40.6 (33.7-49.5). Sixty-three (14.8%) patients had an aBL<10 mL/kg, nearly half (45.4%) of the patients were in the range of 10 ≤aBL<20 mL/kg, and 37 (8.7%) patients had an aBL >40 mL/kg. The spline regression analysis showed a nonlinear incremental association between aBL and CCI; CCI remained flat with an aBL under 10 mL/kg; increased significantly with an aBL ranging from 10 to 20 mL/kg; grew gradually with an aBL over 20 mL/kg. These inflection points of ~10 and 20 mL/kg were almost consistent with the cutoff values identified by the recursive partitioning technique. After adjusting for other risk factors for the postoperative course, the spline regression identified a similar model. CONCLUSIONS: aBL had a nonlinear aggravating effect on CCI after hepatectomy for perihilar cholangiocarcinoma. The primary goal of aBL should be <10 mL/kg to minimize CCI.

Impact of skeletal muscle mass on the prognosis of patients undergoing neoadjuvant chemotherapy for resectable or borderline resectable pancreatic cancer.

BACKGROUND: Neoadjuvant chemotherapy is a common therapeutic procedure for patients with pancreatic cancer. This study aimed to investigate the association between the total psoas area (TPA) and prognosis in patients undergoing neoadjuvant chemotherapy for resectable or borderline resectable pancreatic cancer. STUDY DESIGN: This retrospective study included patients who underwent neoadjuvant chemotherapy for pancreatic cancer. TPA was measured at the level of the L3 vertebra using computed tomography. The patients were divided into low-TPA and normal-TPA groups. These dichotomizations were separately performed in patients with resectable and those with borderline resectable pancreatic cancer. RESULTS: In total, 44 patients had resectable pancreatic cancer and 71 patients had borderline resectable pancreatic cancer. Overall survival among patients with resectable pancreatic cancer did not differ between the normal- and low-TPA groups (median, 19.8 vs. 21.8 months, p = 0.447), whereas among patients with borderline resectable pancreatic cancer, the low-TPA group had shorter overall survival than the normal-TPA group (median, 21.8 vs. 32.9 months, p = 0.006). Among patients with borderline resectable pancreatic cancer, the low-TPA group was predictive of poor overall survival (adjusted hazard ratio, 2.57, p = 0.037). CONCLUSION: Low TPA is a risk factor of poor survival in patients undergoing neoadjuvant chemotherapy for borderline resectable pancreatic cancer. TPA evaluation could potentially suggest the treatment strategy in this disease.

Which modality is better to diagnose high-grade transformation in retroperitoneal liposarcoma? Comparison of computed tomography, positron emission tomography, and magnetic resonance imaging.

BACKGROUND: Survival in patients with retroperitoneal liposarcoma (RPLS) depends on the surgical management of the dedifferentiated foci. The present study investigated the diagnostic yield of contrast-enhanced CT, 18F-fluorodeoxyglucose positron emission tomography (PET), and diffusion-weighted MRI in terms of dedifferentiated foci within the RPLS. METHODS: Patients treated with primary or recurrent RPLS who underwent the above imaging between January 2010 and December 2021 were retrospectively reviewed. The diagnostic accuracy of the three modalities for histologic subtype of dedifferentiated liposarcoma (DDLS) and French Federation of Cancer Center (FNCLCC) grade 2/3 were compared using receiver operating characteristic curves and areas under the curves (AUCs). RESULTS: The cohort involved 32 patients with 53 tumors; 30 of which exhibited DDLS and 31 of which did FNCLCC grades 2/3. The optimal thresholds for predicting DDLS were mean CT value of 31 Hounsfield Unit (HU) (AUC = 0.880, 95% CI 0.775-0.984; p < 0.001), maximum standardized uptake value (SUVmax) of 2.9 (AUC = 0.865 95% CI 0.792-0.980; p < 0.001), while MRI failed to differentiate DDLS. The cutoff values for distinguishing FNCLCC grades 1 and 2/3 were a mean CT value of 24 HU (AUC = 0.858, 95% CI 0.731-0.985; p < 0.001) and SUVmax of 2.9 (AUC = 0.885, 95% CI 0.792-0.978; p < 0.001). MRI had no sufficient power to separate these grades. CONCLUSIONS: Contrast-enhanced CT and PET were useful for predicting DDLS and FNCLCC grade 2/3, while MRI was inferior to these two modalities.

Two-step arterial reconstruction technique for en bloc resection of a large retroperitoneal liposarcoma involving the common iliac artery.

Retroperitoneal liposarcoma (RPLS) is a rare but challenging neoplasm, which is frequently associated with iliac vessel invasion. We describe how we used a two-step arterial reconstruction technique to perform en bloc resection of a large RPLS involving the iliac arteries in three patients. A temporal long in situ graft bypass was established using a prosthetic vascular graft during dissection of the tumor. This bypass provided an unobscured surgical field, while maintaining blood flow in the lower limb during the operation. After removal of the tumor and washing out the abdominal cavity, the new prosthetic vascular graft of a suitable length was placed. No graft-related complications, including vascular graft infection or graft occlusion, occurred during the follow-up period. This novel technique appears to provide a safe and effective way to remove large RPLSs involving the retroperitoneal major vessels.

Clinical value of fluorescent cholangiography for the infraportal type of right posterior bile duct.

BACKGROUND: The infraportal type of the right posterior bile duct (infraportal RPBD) is a well-known anatomical variation that increases the potential risk of intraoperative biliary injury. The aim of this study is to clarify the clinical value of fluorescent cholangiography during single-incision laparoscopic cholecystectomy (SILC) for patients with infraportal RPBD. MATERIAL AND METHODS: Our procedure for SILC utilized the SILS-Port, and another 5-mm forceps was inserted via an umbilical incision. A laparoscopic fluorescence imaging system developed by Karl Storz Endoskope was utilized for fluorescent cholangiography. Between July 2010 and March 2022, 41 patients with infraportal RPBD underwent SILC. We conducted retrospective reviews of patient data, focusing on the clinical value of fluorescent cholangiography. RESULTS: Thirty-one patients underwent fluorescent cholangiography during SILC, but the remaining ten did not. Only one patient who did not undergo fluorescent cholangiography developed an intraoperative biliary injury. The detectability of infraportal RPBD before and during the dissection of Calot's triangle was 16.1% and 45.2%, respectively. These visible infraportal RPBDs were characterized as connections to the common bile duct. The confluence pattern of infraportal RPBD significantly influenced its detectability during the dissection of Calot's triangle (p < 0.001). CONCLUSIONS: The application of fluorescent cholangiography can lead to safe SILC, even for patients with infraportal RPBD. Its benefit is emphasized when infraportal RPBD is connected to the common bile duct.

[A Study of the Safety of Chemotherapy with Generic Oxaliplatin for the Treatment of Colorectal Cancer].

BACKGROUND: Generic oxaliplatin is widely used in colorectal cancer chemotherapy; however, studies on the adverse events of generic drugs are limited. We investigated the safety of brand-name and generic oxaliplatin used in capecitabine plus oxaliplatin(plus bevacizumab: Bmab)for colorectal cancer treatment. PARTICIPANTS AND METHODS: A total of 86 patients who newly started CAPOX(plus Bmab)between January 2018 and January 2022 were included in this retrospective study, excluding those who changed to generic from the brand-name drug during the chemotherapy course. RESULTS: Forty-seven patients(54.6%)were in the generic drug(GE)group, while 39 patients(45.4%)were in the brand drug(EP)group. No significant difference was observed in the patient characteristics between the GE and EP groups. The median number of oxaliplatin administrations were 4 and 5 cycles in the GE and EP groups, respectively. Neutropenia of Grade 2 or higher was observed in 51.1%(24 patients)and 33.3%(13 patients)in the GE and EP groups, respectively. Hypersensitivity was observed in 14.9%(7 patients)and 7.7%(3 patients)in the GE and EP groups, respectively. CONCLUSION: There were no statistically significant differences between generic and brand-name oxaliplatin in the frequency of adverse events.

Clinical and radiographic outcomes of primary total hip arthroplasty with the revelation hip system using density mapping.

The Revelation Hip System is a cementless stem with a lateral flare concept. Stable fixation is achieved by fitting the stem to the medullary cavity of the proximal lateral femoral cortex. Patients who have undergone total hip arthroplasty using the Revelation Hip System show good postoperative clinical and radiographic outcomes. However, to the best of our knowledge, no study has reported the relationship between stem fitting and clinical or radiological outcomes after the surgery. In the present study, we investigated the relationship between stem fitting and clinical or radiological outcomes after total hip arthroplasty (THA) using the Revelation Hip System. In this study, 28 hips of 26 patients who were treated with the Revelation Hip System for osteoarthritis, osteonecrosis of the femoral head, rheumatoid arthritis, and rapidly destructive coxarthropathy and were followed up for > 5 y were enrolled. These patients were divided into two groups, including the rest fit group (11 hips, group R) and the control group (17 hips, group C), according to the results of the density mapping analysis. In group R, the lateral side of the stem fits on the medullary cavity of the proximal lateral femoral cortex, while in group C, the lateral side of the stem did not fit. Radiographic results showed no significant differences between the groups in terms of stem alignment, subsidence, and stress shielding around the cup. The incidence of stress shielding around the stem in zone 7 was not significant but tended to be higher in group R than in group C (p = 0.052). Clinical outcomes showed no significant differences between group R and group C in terms of the Harris hip score, the Japanese Orthopaedic Association (JOA) score, and the Japanese Orthopaedic Association Hip Disease Evaluation Questionnaire (JHEQ) total score. However, pain complaints that were assessed by patient-reported outcomes using the 36-Item Short Form Health Survey (SF-36) bodily pain and vitality subscales and the JHEQ pain subscale were significantly higher in group R than in group C at the final follow-up. These results suggest that some patients had pain complaint even if the stems were inserted as per the concept after THA with the Revelation Hip System.Trial Registration911.

Combined Vascular Resection for Locally Advanced Perihilar Cholangiocarcinoma.

OBJECTIVE: To evaluate the efficacy and safety of combined vascular resection (VR) in advanced perihilar cholangiocarcinoma (PHC). SUMMARY OF BACKGROUND DATA: Hepatectomy combined with portal vein resection (PVR) and/or hepatic artery resection (HAR) is technically demanding but an option only for tumor eradication against PHC involving the hilar hepatic inflow vessels; however, its efficacy and safety have not been well evaluated. METHODS: Patients diagnosed with PHC during 2001-2018 were included. Patients who underwent resection were divided according to combined VR. Patients undergoing VR were subdivided according to type of VR. Postoperative outcomes and OS were compared between patient groups. RESULTS: Among the 1055 consecutive patients, 787 (75%) underwent resection (without VR: n = 484, PVR: n = 157, HAR: n = 146). The incidences of postoperative complications and mortality were 49% (without VR vs with VR, 48% vs 50%; P= 0.715) and 2.1% (without VR vs with VR, 1.2% vs 3.6%; P= 0.040), respectively. The OS of patients who underwent resection with VR (median, 30 months) was shorter than that of those who underwent resection without VR (median, 61 months; P < 0.0001); however, it was longer than that of those who did not undergo resection (median, 10 months; P < 0.0001). OS was not significantly different between those who underwent PVR and those who underwent HAR (median, 29 months vs 34 months; P = 0.517). CONCLUSION: VR salvages a large number of patients from having locally advanced PHC that is otherwise unresectable and is recommended if the hilar hepatic inflow vessels are reconstructable, providing acceptable surgical outcomes and substantial survival benefits.

Mild Prognostic Impact of Postoperative Complications on Long-term Survival of Perihilar Cholangiocarcinoma.

OBJECTIVE: To evaluate the impact of complications on long-term survival in patients with perihilar cholangiocarcinoma. BACKGROUND: Surgical resection for perihilar cholangiocarcinoma is vulnerable to postoperative complications. The prognostic impact of complications in patients with this disease is unknown. METHODS: The medical records of patients who underwent curative-intent hepatectomy for perihilar cholangiocarcinoma between 2010 and 2017 were reviewed retrospectively. The comprehensive complication index (CCI) was calculated based on all postoperative complications, which were graded by the Clavien-Dindo classification (CDC). Patients were divided into high and low CCI groups by the median score, and survival was compared between the 2 groups. RESULTS: Excluding 8 patients who died in hospital, 369 patients were analyzed. The CDC grade was I in 20 (5.4%), II in 108 (29.3%), III in 224 (60.7%), and IV in 17 (4.6%) patients. The CCI increased with increasing CDC grade; the median was 42.9 (range, 15.0-98.9). Overall survival differed significantly between the high (n = 187) and low (n = 182) CCI groups (41.2% vs 47.9% at 5 years; P = 0.041). However, multivariable analyses demonstrated that traditional clinicopathological factors were independent predictors of survival and that the dichotomized CCI was not. In addition, the CCI score as a continuous variable was not an independent prognostic factor for overall survival in the multivariable analyses (hazard ratio per 1 CCI score: 1.00, 95% confidence interval: 0.99-1.01, P = 0.775). CONCLUSIONS: Cumulative postoperative complications after resection of perihilar cholangiocarcinoma only moderately deteriorate long-term survival, and should not be an argument to deny surgery in this high-risk population.

Differences among the observers in the assessments of Japanese orthopedic association hip scores between surgeons and physical therapists and the correlations to patients' reported outcomes after total hip arthroplasty.

BACKGROUND: We aimed to assess the utility of a clinician-reported outcome (the Japanese Orthopedic Association [JOA] hip score) as evaluated by clinicians and physiotherapists. This assessment was made by comparing these scores to those of the JOA hip disease evaluation questionnaire (JHEQ), which is a measurement of patient-reported outcomes after total hip arthroplasty. METHODS: In this retrospective case-control study, 52 hips that underwent primary total hip arthroplasty were included in the analyses. The mean age of the participants was 66.8 years (sex, seven male and 45 female participants). The JOA hip score included four categories: pain, range of motion, ability to walk, and active daily living. The JHEQ included three categories: pain, movement, and mental health. These scores were evaluated preoperatively and postoperatively by clinicians or physiotherapists. Pearson's correlation coefficients were utilized to analyze the association of the JOA hip scores to those of the JHEQ. RESULTS: The JOA hip scores were determined by clinicians and physiotherapists (scores of 46.8 and 57.3, respectively) preoperatively and at 24 months (scores of 94.4 and 91.7, respectively) postoperatively. The JHEQ points were 28.8 and 66.2 preoperatively and at 24 months postoperatively, respectively. The correlation coefficients between the JOA hip and JHEQ scores were .66 and .69 preoperatively and .57 and .76 at 24 months postoperatively, as evaluated by clinicians and physiotherapists, respectively. CONCLUSIONS: Although the JHEQ scores were positively correlated to the JOA hip scores by clinicians and physiotherapists preoperatively and postoperatively, this study implies that clinicians may interpret the results in a way that might have been beneficial to them. To comprehend a patients' health status, we should inclusively understand the varying range of information among different evaluators.

A Study on Radial Margin Status in Resected Perihilar Cholangiocarcinoma.

OBJECTIVE: To investigate radial margin (RM) status in resected perihilar cholangiocarcinoma (PHCC) and to evaluate the incidence of positive RM and its effect on survival. BACKGROUND: Although numerous studies have reported on ductal margin (DM) status in resected PHCC, no studies have addressed RM status. METHODS: Patients who underwent hepatectomy for PHCC between 2001 and 2014 were retrospectively reviewed. After formalin fixation, resected specimens were serially sectioned at 5-mm intervals. All serial sections were color-copied, and RMs and DMs were identified and indicated on the color copies. RESULTS: Among 478 patients, 85 (17.8%) had positive surgical margins (R1 resection); of the 85 patients, 37 had positive RM alone, 33 had positive DM alone, and the remaining 15 had both positive RM and positive DM. Overall, 52 (61.2%) patients had positive RM. The sites of positive RM included the liver transection plane (n = 20) and the dissection plane in the hepatoduodenal ligament (n = 32). RM positivity on the liver transection plane was higher in left hepatectomy than in other hepatectomies (9.2% vs 1.9%, P < 0.001). RM positivity in the hepatoduodenal ligament was higher in left-sided hepatectomy than in right-sided hepatectomy (8.7% vs 3.6%, P = 0.031). The survival of the patients with positive RM was poorer than that of R0 patients (MST 2.1 vs 4.9 yrs, P < 0.001) and was similar to that of patients with positive DM. Multivariate analysis identified positive RM as one of the independent prognostic factors. CONCLUSIONS: Positive RM was the most common cause of R1 resection of PHCC and had similarly negative effects on survival as positive DM. Meticulous handling of the resected specimen is important to accurately evaluate RM status together with DM status.

Impact of Perioperative Steroid Administration in Patients Undergoing Major Hepatectomy with Extrahepatic Bile Duct Resection: A Randomized Controlled Trial.

BACKGROUND: To date, five randomized controlled trials have assessed the clinical benefit of perioperative steroid administration in hepatectomy; however, all of these studies involved a substantial number of 'minor' hepatectomies. The benefit of steroid administration for patients undergoing 'complex' hepatectomy, such as major hepatectomy with extrahepatic bile duct resection, is still unclear. This study aimed to evaluate the clinical benefit of perioperative steroid administration for complex major hepatectomy. METHODS: Patients with suspected hilar malignancy scheduled to undergo major hepatectomy with extrahepatic bile duct resection were randomized into either the control or steroid groups. The steroid group received hydrocortisone 500 mg immediately before hepatic pedicle clamping, followed by hydrocortisone 300 mg on postoperative day (POD) 1, 200 mg on POD 2, and 100 mg on POD 3. The control group received only physiologic saline. The primary endpoint was the incidence of postoperative liver failure. RESULTS: A total of 94 patients were randomized to either the control (n = 46) or steroid (n = 48) groups. The two groups had similar baseline characteristics; however, there were no significant differences between the groups in the incidence of grade B/C postoperative liver failure (control group, n = 8, 17%; steroid group, n = 4, 8%; p = 0.188) and other complications. Serum bilirubin levels on PODs 2 and 3 were significantly lower in the steroid group than those in the control group; however, these median values were within normal limits in both groups. CONCLUSION: Perioperative steroid administration did not reduce the risk of postoperative complications, including liver failure following major hepatectomy with extrahepatic bile duct resection.

Impact of the preoperative body composition indexes on intraoperative blood loss in patients undergoing pancreatoduodenectomy.

PURPOSES: This study sought to identify any significant predictors of blood loss during pancreatoduodenectomy (PD) among preoperative variables, including the body composition indexes. METHODS: The preoperative data of patients undergoing PD were retrospectively reviewed. The objective variable was the percentage of blood loss during PD to the estimated circulating blood volume (proportional blood loss: PBL). The circulating blood volume was estimated using Nadler's formula. The total psoas area, average Hounsfield units of psoas area (psoas muscle density: PMD), and visceral to subcutaneous adipose tissue area ratio (VSR) were measured at the third vertebra using preoperative plain computed tomography images. A univariate analysis and multiple linear regression analysis for PBL were conducted using the preoperative variables. RESULTS: A total of 415 patients were analyzed. The median PBL was 24.5%. The PMD (coefficient - 0.267; 95% CI - 0.518, - 0.015), VSR (coefficient 2.719; 95% CI 0.238, 5.201), serum albumin level (coefficient - 8.458; 95% CI - 13.02, - 3.898), neoadjuvant therapy (coefficient 9.605; 95% CI 1.722, 17.49), and prothrombin time-international normalized ratio (PT-INR, coefficient 38.63; 95% CI 10.94, 66.31) were independently associated with PBL. CONCLUSIONS: The preoperative PMD, VSR, serum albumin level, neoadjuvant therapy, and PT-INR independently affected PBL. These factors could therefore be potential targets to reduce blood loss during PD.

A clinicopathological reappraisal of intraductal papillary neoplasm of the bile duct (IPNB): a continuous spectrum with papillary cholangiocarcinoma in 181 curatively resected cases.

BACKGROUND: Intraductal papillary neoplasm of the bile-duct (IPNB) has recently been further subclassified into "so-called IPNBs" (Type-1) and "narrow-sense papillary cholangiocarcinomas" (Type-2), but their differential diagnosis is challenging. This study aimed to reevaluate Type-1 and Type-2 IPNBs. METHODS: Consecutive patients who underwent papillary bile-duct tumor resection were included. Using six pathological features (location, mucin secretion, histological architecture, histological type, presence of a low/intermediate-dysplasia component, and proportion of the invasive component), all papillary tumors were scored. Tumors scoring 5-6 were classified as Type-1, 0-1 as Type-2, and 2-4 as Type-Unclassifiable. RESULTS: The 181 papillary bile-duct tumor patients were divided into three groups, consisting of 12 Type-1, 46 Type-2, and 123 Type-Unclassifiable-gray-zone lesions between Type-1 and Type-2 that constituted the largest proportion of papillary tumors. Type-1 tumors were pathologically the least advanced, while the other types showed gradual advancement. The 5-year survival rate was better for patients with Type-1 tumors than for those with Type-Unclassifiable or Type-2 tumors. CONCLUSION: The scoring system worked well to delineate a continuous spectrum of pathologic features ranging from Type-1, through Type-Unclassifiable, to Type-2, the latter two being challenging to differentially diagnose. Type-1 is regarded as an early neoplasm of Type-Unclassifiable and Type-2.

Study of the Portal Branches Arising from the Cranial Part of the Umbilical Portion of the Left Portal Vein: Implications for Anatomic Right Hepatic Trisectionectomy.

BACKGROUND: In "anatomic" right hepatic trisectionectomy for advanced perihilar cholangiocarcinoma, the left hepatic duct is divided at the left side of the umbilical portion (UP) of the left portal vein (LPV). For this reason, the left hepatic duct is completely detached from the UP after all division of the portal branches arising cranially from the UP. However, little is known about these thin portal branches. METHODS: Using 3D imaging processing software, we examined the portal branches arising cranially from the UP of the LPV in 100 patients who underwent multidetector row computed tomography (MDCT). Special attention was paid to the portal branch running to the left lateral sector, designated as the left cranio-lateral branch. RESULTS: The left cranio-lateral portal branch number was 0 in 57 patients, 1 in 32 patients, and 2 in 11 patients. Thus, 54 left cranio-lateral branches were identified, arising from near the cul-de-sac of the UP, from near the elbow of the LPV, or from the UP trunk. The median volume of the territory supplied by the left cranio-lateral portal branch was 21 mL (range, 5-47 mL), and the median ratio to the left lateral sector was 11.8% (range, 1.7-25.0%). CONCLUSION: Approximately 40% of patients had the left cranio-lateral portal branches arising cranially from the UP and running to the left lateral sector. When planning anatomic right hepatic trisectionectomy, the presence or absence of this branch should be checked by using 3D imaging with MDCT.