Physalin H, physalin B, and isophysalin B suppress the quorum-sensing function of Staphylococcus aureus by binding to AgrA.

The virulence of Staphylococcus aureus, including methicillin-resistant S. aureus (MRSA), depends on the expression of toxins and virulence factors controlled by the quorum-sensing (QS) system, encoded on the virulence accessory gene regulator (agr) locus. The aim of this study was to identify a phytochemical that inhibits Agr-QS function and to elucidate its mechanism. We screened 577 compounds and identified physalin H, physalin B, and isophysalin B--phytochemicals belonging to physalins found in plants of the Solanaceae family--as novel Agr-QS modulators. Biological analyses and in vitro protein-DNA binding assays suggested that these physalins suppress gene expression related to the Agr-QS system by inhibiting binding of the key response regulator AgrA to the agr promoters, reducing the function of hemolytic toxins downstream of these genes in MRSA. Furthermore, although physalin F suppressed gene expression in the Agr-QS system, its anti-hemolytic activity was lower than that of physalins H, B, and isophysalin B. Conversely, five physalins isolated from the same plant with the ability to suppress Agr-QS did not reduce bacterial Agr-QS activity but inhibited AgrA binding to DNA in vitro. A docking simulation revealed that physalin interacts with the DNA-binding site of AgrA in three docking states. The carbonyl oxygens at C-1 and C-18 of physalins, which can suppress Agr-QS, were directed to residues N201 and R198 of AgrA, respectively, whereas these carbonyl oxygens of physalins, without Agr-QS suppression activity, were oriented in different directions. Next, 100-ns molecular dynamics simulations revealed that the hydrogen bond formed between the carbonyl oxygen at C-15 of physalins and L186 of AgrA functions as an anchor, sustaining the interaction between the carbonyl oxygen at C-1 of physalins and N201 of AgrA. Thus, these results suggest that physalin H, physalin B, and isophysalin B inhibit the interaction of AgrA with the agr promoters by binding to the DNA-binding site of AgrA, suppressing the Agr-QS function of S. aureus. Physalins that suppress the Agr-QS function are proposed as potential lead compounds in the anti-virulence strategy for MRSA infections.

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.

Intraductal papillary neoplasms of the bile ducts: a comparative study of a rare disease in Europe and Nagoya, Japan.

BACKGROUND: Intraductal papillary neoplasm of the bile ducts (IPNB) is a rare disease in Western countries. The aim of this study was to compare tumor characteristics, management strategies, and outcomes between Western and Eastern patients who underwent surgical resection for IPNB. METHODS: A multi-institutional retrospective series of patients with IPNB undergoing surgery between January 2010 and December 2020 was gathered under the auspices of the European-African Hepato-Pancreato-Biliary Association (E-AHPBA), and at Nagoya University Hospital, Japan. RESULTS: A total of 85 patients (51% male; median age 66 years) from 28 E-AHPBA centers were compared to 91 patients (64% male; median age 71 years) from Nagoya. Patients in Europe had more multiple lesions (23% vs 2%, P < .001), less invasive carcinoma (42% vs 85%, P < .001), and more intrahepatic tumors (52% vs 24%, P < .001) than in Nagoya. Patients in Europe experienced less 90-day grade >3 Clavien-Dindo complications (33% vs 68%, P < .001), but higher 90-day mortality rate (7.0% vs 0%, P = .03). R0 resections (81% vs 82%) were similar. Overall survival, excluding 90-day postoperative deaths, was similar in both regions. DISCUSSION: Despite performing more extensive resections, the low perioperative mortality rate observed in Nagoya was probably influenced by a combination of patient-, tumor-, and surgery-related factors.

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.

Impact of sarcopenia on biliary drainage during neoadjuvant therapy for pancreatic cancer.

BACKGROUND/AIMS: Since the usefulness of neoadjuvant chemo(radiation) therapy (NAT) for pancreatic cancer has been demonstrated, recurrent biliary obstruction (RBO) in patients with pancreatic cancer with a fully covered self-expandable metal stent (FCSEMS) during NAT is expected to increase. This study investigated the impact of sarcopenia on RBO in this setting. METHODS: Patients were divided into normal and low skeletal muscle index (SMI) groups and retrospectively analyzed. Patient characteristics, overall survival, time to RBO (TRBO), stent-related adverse events, and postoperative complications were compared between the two groups. A Cox proportional hazard model was used to identify the risk factors for short TRBO. RESULTS: A few significant differences were observed in patient characteristics, overall survival, stent-related adverse events, and postoperative complications between 38 patients in the normal SMI group and 17 in the low SMI group. The median TRBO was not reached in the normal SMI group and was 112 days in the low SMI group (p=0.004). In multivariate analysis, low SMI was the only risk factor for short TRBO, with a hazard ratio of 5.707 (95% confidence interval, 1.148-28.381; p=0.033). CONCLUSION: Sarcopenia was identified as an independent risk factor for RBO in patients with pancreatic cancer with FCSEMS during NAT.

Liver remnant volume to body weight ratio of 0.65% as a lower limit in right hepatic trisectionectomy with bile duct resection.

BACKGROUND: Previous studies have suggested the utility of an indocyanine green plasma clearance rate of the future liver remnant (FLR) (ICGK-F) ≥0.05 in hepatobiliary resection to reduce the surgical risk. The present study aimed to verify whether future liver remnant size rather than ICGK-F matters in extended hepatobiliary resection. METHODS: Between 2004 and 2021, patients who underwent right hepatic trisectionectomy with bile duct resection were included. The effect of the FLR volume-to-body weight ratio (FLR/BW) and ICGK-F on posthepatectomy liver failure was evaluated along with other parameters. RESULTS: Among 91 study patients, the median ICGK-F, FLR, and FLR/BW were 0.057 (range, 0.027-0.099), 392 mL (145-705), and 0.78% (0.40-1.37), respectively. Posthepatectomy liver failure occurred in 23 patients. The incidence was 10 (40%) in 25 patients with an ICGK-F <0.05 and 12 (18%) in 65 patients with an ICGK-F ≥0.05 (P = .053); 13 (52%) in 25 patients with a FLR/BW <0.65% and 10 (15%) in 66 patients with a FLR/BW ≥0.65% (P = .001). Multivariate analysis showed that a FLR/BW <0.65% (odds ratio, 11.7; P = .005), age ≥65 years (odds ratio, 31.7; P < .001), and blood loss ≥25 mL/kg (odds ratio, 22.1; P = .004) were independent predictors of posthepatectomy liver failure, but ICGK-F <0.05 was not (P = .499). According to the meeting number of 3 factors, posthepatectomy liver failure incidence was 0 of 22 (0%) in patients with 0 factors, 6 of 43 (14%) in patients with 1, and 17 of 26 (65%) in patients with 2 or 3 (P < .001). CONCLUSION: A FLR/BW ≥0.65% may serve as a volumetric basis to reduce posthepatectomy liver failure after extended hepatobiliary resection.

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.

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.

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.

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.

Cyclodextrin Conjugated α-Bisabolol Suppresses FAK Phosphorylation and Induces Apoptosis in Pancreatic Cancer.

BACKGROUND/AIM: α-Bisabolol is an essential oil component extracted from plants, such as chamomile. We have previously reported that α-bisabolol suppressed proliferation, invasion, and motility of pancreas cancer. Cyclodextrin improved the solubility of α-bisabolol, therefore it enabled to administer intravenously. The aim of this study was to clarify the effect of cyclodextrin conjugated α-bisabolol (CD-BSB) and the signals pathways associated with α-bisabolol for pancreatic cancer. MATERIALS AND METHODS: Human pancreatic cancer cell lines were treated with or without CD-BSB. Cytomorphology and apoptosis were assessed in these treated groups. In addition, several phosphorylated proteins were analyzed to clarify the signal pathway concerning CD-BSB. In subcutaneous xenograft model, tumor volume and Ki-67 expression were evaluated among Control (untreated), CD-BSB, or Gemcitabine (GEM). RESULTS: CD-BSB significantly changed cytomorphology and induced apoptosis in pancreatic cancer cells. CD-BSB suppressed phosphorylation of focal adhesion kinase (FAK). In addition, pFAK 397 was inhibited by CD-BSB in a concentration-dependent manner in cancer cells. In the subcutaneous xenograft models, the tumor volume in the CD-BSB groups was lower than Control groups. Ki67-positive cells in CD-BSB treated group were lower than the GEM-treated groups. CONCLUSION: We clarified the efficiency of CD-BSB in xenograft tumor using intravenous administration. α-Bisabolol suppresses phosphorylation of FAK 397 and impairs cytoskeletal polymerization in a pancreatic cancer cell line. Further investigations are required to reveal the precise mechanisms of the antitumor effects of solubilized α-bisabolol to facilitate its clinical application. Our data indicate that solubilized α-bisabolol has therapeutic potential and could improve the prognosis of cancer patients.

Antitumor Effects of Deep Ultraviolet Irradiation for Pancreatic Cancer.

BACKGROUND/AIM: Deep ultraviolet (DUV) light spans within the 250 nm to 350 nm invisible wavelength range. Although it strongly damages various cells, the efficacy of DUV irradiation on pancreatic cancer cells has never been clarified. The purpose of this study was to reveal the antitumor effects of DUV irradiation on pancreatic cancer cells. MATERIALS AND METHODS: Human pancreatic cancer cell lines were eradicated with DUV or ultraviolet A (UVA) for 5 s. Several angiogenesis-related proteins were studied in cancer cells after DUV irradiation using a protein antibody array. A subcutaneous xenograft model was established by inoculation of pancreatic cancer cells into mice. Tumors in this model were irradiated with DUV or UVA once or twice for two weeks. Tumor volumes in these groups (DUV×1: one irradiation, DUV×2: two irradiations, and untreated) were analyzed one week after the second irradiation. RESULTS: DUV irradiation significantly changed the cytomorphology of pancreatic cancer cells. In addition, DUV irradiation induced apoptosis on pancreatic cancer cells more strongly than UVA irradiation and no irradiation. Interestingly, lower expression of thrombospondin 1 (TSP1) and tissue inhibitor of metalloproteinase 1 (TIMP1) was identified after DUV treatment. The tumor volume in the DUV-treated groups (DUV×1 and DUV×2) was smaller than that in the untreated group. CONCLUSION: Further investigations are required to reveal the precise mechanisms of the antitumor effects of DUV irradiation and to facilitate its clinical application as a new therapy for pancreatic cancer. Overall, DUV irradiation can be potentially used as a therapeutic option of pancreatic malignancy.

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.

Impact of preoperative muscle mass and quality on surgical outcomes in patients undergoing major hepatectomy for perihilar cholangiocarcinoma.

PURPOSES: This study sought to define the impact of skeletal muscle mass and quality on postoperative outcomes in patients with perihilar cholangiocarcinoma. METHODS: Patients who underwent major hepatectomy for perihilar cholangiocarcinoma were included. The normalized total psoas area (TPA) (psoas muscle index [PMI]) and average Hounsfield units of the TPA (psoas muscle density [PMD]) were measured using preoperative computed tomography images. The cohort was dichotomized using the following indices: sex-specific lowest tertile (low PMI and low PMD) and other (normal PMI and normal PMD). Intraoperative and postoperative outcomes were compared, focusing on PMI and PMD. RESULTS: A total of 456 patients were analyzed. The intraoperative blood loss (IBL) was 21.3 ml/kg in the low PMI group and 17.2 ml/kg in the normal PMI group (P = .008). Patients in the low PMI or PMD group experienced postoperative infectious complications more frequently than those in the other groups. The median survival time was 37.8 months in the low PMI group and 54.2 months in the normal PMI group (P = .027). CONCLUSIONS: PMI and PMD were closely associated with IBL and postoperative infectious complications. Additionally, PMI impacted long-term survival. These results suggest an importance of improving muscle mass and quality before surgery.

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.

Is a specific T classification needed for extrahepatic intraductal papillary neoplasm of the bile duct (IPNB) type 2 associated with invasive carcinoma?

BACKGROUND: The necessity of a specific T classification for extrahepatic intraductal papillary neoplasm of the bile duct (IPNB) type 2, one of the precursors of cholangiocarcinoma (CC), remains unclear. METHODS: Patients who underwent resection for extrahepatic biliary tumors were reviewed. Relapse-free survival (RFS) was compared between IPNB type 2 and CC, stratified by T classification. RESULTS: The cohort involved 443 patients with IPNB type 2 (n = 57) and CC (n = 386). In 342 patients with perihilar tumors, 5-year RFS of IPNB type 2 and CC group was 49.8% versus 34.5% (p = .012), respectively. The RFS was 54.6% versus 47.2% (p = .110) for pT1-2 tumors and 28.6% versus 22.7% (p = .436) for pT3-4 tumors, respectively. In 92 patients with distal tumors, 5-year RFS was 47.4% versus 42.1% (p = .678). The RFS was 68.2% versus 49.6% (p = .422) for pT1 tumors and 18.8% versus 38.3% (p = .626) for pT2-3 tumors, respectively. Multivariate analysis identified that poor histologic grade (HR, 2.105; p < .001), microscopic venous invasion (HR, 1.568; p = .002), and nodal metastasis (HR, 1.547; p < .001) were independent prognostic deteriorators, while tumor type (IPNB type 2 vs. CC) was not. CONCLUSIONS: Prognostic impact of IPNB type 2 was limited, suggesting unnecessity of a specific T classification for IPNB type 2 with invasive carcinoma.

A proposal of drain removal criteria in hepatobiliary resection.

BACKGROUND: Standardized criteria for drain removal in hepatobiliary resection are lacking. Here, we evaluated the outcomes of delayed removal policy in this extended surgery. METHODS: Patients undergoing hepatectomy with biliary reconstruction between 2012 and 2018 were retrospectively reviewed. The drains were removed on postoperative day (POD) 7 when the drainage fluid was grossly serous, biochemically normal, and negative for bacterial contamination as assessed by Gram staining; additionally, no abnormal fluid collection was confirmed by computed tomography. Clinically relevant abdominal complications (CRACs), including biliary leakage, pancreatic fistula or intra-abdominal abscess, served as the primary outcome measure. RESULTS: Among 374 study patients, surgical drains were removed in 166 (44.3%) patients who met the criteria. Of these patients, 16 (9.6%) patients subsequently required additional drainage due to CRAC. Drains were retained and exchanged in 208 (55.6%) patients who did not meet the criteria. Of these, exchanged drains were soon removed in 34 patients due to no signs of CRAC. The diagnostic ability of the criteria revealed 0.916 sensitivity, 0.815 specificity, and 0.866 accuracy. CONCLUSION: The four findings on POD 7 worked well as criteria for drain removal, and these criteria may be helpful in drain management after hepatobiliary resection.

Minimum radial margin in pelvic exenteration for locally advanced or recurrent rectal cancer.

PURPOSE: The aim of this study was to clarify the suitable radial margin (RM) for favourable outcomes after pelvic exenteration (PE), focusing on the discrepancy between the concepts of circumferential resection margin (CRM) and traditional R status. METHODS: Seventy-three patients with locally advanced (LARC, n = 24) or locally recurrent rectal cancer (LRRC, n = 49) who underwent PE between 2006 and 2018 were retrospectively analysed. Patients were histologically classified into the following 3 groups; wide RM (≥1 mm, n = 45), narrow RM (0-1 mm, n = 10), and exposed RM (n = 18). The analysis was performed not only in the entire cohort but also in each disease group separately. RESULTS: The rates of traditional R0 (RM > 0 mm) and wide RM were 75.3% and 61.6%, respectively, resulting in the discrepancy rate of 13.7% between the two concepts. Preoperative radiotherapy was given in 12.3%. In the entire cohort, the local recurrence and overall survival (OS) rates for narrow RMs were significantly worse than those for wide RMs (p < 0.001 and p = 0.002), but were similar to those for exposed RMs. In both LARC and LRRC, RM < 1 mm resulted in significantly worse local recurrence and OS rates compared to the wide RMs. Multivariate analysis showed that RM < 1 mm was an independent risk factor for local recurrence in both LARC (HR 15.850, p = 0.015) and LRRC (HR 4.874, p = 0.005). CONCLUSIONS: Narrow and exposed RMs had an almost equal impact on local recurrence and poor OS after PE. Preoperative radiotherapy might have a key role to ensure a wide RM.

A long-term survivor of advanced retroperitoneal dedifferentiated liposarcoma: a successful multimodal approach with extended resection and chemotherapy.

Surgical resection is the mainstay of treatment for retroperitoneal liposarcoma (RPLS). Herein, we describe a case of dedifferentiated RPLS successfully treated with an extended surgical approach with adjuvant chemotherapy. A 61-year-old male was referred to our hospital with a chief complaint of chest tightness. Abdominal computed tomography revealed a large retroperitoneal tumor, 11 cm in diameter, extensively invading the surrounding organs: the celiac axis, the splenic artery, the pancreatic body and tail, the lesser curvature of the stomach and the left adrenal gland. Endoscopic ultrasound-guided fine-needle aspiration biopsy confirmed dedifferentiated liposarcoma, suggesting aggressive tumor biology. We performed total gastrectomy combined with distal pancreatectomy with celiac axis and left adrenal gland resection with a curative intent. The postoperative course was almost uneventful. As the pathological findings indicated a positive margin with a well-differentiated liposarcoma component, we added adjuvant chemotherapy with four cycles of doxorubicin and ifosfamide (AI). Five years after primary surgery, regular follow-up CT demonstrated a pulmonary hilar lymph node enlargement and a tumor at paraesophageal locations. After downsizing chemotherapy with eribulin followed by pazopanib, he underwent partial esophagectomy with dissection of the paraesophageal tumor. The pathological findings indicated recurrence of dedifferentiated liposarcoma with a tumor-free surgical margin. He is currently alive without any evidence of recurrence almost 7 years after the first surgery and 15 months after the second surgery. The long-term survival gained in this patient indicates that extended resections and adjuvant chemotherapy could prolong survival in patients even with RPLS with dedifferentiated tumor histology.