The effectiveness of combined extra-hepatic bile duct resection in radically-resected cases with intrahepatic cholangiocarcinoma: a SEER-based retrospective cohort study and an external validation.

OBJECTIVE: To evaluate the effectiveness of the combined extra-hepatic bile duct resection (EHBDR) in cases with intrahepatic cholangiocarcinoma (IHCC) in terms of clinicopathological features and long-term survival. METHODS: Radically resected cases with IHCC from 2000 to 2020 were identified from Surveillance, Epidemiology, and End Results (SEER) database. Comparative analyses were performed between resected IHCC patients who received EHBDR and those without EHBDR. Moreover, an external validation was further performed based on a single-center cohort. RESULTS: A total of 1521 radically resected cases with IHCC (EHBDR: 189) were identified from SEER database. Comparable age, sex, race, marital status, liver cirrhosis, differentiation status, and adjuvant chemotherapy were acquired between two groups. EHBDR was associated with a higher incidence of adequate lymphadenectomy (P<0.001). The incidence of cases with T3-4 or N+ disease was significantly higher in EHBDR group (P<0.001). Adjuvant radiotherapy was more frequently performed in cases with EHBDR (P<0.001). EHBDR failed to brought any survival benefit and was associated with a worse prognosis even after matching. Similar findings have also been revealed in the external validation cohort (n=522, EHBDR: 117). EHBDR was associated with more extended resections, more aggressive tumor biological features, and worse prognosis. In the matched validation cohort, EHBDR was still associated with a higher incidence of early recurrence. CONCLUSION: EHBDR was an indicator of advanced stage and failed to brought any survival benefit. It is the tumor stage which really determines the prognosis. More in-depth analyses focusing on different situations of EHBDR with more detailed clinical data are required.

Integrative analyses of bulk and single-cell transcriptomics reveals the infiltration and crosstalk of cancer-associated fibroblasts as a novel predictor for prognosis and microenvironment remodeling in intrahepatic cholangiocarcinoma.

BACKGROUND: Intrahepatic cholangiocarcinoma (ICC) is a highly malignant neoplasm and characterized by desmoplastic matrix. The heterogeneity and crosstalk of tumor microenvironment remain incompletely understood. METHODS: To address this gap, we performed Weighted Gene Co-expression Network Analysis (WGCNA) to identify and construct a cancer associated fibroblasts (CAFs) infiltration biomarker. We also depicted the intercellular communication network and important receptor-ligand complexes using the single-cell transcriptomics analysis of tumor and Adjacent normal tissue. RESULTS: Through the intersection of TCGA DEGs and WGCNA module genes, 784 differential genes related to CAFs infiltration were obtained. After a series of regression analyses, the CAFs score was generated by integrating the expressions of EVA1A, APBA2, LRRTM4, GOLGA8M, BPIFB2, and their corresponding coefficients. In the TCGA-CHOL, GSE89748, and 107,943 cohorts, the high CAFs score group showed unfavorable survival prognosis (p < 0.001, p = 0.0074, p = 0.028, respectively). Additionally, a series of drugs have been predicted to be more sensitive to the high-risk group (p < 0.05). Subsequent to dimension reduction and clustering, thirteen clusters were identified to construct the single-cell atlas. Cell-cell interaction analysis unveiled significant enhancement of signal transduction in tumor tissues, particularly from fibroblasts to malignant cells via diverse pathways. Moreover, SCENIC analysis indicated that HOXA5, WT1, and LHX2 are fibroblast specific motifs. CONCLUSIONS: This study reveals the key role of fibroblasts - oncocytes interaction in the remodeling of the immunosuppressive microenvironment in intrahepatic cholangiocarcinoma. Subsequently, it may trigger cascade activation of downstream signaling pathways such as PI3K-AKT and Notch in tumor, thus initiating tumorigenesis. Targeted drugs aimed at disrupting fibroblasts-tumor cell interaction, along with associated enrichment pathways, show potential in mitigating the immunosuppressive microenvironment that facilitates tumor progression.

A meta-analysis between robotic hepatectomy and conventional open hepatectomy.

Current meta-analysis was performed to compare robotic hepatectomy (RH) with conventional open hepatectomy (OH) in terms of peri-operative and postoperative outcomes. PubMed, EMBASE, and the Cochrane Library were all searched up for comparative studies between RH and OH. RevMan5.3 software and Stata 13.0 software were used for statistical analysis. Nineteen studies with 1747 patients who received RH and 23,633 patients who received OH were included. Pooled results indicated that patients who received RH were generally younger than those received OH (P < 0.00001). Moreover, RH was associated with longer operative time (P = 0.0002), less intraoperative hemorrhage (P < 0.0001), lower incidence of intraoperative transfusion (P = 0.003), lower incidence of postoperative any morbidity (P < 0.00001), postoperative major morbidity (P = 0.0001), mortalities with 90 days after surgery (P < 0.0001), and shorter length of postoperative hospital stay (P < 0.00001). Comparable total hospital costs were acquired between RH and OH groups (P = 0.46). However, even at the premise of comparable R0 rate (P = 0.86), RH was associated with smaller resected tumor size (P < 0.00001). Major hepatectomy (P = 0.02) and right posterior hepatectomy (P = 0.0003) were less frequently performed in RH group. Finally, we concluded that RH was superior to OH in terms of peri-operative and postoperative outcomes. RH could lead to less intraoperative hemorrhage, less postoperative complications and an enhanced postoperative recovery. However, major hepatectomy and right posterior hepatectomy were still less frequently performed via robotic approach. Future more powerful well-designed studies are required for further exploration.

Lateral lymph node metastasis in papillary thyroid cancer: Is there a difference between PTC and PTMC?

Papillary thyroid carcinoma (PTC) and papillary thyroid microcarcinoma (PTMC) are generally characterized as less invasive forms of thyroid cancer with favorable prognosis. However, once lateral cervical lymph node metastasis takes place, the prognosis may be significantly impacted. The purpose of this study was to evaluate whether there is a difference in the pattern of lateral lymph node metastasis between PTC and PTMC. A retrospective analysis was performed for PTC and PTMC patients that underwent central area dissection and unilateral lateral neck lymph node dissection (II-V area) between January 2020 and December 2021. Compared with PTMC group, the PTC group exhibited higher incidence of capsule invasion, extrathyroid invasion and lymphatic vessel invasion. Both the number and rate of central lymph nodes metastasis were elevated in the PTC group. While the number of lateral cervical lymph node metastasis was higher, the metastasis rate did not demonstrate significant difference. No significant differences were identified in the lymph node metastasis patterns between the 2 groups. The determination of the extent of lateral neck lymph node dissection solely based on the tumor size may be unreliable, as PTC and PTMC showed no difference in the number and pattern of lateral neck metastasis. Additional clinical data are warranted to reinforce this conclusion. For patients categorized as unilateral, bilateral, or contralateral cervical lymph node metastasis (including level I, II, III, IV, or V) or retropharyngeal lymph node metastasis who require unilateral lateral neck dissection, the size of the primary tumor may not need to be a central consideration when assessing and deciding the extent of lateral neck dissection.

Effects of no perforation margin trimming and EAC packing in cartilage underlay myringoplasty for chronic large perforations in children.

OBJECTIVE: Trimming of perforation margins and external auditory canal (EAC) packing are basic procedures in underlay myringoplasty for repairing chronic perforations. The objective of this study was to compare the operation time, graft outcome, hearing improvement, and complications of endoscopic cartilage underlay myringoplasty with and without trimming of perforation margins and EAC packing in children. STUDY DESIGN: Prospective, randomized study. SETTING: Tertiary referral center. MATERIAL AND METHODS: Pediatric patients older than 12 years with chronic perforations were randomly divided into two groups: myringoplasty with trimming of perforation margin and EAC packing (TPME) group or no trimming of perforation margin and EAC packing (NTPME) group. The operation time, graft success rate, hearing improvement, and complications were compared between the two groups. RESULTS: Fifty-two patients were ultimately included in the study. The mean operation time was 31.4 ± 4.2 min in the TPME group and 23.6 ± 1.7 min in the NTPME group; the difference was significant (P < 0.01). The rate of aural fullness significantly differed between the TPME and NTPME groups (P = 0.000). All participants were followed up for 12 months; the graft success rate did not significantly differ between the groups (88.5% vs. 96.2%; P = 0.603). No patients developed adhesive otitis media. Between the preoperative and postoperative measurements, the mean air-bone gap improved by 10.2 ± 2.8 dB in the TPME group and 11.6 ± 0.7 dB in the NTPME group; this was significant (P < 0.001) in both groups. CONCLUSIONS: Endoscopic cartilage underlay myringoplasty NTPME shorted the operation time and avoided aural fullness and EAC discomfort compared with the TPME technique; however, graft success and hearing improvement were comparable between the two techniques for repairing large perforations in children.

Prognostic factors for resected cases with gallbladder carcinoma: A systematic review and meta-analysis.

OBJECTIVE: Current meta-analysis was performed to systematically evaluate the potential prognostic factors for overall survival (OS) among resected cases with gallbladder carcinoma (GBC). METHODS: PubMed, EMBASE, and the Cochrane Library were systematically retrieved and hazard ratio (HR) and its 95% confidence interval (CI) were directly extracted from the original study or roughly estimated via Tierney's method. Standard Parmar modifications were used to determine pooled HRs. RESULTS: A total of 36 studies with 11502 cases were identified. Pooled results of univariate analyses indicated that advanced age (HR=1.02, P =0.00020), concurrent gallstone disease (HR=1.22, P =0.00200), elevated preoperative CA199 level (HR=1.93, P <0.00001), advanced T stage (HR=3.09, P <0.00001), lymph node metastasis (HR=2.78, P <0.00001), peri-neural invasion (HR=2.20, P <0.00001), lymph-vascular invasion (HR=2.37, P <0.00001), vascular invasion (HR=2.28, P <0.00001), poorly differentiated tumor (HR=3.22, P <0.00001), hepatic side tumor (HR=1.85, P <0.00001), proximal tumor (neck/cystic duct) (HR=1.78, P <0.00001), combined bile duct resection (HR=1.45, P <0.00001), and positive surgical margin (HR=2.90, P <0.00001) were well-established prognostic factors. Pathological subtypes ( P =0.53000) and postoperative adjuvant chemotherapy ( P =0.70000) were not prognostic factors. Pooled results of multi-variate analyses indicated that age, gallstone disease, preoperative CA199, T stage, lymph node metastasis, peri-neural invasion, lymph-vascular invasion, tumor differentiation status, tumor location (peritoneal side vs hepatic side), surgical margin, combined bile duct resection, and postoperative adjuvant chemotherapy were independent prognostic factors. CONCLUSION: Various prognostic factors have been identified beyond the 8th AJCC staging system. By incorporating these factors into a prognostic model, a more individualized prognostication and treatment regime would be developed. Upcoming multinational studies are required for the further refine and validation.

The prognostic value of combined preoperative PLR and CA19-9 in patients with resectable gallbladder cancer.

The platelet to lymphocyte ratio (PLR) is the marker of host inflammation and it is a potential significant prognostic indicator in various different tumors. The serum carbohydrate antigen 19-9 (CA19-9) is a tumor-associated antigen and it is associated with poor prognosis of gallbladder cancer (GBC). We aimed to analyze the prognostic value of the combination of preoperative PLR and CA19-9 in patients with GBC. A total of 287 GBC patients who underwent curative surgery in our institution was included. To analyze the relationship between PLR and CA19-9 and clinicopathological features. A receiver operating characteristic (ROC) curve was used to identify the optimal cutoff value for PLR and CA19-9. The Kaplan-Meier method was used to estimate the overall survival (OS). Meanwhile, the univariate and multivariate Cox regression models were used to assess the risk factors for OS. The cutoff values of 146.82 and 36.32U/ml defined as high PLR and high CA19-9, respectively. Furthermore, survival analysis showed that patients with PLR > 146.82 and CA19-9 > 36.32 U/ml had a worse prognosis than patients with PLR ≤ 146.82 and CA19-9 ≤ 36.32 U/ml, respectively. The multivariate analysis demonstrated that PLR (hazard ratio (HR) = 1.863, 95% CI: 1.366-2.542, P < 0.001) and CA19-9 (HR = 1.412, 95% CI: 1.021-1.952, P = 0.037) were independent prognostic factors in the GBC patients. When we combined these two parameters, the area under the ROC curve increased from 0.624 (PLR) and 0.661 (CA19-9) to 0.711. In addition, the 1-, 3-, and 5-year OS of group A (patients with PLR ≤ 146.82 and CA19-9 ≤ 36.32 U/ml), group B (patients with either of PLR > 146.82 or CA19-9 > 36.32 U/ml) and group C (patients with PLR > 146.82 and CA19-9 > 36.32 U/ml) were 83.6%, 58.6%, 22.5%, 52.4%, 19.5%, 11.5%, and 42.3%, 11.9%, 0%, respectively. The preoperative PLR and serum CA19-9 are associated with prognosis of patients with GBC. The combination of PLR and CA19-9 may serve as a significant prognostic biomarker for GBC patients superior to either PLR or CA19-9 alone.

Isolation and characterization of seven neovibsane-type diterpenoids from Viburnum odoratissimum and their neuroblastoma cell protective effects.

Seven undescribed neovibsane-type diterpenoids (1-7) were isolated from the leaves of Viburnum odoratissimum. Their planar structures and relative configurations were elucidated based on a combination of 1D and 2D NMR analysis. The absolute configurations were confirmed by Rh2(OCOCF3)4-induced ECD analysis and comparison of experimental and TDDFT-calculated ECD spectrum. Based on the empirical results of the ECD of in situ formed Rh-complexes, rapid determination of the absolute configuration of C-14 within vibsane-type diterpenoids was proposed. In addition, 3 exhibited a high neuroblastoma cell protective effect of 81.8 % at 50 µM (the control group showed a neuroblastoma cell protective effect of 56.2 % at 50 µM).

Additional cartilage reinforcement of the annulus in myringoplasty for subtotal perforation.

OBJECTIVE: In this study, graft success, hearing outcome, and complications were compared following the repair of subtotal perforation using a cartilage reinforcement underlay technique (CRUT) versus the traditional cartilage underlay technique (TCUT). STUDY DESIGN: Randomized controlled trial. MATERIALS AND METHODS: Seventy-six patients with subtotal perforations were prospectively randomized to the CRUT (n = 38) or TCUT (n = 38) group. The graft success rate, hearing outcome, and complications were compared at 12 months. RESULTS: The mean operation time was 32.9 ± 4.2 (range: 26-47) min in the CRUT group and 51.8 ± 6.3 (range: 48-73) min in the TCUT group (P < 0.001). At 12 months postoperatively, no residual perforation was seen in either group. The graft success rate was 94.7 % (36/38) in the CRUT group and 92.1 % (35/38) in the TCUT group; the difference was not significant (P = 0.643). The postoperative air bone gap (ABG) was significantly improved compared to the preoperative value in both groups, without significant between-group differences in either the preoperative (P = 0.741) or postoperative (P = 0.865) ABG or the mean ABG gain (P = 0.812). Additionally, there were no significant between-group differences in the preoperative (P = 0.887) or postoperative (P = 0.753) mean bone-conduction pure tone average. In the TCUT group, seven (18.4 %) patients developed temporary hypogeusia and two (5.3 %) had external auditory canal scarring. Graft cholesteatoma was not observed in either group. CONCLUSION: In the treatment of subtotal perforations, lateral reinforcement of the annulus with additional cartilage is simpler than traditional cartilage underlay for achieving graft and hearing success. The technique also does not involve raising the tympanomeatal flap or removing perforation margins.

Quantitative comparison of three thyroidectomy approaches in neck muscles, voice, and swallowing functions.

OBJECTIVE: This study compares endoscopic thyroidectomy by gasless unilateral axillary approach (ETGUA) and sternocleidomastoid leading-edge approach (SLEA) with conventional open thyroidectomy (COT) in hemithyroidectomy. The main focus is on the protection of neck muscles (sternocleidomastoid, omohyoid, sternothyroid) and the postoperative function of voice and swallowing yielded through these common approaches. METHODS: A total of 302 patients who underwent hemithyroidectomy were enrolled and divided into three groups: ETGUA (n = 101), SLEA (n = 100), and COT (n = 101). Ultrasound was used to measure the thickness of bilateral neck muscles, including the sternocleidomastoid, omohyoid, and sternothyroid. The changes in thickness on the surgical side compared to the non-surgical side. Analyzed factors included muscle thickness changes, Swallowing Impairment Score (SIS), Voice Handicap Index (VHI), Scar Cosmesis Assessment and Rating (SCAR), Neck Injury Index (NII), surgery duration, drainage volume, hospitalization, and number of lymph nodes. RESULTS: The clinical characteristics among the three groups were consistent except for differences in sex, age, and BMI. Metrics such as sternocleidomastoid muscle, NII, hypocalcemia, postoperative PTH, transient hoarseness, and number of lymph nodes showed no significant differences among the three groups. However, significant differences were found in the duration of surgery, drainage volume, hospitalization period omohyoid muscle, Sternohyoid muscle, VHI, SIS, and SCAR (all p < 0.001). CONCLUSION: In comparison to COT, ETGUA and SLEA demonstrate superiority in protecting neck muscles and preserving voice and swallowing function without compromising surgical safety or radicality.

Tailored Polypyrrole Nanofibers as Ion-to-Electron Transduction Membranes for Wearable K+ Sensors.

Conductive polymers are recognized as ideal candidates for the development of noninvasive and wearable sensors for real-time monitoring of potassium ions (K+ ) in sweat to ensure the health of life. However, the low ion-to-electron transduction efficiency and limited active surface area hamper the development of high-performance sensors for low-concentration K+ detection in the sweat. Herein, a wearable K+ sensor is developed by tailoring the nanostructure of polypyrrole (PPy), serving as an ion-to-electron transduction layer, for accurately and stably tracing the K+ fluctuation in human sweat. The PPy nanostructures can be tailored from nanospheres to nanofibers by controlling the supramolecular assembly process during PPy polymerization. Resultantly, the ion-to-electron transduction efficiency (17-fold increase in conductivity) and active surface area (1.3-fold enhancement) are significantly enhanced, accompanied by minimized water layer formation. The optimal PPy nanofibers-based K+ sensor achieved a high sensitivity of 62 mV decade-1 , good selectivity, and solid stability. After being integrated with a temperature sensor, the manufactured wearable sensor realized accurate monitoring of K+ fluctuation in the human sweat.

Comparison of two endoscopic perichondrium-cartilage graft underlay myringoplasty for large perforations: a randomized controlled trial.

OBJECTIVE: The objective of this study was to compare the graft outcomes and complications of two endoscopic perichondrium-cartilage graft techniques for repairing large perforations. STUDY DESIGN: Single center blinded randomized controlled trial. MATERIALS AND METHODS: 61 large perforations more than 50% of TM area were prospectively randomized to undergo the free perichondrium and free cartilage graft group (FPFC, n = 31) or perichondrium partial attachment the cartilage graft group (PPAC, n = 30). The primary outcome measures were the operation time; secondary outcome measures were the graft success rate and hearing gain at 12 months postoperatively and postoperative complications. RESULTS: All patients completed follow-up of 12 months. The mean operation time was 38.2 ± 2.3 min in the FPFC group and 37.4 ± 5.6 min in the PPAC group (P = 0.658). At postoperative 3 months, the graft success rates were 96.7% in the FPFC group and 93.3% in the PPAC group (P = 0.976). At postoperative 12 months, the graft success rates were 96.7% in the FPFC group and 83.3% in the PPAC group (P = 0.182). However, the residual and re-perforation rate with no infection was 0.0% (0/31) in the FPFC group and 16.7% (5/30) in the PPAC group (P = 0.056). No significant between-group differences were observed pre- (P = 0.842) or post- (P = 0.759) operative air bone gap (ABG) values or mean ABG gain (P = 0.886). However, granular myringitis has been noted in 6.5% in the FPFC group and in 3.3% in the PPAC group. CONCLUSIONS: This study suggested that 12-month graft success and hearing gain were comparable between the perichondrium free and partial attachment the cartilage graft techniques, nevertheless, partial attachment technique could increase residual and re-perforations.

The significance of peri-neural invasion in patients with resected hilar cholangiocarcinoma: A single-center experience in China.

BACKGROUND: The significance of peri-neural invasion (PNI) in resected patients with hilar cholangiocarcinoma (HCCA) has been rarely explored. Our study was performed to evaluate the significance of PNI in resected HCCA patients in terms of tumor biological features and long-term survival. METHODS: We retrospectively reviewed surgically-treated HCCA patients between June, 2000 and June 2018. SPSS 25.0 software was used for statistical analysis. RESULTS: A total of 239 resected HCCA patients were included (No. PNI: 138). PNI indicated more aggressive tumor biological features. Major vascular reconstruction was more frequently performed in patients with PNI (34.8% vs 24.8%, P = 0.064). Patients with PNI shared a significantly higher percentage of surgical margin width <5 mm (29.0% vs 16.8%, P = 0.02). The proportion of patients with T1-2 disease (31.2% vs 40.6%, P = 0.085) or I-II disease (21% vs 34.7%, P = 0.014) was significantly lower in patients with PNI. The overall morbidity rate was significantly higher in patients with PNI (P = 0.042). A much worse overall survival (OS) (P = 0.0003) or disease-free survival (DFS) (P = 0.0011) in patients with PNI. Even after matching vital prognostic factors, a significantly worse OS (P = 0.0003) or DFS (P = 0.0002) was still observed in patients with PNI. PNI was an independent prognostic factor in both OS (P = 0.011) and DFS (P = 0.024). CONCLUSION: PNI indicated more aggressive tumor biological features and more advanced tumor stage in patients with resected HCCA. PNI can be an independent prognostic factor in both OS and DFS. Future multi-center studies covering various races or populations are required for further validation.

Outcomes of perichondrium graft covering the epithelium of the tympanic membrane for large-sized perforations: A 3-5-year follow-up study.

OBJECTIVE: The objective of this study was to evaluate the graft outcomes and iatrogenic cholesteatomas for 3 years following cartilage-perichondrium over-underlay technique with perichondrial graft covering the epithelium for large-sized tympanic membrane (TM) perforations. MATERIALS AND METHODS: This prospective case series enrolled patients with large-sized perforation who underwent endoscopic cartilage-perichondrium over-underlay technique. The graft success rate, hearing outcomes, and development of iatrogenic middle ear cholesteatomas and graft cholesteatomas were assessed at 3 years postoperatively. RESULTS: This study included 62 ears of 62 patients. The mean follow-up duration was 47.3 ± 10.8 (38-64) months. Neovascularization was observed in the lateral perichondrium graft in 55 (88.7 %) patients, which inosculated into the TM remnant at 4-5 weeks. However, graft neovascularization was not observed in the four patients with excessive perichondrium graft that migrated into the external auditory canal and the three patients with middle ear infections. The graft failure rate was 6.5 % at 6 months, 11.3 % at 12 months, 6.5 % at 24 months, and the overall graft success rate was 91.8 % at the last follow-up. Granular myringitis developed in 11.3 % (7/62) of the patients. High-resolution computed tomography revealed well-pneumatized mastoids and middle ear at the final follow-up. However, graft cholesteatomas were observed in 3 (4.8 %) patients at 7-24 months postoperatively. CONCLUSIONS: The cartilage-perichondrium over-underlay technique with perichondrial graft covering TM epithelium is safe and effective for the repair of large perforations, with good short- and long-term graft outcomes, minimal risk of graft cholesteatoma development, and no risk of iatrogenic middle ear cholesteatomas.

Meta-analysis of prognostic factors for overall survival and disease-free survival among resected patients with combined hepatocellular carcinoma and cholangiocarcinoma.

BACKGROUND: Combined hepatocellular carcinoma and cholangiocarcinoma (CHCC-CC) is a rare subtype of primary liver malignancy and has been treated equally as intra-hepatic cholangiocarcinoma (IHCC) according to the 8th AJCC staging system. Owing to its rarity, its prognostic factors have been rarely explored and defined. METHODS: PubMed, EMBASE, the Cochrane Library and Web of Science were searched up till January 1st, 2023 and eligible studies were restricted to studies reported prognostic factors of resected CHCC-CC. Standard Parmar modifications were used to determine pooled univariable hazard ratios (HRs). RESULTS: A total of eleven studies with 1286 patients with resected classical CHCC-CC were finally included. Pooled results indicated that serum tumor biomarkers, including AFP, CA199, and CEA, were prognostic factors for postoperative overall survival (OS) and disease-free survival (DFS). Moreover, liver cirrhosis (P = 0.010), HBV infection (P = 0.030), and HCV infection (P < 0.001) were prognostic factors for OS. Age (HR = 1.03, P = 0.005) was a prognostic factor for DFS. Tumor size (OS: HR = 2, P < 0.001, DFS: HR = 2.15, P < 0.001), tumor number (OS: HR = 2.05, P < 0.001; DFS: HR = 1.96, P = 0.006), surgical margin (OS: HR = 2.33, <0.001001; DFS: HR = 2.35, P < 0.001), node metastasis (OS: HR = 2.96, P < 0.001; DFS: HR = 2.1, P < 0.001), vascular invasion (OS: HR = 2.17, P < 0.001; DFS: HR = 2.64, P < 0.001), and postoperative prophylactic trans-arterial chemotherapy embolization (PPTACE) (OS: HR = 1.67, P = 0.04; DFS: HR = 2.31, P < 0.001) were common prognostic factors for OS and DFS. CONCLUSION: Various risk factors unmentioned in the 8th AJCC staging system were identified. These promising findings would facilitate a more personalized predictive model and help clinicians to stratify patients with different survival outcomes.

Prognostic Significance of Tumor Necrosis in Patients with Gallbladder Carcinoma Undergoing Curative-Intent Resection.

BACKGROUND: Tumor necrosis has been indicated to correlate with dismal survival outcomes of a variety of solid tumors. However, the significance and prognostic value of tumor necrosis remain unclear in gallbladder carcinoma. The aim of this research is to explore the relationships between necrosis with long-term survival and tumor-related biological characteristics of patients with gallbladder carcinoma. PATIENTS AND METHODS: Patients with gallbladder carcinoma who accepted curative-intent resection in West China Hospital of Sichuan University (China) between January 2010 and December 2021 were retrospectively analyzed. Tumor necrosis was determined by staining the patient's original tissue sections with hematoxylin and eosin. Based on the presence of tumor necrosis, the pathologic features and survival outcomes were compared. RESULTS: This study enrolled 213 patients with gallbladder carcinoma who underwent curative-intent surgery, of whom 89 had tumor necrosis. Comparative analyses indicated that patients with tumor necrosis had more aggressive clinicopathological features, such as larger tumor size (p = 0.002), poorer tumor differentiation (p = 0.029), more frequent vascular invasion (p < 0.001), presence of lymph node metastasis (p = 0.014), and higher tumor status (p = 0.01), and experienced poorer survival. Univariate and multivariate analyses revealed that tumor necrosis was an independent prognostic factor for overall survival (multivariate: HR 1.651, p = 0.026) and disease-free survival (multivariate: HR 1.589, p = 0.040). CONCLUSIONS: Tumor necrosis can be considered as an independent predictive factor for overall survival and disease-free survival among individuals with gallbladder carcinoma, which was a valuable pathologic parameter.

Comparison of temporalis fascia and cartilage graft over-under myringoplasty for repairing large perforations.

OBJECTIVE: The objective of this study was to compare the operation time, graft success, audiometric outcomes and complications of over-under technique using a temporalis fascia (TMF) and cartilage grafts for the repair of large perforations. STUDY DESIGN: Randomized controlled trial. MATERIALS AND METHODS: 80 large perforations >2 quadrants of eardrum were prospectively randomized to undergo TMF over-under technique group (TFON, n = 40) or cartilage-perichondrium over-under technique group (CPON, n = 40). The graft success rate, audiometric outcomes, and complications were compared among two groups at 12 months. RESULTS: The mean operation time was 56.8 ± 4.2 (range:52-71) min in the TFON group and 37.9 ± 2.8 (range: 31-47) min in the CPON group (P < 0.001). The lost follow-up rate was 3 (7.5 %) patients in the TFON group and 2 (5.0 %) patient in the CPON group (P = 0.644). Finally, 37 patients in the TFON group and 38 patients in the CPON group were included in this study. The graft infection rate was 2 (5.4 %) patients in the TFON group and 2 (5.3 %) patient in the CPON group (P = 0.626), all the graft infection resulted in the residual perforation. The remaining residual perforation was 2 (5.4 %) patients in the TFON group and 1 (2.6 %) patient in the CPON group; the re-perforation was 3 (8.1 %) patients in the TFON group and 0 (0.0 %) patient in the CPON group. The graft success rate was 81.1 % (30/37) patients in the TFON group and 92.1 % (35/38) patient in the CPON group. The mean preoperative and 12-month postoperative ABGs were significantly different in any group (P < 0.01). However, there were no significant difference among two groups regardless of pre-or post-ABGs or ABG closure. No lateralization of the graft or blunting was noted in any group. Four (10.8 %)patients developed atelectasis and one (2.7 %) developed the EAC scarring in the TFON group. Graft cholesteatomas was found in 2 (5.4 %) patients in the TFON group and in 5 (13.2 %) patients in the CPON group (P = 0.449). Three (8.1 %) patients had temporary hypogeusia in the TFON group. CONCLUSION: Although temporalis fascia graft over-under technique obtained similar graft success rates and hearing outcomes for large chronic perforations to the cartilage-perichondrium over-under technique, temporalis fascia graft technique prolonged the operation time and increased the re-perforation and graft atelectasis. Nevertheless, the graft cholesteatomas were comparable among two techniques.

Comparative analyses between radically re-resected incidental gallbladder carcinoma and primary radically resected gallbladder carcinoma: a single-center experience in China.

PURPOSES: The current study was performed to comparatively evaluate the similarities and differences between cases with radically re-resected incidental gallbladder carcinoma (RRIGBC) and those with primary radically resected gallbladder carcinoma (PRGBC). METHODS: Comparative analysis between patients with RRIGBC and those with PRGBC were performed in terms of clinic-pathological features and long-terms survival. RESULTS: A total of 330 surgically treated GBC patients with 110 patients with IGBC were identified. PRGBCs were generally in a more advanced tumor stage, sharing more aggressive tumor biological features and worse prognosis than those with RRIGBC. Subgroup analyses indicated a comparable prognosis among T1-2 patients between RRIGBC and PRGBC groups. However, among T3-4 patients, patients in the PRGBC group shared a much worse prognosis. Moreover, IGBC itself can be regarded as a prognostic factor but cannot be regarded as an independent prognostic factor. It is the tumor stage which really determined the overall prognosis. CONCLUSION: Patients with RRIGBC were generally in a much earlier tumor stage and shared a much better prognosis than those with PRGBC. IGBC itself can be regarded as a prognostic factor but cannot be regarded as the independent prognostic factors. It is the tumor stage which really determine the overall prognosis.

Role of topical antibiotic ointment in the lateral graft following underlay myringoplasty: a prospective randomised study.

OBJECTIVE: The objective of this study was to compare the graft outcome and postoperative infection of with and without the use of antibiotic ointment following myringoplasty for the treatment of chronic perforations. STUDY DESIGN: Randomized controlled trial. MATERIAL AND METHODS: 135 chronic perforations were prospectively randomized to use of antibiotic ointment group (UAO, n = 68) or no use of antibiotic ointment group (NAO, n = 67) following myringoplasty. The graft outcomes and postoperative infection were compared among two groups at 6 months. RESULTS: At postoperative 6 months, the graft infection rate was 4.4% in the UAO group and 10.4% in the NAO group, the difference was not significant (P = 0.312).The graft success rates were 92.6% in the UAO group and 91.0% in the NAO group, the difference was not significant (P = 0.979). In the UAO group, 3 patients with purulence ear discharge resulted in a residual perforation although they received ofloxacin ear drops and intravenous antibiotic therapy treatment. In the NAO group, 6 patients with purulence ear discharge resulted in a residual perforation, only one, with mild purulence discharge was successfully treated and closed. In addition, no significant between-group differences were observed pre- (P = 0.746) or post- (P = 0.521) operative air bone gap (ABG) values or mean ABG gain (P = 0.745). However, granular myringitis with minimal moistness but without infection has been noted in 3 (4.4%) patients in the UAO group and in 5 (7.5%) in the NAO group, the difference was not significant (P = 0.699). CONCLUSIONS: Use and non-use of antibiotic ointments for lateral packing of graft are both comparable methods following myringoplasty for postoperative infection and graft outcomes.

DNA damage repair mutations in pancreatic cancer- prognostic or predictive?

Objective: The efficacy of platinum-based chemotherapy (PtCh) for pancreatic cancer (PC) patients with DNA damage repair gene mutations (DDRm) compared to those without DDRm remains uncertain. Methods: After a thorough database searching in PubMed, Embase, and Web of Science, a total of 19 studies that met all the inclusion criteria were identified. The primary outcomes were overall survival (OS) and progression-free survival (PFS) for PC patients with DDRm versus those without DDRm after PtCh. Results: Patients with advanced-stage PC who have DDRm tend to have longer OS compared to patients without DDRm, regardless of their exposure to PtCh (HR=0.63; I2 = 66%). Further analyses indicated that the effectiveness of PtCh for OS was modified by DDRm (HR=0.48; I2 = 59%). After the first- line PtCh (1L-PtCh), the PFS of advanced-stage PC with DDRm was also significantly improved (HR=0.41; I2 = 0%). For patients with resected PC, regardless of their exposure to PtCh, the OS for patients with DDRm was comparable to those without DDRm (HR=0.82; I2 = 71%). Specifically, for patients with resected PC harboring DDRm who received PtCh (HR=0.85; I2 = 65%) and for those after non-PtCh (HR=0.87; I2 = 0%), the presence of DDRm did not show a significant association with longer OS. Conclusion: 1L-PtCh treatment is correlated with favorable survival for advanced-stage PC patients with DDRm. For resected-stage PC harboring DDRm, adjuvant PtCh had limited effectiveness. The prognostic value of DDRm needs to be further verified by prospective randomized controlled trials. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42022302275.