Preoperative albumin-bilirubin score and liver resection percentage determine postoperative liver regeneration after partial hepatectomy.

BACKGROUND: The success of liver resection relies on the ability of the remnant liver to regenerate. Most of the knowledge regarding the pathophysiological basis of liver regeneration comes from rodent studies, and data on humans are scarce. Additionally, there is limited knowledge about the preoperative factors that influence postoperative regeneration. AIM: To quantify postoperative remnant liver volume by the latest volumetric software and investigate perioperative factors that affect posthepatectomy liver regeneration. METHODS: A total of 268 patients who received partial hepatectomy were enrolled. Patients were grouped into right hepatectomy/trisegmentectomy (RH/Tri), left hepatectomy (LH), segmentectomy (Seg), and subsegmentectomy/nonanatomical hepatectomy (Sub/Non) groups. The regeneration index (RI) and late regeneration rate were defined as (postoperative liver volume)/[total functional liver volume (TFLV)] × 100 and (RI at 6-months - RI at 3-months)/RI at 6-months, respectively. The lower 25th percentile of RI and the higher 25th percentile of late regeneration rate in each group were defined as "low regeneration" and "delayed regeneration". "Restoration to the original size" was defined as regeneration of the liver volume by more than 90% of the TFLV at 12 months postsurgery. RESULTS: The numbers of patients in the RH/Tri, LH, Seg, and Sub/Non groups were 41, 53, 99 and 75, respectively. The RI plateaued at 3 months in the LH, Seg, and Sub/Non groups, whereas the RI increased until 12 months in the RH/Tri group. According to our multivariate analysis, the preoperative albumin-bilirubin (ALBI) score was an independent factor for low regeneration at 3 months [odds ratio (OR) 95%CI = 2.80 (1.17-6.69), P = 0.02; per 1.0 up] and 12 months [OR = 2.27 (1.01-5.09), P = 0.04; per 1.0 up]. Multivariate analysis revealed that only liver resection percentage [OR = 1.03 (1.00-1.05), P = 0.04] was associated with delayed regeneration. Furthermore, multivariate analysis demonstrated that the preoperative ALBI score [OR = 2.63 (1.00-1.05), P = 0.02; per 1.0 up] and liver resection percentage [OR = 1.02 (1.00-1.05), P = 0.04; per 1.0 up] were found to be independent risk factors associated with volume restoration failure. CONCLUSION: Liver regeneration posthepatectomy was determined by the resection percentage and preoperative ALBI score. This knowledge helps surgeons decide the timing and type of rehepatectomy for recurrent cases.

Aberrant Glycosylation in Pancreatic Ductal Adenocarcinoma 3D Organoids Is Mediated by KRAS Mutations.

Aberrant glycosylation in tumor cells is a hallmark during carcinogenesis. KRAS gene mutations are the most well-known oncogenic abnormalities but their association with glycan alterations in pancreatic ductal adenocarcinoma (PDAC) is largely unknown. We employed patient-derived 3D organoids to culture pure live PDAC cells, excluding contamination by fibroblasts and immune cells, to gasp the comprehensive cancer cell surface glycan expression profile using lectin microarray and transcriptomic analyses. Surgical specimens from 24 PDAC patients were digested and embedded into a 3D culture system. Surface-bound glycans of 3D organoids were analyzed by high-density, 96-lectin microarrays. KRAS mutation status and expression of various glycosyltransferases were analyzed by RNA-seq. We successfully established 16 3D organoids: 14 PDAC, 1 intraductal papillary mucinous neoplasm (IPMN), and 1 normal pancreatic duct. KRAS was mutated in 13 (7 G12V, 5 G12D, 1 Q61L) and wild in 3 organoids (1 normal duct, 1 IPMN, 1 PDAC). Lectin reactivity of AAL (Aleuria aurantia) and AOL (Aspergillus oryzae) with binding activity to α1-3 fucose was higher in organoids with KRAS mutants than those with KRAS wild-type. FUT6 (α1-3fucosyltransferase 6) and FUT3 (α1-3/4 fucosyltransferase 3) expression was also higher in KRAS mutants than wild-type. Meanwhile, mannose-binding lectin (rRSL [Ralstonia solanacearum] and rBC2LA [Burkholderia cenocepacia]) signals were higher while those of galactose-binding lectins (rGal3C and rCGL2) were lower in the KRAS mutants. We demonstrated here that PDAC 3D-cultured organoids with KRAS mutations were dominantly covered in increased fucosylated glycans, pointing towards novel treatment targets and/or tumor markers.

Hypoxia at 3D organoid establishment selects essential subclones within heterogenous pancreatic cancer.

Pancreatic ductal adenocarcinoma (PDAC) is especially hypoxic and composed of heterogeneous cell populations containing hypoxia-adapted cells. Hypoxia as a microenvironment of PDAC is known to cause epithelial-mesenchymal transition (EMT) and resistance to therapy. Therefore, cells adapted to hypoxia possess malignant traits that should be targeted for therapy. However, current 3D organoid culture systems are usually cultured under normoxia, losing hypoxia-adapted cells due to selectivity bias at the time of organoid establishment. To overcome any potential selection bias, we focused on oxygen concentration during the establishment of 3D organoids. We subjected identical PDAC surgical samples to normoxia (O2 20%) or hypoxia (O2 1%), yielding glandular and solid organoid morphology, respectively. Pancreatic cancer organoids established under hypoxia displayed higher expression of EMT-related proteins, a Moffitt basal-like subtype transcriptome, and higher 5-FU resistance in contrast to organoids established under normoxia. We suggest that hypoxia during organoid establishment efficiently selects for hypoxia-adapted cells possibly responsible for PDAC malignant traits, facilitating a fundamental source for elucidating and developing new treatment strategies against PDAC.

Evaluation of the risk of diarrhea induced by epidermal growth factor receptor tyrosine kinase inhibitors with cultured intestinal stem cells originated from crypts in humans and monkeys.

Severe diarrhea is a common side effect of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs). We aimed to evaluate the risk of EGFR-TKI-induced diarrhea using spheroids of human and monkey crypt-derived intestinal stem cells. Intestinal spheroids exhibited higher toxic susceptibility to EGFR-TKIs than Caco-2 cells. As concentration of EGFR-TKIs increased, cellular ATP first decreased relative to the control condition, followed by an increase in LDH release, in contrast with their simultaneous changes with traditional cytotoxic anticancer drugs. The toxic sensitivity of spheroids to various EGFR-TKIs corresponded to clinical diarrhea incidence. Afatinib, a second-generation EGFR-TKI, exhibited higher toxic sensitivity compared with the first-generation ones, corresponding to the clinical evidence that afatinib-induced diarrhea is almost inevitable and severe. By contrast, the third-generation osimertinib, which reduces the risk of diarrhea, showed mitigated cytotoxicity compared with afatinib. For irreversible EGFR-TKIs, the decreased ATP level persisted or its recovery was delayed even after drug removal compared with reversible ones. Furthermore, the highest drug accumulation in spheroids (TKIspheroids) and inhibition potency against EGFR (TKIspheroids/Ki) were observed for afatinib. This system would be useful for predicting the risk of EGFR-TKI-induced diarrhea; moreover, on-target cytotoxicity against intestinal stem cells might contribute to clinically observed diarrhea.

Total Superior Mesenteric Artery Nerve Plexus Preservation During Pancreaticoduodenectomy for Pancreatic Cancer.

BACKGROUND: Superior mesenteric artery (SMA) nerve plexus (PLsma) dissection has been performed to achieve R0 resection in pancreaticoduodenectomy (PD) for pancreatic ductal adenocarcinoma (PDAC) in high-volume centers. However, full-extent PLsma preservation in PD is employed in our institution. The feasibility of the PLsma preservation strategy was investigated. METHODS: Between January 2010 and December 2020, 156 patients underwent PLsma preservation PD for PDAC at our institution. Of these, 118 patients had resectable PDAC (R group) and 38 patients had borderline resectable artery (BR-A group). Clinical and oncological outcomes focusing on local recurrence, patient prognoses, and morbidities (including postoperative refractory diarrhea) were retrospectively analyzed and our postoperative outcomes were compared with those of other institutions. RESULTS: Pathological R0 resection by PLsma preservation PD was achieved in 96 R group patients (81.4%) and 27 BR-A group patients (71.1%). The median postoperative hospital stay was 15.0 days in both groups. Local site-only recurrence was observed in 10.2% (12/118) of R-group and 10.5% (4/38) of BR-A-group patients, whereas distant site-only recurrence occurred in 21.2% (25/118) of R-group and 28.9% (11/38) of BR-A-group patients. Median survival times were 64.3 months (R group) and 35.4 months (BR-A group, p = 0.07). Median disease-free survival (DFS) times were 31.0 months (R group) and 12.0 months (BR-A group). No diarrhea requiring opioids was observed in either group. These results were equal or superior to those of PLsma dissection PD in other institutions. CONCLUSIONS: PLsma preservation in PD was feasible compared to PLsma dissection in recurrence and overall survival.

Triple modal treatment comprising with proton beam radiation, hyperthermia, and gemcitabine/nab-paclitaxel for locally advanced pancreatic cancer: a phase I/II study protocol (TT-LAP trial).

BACKGROUND: Locally advanced pancreatic ductal adenocarcinoma (PDAC), accounting for about 30% of PDAC patients, is difficult to cure by radical resection or systemic chemotherapy alone. A multidisciplinary strategy is required and our TT-LAP trial aims to evaluate whether triple-modal treatment with proton beam therapy (PBT), hyperthermia, and gemcitabine plus nab-paclitaxel is a safe and synergistically effective treatment for patients with locally advanced PDAC. METHODS: This trial is an interventional, open-label, non-randomized, single-center, single-arm phase I/II clinical trial organized and sponsored by the University of Tsukuba. Eligible patients who are diagnosed with locally advanced pancreatic cancer, including both borderline resectable (BR) and unresectable locally advanced (UR-LA) patients, and selected according to the inclusion and exclusion criteria will receive triple-modal treatment consisting of chemotherapy, hyperthermia, and proton beam radiation. Treatment induction will include 2 cycles of chemotherapy (gemcitabine plus nab-paclitaxel), proton beam therapy, and 6 total sessions of hyperthermia therapy. The initial 5 patients will move to phase II after adverse events are verified by a monitoring committee and safety is ensured. The primary endpoint is 2-year survival rate while secondary endpoints include adverse event rate, treatment completion rate, response rate, progression-free survival, overall survival, resection rate, pathologic response rate, and R0 (no pathologic cancer remnants) rate. The target sample size is set at 30 cases. DISCUSSION: The TT-LAP trial is the first to evaluate the safety and effectiveness (phases1/2) of triple-modal treatment comprised of proton beam therapy, hyperthermia, and gemcitabine/nab-paclitaxel for locally advanced pancreatic cancer. ETHICS AND DISSEMINATION: This protocol was approved by the Tsukuba University Clinical Research Review Board (reference number TCRB22-007). Results will be analyzed after study recruitment and follow-up are completed. Results will be presented at international meetings of interest in pancreatic cancer plus gastrointestinal, hepatobiliary, and pancreatic surgeries and published in peer-reviewed journals. TRIAL REGISTRATION: Japan Registry of Clinical Trials, jRCTs031220160. Registered 24 th June 2022, https://jrct.niph.go.jp/en-latest-detail/jRCTs031220160 .

Novel positron emission tomography imaging targeting cell surface glycans for pancreatic cancer: 18 F-labeled rBC2LCN lectin.

Advancement in early detection modalities will greatly improve the overall prognoses of pancreatic ductal adenocarcinoma (PDAC). For this purpose, we report a novel class of tumor-specific probes for positron emission tomography (PET) based on targeting cell surface glycans. The PDAC-targeting ability of rBC2LCN lectin, combined with fluorine-18 (18 F) ([18 F]FB-rBC2LCN), resulted in reproducible, high-contrast PET imaging of tumors in a PDAC xenograft mouse model. [18 F]N-succinimidyl-4-fluorobenzoate ([18 F]SFB) was conjugated to rBC2LCN, and [18 F]FB-rBC2LCN was successfully prepared with a radiochemical purity >95%. Cell binding and uptake revealed that [18 F]FB-rBC2LCN binds to H-type-3-positive Capan-1 pancreatic cancer cells. As early as 60 min after [18 F]FB-rBC2LCN (0.34 ± 0.15 MBq) injection into the tail vein of nude mice subcutaneously bearing Capan-1 tumors, tumor uptake was high (6.6 ± 1.8 %ID/g), and the uptake increased over time (8.8 ± 1.9 %ID/g and 11 ± 3.2 %ID/g at 150 and 240 min after injection, respectively). Tumor-to-muscle ratios increased over time, up to 19 ± 1.8 at 360 min. High-contrast PET imaging of tumors relative to background muscle was also achieved as early as 60 min after injection of [18 F]FB-rBC2LCN (0.66 ± 0.12 MBq) and continued to increase up to 240 min. Our 18 F-labeled rBC2LCN lectin warrants further clinical development to improve the accuracy and sensitivity of early-stage pancreatic cancer detection.

Clinical advantage of transmediastinal esophagectomy in terms of postoperative respiratory complications.

BACKGROUND: Although the transmediastinal approach as a radical esophagectomy for esophageal carcinoma patients has attracted attention, its advantages over the transthoracic approach remain unclear. This study aimed to evaluate the efficacy of transmediastinal esophagectomy (TME) in terms of postoperative respiratory complications compared to that of open transthoracic esophagectomy (TTE). METHODS: We reviewed patients with thoracic and abdominal esophageal carcinoma who underwent TME or TTE between February 2014 and November 2021. We compared postoperative respiratory complications as the primary outcome. The secondary outcomes included perioperative operation time, blood loss, postoperative complications, and the number of harvested mediastinal lymph nodes. RESULTS: Overall, 60 and 54 patients underwent TME and TTE, respectively. The baseline characteristics were similar between the two groups, except for age and histological type. There were no intraoperative lethal complications in either group. The incidence of respiratory complications was significantly lower in the TME group than in the TTE group (6.7 vs. 22.2%, p = 0.03). The TME group had a shorter operation time (403 vs. 451 min, p < 0.01), less blood loss (107 vs. 253 mL, p < 0.01), and slightly higher anastomotic leakage (11.7 vs. 5.6%, p = 0.33). The number of harvested lymph nodes was similar in both groups (24 vs. 26, p = 0.10). Multivariate analysis revealed that TME is an independent factor in reducing respiratory complications (odds ratio = 0.27, p = 0.04). CONCLUSIONS: TME for esophageal carcinoma was performed safely. TME was superior to TTE in terms of postoperative respiratory complications; however, the relatively higher frequency of anastomotic leakage should be considered and requires further evaluation.

DBU-intercalated γ-titanium phosphate as a latent thermal catalyst in the reaction of glycidyl phenyl ether (GPE) and hexahydro-4-methylphthalic anhydride (MHHPA).

The capabilities and performance of γ-titanium phosphate (γ-TiP) with 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) as a latent thermal catalyst were investigated by the copolymerization of glycidyl phenyl ether (GPE) and hexahydro-4-methylphthalic anhydride (MHHPA) at different temperatures for a period of one hour. Polymerization was not observed until the reactants were heated to 100 °C. Upon increasing the temperature to 120 °C, the conversion in the presence of γ-TiP·DBU as a catalyst showed 98% conversion in 1 h. The thermal stability of GPE and MHHPA reacted in the presence of γ-TiP·DBU at 40 °C for 144 h resulted in less than 7% conversion of GPE. The conversion of GPE did not show a significant increase at 40 °C.

Culture of circulating tumor cells using a microfilter device.

Circulating tumor cells (CTCs) are associated with cancer metastasis and prognosis but their scarcity in whole blood prevents their use as a diagnostic tool. The purpose of the present study was to establish a novel approach to capture and cultivate CTCs using a microfilter device. The present study was a prospective study of patients with pancreatic cancer at the University of Tsukuba Hospital (Tsukuba, Japan). From each patient, 5 ml of whole blood was collected into an EDTA collection tube. Whole blood was filtered to isolate CTCs and cells captured on the microfilter were cultured in place. A total of 15 patients were enrolled. CTCs and/or CTC clusters were detected in 2 of 6 cases on day 0. In all cases, CTCs and/or formed clusters and/or colonies were observed during long­term culture periods of up to 103 days. In samples where CTCs were not immediately evident, CTC clusters and colonies emerged after long­term culture. To confirm activity of the cultured CTCs on the filters, staining with Calcein AM was performed and epithelial cellular adhesion molecule­positive cells were observed. The system enables the capture and culture of CTCs. Cultured CTCs may be used for patient­specific drug susceptibility testing and genomic profiling of cancer.

Well-concealed advanced duodenal carcinoma with Muir-Torre syndrome: a case report and review of literature.

BACKGROUND: Muir-Torre syndrome is an autosomal-dominant mutation in mismatch repair genes that gives rise to sebaceous tumors and visceral malignancies over time. Because colorectal and genitourinary cancers are common in Muir-Torre syndrome, duodenal carcinoma diagnoses are often delayed. CASE PRESENTATION: A 58-year-old woman presented with severe emaciation, anorexia, and upper abdominal pain. She had a history of rectal carcinoma, ascending colon carcinoma, and a right shoulder sebaceous carcinoma. Upper gastrointestinal endoscopy and computed tomography examinations suggested duodenal obstruction due to superior mesenteric artery syndrome, leading to long-term observation. Seven months later, she was finally diagnosed with duodenal carcinoma of the third portion. As the papilla of Vater was preservable due to tumor location, she received a partial duodenectomy in lieu of a pancreatoduodenectomy. Pathologically, the tumor was a well-differentiated adenocarcinoma with a classification of T3N0M0 Stage IIA (UICC, 8th edition). The postoperative course was uneventful and her appetite returned. A mutation in mismatch repair gene MSH2 confirmed the diagnosis of Muir-Torre syndrome genetically. Three years later, her nutritional status has fully recovered and she is free from both recurrence and metastasis. CONCLUSION: In patients with comorbid skin sebaceous tumors and gastrointestinal malignancies, genetic screening is strongly recommended. Patients with Muir-Torre syndrome require long-term follow-up, and function-preserving treatment is desirable.

rBC2LCN-reactive SERPINA3 is a glycobiomarker candidate for pancreatic ductal adenocarcinoma.

Early detection is urgently needed to improve the patient's pancreatic ductal adenocarcinoma (PDAC) survival. Previously, we identified a novel tumor-associated glycan, H-type3, which is expressed on PDAC cells and is detected by rBC2LCN (recombinant N-terminal domain of BC2L-C identified from Burkholderia cenocepacia) lectin. Here, we identified that SERPINA3 is an rBC2LCN-reactive glycoprotein (BC2-S3) secreted from PDAC cells into the blood in patients with PDAC by liquid chromatography-tandem mass spectrometry analysis and lectin blotting. In immune staining, BC2-S3 was detected specifically in the tumor but not in normal tissues of PDAC. Lectin-ELISA was then developed to measure the serum level of BC2-S3 in healthy control (HC, n = 99) and patients with PDAC (n = 88). BC2-S3 exhibited higher in patients with PDAC than in those with HC. BC2-S3 showed similar diagnostic performance in all stages of PDAC (stages IA-IV, true positive rate = 76.1%, true negative rate = 81.8%) to CA19-9 (72.7%, 75.8%). Remarkably, BC2-S3 showed a significantly higher detection rate (89.7%) for early stage PDAC (IA-IIA) than CA19-9 (62.1%, P = 0.029). The combination of BC2-S3 and CA19-9 further improved the diagnostic ability for all stages of PDAC (81.8%, 87.9%). In conclusion, BC2-S3 is a glycobiomarker candidate for PDAC.

Lectin-based phototherapy targeting cell surface glycans for pancreatic cancer.

Pancreatic ductal adenocarcinoma (PDAC) is resistant to current treatments but lectin-based therapy targeting cell surface glycans could be a promising new horizon. Here, we report a novel lectin-based phototherapy (Lec-PT) that combines the PDAC targeting ability of rBC2LCN lectin to a photoabsorber, IRDye700DX (rBC2-IR700), resulting in a novel and highly specific near-infrared, light-activated, anti-PDAC therapy. Lec-PT cytotoxicity was first verified in vitro with a human PDAC cell line, Capan-1, indicating that rBC2-IR700 is only cytotoxic upon cellular binding and exposure to near-infrared light. The therapeutic efficacy of Lec-PT was subsequently verified in vivo using cell lines and patient-derived, subcutaneous xenografting into nude mice. Significant accumulation of rBC2-IR700 occurs as early as 2 hours postintravenous administration while cytotoxicity is only achieved upon exposure to near-infrared light. Repeated treatments further slowed tumor growth. Lec-PT was also assessed for off-target toxicity in the orthotopic xenograft model. Shielding of intraperitoneal organs from near-infrared light minimized off-target toxicity. Using readily available components, Lec-PT specifically targeted pancreatic cancer with high reproducibility and on-target, inducible toxicity. Rapid clinical development of this method is promising as a new modality for treatment of pancreatic cancer.

Transhiatal bilateral thoracic duct ligation for duplicated thoracic duct injury after esophagectomy: a case report.

BACKGROUND: The treatment of duplicated thoracic ducts (TDs) injury after esophagectomy generally requires a bilateral transthoracic approach. We present the cases of two patients with postoperative chylothorax who underwent transhiatal bilateral TD ligation for duplicated TDs. CASE PRESENTATION: Two patients diagnosed with chylothorax after esophagectomy performed for thoracic esophageal cancer underwent transhiatal TD ligation. Although supradiaphragmatic mass ligation was performed on the fat tissue of the right side of the aorta containing the TD, chyle leakage persisted. To tackle this, the fat tissue of the left side of the aorta was ligated, after which the chyle leakage stopped. CONCLUSION: Compared to the conventional transthoracic approach, the transhiatal approach enables the ligation of both left- and right-sided TD in a single surgical operation, without the need to change the patient's posture. This approach may be appropriate for the treatment of chylothorax after esophagectomy, considering the possibility of duplicated TDs.

Potential Applicability of Local Resection With Prophylactic Left Gastric Artery Basin Dissection for Early-Stage Gastric Cancer in the Upper Third of the Stomach.

PURPOSE: Total or proximal gastrectomy of the upper-third early gastric cancer (u-EGC) often causes severe post-gastrectomy syndrome, suggesting that these procedures are extremely invasive for patients without pathologically positive lymph node (LN) metastasis. This study aimed to evaluate the clinical applicability of a stomach function-preserving surgery, local resection (LR), with prophylactic left gastric artery (LGA)-basin dissection (LGA-BD). MATERIALS AND METHODS: The data of patients with u-EGC (pathologically diagnosed as T1) were retrospectively analyzed. Total gastrectomy was performed in 30 patients, proximal gastrectomy in 45, and subtotal gastrectomy in 6; the LN status was evaluated assuming that the patients had already underwent LR + LGA-BD. This procedure was considered feasible in patients without LN metastases or in patients with cancer in the LGA basin. The reproducibility of the results was also evaluated using an external validation dataset. RESULTS: Of the 82 eligible patients, 79 (96.3%) were cured after undergoing LR + LGA-BD, 74 (90.2%) were pathologically negative for LN metastases, and 5 (6.1%) had LN metastases, but these findings were only observed in the LGA basin. Similarly, of the 406 eligible tumors in the validation dataset, 396 (97.5%) were potentially curative. Tumors in the lesser curvature, post-endoscopic resection status, and small tumors (<20 mm) were considered to be stronger indicators of LR + LGA-BD as all subpopulation cases met our feasibility criteria. CONCLUSIONS: More than 95% of the patients with u-EGC might be eligible for LR + LGA-BD. This function-preserving procedure may contribute to the development of u-EGC without pathological LN metastases, especially for tumors located at the lesser curvature.

Pancreatic juice outflow in pancreatojejunostomy monitoring with the inter-anastomosis drainage tube; a retrospective observational study.

BACKGROUND: Pancreatic fistula remains the biggest problem in pancreatic surgery. We have previously reported a new pancreatojejunostomy method using an inter-anastomosis drainage (IAD) suction tube with Blumgart anastomosis for drainage of the pancreatic juice leaking from the branched pancreatic ducts. This study aimed to evaluate the postoperative outcomes of our novel method, in pancreatojejunostomy and investigate the nature of the inter-anastomosis space between jejunal wall and pancreas parenchyma. METHODS: This retrospectively study consist of 282 pancreatoduodenectomy cases, including 86 reconstructions via the Blumgart method plus IAD (B + IAD group) and 196 cases reconstructed using the Blumgart method alone (B group). Postoperative outcomes and the amylase value and the volume of the drainage fluids were compared between the two groups. The IAD tube was placed to collect amylase-rich fluid from the inter-anastomosis space during operative procedure between the jejunal wall and pancreatic stump. RESULTS: The daily IAD drainage volume and the amylase level was significantly higher in patients with a soft pancreas (vs hard pancreas; 16.5 vs. 10.0 mL/day, p = 0.012; 90,900 vs. 1634 IU/L, p < 0.001, respectively). The mean amylase value of IAD collection in 86 cases of B + IAD group was 63,100 IU/L. The incidence of clinically relevant pancreatic fistula grade B and C (23.2% vs. 23.0%, p = 0.55) and the hospital stay was similar between the groups (median 17 vs. 18 days, p = 0.55). In 176 patients with soft pancreas, the incidence of pancreatic fistula grade B and C (33.3% vs. 35.3%, p = 0.67) and the hospital stay was also similar between the groups (median 22.5 vs. 21 days, p = 0.81). CONCLUSIONS: Positive effect of the IAD method observed in the pilot cases was not reproduced in the current study. IAD tube objectively demonstrated the existence of amylase-rich discharge at the anastomosis site, and countermeasures to eliminate this liquid are highly desired for preventing pancreatic fistula, especially in patients with soft pancreatic texture. Trial registration Retrospectively registered.

Prevalence of work-related musculoskeletal disorders among general surgeons in Japan.

PURPOSE: General surgeons are at high risk for work-related musculoskeletal disorders (WRMSDs), especially in their neck and back. The prevalence and risk factors for surgeons' WRMSDs in Japan have not been well surveyed. METHODS: A cross-sectional questionnaire survey on WRMSDs was conducted among general surgeons in Japan. Surgeons were asked about the presence and degree of neck, shoulder, and back disability in relation to open and laparoscopic surgery. RESULTS: The questionnaire was sent to 174 general surgeons in 21 hospitals and 106 (60.9%) responded. The prevalence of WRMSDs in the last month was 65.1%, and the prevalence at least once in a lifetime was 79.2%. The rate of WRMSDs of the neck and back was higher after open surgery (44.3%, 42.5%) than after laparoscopic surgery (28.2%, 31.1%), but there was no marked difference in shoulder pain. Age was the strongest risk factor for WRMSDs, and the pain scores, prevalence of chronic pain, and rate of WRMSD-related absence from work tended to increase with age. CONCLUSION: A questionnaire survey of surgeons in Japan showed that about 80% of surgeons suffer from WRMSDs. Countermeasures for WRMSDs among surgeons are urgently desired to ensure that limited numbers of surgeons work in the operating theatre throughout their career. CLINICAL TRIAL REGISTRATION: Registry name: a survey of surgeons' musculoskeletal pain associated with performing surgery. University of Tsukuba Institutional Review Board registration number: 1519.

Glycan expression profile of signet ring cell gastric cancer cells and potential applicability of rBC2LCN-targeted lectin drug conjugate therapy.

BACKGROUND: Signet ring cell carcinoma (SRC) is a distinct subtype of gastric cancer (GC); however, the specific characteristics of cancer cell surface glycans and glycosylation remain unclear. In this study, we investigated SRC-specific glycans using lectin microarray and evaluated the potential applicability of a glycan-targeting therapy. METHODS: SRC cell lines (NUGC-4 and KATO-III) and non-SRC (NSRC) cell lines (NCI-N87, SNU-1, and MKN-45) were subjected to lectin microarray analysis to identify the SRC-specific glycans. Additionally, we performed immunohistochemical lectin staining and evaluated the anti-tumor effects of lectin drug conjugates (LDCs) using high-affinity lectins for SRC. RESULTS: Among the 96 lectins tested, 11 high-affinity and 8 low-affinity lectins were identified for SRC. Glycan-binding motifs varied in the high-affinity lectins, but 5 (62.5%) low-affinity lectins bound the same glycan structure, α2-6-linked sialic acids. The ratio of signal intensity in SRC to NSRC (SRC/NSRC) was highest in the rBC2LCN lectin (1.930-fold), followed by the BPL lectin (1.786-fold). rBC2LCN lectin showed high affinity for both SRC cell lines and one of the three NSRC cell lines (NCI-N87). The therapeutic effects of the LDC, rBC2LCN-PE38 (rBC2LCN, and Pseudomonas exotoxin A), showed cytocidal effects in vitro and tumor regression in in vivo mouse xenograft models. CONCLUSION: We reported specific glycan profiles in SRC cells, showing reduced α2-6-linked sialic acids. Additionally, we found a targeted therapy using rBC2LCN lectin might be applicable as an alternative treatment option for patients with SRC.

Splenic artery transposition for reconstruction of a large hepatic artery aneurysm: A case report and literature review.

INTRODUCTION AND IMPORTANCE: Hepatic artery aneurysms (HAAs) are rare. Typical treatment options for HAAs are surgical resection and endovascular treatment but treatment choices remain controversial. CASE PRESENTATION: A 65-year-old woman was rushed to our hospital suspected to have hemorrhage. Contrast-enhanced CT showed a large 12 cm aneurysm of the common hepatic artery (CHA). We diagnosed duodenal hemorrhage due to imminent rupture of the HAA. Angiography was first performed. The inferior pancreaticoduodenal artery was embolized with a coil under interventional radiology technique for arterial bleeding control. Next, we performed resection of the aneurysm and total pancreatectomy with splenic artery reservation. We reconstructed via splenic artery transposition because of the reconstruction distance, vascular system, and stability of the anastomosis. The patient was discharged from the hospital on postoperative day 21 without any complications. CLINICAL DISCUSSION: There are two key points in this report. Firstly, the choice of splenic artery transposition is optimal for caliber difference and reconstruction distance. The choice of splenic artery should be considered a reliable option. Secondly, total pancreatectomy avoids exposure to pancreatic juice at the anastomosis site due to pancreatic fistula. CONCLUSION: Splenic artery transposition for HAA is advantageous in adjustability of the caliber difference and securing of sufficient distance. In addition, total pancreatectomy may be acceptable in patients with a normal pancreas to avoid fatal complications such as disruption of the anastomosis and reconstructed artery due to pancreatic juice exposure.

Prediction of Posthepatectomy Liver Failure with a Combination of Albumin-Bilirubin Score and Liver Resection Percentage.

BACKGROUND: Posthepatectomy liver failure (PHLF) is a main cause of death after partial hepatectomy. The aim of this study was to develop a practical stratification system using the albumin-bilirubin (ALBI) score and liver resection percentage to predict severe PHLF and conduct safe hepatectomy. METHODS: Between January 2002 and March 2021, 361 hepatocellular carcinoma (HCC) patients who underwent partial hepatectomy were enrolled. Medical image analysis software was applied postoperatively to accurately simulate hepatectomy. The liver resection percentage was calculated as follows: (postoperatively reconstructed resected specimen volume [ml] - tumor volume [ml])/total functional liver volume (ml) × 100. Multivariate analysis was performed to identify risk factors for PHLF grade B/C. A heatmap for predicting grade B/C PHLF was generated by combining the ALBI score and liver resection percentage. RESULTS: Thirty-nine patients developed grade B/C PHLF; 2 of these patients (5.1%) died. Multivariate analysis demonstrated that a high ALBI score and high liver resection percentage were independent predictors of severe PHLF (odds ratio [OR], 8.68, p < 0.001; OR, 1.10, p < 0.001). With a threshold PHLF probability of 50% for the heatmap, hepatectomy was performed for 346 patients meeting our criteria (95.8%) and 325 patients meeting the Makuuchi criteria (90.0%). The positive predictive value and negative predictive value for severe PHLF were 91.6% and 66.7% for our system and 91.7% and 33.3% for the Makuuchi criteria. CONCLUSION: Our stratification system could increase the number of hepatectomy candidates and is practical for deciding the surgical indications and determining the upper limit of the liver resection percentage corresponding to each patient's liver function reserve, which could prevent PHLF and yield better postoperative outcomes.