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BackgroundTo date, postoperative prognostic factors for intraductal papillary neoplasm of the bile duct (IPNB) have not been well-established. This study aimed to examine the histopathologic features and postoperative prognosis of the two IPNB subclassifications, as well as factors affecting prognosis, based on the authors’ experience at a single institution.MethodsThe study enrolled 83 patients who underwent surgical resection for pathologically diagnosed IPNB at the authors’ institution. The clinicopathologic features and postoperative outcomes for these patients were examined. The study also investigated postoperative prognostic factors for IPNB using uni- and multivariate analyses.ResultsMore than half of the tumors (64%) diagnosed as IPNB were early-stage cancer (UICC Tis or T1). However, none were diagnosed as benign. The multivariate analysis showed that lymph node metastasis (hazard ratio [HR], 5.78; p = 0.002) and bile duct margin status with carcinoma in situ (D-CIS; HR, 5.10; p = 0.002) were independent prognostic factors, whereas MUC6 expression showed only a marginal influence on prediction of prognosis (HR, 0.32; p = 0.07). The tumor recurrence rate and the proportion of locoregional recurrence were significantly greater among the patients with D-CIS than among those with negative bile duct margins, including those patients with low-grade dysplasia. The patients with D-CIS showed a significantly poorer prognosis than those with negative bile duct margins (5-year survival, 38% versus 87%; p = 0.0002).ConclusionsEvaluation of resected IPNBs showed cancer in all cases. Avoiding positive biliary stumps during surgery, including resection of carcinoma in situ, would improve the prognosis for patients with IPNB.

Carcinoma showing thymus-like differentiation (CASTLE) is a rare tumor, especially in the parotid gland. We encountered a CASTLE of the parotid gland and analyzed its clinicopathological features, as well as the genotype using whole exome sequencing (WES). Moreover, we successfully established an organoid culture cell line from the primary tumor tissue. The patient was a 23-year-old woman who underwent superficial parotidectomy with peripheral neck dissection, followed by radiotherapy. Pathologically, the resected specimen showed atypical epithelioid nests and trabeculae with squamous differentiation, separated by thick fibrous septa, accompanied by dense lymphocytes and plasma cell infiltration. Immunohistochemistry revealed that the tumor cells were positive for AE1/AE3, p40, p63, p16, CK5/6, and CD5, and the background lymphocytes were positive for CD5 and CD99. Based on these findings, the tumor was diagnosed as CASTLE. WES uncovered five nonsynonymous and splicing somatic mutations, namely, FREM2 p.Val861Phe, CLK3 p.Phe376Leu, DLGAP1 p.Lys294Asn, NOX1 p.Val165Met, and PSG9 c.430 + 4A > T. Organoid culture cells preserved the histopathological characteristics of the epithelioid component of CASTLE and harbored all five somatic mutations detected in the primary tumor. In conclusion, for the first time to the best of our knowledge, we successfully analyzed a comprehensive genotype and established an organoid culture cell line of a parotid gland CASTLE, which should serve for analyzing the nature of this rare tumor.

Background We investigated whether the standardized “can‐opener method” surgical technique is an adequate surgical procedure for hemispheric hepatectomy in segments 7 and 8. Methods Forty‐two patients who underwent laparoscopic hemispheric liver resection for segments 7 and 8 using our standardized surgical technique were enrolled. To examine the effect of this standardized surgical procedure on short‐term outcomes, patients were classified into two groups based on the timing of the standardization of their procedures (Group A, the first half of the cases, and Group B, the second half of the cases). Short‐term outcomes were subsequently compared between the two groups. Results Significant differences in operation time (465 min vs. 332 min, p = 0.001), intraoperative blood loss volume (645 g vs. 105 g, p = 0.011), postoperative complications (Clavien‒Dindo Grade I and Grade II) (7 vs. 1, p = 0.011), and length of postoperative hospital stay (10 days vs. 7 days, p = 0.001) were detected between the two groups. All patients had negative surgical margins. With respect to postoperative complications, four patients had Grade I complications, such as wound infection and minor pneumonia, and four patients had Grade II complications, such as bile duct infection and intra‐abdominal abscess. No patients experienced 90‐day mortality. Conclusion Our standardized surgical technique is an adequate surgical procedure for hemispheric hepatectomy in segments 7 and 8 and is referred to as the “can‐opener method”.

PurposeTo investigate the risk factors for post-pancreatectomy hemorrhage (PPH).MethodsThe incidence, outcome, and risk factors for PPH were evaluated in 1169 patients who underwent pancreatectomy.ResultsThe incidence and mortality rates of PPH were 3% and 11% in all pancreatectomies, 4% and 11% in pancreatoduodenectomy, 1% and 20% in distal pancreatectomy, and 3% and 0% in total pancreatectomy, respectively. Male sex [odds ratio (OR) 2.32], body mass index (BMI) ≥ 25 kg/m2 (OR 3.70), absence of diabetes mellitus (DM; HbA1c ≤ 6.2%; OR 3.62), and pancreatoduodenectomy (OR 3.06) were risk factors for PPH after all pancreatectomies. The PPH incidence was 0%, 1%, 2%, 6%, and 20% in patients with risk scores of 0 (n = 65), 1 (n = 325), 2 (n = 455), 3 (n = 299), and 4 (n = 25), respectively. The differences between risk-score groups 0–2 (2%) and 3–4 (7%) were significant (P < 0.05, OR 4.7). In patients who had undergone pancreatoduodenectomy, postoperative pancreatic fistula (POPF; OR 31.7) and absence of DM (OR 3.45) were risk factors for PPH. There was no significant association between POPF and PPH after distal pancreatectomy (P = 0.28). The incidence of POPF post-pancreatoduodenectomy was 20%. BMI ≥ 25 kg/m2 (OR 3.17), serum albumin < 3.5 g/dl (OR 1.77), absence of DM (OR 1.75), distal extrahepatic bile duct carcinoma (OR 4.05), and carcinoma of the papilla of Vater (OR 5.19) were risk factors for POPF post-pancreatoduodenectomy.ConclusionOur study clarified the preoperative risk factors for PPH and recommends using a risk scoring system that includes “absence of DM” for predicting PPH.

Cell models are indispensable for the research and development of cancer therapies. Cancer medications have evolved with the establishment of various cell models. Patient-derived cell lines are very useful for identifying characteristic phenotypes and susceptibilities to anticancer drugs as well as molecularly targeted therapies for tumors. However, conventional 2-dimensional (2D) cell cultures have several drawbacks in terms of engraftment rate and phenotypic changes during culture. The organoid is a recently developed in vitro model with cultured cells that form a three-dimensional structure in the extracellular matrix. Organoids have the capacity to self-renew and can organize themselves to resemble the original organ or tumor in terms of both structure and function. Patient-derived cancer organoids are more suitable for the investigation of cancer biology and clinical medicine than conventional 2D cell lines or patient-derived xenografts. With recent advances in genetic analysis technology, the genetic information of various tumors has been clarified, and personalized medicine based on genetic information has become clinically available. Here, we have reviewed the recent advances in the development and application of patient-derived cancer organoids in cancer biology studies and personalized medicine. We have focused on the potential of organoids as a platform for the identification and development of novel targeted medicines for pancreatobiliary cancer, which is the most intractable cancer.

PurposeThe controlling nutritional status (CONUT) score is a useful biomarker to evaluate undernutrition. However, there have been few reports describing the correlation between postoperative complications and the CONUT score for pancreatic cancer. Therefore, this study aimed to assess the impact of the CONUT score on the postoperative complications of pancreaticoduodenectomy (PD) in patients with pancreatic cancer.MethodsWe retrospectively analyzed 206 consecutive patients with pancreatic cancer who underwent PD over a 12-year duration at our institution. The patients were divided into two groups based on preoperative CONUT scores; their clinicopathological characteristics and surgical outcomes were compared. Furthermore, we compared the CONUT score with preoperative clinical factors and several nutritional biomarkers for postoperative complications using univariate and multivariate analyses.ResultsPostoperative complications of Clavien–Dindo grade ≥ IIIa and those of Clavien–Dindo grade ≥ IIIb occurred in 29 (14.1%) and 9 (4.4%) patients, respectively. The high CONUT score (≥5) group indicated that patients with an undernutrition status had a higher postoperative complication rate, poorer relapse-free survival, and overall survival rates than the low CONUT score (≤4) group. Among preoperative clinical factors, a high CONUT score was an independent risk factor for severe postoperative complications.ConclusionsThe CONUT score may be a useful parameter in the identification of patients undergoing pancreatic surgery who are susceptible to postoperative complications.

Background During pancreatic ductal adenocarcinoma (PDAC) resection, it is essential to secure a negative surgical margin for cancer cells. However, the prognostic impact of pancreatic intraepithelial neoplasia (PanIN) at the resection margin remains unclear. Methods Patients with PDAC who underwent pancreatectomy at our institution were retrospectively analyzed. Based on the pathological diagnosis of the pancreatic resection margin, the patients were classified into three groups: cancer-negative (Neg), low-grade PanIN (LG-PanIN), and cancer-positive (Pos). The postoperative prognoses between the groups were compared. Prognostic factors were compared using the Cox regression analysis. Results Of the 101 patients, the numbers per margin category were as follows: Neg, n=74; LG-PanIN, n=18; and Pos, n=9. Regarding disease-specific survival (DSS) or recurrence-free survival (RFS), the LG-PanIN group had the best prognosis, while the Pos group had the worst. Multivariate cox regression analysis showed that being positive for peritoneal lavage cytology was the independent poor prognostic factor for DSS (hazard ratio, 2.42 [95% confidence interval {CI}, 1.01–5.80]; P=0.047). The microscopically poorly differentiated type had poorer DSS ( P =0.049) and RFS ( P =0.031) prognoses than did the others. Conclusions In our hypothesis generating study for observational cohort, the presence of LG-PanIN at the resection margin did not negatively affect the prognosis. Although the results cannot imply the direct surgical recommendations, it would affect to determine whether additional resection of pancreatic margin should be performed during surgery.

We have demonstrated the utility of SYNAPSE VINCENT (version 6.6; Fujifilm Medical Co., Ltd., Tokyo, Japan), a 3D image analysis system, in semi-automated simulations of the peripancreatic vessels, pancreatic ducts, pancreatic parenchyma, and peripancreatic organs using an artificial intelligence (AI) engine developed with deep learning algorithms. Furthermore, we investigated the usefulness of this AI engine for patients with pancreatic cancer. Here, we present a case of laparoscopic distal pancreatectomy with an extended surgical procedure performed using surgical simulation and navigation via an AI engine. An 80-year-old woman presented with abdominal pain. Enhanced abdominal computed tomography (CT) revealed main pancreatic duct dilatation with a maximum diameter of 40 mm. Furthermore, there was a 17 mm cystic lesion between the pancreatic head and the pancreatic body and a 14 mm mural nodule in the pancreatic tail. Thus, the lesion was preoperatively diagnosed as an intraductal papillary carcinoma (IPMC) of the pancreatic tail and classified as T1N0M0 stage IA according to the 8th edition of the Union for International Cancer Control guidelines. The present patient had laparoscopic distal pancreatectomy and regional lymphadenectomy. In particular, since it was necessary to include the cystic lesion in the pancreatic neck, pancreatic resection was performed at the right edge of the portal vein, which is closer to the head of the pancreas than usual. We routinely employed three-dimensional computer graphics (3DCG) surgical simulation and navigation, which allowed us to recognize the surgical anatomy, including the location of pancreatic resection. In addition to displaying the detailed 3DCG of the surgical anatomy, this technology allowed surgical staff to share the situation, and it has been reported that this approach improves the safety of surgery. Furthermore, the remnant pancreatic volume (47.6%), pancreatic resection surface area (161 mm ), and thickness of the pancreatic parenchyma (12 mm) at the resection location were investigated using 3DCG imaging. Intraoperative frozen biopsy confirmed that the resection margin was negative. Histologically, an intraductal papillary mucinous neoplasm with low-grade dysplasia was observed in the pancreatic tail. No malignant findings, including those related to the resection margin, were observed in the specimen. At the 12-month postoperative follow-up examination, the patient's condition was unremarkable. We conclude that the SYNAPSE VINCENT AI engine is a useful surgical support for the extraction of the surrounding vessels, surrounding organs, and pancreatic parenchyma including the location of the pancreatic resection even in the case of extended surgical procedures.

Purpose The treatment strategies for acute appendicitis differ depending on the facility, and various studies have investigated the usefulness of conservative treatment with antibiotics, laparoscopic surgery, and interval appendectomy (IA). However, although laparoscopic surgery is widely used, the clinical strategy for acute appendicitis, especially complicated cases, remains controversial. We assessed a laparoscopic surgery-based treatment strategy for all patients diagnosed with appendicitis, including those with complicated appendicitis (CA). Methods We retrospectively analysed patients with acute appendicitis treated in our institution between January 2013 and December 2021. Patients were classified into uncomplicated appendicitis (UA) and CA groups based on computed tomography (CT) findings on the first visit, and the treatment course was subsequently compared. Results Of 305 participants, 218 were diagnosed with UA and 87 with CA, with surgery performed in 159 cases. Laparoscopic surgery was attempted in 153 cases and had a completion rate of 94.8% (145/153). All open laparotomy transition cases ( n  = 8) were emergency CA surgery cases. No significant differences were found in the incidence of postoperative complications in successful emergency laparoscopic surgeries. In univariate and multivariate analyses for the conversion to open laparotomy in CA, only the number of days from onset to surgery ≥ 6 days was an independent risk factor (odds ratio: 11.80; P  < 0.01). Conclusion Laparoscopic surgery is preferred in all appendicitis cases, including CA. Since laparoscopic surgery is difficult for CA when several days from the onset have passed, it is necessary that surgeons make an early decision on whether to operate.

Background Pancreaticoduodenectomy (PD) has recently been improved due to its increased safety. However, postoperative pancreatic fistula (POPF) remains a lethal complication of PD. Identifying novel clinicophysiological risk factors for POPF during the early post-PD period would help improve patient morbidity and mortality. Therefore, this retrospective study aimed to evaluate possible risk factors during the early postoperative period after pancreaticoduodenectomy (PD). Methods Data from 349 patients who underwent PD between 2007 and 2012 were examined retrospectively. All patients were classified into 2 groups: group A, patients without fistulae or biochemical leaks (288 patients), and group B, those with grade B or C POPF (61 patients). Data on various clinicophysiological parameters, including serum and drain laboratory data, were collected. Univariate and multivariate analyses were performed to evaluate POPF predictors. A predictive nomogram was established for these results. Results Univariate analysis showed that various serum and drain-related factors, such as white blood cell count, C-reactive protein levels, drain amylase (DAMY) levels, and drain lipase (DLIP) levels, were possible POPF risk factors. Multivariate analysis confirmed that postoperative day (POD) 1 DLIP levels (hazard ratio, 15.393; p  = 0.037) and decreased rate (POD3/1) of DAMY levels (hazard ratio, 4.415; p  = 0.028) were independent risk factors. Further, POD1 DLIP levels and decreased rate of DAMY levels were significantly lower in group A than in group B. The accuracy of nomogram was 0.810. Conclusions POD1 DLIP levels (> 245 U/mL) and decreased rate of DAMY levels (> 0.44) were POPF risk factors, making them possible biomarkers for POPF.