Laparoscopic Distal Pancreatectomy Using Three-Dimensional Computer Graphics for Surgical Navigation With a Deep Learning Algorithm: A Case Report.

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 mm2), 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.

Preoperative difficulty assessment of interval laparoscopic cholecystectomy for gallstones.

BACKGROUND: Laparoscopic cholecystectomy is the gold standard treatment for benign gallbladder disease. However, few studies have reported the difficulty of interval cholecystectomy after cholecystitis because early cholecystectomy is recommended for acute cholecystitis. In this study, we evaluated the difficulties associated with interval cholecystectomy for cholecystitis with gallstones. METHODS: We retrospectively analyzed patients with gallstones who underwent interval laparoscopic cholecystectomy for cholecystitis at our institution between January 2012 and December 2021. Patients were classified into laparoscopic total cholecystectomy and bailout procedure groups depending on whether they were converted to a bailout procedure, and their characteristics and outcomes were subsequently compared. Additionally, a logistic regression analysis of the preoperative factors contributing to bailout procedure conversion was performed. RESULTS: Of the 269 participants, 39 converted to bailout procedure, and bile duct injury occurred in one case (0.4%). In patient characteristics comparison, patients in the bailout procedure group were significantly older, had more impacted stones, had higher post-treatment choledocholithiasis, had severe cholecystitis, and had a higher rate of percutaneous transhepatic gallbladder drainage. There were no differences in the bile duct injury or perioperative complications between the two groups. In logistic regression multivariate analysis of the factors contributing to the bailout procedure, post-treatment of choledocholithiasis (P < .001), impacted stone (P = .002), and age ≥71 (P = .007) were independent risk factors. CONCLUSION: Impacted stones and choledocholithiasis are risk factors for conversion to bailout procedure and high difficulty in interval cholecystectomy. For such patients, interval cholecystectomy should be performed cautiously.

Recurrent Primary Abdominal Wall Abscess: A Case Report and Review of the Literature.

Primary abdominal wall abscess is extremely rare and difficult to diagnose because abdominal wall abscesses usually occur secondary to malignant tumors or inflammatory diseases. We experienced a case of an 80-year-old man with an asynchronous primary abdominal wall abscess with recurrence. Both abscesses were successfully treated with surgical drainage. A patient without any history of cancer or trauma presented to our department with right upper abdominal pain. His laboratory data showed an abnormal high inflammatory response, and computed tomography revealed a 40 × 30 mm mass formed in the rectus abdominis muscle of the upper right abdomen. The mass had no continuity with the surgical scar after cholecystectomy or intra-abdominal organs. Citrobacter diversus was detected in the culture from the mass and any epithelial components were not detected by biopsy. For the diagnosis of primary abdominal wall abscess, the patient underwent surgical drainage because antibiotic treatment was ineffective. The abscess disappeared promptly after the drainage. Thirteen months after the first treatment, another primary abdominal wall abscess was noted in the lower right abdomen. The abscess also promptly disappeared with surgical drainage. Primary abdominal wall abscess is difficult to diagnose because of its rarity. Prompt diagnosis and drainage are important to prevent exacerbation.

Usefulness of Preoperative Predictors of Pathological Complicated Appendicitis.

INTRODUCTION: Complicated appendicitis (CA) is often indicated for emergency surgery; however, preoperative predictors of pathological CA (pCA) remain unclear. Furthermore, characteristics of CA that can be treated conservatively have not yet been established. METHODS: 305 consecutive patients diagnosed with acute appendicitis were reviewed. The patients were divided into two groups: an emergency surgery and a conservative treatment group. The emergency surgery group was pathologically classified as having uncomplicated appendicitis (pUA) and pCA, and the preoperative predictors of pCA were retrospectively assessed. Based on the preoperative pCA predictors, a predictive nomogram whether conservative treatment would be successful or not was created. The predictors were applied to the conservative treatment group, and the outcomes were investigated. RESULTS: In the multiple logistic regression analysis of the factors contributing to pCA, C-reactive protein ≥3.5 mg/dL, ascites, appendiceal wall defect, and periappendiceal fluid collection were independent risk factors. Over 90% of cases without any of the above four preoperative pCA predictors were pUA. The accuracy of the nomogram was 0.938. CONCLUSION: Our preoperative predictors and nomogram are useful to aid in distinguishing pCA and pUA and to predict whether or not conservative treatment will be successful. Some CA can be treated with conservative treatment.

Therapeutic strategy for acute appendicitis based on laparoscopic surgery.

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.

Salivary gland cancer organoids are valid for preclinical genotype-oriented medical precision trials.

Salivary gland cancers (SGCs) are heterogeneous tumors, and precision oncology represents a promising therapeutic approach; however, its impact on SGCs remains obscure. This study aimed to establish a translational model for testing molecular-targeted therapies by combining patient-derived organoids and genomic analyses of SGCs. We enrolled 29 patients, including 24 with SGCs and 5 with benign tumors. Resected tumors were subjected to organoid and monolayer cultures, as well as whole-exome sequencing. Organoid and monolayer cultures of SGCs were successfully established in 70.8% and 62.5% of cases, respectively. Organoids retained most histopathological and genetic profiles of their original tumors. In contrast, 40% of the monolayer-cultured cells did not harbor somatic mutations of their original tumors. The efficacy of molecular-targeted drugs tested on organoids depended on their oncogenic features. Organoids recapitulated the primary tumors and were useful for testing genotype-oriented molecular targeted therapy, which is valuable for precision medicine in patients with SGCs.

Application of Patient-Derived Cancer Organoids to Personalized Medicine.

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.

Evaluation of the Significance of Lymphatic, Microvascular and Perineural Invasion in Patients With Pancreatic Neuroendocrine Neoplasms.

Background: Some prognostic factors for pancreatic neuroendocrine neoplasms (PanNENs) have been reported; however, the significance of lymphatic, microvascular, and perineural invasion remains unclear. We aimed to clarify the role of these factors in PanNEN recurrence. Patients and Methods: We analyzed 138 patients who underwent curative pancreatectomy and were pathologically diagnosed with PanNEN. We evaluated the association between clinicopathological factors and the recurrence of PanNENs. Results: The numbers of patients with lymphatic, microvascular, and perineural invasion were 34 (25%), 43 (31%) and 17 (12%), respectively. Twenty-four patients (17%) had recurrences, and the 3, 5, and 10-year recurrence-free survival (RFS) rates were 88%, 84%, and 76%, respectively. The recurrence sites (with duplication) were mainly the liver (twenty-two patients), followed by the lymph nodes (seven patients), and bone (two patients). In multivariate analyses, grade 2-3 and the presence of microvascular invasion were significant risk factors for RFS (hazard ratio=7.5 and 7.9, respectively). When examining outcomes according to these factors, the 5-year RFS rates of patients with risk scores of 0, 1, and 2 were 100%, 91%, and 32%, respectively (p<0.001). Even in patients with grade 1 (n=97) or limited resection (enucleation, splenic-preserving distal pancreatectomy, central pancreatectomy, and duodenum-preserving pancreatic head resection, n=62), the presence of microvascular invasion was a significant risk factor for RFS (hazard ratio=13.4 and 18.0, respectively). Conclusion: The presence of microvascular invasion is an independent risk factor for recurrence in patients with PanNEN.

The association between ERK inhibitor sensitivity and molecular characteristics in colorectal cancer.

The mitogen-activated protein kinase (MAPK) pathway plays an important role in the colorectal cancer (CRC) progression, being supposed to be activated by the gene mutations, such as BRAF or KRAS. Although the inhibitors of extracellular signal-regulated kinase (ERK) have demonstrated efficacy in the cells with the BRAF or KRAS mutations, a clinical response is not always associated with the molecular signature. The patient-derived organoids (PDO) have emerged as a powerful in vitro model system to study cancer, and it has been widely applied for the drug screening. The present study aims to analyze the association between the molecular characteristics which analyzed by next-generation sequencing (NGS) and sensitivity to the ERK inhibitor (i.e., SCH772984) in PDO derived from CRC specimens. A drug sensitivity test for the SCH772984 was conducted using 14 CRC cell lines, and the results demonstrated that the sensitivity was in agreement with the BRAF mutation, but was not completely consistent with the KRAS status. In the drug sensitivity test for PDO, 6 out of 7 cases with either BRAF or KRAS mutations showed sensitivity to the SCH772984, while 5 out of 6 cases of both BRAF and KRAS wild-types were resistant. The results of this study suggested that the molecular status of the clinical specimens are likely to represent the sensitivity in the PDOs but is not necessarily absolutely overlapping. PDO might be able to complement the limitations of the gene panel and have the potential to provide a novel precision medicine.

Evaluation of the validity of pancreatectomy for very elderly patients with pancreatic ductal adenocarcinoma.

PURPOSE: The role of pancreatectomy for very elderly patients with pancreatic adenocarcinoma is controversial. This study aimed to clarify the validity of pancreatic resection in octogenarian patients with pancreatic ductal adenocarcinoma. METHODS: We compared 31 patients aged ≥ 80 years and 548 patients aged < 80 years who underwent pancreatectomy for pancreatic ductal adenocarcinoma and evaluated the relationship between age, clinicopathological factors, recurrence, and outcomes. RESULTS: Postoperative mortality, morbidity, and completion of adjuvant chemotherapy rates did not differ between groups. There were no significant differences in median recurrence-free survival, disease-specific survival, and overall survival between groups (1.0, 2.3, and 2.2 years in patients ≥ 80 years and 1.2, 2.8, and 2.7 years in patients < 80 years; P = 0.67, 0.47, and 0.46, respectively). The median time from recurrence to death of octogenarian patients was significantly shorter than that of younger patients (0.6 vs. 1.1 years, P = 0.0070). In multivariate analysis, age ≥ 80 years (hazard ratio, 1.5), resection of other organs (hazard ratio, 1.8), pathological grade 2/3 (hazard ratio, 1.6), and failure to implement of treatment after recurrence (hazard ratio, 3.6) were independent risk factors for a short time from recurrence to death. Furthermore, age ≥ 80 years (odds ratio, 0.32) was an independent risk factor for the implementation of treatment after recurrence. CONCLUSIONS: Pancreatectomy for octogenarians may be acceptable, but median survival time from recurrence to death was shorter due to lower rates of implementation of treatment after recurrence in octogenarian patients.

Impact of the controlling nutritional status score on severe postoperative complications of pancreaticoduodenectomy for pancreatic cancer.

PURPOSE: The 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. METHODS: We 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. RESULTS: Postoperative 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. CONCLUSIONS: The CONUT score may be a useful parameter in the identification of patients undergoing pancreatic surgery who are susceptible to postoperative complications.

Development of a system combining comprehensive genotyping and organoid cultures for identifying and testing genotype-oriented personalised medicine for pancreatobiliary cancers.

BACKGROUND: Pancreatobiliary cancer is a highly aggressive tumour with a dismal prognosis. Personalised medicine represents a promising and effective therapeutic approach for this intractable disease. In this study, we aimed to establish a system for identifying and testing genotype-oriented targeted drugs for pancreatobiliary cancers by combining exome sequencing and organoid culture of primary tumours. METHODS: Tumour cells isolated from resected tumours were subjected to organoid cultures based on published protocols with modifications. Exome sequencing was performed on the primary tumours. Histopathological and molecular features of the primary tumours were validated in the corresponding organoids. Genotype-oriented candidate targeted drugs were identified from exome sequencing, and their efficacies were tested in the organoids. RESULTS: Organoid cultures succeeded in 30 of 54 (55.6%) cases. Six primary cancers of the biliary tract and gall bladder were subjected to exome sequencing, which revealed a variety of somatic mutations of genes involved in signalling pathways, epigenetic modifiers, genome maintenance and metabolic enzymes. Most of the organoids of these 6 cases showed identical histopathological features and genomic aberrations as those of the primary tumours. Some of the aberrations were candidates for targeted therapies. Integrin-linked kinase (ILK) was one such candidate target, and an ILK inhibitor was confirmed to suppress proliferation of patient-derived organoids. CONCLUSIONS: By combining exome sequencing and organoid culture, our model enabled to identify genotype-oriented targets for personalised medicine and to test efficacies of candidate targeted drugs in the organoids. The current proof-of-concept approach could increase therapeutic opportunities for patients with pancreatobiliary cancers.

Drain Lipase Levels and Decreased Rate of Drain Amylase Levels as Independent Predictors of Pancreatic Fistula with Nomogram After Pancreaticoduodenectomy.

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.

Evaluation of the significance of adjuvant chemotherapy in patients with stage â A pancreatic ductal adenocarcinoma.

BACKGROUND: Although adjuvant chemotherapy is considered a standard treatment for resected pancreatic ductal adenocarcinoma (PDAC), its utility in stage ⅠA patients is unclear. We aimed to investigate the recurrence rate, surgical outcome, prognostic factors, effectiveness of adjuvant chemotherapy, and determination of groups in whom adjuvant chemotherapy is effective in patients with stage ⅠA PDAC. METHODS: We retrospectively analyzed 73 patients who underwent pancreatectomy and were pathologically diagnosed with stage ⅠA PDAC between 2000 and 2018. We evaluated the relation between clinicopathological factors, recurrence rates, and outcomes such as the recurrence-free and disease-specific survival rates (RFS and DSS, respectively). RESULTS: The 5-year RFS and DSS rates were 52% and 58%, respectively. In multivariate analysis, a platelet-to-lymphocyte ratio (PLR) ≥ 170, prognostic nutrition index (PNI) < 47.5, and pathological grade 2 or 3 constituted risk factors for a shorter DSS (hazard ratios: 4.7, 4.6, and 4.1, respectively). Patients with 0-1 of these risk factors (low-risk group; n = 47) had significantly higher 5-year DSS rates than those with 2-3 risk factors (high-risk group; n = 26) (80% vs. 23%; P < 0.001). Patients in the low-risk group showed similar 5-year RFS rates regardless of whether they received or not adjuvant chemotherapy (75% vs 70%, respectively; P = 0.49). Contrarily, high-risk patients who underwent adjuvant chemotherapy had higher 5-year RFS rates than those who did not receive adjuvant chemotherapy (32% vs 0%; P = 0.045). CONCLUSIONS: In stage IA PDAC, adjuvant chemotherapy seems to be effective only in a subgroup of high-risk patients.

Whole exome sequencing and establishment of an organoid culture of the carcinoma showing thymus-like differentiation (CASTLE) of the parotid gland.

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.

Evaluation of Early Prognostic Factors in Patients With Pancreatic Ductal Adenocarcinoma Receiving Gemcitabine Together With Nab-paclitaxel.

Background: Gemcitabine together with nab-paclitaxel (GnP) has been shown to improve outcomes in patients with pancreatic ductal adenocarcinoma (PDAC). However, the predictive markers for treatment effects remain unclear. This study aimed to identify early prognostic factors in patients with PDAC receiving GnP. Patients and Methods: We analyzed 113 patients who received GnP for PDAC and evaluated the relationship between clinical factors and outcomes. Results: The median survival time (MST) was 1.2 years. In multivariate analysis, baseline carbohydrate antigen 19-9 (CA19-9) ≥747 U/ml [hazard ratio (HR)=1.9], baseline controlling nutrition status (CONUT) score ≥5 (HR=3.7) and changing rate of CA19-9 after two GnP cycles ≥0.69 (HR=3.7) were independent risk factors for poor prognosis. When examining outcomes according to pre-chemotherapeutic measurable factors (baseline CA19-9 and CONUT), the MSTs of patients with pre-chemotherapeutic zero risk factors (pre-low-risk group, n=63) and one or more risk factors (pre-high-risk group, n=50) were 1.7 and 0.65 years (p<0.001), respectively. The MST for those with a changing rate of CA19-9 after two GnP cycles <0.69 and ≥0.69 was significantly different in both groups (2.0 and 1.2 years in the pre-low-risk group, p<0.001; 1.0 and 0.52 years in the pre-high-risk group, p<0.001). Conclusion: These results may be useful for decision-making regarding treatment strategies in patients with PDAC receiving GnP.

Prognostic Factors for Surgically Resected Intraductal Papillary Neoplasm of the Bile Duct: A Retrospective Cohort Study.

BACKGROUND: To 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. METHODS: The 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. RESULTS: More 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). CONCLUSIONS: Evaluation 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.

Comparison of Clinicopathological Features of Biliary Neuroendocrine Carcinoma with Adenocarcinoma.

OBJECTIVE: This study aimed to demonstrate the clinical features and postoperative outcomes of extrahepatic bile duct (EHBD) neuroendocrine carcinoma (NEC) and compared with those of adenocarcinoma. METHODS: We retrospectively analyzed patients with EHBD cancer operated in our institution between 1995 and 2015. RESULTS: Of 475 patients, 468 had adenocarcinoma, while 7 had NEC/mixed adenoneuroendocrine carcinoma (MANEC) in this study. There were no notable preoperative and pathological features in patients with NEC/MANEC. However, patients with NEC/MANEC had a higher recurrence rate (51.8 vs. 100%, p = 0.016), poorer relapse-free survival (RFS) time (the median RFS time: 35 vs. 12 months, p = 0.006), and poorer overall survival (OS) time (the median OS time: 60 vs. 19 months, p = 0.078) than those with adenocarcinoma. Furthermore, patients with NEC/MANEC had higher rates of liver metastasis (11.9 vs. 85.7%, p < 0.001) than those with adenocarcinoma. In multivariable regression analysis, pathological type with NEC/MANEC was a risk factor for poorer RFS (p = 0.022, hazard ratio: 6.09). CONCLUSIONS: Patients with NEC/MANEC have high malignant potential and poor outcomes. It is necessary to develop an effective approach and postoperative adjuvant treatment for patients with NEC/MANEC.

Evaluation of allowable pancreatic resection rate depending on preoperative risk factors for new-onset diabetes mellitus after distal pancreatectomy.

BACKGROUND: Although more patients have long-term survival after pancreatectomy, the details of pancreatogenic diabetes mellitus (DM) are still unclear. We aimed to investigate the incidence of new-onset DM (NODM) after distal pancreatectomy (DP) and to clarify the risk factors, including allowable pancreatic resection rate (PR), for NODM. METHODS: The incidence, onset time, and risk factors for NODM were retrospectively evaluated in 150 patients who underwent DP without preoperative DM and with >5 years of postoperative follow-up between 2005 and 2015. RESULTS: The incidence rate of NODM was 39%, and 60% of this incidence was noted within 6 months postoperatively. In the multivariate analysis, hemoglobin A1c ≥ 5.8% (odds ratio [OR] 7.6), impaired glucose tolerance and/or impaired fasting glucose (OR 4.2), homeostasis model assessment of insulin resistance ≥1.4 (OR 5.5), and insulinogenic index <0.7 (OR 3.9) were the preoperative risk factors for NODM. Based on these four preoperative risk factors of NODM, we made the new scoring system to predict the NODM after DP. The NODM incidence was 0%, 8%, 48%, 60%, and 86% in patients with risk scores 0 (n = 25), 1 (n = 36), 2 (n = 33), 3 (n = 35), and 4 (n = 21), respectively. PRs ≥42.1% and ≥30.9% were allowable in the preoperative risk-score 0-1 and 2-4 groups. In the former group, the NODM incidence for PR ≥ 42.1% and <42.1% was significantly different (20% vs 0%, P < 0.05). In the latter group, the NODM incidence for PR ≥ 30.9% vs <30.9% was significantly different (75% vs 23%, P < 0.05). CONCLUSIONS: We clarified the preoperative risk factors and allowable PR for NODM and recommended the use of a risk scoring system for predicting NODM preoperatively.