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.

Continuous suture closure using a LapraTy® suture clips is an effective method for reconstruction of cystic duct stump after laparoscopic subtotal cholecystectomy.

Objective: Recently, number of laparoscopic subtotal cholecystectomy (LSC) has been increasing. Summary background data: LSC is suitable as a treatment as it can avoid intraoperative bile duct injury and bleeding for difficult laparoscopic cholecystectomy. On the other hand, improper handling of remnant of GB can lead to postoperative bile leakage. Methods: Here, we report our positive experience utilizing new technique of continuous suture closure and omental covering using Lapra Ty® suture clips on the remnant of GB. Results: From January 2016 to July 2021, we experienced 30 cases of LSC for LC patients who had difficulty securing critical view of safety (CVS). In six of the 30 cases, we repaired remnant of GB using continuous suture closure and omental covering with Lapra Ty® suture clips. The median operating time was 136 min (range 112-199 ml), and amount of bleeding was 1 ml (range 1-100). There were no cases of postoperative bile leakage (postope. BL), remnant cystic duct stone, and abscess formation in abdomen. Conclusion: we recommend this new suturing technique for closure of remnant of GB as it was very effective in preventing postope. BL after LSC.

Prognostic impact of postoperative infection after resection of biliary malignancy: A multicenter retrospective cohort study.

BACKGROUND: The aim of this study was to investigate the prognostic impact of postoperative infections in patients who underwent resection for biliary malignancy, including intrahepatic cholangiocarcinoma, perihilar cholangiocarcinoma, distal cholangiocarcinoma, gallbladder carcinoma, and carcinoma of the ampulla of Vater. METHODS: This study was conducted in an 11-center retrospective cohort study. Patients with biliary tract cancer who underwent curative resection between April 2013 and March 2015 at 11 institutions in Japan were enrolled. We analyzed the prevalence of postoperative infection, infection-related factors, and prognostic factors. RESULTS: Of the total 290 cases, 33 were intrahepatic cholangiocarcinoma, 60 were perihilar cholangiocarcinoma, 120 were distal cholangiocarcinoma, 55 were gallbladder carcinoma, and 22 were carcinoma of the ampulla of Vater. Postoperative infectious complications, including remote infection, were observed in 146 patients (50.3%), and Clavien-Dindo ≥III in 115 patients (39.7%). Postoperative infections occurred more commonly in the patients who received pancreaticoduodenectomy and bile duct resection. Patients with infectious complications had a significantly poorer prognosis than those without (median overall survival 38 months vs 62 months, P = .046). In a diagnosis-specific analysis, although there was no correlation between infectious complications and overall survival in intrahepatic cholangiocarcinoma, perihilar cholangiocarcinoma, distal cholangiocarcinoma, and carcinoma of the ampulla of Vater, infectious complications were a significantly poor prognostic factor in gallbladder carcinoma (P = .031). CONCLUSION: Postoperative infection after surgery for biliary tract cancer commonly occurred, especially in patients who underwent pancreaticoduodenectomy and bile duct resection. Postoperative infection is relatively associated with the prognosis of patients with biliary malignancy, especially gallbladder carcinoma.

Laparoscopic bailout surgery effective procedure for patients with difficult laparoscopic cholecystectomy.

TG18 recommends bailout surgery (BOS) for difficult laparoscopic cholecystectomy. However, there is not a clear criterion on the decision process on whether to continue laparoscopic BOS or open BOS, and optimal procedure for treatment for the remnant cystic bile duct also awaits discussion. We comparted with open BOS and laparoscopic BOS, and compared with suture close and clipping or ligating of remnant cystic duct. We have accrued 57 patients underwent BOS during study period. Seventeen cases underwent laparoscopic BOS, and 38 cases underwent open BOS. There were 22 patients were accrued in suture closing and 35 patients were accrued in clipping or ligating. Open BOS experienced high levels of CRP, WBC, NLR, and CAR, and was associated with significantly longer hospitalization, operating time, and amount of bleeding. Suture close was higher in patients with preoperative endoscopic lithotripsy (EL). BOS can be sufficiently performed under laparoscopy. Patients underwent preoperative EL tended to be higher necessity to suture close of cystic duct.

Possibility for avoidance of urgent nighttime operations for acute appendicitis in a regional core university hospital.

INTRODUCTION: In recent years, a shortage of surgeons and anesthesiologists, particularly in regional hospitals, has become a social issue in Japan. In such hospitals, urgent surgery at night has been performed with difficulty. Therefore, we retrospectively assessed the outcomes of appendectomies for the patients visited at nighttime in our hospital categorized as a local university hospital. METHODS: A retrospective review was conducted on 82 patients of acute appendicitis presented to our hospital between 5:30 p.m. to 8:30 a.m., between January 2014 and April 2019. We compared patients who underwent urgent nighttime appendectomy (group A) and patients who underwent appendectomy during the daytime, or so-called short interval appendectomy (group B). The evaluated factors were preoperative characteristics (age, sex, body mass index, cardiopulmonary complications, laboratory data, body temperature, presence of the Blumberg sign, and CT findings), operation characteristics, and postoperative characteristics (surgical-site infection [SSI], complications, and length of hospital stay). RESULTS: Patients in group A were significantly younger than patients in group B. Patients in group A were significant more likely to experience an SSI. DISCUSSION: Patients diagnosed with acute appendicitis during the nighttime can undergo short interval appendectomy, which leads to a decreased risk of SSI, has no effect on length of hospital stay after surgery, and lessens medical staff burden.

Carbohydrate Antigen 19-9 Is an Invasive Malignancy Preoperative Prognostic Factor for Intraductal Papillary Mucinous Neoplasms.

INTRODUCTION: This study aimed to determine the preoperative clinicophysiological and postoperative clinicopathological predictors of malignancy in patients with intraductal papillary mucinous neoplasm (IPMN). METHODS: This was a retrospective observational study. We included 121 patients (73 men and 48 women; mean age: 68.7 years) who had undergone pancreatic resection for IPMN between 2007 and 2018. These patients were grouped into invasive carcinoma (IPMN-INV, N = 21) and low/high-grade IPMN (IPMN-LG/HG, N = 100) groups. Univariate and multivariate analyses of clinicophysiological parameters were carried out. These parameters were also compared between the IPMN-INV/HG (N = 53) and IPMN-LG (N = 68) groups. Survival analyses according to macroscopic type and IPMN subtypes were performed. RESULTS: On univariate analysis, age (p = 0.038), carbohydrate antigen (CA) 19-9 (p < 0.001), IPMN macroscopic type (p = 0.001), IPMN subtype (p < 0.001), pancreatic duct diameter (p < 0.001), and mural nodule (p = 0.042), between IPMN-INV and IPMN-LG/HG were found to be significant prognostic factors of malignancy. CA 19-9 was found to be an independent prognostic factor of IPMN malignancy on multivariate analysis (p = 0.035). The 1-, 3-, and 5-year overall survival (OS) rates of the IPMN-INV and IPMN-LG/HG groups were 94.4/100%, 94.4/100%, and 67.2/100%, respectively. The OS rate in the IPMN-LG/HG group was significantly higher than that in the IPMN-INV group (p < 0.001). On univariate analysis, platelet (p = 0.043), CA 19-9 (p = 0.039), prognostic nutritional index (p = 0.034), platelet/lymphocyte ratio (p = 0.01), IPMN macroscopic type (p < 0.001), IPMN subtype (p < 0.001), pancreatic duct diameter (p = 0.036), and mural nodule (p = 0.032) between IPMN-INV/HG and IPMN-LG were found to be significant prognostic factors of malignancy. On multivariate analysis, CA 19-9 was found to be an independent prognostic factor (p = 0.042) between IPMN-INV/HG and IPMN-LG of malignancy. The 1-, 3-, and 5-year OS rates of the IPMN-INV/HG and IPMN-LG groups were 97.9/100%, 97.9/100%, and 82.6/100%, respectively. The OS rate was significantly higher in the IPMN-LG group than in the IPMN-INV/HG group (p = 0.03). No significant differences in survival were observed in patients with macroscopic tumors (p= 0.544). CONCLUSION: CA 19-9 is an independent invasive malignancy predictor of IPMN.

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.

Loss of antibodies to hepatitis E virus in organ transplant patients with hepatitis E.

AIM: Studies regarding changes in antibodies to hepatitis E virus (HEV) after HEV infection in organ transplant patients are limited. This study aimed to clarify HEV infection trends in organ transplant patients who contracted HEV using data from a previous Japanese nationwide survey. METHODS: This study was undertaken from 2012 to 2019. Among 4518 liver, heart, and kidney transplant patients, anti-HEV immunoglobulin G (IgG) antibodies were positive in 164; data were collected from 106 of these patients, who consented to participate in the study. In total, 32 liver transplant patients, seven heart transplant patients, and 67 kidney transplant patients from 16 institutions in Japan were examined for IgG, IgM, and IgM antibodies to HEV and the presence of HEV RNA in the serum. The χ2 -test was used to determine the relationship between the early and late postinfection groups in patients with anti-HEV IgG positive-to-negative conversion rates. The Mann-Whitney U-test was used to compare clinical factors. RESULTS: Anti-HEV IgG positive-to-negative conversion occurred in 25 (23.6%) of 106 organ transplant patients. Of eight patients with hepatitis E who tested positive for HEV RNA, one (14.0%) had anti-HEV IgG positive-to-negative conversion. Twenty-four (24.5%) of 98 patients negative for HEV RNA had anti-HEV IgG positive-to-negative conversion. CONCLUSIONS: This study revealed, for the first time, the changes in HEV antibodies in organ transplant patients. Loss of anti-HEV IgG could often occur unexpectedly in organ transplant patients with previous HEV infection.

What are the risk factors of conversion from total cholecystectomy to bailout surgery?

BACKGROUND: Laparoscopic cholecystectomy (LC) is regarded as the first choice for patients with gallbladder diseases, but biliary injury (BDI) still poses serious risks upon implementation of LC. Recently, bailout surgery (BOS; partial cholecystectomy or subtotal cholecystectomy) has been proposed to avoid not only BDI but also major vessels injuries. In this retrospective study, we evaluated the preoperative and perioperative risk factors regarding conversion from total cholecystectomy (TC) to BOS. METHODS: A total of 584 patients who underwent elective LC for gallbladder diseases between January 2006 and April 2018 were analyzed. The patients were divided into the TC group (including conversion open TC) and the BOS group. Univariate and multivariate analyses using preoperative and perioperative clinicolaboratory characteristics were performed to investigate the most significant risk factors associated with conversion to BOS. RESULTS: There were a total of 33 patients in the BOS group (35 men and 18 women), with 19 patients who underwent open BOS and 14 patients who underwent laparoscopic BOS. From the univariate analyses, age, albumin level, CRP level, WBC, lymph. ratio, neutro. ratio, platelet count (PLt), neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, CRP-to-alb ratio, intercurrent acute cholecystitis (AC), and previous biliary tract drainage (PBTD) were considered as risk factors for the conversion to BOS. Multivariate analysis using the 13 parameters selected from the univariate analyses demonstrated that AC (p = 0.04), albumin level (p = 0.01) and age (p = 0.04) were significant risk factors. CONCLUSION: Patients with PBTD and AC have a high risk upon conversion from LTC to BOS, and for such patients, LC should be performed cautiously.

Preoperative prognostic nutritional index predicts risk of recurrence after curative resection for stage IIA colon cancer.

BACKGROUND: Preoperative nutritional and inflammatory indices have been reported to be associated with the prognosis of patients with malignancy. We evaluated clinicopathological factors, including nutritional and inflammatory indices, and recurrence prognosis in patients with stage IIA colon cancer (CC) who underwent curative surgery. METHODS: This retrospective study included 197 patients with stage IIA CC who had undergone curative resection. We evaluated the association between prognostic nutritional index (PNI), neutrophil-lymphocyte ratio (NLR), and platelet-lymphocyte ratio (PLR) with clinicopathological factors and prognosis for recurrence. For the recurrence-free survival (RFS) analysis, receiver operating characteristic (ROC) curves were used to determine appropriate cutoff values for PNI, NLR, and PLR. RESULTS: Univariate analyses showed that PNI<44.8 (P = 0.028) was significantly associated with worse RFS in patients with stage IIA CC patients. In the multivariate analyses, PNI<44.8 (hazard ratio [HR] 2.082; 95% confidence interval [CI] 1.005-4.317; P = 0.049) independently and significantly predicted RFS. CONCLUSION: PNI is a useful marker for predicting recurrence prognosis in post-resection patients with stage IIA CC.

Predictive Effectiveness of the Glasgow Prognostic Score for Gastrointestinal Stromal Tumors.

The aim of this study was to evaluate the significance of the Glasgow prognostic score (GPS) in patients with resected gastrointestinal stromal tumors (GISTs). Forty-six GIST patients who underwent radical resection between January 2004 and December 2011 were enrolled in this retrospective study. The clinicopathological parameters examined included predictors of recurrence-free survival (RFS). Univariate and multivariate analysis of prognostic factors related to RFS were calculated using Cox proportional hazards model. The GPS classification system revealed 37 (80.4%), 6 (13.1%), and 3 (6.5%) patients with a GPS of 0, 1, and 2, respectively. Patients with GPS 1/2 had a significantly shorter RFS compared to those with GPS 0 (P = 0.01). The 3- and 5-year RFS rates for patients with GPS 0 were 94.0% and 90.9%, respectively, compared to 66.7% and 53.3%, respectively, for patients with GPS 1/2. Univariate analyses indicated that tumor size (P < 0.01), mitotic rate (P < 0.01), higher GPS (P < 0.01), and platelet count (P = 0.04) were prognostic factors for RFS; tumor size (P = 0.01) and GPS (P = 0.04) were independent prognostic factors in multivariate analysis. Preoperative high GPS were predictors of long-term prognosis in patients with resected GISTs.

Leiomyosarcoma of the transverse colon with lymph node metastasis and malignant transformation: a case report.

BACKGROUND: The concept of GIST was established in 1998, clearly differentiating between gastrointestinal leiomyosarcoma and GISTs among gastrointestinal mesenchymal tumors. Lymph node metastasis is extremely rare in true gastrointestinal leiomyosarcoma, and there are no reports of malignant transformation from leiomyoma. CASE PRESENTATION: The patient was an old woman who had undergone endoscopic mucosal resection for an Is polyp on the left side of the transverse colon at the age of 73. She was diagnosed with leiomyoma with positive surgical margins. Subsequently, she presented to our institution with a sensation of pressure in the upper abdominal region as a chief complaint at the age of 76 years. Abdominal computed tomography and colorectal endoscopy showed a tumor lesion with invagination of the intestines in the transverse colon, the same site as that of the previously resected leiomyoma. A biopsy suggested a smooth muscle tumor, and we performed partial left transverse colectomy and lymph node dissection under a diagnosis of recurrence and enlargement of the previously incompletely resected leiomyoma. Histopathological examination revealed spindle-shaped tumor cells, and the mitotic activity was 30-40/10 high-power field. Tumor cells were immunohistologically positive for α-smooth muscle actin and h-caldesmon; partially positive for desmin; negative for c-kit, CD34, DOG-1, and the S-100 protein; and showed a Ki-67 labeling index of 70-80%. She was diagnosed with leiomyosarcoma malignantly transformed from leiomyoma. Metastasis was found in 1 of the 14 resected lymph nodes. The patient did not undergo adjuvant chemotherapy, but has survived with no recurrence at 2 years after the surgery. CONCLUSIONS: We have reported a case of leiomyosarcoma of the transverse colon with lymph node metastasis that was malignantly transformed from a leiomyoma.

Urinary titin N-terminal fragment concentration is an indicator of preoperative sarcopenia and nutritional status in patients with gastrointestinal tract and hepatobiliary pancreatic malignancies.

OBJECTIVES: Recent reports indicate that preoperative patients with gastrointestinal malignancies often have sarcopenia. The diagnosis of sarcopenia is generally done by evaluation of walking speed, grip strength, and skeletal muscle volume of the limbs on computed tomography (CT). However, these parameters are objective indices, and new indicators for diagnosis, such as molecular biomarkers, have been anticipated. The aim of this study was to investigate whether titin, a muscular contractile protein present in sarcomeres, is an indicator of sarcopenia. METHODS: We analyzed 39 patients with gastrointestinal tract and hepatobiliary pancreatic malignancies who underwent surgery. We compared urinary titin n-terminal fragment concentration (UTF) with clinical factors, subcutaneous fat volume, and skeletal muscle volume index, and also compared UTF levels between patients with and without sarcopenia. RESULTS: The patients comprised 24 men and 15 women, with a mean age of 72 y (range: 35-85 y). Cancer locations were the pancreas (n = 17), liver (n = 9), stomach (n = 5), colorectum (n = 5), and esophagus (n = 3). UTF was significantly higher in patients with sarcopenia (P = 0.04), and showed statistically significant negative correlations with albumin (r = -2.61, P = 0.001), pre-albumin (r = -2.14, P = 0.02), body mass index (r = -0.49, P = 0.007), cholinesterase (r = -0.02, P = 0.01, skeletal muscle volume index (r = -0.16, P = 0.04), and subcutaneous fat volume (r = -0.03, P = 0.007). CONCLUSION: UTF may be a new index for preoperative nutritional assessment in patients with gastrointestinal malignancies.

Investigation of morphological and functional changes in the liver and pancreas during bevacizumab treatment.

Objectives: Recently, there have been reports regarding the atrophy of various organs caused by molecular targeted drugs. We investigated morphological and clinical changes in the liver and pancreas caused by treatment with bevacizumab.Methods: We investigated 30 patients with colorectal cancer who received bevacizumab-containing chemotherapy (study group) and 11 patients with colorectal cancer who received chemotherapy without bevacizumab (control group) from 2010 to 2014. We obtained computed tomography data of the liver and pancreas and performed three-dimensional image analysis and volumetry. Laboratory data before and after chemotherapy were analyzed.Results: There was no significant difference in liver volume before and after bevacizumab-containing chemotherapy, but the pancreatic volume was found to be significantly reduced after bevacizumab-containing chemotherapy (57.9 ± 16 mL versus 47.4 ± 15.3 mL; p = .005). The liver and pancreatic volume did not change statistically in the control group. With regard to complete blood cell counts and laboratory data, no significant differences were observed in the leukocyte count and hemoglobin, hemoglobin A1c, triglyceride, albumin, and C-reactive protein levels. In contrast, there was a significant decrease in the platelet count, total cholesterol level and a significant increase in the amylase level. A chemotherapy regimen that included bevacizumab reduced pancreatic volume and significantly altered the morphology of the pancreas.Conclusions: Although bevacizumab caused atrophy of the pancreas and reduced pancreatic volume, pancreatic endocrine function showed no change. Future studies should investigate the survival rate and functional changes caused by bevacizumab treatment.

Development of new software enabling automatic identification of the optimal anatomical liver resectable region, incorporating preoperative liver function.

Determining the resectable region and volume of the liver prior to anatomical resection is important. The synapse Vincent (SV) system is the current method for surgical liver resection that relies on the surgeon's individual experience and skill. Additionally, in cases involving abnormal liver function, the resectable region is limited due to deteriorating liver function, thus making the determination of the hepatectomy region challenging. The current study outlines a novel 3D Hariyama-Shimoda Soft (HSS) simulation software that can be used to automatically simulate the optimal hepatectomy region under a limited resectable liver volume. The current study recruited patients with hepatic malignant tumors that were scheduled for anatomical resection. The influence of the tumor on each portal vein point was quantified in accordance with the tumor domination ratio (TDR). The resectable region was subsequently determined so that the sum of the TDR was the maximum estimated resectable liver volume (ERLV). The maximum ERLV settings utilized were within Makuuchi's criteria. ERLV was compared with the actual resected liver volume (ARLV) using SV and HSS. A total of 15 patients were included in the present study. The median ERLV was not significantly different between the two groups (P=0.15). However, the correlation between ERLV and ARLV, for SV and HSS, was statistically significant [SV ERLV (ml) = 1.139 × HSS ERLV (ml) + 30.779 (P=0.001)]. In conclusion, HSS may be an effective 3D simulation system. TDR and ERLV were indicated to be novel factors that may be incorporated into simulation software for use in anatomical resection surgery.

Cancer-associated fibroblasts show heterogeneous gene expression and induce vascular endothelial growth factor A (VEGFA) in response to environmental stimuli.

AIM: Cancer-associated fibroblasts (CAF) play a crucial role in angiogenesis in the complex tumor microenvironment. However, fibroblasts show extensive heterogeneity and their dynamic functions against stressors remain largely unknown. METHODS: We collected patient-derived CAF and carried out perturbation-based monitoring of the dynamic functions. Clinically relevant experimental stimuli were defined as follows: hypoxia, cisplatin, fluorouracil, coculture with cancer spheroids (interaction through paracrine signals). We selected 18 marker genes that encode components for fibroblast activation, intracellular communication, and extracellular matrix remodeling. Quantitative reverse transcription polymerase chain reaction was carried out for data collection and statistical analyses were carried out using SPSS software. RESULTS: Kruskal-Wallis multivariate analysis of variance showed that variations in expression of 11 marker genes were explained, in part, by a difference in tissue of origin. Friedman and two-sided Wilcoxon signed rank tests detected significant perturbations in expression of marker genes. Paracrine signal from cancer spheroids induced vascular endothelial growth factor A (VEGFA) in CAF but not in fetal lung fibroblasts. CONCLUSION: We have established perturbation-based monitoring of patients' CAF. Further data collection and individual patient follow up is ongoing to identify critical determinants of disease outcome.

Number of positive lymph nodes and lymphatic invasion are significant prognostic factors after pancreaticoduodenectomy for distal cholangiocarcinoma.

Background: Early recurrence of distal cholangiocarcinoma (DCC) may result in a poorer prognosis. This study aimed to evaluate the clinicopathological factors that predict survival and recurrence in patients with DCC. Methods: Fifty-five patients with DCC who underwent pancreaticoduodenectomy between 2005 and 2015 were studied retrospectively. The following clinicopathological parameters were analyzed as predictors of disease-free survival (DFS) and overall survival (OS): sex, age, body mass index, presence of biliary tract decompression, macroscopic type, histological type, tumor size, TNM classification, lymph node metastasis ratio, number of positive lymph nodes (PLNs), lymphatic invasion, venous invasion, perineural invasion, proximal bile duct margin, dissected margin, portal system invasion, arterial system invasion, stage, and residual tumor. Results: Univariate analysis showed that contiguous extension of the primary tumor, PLN, lymphatic invasion, venous invasion, perineural invasion, and stage were significant prognostic factors for DFS and OS. Multivariate analysis revealed that PLN and lymphatic invasion were prognostic for DFS and OS (P<0.001). Significant differences in OS and DFS were found in analyses stratified by PLN (0, 1, 2 vs ≥3) and lymphatic invasion (0 vs 1, 2, 3). Conclusion: Among the clinicopathological parameters analyzed, PLN and lymphatic invasion were confirmed as prognostic factors for DCC.

Preoperative high C-reactive protein level is associated with an increased likelihood for conversion from laparoscopic to open appendectomy in patients with acute appendicitis.

Background: Laparoscopic appendectomy (LA) has been increasingly adopted for its advantages over the open appendectomy, but there are possibilities of conversion from laparoscopic to open appendectomy (CA) if the patients had complicated appendicitis concurrently, or when the extent of inflammation prohibits successful procedure. In this retrospective study, we aimed to clarify the preoperative predictors for CA. Patients and methods: From January 2010 to April 2016, medical records of 93 consecutive patients who underwent LA for suspected appendicitis were reviewed retrospectively. Factors evaluated were age, gender, body mass index, C-reactive protein (CRP), white cell count, albumin, Neutrophil count, lymphocyte count, Neutrophil/lymphocyte ratio, preoperative CT imaging (abscess formation: yes/no, appendicolith: yes/no), operative factors (time to operation, amount of bleeding), length of hospital stay, period until oral intake after surgery, and period from initial symptoms to surgery. Results: CA occurred in nine patients (9.7%). The reason for conversion was severe dense adhesion in two cases, inadequate exposure of appendix in two cases, uncompleted appendectomy in two cases, perforated appendicitis in one case, gangrenous appendicitis in one case, and abscess formation in one case. Based on 93 patients evaluated by preoperative CT scan, significant factors in the final multivariate analysis associated with CA was CRP [odds ratio=1.13, 95% CI:1.00-1.28, p=0.04]. Conclusion: Identifying the potential factors for conversion preoperatively may assist the surgeons in making decisions concerning the management of patients with appendicitis and in the judicious use of LA.

Clinical Outcome of Resected Remnant Pancreatic Cancer After Resection of the Primary Pancreatic Cancer.

Purpose: Pancreatic cancer (PC) has high morbidity and mortality rates, with a poor prognosis and frequent recurrence. The postresection survival rate has increased but remains low, and remnant PC is becoming more common. This review evaluates the current literature pertaining to the clinical outcomes of patients with resected remnant PC. Material and Methods: We reviewed publications on remnant PC that included repeated and completion pancreatectomy. Clinicophysiological data were analyzed, and survival rates were calculated using the Kaplan-Meier method. Remnant PC was defined by negative margins at the initial operation, a cancer-free interval >1 year, and presence in the remnant pancreas. Results: Forty-nine cases of remnant PC selected from the literature were examined. Primary and remnant PCs had the same histopathological features in 29 of 45 patients (64.4%). The median disease-free interval was 44.3 months (12-143 months). The 1- and 3-year survival rates after repeat pancreatectomy were 81.5% and 50%, respectively, and the median survival time was 32 months. The age of the patient at the time of the first operation independently predicted survival in a multivariate analysis. Conclusion: In long-term survivors after curative resection for PC, resectable remnant PCs should be aggressively removed to improve prognosis.

Predictive Early Recurrence Factors of Preoperative Clinicophysiological Findings in Pancreatic Cancer.

BACKGROUND: We aimed to evaluate the use of preoperative clinicophysiological parameters as predictive risk factors for early recurrence of pancreatic ductal adenocarcinoma (PDAC) after curative resection. METHODS: A total of 260 patients who underwent pancreatic resection for PDAC between 2007 and 2015 were examined retrospectively. We divided the patients into those with early recurrence (within 6 months; group A, n = 52) and those with relapse within ≥6 months or without recurrence (group B, n = 208). Data regarding clinicophysiological parameters were analyzed as predictors of disease-free survival (DFS). These factors were analyzed by χ2 tests on univariate analysis and Cox proportional hazard models on multivariate analyses. Kaplan-Meier survival curves were generated using log-rank tests. RESULTS: Groups A and B had significantly different preoperative carbohydrate antigen 19-9 (CA19-9) levels, carcinoembryonic antigen (CEA) levels, and curability. Univariate and multivariate analysis showed that CA19-9 and CEA were independent prognostic factors for early recurrence. Patients with CA19-9 levels > 124.65 U/mL had significantly shorter DFS than those with lower levels, as did patients with CEA levels > 4.45 ng/mL. CONCLUSIONS: Our results show that elevated CA19-9 (> 124.65 U/mL) and CEA (> 4.45 ng/mL) were independent predictors of early recurrence after pancreatic resection in PDAC patients.