Early Identification of Patients with Potential Failure of Nonoperative Management for Gastroduodenal Peptic Ulcer Perforation.

INTRODUCTION: We aimed to identify objective factors associated with failure of nonoperative management (NOM) of gastroduodenal peptic ulcer perforation (GDUP) and establish a scoring model for early identification of patients in whom NOM of GDUP may fail. METHODS: A total of 71 patients with GDUP were divided into NOM (cases of NOM success) and operation groups (cases requiring emergency operation or conversion from NOM to operation). Using logistic regression analysis, a scoring model was established based on the independent factors. The patients were stratified into low-risk and high-risk groups according to the scores. RESULTS: Of the 71 patients, 18 and 53 were in the NOM and operation groups, respectively. Ascites in the pelvic cavity on computed tomography (CT) and sequential organ failure assessment (SOFA) score at admission were identified as independent factors for NOM failure. The scoring model was established based on the presence of ascites in the pelvic cavity on CT and SOFA score ≥2 at admission. The operation rates for GDUP were 28.6% and 86.0% in the low-risk (score, 0) and high-risk groups (scores, 2 and 4), respectively. CONCLUSION: Our scoring model may help determine NOM failure or success in patients with GDUP and make decisions regarding initial treatment.

Robotic search for optimal cell culture in regenerative medicine.

Induced differentiation is one of the most experience- and skill-dependent experimental processes in regenerative medicine, and establishing optimal conditions often takes years. We developed a robotic AI system with a batch Bayesian optimization algorithm that autonomously induces the differentiation of induced pluripotent stem cell-derived retinal pigment epithelial (iPSC-RPE) cells. From 200 million possible parameter combinations, the system performed cell culture in 143 different conditions in 111 days, resulting in 88% better iPSC-RPE production than that obtained by the pre-optimized culture in terms of the pigmentation scores. Our work demonstrates that the use of autonomous robotic AI systems drastically accelerates systematic and unbiased exploration of experimental search space, suggesting immense use in medicine and research.

Automated evaluation of retinal pigment epithelium disease area in eyes with age-related macular degeneration.

The retinal pigment epithelium (RPE) is essential for the survival and function of retinal photoreceptor cells. RPE dysfunction causes various retinal diseases including age-related macular degeneration (AMD). Clinical studies on ES/iPS cell-derived RPE transplantation for RPE dysfunction-triggered diseases are currently underway. Quantification of the diseased RPE area is important to evaluate disease progression or the therapeutic effect of RPE transplantation. However, there are no standard protocols. To address this issue, we developed a 2-step software that enables objective and efficient quantification of RPE-disease area changes by analyzing the early-phase hyperfluorescent area in fluorescein angiography (FA) images. We extracted the Abnormal region. This extraction was based on deep learning-based discrimination. We scored the binarized extracted area using an automated program. Our program's performance for the same eye from the serial image captures was within 3.1 ± 7.8% error. In progressive AMD, the trend was consistent with human assessment, even when FA images from two different visits were compared. This method was applicable to quantifying RPE-disease area changes over time, evaluating iPSC-RPE transplantation images, and a disease other than AMD. Our program may contribute to the assessment of the clinical course of RPE-disease areas in routine clinics and reduce the workload of researchers.

Prediction Model for Failure of Nonoperative Management of Uncomplicated Appendicitis in Adults.

BACKGROUND: Prediction of failure of nonoperative management (NOM) in uncomplicated appendicitis (UA) is difficult. This study aimed to establish a new prediction model for NOM failure in UA. METHODS: We included 141 adults with UA who received NOM as initial treatment. NOM failure was defined as conversion to operation during hospitalization. Independent predictors of NOM failure were identified using logistic regression analysis. A prediction model was established based on these independent predictors. Receiver operating characteristic (ROC) curve analysis and the Hosmer-Lemeshow test were used to assess the discrimination and calibration of the model, respectively, and risk stratification using the model was performed. RESULTS: Among 141 patients, NOM was successful in 120 and unsuccessful in 21. Male sex, maximal diameter of the appendix, and the presence of fecalith were identified as independent predictors of NOM failure for UA. A prediction model with scores ranging from 0 to 3 was established using the three variables (male sex, maximal diameter of the appendix ≥ 15 mm, and the presence of fecalith). The area under the ROC curve for the new prediction model was 0.778, and the model had good calibration (P = 0.476). A score of 2 yielded a sensitivity of 71.4% and a specificity of 90.8%. Patients were stratified into low (0-1), moderate (2), and high (3) risk categories, which had NOM rates of 5.2%, 47.1%, and 77.8%, respectively. CONCLUSIONS: Our prediction model may predict NOM failure in UA with good diagnostic accuracy and help surgeons select appropriate treatments.

Advanced Formulation Design for Topical Creams Assisted with Vibrational Spectroscopic Imaging.

Vibrational spectroscopic imaging has become useful analytical tools for quality control of drug products. In this study, we applied microscopic attenuated total reflection (ATR)-IR and confocal Raman microscopy to elucidate microscopic structure of creams and for the formulation design in the development of semi-solid drug products. The model creams were prepared with prednisolone (PRD) and fluconazole (FLC) as active pharmaceutical ingredients and oily solvents such as mineral oil (MO), isopropyl myristate (IPM), benzyl alcohol (BA) and diethyl sebacate (DES). As a result of microscopic ATR-IR imaging, several domains indicating oily internal phase were observed, which had absorption around 1732 and 1734 cm-1 derived from MO, IPM and DES. In addition, domains of BA around 1009 cm-1 were observed at the complemental or similar position in the formulation with MO or DES, respectively. These results suggested that the creams were oil-in-water type and the distribution of domains would reflect the compatibility of the solvents. The contents of PRD and BA were determined quantitatively in each layer after the intentional separation of the creams and the results agreed well with the imaging analysis. Whereas, confocal Raman imaging allowed to visualize the distribution of the components in depth direction as well as two-dimensional plane. In particular, the Raman imaging would ensure the coexistence of FLC and BA as oily phase in the cream. From these results, the feasibility of spectroscopic imaging techniques was successfully demonstrated for the formulation design of semi-solid dosage forms.

New risk factors of postoperative complications in elective gastrointestinal surgery of elderly patients: a prospective cohort study.

BACKGROUND: Gastrointestinal surgery in elderly individuals presents unexpected postoperative complications. However, predicting postoperative complications in elderly patients undergoing gastrointestinal surgeries is challenging because of the lack of a reliable preoperative evaluation system. We aimed to prospectively evaluate three new preoperative assessment methods to predict the postoperative complications in elderly patients undergoing elective gastrointestinal surgery. Moreover, we aimed to identify new risk factors of postoperative complications in this patient group. METHODS: This prospective cohort study enrolled 189 patients (age ≥ 65 years) who underwent elective gastrointestinal surgery at Tokyo Medical University Hachioji Medical Center between April 2017 and March 2019. Assessments performed preoperatively included the biological impedance analysis for evaluating the skeletal muscle mass, the SF-8 questionnaire for evaluating the subjective health-related quality of life, and the blood pressure/pulse wave test for assessing arteriosclerosis. The risk factors for Clavien-Dindo Grade ≥ III postoperative complications were assessed using these new evaluation methods. RESULTS: Clavien-Dindo Grade ≥ III postoperative complications were observed in 28 patients (14.8%). Univariate and multivariate analyses identified male sex, low skeletal muscle mass, and cardio-ankle vascular index ≥ 10 (arteriosclerosis) as significant independent risk factors of developing Grade ≥ III complications. CONCLUSIONS: Male sex, low skeletal muscle mass, and arteriosclerosis were significant risk factors of postoperative complications in elderly patients undergoing elective gastrointestinal surgery. The obtained knowledge could be useful in identifying high-risk patients who require careful perioperative management.

Efficacy of the Milan criteria as a prognostic factor in patients with colorectal liver metastases.

PURPOSE: This study aimed to apply the principles of the "Milan criteria" to patients undergoing hepatic resection for CRLM and to evaluate the efficacy of prognostic factors. METHODS: The medical records of consecutive patients who underwent curative resection for CRLM from April 2007 to April 2019 were retrospectively reviewed. Time to aggressive treatment failure (TATF) was defined as the time interval from the initial surgery until the first unresectable recurrence or recurrence that could only be treated with doublet or lower dose chemotherapy, or death. The risk factors associated with recurrence-free survival (RFS), TSF, TATF, and overall survival (OS) were evaluated. RESULTS: On univariate analysis, the Milan criteria significantly predicted long-term OS, TATF, TSF, and RFS. Moreover, the Milan criteria were able to stratify patients with CRLM into distinct prognostic groups with regard to long-term OS, TATF, TSF, and RFS. CONCLUSIONS: Milan criteria, a simple index, are a factor contributing to all the survival time and are a very important factor in discussing the prognosis of CRLM.

A New Preoperative Risk Score for Predicting Postoperative Complications in Elderly Patients Undergoing Hepatectomy.

BACKGROUND: Postoperative complications are not rare in the elderly population after hepatectomy. However, predicting postoperative risk in elderly patients undergoing hepatectomy is not easy. We aimed to develop a new preoperative evaluation method to predict postoperative complications in patients above 65 years of age using biological impedance analysis (BIA). METHODS: Clinical data of 59 consecutive patients (aged 65 years or older) who underwent hepatectomy at our institution between 2017 and 2020 were retrospectively analyzed. Risk factors for postoperative complications (Clavien-Dindo ≥ III) were evaluated using multivariate regression analysis. Additionally, a new preoperative risk score was developed for predicting postoperative complications. RESULTS: Fifteen patients (25.4%) had postoperative complications, with biliary fistula being the most common complication. Abnormal skeletal muscle mass index from BIA and type of surgical procedure were found to be independent risk factors in the multivariate analysis. These two variables and preoperative serum albumin levels were used for developing the risk score. The postoperative complication rate was 0.0% with a risk score of ≤ 1 and 57.1% with a risk score of ≥ 4. The area under the receiver operating characteristic curve of the risk score was 0.810 (p = 0.001), which was better than that of other known surgical risk indexes. CONCLUSION: Decreased skeletal muscle and the type of surgical procedure for hepatectomy were independent risk factors for postoperative complications after elective hepatectomy in elderly patients. The new preoperative risk score is simple, easy to perform, and will help in the detection of high-risk elderly patients undergoing elective hepatectomy.

Overexpression of hydroxyproline via EGLN/HIF1A is associated with distant metastasis in pancreatic cancer.

For pancreatic cancer, the probability of distant metastasis can help choose the best course of treatment. The aim of this study is to establish the efficacy of hydroxyproline as a biomarker for distant metastasis for pancreatic cancer and to clarify the mechanism of EGLN/HIF1A axis that controls the invasion and metastasis. Metabolites (hydroxyproline) and genes (EGLN2 and EGLN3) were identified by metabolome analysis of the serum with pancreatic cancers with and without distant metastasis. The mechanism of EGLN/HIF1A axis including angiogenesis was examined in pancreatic cancer cells. Hydroxyproline associated with these mechanisms was evaluated to suggest the association with overall survival in pancreatic cancer. Decreased expression of EGLN2 and EGLN3 in pancreatic cancer, via the HIF1A and TGF ß1 pathway, was associated with the induction of angiogenic factors, increased vascular invasion, and poor overall patient survival. Hydroxyproline concentrations were regulated via the HIF1A pathway by EGLN2 and EGLN3, and that increased concentrations of hydroxyproline promote the invasion and metastasis of pancreatic cancer cells. These results suggested that the expression of hydroxyproline through the HIF1A pathway induced by EGLN2 and EGLN3 could be a surrogate marker for treatment and might predict distant metastasis in pancreatic cancer.

Right trisectionectomy for liver metastasis of granulosa cell tumor: a case report and literature review.

BACKGROUND: Granulosa cell tumor (GCT) is a type of ovarian sex cord-stromal tumor with low-grade malignancy, which can recur long after primary resection. All reports on GCTs in the liver describe cases of metastases, while there are no previous reports of primary GCTs originating from the liver. We report a case of GCT, with recurrence of liver metastasis long after ovariectomy, which was subsequently resected by a right trisectionectomy. CASE PRESENTATION: A 76-year-old woman presented with a history of surgical resection of an ovarian tumor performed 30 years previously; no details of the tumor were available. When she was 68 years old, an abdominal ultrasound revealed a small liver mass, which was diagnosed as a hepatic hemangioma with slow growth. Outpatient follow-up was discontinued for 5 years, and the patient was not examined again until the age of 76 years. At this point, the tumor had substantially increased in size, and surgical resection was required owing to suspicion of malignancy. The patient was then referred to our hospital. Contrast-enhanced computed tomography (CT) showed a large tumor, approximately 18 cm in size, occupying the right lobe and medial section of the liver. After percutaneous transhepatic portal vein embolization, a right trisectionectomy was performed. The histopathological findings of the resected specimen showed that the tumor cells had "coffee bean-like" nuclear grooves, which are characteristic of a GCT. Acidophilic non-structural Call-Exner bodies were also observed. Inhibin-α, CD99, and CD56 markers of sex cord-stromal tumors were detected on immunohistological examination; all pathology suggested a GCT. We considered the tumor to be a liver metastasis of a previous ovarian GCT that was resected 30 years prior by ovariectomy. There was no recurrence for > 15 months after the hepatectomy. CONCLUSIONS: We report a case of a GCT in the liver, which was identified to be a liver metastasis. Right trisectionectomy was subsequently performed for tumor resection. Clinicians should be aware that ovarian GCTs may recur in the liver, and that GCT recurrence may occur long after ovariectomy of the primary ovarian GCT.

Resection of recurrent hepatocellular carcinoma with thrombi in the inferior vena cava, right atrium, and phrenic vein: a report of three cases.

BACKGROUND: Prognosis for patients with advanced hepatocellular carcinoma with a tumor thrombus in the inferior vena cava or right atrium is extremely poor due to cancer progression, pulmonary embolism, and congestion of the circulatory system caused by right heart failure. Surgical resection of the tumor thrombi may potentially yield better results than non-surgical treatments through prevention of sudden death. However, the benefits of surgical resection in patients with hepatocellular carcinoma and a tumor thrombus extending to the inferior vena cava, right atrium, and potentially in the phrenic vein are unclear. Here, we report three such cases. CASE PRESENTATION: Of the total 136 patients who underwent hepatectomies for hepatocellular carcinoma in our institution, three patients with prior hepatectomies and recurrent hepatocellular carcinoma had tumor thrombi in the inferior vena cava, right atrium, and phrenic vein. Surgical resections were performed, as there was a possibility of sudden death, despite the risk of leaving residual tumor. For all patients, we performed resection of the tumor thrombi in the inferior vena cava and right atrium and combined diaphragm resection. Surgical resection was performed using the total hepatic vascular exclusion technique in all cases. Additional passive veno-venous bypass was also performed in two cases, in which complete tumor resections could not be achieved. The microscopic surgical margins of the combined resected diaphragms were positive in all cases. Progression-free survival was 20.2, 3.8, and 9.5 months for case 1, 2, and 3, respectively. The respective overall postoperative survival was 98.0, 38.9, and 30.9 months. The patients died due to liver cirrhosis, acute heart failure, and hepatocellular carcinoma, respectively. Sudden death did not occur for any of the patients. CONCLUSION: Surgical resections may extend prognosis for patients with recurrent hepatocellular carcinoma with tumor thrombi in the inferior vena cava, right atrium, and phrenic vein, although the indications should be considered carefully.

The "Tenting Sign of the Hepatic Vein" Is Important for Laparoscopic Anatomical Hepatectomy Along the Major Hepatic Vein.

BACKGROUND: Laparoscopic hepatectomy has rapidly evolved and has become a viable alternative to open hepatectomy. However, the dissection of liver parenchyma via the laparoscopic caudal approach (parenchymal transection from the caudal to cranial direction under a laparoscopic caudal view) has several limitations. To avoid these limitations in anatomical hepatectomy along the hepatic vein with the caudal approach, it is important to recognize the "tenting sign of the hepatic vein," which helps to identify the running of the main trunk of the hepatic vein. TECHNICAL PRESENTATION: In the bifurcation of the hepatic vein, there is a possibility of splitting of the hepatic vein branch or disorientation between the main trunk and branch. Therefore, it is vital that when the branch is pulled, the main trunk of the hepatic vein appears to be toward the direction of the branch. As a result, the main trunk appears in the direction from the original route to the pseudo route. In the caudal approach, this phenomenon is called "tenting sign of the hepatic vein." Therefore, liver dissection should be performed in the contralateral and cranial sides of the main trunk, with the "tenting sign of the hepatic vein" in mind. This report describes specific cases of the "tenting sign of the hepatic vein." CONCLUSION: The "tenting sign of the hepatic vein" from the caudal approach is essential knowledge for safe and reliable anatomical laparoscopic hepatectomy and can lead to expansion of indications in the future.

[A Case of Duodenal Perforation during Bevacizumab Combination Chemotherapy in a Patient with Multiple Lung Metastasis after a Sigmoidectomy].

A 73-year-old man underwent laparoscopic sigmoidectomy for sigmoid colon cancer. Two years after the operation, multiple lung metastasis was diagnosed and chemotherapy with bevacizumab, irinotecan, and TS-1®was started in the patient. However, epigastric pain developed 73 days after the initial course of chemotherapy. Abdominal CT revealed duodenal perforation and generalized peritonitis. Emergency operation with omental patch closure was immediately performed. The patient was discharged 15 days after the emergency operation without any complication. This is an extremely rare case of bevacizu- mab-related duodenal perforation.

Efficacy of Enteral Nutrition by Double Elementary Diet Tube after Pylorus-Preserving Pancreatoduodenectomy.

Nutritional support after pylorus-preserving pancreaticoduodenectomy (PpPD) is still controversial. This study aimed to evaluate the efficacy of enteral nutrition (EN) via the double elementary diet (W-ED) tube after PpPD. One hundred two patients who received EN by the W-ED tube were compared with 52 patients who received total parental nutrition (TPN) previously. Clinicopathological and postoperative features were analyzed among the two groups. Patients with EN by the W-ED tube after PpPD had a lower incidence of postoperative pancreatic fistula than those with TPN. The total protein and albumin levels on discharge in the EN group were significantly higher than those in the TPN group. In the case without complication, decreasing rate of the third lumbar vertebra skeletal muscle area was significantly lower in the EN group. In the cases of soft pancreas, drainage volume by the W-ED tube until four postoperative day was significantly larger in the case without postoperative pancreatic fistula. The W-ED tube offers the advantages of reducing gastrointestinal pressure and enabling reduction of complications after PpPD surgery.

Resection of a pancreatic capillary lymphatic malformation through a partial pancreatectomy: a case report.

BACKGROUND: Pancreatic vascular malformation causes epigastric pain, pancreatitis, portal vein hypertension, bleeding, and rupture. It is a rare disease, with most pancreatic vascular malformations being arteriovenous malformations (AVMs) and the other types of malformations being rare. We report a case of capillary lymphatic malformation (CLM) in the pancreatic uncinate process. CASE PRESENTATION: A 74-year-old woman, who presented with complaints of repeated upper abdominal pain, was admitted to our institution. Contrast-enhanced dynamic computed tomography (CT) scan revealed that the tumor in the pancreatic uncinate process had a poor contrast effect in the arterial phase and a small contrast effect in the equilibrium phase, which are suggestive of a benign disease-like vascular malformation. However, we suspected that it could possibly be a malignant tumor because the tumor size tended to increase over time; thus, we decided to perform a surgery. We resected the tumor through a partial resection of the pancreas. Macroscopically, the cut surface of the tumor had a spongioid appearance. Histopathological examination findings showed a mixed shape of small capillaries and lymphatic ducts. The patient was diagnosed with CLM according to the International Society for the Study of Vascular Anomalies (ISSVA) classification, based on the histological appearance and immunostaining findings. The postoperative course of the patient was uneventful. CONCLUSIONS: We reported a case of pancreatic vascular malformation, specifically a CLM, which was completely resected through a partial pancreatectomy.

Superficial Surgical Site Infection in Hepatobiliary-Pancreatic Surgery: Subcuticular Suture Versus Skin Staples.

PURPOSE: Postoperative superficial surgical site infection is a major complication in hepatobiliary-pancreatic surgery. We aimed to compare the efficacy of subcuticular sutures versus staples for skin closure in preventing superficial surgical site infection in hepatobiliary-pancreatic surgery. METHODS: Consecutive patients who underwent hepatobiliary-pancreatic surgery at our hospital from October 2006 to March 2011 and from April 2012 to March 2015 were reviewed retrospectively. Superficial surgical site infection incidence was evaluated in patients who received subcuticular sutures and those who received staples for skin closure. Propensity score matching analysis was used to adjust bias from confounding factors. RESULTS: A total of 691 patients were included. Patients with skin staple closures (n = 346) were compared with patients with subcuticular suture closures (n = 345). After a propensity score matching analysis, a significant difference in superficial surgical site infection incidence was found between the skin stapler group (11.3%) and subcuticular sutures group (2.6%). The same comparison was performed by a subgroup analysis and supported this finding in patients after hepatectomy without biliary reconstruction, pancreatoduodenectomy, or open laparotomy surgeries and in patients with body mass index < 25. CONCLUSIONS: Subcuticular suturing after hepatobiliary-pancreatic surgery was more efficacious in reducing postoperative superficial surgical site infection incidence than staples for skin closure.

Predicting hepatic failure with a new diagnostic technique by preoperative liver scintigraphy and computed tomography: a pilot study in 123 patients undergoing liver resection.

BACKGROUND: A novel index, total liver LU15, has been identified as a surrogate marker for liver function. We evaluated the ability of preoperative remnant liver LU15 values to predict postoperative hepatic failure. METHODS: Preoperative risk factors for postoperative hepatic failure and remnant liver LU15 were evaluated in 123 patients undergoing liver resection for several diseases from September 1st, 2007 to December 1st, 2016. We calculated the remnant liver LU15 value from the total liver LU15 value and the functional remnant liver ratio. Risk factors for postoperative hepatic failure was determined by univariate and multivariate analysis. RESULTS: Hepatic failure grade B/C developed postoperatively in six patients of seven patients within Makuuchi criteria / without criteria for remnant liver LU15. Operative time (p = 0.0242) and criteria for remnant liver LU15 (p = 0.0001) were prognostic factors for hepatic failure according to the univariate analysis. And criteria for remnant liver LU15 (p = 0.0009) was only prognostic factor by multivariate analysis. CONCLUSION: Based on the findings form this pilot study, it appears that patients with a remnant liver LU15 value of 13 or less may have a high risk of postoperative hepatic failure.