Clinical significance of preoperative nutritional parameter and patient outcomes after pancreatectomy: A retrospective study at two academic institute.

BACKGROUNDS/AIMS: Preoperative nutritional status has been reported to influence patient outcomes after pancreatectomy. The Prognostic Nutritional Index (PNI) is a useful parameter to reflect the outcomes of patients undergoing gastrointestinal surgery. Therefore, the relationship between the PNI and clinicopathological factors, surgical data, and postoperative morbidity were retrospectively evaluated at two academic institutes in a cohort study. METHODS: Curative pancreatectomy was performed on 222 patients at the University of Nagasaki between 1995 and March 2015, and 101 at the University of Miyazaki between April 2015and March 2018. The PNI was calculated using preoperative albumin and total cholesterol levels. RESULTS: The mean PNI in our series was 39.2±5.4 and the prevalence of PNIs less than 40 was observed in 134 patients (44%). The PNI was not significantly different between normal, hard, and fatty architecture of the pancreatic parenchyma. The PNIs were significantly negatively correlated with higher age (p<0.01), but not with gender, co-morbidity, or habits. The PNI was significantly correlated with levels of hemoglobin, prothrombin activity, choline esterase, total protein, albumin and cholesterol (p<0.01), and with postoperative total protein and albumin levels (p<0.05). Although the preoperative PNI tended to be lower in patients with total postoperative complications, no significant differences for each complication were observed. CONCLUSIONS: Although the preoperative PNIs reflect the perioperative nutritional status, its predictive usefulness for postoperative complications could not be significantly confirmed.

Correction: Regeneration of esophagus using a scaffold-free biomimetic structure created with bio-three-dimensional printing.

[This corrects the article DOI: 10.1371/journal.pone.0211339.].

Regeneration of esophagus using a scaffold-free biomimetic structure created with bio-three-dimensional printing.

Various strategies have been attempted to replace esophageal defects with natural or artificial substitutes using tissue engineering. However, these methods have not yet reached clinical application because of the high risks related to their immunogenicity or insufficient biocompatibility. In this study, we developed a scaffold-free structure with a mixture of cell types using bio-three-dimensional (3D) printing technology and assessed its characteristics in vitro and in vivo after transplantation into rats. Normal human dermal fibroblasts, human esophageal smooth muscle cells, human bone marrow-derived mesenchymal stem cells, and human umbilical vein endothelial cells were purchased and used as a cell source. After the preparation of multicellular spheroids, esophageal-like tube structures were prepared by bio-3D printing. The structures were matured in a bioreactor and transplanted into 10-12-week-old F344 male rats as esophageal grafts under general anesthesia. Mechanical and histochemical assessment of the structures were performed. Among 4 types of structures evaluated, those with the larger proportion of mesenchymal stem cells tended to show greater strength and expansion on mechanical testing and highly expressed α-smooth muscle actin and vascular endothelial growth factor on immunohistochemistry. Therefore, the structure with the larger proportion of mesenchymal stem cells was selected for transplantation. The scaffold-free structures had sufficient strength for transplantation between the esophagus and stomach using silicon stents. The structures were maintained in vivo for 30 days after transplantation. Smooth muscle cells were maintained, and flat epithelium extended and covered the inner surface of the lumen. Food had also passed through the structure. These results suggested that the esophagus-like scaffold-free tubular structures created using bio-3D printing could hold promise as a substitute for the repair of esophageal defects.

Usefulness of FDG PET/CT derived parameters in prediction of histopathological finding during the surgery in patients with pancreatic adenocarcinoma.

PURPOSE: Pancreatic cancer is the 4th most common cause of cancer death in Japan and exhibits a 5-year overall survival rate of approximately 7%. The accurate diagnosis of pancreatic cancer is important for determining the optimal management strategy. Fludeoxyglucose-positron emission tomography (FDG PET) integrated with computed tomography (18F-FDG PET/CT) has emerged as a powerful imaging tool for detecting and evaluating various cancers, and it is used for staging, detecting local recurrence and distant metastasis, measuring therapeutic effects, and predicting prognosis in pancreatic cancer patients. Lately, FDG PET/CT-derived parameters, such as standardized uptake values (SUV), the metabolic tumor volume (MTV), and total lesion glycolysis (TLG), have been suggested as prognostic factors for various types of cancer, including pancreatic cancer. However, there is no consensus regarding the best parameters for evaluating patient prognosis, operability, etc. The purpose of this study was to examine the differences between operable and non-operable pancreatic cancer using FDG PET/CT-derived parameters, and to investigate whether volumetric parameters (TLG and the MTV) are superior to SUV-based parameters for predicting infiltration status/determining operability. MATERIALS AND METHODS: We conducted a retrospective study of the cases of 48 patients with clinically proven pancreatic adenocarcinoma, who underwent FDG PET/CT imaging before treatment. In the operable group, the surgical specimens were subjected to histopathological examinations, and the cases were separated into those exhibiting less and greater infiltration. SUVmax, SUVpeak, the tumor background ratio (TBR), TLG, and the MTV were compared between these groups as well as between the operable and non-operable groups. RESULTS: Venous infiltration showed significant associations with several metabolic parameters (SUVmax, SUVpeak, and the TBR). However, it did not display any significant associations with volumetric parameters, such as TLG or the MTV. None of the FDG PET/CT-derived parameters exhibited significant associations with lymphatic or neural infiltration. Significant differences in volumetric parameters, such as the MTV and TLG, were detected between the operable and non-operable subgroups. CONCLUSIONS: Metabolic 18F-FDG PET/CT-derived parameters, such as SUVmax, SUVpeak, and the TBR, are useful for predicting venous infiltration status in patients with operable pancreatic adenocarcinoma.

Efficacy of Hepatic Segmental Visualization Using Indocyanine Green Photodynamic Eye Imaging.

BACKGROUND: To clarify the usefulness of identification of hepatic segmentation stained with an indocyanine green-photodynamic eye (ICG-PDE) system, we sequentially investigated the matching of visualization during hepatectomy in 40 patients at two institutions between 2009 and 2017. METHODS: A low dose of ICG was administered into the portal flow to stain the estimated segments of the liver to be resected during hepatectomy, and segmentation images were observed using a PDE camera. Intraoperative ICG-PDE could be carried out for all patients without side effects. RESULTS: Complete segmental identification of the liver by blue dye stain and ICG-PDE was achieved in 30 (75%) and 35 (88%) patients, respectively, but the prevalence between them was not significantly different (p = 0.302). ICG-PDE segmentation in the estimated area was incomplete in three patients, and complete failure (no staining) was observed in two patients. The border between the posterior section and the caudate was identified in two patients. CONCLUSION: This preliminary study showed ICG-PDE to be a useful tool for clearly determining liver segmentation to estimate the area for resection.

Liver resection for metastases of tracheal adenoid cystic carcinoma: Report of two cases.

INTRODUCTION: Tracheal adenoid cystic carcinoma (ACC) is rare and accounts for <1% of all lung cancers. Although ACC is classified as a low-grade tumor, metastases are frequently identified in the late period. Extrapulmonary metastases are rare, and their resection has rarely been reported. PRESENTATION OF CASE: Case 1: A 77-year-old man underwent tracheal resection for ACC with postoperative radiation (60 Gy) 14 years before　(at the age of 63). He underwent two subsequent pulmonary resections for metastases. Fourteen years after the first operation, he underwent extended right posterior segmentectomy with resection of segment IV and radiofrequency ablation for metastases of ACC to the liver. He was diagnosed with metastases to the kidney with peritoneal dissemination 4 years after the liver resection and died of pneumonia 2 years later. Case 2: A 53-year-old woman underwent a two-stage operation involving tracheal resection for ACC and partial resection of liver segments II and V for metastases of ACC to the liver. The tracheal margin was histopathologically positive. Postoperative radiation was performed, and she was tumor-free for 10 months after the liver resection. DISCUSSION: Complete resection of tracheal ACC provides better survival. Radiotherapy is also recommended. However, the optimal treatment for metastases of ACC is unclear, especially because liver resection for metastases of tracheal ACC is rarely reported. Our two cases of metastases of tracheal ACC were surgically managed with good outcomes. CONCLUSION: Liver resection for metastases of tracheal ACC may contribute to long survival.

Indocyanine green identification for tumor infiltration or metastasis originating from hepatocellular carcinoma.

INTRODUCTION: The indocyanine green-photodynamic eye (ICG-PDE) system is useful to detect small hypervascular liver tumors, hepatocellular carcinoma (HCC), on the liver surface. This system may be also applied to improve determining the location of metastasis or tumor thrombus (TT). We herein report three case reports. ICG was administered preoperatively for functional testing and images of the tumor were observed during hepatectomy using a PDE camera. CASE SERIES: The patient in case 1 exhibited advanced HCC with TT in the portal trunk. The TT in the right portal vein was clearly fluorescent by ICG-PDE and the right portal vein was adequately transected to remove TT. The patient in case 2 exhibited a large HCC in the right liver and the right adrenal gland was simultaneously swollen with enhancement. By confirming the fluorescent spot in the right adrenal gland, the metastasized lesion was completely resected. The patient in case 3 previously underwent central bi-segmentectomy, and lymph node metastasis and TT in the vena cava was observed during one-year follow-up. Although it was difficult to detect the definite margin of these lesions by the outline appearance, both lesions could be clearly observed with strong fluorescence and were completely resected. DISCUSSION AND CONCLUSION: ICG-PDE is a useful tool for detecting the precise tumor location even in extrahepatic tumor lesions, such as metastases or tumor thrombus, which is useful for deciding which parts to resect.

Significance of a soft-coagulation system with monopolar electrode for hepatectomy: A retrospective two-institution study by propensity analysis.

BACKGROUND: The VIO soft-coagulation system (VIO) with a monopolar electrode is a novel hemostatic device that provides hemostasis by superficial contact at the bleeding site without carbonization. Because heat injury remains a concern, surgical records and postoperative liver dysfunction were retrospectively evaluated in a cohort study. METHODS: Between September 2010 and March 2016, 322 patients underwent hepatectomy in which hemostatic devices were used at two institutions. Surgical results with use of VIO at one institute (VIO group) were compared with those without use of VIO at a second institute (control group), and propensity analysis was performed. RESULTS: In limited resection and segmentectomy or sectionectomy performed in the VIO group, the prevalence of liver cirrhosis was significantly higher and the operation time was significantly longer in comparison with the control group (p < 0.05). In all hepatectomies, postoperative levels of total bilirubin and aspartate or alanine transaminase tended to be increased and prothrombin activity tended to be lower in the VIO group in comparison with the control group (p < 0.05). The prevalence of hepatic failure in the VIO group was significantly higher in comparison with that in the control group (p < 0.05). In cases of segmentectomy or sectionectomy, blood loss was significantly increased in the VIO group in comparison with that in the control group (p < 0.05) Propensity score matching showed that although the surgical records and outcomes were not significantly different between the groups, postoperative liver dysfunction was significant in the VIO group in comparison with the control group (p < 0.05). CONCLUSIONS: Mild postoperative hepatic thermal injury with VIO was confirmed, and therefore, surgeons should take care when using the VIO system to make frequent wide resected cuts on the surface of the liver.

A case of multiple synchronous quadruple cancers of the stomach, sigmoid colon, rectum, and pancreas.

INTRODUCTION: Multiple primary neoplasms are relatively rare, but their incidence has increased because of aging and improvements in diagnostic imaging. PRESENTATION OF CASE: A 67-year-old man presented with epigastric pain. On upper gastrointestinal endoscopy, an ulcer was seen at the gastric angle, and biopsy showed moderately differentiated adenocarcinoma (AC). Colonoscopy demonstrated a 15-mm lesion in the sigmoid colon and a submucosal lesion in the lower rectum. The biopsy showed well differentiated AC and neuroendocrine tumor (NET). In addition, abdominal CT and MRI showed a 14-mm nodular lesion in the pancreatic body suggesting pancreatic duct cancer. Based on the above findings, four synchronous cancers, including the pancreas, stomach, sigmoid colon and rectum, were diagnosed, and surgery was performed. A midline incision was made in the upper abdomen, and a distal gastrectomy, pancreatic body and tail resection, and sigmoidectomy were performed. Trans-anal tumor resection was performed for the rectal lesion. Histopathology showed invasive pancreatic duct cancer, moderately differentiated AC of the stomach, moderately differentiated AC of the sigmoid colon, and NET G1 of the rectum. The patient had no postoperative complications, 4 years 3 months after resection, and he was disease-free from all of the cancers. DISCUSSION: The strategy of perioperative diagnosis and treatment for multiple primary tumors is usually difficult. This process was performed by consulting a cancer board, which could be useful as a practice guideline. CONCLUSION: This patient in whom four tumors were completely resected at the same time and who has had a good clinical course was reported.

Single-incision laparoscopic ileocecal resection using an organ retractor.

INTRODUCTION: Single-incision laparoscopic surgery has been reported to be a safe and feasible technique for colorectal cancer. However, the technique needs skill due to the limitations of the device. An organ retractor is a new grasp device that has the potential to overcome these limitations. PRESENTATION OF CASE: A 63-year-old woman with a tumor palpated in the right lower quadrant of the abdomen presented to hospital. Colonoscopy showed a type 2 mass with nearly complete stenosis, and a biopsy specimen showed well-differentiated adenocarcinoma. Single-incision laparoscopic surgery ileocecal resection was performed using an organ retractor. A 3-cm incision was placed in the umbilicus, and three conventional ports were inserted. An organ retractor was used for hepatocolic ligament resection, resection of the ileocolic vessels, and resection of the insertion of the mesentery proper. For each resection, the trailer line's tension was adjusted to provide a good operative view. The patient's postoperative course was good, and she was discharged 7days after surgery. DISCUSSION: An organ retractor was effective for single-incision laparoscopic surgery technique not only to maintain a good operative view, but also to change trailer line tension, which enabled safe dissection. CONCLUSION: An organ retractor could facilitate single-incision laparoscopic surgery.

A case of single-incision laparoscopic surgery for a bleeding Meckel's diverticulum diagnosed pre-operatively by double-balloon endoscopy.

INTRODUCTION: 　Meckel's diverticulum (MD) is a congenital true diverticulum that is residual yolk duct tissue, and some cases with complications require surgery. It has been reported that laparoscopic surgery is effective for patients with an MD. PRESENTATION OF CASE: A 79-year-old man with melena visited our hospital. Upper gastrointestinal series and colonoscopy showed no bleeding lesion. Double-balloon endoscopy was then performed to examine the small intestine. The examination showed a large diverticulum 80cm proximal to the ileocecal valve and a circular ulcer. MD resection was performed using single-incision laparoscopic surgery (SILS) technique through a 3-cm zig-zag incision in the umbilicus. Three ports were inserted for the scope and forceps devices. The MD was located 80cm proximal to the ileocecal valve. There were no other intestinal lesions. From the wound, the lesion could be easily moved outside the body. The MD including the ulcer lesion was then resected. The patient's postoperative course was good, and he rarely felt wound pain. He started dietary intake three days after surgery and was discharged from hospital eight days after surgery. DISCUSSION: SILS technique has attracted attention in the field of laparoscopic surgery. Using a single port with multiple working channels, SILS can reduce the number of incisions and the rates of incisional hernia port site-related complications, as well as improve cosmesis. CONCLUSION: A definite diagnosis of an MD was made by double-balloon endoscopy preoperatively. The SILS approach was effective for cosmesis, postoperative pain, and a shortened hospital stay.

Keratinocyte Growth Factor Gene Electroporation into Skeletal Muscle as a Novel Gene Therapeutic Approach for Elastase-Induced Pulmonary Emphysema in Mice.

Pulmonary emphysema is a progressive disease with airspace destruction and an effective therapy is needed. Keratinocyte growth factor (KGF) promotes pulmonary epithelial proliferation and has the potential to induce lung regeneration. The aim of this study was to determine the possibility of using KGF gene therapy for treatment of a mouse emphysema model induced by porcine pancreatic elastase (PPE). Eight-week-old BALB/c male mice treated with intra-tracheal PPE administration were transfected with 80 µg of a recombinant human KGF (rhKGF)-expressing FLAG-CMV14 plasmid (pKGF-FLAG gene), or with the pFLAG gene expressing plasmid as a control, into the quadriceps muscle by electroporation. In the lung, the expression of proliferating cell nuclear antigen (PCNA) was augmented, and surfactant protein A (SP-A) and KGF receptor (KGFR) were co-expressed in PCNA-positive cells. Moreover, endogenous KGF and KGFR gene expression increased significantly by pKGF-FLAG gene transfection. Arterial blood gas analysis revealed that the PaO2 level was not significantly reduced on day 14 after PPE instillation with pKGF-FLAG gene transfection compared to that of normal mice. These results indicated that KGF gene therapy with electroporation stimulated lung epithelial proliferation and protected depression of pulmonary function in a mouse emphysema model, suggesting a possible method of treating pulmonary emphysema.

[Efficacy and safety of administration of low-dose unfractionated heparin (LDUH) for the prevention of pulmonary thromboembolism after surgery for lung cancer; the long term outcome].

We evaluated the efficacy and safety of the administration of low-dose unfractionated heparin(LDUH)for the prevention of pulmonary thromboembolism after lung cancer surgery. We operated on 206 patients with primary lung cancer for 8 years;128 males and 78 females, mean age:69.9±8.8 years. All patients were administrated LDUH 5,000 units every 12 hours from the operation day until the day when the patient could walk around the floor. No patients suffered from clinical pulmonary thromboembolism in this period. The duration of treatment was 4.6±2.6 days and the chest tube duration was 5.4±3.0 days. We experienced post-operative intra-thoracic bleeding in 2 patients during the previous 4 years. Based on this experience, we introduced new eligibility criteria;we discontinued LDUH administration on the operation day if diffuse adhesion in the thoracic cavity was observed at operation or intraoperative blood loss was over 500 ml. The dose of LDUH was decreased to 2,500 unit every 12 hours if the postoperative bleeding was over 400 ml on the operation day or the patient's body weight was less than 40 kg. After introduction of the new criteria, no severe bleeding complications occurred during the latter 4 years.

Intratracheal Administration of Recombinant Human Keratinocyte Growth Factor Promotes Alveolar Epithelial Cell Proliferation during Compensatory Lung Growth in Rat.

Keratinocyte growth factor (KGF) is considered to be one of the most important mitogens for lung epithelial cells. The objectives of this study were to confirm the effectiveness of intratracheal injection of recombinant human KGF (rhKGF) during compensatory lung growth and to optimize the instillation protocol. Here, trilobectomy in adult rat was performed, followed by intratracheal rhKGF instillation with low (0.4 mg/kg) and high (4 mg/kg) doses at various time-points. The proliferation of alveolar cells was assessed by the immunostaining for proliferating cell nuclear antigen (PCNA) in the residual lung. We also investigated other immunohistochemical parameters such as KGF, KGF receptor and surfactant protein A as well as terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling. Consequently, intratracheal single injection of rhKGF in high dose group significantly increased PCNA labeling index (LI) of alveolar cells in the remaining lung. Surprisingly, there was no difference in PCNA LI between low and high doses of rhKGF with daily injection, and PCNA LI reached a plateau level with 2 days-consecutive administration (about 60%). Our results indicate that even at low dose, daily intratracheal injection is effective to maintain high proliferative states during the early phase of compensatory lung growth.

[Evaluation of local coagulation therapy with hepatectomy for liver metastases].

Hepatectomy is accepted as the standard therapy in patients with resectable liver metastases. In recent years, the techniques such as microwave coagulation therapy (MCT) and radiofrequency ablation therapy (RFA) have been developed, so we have many options to treat. We evaluated nineteen subjects with cases of liver metastases who underwent thermoablative procedures with or without hepatectomy. RFA and MCT were used in 6 cases and 2 cases, respectively. In other 11 cases, they received a combined therapy: RFA+hepatectomy in 5 cases, and MCT+hepatectomy in 6 cases. Thermoablative therapy was used for 39 metastatic tumors. The mean tumor size was 13.7 mm, and a local recurrence was observed in 8 nodules (21%). No significant differences were observed in DFS and OS between thermoablative therapy and hepatectomy. Many patients with liver metastases received a repeated treatment, so we have to care about the remnant liver function. We conclude that thermoablative therapy with hepatectomy seems to be a less invasive procedure and effective therapy.

Keratinocyte growth factor accelerates compensatory growth in the remaining lung after trilobectomy in rats.

OBJECTIVE: In rats pulmonary resection is followed by lung compensatory growth. However, the molecular mechanism underlying lung compensatory growth remains unclear. Keratinocyte growth factor is expressed in lung tissue and is considered a possible mitogen for lung epithelial cells. The objectives of this study were to define the role of keratinocyte growth factor and its receptor in rat lung compensatory growth after trilobectomy and the effect of exogenous keratinocyte growth factor gene transfection. METHODS: Adult Lewis rats were used. Right trilobectomy was performed in the operation group and sham thoracotomy in the sham group. In the operation group, keratinocyte growth factor-FLAG or FLAG expression vector was transfected directly into the lung by means of electroporation. Expression of keratinocyte growth factor and its receptor and alveolar cell proliferation index based on proliferating cell nuclear antigen levels were measured in the right lung at day 14 after the operation. RESULTS: Proliferating cell nuclear antigen, keratinocyte growth factor, and keratinocyte growth factor receptor expression in lung epithelial cells was significantly increased at day 4 after trilobectomy. Transfection of keratinocyte growth factor-FLAG expression vector resulted in further significant enhancement of proliferating cell nuclear antigen at day 4 after trilobectomy; however, the transfection of FLAG expression vector did not alter the enhancement of proliferating cell nuclear antigen. Exogenous expression of keratinocyte growth factor in the remaining lung by means of electroporation significantly augmented epithelial proliferation and decreased the average airspace distance (mean linear intercept). CONCLUSION: Our results implicate keratinocyte growth factor in the induction of alveolar epithelial cell proliferation for compensatory lung growth and indicate that overexpression of keratinocyte growth factor in the remaining lung by means of electroporation significantly augmented lung epithelial proliferation.