An Experimental Study on the Relationship Among Airway Pressure, Pneumoperitoneum Pressure, and Central Venous Pressure in Pure Laparoscopic Hepatectomy.

OBJECTIVES: To determine optimal settings for airway pressure (AWP), pneumoperitoneum pressure (PPP), and central venous pressure (CVP) in pure laparoscopic hepatectomy. BACKGROUND: High PPP is often employed to control bleeding from the hepatic vein during pure laparoscopic hepatectomy; however, there is a risk of pulmonary gas embolism. We noted that decreases in AWP were often effective. METHODS: After establishing carbon dioxide pneumoperitoneum in 6 male piglets and maintaining PPP at 25 mmHg, CVP was measured 3 times at each of 9 levels of airway pressure, which was increased in increments of 5 cmH2O from 0 to 40 cmH2O. CVP was measured in the same manner by maintaining PPP at 20, 15, 10, 5, and 0 mmHg, and in laparotomy. Correlation and regression analyses were performed among airway pressure, CVP, and pneumoperitoneum pressure. RESULTS: Positive correlations were observed between AWP and CVP and between PPP and CVP (P < 0.001). Under high airway pressure, CVP was persistently higher than pneumoperitoneum pressure. Under low airway pressure, CVP did not increase or often decreased when PPP was higher than CVP. CONCLUSIONS: By increasing pneumoperitoneum pressure, bleeding from the hepatic vein cannot be controlled under high airway pressure, but can be controlled under low airway pressure. However, under low airway pressure, the risk of pulmonary gas embolism increases when PPP is higher than CVP. We consider that reducing AWP is also effective for controlling bleeding from the hepatic vein and safer than increasing pneumoperitoneum pressure.

The negative impact of insulin therapy for acute hyperglycemia secondary to glucose load on plasma amino acid profiles in a rat model of sepsis.

BACKGROUND: In critical illnesses, insulin therapy under overfed conditions with an excessive glucose infusion may cause metabolic disturbances in skeletal muscle mainly through muscle cell glucose uptake and the inhibition of physiological protein breakdown. The aim of this study was to examine the potential negative aspects of insulin therapy in a rat model of sepsis. MATERIALS AND METHODS: Male Sprague-Dawley rats underwent cecal ligation and puncture (CLP) or sham surgery. A pre-established continuous intravenous glucose infusion was initiated immediately after surgery. Rats with sepsis were divided into four groups (n = 7 in each group) based on target blood glucose (BG) levels: a no glucose (NG) group (100-150 mg/dl), moderate glucose (MG) group (200-300 mg/dl), high glucose (HG) group (>300 mg/dl), and the hyperinsulinemia (HI) group, which received the same glucose infusion as the HG group with the insulin infusion (200-300 mg/dl). The sham group underwent sham surgery and received the same glucose infusion as the HG group. All rats were sacrificed 9 h after surgery, and blood samples were collected to measure plasma amino acid (AA) profiles. To examine survival rates in the 48 h following CLP, the HG, MG, and HI groups were newly prepared according to the aforementioned experimental design. RESULTS: Plasma levels of the branched-chain AAs, glutamine, arginine, citrulline, and alanine among the septic groups slightly and inversely decreased with the amount of glucose infused, and HI had significantly lower values (p < 0.01). A strong correlation was observed among the AAs. Plasma 3-methylhistidine concentrations were the highest in the HI group. The survival rate of the HI group was greater than that of the HG, but did not reach the level of the MG group. CONCLUSION: In critical illnesses, insulin therapy under overfed conditions may impair the physiological supply of AAs and conditionally essential AA starvation, such as glutamine and arginine, and may have an adverse impact on the prognosis of patients.

The manner of the inflammation-boosting effect caused by acute hyperglycemia secondary to overfeeding and the effects of insulin therapy in a rat model of sepsis.

BACKGROUND: The aim of the study was to investigate both the inflammation-boosting effect and the metabolic stress induced by acute hyperglycemia secondary to overfeeding with excessive glucose infusion and the effects of insulin therapy on those events in a rat model of sepsis. MATERIALS AND METHODS: Sprague-Dawley rats underwent cecal ligation and puncture (CLP) or sham operation. Preestablished continuous intravenous glucose infusion was initiated immediately after surgery. First, rats with CLP-inducing sepsis were divided into three groups on the basis of the target blood glucose (BG) levels: high glucose (HG) group (overfed, >300 mg/dL), moderate glucose group (moderate hyperglycemia, 200-300 mg/dL), and no glucose group (100-150 mg/dL). The sham group received the same glucose infusion as that of the HG group. BG and plasma interleukin (IL) 6 levels were monitored over time. All rats were sacrificed 9 h after surgery to evaluate lung histology and measure hepatic total glutathione and malondialdehyde contents. Based on the results, the high glucose and insulin (HI) group was added to septic groups as a model of insulin therapy, in which insulin with the same HG dose as that in the HG group was administered to maintain moderate hyperglycemia. RESULTS: BG level in all groups remained in the preestablished target range throughout the experiment. Plasma IL-6 level in all septic groups increased in a time-dependent manner, whereas that in the sham group with moderate hyperglycemia hardly increased. Nine hours after CLP, plasma IL-6 level in the HG group rose to 7407.5 ± 1987.3 pg/mL, which was three times higher than that in the other septic groups. There was no significant difference among moderate glucose, no glucose, and HI groups, in which BG level remained constant at <300 mg/dL. The HG group showed the worst consequences of lung injury and oxidative stress in the liver, which were completely stable in HI group. CONCLUSIONS: Acute severe hyperglycemia in critical illness might excessively boost the existing systemic inflammatory response in a threshold-based manner. Insulin therapy under overfeeding could strongly inhibit such a boosting effect and oxidative stress in the liver.

Effects of platelet-rich plasma on intestinal anastomotic healing in rats: PRP concentration is a key factor.

BACKGROUND: Few studies have examined the effects of platelet-rich plasma (PRP) on intestinal anastomotic healing. The applied preparation methods and PRP concentrations used in the few studies that have been carried out varied markedly. Therefore, the positive effects of PRP on the anastomotic healing process remain unclear. The aim of this study is to examine the effects of different concentrations of PRP on intestinal anastomotic healing. MATERIAL AND METHODS: From SD rat blood, three different concentrations of plasma were prepared: high-concentrated PRP (H-PRP: platelet count 5 × 10(6)/mm(3)), low-concentrated PRP (L-PRP: 2 × 10(6)/mm(3)), and platelet-poor plasma (PPP). Male SD rats underwent proximal jejunal anastomosis and central venous catheterization. Rats were divided into four groups (n = 12 for each group): control, PPP, L-PRP, and H-PRP groups. Two types of PRP and PPP (0.21 mL) were applied to each anastomosis line, with the exception of the control group. Total parenteral nutrition (TPN) solutions were administered (151 kcal/kg/d). Five days after surgery, anastomotic bursting pressure (ABP) in situ and hydroxyproline concentration (HYP) in anastomotic tissue were evaluated. RESULTS: The ABP values of control, PPP, L-PRP, and H-PRP groups were 171 ± 20, 174 ± 23, 189 ± 17, and 148 ± 25 mmHg, respectively. The HYP values of each group were 516 ± 130, 495 ± 123, 629 ± 120, and 407 ± 143 µg/g dry tissue. Compared with the other groups, the L-PRP group exhibited a significant increase in both ABP and HYP, while the H-PRP group exhibited a significant decrease in these two variables. As a result, L-PRP was considered to promote anastomotic wound healing, but H-PRP was considered to inhibit it. There was no significant difference between the PPP group and the control group. CONCLUSIONS: PRP concentration plays a crucial role in the efficacy of PRP. PRP might exert positive effects on intestinal anastomotic healing in a dose-dependent manner up to a certain level, but adverse effects occur when it is highly concentrated. The essential PRP action appears to be driven by the platelets themselves.

Early postoperative oral intake accelerates upper gastrointestinal anastomotic healing in the rat model.

BACKGROUND: In our previous study, we reported that early postoperative oral feeding accelerated upper gastrointestinal anastomotic healing in rats. To investigate its underlying mechanism, we performed in vivo and in vitro experiments. MATERIALS AND METHODS: Rats that received proximal jejunal anastomosis were divided into four groups: the enteral nutrition (EN) group were fed via gastrostomy, the total parental nutrition (TPN alone) group were fed via a venous catheter, the TPN + saline group received an additional administration of normal saline solution via gastrostomy, and the TPN + water group received an additional administration of distilled water via gastrostomy. The anastomotic bursting pressure (ABP) and the hydroxyproline content of the anastomotic tissue were measured 5 d postoperatively. In an in vitro setting, the rat gastrointestinal fibroblasts were subjected to uniaxial stretching for 60 min, and the expression of type I and type III collagen mRNA was evaluated. RESULTS: The ABP and hydroxyproline content in the EN group, the TPN + saline group, and the TPN + water group were significantly higher than those in the TPN alone group (ABP; 214.6 ± 42, 199.4 ± 36, and 187.3 ± 29 versus 149.5 ± 49 mmHg; P < 0.01, hydroxyproline; 63.5 ± 10, 67.8 ± 13, and 64.1 ± 14 versus 50.5 ± 12 µmol/g dry tissue; P < 0.01). The mRNA levels of type I and type III collagen were increased by stretch stimulation. CONCLUSIONS: These results suggest that mechanical loading plays a key role in anastomotic healing. Further investigations are necessary to confirm this suggestion.

Pathological complete response after preoperative chemotherapy including FOLFOX plus bevacizumab for locally advanced rectal cancer: A case report and literature review.

BACKGROUND: In Japan, the significance and efficacy of preoperative chemotherapy alone for locally advanced rectal cancer remain controversial. This case report presents the apparent effectiveness of preoperative FOLFOX plus bevacizumab as shown by pathological complete response (pCR). Additionally, we review the relevant literature and discuss the clinical management of locally advanced rectal cancer with preoperative chemotherapy. CASE PRESENTATION: A 59-year-old male presented with severe constipation, bloody stool and a loss of 10% of his body weight over 3 months. Preoperative examination revealed locally advanced rectal cancer with extensive invasion of the bladder wall and enlarged regional lymph nodes. Thus, this lesion was assigned a preoperative classification of T4bN2bM0 stage IIIC according to the 8th Union for International Cancer Control (UICC) guidelines. Therefore, the patient initially underwent an external loop colostomy of the transverse colon. Next, the patient received chemotherapy including FOLFOX plus bevacizumab. After 12 cycles of chemotherapy, the tumor size was markedly decreased, and all lymph node metastases had disappeared. Therefore, the patient underwent conventional resection of the rectum with D3 lymph node dissection and closure of the colostomy. Histopathological analysis of the resected specimen revealed that all lesions were fibrotic and devoid of any viable cancer cells. Thus, this lesion was assigned a final classification of ypT0N0M0 stage 0. CONCLUSIONS: We present the rare case of a patient with surgically resected locally advanced rectal cancer who demonstrated an impressive pCR with preoperative chemotherapy, which included FOLFOX plus bevacizumab.

Platelet dynamics in the early phase of postischemic liver in vivo.

BACKGROUND: In liver surgery, ischemia/reperfusion injury occasionally leads to liver failure by activating Kupffer cells (KCs) and leukocytes. However, few reports have demonstrated a relationship between KCs and platelets in vivo. This study investigated the relationship between these cells using intravital microscopy. MATERIALS AND METHODS: Male Wistar rats were divided into two groups: (1) KC+ group, receiving 1 mL saline; and (2) KC- group, intravenously injected with liposome-encapsulated dichloromethylene disphosphonate for elimination of KCs. At 48 h after administration, 20 min of total normothermic hepatic ischemia was induced. Rhodamine-6G-labeled platelets and sinusoidal alterations were monitored using intravital microscopy up to 120 min after reperfusion. P-selectin, accumulated leukocytes and morphological damage, and alanine aminotransferase were evaluated. RESULTS: In the KC+ group, numbers of adherent platelets increased significantly within 30 min after reperfusion. Endothelial cells of sinusoids in which KCs were mainly located were destroyed and the sinusoids were significantly constricted after reperfusion. Conversely, in the KC- group, adherent platelets in sinusoids were suppressed, and sinusoidal perfusion, endothelial cell damage and serum alanine aminotransferase levels were significantly improved. P-selectin on sinusoidal endothelial cells was not observed up to 120 min after reperfusion in either group. CONCLUSIONS: Adherent platelets appear to reflect activation of KCs and lead to leukocyte accumulation, resulting in sinusoidal perfusion disturbance and liver failure. Evaluation of adherent platelets in the microcirculation offers an important marker of hepatic injury.

The neutrophil-to-lymphocyte ratio (NLR) predicts short-term and long-term outcomes in gastric cancer patients.

BACKGROUND: The preoperative neutrophil-to-lymphocyte ratio (NLR) is a well-known prognostic marker for gastric cancer patients. However, the utility of the NLR in predicting short-term outcomes in gastric cancer patients remains unclear. Here, we investigated whether the preoperative NLR is a predictor of short-term outcomes in gastric cancer patients. METHODS: We retrospectively evaluated 154 consecutive gastric cancer patients. We compared the perioperative outcomes and median survival times (MSTs). In particular, for stage II/III (UICC, 7th edition) gastric cancer patients, we compared median disease-free survival time (MDFST) between the low- and high-NLR groups. RESULTS: Between the low-NLR group (n = 110) and the high-NLR group (n = 44), significant differences were observed in perioperative outcomes, including postoperative complications (3 (2.7%) vs. 5 (11.3%); p = 0.015), intraoperative blood loss (158 ± 168 g vs. 232 ± 433 g; p = 0.022), and intraoperative blood transfusions (0 vs. 3 (6.8%); p = 0.042). MSTs and MDFSTs were also significantly different (812 vs. 594 days, p = 0.04; and 848 vs. 475 days, p = 0.03, respectively). Multivariate analysis identified the NLR (hazard ratio [HR], 2.015; p = 0.004), Glasgow Prognostic Score (GPS) (HR, 1.533; p = 0.012), and presence of stage III/IV disease (HR, 5.488; p < 0.001), preoperative symptoms (HR, 3.412; p = 0.008), or postoperative complications (HR, 2.698; p < 0.001) as independent prognostic factors. CONCLUSIONS: We suggest that the preoperative NLR is an additional useful predictor of both long-term and short-term outcomes in gastric cancer patients.

Collision tumor consisting of a colorectal adenocarcinoma and dissemination of a gastric adenocarcinoma.

BACKGROUND: Collision tumors, composed of histologically distinct tumor types, are rare entities, especially in the colorectum, and corresponding evidence-based clinical management or treatment strategies are poorly defined. This is the first report of a collision tumor composed of two histologically distinct adenocarcinomas. CASE PRESENTATION: A 78-year-old male showed severe anemia and a 10% body weight loss over 1 month. Preoperative examination revealed T3N1M0 stage IIIA gastric cancer and T3N0M0 stage IIA rectal cancer. Distal gastrectomy and rectectomy with regional lymph node dissection were performed. Immunohistochemistry revealed two distinct adenocarcinomas with gland duct structures - a colorectal adenocarcinoma and a disseminated gastric adenocarcinoma - that had collided to form an invasive tumor on the serosal surface of the anterior rectum wall. CONCLUSION: This extremely rare case of a collision tumor supports that precise immunohistochemical identification of all tumor components is needed for guiding decisions affecting overall prognosis, adjuvant treatment and survival.

Hepatic sarcoidosis mimicking cholangiocellular carcinoma: A case report and literature review.

INTRODUCTION: Sarcoidosis is a multisystem disease characterized by the presence of non-caseating granulomas in affected organs. Almost 70% of patients with a sarcoidosis reaction have hepatic involvement. However, evidence-based clinical management or treatment strategies for hepatic sarcoidosis are poorly defined. Here, we present a case of a resected hepatic sarcoidosis patient. Additionally, we review the relevant hepatic sarcoidosis literature and discuss the clinical management of hepatic sarcoidosis. PRESENTATION OF CASE: A 20-mm liver tumor of segment 8 was incidentally detected in a 64-year-old female. Radiological images resembled the enhancement pattern of cholangiocellular carcinoma. Thus, this lesion was assigned a preoperative classification of pT1N0M0 stage I according to the 7th Union for International Cancer Control guidelines. The patient underwent a partial liver resection. Histologically, the tumor contained sarcoidosis lesions indicated by a conglomerate of epithelioid granulomas with giant cells. These histopathological findings were consistent with the diagnosis of hepatic sarcoidosis. DISCUSSION: Histopathological examination has been established as the definitive diagnostic tool for hepatic sarcoidosis. Therefore, liver biopsy or surgical resection of a liver tumor should be considered in cases that are difficult to preoperatively distinguish from malignant tumors. CONCLUSION: We present the case of a patient with surgically resected hepatic sarcoidosis that was difficult to preoperatively distinguish from cholangiocellular carcinoma.

The impact of three-dimensional reconstruction on laparoscopic-assisted surgery for right-sided colon cancer.

INTRODUCTION: During laparoscopic-assisted colorectal surgery (LACS) for right-sided colon cancer patients, we performed three-dimensional (3D) surgical simulation to investigate vascular anatomy, including the ileocolic artery (ICA), right colic artery (RCA) and superior mesenteric vein (SMV). AIM: We also used 3D imaging to examine the shortest distance from the root of the ileocolic vein (ICV) to the gastrocolic trunk (GCT). MATERIAL AND METHODS: We analyzed 46 right-sided colon cancer patients who underwent 3D-simulated LACS. We also examined a control group of 20 right-sided colon cancer patients who underwent LACS without 3D imaging. Patients who received such assessments were classified into the following two groups based on the vessel arrangement patterns of the ICA and SMV: the type A group, in which the ICA crosses anterior to the SMV, and the type B group, in which the ICA crosses posterior to the SMV. The shortest length from the root of the ICV to the GCT (D mm) was measured via 3D imaging. Patient characteristics and perioperative outcomes for these three groups were compared. RESULTS: The mean D mm for all cases was 29.2 ±5.21 mm. Mean D mm values for the type A and type B groups were 27.8 ±4.21 and 30.5 ±5.53 mm, respectively. Intraoperative blood loss was lower in the type A group (41.8 ±27.5 g) and the type B group (44.5 ±31.6 g) than that in the control group (86.8 ±27.5 g) (p = 0.013). CONCLUSIONS: 3D imaging was useful for understanding anatomical relationships during LACS.

The Impact of Laparoscopic-assisted Colorectal Surgery Using 3-dimensional Reconstruction for Highly Obese Patients With Colorectal Cancer.

OBJECTIVES: During laparoscopic-assisted colorectal surgery (LACS), precise recognition of the anatomic variations and relationships among tumor and vessels is required. However, in highly obese patients, it is more difficult to grasp the surgical anatomy due to the presence of dense mesenteric fat tissue. We utilized a 3-dimensional (3D) reconstructed image for preoperative simulation and intraoperative navigation for LACS. In this study, we examined the correlation between patient obesity and 3D-simulated perioperative outcomes. MATERIALS AND METHODS: We retrospectively analyzed 124 patients who underwent LACS using 3D surgical simulation at Tsukuba Medical Center Hospital. We sequentially divided our cohort into 2 groups: patients with a low body mass index (BMI<25 kg/m, n=60) and patients with a high BMI (BMI ≥25 kg/m, n=64). Patient characteristics and perioperative outcomes, including conversion rate, postoperative complications, operating time, intraoperative blood loss, and length of postoperative hospital stay, were compared for these 2 groups. RESULTS: There were no significant differences in patient background between the 2 groups.We found it more difficult to grasp the surgical anatomy, including vessel arrangement, for high-BMI patients than for low-BMI patients because of the dense mesenteric fat tissue in high-BMI patients. There were no significant differences between the 2 groups with respect to perioperative outcomes. CONCLUSIONS: The utilized reconstructed 3D images were useful for understanding anatomic relationships, including vessel arrangement, during LACS, particularly in highly obese patients.

Incidental esophageal submucosal tumor detection by chest radiography: A case report.

Esophageal submucosal tumors are occasionally detected incidentally during a gastrointestinal survey. In the present study, a case of esophageal leiomyoma is reported, which was incidentally detected by chest radiography during an annual survey of mass-screening for lung cancer. The patient underwent a laparoscopic lower esophagectomy, a proximal gastrectomy and a gastric tube reconstruction. Macroscopic examination revealed a 50×40×28-mm mass, while microscopic examination identified submucosal smooth muscle tissue without mitotic activity or necrosis. The tumor was diagnosed as an esophageal leiomyoma. The patient was asymptomatic during the three-month follow-up period. However, when a mass lesion adjacent to the gastrointestinal tract is detected during chest radiography, the possibility of a rare disease should be considered. Therefore, further investigation with upper gastrointestinal radiography and gastroendoscopy should be performed.

Totally laparoscopic hepatectomy exposing the major vessels.

BACKGROUND: Even during laparoscopic hepatectomy, a technique is often required to expose the major vessels, for example, in anatomical hepatectomy. We have standardized and performed such laparoscopic hepatectomy as successfully as open hepatectomy. METHODS: We divide the liver parenchyma without pre-coagulation, exposing the major vessels using CUSA. To control the bleeding, we keep the central venous pressure low and often perform Pringle's maneuver. Over 49 months, we performed totally laparoscopic hepatectomies in 41 patients with the technique of exposing the major vessels. These included major hepatectomy in 7, sectorectomy in 17, segmentectomy in 14, and others in 3. RESULTS: The median operative time was 361 (range 176-605) minutes, with median blood loss of 216 (range 0-1600) g. The conversion rate was 4.9 %. Postoperative morbidity rate was 9.8 % (prolonged ascites in 1, port site infection in 1, peroneal palsy in 2). Mortality was zero. The median length of hospital stay after surgery was 8 (range 5-28) days. No local recurrence was found at the time of writing. CONCLUSIONS: By using our standardized procedure exposing the major vessels, we could raise the quality of laparoscopic hepatectomy toward the level of open hepatectomy significantly.

Platelets prevent acute liver damage after extended hepatectomy in pigs.

BACKGROUND/PURPOSE: Platelets develop tissue repair and promote liver regeneration. We investigated whether platelets prevented acute liver damage after extended hepatectomy in pigs. METHODS: Thrombocytosis was induced by the following two methods; afterwards 80% hepatectomy was performed in pigs. In the first method, the pigs received administration of thrombopoietin [TPO (+) group], and they were compared with a control group [TPO (-) group]. In the second method, the pigs received a splenectomy [Sp (+) group], and theywere compared with another control group [Sp (-) group]. Platelet counts, biochemical examination of blood, and histopathological findings of the residual liver were examined. RESULTS: Serum aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP), and total bilirubin (T-Bil) levels were significantly decreased in the thrombocytotic groups compared with the control groups in the early period after hepatectomy. In the histopathological findings, hemorrhagic necrosis with a bile plug was observed in the control groups, but this phenomenon was not observed in the thrombocytotic groups. On transmission electron microscopy, the sinusoidal endothelial lining was destroyed and detached into the sinusoidal space with enlargement of Disse's spaces in the thrombocytotic groups, but these findings were not observed in the control groups. CONCLUSION: An increased number of platelets prevents acute liver damage after extended hepatectomy.