Assessing the economic advantage of laparoscopic vs. open approaches for colorectal cancer by a propensity score matching analysis.

PURPOSES: This study investigated the surgical outcomes and potential economic advantage of open vs. laparoscopic surgery for colorectal cancer using a propensity score matching analysis. METHODS: We examined the surgical and economic outcomes of patients undergoing laparoscopic (N = 127) and open surgery (N = 253) for colorectal cancer and then compared these outcomes in two groups (N = 103 each) using a propensity score matching analysis. RESULTS: Compared to open surgery, the laparoscopic approach was associated with a significantly lower overall morbidity rate (14 vs. 40%; P < 0.001) and shorter mean (± standard deviation) postoperative hospital stay (12.6 ± 8.3 vs. 16.8 ± 9.9 days, respectively; P = 0.001). Despite generating higher mean surgical costs (Japanese yen) (985,000 ± 215,000 vs. 812,000 ± 222,000 yen; P < 0.001), utilizing a laparoscopic approach significantly reduced the non-surgical costs (773,000 ± 440,000 vs. 1075,000 ± 508,000 yen; P < 0.001). The mean total cost of laparoscopic-assisted surgery (1758,000 ± 576,000 yen) was decreased by approximately 130,000 yen compared with open surgery (1886,000 ± 619,000 yen), although the difference was not statistically significant (P = 0.125). CONCLUSIONS: Laparoscopic surgery for colorectal cancer is advantageous in reducing morbidity and facilitating an early discharge and does not increase hospital costs. These findings are consistent with the general consensus supporting the benefits of laparoscopic surgery as a minimally invasive approach.

Significance of lymph node metastasis in pancreatic neuroendocrine tumor.

PURPOSE: Pancreatic neuroendocrine tumor (PNET) is relatively rare and has a generally better prognosis than does pancreatic cancer. However, as its prognosis in patients with lymph node metastasis (LNM) is unclear, lymph node dissection for PNET is controversial. Our study aimed to clarify the significance of LNM in PNET. METHODS: We retrospectively examined 83 PNET patients who underwent pancreatic resections with lymph node dissection at Kumamoto University Hospital, Saiseikai Kumamoto Hospital, and Kumamoto Regional Medical Center from April 2001 to December 2014. Their clinicopathological parameters were analyzed by the absence or presence of LNM, and with regard to the disease-free survival (DFS) and overall survival (OS). A predictive score of LNM was also made using the age, tumor size, primary tumor location, and tumor function. RESULTS: Although the 5-year OS was 74.8% for LNM+ and 94.6% for LNM- (P = 0.002), LNM was not an independent risk factor for the OS in a multivariate analysis. However, tumors larger than 1.8 cm were found to be an independent prognostic factor, and the cut-off value for the predictive score was 1.69. CONCLUSIONS: Although LNM was not an independent prognostic factor, lymph node dissection is recommended for patients whose predictive score is larger than 1.69.

Transnasal inner drainage: an option for managing anastomotic leakage after esophagectomy.

PURPOSE: Anastomotic leakage, a serious complication of esophagectomy, continues to contribute to high surgery-related mortality. Management of anastomotic leakage has become a serious concern for surgeons. This study aimed to evaluate the utility of transnasal inner drainage using a Salem Sump tube for anastomotic leakage after esophagectomy. METHODS: We inserted a Salem Sump tube into the esophagus through one nostril. By using a 0.035-inch guide wire under fluoroscopic guidance, we advanced this drainage tube into the abscess through the site of the anastomotic leakage. We also used upper endoscopy if necessary. RESULTS: We performed transnasal inner drainage in five patients with anastomotic leakage after esophagectomy. The average interval from the operation to diagnosis of anastomotic leakage was 7.8 days (median: 7, range: 3-18 days). The average duration of drainage was 15.8 days (median: 16, range: 11-21 days). No patients required additional surgical treatment and there was no operative mortality. No stricture was observed during the follow-up period. CONCLUSIONS: Transnasal inner drainage is successful, and may decrease the duration of drainage and reduce surgery-related mortality caused by anastomotic leakage. Additionally, this technique enables treatment of abscesses that cannot be managed by percutaneous drainage because of their locations, and can be safely undertaken in most institutions. Transnasal inner drainage is a safe, useful, inexpensive, and minimally invasive method, which may be an option for management of post-esophagectomy anastomotic leakage.

[A Case of Intestinal Diverticular Perforation in Roux-en-Y Reconstruction after Laparoscopic Distal Gastrectomy].

An 81-year-old woman who had undergone laparoscopic distal gastrectomy complained of abdominal pain 21 days after the operation.Blood tests showed a strong inflammatory reaction.Abdominal CT revealed a perforation in the small intestinal diverticula.Partial jejunectomy including the diverticulum was performed.The diverticular perforation was attributed to the presence of undigested food in the diverticulum.The patient had an uneventful postoperative course, and she was discharged on postoperative day 32.

Autophagy regulation in pancreatic acinar cells is independent of epidermal growth factor receptor signaling.

Autophagy is an intracellular degradation system in eukaryotic cells that occurs at a basal level. It can also be induced in response to environmental signals including nutrients, hormones, microbial pathogens, and growth factors, although the mechanism is not known in detail. We previously demonstrated that excessive autophagy is induced within pancreatic acinar cells deficient in Spink3, which is a trypsin inhibitor. SPINK1, the human homolog of murine Spink3, has structural similarity to epidermal growth factor (EGF), and can bind and stimulate the EGF receptor (EGFR). To analyze the role of the EGFR in pancreatic development, in the regulation of autophagy in pancreatic acinar cells, and in cerulein-induced pancreatitis, we generated and examined acinar cell-specific Egfr-deficient (Egfr(-/-)) mice. Egfr(-/-) mice showed no abnormalities in pancreatic development, induction of autophagy, or cerulein-induced pancreatitis, suggesting that Egfr is dispensable for autophagy regulation in pancreatic acinar cells.

Risk factors for pulmonary complications after esophagectomy for esophageal cancer.

PURPOSE: Pulmonary complications after esophagectomy are still common and are a major cause of mortality. The aim of this study was to clarify the risk factors for the occurrence of pulmonary complications after esophagectomy. METHODS: The clinical courses of 299 patients who underwent elective subtotal esophagectomy with lymph node dissection for esophageal cancer were retrospectively analyzed. Group I included patients who had pulmonary complications (n = 53), and group II included patients who did not (n = 246). The clinicopathological factors, surgical procedures and surgical results were compared between the groups. RESULTS: The frequency of any pulmonary complication was 17.7 %. Pneumonia (n = 26; 8.7 %) and respiratory failure that needed initial ventilatory support for 48 h or reintubation (n = 16; 5.4 %) were the major morbidities. The results of the logistic regression analysis suggested that smoking with a Brinkman index ≥800, salvage esophagectomy after definitive chemoradiotherapy and the amount of blood loss/body weight were independent factors associated with the occurrence of pulmonary complications. CONCLUSION: Pulmonary complications after esophagectomy remain common despite advances in perioperative management. Cases with a history of heavy smoking, preoperative definitive chemoradiotherapy, and high blood loss during surgery require more careful postoperative pulmonary care.

[Intraoperative complications and short-term outcomes of total laparoscopic distal gastrectomy (TLDG) for gastric cancer].

In recent years there has been an increase in the number of laparoscopic surgeries for gastric cancer, with over 8,000 cases reported nationwide in 2012. To date, we have performed 420 total laparoscopic distal gastrectomy (TLDG) procedures. In all cases, the mean operative time was 304 minutes, intraoperative bleeding was at 52 g, 30 lymph nodes were dissected, and the length of postoperative hospital stay was 10.6 days, on average. We experienced 5 intraoperative complications and 13 postoperative complications. Of 4 patients, there were 2 cases of postoperative recurrence in liver metastases, 1 case of metastatic lung tumor, and 1 case of peritoneal metastasis. Based on surgical outcomes, TLDG is a safe and feasible procedure for gastric cancer.

[Laparoscopic total colectomy (TPC) for familial adenomatous polyposis - a case report].

A 30-year-old man was admitted with anemia. Colonoscopy showed diffuse small polyps in the colon, 1 cancer in the sigmoid colon, and 2 cancers in the rectum. He was diagnosed with familial adenomatous polyposis (FAP). Total colectomy was conducted laparoscopically through 5 trocars, and a total proctocolectomy (TPC ) was performed. The operating time was 9 hours and 30 minutes, and intraoperative blood loss was 20 g. On the 1st postoperative day, he started oral intake. On the 14th postoperative day, he was discharged from our hospital. We thus consider laparoscopic resection to be a very useful technique for FAP.

Hepatic hemangioma in a simple liver cyst mimicking biliary cystic neoplasm.

BACKGROUND: Follow-up is recommended for an asymptomatic unilocular hepatic cystic lesion without wall-thickness and nodular components. A few liver cystic lesions represent biliary cystic neoplasms, which are difficult to differentiate from simple cysts with benign mural nodules on imaging alone. CASE PRESENTATION: An 84-year-old woman with a history of simple liver cyst diagnosed one year prior was admitted for evaluation of a developed mural nodule in the cystic lesion. She had no specific symptoms and no abnormalities in blood tests except for carcinoembryonic antigen (5.0 ng/mL) and carbohydrate antigen (43.5 U/mL) levels. Contrast-enhanced computed tomography revealed a well-defined, low-attenuation lesion without a septum that had enlarged from 41 to 47 mm. No dilation of the bile duct was observed. A gradually enhancing mural nodule, 14 mm in diameter, was confirmed. MRI revealed a uniform water-intense cystic lesion with a mural nodule. This was followed by T2-enhanced imaging showing peripheral hypointensity and central hyperintensity. Enhanced ultrasonography revealed an enhanced nodule with a distinct artery within it. A needle biopsy of the wall nodule or aspiration of intracystic fluid was not performed to avoid tumor cell spillage. The possibility of a neoplastic cystic tumor could not be ruled out, so a partial hepatectomy was performed with adequate margins. Pathologically, the cystic lesion contained a black 5 mm nodule consisting of a thin, whitish fibrous wall and dilated vessels lined by CD31 and CD34 positive endothelial cells. The final diagnosis was a rare cavernous hemangioma within a simple liver cyst. CONCLUSIONS: Cavernous hemangiomas mimicking well-enhanced mural nodules can arise from simple liver cysts. In less malignant cases, laparoscopic biopsy or percutaneous targeted biopsy of the mural nodules, together with needle ablation, may be recommended to avoid unnecessary surgery.

A rare incidence of a hepatic artery pseudoaneurysm following plastic biliary stent insertion.

Hepatic artery pseudoaneurysms have been reported to occur in approximately 1% of cases after metal stenting for malignant biliary obstruction. In contrast, only a few cases have been reported as complications after plastic stenting for benign biliary disease. We report a 61-year-old man with cholangitis who presented with a rare complication of hemobilia after implantation of 7 Fr double pigtail plastic biliary stents. No bleeding was observed approximately one month after biliary stent tube removal. Contrast-enhanced CT scan revealed a circularly enhanced lesion (5 mm in diameter) in the arterial phase at the tip of the previously inserted plastic bile duct stent. Color Doppler ultrasonography enhanced the lesion and detected arterial blood flow inside. He was diagnosed with a hepatic artery pseudoaneurysm. However, he had no risk factors such as prolonged catheterization, severe cholangitis, liver abscess, or long-term steroid use. Superselective transarterial embolization using two metal microcoils was successfully completed without damage to the surrounding liver parenchyma. If hemobilia is suspected after insertion of a plastic bile duct stent, immediate monitoring using contrast-enhanced computed tomography or Doppler ultrasonography is recommended.

Surgery for Hepatocellular Carcinoma With Macroscopic Vascular Invasion in the Era of Modern Molecular Therapy.

It has been reported that patients with macroscopic vascular invasion accompanying hepatocellular carcinoma have a poor prognosis. Modern molecular therapy with multitargeted tyrosine kinase inhibitors and immune checkpoint inhibitors has shown promising results in patients with metastatic hepatocellular carcinoma; however, molecular therapy is limited to patients with Child-Pugh class A disease. This review summarizes the present status of surgical therapies, including conversion hepatectomy, for patients with MVI in the developing era of novel molecular therapy. Phase III studies showed patients with macroscopic vascular invasion had significant survival benefits from sorafenib [hazard ratio (HR)=0.68] and regorafenib (HR=0.67) versus placebo, and nivolumab (HR=0.74) versus sorafenib. Lenvatinib and atezolizumab plus bevacizumab showed marginal effects. It is currently widely assumed that molecular therapy alone will not cure the disease but that additional conversion hepatectomy will be required. A response other than progressive disease is essential but a pathological complete response is not always required. A significant randomized controlled trial has already started in China to assess the necessity for conversion hepatectomy after effective atezolizumab plus bevacizumab treatment, and the results are still awaited. According to Japanese national data, upfront hepatectomy can be recommended for patients with initially resectable disease and macroscopic vascular invasion other than for those with tumors in the main portal vein and the inferior vena cava. In addition, adequate adjuvant therapies with hepatic arterial chemotherapy and transarterial chemoembolization may be beneficial but an effective adjuvant molecular therapy is currently unavailable. In conclusion, novel molecular therapies with higher response rates customized to the oncologic characteristics of each hepatocellular carcinoma with macroscopic vascular invasion are needed to increase the likelihood of conversion surgery and improve long-term outcomes.

Durable Stable Disease by Atezolizumab/Bevacizumab Can Provide Long-term Survival of Patients With Hepatocellular Carcinoma Lung Metastases.

BACKGROUND: Multiple bilateral lung metastases secondary to hepatocellular carcinoma (HCC) are mainly treated with molecular therapy. Atezolizumab plus bevacizumab can provide excellent long-term survival for patients with a good response. CASE REPORT: A 67-year-old woman underwent right hepatectomy for a primary solitary HCC, 11 cm in diameter, after portal embolization. After 2 years, she developed bilateral lung metastases with >100 nodules, <1 cm in size. She had no viral hepatitis or liver cirrhosis, and the Child-Pugh Grade was A (5 points). Lenvatinib (12 mg daily) was administered as a first-line treatment and continued for 18 months. The best response was stable disease (SD). Subsequently, intravenous atezolizumab (1,200 mg) plus bevacizumab (15 mg/kg) was administered once every three weeks. The best response was SD, which continued for 26 months. After that, cabozantinib treatment was initiated and discontinued after one cycle. Subsequently, dual immune checkpoint inhibitor treatment (durvalumab + tremelimumab) was administered. She has had multiple, but lung-only, metastases over four years. She has been well as an outpatient with the Child-Pugh Grade of A and a performance status of 0. CONCLUSION: Even if atezolizumab plus bevacizumab does not induce a good response, a durable SD could prolong survival in patients with metastatic HCC while maintaining liver function and a good quality-of-life.

[Evaluating the effectiveness and timing of modification of anti-cancer drug therapies for colorectal cancer].

Although treatments for unresectable colorectal cancer have made great progress with new anticancer agents, they are still unsatisfactory. Development of anti-cancer therapy and its management are important in order to improve the treatment outcome of colorectal cancer. In the evaluation of treatment effect, obtaining a baseline image at the start of treatment is very important, and CT scan is generally performed for this purpose. In daily clinical practice, response evaluation criteria in solid tumors(RECIST)is usually adapted for the assessment of treatment outcomes. In addition, we should make decisions about continued therapy on the basis of both objective and symptomatic findings. Patients receiving palliative chemotherapy should be monitored with a CT scan every 2 to 3 months. It is important to make a treatment strategy individually in consideration of adverse events, purposes of the treatment, and tumor progression.

Relationship of strain-dependent susceptibility to experimentally induced acute pancreatitis with regulation of Prss1 and Spink3 expression.

To analyze susceptibility to acute pancreatitis, five mouse strains including Japanese Fancy Mouse 1 (JF1), C57BL/6J, BALB/c, CBA/J, and C3H/HeJ were treated with either a cholecystokinin analog, cerulein, or a choline-deficient, ethionine-supplemented (CDE) diet. The severity of acute pancreatitis induced by cerulein was highest in C3H/HeJ and CBA/J, moderate in BALB/c, and mildest in C57BL/6J and JF1. Basal protein expression levels of the serine protease inhibitor, Kazal type 3 (Spink3) were higher in JF1 and C57BL/6J mice than those of the other three strains under normal feeding conditions. After treatment with cerulein, expression level of Spink3 increased remarkably in JF1 and mildly in C57BL/6J, BALB/c, CBA/J, and C3H/HeJ strains. Increased proteinase, serine, 1 (Prss1) protein expression accompanied by increased trypsin activity with cerulein treatment was observed in susceptible strains such as CBA/J and C3H/HeJ. Similar results were obtained with a CDE diet. In the 3 kb Spink3 promoter region, 92 or 8 nucleotide changes were found in JF1 or C3H vs C57BL/6J, respectively, whereas in the Prss1 promoter region 39 or 46 nucleotide changes were found in JF1 or C3H vs C57BL/6J, respectively. These results suggest that regulation of Prss1 and Spink3 expression is involved in the susceptibility to experimentally induced pancreatitis. The JF1 strain, which is derived from the Japanese wild mouse, will be useful to examine new mechanisms that may not be found in other laboratory mouse strains.

[Acute liver injury with hepatic encephalopathy associated with gemcitabine administration for adjuvant chemotherapy in an HBV carrier with pancreatic cancer].

A 75-year-old woman was admitted to our department because of epigastric pain. Imagings revealed cancer of the head of the pancreas. She was an HBV carrier, although no liver dysfunction was observed. Her serum HBV-DNA level was lower than 2.6. We performed pancreaticoduodenectomy for pancreatic cancer. No postoperative complication was observed. The histopathological diagnosis was tubular adenocarcinoma of the pancreas. As a postoperative adjuvant chemotherapy, gemcitabine hydrochloride (GEM) was injected at a dose of 800mg/m2 once a week. Disorientation and jaundice were observed after six doses of GEM. Blood chemistry revealed that total bilirubin and ammonia were abnormally elevated, and that blood coagulant factors were diminished. Serum HBV-DNA level was lower than 2.6. It showed no reactivation of HBV. Abdominal CT showed no recurrence but fatty liver. Fresh frozen plasma was supplied and branched chain amino acids were injected after GEM was administration discontinued. Lactulose was also given orally. With these conservative treatments, she recovered completely. Careful monitoring of liver function during GEM administration is required in a HBV carrier.

Significance of endothelial molecular markers in the evaluation of the severity of acute pancreatitis.

PURPOSE: In acute pancreatitis, neutrophil elastase is secreted which damages the endothelial cells. This study was designed to demonstrate that the plasma levels of soluble E-selectin (sES) and soluble thrombomodulin (sTM) serve as endothelial molecular markers; the former is used as an endothelial activation marker, while the latter, as an endothelial injury marker. METHODS: A total of 27 acute pancreatitis patients were enrolled. The plasma sES and sTM levels were assessed for 10 days after admission. RESULTS: The plasma sES levels of all the patients in different disease stages were elevated at the time of admission day (day 1). The plasma sTM levels correlated with the severity and prognosis of acute pancreatitis. The required cutoff to predict a fatal outcome was set as 32 Teijin Units (TU)/ml (sensitivity, 80%; specificity, 91%). On day 1, the mortality rate of patients with the sTM levels of > or = 32 TU/ml (67%, 4/6) was significantly higher than of those with the sTM levels of <32 TU/ml (5%, 1/21). CONCLUSION: These results indicated that (1) the activation of the vascular endothelial cells and the resultant increase in the plasma sES levels might be evoked in all disease stages, and (2) an elevation of the plasma sTM level, which indicates the presence of vascular endothelial injury, might therefore result in a poor prognosis.

Frailty predicts severe postoperative complications after elective colorectal surgery.

BACKGROUND: We aim to clarify if frailty affects severe postoperative complications in elective colorectal surgery. METHODS: Consecutive 269 colorectal cancer patients older than 65 years undergoing curative surgery were enrolled in this study. The relevance of the frailty and sarcopenia to postoperative outcome was assessed. Clinical frailty (CF) was defined as clinical frailty scale (CFS) ≥ 4. Sarcopenia was assessed by measuring skeletal muscle area using computed tomography. RESULTS: Seventy-eight patients (29%) had CF and 159 patients (59%) had sarcopenia. CF was significantly associated with older age (P = 0.0008), postoperative severe complications (P = 0.001), and postoperative in-hospital stay (P < 0.0001), although sarcopenia was not. Logistic regression analysis revealed that low anterior resection and CF were independent predictors of severe postoperative complications (P = 0.038 and P = 0.001, respectively). CONCLUSION: CF, but not sarcopenia, is a robust predictor of severe postoperative complications in patients with colorectal cancer.

Frailty Predicts Severe Postoperative Complication after Elective Hepatic Resection.

BACKGROUND: Frail patients are likely to suffer from postoperative complication, but this assumption has not been well confirmed. OBJECTIVES: This study aims to clarify the importance of frailty in patients undergoing hepatectomy for predicting severe postoperative complications. METHOD: One hundred and forty-three patients aged >65 years undergoing hepatectomy between 2011 and 2016 were enrolled in this study. The relevance of frailty versus sarcopenia for postoperative outcome was assessed. We defined clinical frailty (CF) as a CF scale >4. Sarcopenia was defined by the total muscle area at the level of the third lumbar vertebra measured on computed tomography. RESULTS: There were 16 patients (11%) with CF and 80 patients (56%) with sarcopenia. CF was associated with high age (p < 0.0001), severe postoperative complications (Clavien-Dindo classification ≥3) (p = 0.0059), and postoperative in-hospital stay (p = 0.0013). On the other hand, sarcopenia was not associated with postoperative outcome. Logistic regression analysis revealed that only CF was an independent predictor of severe postoperative complication (risk ratio of 4.2; p = 0.017). The occurrence of organ/space surgical site infection was significantly higher in the frailty group than in the non-frailty group. CONCLUSION: CF, but not sarcopenia, is a robust predictor of severe postoperative complications for patients undergoing hepatectomy.

C/EBP homologous protein is crucial for the acceleration of experimental pancreatitis.

C/EBP homologous protein (CHOP) is one of the main mediating factors in the ER stress pathway. To elucidate the role of the ER stress-CHOP pathway in experimental pancreatitis, wild-type (Chop(+/+)) and Chop deficient (Chop(-/-)) mice were administered cerulein, a cholecystokinin analogue, or both cerulein and lipopolysaccharide (LPS). In cerulein-induced acute pancreatitis, ER stress, serum amylase elevation and histological interstitial edema were induced. However, there was no remarkable activation downstream of the CHOP pathway regardless of the presence or absence of CHOP. Whereas, in the cerulein and LPS model, inflammation-associated caspases (caspase-11, caspase-1) and IL-1beta, but not apoptosis-associated caspases, were activated. In Chop(-/-) mice, the expression levels of these mediators returned to basal levels resulting in a milder pancreatitis and decreased serum amylase level. These results indicated that the ER stress-CHOP pathway has a pivotal role in the acceleration of pancreatitis through the induction of inflammation-associated caspases and IL-1beta.