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.

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.

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.

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.

Gastrointestinal perforation during regorafenib administration in a case with hepatic metastases of colon cancer.

Although common side effects of regorafenib include hand-and-foot syndrome and diarrhoea, the incidence of gastrointestinal perforation is reportedly unknown. We describe our experience with the case of a 65-year-old woman treated with regorafenib as a third-line therapy for progressive caecal cancer with multiple hepatic metastases after 4 and 6 courses of systemic mFOLFOX6 + bevacizumab (BV) and FOLFIRI + BV chemotherapy, respectively. The patient used regorafenib for 32 days but visited our hospital with abdominal pain during the second course. She was diagnosed with acute appendicitis and treated conservatively with antibiotics. The abdominal findings did not improve, and a computed tomography evaluation on day 4 of hospitalization revealed free air lateral to the caecal tumour, liver surface, and epigastric region. The patient underwent same-day emergency surgery based on a diagnosis of gastrointestinal perforation with generalized peritonitis. Upon observing digestive fluid leakage into the peri-ileocaecal area and a 5-mm perforation in the appendix, the patient was diagnosed with peritonitis due to gastrointestinal perforation. Ileocaecal resection with D2 debridement was performed, and a colostomy was opened into the ileum and ascending colon. We conclude that our patient developed gastrointestinal perforation during regorafenib therapy and note that clinicians should be aware of this possible complication in patients with a history of prior treatment with BV.

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.

SPINK1 Status in Colorectal Cancer, Impact on Proliferation, and Role in Colitis-Associated Cancer.

UNLABELLED: Colorectal cancer is a major cause of deaths due to cancer; therefore, research into its etiology is urgently needed. Although it is clear that chronic inflammation is a risk factor for colorectal cancer, the details remain uncertain. Serine protease inhibitor, Kazal type 1 (SPINK1) is mainly produced in pancreatic acinar cells. However, SPINK1 is expressed in various cancers and in inflammatory states, such as colon cancer and inflammatory bowel disease. There are structural similarities between SPINK1 and epidermal growth factor (EGF). Hence, it was hypothesized that SPINK1 functions as a growth factor for tissue repair in inflammatory states, and if prolonged, acts as a promoter for cell proliferation in cancerous tissues. Here, immunohistochemical staining for SPINK1 was observed in a high percentage of colorectal cancer patient specimens and SPINK1 induced proliferation of human colon cancer cell lines. To clarify its role in colon cancer in vivo, a mouse model exposed to the colon carcinogen azoxymethane and nongenotoxic carcinogen dextran sodium sulfate revealed that Spink3 (mouse homolog of SPINK1) is overexpressed in cancerous tissues. In Spink3 heterozygous mice, tumor multiplicity and tumor volume were significantly decreased compared with wild-type mice. These results suggest that SPINK1/Spink3 stimulates the proliferation of colon cancer cells and is involved in colorectal cancer progression. IMPLICATIONS: Evidence suggests that SPINK1 is an important growth factor that connects chronic inflammation and cancer.

Simultaneous total laparoscopic curative resection for synchronous gastric, cecal and rectal cancer: Report of a case.

INTRODUCTION: Gastric cancer (GC) and colorectal cancer (CRC) are often diagnosed simultaneously. Recent technological advances in surgical techniques and devices have enabled the use of laparoscopic approaches for GC and CRC. Laparoscopic resection is expected to increase the number of cases of synchronous gastrointestinal (GI) cancers that meet the indication for laparoscopic surgery, owing to early detection of GI cancers and extended indications for laparoscopic surgery. PRESENTATION OF CASE: We herein report a successful simultaneous total laparoscopic curative resection for synchronous early GC, early cecal cancer and advanced rectal cancer. The total time of the operation was 600min, and the estimated blood loss was 250ml. The patient was discharged on postoperative day (POD) 10 without postoperative complications. CONCLUSION: Simultaneous total laparoscopic surgery is a minimally invasive, feasible treatment option for synchronous GI cancers.

Repeated recurrence of a gastric gastrointestinal stromal tumor on the chest wall after initial curative resection: Report of a case.

INTRODUCTION: Extra-abdominal recurrence or metastasis of a gastrointestinal stromal tumor (GIST) is very rare. Chest wall recurrence of a resected gastric GIST is extremely rare. PRESENTATION OF CASE: A 64-year-old Japanese man had undergone proximal gastrectomy for a gastric submucosal tumor 11 years previously. The histopathological diagnosis was GIST (size, 8cm). He did not receive adjuvant therapy, and underwent imaging evaluations every 6 months for the first 5 years after surgery and then annually. He was admitted to our hospital because of a lump on his right anterior chest wall 7 years after curative resection. We resected the tumor, and histopathologic findings revealed metastatic GIST. Four years after metastasectomy, another lump appeared at a different location on the right anterior chest wall. The patient was diagnosed with a second recurrence of gastric GIST and began adjuvant treatment with imatinib after second resection. He has remained alive without tumor recurrence for 2 years. DISCUSSION: Most recurrences were predominantly found in the intra-abdominal cavity, either locally or involving the liver or peritoneum. Extra-abdominal recurrence was much less common. Although we assume that the recurrent tumor of our patient was derived from his gastric GIST, based on the histopathological examinations and clinical course, it is possible that the recurrent tumor of our case was an "extragastrointestinal GIST". CONCLUSION: Because extra-abdominal recurrence can occur many years after curative resection, continued, careful whole-body follow-up is required for patients with high-risk GIST.

Pyoderma gangrenosum in an abdominal surgical site: a case report.

Pyoderma gangrenosum (PG) is an uncommon, ulcerative skin disease that is often associated with systemic diseases. Herein, we report a development of PG in a surgical site after cholecystectomy that was difficult to discriminate from surgical site infection. The patient was a 74-year-old man who had previously been diagnosed with myelodysplastic syndrome (MDS). Laparoscopic cholecystectomy was planned under diagnosis of cholecystolithiasis, but we converted to open cholecystectomy. The surgical wound was partially erythematous 4 days after surgery. In spite of opening the wound, cleansing it with sterile saline, and administration of antibiotics, inflammation spread with erosion. The clinical manifestations and histopathologic features of biopsy specimen indicated that diagnosis of PG associated with MDS was most likely. Administration of glucocorticoids made a rapid response of skin inflammation. The differential diagnosis of postoperative wound healing complications that were unresponsive to conventional wound local care and antibiotic therapy should include PG, especially in patients with systemic diseases such as MDS.

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.

Definitive diagnosis of a duplicate gallbladder can only be made intraoperatively: report of a case.

Duplicated gallbladders are rare congenital anomalies that are important in clinical practice as they may cause clinical, surgical, and diagnostic problems. Here, we describe the case of a 79-year-old female patient who presented with acute cholangitis. Abdominal ultrasonography, endoscopic ultrasonography, computed tomography, and magnetic resonance imaging revealed an intrahepatic cystic lesion, suggesting communication with the intrahepatic bile duct; no evidence of a polypoid lesion within the cystic lesion was observed. Based on these findings, intrahepatic cholangiectasis, intrahepatic bile duct cystadenoma, and the presence of a duplicated gallbladder were suspected, and surgery was performed. During surgery, a tube inserted into the common bile duct from a cystic duct facilitated intraoperative cholangiography, which indicated the presence of a duplicated gallbladder. Thus, we believe that a duplicated gallbladder should be an additional consideration when typical gallbladder disease symptoms are present under certain circumstances. A multimodal imaging approach can help to establish the diagnosis preoperatively or intraoperatively.

[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.

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.