Clinical impact of C-reactive protein to albumin ratio of the 7th postoperative day on prognosis after laparoscopic colorectal cancer surgery.

PURPOSE: C-reactive protein to albumin ratio (CAR) has been utilized as a prognostic factor in various carcinomas. We investigated the relationship between preoperative, postoperative day (POD) 1, and POD 7 CARs and the prognosis of patients with colorectal cancer (CRC). METHODS: Three hundred twenty patients with CRC who underwent laparoscopic radical resection between May 2011 and December 2016 were enrolled. Patients were selected into 2 groups, high CAR and low CAR (n=72/group), based on preoperative, POD 1, and POD 7 CARs. The relapse-free survival (RFS) and overall survival (OS) were compared between groups using propensity score matching. RESULTS: The high CAR group had a significantly worse RFS (P<0.001) and OS (P=0.002) at POD 7 than those in the low CAR group. However, in preoperative and POD 1 analysis, no differences were observed. CONCLUSION: In patients with CRC, CAR of POD 7 was a significant prognostic factor.

Reconsideration of the Appropriate Dissection Range Based on Japanese Anatomical Classification for Resectable Pancreatic Head Cancer in the Era of Multimodal Treatment.

Patients with resectable pancreatic cancer are considered to already have micro-distant metastasis, because most of the recurrence patterns postoperatively are distant metastases. Multimodal treatment dramatically improves prognosis; thus, micro-distant metastasis is considered to be controlled by chemotherapy. The survival benefit of "regional lymph node dissection" for pancreatic head cancer remains unclear. We reviewed the literature that could be helpful in determining the appropriate resection range. Regional lymph nodes with no suspected metastases on preoperative imaging may become areas treated with preoperative and postoperative adjuvant chemotherapy. Many studies have reported that the R0 resection rate is associated with prognosis. Thus, "dissection to achieve R0 resection" is required. The recent development of high-quality computed tomography has made it possible to evaluate the extent of cancer infiltration. Therefore, it is possible to simulate the dissection range to achieve R0 resection preoperatively. However, it is often difficult to distinguish between areas of inflammatory changes and cancer infiltration during resection. Even if the "dissection to achieve R0 resection" range is simulated based on the computed tomography evaluation, it is difficult to identify the range intraoperatively. It is necessary to be aware of anatomical landmarks to determine the appropriate dissection range during surgery.

Effective and safe reduction in visceral fat using a formula diet in a short period before highly invasive endoscopic surgery - Case series.

INTRODUCTION: We retrospectively assessed the efficacy and safety of use of short-term formula diet therapy to achieve preoperative reduction in visceral fat immediately prior to highly invasive endoscopic surgery. PRESENTATION OF CASE: We reviewed 5 cancer patients who underwent thoracoscopic and/or laparoscopic-assisted esophagectomy or gastrectomy. The cases were those with a BMI ≥30 kg/m2 or waist circumference ≥100 cm. Patients replaced one meal out of the three main meals with one or two sachets of formula diet (170-340 kcal). The other two meals were set to 600 kcal. The dietary therapy was implemented approximately 1 month before the operation. Weight loss achieved after dietary therapy ranged from 6.4% to 14.1% (p < 0.01). With the exception of one case, the decrease in visceral fat area ranged from 17.0%-40.7% (p = 0.03). Postoperative complications were anastomotic insufficiency in two cases. DISCUSSION: Although the decreases of the visceral fat were effectively implemented, the adverse effects on postoperative complications must be examined in the farther study. CONCLUSION: It was suggested that use of formula diet to achieve preoperative visceral fat reduction in a short period of time immediately prior to highly invasive endoscopic cancer surgery would be an effective and safe strategy.

Causative bacteria associated with a clinically relevant postoperative pancreatic fistula infection after distal pancreatectomy.

PURPOSE: Clinically relevant postoperative pancreatic fistulas (CR-POPF) occurring after distal pancreatectomy often cause intra-abdominal infections. We monitored the presence of bacterial contamination in the ascitic fluid after distal pancreatectomy to clarify the bacterial origin of intra-abdominal infections associated with CR-POPF. METHODS: In 176 patients who underwent distal pancreatectomy, ascitic fluid bacterial cultures were performed on postoperative days (POD) 1-4 and when the drainage fluid became turbid. The association between postoperative ascitic bacterial contamination and CR-POPF incidence was investigated. RESULTS: CR-POPF occurred in 18 cases (10.2%). Among the patients with CR-POPF, bacterial contamination was detected in 0% on POD 1, in 38.9% on POD 4, and in 72.2% on the day (median, day 9.5) when the drainage fluid became turbid. A univariate analysis revealed a significant difference in ascitic bacterial contamination on POD 4 (p < 0.001) and amylase level on POD 3-4 (p < 0.001). A multivariate analysis revealed the amylase level and ascitic bacterial contamination on POD 4 to be independent risk factors. CONCLUSIONS: In the CR-POPF group, ascitic bacterial contamination was not observed in the early postoperative stage, but the bacterial contamination rate increased after pancreatic juice leakage occurred. Therefore, CR-POPF-related infections in distal pancreatectomy may be caused by a retrograde infection of pancreatic juice.

Blumgart method using LAPRA-TY clips facilitates pancreaticojejunostomy in laparoscopic pancreaticoduodenectomy.

The modified Blumgart method for pancreaticojejunostomy has been shown to reduce the rate of postoperative pancreatic fistula (POPF) in open surgery. We describe a modified Blumgart method using LAPRA-TY suture clips to facilitate laparoscopic pancreaticojejunostomy.We prepared a double-armed 4-0 nonabsorbable monofilament, which was ligated using the LAPRA-TY clip at the tail end, 12-cm in length. Next, the U-suture was placed through the pancreatic stump and the seromuscular layer of the jejunum. We performed duct-to-mucosa suturing with a 5-0 absorbable monofilament. After completing the duct-to-mucosa suturing, as a final step we placed the sutures through the seromuscular layer of the jejunum on the ventral side and tightly secured the thread with the LAPRA-TY clips. We performed laparoscopic Blumgart pancreaticojejunostomy during pancreaticoduodenectomy in 39 patients. We compared the surgical outcomes of 19 patients who underwent Blumgart pancreaticojejunostomy using the LAPRA-TY clips (LAPRA-TY group) with 20 patients undergoing surgery not using the LAPRA-TY clips (conventional group).The rate of clinically relevant postoperative pancreatic fistula in the LAPRA-TY group was 21.1%, which did not differ significantly from the rate of the conventional group. However, the mean time of pancreaticojejunostomy in the LAPRA-TY group was 56.2 min (range, 39-79 min), which was significantly shorter than that of the conventional group (69.7 min; range, 53-105 min, P < .001).Although the modified Blumgart pancreaticojejunostomy using LAPRA-TY suture clips did not improve the pancreatic fistula rate, it allowed for shorter operative times. Thus, this procedure lends itself to positive surgical and patient outcomes.

Why Does Postoperative Pancreatic Fistula Occur After Hand-sewn Parenchymal Closure and Staple Closure in Distal Pancreatectomy?

Hand-sewing (HS) and stapling are common parenchymal closure techniques after distal pancreatectomy. However, these methods cannot completely prevent postoperative pancreatic fistula (POPF). The mechanisms of POPF formation after closure are unknown. We performed distal pancreatectomy in mongrel dogs to identify the mechanisms of POPF formation after HS and staple closure. We measured the closed pancreatic duct burst pressures and examined the histology of the remnant pancreas. The after staple-closure burst pressures depended on stapler height; lower pressures were associated with greater stapler heights. Post-HS closure burst pressures were significantly higher than those at each stapler height (P<0.01). Post-HS closure pathologic findings showed extensive necrosis (day 3), and some regenerated pancreatic duct stumps (day 5). Necrosis was not observed around the stapled tissues. Although HS completely closes the pancreatic ducts, stump necrosis and blood flow disturbances may cause POPF. With stapler closure, pancreatic fluid leakage may occur even with appropriate stapler heights.

Surgical resection of neuroendocrine tumors of the pancreas (pNETs) by minimally invasive surgery: the laparoscopic approach.

Neuroendocrine tumors of the pancreas (pNETs) are a rare group of neoplasms that originate from the endocrine portion of the pancreas. Tumors that either secrete or do not secrete compounds, resulting in symptoms, can be classified as functioning and non-functioning pNETs, respectively. The prevalence of such tumors has recently increased due to the use of more sensitive imaging techniques, such as multidetector computed tomography, magnetic resonance imaging and endoscopic ultrasound. The biological behavior of pNETs varies widely from indolent, well-differentiated tumors to those that are far more aggressive. The most effective and radical treatment for pNETs is surgical resection. Over the last decade, minimally invasive surgery has been increasingly used in pancreatectomy, with laparoscopic pancreatic surgery (LPS) emerging as an alternative to open pancreatic surgery (OPS) in patients with pNETs. Non-comparative studies have shown that LPS is safe and effective. In well-selected groups of patients with pancreatic lesions, LPS was found to results in good perioperative outcomes, including reduced intraoperative blood loss, postoperative pain, time to recovery, and length of hospital stay. Despite the encouraging results of studies from highly specialized centers with extensive experience, no randomized trials to date have conclusively validated these findings. Indications for minimally invasive LPS for patients with pNETs remain unclear. This review presents the current state of LPS for pNETs.

Surgical Outcomes of Pancreaticoduodenectomy for Pancreatic Cancer with Proximal Dorsal Jejunal Vein Involvement.

BACKGROUND/PURPOSE: The proximal jejunal vein which branches from the dorsal side of the superior mesenteric vein (SMV) usually drains the inferior pancreatoduodenal veins (IPDVs) and contacts the uncinate process of the pancreas. We focused on this vein, termed the proximal dorsal jejunal vein (PDJV), and evaluated the anatomical classification of the PDJV and surgical outcomes in patients with pancreatic ductal adenocarcinoma (PDAC) with PDJV involvement (PDJVI). METHODS: The jejunal veins that branch from the dorsal side of the SMV above the inferior border of the duodenum are defined as PDJVs. We investigated 121 patients who underwent upfront pancreaticoduodenectomy for PDAC between 2011 and 2017; PDJVs were resected in all patients. The anatomical classification of PDJV was evaluated using multidetector computed tomography. Surgical and prognostic outcomes of pancreticoduodenectomy for PDAC with PDJVI were evaluated. RESULTS: The PDJVs were classified into seven types depending on the position of the first and second jejunal veins relative to the superior mesenteric artery. In all patients, the morbidity and mortality rates were 15.7 and 0.8%, respectively. The rates for parameters including SMV resection, presence of pathological T3-4, R0 resection, and 3-year survival were 46.2, 92.3, 92.3, and 61.1%, respectively, when there was PDJVI (n = 13). When there was no PDJVI (n = 108), the rates were 60.2, 93.5, 86.1, and 58.3%, respectively. Overall, there were no significant differences. CONCLUSIONS: Pancreaticoduodenectomy with PDJV resection is feasible for PDAC with PDJVI and satisfactory overall survival rates are achievable. It may be necessary to reconsider the resectability of PDAC with PDJVI.

Approaching the superior mesenteric artery from the right side using the proximal-dorsal jejunal vein preisolation method during laparoscopic pancreaticoduodenectomy.

BACKGROUND: Although the artery-first approach is widely used in open pancreaticoduodenectomy, it is difficult to laparoscopically expose the origin of the inferior pancreaticoduodenal artery (IPDA) from the left side of the superior mesenteric artery (SMA). By contrast, damaging the inferior pancreaticoduodenal veins (IPDVs) is possible when approaching the IPDA from the right side of the SMA. To facilitate the artery-first approach in laparoscopic pancreaticoduodenectomy (LPD), we focused on the proximal-dorsal jejunal vein (PDJV) that branched from the superior mesenteric vein (SMV) dorsal side and drained the IPDVs. This study aimed to clarify the usefulness of the right SMA approach using the PDJV preisolation method. METHODS: The PDJV was first isolated, and the IPDVs were divided along the PDJV on the right side of the SMA. Then, the IPDA was divided at the root without first separating the pancreatic head from the portal vein and the SMV. Overall, 21 patients underwent this approach, and the results were retrospectively compared with those of 21 patients who underwent the artery-first approach, which was performed on the left side of the SMA. Anatomical characteristics of the PDJV were evaluated using multidetector computed tomography for the two groups. RESULTS: Operative times and resection times were significantly lower for the PDJV preisolation group than for the conventional LPD group (489.3 vs. 541.7 min, respectively; p = 0.002). During anatomical evaluation, 41 patients (97.6%) had a PDJV that drained from the SMV dorsally and was in contact with the anterior aspect of the uncinate process. The PDJV was confirmed as the first jejunal vein in 31 patients (73.8%) and as the second jejunal vein in 10 patients (23.8%). CONCLUSIONS: This approach facilitates dissection of the IPDA on the right side of the SMA, thereby reducing operative times.

[Surgical Case of Ulcerative Colitis Accompanied with Rectal Cancer Combined with Transanal Minimally Invasive Surgery].

A46 -year-old man developed ulcerative colitis at the age of 19 years. Although the colitis was medically treated, it relapsed and repeated over time. Periodic lower gastrointestinal endoscopy revealed lower rectal cancer, and he was referred to our department of surgery. Previous steroid therapy induced diabetes, and he was obese, with a height of 170.3 cm, weight of 89.6 kg, and BMI of 30.89 kg/m2, indicating that laparoscopic dissection near the anus would be difficult to perform. Therefore, the patient was scheduled for transanal minimally invasive surgery(TAMIS). The surgery involved as much laparoscopic rectal dissection as possible in the ventral to dorsal direction, followed by the TAMIS procedure. Dissection was started from the dentate line, and, after the closure of the anal stump, GelPOINT was placed, and made continuous with the previous dissection layer by applying the technique of down-to-up total mesorectal excision(TME)by TAMIS. The large intestine was excised through a small abdominal incision to create an ileal pouch, hand-sewn anastomosis was performed transanally to create a temporary colostomy, and the surgery was completed. Regarding TAMIS-TME several problems remain to be solved, including an understanding of its unique anatomy and the mastery of single-port surgical techniques. However, the herein reported patient with a high BMI had a definite indication for TAMIS-TME.

Correlation between the serum levels of type IV collagen 7s domain and the risk of intractable ascites following liver resection for hepatocellular carcinoma: A propensity score-matched analysis.

BACKGROUND: The severity of liver fibrosis has been reported to be correlated with the risk of intractable ascites after hepatectomy for hepatocellular carcinoma. Since 2009, we have measured routinely the serum concentrations of type IV collagen 7s domain (7s collagen), a biochemical marker of liver fibrosis and applied limited resection to patients with elevation of the serum 7s collagen concentrations above the upper limit of normal (6.0 ng/mL). The aim of this study was to assess the potential benefits of our treatment strategy on the postoperative outcomes of patients with hepatocellular carcinoma. METHODS: A propensity score-matched analysis was performed to compare the outcomes between patients who underwent initial hepatectomy for hepatocellular carcinoma before or after 2009 (2009 to April 2015; period 2) and those who underwent the operation prior to 2009 (1990-2008; period 1; n = 129 in each period). RESULTS: The incidence of intractable ascites was significantly lower in period 2 than in period 1 (2.3 vs 14.7%; P < .001), although the other short-term and long-term outcomes were comparable between the 2 groups. A multivariate analysis identified elevation of the serum 7s collagen concentrations to ≥7.4 ng/mL as an independent predictor of IA (odds ratio 14.1, 95% confidence interval 2.8 to 106.7; P = .001), with the area under the receiver-operating characteristic curve of 0.820 (0.648-0.919, P = .005). CONCLUSION: Modification of the surgical procedure according to the serum 7s collagen concentration is beneficial for reducing the risk of development of intractable ascites after hepatectomy for hepatocellular carcinoma.

Contrast-enhancement ratio on multiphase enhanced computed tomography predicts recurrence of pancreatic neuroendocrine tumor after curative resection.

BACKGROUND/OBJECTIVE: No previous study has quantitatively investigated the degree of enhancement of pancreatic neuroendocrine tumors (pNETs) using a routine preoperative modality. The aim of this study was to evaluate the contrast-enhancement ratio (CER) of pNETs using multiphase enhanced CT and to assess the impact of the CER on disease recurrence after surgery. METHODS: A retrospective study was performed using data from 47 consecutive patients with pNETs who had undergone curative surgery. The CER of the tumor was calculated by dividing the CT attenuation value obtained during the maximum-enhanced phase by that obtained during the pre-enhanced phase. A region of interest was placed in the largest tumor dimension plane so as to cover as much surface of the tumor as possible while avoiding adjacent normal structures, calcification, and necrotic areas of the tumor. RESULTS: During a median follow-up period of 51 months (range, 1-132 months), a total of 4 patients (8.5%) developed disease recurrence. The median CER value was significantly lower for the patients with recurrence than for the patients without recurrence (2.9 vs. 4.3, P = 0.013). Univariate analyses showed that a CER ≤3.2 was significantly associated with disease recurrence (P < 0.001). All the patients with disease recurrence had tumors that were both large (>20 mm) and weakly enhanced (CER ≤ 3.2), whereas no recurrences were observed even in patients with tumors >20 mm when the CER was greater than 3.2. CONCLUSIONS: CER might be a useful predictor of disease recurrence in patients with pNETs.

Genomic Sequencing Identifies ELF3 as a Driver of Ampullary Carcinoma.

Ampullary carcinomas are highly malignant neoplasms that can have either intestinal or pancreatobiliary differentiation. To characterize somatic alterations in ampullary carcinomas, we performed whole-exome sequencing and DNA copy-number analysis on 60 ampullary carcinomas resected from clinically well-characterized Japanese and American patients. We next selected 92 genes and performed targeted sequencing to validate significantly mutated genes in an additional 112 cancers. The prevalence of driver gene mutations in carcinomas with the intestinal phenotype is different from those with the pancreatobiliary phenotype. We identified a characteristic significantly mutated driver gene (ELF3) as well as previously known driver genes (TP53, KRAS, APC, and others). Functional studies demonstrated that ELF3 silencing in normal human epithelial cells enhances their motility and invasion.

Genomic spectra of biliary tract cancer.

The incidence of biliary tract cancer (BTC), including intrahepatic (ICC) and extrahepatic (ECC) cholangiocarcinoma and gallbladder cancer, has increased globally; however, no effective targeted molecular therapies have been approved at the present time. Here we molecularly characterized 260 BTCs and uncovered spectra of genomic alterations that included new potential therapeutic targets. Gradient spectra of mutational signatures with a higher burden of the APOBEC-associated mutation signature were observed in gallbladder cancer and ECC. Thirty-two significantly altered genes, including ELF3, were identified, and nearly 40% of cases harbored targetable genetic alterations. Gene fusions involving FGFR2 and PRKACA or PRKACB preferentially occurred in ICC and ECC, respectively, and the subtype-associated prevalence of actionable growth factor-mediated signals was noteworthy. The subgroup with the poorest prognosis had significant enrichment of hypermutated tumors and a characteristic elevation in the expression of immune checkpoint molecules. Accordingly, immune-modulating therapies might also be potentially promising options for these patients.

Heat Shock Protein 90 Is a Potential Therapeutic Target in Cholangiocarcinoma.

Cholangiocarcinoma is an aggressive malignancy with a poor prognosis, with no effective therapy other than surgical resection. Heat shock protein 90 (HSP90) is a key component of a multichaperone complex involved in the posttranslational folding of a number of client proteins, many of which play essential roles in tumorigenesis. Here, we attempted to clarify its prognostic significance and potential utility as a therapeutic target in cholangiocarcinoma. Immunohistochemical expression of HSP90 was assessed retrospectively in 399 cholangiocarcinoma cases and 17 human cholangiocarcinoma cell lines, along with the effect of a small-molecule HSP90 inhibitor (NVP-AUY922) on cholangiocarcinoma tumor growth and angiogenesis in human cholangiocarcinoma cell lines and xenografts. The positivity of HSP90 was 44.6% in intrahepatic cholangiocarcinoma (IHCC) and 32.8% in extrahepatic cholangiocarcinoma (EHCC), respectively. HSP90 expression was significantly associated with the 5-year survival rate for IHCC (P < 0.001) and EHCC (P < 0.001). HSP90 inhibition showed potent antiproliferative activity and reduced growth-associated signaling in human cholangiocarcinoma cells in vitro. Furthermore, treatment of cholangiocarcinoma xenograft-bearing mice with NVP-AUY922 significantly inhibited growth at doses far below the maximum-tolerated dose. HSP90 overexpression is a prognostic marker for cholangiocarcinoma. HSP90-targeted therapy may be an option for a subset of cholangiocarcinoma.

Successful living donor liver transplantation for acute liver failure after acetylsalicylic acid overdose.

A 20-year-old woman was admitted to an emergency hospital after ingesting 66 g of acetylsalicylic acid in a suicide attempt. Although she was treated with gastric lavage, oral activated charcoal, and intravenous hydration with sodium bicarbonate, her hepatic and renal function gradually deteriorated and serum amylase levels increased. Steroid pulse therapy, plasma exchange, and continuous hemodiafiltration did not yield any improvement in her hepatic or renal function, and she was transferred to our hospital for living donor liver transplantation. Nine days after drug ingestion, she developed hepatic encephalopathy: thus, we diagnosed the patient with acute liver failure with hepatic coma accompanied by acute pancreatitis due to the overdose of acetylsalicylic acid. Living donor liver transplantation was immediately performed using a left lobe graft from the patient's mother. Following transplantation, the patient's renal and hepatic function and consciousness improved, and she was discharged. In this report, we describe a rare case of acetylsalicylic acid-induced acute liver failure with acute hepatic coma and concomitant acute pancreatitis and acute renal failure, which were treated successfully with emergency living donor liver transplantation.

Fibroblast growth factor receptor 2 tyrosine kinase fusions define a unique molecular subtype of cholangiocarcinoma.

UNLABELLED: Cholangiocarcinoma is an intractable cancer, with limited therapeutic options, in which the molecular mechanisms underlying tumor development remain poorly understood. Identification of a novel driver oncogene and applying it to targeted therapies for molecularly defined cancers might lead to improvements in the outcome of patients. We performed massively parallel whole transcriptome sequencing in eight specimens from cholangiocarcinoma patients without KRAS/BRAF/ROS1 alterations and identified two fusion kinase genes, FGFR2-AHCYL1 and FGFR2-BICC1. In reverse-transcriptase polymerase chain reaction (RT-PCR) screening, the FGFR2 fusion was detected in nine patients with cholangiocarcinoma (9/102), exclusively in the intrahepatic subtype (9/66, 13.6%), rarely in colorectal (1/149) and hepatocellular carcinoma (1/96), and none in gastric cancer (0/212). The rearrangements were mutually exclusive with KRAS/BRAF mutations. Expression of the fusion kinases in NIH3T3 cells activated MAPK and conferred anchorage-independent growth and in vivo tumorigenesis of subcutaneous transplanted cells in immune-compromised mice. This transforming ability was attributable to its kinase activity. Treatment with the fibroblast growth factor receptor (FGFR) kinase inhibitors BGJ398 and PD173074 effectively suppressed transformation. CONCLUSION: FGFR2 fusions occur in 13.6% of intrahepatic cholangiocarcinoma. The expression pattern of these fusions in association with sensitivity to FGFR inhibitors warrant a new molecular classification of cholangiocarcinoma and suggest a new therapeutic approach to the disease.

Hepatectomy preserving drainage veins of the posterior section for liver malignancy invading the right hepatic vein: an alternative to right hepatectomy.

BACKGROUND: Although a right hepatectomy (RH) traditionally has been performed for liver tumors infiltrating the main trunk of the right hepatic vein (RHV), the presence of drainage veins of the posterior section (DVPS) beside the RHV provides a chance to preserve their draining area even if the main trunk of the RHV is removed. METHODS: Since 2005, we systematically have performed DVPS-preserving hepatectomies whenever possible. In the present study, we describe our experience treating 12 consecutive patients who underwent this procedure. RESULTS: We performed the following types of liver resections concomitant with the main trunk of the RHV without packed red cell transfusion, liver failure, or 90-day mortality: extended right anterior sectionectomy in 2 patients, extended segmentectomy 7 in 3, extended segmentectomy 8 in 2, and partial resection of segment 7 in 2 and segment 8 in 3. Postoperative morbidity was observed in 4 (33%) cases, all of which had pleural effusion requiring a tap. A free resection margin was obtained in all patients. CONCLUSIONS: This procedure could be a useful alternative to RH, providing a chance for radical liver resection with minimal parenchymal sacrifice in selected patients with DVPS.