Effect of emergency general surgery on postoperative performance status in patients aged over 90 years.

Background: Functional deterioration following emergency general surgery (EGS) poses a significant challenge in super-elderly patients. However, limited research has focused on assessing the deterioration in postoperative performance status (PS). This study aimed to investigate the impact of EGS on PS deterioration in super-elderly patients, and the extent to which deteriorated PS is recovered. Methods: This historical cohort study comprised 77 super-elderly patients who underwent EGS between July 2015 and December 2020. Functional deterioration was evaluated by comparing preoperative and postoperative Eastern Cooperative Oncology Group Performance Status (ECOG-PS). The Emergency Surgical Score (ESS) was used as a risk-adjustment tool. Questionnaires were mailed to the patients and their families to assess post-discharge PS and obtain their impressions of EGS. Results: Postoperative PS deteriorated in 35/77 patients (45.5 %). Significant differences were observed between the groups in terms of sex, serum C-reactive protein (CRP) levels, ESS scores, preoperative ECOG-PS, duration of operation, and major complications. Multivariate analysis of preoperative factors showed that ESS ≥7 (OR: 3.7, 95 % CI: 1.0-13), preoperative ECOG-PS ≤2 (OR: 5.9, 95 % CI: 1.7-21), and female sex (OR: 5.8, 95 % CI: 1.6-21) were associated with postoperative ECOG-PS deterioration. According to the questionnaire results, PS recovery post-discharge was observed in 6/36 (17 %) patients, and 34/36 (94 %) patients and their families expressed positive impressions of EGS. Conclusions: EGS in super-elderly patients highly caused a deterioration in their PS, particularly in patients with maintained preoperative PS. PS hardly recovered; however, most patients and their families had positive impressions of the EGS. Key message: We assessed the pre- and postoperative performance status of super-elderly patients who underwent emergency general surgery. Surgery caused a marked deterioration in patients' functional performance, which seldom recovered postoperatively.

Evaluating the outcomes of primary anastomosis with hand-sewn full-circular reinforcement in managing perforated left-sided colonic diverticulitis.

Background: It is a challenge to avoid stoma formation in emergency surgery of perforated left-sided diverticulum. The hand-sewn full-circular reinforcement of the colorectal anastomosis is used during complete pelvic peritonectomy to avoid a diverting ileostomy. This study examined the effect of applying the reinforcement method to perforated left-sided colonic diverticulitis with respect to the permanent stoma rate and cost-effectiveness. Materials and methods: This historical cohort study examined all patients who underwent emergency surgery for perforation of a left-sided diverticulum at the Hyogo Prefectural Amagasaki General Medical Center between July 2015 and September 2019. The cohort was divided into two groups: those who underwent conventional method (Group F) and those for whom the hand-sewn full-circular reinforcement method was actively performed (Group L). Results: The number of patients who underwent emergency surgery which did not lead to an ostomy increased significantly from 12% (3/25) in Group F to 42% (11/26) in Group L (P = 0.0015). The rate of permanent stoma decreased from 80% in Group F to 27% in Group L (P < 0.001). Total treatment costs for patients under the age of 80 in Group L were significantly lower than those in Group F (2170000 ± 1020000 vs 3270000 ± 1960000 JPY; P = 0.018). Conclusions: In emergency surgery for left-sided perforated colonic diverticulitis, applying the hand-sewn full-circle reinforcement of the anastomotic site may reduce stoma formation at the initial surgery and consequently decrease permanent stoma rate and contribute to cost-effectiveness without increasing complications such as anastomotic leakage.

[Primary Volvulus of the Small Intestine Mimicking Nonocclusive Mesenteric Ischemia Following Open-heart Surgery].

A 73-year-old female who underwent aortic valve replacement with a biological valve, coronary artery bypass, and left atrial appendage closure had sudden onset of nausea and abdominal pain 43 days after surgery. She had a history of nonocclusive mesenteric ischemia on 4th postoperative day, for which conservative management was successfully carried out. A contrast-enhanced computed tomography(CT) was performed because a recurrence of nonocclusive mesenteric ischemia was suspected. It revealed a whirl sign in the small intestine, suggestive of small intestine volvulus. At the subsequent emergency laparotomy, volvulus caused severe congestion in the small intestine, aproximately 40 cm from the cecum. However, there was no evidence of transmural necrosis, and reduction of torsion notably improved blood supply to the small intestine. Her regular diet was resumed on 4th postoperative day, and her postoperative course was uneventful. Volvulus should be considered as a differential diagnosis in the setting of acute abdominal pain after open-heart surgery.

Emergency open drainage of massive hemoperitoneum and early stage left hepatectomy for abdominal compartment syndrome due to hepatocellular carcinoma rupture: a case report.

BACKGROUND: Spontaneous rupture is one of the most life-threatening complications of hepatocellular carcinoma (HCC). Transcatheter arterial embolization (TAE) effectively achieves hemostasis in patients with hemodynamic instability. However, there have been no reports of abdominal compartment syndrome (ACS) caused by massive intra-abdominal hematoma after TAE. We report emergency open drainage of a massive hematoma for abdominal decompression and early stage left hepatectomy at the same time. CASE PRESENTATION: A 75-year-old woman was transported to our emergency department with hypovolemic shock. Dynamic contrast-enhanced computed tomography revealed extravasation of contrast medium from a HCC lesion in the medial segment of the liver and a large amount of high-density ascites. TAE was immediately performed to achieve hemostasis. Three hours after the first TAE, we decided to perform a second TAE for recurrent bleeding. After the second TAE, the patient's intra-abdominal pressure increased to 35 mmHg, her blood pressure gradually decreased, and she had anuria. Thus, she was diagnosed with ACS due to spontaneous HCC rupture. Twenty-seven hours after her arrival to the hospital, we decided to perform open drainage of the massive hematoma and left hepatectomy for ACS relief, prevention of re-bleeding, tumor resection, and intraperitoneal lavage. The operative duration was 225 min, and the blood loss volume was 4626 g. Postoperative complications included pleural effusion and grade B liver failure. She was discharged on postoperative day 33. The patient survived for more than 3 years without functional deterioration. CONCLUSIONS: Even after hemostasis is achieved by TAE for hemorrhagic shock due to spontaneous rupture of HCC, massive hemoperitoneum may lead to ACS, particularly in cases of re-bleeding. Considering the subsequent possibility of ACS and the recurrence of bleeding, early stage hepatectomy and removal of intra-abdominal hematoma after hemodynamic stabilization could be a treatment option for HCC rupture.

A case of pancreaticoduodenectomy and partial hepatic resection as repeat cytoreductive surgery for recurrent pseudomyxoma peritonei.

BACKGROUND: For recurrent pseudomyxoma peritonei (PMP), repeat cytoreductive surgery (CRS) with or without hyperthermic intraperitoneal chemotherapy (HIPEC) can provide survival benefits if patients are carefully selected. We describe a case of pancreaticoduodenectomy and partial liver resection (HPD) as the repeat CRS for a recurrent tumor that infiltrated the pancreatic head around the hepatic hilum. This is the first report of HPD for recurrent PMP. CASE PRESENTATION: The patient was a 58-year-old male without comorbidities. In 2001, he was diagnosed with PMP at the time of laparoscopic cholecystectomy. In 2004, CRS, including total peritoneal resection, pyloric gastrectomy, splenectomy, and right hemicolectomy with HIPEC was performed (peritoneal cancer index (PCI) = 28). In 2008, the first repeat CRS with HIPEC was performed (PCI = 14). In 2016, fourth repeat CRS, including partial hepatectomy with HIPEC for recurrence of the round ligament of the liver, was performed. In 2017, a tumor of 5 cm in size was observed from the hepatic hilum to the pancreatic head, which infiltrated the main pancreatic duct. Other tumors 2 cm in size were observed (PCI = 7). We performed the fifth repeat CRS, including HPD. The adhesions of the small intestine from around the liver to the lower abdomen were detached for the reconstruction of pancreatojejunostomy and cholangiojejunostomy. The uncinate approach was applied for the pancreatic head resection because it was difficult to identify the cranial part of the pancreas due to adhesions in the hepatoduodenal ligament and the omental bursa. We approached to the origin of the extrahepatic Glissonean pedicle by resecting a part of the liver around the hepatic hilum using transhepatic hilar approach. A complete cytoreduction was achieved. The postoperative pathological diagnosis was a recurrence of PMP, which is equivalent to peritoneal mucinous carcinomatosis. He was discharged on the 22nd postoperative day without major postoperative complications. The patient survived without recurrence four years after HPD. CONCLUSIONS: Even for recurrence around the hepatic hilum and the pancreatic head, repeat CRS can be safely performed by applying the techniques of hepatobiliary pancreatic surgery.

Endovascular repair using a covered stent for a ruptured infected aneurysm of the superior mesenteric artery after pancreaticoduodenectomy: a case report.

BACKGROUND: Delayed arterial hemorrhage after pancreaticoduodenectomy is a life-threatening complication. There are no reports about infected aneurysms of the superior mesenteric artery after pancreaticoduodenectomy without clinically relevant pancreatic fistula. CASE PRESENTATION: A 78-year-old woman with borderline resectable pancreatic ductal adenocarcinoma involving the superior mesenteric arterial nerve plexus underwent pancreaticoduodenectomy with en bloc resection of the superior mesenteric vein and the superior mesenteric arterial nerve plexus after neoadjuvant chemotherapy. On postoperative day 14, she had bacteremia and sudden fever with chills. During the postoperative course, macroscopic abscesses or distinct infectious signs, including pancreatic fistula or bile fistula, were not present, but pylephlebitis was observed. After the antimicrobial treatment course, the patient was discharged. After 17 days, she was hospitalized for melena. Contrast-enhanced computed tomography showed a ruptured aneurysm of the superior mesenteric artery into the small intestine without a major intraabdominal abscess. E. coli was isolated from blood cultures. The patient was diagnosed with a ruptured infected aneurysm of the superior mesenteric artery. She was treated successfully with a covered stent by the cardiology team. There was no recurrence of bleeding at the 4-month follow-up, and the stent was patent in all subsequent computed tomography scans. CONCLUSIONS: Endovascular repair using a covered stent was effective in palliating acute bleeding from an infected aneurysm of the superior mesenteric artery.

Surgical management for peritoneal carcinomatosis of appendiceal origin with a high-tumor burden.

PURPOSE: Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS + HIPEC) is the active treatment for peritoneal carcinomatosis of appendiceal origin. However, surgical management is sometimes difficult in patients with a high-tumor burden. METHODS: A high-tumor burden was defined as a peritoneal cancer index (PCI) ≥ 28. Among 49 patients receiving CRS + HIPEC, 29 had a PCI ≥ 28. RESULTS: Complete cytoreduction (CC-0/1) was achieved in 20 of the 29 patients with a PCI ≥ 28 and in all 20 patients with a PCI < 28. Among the patients achieving CC-0/1, gastrectomy or total colectomy was performed more frequently, the hospital stay was longer and postoperative complications were more frequent in those with a PCI ≥ 28 than in those with a PCI < 28. If CC-0/1 was achieved, the overall survival was comparable between patients with a PCI ≥ 28 and a PCI < 28. However, the recurrence-free survival was significantly worse for patients with a PCI ≥ 28 than for those with a PCI < 28 (5-year survival: 73.7% vs. 5.9%). Patients with recurrence who underwent repeat CRS showed a better overall survival than those without repeat CRS. Among patients with a PCI ≥ 28, a performance status (PS) of 2/3 was a significant prognostic factor (hazard ratio = 5.132). CONCLUSIONS: In patients with a high-tumor burden undergoing CRS + HIPEC, postoperative complications were more frequent, and the recurrence rate was higher than in those without a high-tumor burden. Repeat CRS improved the survival of patients with recurrence. The PS was a key indicator when selecting patients suitable for aggressive resection.

Duodenal intussusception secondary to ampullary adenoma: A case report.

BACKGROUND: Because the duodenum is fixed onto the retroperitoneum, duodenal intussusception is usually impossible except in cases of malrotational abnormality. Although cases of duodenal intussusception without malrotational abnormalities have been reported, it is unclear whether they constitute true intussusception or simple mucosal prolapse. CASE SUMMARY: A 66-year-old woman presented with whole-body edema and malaise. Blood analysis indicated severe anemia and cholestasis. Endoscopic examination revealed a pedunculate polyp on the second part of the duodenum that migrated distally with mucosal elongation. Computed tomography showed duodenal intussusception. A tumor as the lead point and retroperitoneal structure, including the head of the pancreas and fat, invaginated beyond the duodenojejunal flexure. She was diagnosed with ampullary adenoma caused repeated intussusception that reduced spontaneously and underwent pancreaticoduodenectomy. Laparotomy showed tumor prolapse beyond the duodenojejunal flexure without intussusception. There was no evidence of malrotational abnormality. She was discharged with no complications. CONCLUSION: We report true duodenal intussusception without malrotational abnormality. This phenomenon was also associated with mucosal prolapse.

The Efficacy and Limitations of Postoperative Adjuvant Chemotherapy in Patients With Extrahepatic Cholangiocarcinoma.

BACKGROUND/AIM: The impact of adjuvant chemotherapy (AC) for extrahepatic cholangiocarcinoma (ECC) remains unclear. This study evaluated the efficacy and limitations of AC. PATIENTS AND METHODS: Between 2006 and 2016, 106 patients with stage II-IV ECC who underwent curative resection with biliary tract reconstruction were retrospectively analyzed. Patients were divided into two groups: Those who received AC (n=57) and those who did not (n=49). RESULTS: Fewer grade 3-4 complications were observed in the AC group compared to the non-AC group (38.6 vs. 61.2%, p=0.03). In the non-AC group, complications were the most frequent reason for omitting AC (n=21, including 13 with biliary fistula). In the AC group, the therapy completion rate was 56.1% and the main reason for discontinuation was adverse events (n=12, including six with cholangitis). AC was not associated with survival benefits (median survival: 50.4 vs. 37.3 months, p=0.916). CONCLUSION: AC for ECC might be inadequate as a standard strategy due to the low implementation and completion rates because complications often hamper administration.

Repeat cytoreduction and hyperthermic intraperitoneal chemotherapy for recurrent peritoneal carcinomatosis of appendiceal origin.

BACKGROUND: The purpose of this study was to clarify the role of repeat cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS + HIPEC) in the management of recurrent peritoneal carcinomatosis of appendiceal origin. METHODS: Data were retrieved on 42 patients who underwent CRS + HIPEC; 29 repeat surgical procedures were performed in 13 patients. RESULTS: Complete cytoreduction was achieved in 12 of 13 patients by the second CRS. Repeat recurrence was detected in 11 patients, eight of whom underwent a third CRS. The peritoneal cancer index decreased from initial CRS to repeat CRS but was still higher than 18 in nine patients at the second CRS. Preoperative chemotherapy was given to three patients with early recurrence. Grade 3-5 morbidity and 90-day mortality were not significantly different between initial and repeat CRS. Five-year survival rates after first and second CRS were 75.5 and 67.7%, respectively. Complete cytoreduction at second CRS was a significant prognostic factor. Among patients with recurrence after the second CRS, patients who underwent a third CRS showed a better prognosis than those who did not. CONCLUSIONS: Repeat CRS is oncologically beneficial, and the morbidity rate was as high as that of initial CRS. Complete cytoreduction was the key to successful long-term results. Although further recurrence was common, aggressive resection was useful, even in cases of diffuse recurrence.

Indications for cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in elderly patients with peritoneal malignancy.

PURPOSE: A combination of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS + HIPEC) is effective for some peritoneal malignancies. However, the indications for elderly patients remain unclear, with substantial postoperative morbidity and mortality being problematic. MATERIALS: Clinical data were analyzed in 42 patients undergoing CRS + HIPEC for peritoneal malignancy. The primary tumor was located in the appendix in 32 cases and elsewhere in 10 cases. Operative results and survival data were compared between patients aged ≥70 and <70 years. RESULTS: Fourteen patients were older than 70 years. Elderly patients had a higher peritoneal cancer index (32.0 vs. 21.5), higher CA19-9 level (189.0 vs. 28.1), and higher frequency of grade 4-5 complications (5/9 vs. 2/26) than the younger patients. Grade 4-5 respiratory failure occurred in three elderly patients. There was a significant difference of postoperative survival between the elderly patients and younger patients, with 5-year survival rates being 41.3 and 74.2%, respectively (p = 0.0166). The poor prognosis of elderly patients was related to the higher frequency of grade 4-5 complications. CONCLUSIONS: Elderly patients were referred for treatment with more advanced disease than younger patients. An age ≥70 years was associated with more frequent grade 4-5 complications and worse survival. Performing CRS + HIPEC in elderly patients should be considered carefully due to the risk of severe complications, especially respiratory failure.

Chronological Profiling of Plasma Native Peptides after Hepatectomy in Pigs: Toward the Discovery of Human Biomarkers for Liver Regeneration.

Liver regeneration after partial hepatectomy (PHx) is a time-dependent process, which is tightly regulated by multiple signaling cascades. Failure of this complex process leads to posthepatectomy liver failure (PHLF), which is associated with a high rate of mortality. Thus, it is extremely important to establish a useful biomarker of liver regeneration to help prevent PHLF. Here, we hypothesized that alterations in the plasma peptide profile may predict liver regeneration following PHx and hence we set up a diagnostic platform for monitoring posthepatectomy outcome. We chronologically analyzed plasma peptidomic profiles of 5 partially hepatectomized microminipigs using the ClinProtTM system, which consists of magnetic beads and MALDI-TOF/TOF MS. We identified endogenous circulating peptides specific to each phase of the postoperative course after PHx in pigs. Notably, peptide fragments of histones were detected immediately after PHx; the presence of these fragments may trigger liver regeneration in the very acute phase after PHx. An N-terminal fragment of hemoglobin subunit α (3627 m/z) was detected as an acute-phase-specific peptide. In the recovery phase, the short N-terminal fragments of albumin (3028, 3042 m/z) were decreased, whereas the long N-terminal fragment of the protein (8926 m/z) was increased. To further validate and extract phase-specific biomarkers using plasma peptidome after PHx, plasma specimens of 4 patients who underwent PHx were analyzed using the same method as we applied to pigs. It revealed that there was also phase-specificity in peptide profiles, one of which was represented by a fragment of complement C4b (2378 m/z). The strategy described herein is highly efficient for the identification and characterization of peptide biomarkers of liver regeneration in a swine PHx model. This strategy is feasible for application to human biomarker studies and will yield clues for understanding liver regeneration in human clinical trials.

Phase I clinical trial of olprinone in liver surgery.

PURPOSE: Post-hepatectomy liver failure is one of the most serious complications liver surgeons must overcome. We previously examined olprinone, a selective phosphodiesterase III inhibitor, and demonstrated its hepatoprotective effects in rats and pigs. We herein report the results of a phase I clinical trial of olprinone in liver surgery (UMIN000004975). METHODS: Twenty-three patients who underwent hepatectomy between 2011 and 2015 were prospectively registered. In the first 6 cases, olprinone (0.1 µg/kg/min) was administered for 24 h from the start of surgery. In the remaining 17 cases, olprinone (0.05 µg/kg/min) was administered from the start of surgery until just before the transection of the liver parenchyma. The primary endpoint was safety, and the secondary endpoint was efficacy. For the evaluation of efficacy, the incidence of post-hepatectomy liver failure in 20 hepatocellular carcinoma patients was externally compared with 20 propensity score-matched patients. RESULTS: No intraoperative side effects were observed, and the morbidity rates in the analyzed cohorts were acceptable. The rate of post-hepatectomy liver failure frequency tended to be lower in the olprinone group. CONCLUSIONS: The safety of olprinone in liver surgery was confirmed. The efficacy of olprinone will be re-evaluated in clinical trials.

Prospective registry for laparoscopic liver resection.

INTRODUCTION: Laparoscopic liver resection (LLR) has been widely performed throughout the world. Although prospective registry studies to clarify the safety of LLR have been feasible, no prior multicenter prospective study has addressed this issue. We have conducted a multicenter prospective cohort study to reveal the current status of LLR in Japan. METHODS: From April 2015 to March 2016, candidates for LLR were preoperatively enrolled at 12 institutions. The primary end-point was surgical safety, which was evaluated based on surgical factors and on short-term and midterm outcomes. RESULTS: A total of 102 patients were enrolled. Planned laparoscopic procedures included 96 pure laparoscopies, 1 hand-assisted laparoscopy, and 5 hybrid techniques. Non-anatomical partial resection or left lateral sectionectomy were performed in almost all cases. The median duration of surgery was 221 min. The median blood loss was 80.5 mL. Conversion was required for four patients (3.9%). The 90-day postoperative morbidities with grades more severe than II in the Clavien-Dindo classification were observed in six patients (5.9%). The median postoperative hospital stay was 9.5 days. No cases involved reoperation or mortality. CONCLUSION: Minor resection of LLR has been performed safely. To ensure the safe dissemination of LLR, including for major resection, a larger multicenter prospective study is required.

Is Surgical Resection Justified for Advanced Intrahepatic Cholangiocarcinoma?

BACKGROUNDS: Prognosis for patients with advanced intrahepatic cholangiocarcinoma (ICC) with intrahepatic metastasis (IM), vascular invasion (VI), or regional lymph node metastasis (LM) remains poor. The aim of this study was to clarify the indications for surgical resection for advanced ICC. METHODS: We retrospectively divided 213 ICC patients treated at Kyoto University Hospital between 1993 and 2013 into a resection (n=164) group and a non-resection (n=49) group. Overall survival was assessed after stratification for the presence of IM, VI, or LM. RESULTS: Overall median survival times (MSTs) for the resection and non-resection groups were 26.0 and 7.1 months, respectively (p<0.001). After stratification, MSTs in the resection and non-resection groups, respectively, were 18.7 vs. 7.0 months for patients with IM (p<0.001), 23.4 vs. 5.7 months for those with VI (p<0.001), and 12.8 vs. 5.5 months for those with LM (p<0.001). CONCLUSION: When macroscopic curative resection is possible, surgical resection can be justified for some advanced ICC patients with IM, VI, or LM.

A non-smooth tumor margin on preoperative imaging predicts microvascular invasion of hepatocellular carcinoma.

PURPOSES: Microvascular invasion (mVI) is known to be a risk factor of hepatocellular carcinoma (HCC) recurrence. Several factors such as the tumor grade, tumor size, tumor margin status on imaging studies, fluorine-18 fluorodeoxyglucose-positron emission tomography ((18)F-FDG-PET) results, and tumor markers have been proposed to predict mVI of HCC. However, the values of these factors have not yet been validated. METHODS: Among the patients evaluated using enhanced CT/MRI, (18)F-FDG-PET, and tumor markers prior to hepatectomy from 2007 to 2012, 79 HCC patients without apparent macrovascular invasion in preoperative imaging were enrolled in this study. The image tumor margin status (smooth/non-smooth), (18)F-FDG-PET, and tumor markers, which were previously described as predictors for mVI, were evaluated. RESULTS: Fifteen patients had mVI (mVI+ group) and 64 patients had no evidence of mVI (mVI- group) on pathological examinations. A univariate analysis showed that the mVI+ group had a higher SUV and TNR (5.2 vs 3.8, p = 0.02 and 1.8 vs 1.3, p = 0.02, respectively) and a higher portion of non-smooth tumor margin (87 vs 27 %, p = 0.0001). There was no significant difference in the tumor markers. A multivariate analysis showed that non-smooth tumor margin alone could independently predict mVI (odds ratio 18.3, 95 % CI 3.27-102.6, p = 0.0009). CONCLUSION: A non-smooth tumor margin on preoperative imaging predicts microvascular invasion of HCC.

Validation of the Conventional Resection Criteria in Patients with Hepatocellular Carcinoma in Terms of the Incidence of Posthepatectomy Liver Failure and Long-Term Prognosis.

BACKGROUND/AIMS: Resection criteria in hepatocellular carcinoma (HCC) should be established based on the risk of posthepatectomy liver failure (PHLF) and the survival benefit from hepatectomy. This study aimed at verifying the validity of the conventional criteria regarding the incidence of PHLF and the long-term prognosis of HCC patients. METHODS: A retrospective study was performed on 265 patients who underwent major hepatectomy. Makuuchi's criteria and the future liver remnant plasma clearance rate of indocyanine green (ICGK-rem) ≥0.05 criterion were evaluated. RESULTS: A total of 107 and 158 patients were within and beyond Makuuchi's criteria, respectively. Makuuchi's criteria were associated with the incidence of PHLF (p = 0.03) but not with its severity (p = 0.12). No differences in disease-free survival (DFS) or overall survival (OS) were observed between the groups (p = 0.75 and p = 0.94, respectively). Using the ICGK-rem ≥0.05 criterion, 223 and 42 patients were within and beyond the criterion, respectively. ICGK-rem was correlated with both the incidence of PHLF (p = 0.002) and its severity (p = 0.03). No differences in DFS or OS were observed between the groups (p = 0.75 and p = 0.29, respectively). CONCLUSIONS: Strict criteria are likely to preclude some patients from obtaining the greater survival benefits of hepatectomy. New criteria that consider patient prognosis are needed.

Hepatoprotective effect by pretreatment with olprinone in a swine partial hepatectomy model.

Excessive portal flow to a small remnant liver or small-for-size graft is a primary factor of small-for-size syndrome. We demonstrated that olprinone (OLP), a phosphodiesterase III inhibitor, had a hepatoprotective effect in a rat extended hepatectomy model and a small-for-size liver transplantation model through a modification of the portal venous pressure (PVP). To identify the appropriate dose and duration of treatment for clinical applications, we conducted experiments with a swine partial hepatectomy model. Twenty microminipigs were divided into 4 groups that received the following treatments: (A) saline (control group), (B) OLP at 0.3 µg/kg/minute (preoperative and postoperative administration), (C) OLP at 0.1 µg/kg/minute (preoperative administration), and (D) OLP at 0.3 µg/kg/minute (preoperative administration). The pigs underwent 70% partial hepatectomy. Hemodynamic changes, including changes in PVP, were examined. Liver biopsy was performed 1 and 3 hours after hepatectomy. Blood samples were collected until postoperative day 7 (POD7). In comparison with group A, PVP elevations, periportal edema, and sinusoidal hemorrhaging were attenuated after left Glisson's ligation in groups C and D. Pretreatment with OLP in groups C and D preserved the microstructure of sinusoids and improved the prothrombin activity 1 and 3 hours after hepatectomy. These animals showed better recovery of the remnant liver volume and the plasma disappearance rate of indocyanine green on POD7. In contrast, group B showed exacerbation of liver damage. Measurements of the serum OLP concentration showed that 10 ng/mL OLP was appropriate for a hepatoprotective effect. In conclusion, pretreatment with OLP shows hepatoprotective effects in a swine partial hepatectomy model. OLP may have the potential to ameliorate patients' outcomes after hepatectomy or liver transplantation.

Glycine inhibits angiogenic signaling in human hepatocellular carcinoma cells.

Hepatocellular carcinoma (HCC) is a highly vascularized tumor with limited susceptibility to chemotherapy. Modern targeted therapies are aimed at specific properties of this neoplasm. Glycine is a simple non-essential amino acid with potential antiangiogenic effects. In this study, the amino acid's effect on angiogenic signaling in an in vitro model of HCC was evaluated. HepG2 and Huh7 cells were treated with glycine-free DMEM supplemented with 0, 0.01, 0.1, 1.0, 2.0, 5.0 and 10 mM glycine. The direct effects of glycine on the viability of HCC cells were monitored using MTT assay. To detect angiogenic signaling, mRNA and protein levels of vascular endothelial growth factor (VEGF-A) were measured using RT-PCR and Western Blot assays. To determine whether or not glycine receptors (GlyR) played a significant role, the specific antagonist, strychnine, was used as a direct inhibitor. Western Blotting was performed to show the presence of GlyR. While there was no direct pro- or antiproliferative effect of either glycine or strychnine in both cell lines, glycine was shown to significantly decrease VEGF-A expression on mRNA and protein level up to 63 % in both cell lines. This effect was blunted by the presence of strychnine. GlyR was also identified in both cell lines. Glycine decreases GlyR-dependent, VEGF-A-mediated, angiogenic signaling in human HCC and thus might be a promising additive to chemotherapy treatment strategies for highly vascularized tumors.

A single-center analysis of the survival benefits of adjuvant gemcitabine chemotherapy for biliary tract cancer.

BACKGROUND: Surgical resection is the only curative treatment of biliary tract cancer (BTC). However, the prognosis of BTC remains unsatisfactory. The aim of this study is to evaluate the benefits of adjuvant gemcitabine chemotherapy for BTC. METHODS: We performed a historical cohort study that involved 198 patients who underwent R0 surgical resection. Patients who underwent major hepatectomy were administered biweekly intravenous gemcitabine at a dose of 800 mg/m(2). Otherwise, patients were administered intravenous gemcitabine at a dose of 1,000 mg/m(2) in 3 weekly infusions, which were followed by a 1-week pause. The primary outcome was overall survival. The hazard ratio (HR) of adjuvant chemotherapy was estimated by propensity score-stratified Cox regression that was adjusted for confounders. RESULTS: Forty patients received adjuvant chemotherapy. The HR of adjuvant chemotherapy was 0.47 [95 % confidence interval (CI) 0.28-0.95; P = 0.03]. Subgroup analysis showed that the survival benefits were possibly modified by lymph node positivity (HR 0.19; 95 % CI 0.07-0.58; interaction, P = 0.22), stage III (HR 0.11; 95 % CI 0.02-0.50; interaction, P < 0.01), intrahepatic cholangiocarcinoma (ICC) (HR 0.09; 95 % CI 0.01-0.67; interaction, P = 0.05), and poorly differentiated tumor (HR 0.16; 95 % CI 0.03-0.85; interaction, P = 0.13). CONCLUSIONS: Adjuvant gemcitabine chemotherapy for BTC may be effective, particularly for patients with stage III and ICC.