Introduction:The Pringle manoeuvre is used in most hospitals to counteract intraoperative haemorrhage in laparoscopic hepatectomy by occluding the flow of blood to the liver. However, in laparoscopic repeat hepatectomy (LRH), outcomes of previous surgery and the influence of other factors frequently make it difficult to occlude the inflow of blood.Aim:To discuss the value of inflow occlusion during LRH and provide tips for its performance.Material and methods:Sixty-three patients who underwent LRH with or without the Pringle manoeuvre were analysed retrospectively. We investigated the efficacy and safety of the Pringle manoeuvre in LRH. Student's t and χ2 tests, Mann-Whitney's U test, Wilcoxon's signed-rank test, and Fisher's exact test were used in the statistical analysis.Results:Nineteen patients underwent LRH with the Pringle manoeuvre, and 44 patients underwent LHR without the Pringle manoeuvre. After propensity score matching, there were no significant differences in terms of operative time, estimated blood loss, and postoperative complication rate (p = 0.973, 0.120, and not applicable, respectively). However, the rate of conversion to open repeat hepatectomy (ORH) was significantly lower in the Pringle manoeuvre group (p = 0.034). In many cases, the cause of conversion to ORH was the non-use of inflow occlusion and the resulting inability to control intraoperative haemorrhage. Laboratory data collected after surgery showed no significant difference between the 2 groups regardless of whether blood flow was occluded or not.Conclusions:LRH with the Pringle manoeuvre can be performed safely using various surgical devices. However, it is often challenging to perform the Pringle manoeuvre in patients with a history of cholecystectomy or segment 5 resection of the liver, and caution is required.

Ascites is generally considered a consequence of liver cir-rhosis and/or portal hypertension, and patients with massive ascites may have a higher risk of mortality. Similarly, hepatic resection may lead to impaired liver function and increased portal pressure as the blood inflow of the portal vein to the postoperative remnant liver is similar to the blood inflow to the preoperative liver, which may in turn result in massive ascites and thus increase the risk of death. Hence, a for managing postoperative ascites is to ensure the safety of hepatic resection. This retrospective study aimed to clarify the perioperative risk factors for massive ascites that occur after elective hepatic resection in patients with hepatocellular carcinoma (HCC) at a single institution and to evaluate the effects of massive ascites on remnant liver regeneration after hepatic resection.

【背景】肝細胞癌に対する肝切除術の有効性は確立しているが, 発症年齢は一貫して上昇しており, 今後高齢者の手術症例の増加が推察される. 【対象・方法】2009年から2019年までに施行した肝細胞癌肝切除症例344例を対象とし, 高齢者 (75歳以上) 肝細胞癌肝切除症例の術後成績を非高齢者 (75歳未満) と比較・検討した. なお, 手術適応基準は, 全症例で残肝重量/体重比≥0.8%および幕内基準に準じた. 【結果】高齢者群で心疾患の併存や他臓器悪性腫瘍の既往が多かった. 術前アルブミン値は有意に低値であり, 全肝容積も小さかった. 手術成績, 術後合併症発生率, 在院死亡率や術後在院日数は2群間に有意差を認めなかった. 残肝の容積・機能変化, 無再発および累積生存率は2群間に有意差を認めなかった. 【結語】高齢者の肝切除術は, 非高齢者と同様の手術適応基準で, 同等の安全性・根治性を期待しうると考えられた.

Progressive colorectal cancer frequently presents with various manifestations, including hepatic, pulmonary, and peritoneal metastases, as well as local and anastomotic site recurrences. However, pancreatic metastasis is extremely rare. Complete surgical resection is currently considered the most effective and only potentially curative treatment for colorectal cancer with distant metastases. We report the successful laparoscopic treatment of a patient with pancreatic metastasis after initial surgery for Stage IV sigmoid colon cancer with pulmonary metastasis. An 84-year-old man was initially diagnosed with sigmoid colon cancer and pulmonary metastasis. Laparoscopic sigmoidectomy and thoracoscopic partial resection of the right lung were performed in 2017. After 8 months, an approximately 20-mm tumor was detected in the pancreatic tail during imaging investigations. We performed laparoscopic distal pancreatectomy without lymph node dissection at 1 year after the initial operation. The histopathological findings suggested metachronous pancreatic metastasis from the sigmoid colon cancer. The patient has had an uneventful postoperative course with no signs of recurrent disease during 29 months of follow-up after the pancreatic surgery. After prior surgery for Stage IV sigmoid colon cancer with pulmonary metastasis, curative resection was performed for pancreatic metastasis. We believe that curative resection may be useful for pancreatic tumors that involve hematogenous metastasis.

A 74-year-old woman with recurrent gastric cancer underwent laparotomy for peritoneal dissemination, and the damaged jejunum formed a jejunocutaneous fistula. Because conservative treatment alone could not cure the fistula, we performed an endoscopic placement of a partially covered self-expandable metallic stent (SEMS) to cover the fistula. After the procedure, the contrast medium no longer leaked from the intestinal lumen. One month after stent placement, the cutaneous opening had closed. This case report demonstrates the potential for using partially covered SEMS to treat intractable jejunocutaneous fistula in patients with terminal-stage malignant tumors.

Hepatectomy is currently recommended as the most reliable treatment for hepatocellular carcinoma. However, the association between the choice of treatment for recurrence and the timing of recurrence remains controversial. Three-hundred thirty-nine patients who underwent hepatectomy were retrospectively analyzed using a propensity score matching analysis for the risk factors and outcomes for early recurrences within 6 months. The remnant liver volumes and laboratory data were measured postoperatively using multidetector computed tomography on days 7 and months 1, 2, and 5 after surgery. The Student’s t test and chi-square test, the likelihood-ratio test, Fisher’s exact test, Mann–Whitney U test, or Wilcoxon signed-rank test were used in the statistical analyses. Early recurrence developed in 41/312 patients (13.1%). Vascular invasion and non-curative resection were independent risk factors for the occurrence of early recurrence (P < 0.001 and < 0.001, respectively). Patients with early recurrence had a poorer prognosis than patients who developed later recurrences (P < 0.001). Patients who underwent surgery or other local treatments had better outcomes (P < 0.001). The changes in remnant liver volumes and laboratory data after postoperative month 2 were not significantly different between the two groups. Patients with early recurrence within 6 months had a poorer prognosis than patients who developed a later recurrence. However, patients who underwent repeat hepatectomy for recurrences had a better prognosis than did those who underwent other treatments, with good prospects for long-term survival.

The Pringle maneuver is currently used in most institutions to prevent intraoperative hemorrhage during hepatectomy by occluding the blood flow to the liver. We investigated the postoperative effects of hepatic inflow occlusion time during hepatectomy. The surgical outcomes of 831 patients who underwent hepatic resection for liver tumors were retrospectively reviewed, including the association of hepatic inflow occlusion time with surgical outcomes and remnant liver regeneration. The Student’s t and χ2 tests, Mann–Whitney’s U test, Wilcoxon’s signed-rank test, or Fisher’s exact test were used. Patients were divided into two groups: the normal liver group (fibrosis stage 0–1; n = 560) and diseased liver group (fibrosis stage 2–4; n = 271). The Pringle maneuver was performed in 522 (62.8%) patients. The median occlusion time was 45 (9–167) min. There was an association between extended ischemia time and unfavorable blood test results in the early postoperative period. However, regardless of the ischemia time, the patients recovered by the 14th postoperative day. There were no correlations between total ischemia time and the frequency of postoperative complications in either the normal or diseased liver groups (p = 0.262 and 0.099, respectively). There were no correlations between ischemia time and remnant liver regeneration at 7 days, and 1, 2, 5, and 12 months, postoperatively, in either the normal or diseased liver groups. The intermittent Pringles maneuver over shorter periods was associated with favorable postoperative outcomes and complications, and had no significant effect on remnant liver regeneration.

Introduction Laparoscopic liver resection (LLR) in obese patients has been reported to be particularly challenging owing to technical difficulties and various comorbidities. Methods The safety and efficacy outcomes in 314 patients who underwent laparoscopic or open nonanatomical liver resection for colorectal liver metastases (CRLM) were analyzed retrospectively with respect to the patients' body mass index (BMI) and visceral fat area (VFA). Results Two hundred and four patients underwent LLR, and 110 patients underwent open liver resection (OLR). The rate of conversion from LLR to OLR was 4.4%, with no significant difference between the BMI and VFA groups (P = .647 and .136, respectively). In addition, there were no significant differences in terms of operative time and estimated blood loss in LLR (P = .226 and .368; .772 and .489, respectively). The incidence of Clavien-Dindo grade IIIa or higher complications was not significantly different between the BMI and VFA groups of LLR (P = .877 and .726, respectively). In obese patients, the operative time and estimated blood loss were significantly shorter and lower, respectively, in LLR than in OLR (P = .003 and < .001; < .001 and < .001, respectively). There was a significant difference in the incidence of postoperative complications, organ/space surgical site infections, and postoperative bile leakage between the LLR and OLR groups (P = .017, < .001, and < .001, respectively). Conclusion LLR for obese patients with CRLM can be performed safely using various surgical devices with no major difference in outcomes compared to those in nonobese patients. Moreover, LLR has better safety outcomes than OLR in obese patients.

Background Hepatectomy has a high risk of perioperative bleeding due to the underlying disease. Here, we investigated the postoperative impact of allogeneic blood transfusion during hepatectomy. Methods The surgical outcomes in 385 patients who underwent hepatic resection for hepatocellular carcinoma were retrospectively reviewed. The association of allogeneic blood transfusion with surgical outcomes and remnant liver regeneration data was analyzed. Results Eighty-six patients (24.0%) received an allogeneic blood transfusion and 272 patients (76.0%) did not. After propensity score matching, the incidence rates of postoperative complication (Clavien-Dindo grade >IIIA), posthepatectomy liver failure, and massive ascites were significantly higher for the group that received a blood transfusion than for the group that did not receive blood transfusion (P < .001, P = .001, and <.001, respectively). Postoperative measures of total bilirubin, albumin, platelet count, prothrombin time, aspartate aminotransferase, and alanine aminotransferase were significantly more favorable in patients without blood transfusion until day 7 after surgery. There were no correlations in the remnant liver regeneration at 7 days, and 1, 2, 5, and 12 months postoperatively between the 2 groups (P = .585, .383, .507, .261, and .430, respectively). Regarding prognosis, there was no significant difference in overall and recurrence-free survival between the 2 groups (P = .065 and .166, respectively). Conclusion Allogeneic transfusion during hepatectomy strongly affected remnant liver function in the early postoperative period; however, this was not related to the remnant liver regeneration volume. Despite that the allogeneic transfusion resulted in poorer postoperative laboratory test results and increased postoperative complication and mortality rates, it had no effect on the long-term prognosis.

Introduction Laparoscopic hepatectomy (LH) is very difficult to perform in patients with cirrhosis because of the haemorrhagic and fibrotic nature of the liver, although there are various advantages to laparoscopic surgery. Aim To investigate the surgical outcomes, and efficacy and safety of LH versus open hepatectomy (OH) for hepatocellular carcinoma (HCC) resection. Material and methods A total of 112 patients with cirrhosis, who underwent hepatectomy, were analysed retrospectively. We investigated the safety and efficacy of LH for HCC with cirrhosis. Student’s t and χ2 tests, Mann-Whitney’s U test, Wilcoxon’s signed-rank test, and Fisher’s exact test were used in the statistical analysis. Results Seventy-one patients underwent LH, and 41 underwent OH. The conversion rate from LH to OH was 12.7%. After propensity score matching, the estimated blood loss was significantly lower in the LH group than in the OH group (25 vs. 310 ml; p < 0.001), and there was a significant difference between the groups in the operative time (p = 0.091). The LH group had complication rates of 3.6% and 0% for refractory ascites and pleural effusion, respectively, while those were 17.9% and 10.7%, respectively, in the OH group (p = 0.019 and p = 0.005, respectively). The LH group had no mortality, whereas the OH group had a mortality rate of 10.7% (p = 0.038). The postoperative length of stay was significantly longer in the LH group than in the OH group (9 days vs. 14 days) (p = 0.002). Conclusions LH can be performed safely for HCC with cirrhosis. More favourable results are achieved with LH than with OH in terms of surgical outcomes.

Preoperative radiotherapy improves local disease control and disease-free survival in patients with advanced rectal cancer; however, a reliable predictive biomarker for the effectiveness of irradiation has yet to be elucidated. Phosphorylation of H2A histone family member X (H2AX) to γ-H2AX is induced by DNA double-strand breaks and is associated with the development of colorectal cancer (CRC). The current study aimed to clarify the relationship between γ-H2AX expression and CRC radiosensitivity in vitro and in vivo. H2AX levels were analyzed in datasets obtained from cohort studies and γ-H2AX expression was investigated by performing immunohistochemistry and western blotting using clinical CRC samples from patients without any preoperative therapy. In addition, the CRC cell lines WiDr and DLD-1 were subjected to irradiation and/or small interfering RNA-H2AX, after which the protein levels of γ-H2AX were examined in samples obtained from patients undergoing preoperative chemoradiotherapy. To quantify the observable effect of treatment on cancer cells, outcomes were graded as follows: 1, mild; 2, moderate; and 3, marked, with defined signatures of cellular response. Datasets obtained from cohort studies demonstrated that H2AX mRNA levels were significantly upregulated and associated with distal metastasis and microsatellite instability in CRC tissues, in contrast to that of normal tissues. In addition, γ-H2AX was overexpressed in clinical samples. In vitro, following irradiation, γ-H2AX expression levels increased and cell viability decreased in a time-dependent manner. Combined irradiation and γ-H2AX knockdown reduced the viability of each cell line when compared with irradiation or γ-H2AX knockdown alone. Furthermore, among clinical CRC samples from patients undergoing preoperative chemoradiotherapy, levels of γ-H2AX in the grade 1 group were significantly higher than those in grade 2 or grade 3. In conclusion, γ-H2AX may serve as a novel predictive marker and target for preoperative radiotherapy effectiveness in patients with CRC.

IntroductionIn recent years, natural orifice specimen extraction (NOSE) has been attracting attention as a further minimally invasive operation for colorectal cancer, and not only improvement of appearance, but also reduction of pain and wound-related complications due to abdominal wall destruction has been reported. However, NOSE is technically complicated and difficult, and it has not yet been widely used. The aim of this study was to confirm the feasibility, safety, and short-term outcomes of total laparoscopic colon cancer surgery with NOSE.Case presentationFrom May 2018 to October 2019, eight patients with stage 0 or I colon cancer underwent NOSE surgery in our hospital. Transanal specimen extraction was performed in six cases, and transvaginal specimen extraction was performed in two cases. All operations were successfully accomplished without conversion to open surgery. The anastomosis method was double stapling technique in three cases and overlap method in five cases. The median operative time was 224 min. The median blood loss was 10 mL. The median time to first flatus was 1 day, and the median time to first stool was 2 days. The median postoperative observation period was 18 months, but there was no recurrence. There were no postoperative complications in these cases.ConclusionTotal laparoscopic colon cancer surgery with NOSE appears to be feasible, safe, and show promising efficacy for selected patients.

Background The effectiveness of adjuvant transcatheter arterial chemo- or/and chemoembolization therapy after curative hepatectomy of initial hepatocellular carcinoma (HCC) is controversial. This study aimed to evaluate whether hepatectomy combined with adjuvant transcatheter arterial infusion therapy (TAI) for initial HCC has better long-term survival outcomes than hepatectomy alone. Methods From January 2012 to December 2014, a prospective randomized controlled trial of patients with initial HCC was conducted. Then, 114 initial HCC patients were recruited to undergo hepatectomy with adjuvant TAI (TAI group, n = 55) or hepatectomy alone (control group, n = 59) at our institution. The TAI therapy was performed twice, at 3 and 6 months after curative hepatectomy (UMIN 000011900). Results The patients treated with TAI had no serious side effects, and operative outcomes did not differ between the two groups. No significant differences were found in the pattern of intrahepatic recurrence or time until recurrence between the two groups. Moreover, no significant differences were found in the relapse-free survival or overall survival. Low cholinesterase level (< 200) had been identified as a risk factor affecting relapse-free survival. Furthermore, compared with surgery alone, adjuvant TAI with hepatectomy improved the overall survival for lower-cholinesterase patients. Conclusions Adjuvant TAI is safe and feasible, but it cannot reduce the incidence of postoperative recurrence or prolong survival for patients who underwent curative hepatectomy for initial HCC.

Background Total pancreatectomy is performed for chronic pancreatitis, tumors involving the entire pancreas or remnant pancreas after pancreatectomy. Gastric venous congestion and bleeding may be associated with total pancreatectomy. We report the case of a patient who underwent left gastric vein to splenic vein bypass to relieve gastric venous congestion during total pancreatectomy for remnant pancreatic cancer. Case presentation A 60-year-old woman underwent subtotal stomach-preserving pancreaticoduodenectomy for cancer of the pancreatic head. A follow-up computed tomography revealed a low-density tumor of the remnant pancreas. The pathological diagnosis was adenocarcinoma on endoscopic ultrasound-fine needle aspiration. Total resection of the remnant pancreas was performed for the tumor 3 years after the initial surgery. We ligated the splenic vein at the point of distal side of the left gastric vein confluent. Immediately, the vein congestion around the stomach was confirmed. We found the stenosis of the confluent between the left gastric vein and splenic vein. We subsequently anastomosed the left gastric vein and splenic vein, following which the gastric venous congestion was relieved. Conclusion In cases wherein all the drainage veins from the stomach are removed, an anastomosis between the left gastric vein and splenic vein can be effectively used to prevent gastric venous congestion and bleeding after total pancreatectomy.

Introduction: Reduced port surgery (RPS) has been garnering interest as a novel minimally invasive surgery lately. Aim: The authors examined the relationship between the number of ports and surgical outcomes after laparoscopic hepatectomy (LH). Materials and Methods: Between January 2012 and April 2019, 209 patients who underwent laparoscopic partial resection and lateral sectionectomy were retrospectively analyzed with respect to operative variables and surgical outcomes. Patients were divided into 5 groups by the number of ports used. Student’s t test, the χ2 test, the likelihood-ratio test, Fisher exact test, or Mann-Whitney U test were used to analyze the data. Results: Operative duration was significantly longer in patients with a larger number of ports than in those with a smaller number of ports. Chronological pain scores according to the visual analog scale (VAS) on postoperative days 1, 2, 4, and 7 were not associated with the number of ports and wound length in the umbilical region. The frequency of using additional analgesic agents was not significantly different between the groups. VAS scores and the number of additional analgesic agents used were smaller in patients in whom non–steroidal anti-inflammatory drugs were regularly administered postoperatively than in those in whom the drug was not regularly administered postoperatively. LH had a 3.4% complication rate (Clavien-Dindo classification >IIIA); however, this was not significantly different between the groups. Conclusions: No significant difference in postoperative pain was observed between RPS and conventional methods, although operative durations were shorter with RPS. However, RPS for LH may be associated with excellent cosmetic results compared with conventional methods.

Patients who undergo pancreatectomy for pancreatic ductal adenocarcinoma (PDA) develop relatively early recurrence, but pulmonary metastasis from PDA is rare. Between January 2008 and December 2016, a total of 120 consecutive patients underwent pancreatectomy for primary PDA at Osaka Medical College Hospital. Among these, 13 patients developed pulmonary metastasis and 6 patients underwent pulmonary metastasectomy. Among these patients, the median disease-free survival following initial pancreatic surgery was 26.1 months, and the median overall survival (OS) interval was 39 months. On the other hand, seven patients did not undergo pulmonary resection. The median OS interval of these patients was 33 months. The 1-, 3-, and 5-year OS rates were 100%, 80%, and 60%, respectively, for patients who underwent pulmonary metastasectomy and 100.0%, 42.8%, and 0%, respectively, for those who did not undergo the procedure. Our experience has shown that surgical resection may lengthen the survival time of patients who tolerate surgery.

INTRODUCTION:Hepatectomy is currently the most reliable treatment modality for colorectal liver metastases (CRLM). This paper describes and discusses the outcomes of initial versus repeat hepatic resection for CRLM.MATERIAL AND METHODS:Between January 2008 and December 2018, we retrospectively analyzed the data of 385 patients who underwent initial and repeat hepatic resection for CRLM at a single institution with respect to surgical outcomes and remnant liver regeneration. The remnant liver volume was postoperatively measured via computed tomography on postoperative day 7 and at 1, 2, 5, 12, and 24 months postoperatively.RESULTS:The liver regeneration rate peaked at 1 week postoperatively, and gradually decreased thereafter. Remnant liver volume plateaued around 1-2 months postoperatively, when regeneration was almost complete. There was no difference in the rate of liver volume regeneration during the entire postoperative period between initial and repeat hepatic resection (p = 0.708, 0.511, 0.055, 0.053, 0.102, and 0.110, respectively). After 2 months postoperatively, the laboratory data showed recovery toward near normal levels, and none of the data exhibited significant differences. There were also no significant differences in morbidity rate, mortality rate, overall survival, and recurrence-free survival after hepatic resection (p = 0.488, 0.124, 0.071 and 0.387, respectively).CONCLUSIONS:Initial and repeat hepatectomy showed similar outcomes of remnant liver regeneration and short- and long-term prognoses.

BACKGROUND:Hepatic resection (HR) is not recommended for intermediate-stage hepatocellular carcinoma (HCC) by the Barcelona Clinic Liver Cancer criteria. We examined the prognostic factors of HR for intermediate-stage HCC and developed new HR criteria for intermediate-stage HCC.METHODS:A total of 110 patients who underwent HR without any prior treatment for intermediate-stage HCC between January 2007 and December 2012 were enrolled at eight university hospitals. The outcomes and prognostic factors of HR were evaluated to develop new HR criteria.RESULTS:In terms of tumor size and number, the most significant prognostic factors were within the up-to-seven criteria. Furthermore, serum albumin level ≥35 g/L and serum alpha-fetoprotein (AFP) level.

Immune-related adverse events (irAEs) are induced by immune checkpoint inhibitors (ICIs). Liver is one of the main target organs which irAEs occur and we investigated the influence of liver dysfunction on prognosis of patients after ICIs. From July 2014 to December 2018, 188 patients with diverse cancers who received ICIs (nivolumab or pembrolizumab) were enrolled. Twenty-nine patients experienced liver dysfunction of any grades after ICIs. Progression-free survival (PFS) was significantly shorter in the liver dysfunction-positive group than in the liver dysfunction-negative group, and a similar result was obtained for Overall survival (OS). Multiple logistic regression analysis revealed liver metastasis and alanine aminotransferase before ICIs were associated with a higher incidence of liver dysfunction after ICIs. Regardless of liver metastasis, PFS and OS were significantly shorter in the liver dysfunction-positive group. In conclusion, this study suggests liver dysfunction is associated with poor prognosis in patients after ICIs with diverse cancers.

INTRODUCTION:Patients with diabetes mellitus undergoing hepatectomy for hepatocellular carcinoma (HCC) are at high risk of acquiring perioperative infections. Herein, we investigate the peri-operative impact of diabetes on hepatectomy.MATERIAL AND METHODS:The surgical outcomes in 363 patients who underwent laparoscopic and open hepatic resection for HCC, with or without diabetes mellitus, were reviewed retrospectively. The association of diabetes mellitus with surgical outcomes and remnant liver regeneration was analyzed. The Student's t and χ2 tests, Mann-Whitney's U test, Wilcoxon's signed-rank test, or Fisher's exact test were used in the statistical analysis.RESULTS:Of the 363 patients, 136 (37.5%) had diabetes, while 227 (62.5%) did not. After propensity score matching, there were no significant differences between the groups in surgical outcomes such as surgery duration, bleeding amount, and postoperative complication rate. No significant differences were observed between the groups in terms of incidence rates of not only infectious complications, including surgical site infection and remote site infection, but also postoperative complication (Clavien-Dindo grade > IIIA), post-hepatectomy liver failure, and massive ascites. There were no differences in the remnant liver regeneration at 7 days and 1, 2, 5, and 12 months following the surgery between the groups (p = 0.076, 0.368, 0.864, 0.288, and 0.063, respectively). No significant differences between the groups in the overall and recurrence-free survival were observed (p = 0.613 and 0.937).CONCLUSIONS:Remnant liver regeneration in diabetic patients was not morphologically and functionally delayed compared to that in non-diabetic patients. Moreover, diabetes has no effect on the short- and long-term prognosis.