Comparison between CT volumetry, technetium99m galactosyl-serum-albumin scintigraphy, and gadoxetic-acid-enhanced MRI to estimate the liver fibrosis stage in preoperative patients.

OBJECTIVES: To compare the efficacy of computed tomography volumetry (CTV), technetium99m galactosyl-serum-albumin (99mTc-GSA) scintigraphy, and gadolinium-ethoxybenzyl-diethylenetriamine-pentaacetic-acid-enhanced MRI (EOB-MRI) in estimating the liver fibrosis (LF) stage in patients undergoing liver resection. METHODS: This retrospective study included 91 consecutive patients who had undergone preoperative dynamic CT and 99mTc-GSA scintigraphy. EOB-MRI was performed in 76 patients. CTV was used to measure the total liver volume (TLV), spleen volume (SV), normalised to the body surface area (BSA), and liver-to-spleen volume ratio (TLV/SV). 99mTc-GSA scintigraphy provided LHL15, HH15, and GSA indices. The liver-to-spleen ratio (LSR) was calculated in the hepatobiliary phase of EOB-MRI. Hyaluronic acid and type 4 collagen levels were measured in 65 patients. Logistic regression and receiver operating characteristic (ROC) analyses were performed to identify useful parameters for estimating the LF stage and laboratory data. RESULTS: According to the multivariable logistic regression analysis, SV/BSA (odds ratio [OR], 1.01; 95% confidence interval [CI], 1.003-1.02; p = 0.011), LSR (OR, 0.06; 95%CI, 0.004-0.70; p = 0.026), and hyaluronic acid (OR, 1.01; 95%CI, 1.001-1.02; p = 0.024) were independent variables for severe LF (F3-4). Combined SV/BSA, LSR, and hyaluronic acid correctly estimated severe LF, with an AUC of 0.91, which was significantly larger than the AUCs of the GSA index (AUC = 0.84), SV/BSA (AUC = 0.83), or LSR (AUC = 0.75) alone. CONCLUSIONS: Combined CTV, EOB-MRI, and hyaluronic acid analyses improved the estimation accuracy of severe LF compared to CTV, EOB-MRI, or 99mTc-GSA scintigraphy individually. CLINICAL RELEVANCE STATEMENT: The combined analysis of spleen volume on CT volumetry, liver-to-spleen ratio on gadolinium-ethoxybenzyl-diethylenetriamine-pentaacetic-acid-enhanced MRI, and hyaluronic acid can identify severe liver fibrosis associated with a high risk of liver failure after hepatectomy and recurrence in patients with hepatocellular carcinoma. KEY POINTS: • Spleen volume of CT volumetry normalised to the body surface area, liver-to-spleen ratio of EOB-MRI, and hyaluronic acid were independent variables for liver fibrosis. • CT volumetry and EOB-MRI enable the detection of severe liver fibrosis, which may correlate with post-hepatectomy liver failure and complications. • Combined CT volumetry, gadolinium-ethoxybenzyl-diethylenetriamine-pentaacetic-acid-enhanced MRI (EOB-MRI), and hyaluronic acid analyses improved the estimation of severe liver fibrosis compared to technetium99m galactosyl-serum-albumin scintigraphy.

Impact of tumor shrinkage pattern with biweekly triplet gemcitabine+cisplatin+S-1 regimen for biliary tract cancers: Implications for neoadjuvant therapy from the data of KHBO1401 (KHBO1401-1A study).

BACKGROUND: The multicenter randomized phase III KHBO1401 study (gemcitabine+cisplatin+S-1 [GCS] versus GC in biliary tract cancers [BTC]) demonstrated that GCS not only prolonged patient survival but also achieved a high response rate and that it should be good for neoadjuvant therapy. Therefore, to explore the possibilities of neoadjuvant therapy, we investigated the tumor shrinkage pattern. METHODS: Among the total of 246 patients enrolled in the KHBO1401, the tumor shrinkage pattern and survival were investigated in patients with measurable BTC (n=183, 74%; GCS, n=91; GC, n=92). RESULTS: The tumor shrinkage pattern could be divided to 4 categories based on the response at 100 days after enrollment: category A (<-30% in size), B (-30% to 0%), C (0% to +20%), and D (>+20%). The GCS arm included more category A and B cases (61 [67%] vs. 33 [36%], P<0.0001). Each category predicted best response and overall survival (P<0.0001). Category A showed sustained tumor response compared with category B; in GCS, the time to maximum tumor response was 165 ± 76 days in category A and 139 ± 78 in category B. Categories C and D did not achieve tumor shrinkage. The maximum tumor shrinkage size in category A was -53% in the GCS arm and -65% in the GC arm (P=0.0892). Twenty percent of patients in the GCS showed tumor regrowth 154 ± 143 days later. CONCLUSION: GCS provided faster and greater tumor shrinkage with better survival in comparison to GC, although 20% of patients showed re-growth after 6 cycles.

Reevaluation of Makuuchi's criteria for resecting hepatocellular carcinoma: A Japanese nationwide survey.

AIM: Although Makuuchi's criteria are widely used to determine the cut-off for safe liver resection, there have been few reports of concrete data supporting their validity. Here, we verified the utility of Makuuchi's criteria by comparing the operative mortality rates associated with liver resection between hepatocellular carcinoma (HCC) patients meeting or exceeding the criteria. METHODS: A database was built using data from 15 597 patients treated between 2000 and 2007 for whom values for all three variables included in Makuuchi's criteria for liver resection (clinical ascites, serum bilirubin, and indocyanine green clearance) were available. The patients were divided into those fulfilling (n = 12 175) or exceeding (n = 3422) the criteria. The postoperative mortality (death for any reason within 30 days) and long-term survival were compared between the two groups. RESULTS: The operative mortality rate was significantly lower in patients meeting the criteria than in those exceeding the criteria (1.07% vs. 2.01%, respectively; p < 0.001). On multivariate analysis, exceeded the criteria was significantly associated with the risk for operative mortality (relative risk 2.08; 95% confidence interval (CI), 1.23-3.52; p = 0.007). Surgical indication meeting or exceeding the criteria was an independent factor for overall survival (hazard ratio 1.27; 95% CI, 1.18-1.36; p < 0.001). CONCLUSION: Makuuchi's criteria are suitable for determining the indication for resection of HCC due to the reduction in risk of operative mortality.

The significance of CDT1 expression in non-cancerous and cancerous liver in cases with hepatocellular carcinoma.

We previously reported that chromatin licensing and DNA replication factor 1 (CDT1) expression was associated with the extent of proliferation of atypical hepatocytes and the time to postoperative recurrence in cases of hepatocellular carcinoma (HCC). This study aimed to clarify the clinical significance or pathogenesis of CDT1 expression in both non-cancerous and cancerous liver in HCC cases, including previously published data. We investigated the association between the expression of CDT1 in non-cancerous or cancerous liver tissues and histologic findings or biochemical examination results in 62 cases. We also examined the dual localization between CDT1 and FbxW7, P57kip2, P53 and c-Myc by confocal laser scanning microscopy. CDT1 mRNA expression was significantly higher in cancerous liver than in non-cancerous liver (p<0.0001). Elevated CDT1 mRNA expression indicates a significantly degree of inflammatory cell infiltration within lobules, along with elevated serum transaminase levels, and hepatic spare decline. CDT1 mRNA was highly expressed in a group of poorly differentiated cancer cells. CDT1 co-localized with P57kip2, Fbwx7, P53 and c-Myc in the nucleus or cytoplasm of hepatocytes and cancer cells. We found that CDT1 mRNA expression could represent the degree of hepatic spare ability and the high carcinogenic state.

Comparison between CT volumetry and extracellular volume fraction using liver dynamic CT for the predictive ability of liver fibrosis in patients with hepatocellular carcinoma.

OBJECTIVES: To compare the predictive ability of liver fibrosis (LF) by CT-volumetry (CTV) for liver and spleen and extracellular volume fraction (ECV) for liver in patients undergoing liver resection. METHODS: We retrospectively analysed 90 consecutive patients who underwent CTV and ECV. Manually placed region-of-interest ECV (manual-ECV), rigid-registration ECV (rigid-ECV), and nonrigid-registration ECV (nonrigid-ECV) were calculated as ECV(%) = (1-haematocrit) × (ΔHUliver/ΔHUaorta), where ΔHU = subtraction of unenhanced phase from equilibrium phase (240 s). Manual-ECV was compared with CTV for the estimation of LF. The total liver volume to body surface area (TLV/BSA), splenic volume to BSA (SV/BSA), ratio of TLV to SV (TLV/SV), ratio of right liver volume to SV (RV/SV), and liver segmental volume ratio (LSVR) were measured. ROC analyses were performed for ECV and CTV. RESULTS: After excluding 10 patients, seventy-eight (97.5%) out of 80 patients had a Child-Pugh score of 5 points, and two (2.5%) patients had a Child-Pugh score of 6 points. AUC of ECV showed no significant difference among manual-ECV, rigid-ECV, and nonrigid-ECV. TLV/BSA, SV/BSA, TLV/SV, and RV/SV had a higher correlation with LF grades than manual-ECV. AUC of SV/BSA was significantly higher than that of manual-ECV in F0-1 vs F2-4 and F0-2 vs F3-4. AUC of SV/BSA (0.76-0.83) was higher than that of manual-ECV (0.61-0.75) for all LF grades, although manual-ECV could differentiate between F0-3 and F4 at high AUC (0.75). CONCLUSIONS: In patients undergoing liver resection, SV/BSA is a better method for estimating severe LF grades, although manual-ECV has the ability to estimate cirrhosis (≥ F4). KEY POINTS: The splenic volume is a better method for estimating liver fibrosis grades. The extracellular volume fraction is also a candidate for the estimation of severe liver fibrosis.

Report of the 22nd nationwide follow-up Survey of Primary Liver Cancer in Japan (2012-2013).

In the 22nd Nationwide Follow-up Survey of Primary Liver Cancer in Japan, data from 21 155 newly registered patients and 43 041 previously registered follow-up patients were compiled from 538 institutions over a 2-year period from January 1, 2012 to December 31, 2013. Basic statistics compiled for patients newly registered in the 22nd survey were cause of death, past medical history, clinical diagnosis, imaging diagnosis, treatment-related factors, pathologic diagnosis, recurrence status and autopsy findings. Compared with the previous 21st survey, the population of patients with hepatocellular carcinoma (HCC) was older at the time of clinical diagnosis, had more female patients, more patients with non-B non-C HCC, smaller tumor diameter and was more frequently treated with hepatectomy. Cumulative survival rates were calculated for HCC, intrahepatic cholangiocarcinoma, and combined hepatocellular cholangiocarcinoma (combined HCC and intrahepatic cholangiocarcinoma) by treatment type and background characteristics for patients newly registered between 2002 and 2013 whose final outcome was survival or death. Median overall survival and cumulative survival rates for HCC were calculated by dividing patients by combinations of background factors (number of tumors, tumor diameter or Child-Pugh grade) and by treatment type (hepatectomy, radiofrequency ablation therapy, transcatheter arterial chemoembolization, hepatic arterial infusion chemotherapy and systemic therapy). The same values were also calculated according to registration date by dividing patients newly registered between 1978 and 2013 into five time period groups. The data obtained from this nationwide follow-up survey are expected to contribute to advancing clinical research and treatment of primary liver cancer worldwide.

Evaluation of Safety-Related Outcomes of One-Segment and More-Than-One-Segment High-Level Hepatectomy in Hepatocellular Carcinoma Based on the Japanese Board Certification System.

BACKGROUND: We evaluated the impact of the Japanese board certification system for expert surgeons (JBCSES) on complications and survival outcomes in hepatectomy for hepatocellular carcinoma. METHODS: The postoperative outcomes of 493 patients who underwent high-level liver surgery involving one-segment (OSeg) hepatectomy and more-than-one-segment (MOSeg) resection were compared before and after JBCSES establishment. After the establishment of the JBCSES, the patients' postoperative outcomes were compared using propensity score matching (PSM) to determine the influence of expert surgeons. RESULTS: The establishment of the JBCSES was associated with a decrease in the overall postoperative complication rates after high-level liver surgery from 50.2 to 38.1% (P = 0.008) and a decrease in Clavien-Dindo class ≥ IIIb complications from 10.2 to 5.0% (P = 0.035). The 90-day mortality rate decreased from 5.1 to 0.7% (P = 0.003), and the 5-year survival rate increased from 51.4 to 63.9% (P = 0.009). Using PSM, a comparison of OSeg hepatectomies that involved expert surgeons (n = 48) and those that did not (n = 48) showed significantly lower intraoperative blood loss in surgeries involving an expert surgeon (mean, 340 vs. 473 mL; P = 0.033). There were no significant differences in complication rates or long-term prognosis between these groups. A comparison of MOSeg hepatectomies that involved expert surgeons (n = 26) and those that did not (n = 26) showed no significant difference in surgical factors, complications, or overall survival between the two groups. CONCLUSIONS: After establishment of the JBCSES, postoperative complication rates and mortality rates decreased and survival rates increased following liver surgery. Expert surgeon participation significantly decreased intraoperative blood loss during OSeg hepatectomies.

Validity of the Algorithm for Liver Resection of Hepatocellular Carcinoma in the Caudate Lobe.

BACKGROUND: We aimed to validate our algorithm for resecting Hepatocellular carcinoma (HCC) in the caudate lobe based on tumor location, tumor size, and indocyanine green clearance rate. METHODS: Patients who underwent curative resections for solitary HCC in the caudate lobe were included. The surgical outcomes of patients with HCC in the caudate lobe were compared with those of patients with HCC in other sites of the liver. RESULTS: After one-to-one matching, the caudate-lobe group (n = 150) had longer operation time, greater amount of bleeding, lower weight of resected specimens, and shorter distance between tumor and resection line than the other-sites group (n = 150), but the complication rates were not different between the groups (38.0% vs. 34.1%, P = 0.719). After a median follow-up period of 3.0 years (range, 0.3-16.2 years), the median overall survivals were 6.5 (95% confidence interval [CI], 5.3-7.9) and 7.5 years (95% CI, 6.3-9.7) in the caudate-lobe and other-site groups, respectively (P = 0.430). Median recurrence-free survivals in the caudate-lobe group (1.9 years; 95% CI, 1.4-2.7) had a tendency to be shorter than those in the other-sites group (2.3 years; 1.7-3.4) (P = 0.052). CONCLUSIONS: Patients' survival and complication rates in the caudate-lobe group were comparable to those in the other-sites group; therefore, our algorithm for resecting HCC in the caudate lobe is of clinical use.

A multicenter phase II trial evaluating the efficacy of bevacizumab plus mFOLFOX6 for R0 surgical resection in advanced colorectal liver metastases harboring mutant-type KRAS: NEXTO-mt trial.

BACKGROUND: The effect of bevacizumab plus mFOLFOX6 on downsizing of liver metastases for curative resection has not been well assessed for patients with advanced colorectal liver metastases (CRLMs). This multicenter phase II trial aimed to examine the efficacy and safety of bevacizumab plus mFOLFOX6 for advanced CRLMs harboring mutant-type KRAS. METHODS: Patients with advanced CRLMs (tumor number of ≥5 and/or technically unresectable) harboring mutant-type KRAS were included. Surgical indication was evaluated every 4 cycles of bevacizumab plus mFOLFOX6. Liver resection was planned if the CRLMs were resectable. The primary endpoint was R0 resection rate. The secondary endpoints included overall survival (OS), recurrence-free survival, progression-free survival, and safety. RESULTS: Between 2013 and 2017, 29 patients from six centers were registered. The rates of complete and partial responses were 0% and 62.1%, respectively. R0 and R1 resections were performed in 19 and 1 patient, respectively (R0 resection rate: 65.5%). No mortality occurred. During the median follow-up of 30.7 months, the 3-year OS rate for all the patients was 64.4% with the median survival of 49.1 months. CONCLUSION: For advanced CRLMs harboring mutant-type KRAS, bevacizumab plus mFOLFOX6 achieved a high R0 resection rate, leading to favorable survival.

[Long-Term Survival of Patient Having Advanced Esophageal Cancer with Cirrhosis after Overcoming Anastomotic Leakage, Purulent Osteomyelitis, Cervical Lymph Node Recurrence, and Systemic Edema-A Surgical Case].

We report the surgical case of advanced esophageal cancer with cirrhosis in a patient who has been cancer-free for 6 years after overcoming anastomotic leakage, purulent osteomyelitis, cervical lymph node recurrence, and systemic edema. A 69-year-old woman visited our hospital and presented with the complaint of a food sticking sensation. Endoscopic findings showed a type 3 tumor in the middle thoracic esophagus. Esophagectomy was subsequently performed. Histopathological findings revealed poorly differentiated squamous cell carcinoma, Mt, 17×15 mm, type 3, pT3, pIM0, pPM0, pDM0, pRM0, pN2(7/18), pStage Ⅲ, and liver cirrhosis(F4, A1-2). Postoperative suture failure was observed; however, it conservatively improved in approximately 2 months. The patient had lower back pain since approximately 6 weeks after the surgery, and she was diagnosed with purulent spondylitis and was administered antibiotics. The patient was subsequently discharged 67 days after the surgery. One course of 5-FU+CDDP was administered as postoperative adjuvant chemotherapy. However, renal function deteriorated, and chemotherapy was discontinued. Four months after the surgery, cervical echography revealed recurrence in the left cervical lymph node, and docetaxel(DTX)was administered. Five DTX doses were administered, because of which the left cervical lymph nodes markedly shrunk. Moreover, the sixth dose of DTX resulted in febrile neutropenia and a large amount of abdominal pleural effusion. Consequently, the patient was hospitalized. Tolvaptan treatment was extremely effective, and the thoracic ascites disappeared. Esophageal cancer has not recurred, and the patient is being observed at an outpatient clinic 6 years after the surgery.

[A Long-Term Recurrence-Free Survivor after Resection for Hepatopulmonary Metastases found within One Year after Rectal Cancer Surgery].

We observed a case of long-term survival without recurrence following hepatectomy and lung resection in a patient with hepatopulmonary metastases, which appeared 7 months after rectal cancer surgery. We report the case of a 68-year-old man whose chief complaint was anal pain. The patient was referred to our hospital because of a suspected rectal cancer. He was diagnosed with rectal cancer without distant metastasis, and abdominoperineal excision was then performed. Histopathological findings revealed Rb, type 2, 85×60 mm, tub 2, ly1, v1, pPM0, pDM0, pRM0, pT3(A), pN0(0/27), cM0, and pStage Ⅱa. Seven months after the surgery, abdominal computed tomography(CT)revealed a 3 cm nodule in segment 7 of the liver. In addition, chest CT detected a 2 mm nodule in segment 3 of the upper lobe of the left lung. Hepatectomy was immediately performed, whereas lung nodules were to be followed up. Three months later, chest CT showed that the lung nodules had increased in size(approximately 5 mm); therefore, the patient was diagnosed with lung metastasis, and thoracoscopic partial lung resection was performed. The histopathological findings of the hepatic tumor and lung tumor were similar to those of rectal cancer. The postoperative course was good, and the patient has been alive without recurrence for 8 years since the final surgery(lung resection)without postoperative adjuvant chemotherapy.

[Clinicopathological Examination of Resected Case of Primary Duodenal Cancer at Our Hospital].

Primary duodenal cancer is a rare disease. We examined 8 resected cases of duodenal cancer at our hospital from June 2003 to February 2022. Patients with resected duodenal cancer had an average age of 69.3 years(45-84 years), with a male-female ratio of 3 : 5. Of the 8 cases, 6 cases were adenocarcinomas and 2 were neuroendocrine carcinomas. Among those with adenocarcinomas, 3 cases were Stage Ⅰ, while Stage ⅡA, ⅢA, and ⅢB accounted for one case each(UICC 8th edition). Five patients underwent a pancreaticoduodenectomy(PD), while 1 underwent partial duodenal resection. Except for 1 case of Stage ⅢB(death from tumor recurrence in 1 year), tumor recurrence was not observed in the 5 remaining cases(survival period; >1 month to >97 months). The patient with a pT3pN1M0, Stage Ⅲ neuroendocrine carcinoma underwent a partial duodenal resection due to poor cardiac and renal function. Meanwhile, the patient with a pT4pN0M0, Stage Ⅲ neuroendocrine carcinoma underwent a PD. The survival time was 123 months for the former(death from other diseases, no tumor recurrence)and 7 months for the latter(death from recurrence).

[A 10-Year Survivor with Multidisciplinary Treatment for Pancreatic Carcinoma That Recurred 17 Months after Pancreatoduodenectomy].

Postoperative recurrence of invasive pancreatic ductal carcinoma(PC)has a poor prognosis. We experienced a case of PC that relapsed 17 months after pancreaticoduodenectomy(PD)and survived for more than 10 years after PD. A 51-year-old man underwent PD in December 2011(pT3pN1bM0, pStage Ⅱb). Gemcitabine(GEM)16 cycles were performed as postoperative adjuvant chemotherapy, and a 1 cm nodule was found in the liver on abdominal CT scan, and partial liver resection was performed. After that, adjuvant chemotherapy with S-1 was performed for 12 months. Abdominal CT scan revealed abdominal lymph node metastasis, and radiation therapy(39.6 Gy)was requested from another hospital. Then, the combination therapy of 5-FU/l-LV plus L-OHP(or CPT-11)was started in September 2014. To date, a total of 131 cycles of chemotherapy have been given. 10 years and 5 months after pancreaticoduodenectomy and 9 years after hepatectomy, although recurrence around the superior mesenteric artery plexus was observed, outpatient visits are continued.

Algorithm for Resecting Hepatocellular Carcinoma in the Caudate Lobe.

OBJECTIVE: To propose an algorithm for resecting hepatocellular carcinoma (HCC) in the caudate lobe. BACKGROUND: Owing to a deep location, resection of HCC originating in the caudate lobe is challenging, but a plausible guideline enabling safe, curable resection remains unknown. METHODS: We developed an algorithm based on sublocation or size of the tumor and liver function to guide the optimal procedure for resecting HCC in the caudate lobe, consisting of 3 portions (Spiegel, process, and caval). Partial resection was prioritized to remove Spiegel or process HCC, while total resection was aimed to remove caval HCC depending on liver function. RESULTS: According to the algorithm, we performed total (n = 43) or partial (n = 158) resections of the caudate lobe for HCC in 174 of 201 patients (compliance rate, 86.6%), with a median blood loss of 400 (10-4530) mL. Postoperative morbidity (Clavien grade ≥III b) and mortality rates were 3.0% and 0%, respectively. After a median follow-up of 2.6 years (range, 0.5-14.3), the 5-year overall and recurrence-free survival rates were 57.3% and 15.3%, respectively. Total and partial resection showed no significant difference in overall survival (71.2% vs 54.0% at 5 yr; P = 0.213), but a significant factor in survival was surgical margin (58.0% vs 45.6%, P = 0.034). The major determinant for survival was vascular invasion (hazard ratio 1.7, 95% CI 1.0-3.1, P = 0.026). CONCLUSIONS: Our algorithm-oriented strategy is appropriate for the resection of HCC originating in the caudate lobe because of the acceptable surgical safety and curability.

Effect of Diameter and Number of Hepatocellular Carcinomas on Survival After Resection, Transarterial Chemoembolization, and Ablation.

INTRODUCTION: Most studies predicting survival after resection, transarterial chemoembolization (TACE), and ablation analyzed diameter and number of hepatocellular carcinomas (HCCs) as dichotomous variables, resulting in an underestimation of risk variation. We aimed to develop and validate a new prognostic model for patients with HCC using largest diameter and number of HCCs as continuous variables. METHODS: The prognostic model was developed using data from patients undergoing resection, TACE, and ablation in 645 Japanese institutions. The model results were shown after balanced using the inverse probability of treatment-weighted analysis and were externally validated in an international multi-institution cohort. RESULTS: Of 77,268 patients, 43,904 patients, including 15,313 (34.9%) undergoing liver resection, 13,375 (30.5%) undergoing TACE, and 15,216 (34.7%) undergoing ablation, met the inclusion criteria. Our model (http://www.u-tokyo-hbp-transplant-surgery.jp/about/calculation.html) showed that the 5-year overall survival (OS) in patients with HCC undergoing these procedures decreased with progressive incremental increases in diameter and number of HCCs. For patients undergoing resection, the inverse probability of treatment-weighted-adjusted 5-year OS probabilities were 10%-20% higher compared with patients undergoing TACE for 1-6 HCC lesions <10 cm and were also 10%-20% higher compared with patients undergoing ablation when the HCC diameter was 2-3 cm. For patients undergoing resection and TACE, the model performed well in the external cohort. DISCUSSION: Our novel prognostic model performed well in predicting OS after resection and TACE for HCC and demonstrated that resection may have a survival benefit over TACE and ablation based on the diameter and number of HCCs.

Report of the 21st Nationwide Follow-up Survey of Primary Liver Cancer in Japan (2010-2011).

In the 21st Nationwide Follow-up Survey of Primary Liver Cancer in Japan, data from 22,134 new patients and 41,956 previously followed patients were compiled from 546 institutions over a 2-year period from 1 January 2010 to 31 December 2011. Basic statistics compiled for patients newly registered in the 21st survey were cause of death, medical history, clinical diagnosis, imaging diagnosis, treatment-related factors, pathological diagnosis, recurrence status, and autopsy findings. Compared with the previous 20th survey, the population of patients with hepatocellular carcinoma (HCC) was older at the time of clinical diagnosis, had more female patients, had more patients with non-B non-C HCC, had smaller tumor diameter, and was more frequently treated with hepatectomy and with radiofrequency ablation. Cumulative survival rates were calculated for HCC, intrahepatic cholangiocarcinoma, and combined hepatocellular cholangiocarcinoma (combined HCC and intrahepatic cholangiocarcinoma) by treatment type and background characteristics for patients newly registered between 1998 and 2011 whose final outcome was survival or death (excluding unknown). Cumulative survival rates for HCC were calculated by dividing patients by combinations of background factors (number of tumors, tumor diameter, and Child-Pugh grade) and by treatment type (hepatectomy, local ablation therapy, transcatheter arterial chemoembolization, and hepatic arterial infusion chemotherapy). The same values were also calculated according to registration date by dividing patients newly registered between 1978 and 2011 into four time-period groups. The data obtained from this nationwide follow-up survey are expected to contribute to advancing clinical research and treatment of primary liver cancer.

Hepatocellular adenoma, approximately half and predominantly inflammatory subtype, in 38 Japanese patients with several differences in age, gender, and clinical background factors from Western populations.

AIM: Hepatocellular adenoma (HCA) has a lower prevalence in Japan than in Western countries and HCA subtypes have been reported for only a few Japanese patients. We analyzed HCA subtype data 38 patients from 23 hospitals in Japan in order to examine character and difference between Western countries. METHODS: To confirm HCA and to analyze subtypes, we performed immunohistochemical examinations. RESULTS: Thirty-eight cases were found to have HCA without cirrhosis. The male/female ratio was 18/20. Ages ranged from 15 to 79 (average, 43.2) years. Male and elder patients are not rare, furthermore, most of elder patients are male. Glycogen storage disease, past history of medicament use, hepatitis B virus surface antigen-positivity, antihepatitis C virus -positivity, diabetes mellitus, obesity, lipid metabolism disorder and alcoholism were present in of 6, 8, 1, 1, 6, 6, 4, and 6 cases, respectively. As to HCA subtypes, HNF1alpha-inactivated HCA, beta-catenin activated HCA (b-HCA), inflammatory HCA (IHCA) and unclassified HCA (U-HCA) accounted for nine (23.7%), four (10.5%), 17 (44.7%) and eight (21.1%) cases, respectively. Two cases showed coexistence of HCA and hepatocellular carcinoma (HCC) at surgery, and another had HCC which had been detected 23 years after HCA diagnosis. The HCA subtype of one of the former cases was U-HCA, while the remaining two had b-HCA and U-HCA. CONCLUSIONS: In Japanese HCA cases, the proportions of U-HCA, male and elder cases were slightly higher than in Western countries, and most of elder patients were male. IHCA was however common regardless of race, and was assumed to be the predominant subtype of HCA.

Impact of hepatitis C virus on survival in patients undergoing resection of intrahepatic cholangiocarcinoma: Report of a Japanese nationwide survey.

AIM: We reviewed the data of a nationwide follow-up survey to determine the impact of hepatitis C virus (HCV) infection on the outcomes of hepatectomy for mass-forming (MF) type, and combined mass-forming and periductal infiltrating (MF + PI) type intrahepatic cholangiocarcinoma (ICC). METHODS: In total, 956 patients with ICC who underwent curative hepatic resection were included in this cohort study, and patients were classified according to virus status. Patients were classified according to virus status as follows: HCV-related ICC (n = 138, 14.4%), hepatitis B virus (HBV)-related ICC (n = 43, 4.5%) and non-virus-related ICC (n = 775, 81.1%). To control for variables, we used 1:1 propensity score-matching to compare outcomes after surgery between HCV-related (n = 102) and non-virus-related ICC cases (n = 102). RESULTS: We successfully matched HCV-related and non-virus-related ICC cases with similar liver function and tumor characteristics. Patients with HCV-related ICC had significantly shorter recurrence-free survival (hazard ratio 0.62, 95% confidence interval 0.42-0.92, p = 0.016) and overall survival (hazard ratio: 0.57, 95% confidence interval: 0.37-0.88, p = 0.011) than patients with non-virus-related ICC. Cox proportional hazard analysis showed that HCV-related ICC offered a worse prognosis than non-virus-related ICC. CONCLUSIONS: HCV infection increases the risk of recurrence and worsens overall survival in patients after curative resection for MF and combined MF + PI type ICC.

Transanal minimally invasive surgery for rectal neuroendocrine tumors.

BACKGROUND: There is no literature that mainly searched for rectal neuroendocrine tumor (rNET) using transanal minimal invasive surgery (TAMIS). We report our clinical experiences of TAMIS for rectal neuroendocrine tumors to evaluate the feasibility and safety. METHODS: Between December 2010 and March 2020, the 25 consecutive patients with rectal neoplasma underwent the TAMIS procedure performed by single laparoscopic surgeon at the two hospitals. Of these, ten patients with rectal neuroendocrine tumors were reviewed retrospectively. The full-thickness excision down to the outer fatty tissues was completed using TAMIS technique. Clinicopathological findings, perioperative and postoperative complications were recorded. RESULTS: TAMIS for small rNET was successfully completed in all cases. There were seven cases with a tumor size of less than 10 mm, and three cases with a tumor size between 10 and 15 mm. Six patients underwent the primary tumor excision; the remaining four patients underwent resection for the scar after endoscopic procedure. The median surgical duration was 80.5 (53-124) minutes and the median blood loss was 1 (1-12) ml. All removed tumors in the 6 primary excisions were diagnosed as neuroendocrine tumor G1. The margins of specimens were completely free in all cases. Among the four patients after endoscopic procedure, all had no histological evidence of residual tumor. The median length of hospital stay was 7 days postoperatively. There was no post-operative mortality or severe complication. The median length of observation was 54 months. No recurrence, no local or distant metastasis and no mortality of all patients were observed. CONCLUSIONS: TAMIS is safety and feasible procedure for small rNET. Further experience and clinical trials are needed to fully define the advantages, disadvantages, and indications of TAMIS for rNET.

Subcuticular Sutures Versus Staples for Wound Closure in Open Liver Resection: A Randomised Clinical Trial.

BACKGROUND: Subcuticular sutures reduce wound complication rates only in clean surgeries. Repeat resection is frequently required in liver surgery, due to the high recurrence rate (30-50%) of liver cancers. The aim of this study is to assess that subcuticular sutures is superior to staples in liver surgery. METHODS: This single-centre, single-blinded, randomised controlled trial was conducted at a university hospital between January 2015 and October 2018. Patients were randomly assigned (1:1) to receive either subcuticular sutures or staples for skin closure. Three risk factors (repeat resection, diabetes mellitus and liver function) were matched preoperatively for equal allocation. The primary endpoint was the wound complication rate, while secondary endpoints were surgical site infection (SSI), duration of postoperative hospitalisation and total medical cost. Subset analyses were performed only for the 3 factors allocated as secondary endpoints. RESULTS: Of the 581 enrolled patients, 281 patients with subcuticular sutures and 283 patients with staples were analysed. As the primary outcome, the wound complication rate with subcuticular sutures (12.5%) did not differ from that with staples [15.9%; odds ratio (OR), 1.33; 95% confidence interval (CI), 0.83-2.15; p = 0.241]. As secondary outcomes, no significant differences were identified between the two procedures in the overall cohort while overall wound complications [7 patients (8.5%) vs. 17 patients (20.0%); OR, 2.68; 95% CI, 1.08-7.29; p = 0.035] with repeat incision were significantly less frequent with subcuticular sutures. CONCLUSION: Subcuticular sutures were not shown to reduce wound complications compared to staples in open liver resection, but appear beneficial for repeat incisions.