Preoperative Chemotherapy Followed by Hepatectomy for Potentially Resectable UICC7 Stage IIIA, IIIB Hepatocellular Carcinoma; A Phase II Clinical Trial.

BACKGROUND: The Japanese guideline for therapeutic strategy in HCC does not recognize any benefit of preoperative chemotherapy for potentially resectable hepatocellular carcinoma (HCC), and only upfront resec tion is recommended even for an advanced HCC. Data on preoperative chemotherapy for advanced HCC is still limited. Poor prognostic factors of HCC after resection are tumor more than 5 cm in diameter, multiple lesions, and gross tumor thrombosis, which constitute UICC7 Stage IIIA and IIIB HCC. There are no prospective studies about preoperative chemotherapy in these patients. AIM: To evaluate the benefit of preoperative chemotherapy for UICC7 Stage IIIA and IIIB potentially resectable HCC. DISCUSSION: Our recent study demonstrated that the 5-year overall survival rate (OS) of patients diagnosed as UICC7 Stage IIIA and IIIB who had received upfront resection was only 16.5%. In contrast, the 5-year OS of UICC7 Stage IIIA and IIIB initially unresectable patients who had achieved conversion from unresectable to resect able status under successful hepatic infusion chemotherapy prior to resection was as high as 61.3%. Additionally, recent studies reported transarterial chemoembolization achieved outcomes comparable with those of resection. Therefore, we believe that patients with UICC7 Stage IIIA and IIIB should be considered borderline resectable. To evaluate this hypothesis we registered the present phase II clinical trial to assess the benefit of preoperative chemo therapy followed by hepatectomy in potentially resectable UICC7 Stage IIIA and IIIB HCC patients.

Significance of Desmoplastic Histopathological Growth Pattern for Colorectal Liver Metastases Treated With Preoperative Chemotherapy.

BACKGROUND/AIM: The aim of this study was to evaluate hepatectomy cases that underwent preoperative chemotherapy to examine the relationship between the development of desmoplastic histopathological growth pattern (dHGP) and prognosis and recurrence and determine whether it is useful for evaluating preoperative chemotherapy. PATIENTS AND METHODS: A total of 133 cases with hepatic metastasis for colorectal cancer that underwent surgical resection. RESULTS: Of the 102 cases that underwent preoperative chemotherapy, 34 (33%) were determined to be dHGP positive, which was statistically significantly higher than the 2 of 31 cases (6.5%) that had not undergone preoperative chemotherapy. Regarding the 5-year recurrence-free survival, the dHGP group had a value of 50.3%, whereas the non-dHGP group had a value of 7.1%. For the 5-year overall survival, the dHGP group had a better prognosis than the non-dHGP group (57.6% vs. 37.1%, respectively), with a statistically significant difference. Univariate analysis of recurrence-free survival showed that the number of tumours, the Response Evaluation Criteria in Solid Tumors, and the presence or absence of dHGP were prognostic factors, whereas multivariate analysis showed that the presence or absence of dHGP was an independent prognostic factor. Univariate analysis of the overall survival showed that the number of tumours, the Response Evaluation Criteria in Solid Tumors, and presence or absence of dHGP were prognostic factors. Multivariate analysis showed that the presence or absence of dHGP was an independent prognostic factor. CONCLUSION: dHGP is useful as a new evaluation method for evaluating the efficacy of preoperative chemotherapy.

Prepancreatic postduodenal portal vein: a case report and literature review.

BACKGROUND: Among congenital anomalies of the portal venous system, prepancreatic postduodenal portal vein (PPPV) is very rare and has only been reported to date. Herein, we report a case of PPPV identified in preoperative examinations for hepatocellular carcinoma and a literature review. CASE PRESENTATION: A 63-year-old man was admitted to our hospital for treatment of a liver tumor. After examination, he was diagnosed with hepatocellular carcinoma with a diameter of 40 mm in segment 8. Contrast-enhanced computed tomography scan showed a portal vein passing between the duodenum and pancreas, hence called PPPV. At the hepatic hilus, the portal vein branched off in a complicated course with some porto-portal communications. We determined that anatomical resection with manipulation of the hepatic hilum in this case resulted in major vascular injury. Therefore, we performed partial liver resection, and the patient was discharged uneventfully on postoperative day 14. CONCLUSIONS: Although PPPV is an extremely rare congenital vascular variant, it is important to carefully identify vascular patterns preoperatively and to recognize the possibility of such an anomaly to avoid misidentification and inadvertent injuries during surgery.

Impact of Interferon on the Prognosis of Hepatitis C Virus-Related Hepatocellular Carcinoma Patients with a Sustained Virological Response -An Additional Comparison Between Preoperative and Postoperative Sustained Virological Response.

BACKGROUND: Several studies have reported that interferon (IFN) therapy improves the prognosis of patients with hepatitis C virus (HCV)-related hepatocellular carcinoma (HCC), especially for patients who have achieved a sustained virological response (SVR). We retrospectively evaluated the clinicopathological outcomes of patients who acquired an SVR through IFN therapy pre- or post-hepatectomy for treatment naïve HCC. METHOD: Among the 305 HCV-related HCC patients entered in this study, 59 patients (SVR group) achieved an SVR after IFN therapy and received hepatectomy either after or before achieving an SVR (n=36 and n=23, respectively), while the remaining 179 patients (control group) did not receive IFN therapy, or did not achieve an SVR through IFN therapy (n=67). RESULTS: In the SVR group, the overall survival (OS) and disease-free survival (DFS) rates were significantly higher than in the control group. We evaluated the prognosis of patients with an SVR achieved pre- or post-hepatectomy separately. There were no significant differences in OS and DFS. CONCLUSION: This result suggests that the prognosis of naïve HCC may be improved by additional INF therapy to achieve SVR status after hepatectomy.

[A Case of the Spontaneously Ruptured Recurrence Hepatic Angiosarcoma after Hepatic Resection].

A 67-year-old male was referred to our hospital in a state of shock. Transcatheter arterial embolization(TAE)was performed for the diagnosis of liver tumor rupture, followed by extended posterior area resection 18 days later. Histopathologically, he was diagnosed with hepatic angiosarcoma. The patient was discharged 18 days after the surgery, but readmitted on the 51st day due to bleeding shock caused by the rupture of a recurrent tumor in the liver. Although TAE was performed, the patient developed hepatic failure and died on postoperative day 81. Autopsy revealed multiple intrahepatic recurrence and peritoneal dissemination. Herein, we report a case of ruptured hepatic angiosarcoma that underwent hepatic resection after TAE and had a rapid outcome due to early postoperative rupture of recurrent lesion.

Liberal Application of Portal Vein Embolization for Right Hepatectomy Against Hepatocellular Carcinoma: Strategy to Achieve Zero Mortality for a Damaged Liver.

BACKGROUND/AIM: Right hepatectomy and extended right hepatectomy (Rt-Hr) are identified as risk factors for the development of post-hepatectomy liver failure (PHLF). Although portal vein embolization (PVE) has made it possible to safely perform extended hepatectomy, to ensure safety, in our department, PVE is performed prior to Rt-Hr for hepatocellular carcinoma (HCC) regardless of the resection rate. This study aimed to retrospectively investigate the clinical course of PVE prior to Rt-Hr for HCC cases resected in our department and the appropriateness of our policy by clarifying complications and deaths. PATIENTS AND METHODS: The target period was from 2005 to 2020. Among the HCC cases resected at our hospital, those in which PVE was performed prior to Rt-Hr were included in this study. For PHLF, the definition of the International Study Group of Liver Surgery was used. The Clavien-Dindo classification was used for postoperative complications. Perioperative mortality was defined as the overall mortality within 30 days following surgery and surgery-related deaths within 90 days following surgery. RESULTS: A total of 79 cases were included. Rt-Hr was possible in all cases after PVE and there were no cases in which serious complications occurred after PVE. PHLF was found in 14 cases (17.7%)/5 cases (6.4%)/0 cases (0%) of Grade A/B/C, respectively. Regarding postoperative complications, there were no Grade IV, and Grade IIIa/IIIb were found in 13 cases (16.5%). There were no perioperative deaths. CONCLUSION: Our department's policy of performing PVE prior to all Rt-Hr was considered to be a safe and reasonable treatment strategy.

Assessing the incidence of complications and malignancies in the long-term management of benign biliary strictures with a percutaneous transhepatic drain.

ABSTRACT: Percutaneous drainage catheters (PDCs) are required for the management of benign biliary strictures refractory to first-line endoscopic treatment. While biliary patency after PDC placement exceeds 75%, long-term catheterization is occasionally necessary. In this article, we assess the outcomes of patients at our institution who required long-term PDC placement.A single-institution retrospective analysis was performed on patients who required a PDC for 10 years or longer for the management of a benign biliary stricture. The primary outcome was uncomplicated drain management without infection or complication. Drain replacement was performed every 4 to 12 weeks as an outpatient procedure.Nine patients (three males and six females; age range of 48-96 years) required a long-term PDC; eight patients required the long-term PDC for an anastomotic stricture and one for iatrogenic bile duct stenosis. A long-term PDC was required for residual stenosis or patient refusal. Drain placement ranged from 157 to 408 months. In seven patients, intrahepatic stones developed, while in one patient each, intrahepatic cholangiocarcinoma or hepatocellular carcinoma occurred.Long-term PDC has a high rate of complications; therefore, to avoid the need for using long-term placement, careful observation or early surgical interventions are required.

[A Case of Small Cell Neuroendocrine Carcinoma of the Gallbladder].

A 76-year-old female was referred to our hospital with a tumor of the gallbladder using ultrasonography. CT and MRI of the abdomen and endoscopic ultrasonography revealed thickened walls of the body of her gallbladder. Endoscopic retrograde cholangiopancreatography was performed, adenocarcinoma was suspected based on bile cytology, and extended cholecystectomy with lymphadenectomy was performed. The postoperative pathological diagnosis was small cell neuroendcrine carcinoma. Three months after the surgery, CT revealed that she had multiple recurrences in the distant lymph node, and she died two months later. Gallbladder neuroendocrine carcinoma is rare and which is thought to have a poor prognosis, so effective multidisciplinary treatment must be required for this disease. In this case, it might need not to hesitate to perform preoperative endoscopic ultrasound guided fine needle aspiration(EUS-FNA).

Geriatric nutritional risk index predicts prognosis in hepatocellular carcinoma after hepatectomy: a propensity score matching analysis.

The geriatric nutritional risk index (GNRI) is widely used for nutritional assessment in older inpatients and is associated with postoperative complications and cancer prognosis. We investigated the use of GNRI to predict long-term outcomes in hepatocellular carcinoma of all etiologies after hepatectomy. Overall, 346 patients were examined after propensity score matching. We dichotomized the GNRI score into high GNRI (> 98: N = 173) and low GNRI (≤ 98: N = 173) and evaluated recurrence-free survival (RFS) and overall survival (OS) between both groups. Clinicopathological characteristics between the low- and high-GNRI groups were similar after propensity score matching except for the components of the GNRI score (body mass index and serum albumin level), Child-Pugh score (comprising serum albumin level), and preoperative alpha-fetoprotein level (p < 0.0001, p < 0.0001, p = 0.0030, and p = 0.0007, respectively). High GNRI was associated with significantly better RFS and OS (p = 0.0003 and p = 0.0211, respectively; log-rank test). Multivariate analysis revealed that GNRI is an independent prognostic factor of RFS and OS (low vs. high; hazard ratio [HR], 1.8284; 95% confidence interval [CI] 1.3598-2.4586; p < 0.0001, and HR, 1.5452; 95% CI 1.0345-2.3079; p = 0.0335, respectively). GNRI is an objective, inexpensive, and easily calculated assessment tool for nutritional status and can predict prognosis of hepatocellular carcinoma after hepatectomy.

Hepatic Epithelioid Hemangioendothelioma Presenting Synchronously with Hepatocellular Carcinoma.

Hepatic epithelioid hemangioendothelioma (EHE) is a rare malignant tumor with unknown pathogenesis. Herein, we report a case of a hepatic EHE presenting synchronously with a hepatocellular carcinoma (HCC). To the best of our knowledge, this is the second case report of synchronous hepatic EHE and HCC. An 84-year-old man presented with back pain. During examination, a tumor in liver segment 3 was coincidentally detected. Tumor marker (carbohydrate antigen 19-9, alpha-fetoprotein, and protein induced by vitamin K absence or antagonist-II) levels were elevated. Contrast-enhanced computed tomography revealed perinodular enhancement in the arterial and portal phases. Another tumor was detected in liver segment 2, which was homogeneously enhanced in the arterial phase, followed by washout in the portal and late phases. Based on these imaging findings, we diagnosed the tumor in segment 3 as a solitary cholangiocellular carcinoma and the tumor in segment 2 as a solitary HCC. Lateral sectionectomy of the liver was performed. Microscopically, spindle-shaped and epithelioid cells were present in the tumor in segment 3. On immunohistochemistry, the tumor cells were positive for CD31 and CD34, focally positive for D2-40, and negative for AE1/AE3. Therefore, the tumor in segment 3 was ultimately diagnosed as an EHE and the tumor in segment 2 as a well-differentiated HCC. Preoperative diagnosis of EHE is difficult owing to the lack of specific findings. Intratumoral calcification, halo sign, and lollipop sign are occasionally found in EHE and are useful imaging findings for diagnosis. Clinical behavior is unpredictable, ranging from indolent growth to rapid progression. Clinical or pathological predictors of the course of EHE are urgently required.

Laparoscopic left hepatectomy for a patient with intrahepatic cholangiocarcinoma metastasis in the falciform ligament: a case report.

BACKGROUND: Intrahepatic cholangiocarcinoma (ICC) is primary cancer of the liver with poor prognosis because of its high potential for recurrence and metastasis. We experienced a rare case of ICC with hematogenous metastasis to the falciform ligament. We aimed to clarify the route of metastasis to the mesentery by increasing the accuracy of preoperative imaging and establish a hepatectomy to control cancer. CASE PRESENTATION: An 85-year-old woman was referred to our hospital for a detailed study of progressively increasing liver tumors. She had no subjective symptoms. Her medical history showed hypertension, aneurysm clipping for cerebral hemorrhage, and gallstones. A detailed physical examination and laboratory data evaluation included tumor markers but did not demonstrate any abnormalities. On computed tomography scan, contrast-enhanced ultrasound, and magnetic resonance imaging with gadolinium ethoxybenzyl diethylenetriamine penta-acetic acid, the tumor appeared to be located in liver segment IV, protruding outside the liver. It appeared to contain two distinct components; we suspected ICC in the intrahepatic tumor component. Laparoscopic observation revealed that the extrahepatic lesion was an intra-falciform ligament mass; laparoscopic left hepatectomy was performed. Microscopically, the main tumor in segment IV was 15 mm in diameter and was diagnosed as moderately and poorly differentiated ICC. The tumor of the intra-falciform ligament was not continuous with the main intrahepatic nodule and was also diagnosed as ICC with extensive necrosis. There were no infiltrates in the round ligament of the liver, and several tumor thrombi were found in the small veins of the falciform ligament. CONCLUSIONS: To date, there have been a few reports of metastases of primary liver cancer to the falciform ligament. At the time of preoperative imaging and pathological diagnosis, this case was suggestive of considering that the malignant liver tumor might be suspected of metastasizing to the falciform ligament. Our case improves awareness of this pathology, which can be useful in the future when encountered by hepatic specialists and surgeons.

[Laparoscopic Extirpation of Peritoneal Dissemination of Hepatocellular Carcinoma Using ICG Imaging].

A 71-year-old man who underwent laparoscopic partial liver resection for local recurrence hepatocellular carcinoma (HCC)in segment 4 one year after percutaneous radiofrequency ablation(RFA)for HCC. About 3 years after treatment, the patient showed elevation of serum level of tumor marker and a mass lesion in the round ligament on CT and EOB-MRI. We made a diagnosis of peritoneal dissemination of HCC. Laparoscopic extirpation of peritoneal dissemination using indocyanine green(ICG)imaging was performed and no other tumors were observed in the peritoneal cavity. A lesion was diagnosed as peritoneal dissemination of HCC, and postoperative course was uneventful. This patient underwent repeated RFA and partial resection for recurrence of HCC. The patient was died for intrahepatic multiple recurrence of HCC without peritoneal dissemination 25 months after extirpation of peritoneal dissemination. In the field of hepatobiliary surgery, ICG imaging can be used for the intraoperative real-time visualization of hepatic malignancies. The ICG imaging is restricted to detection of fluorescence for liver tumors 5-10 mm from the liver surface. In the detection of peritoneal dissemination, however, there are no such limitations. Laparoscopic extirpation using ICG imaging is useful for the detection of peritoneal dissemination of HCC and may improve the prognosis in selected patients.

Quercetin Suppresses Proliferation of Liver Cancer Cell Lines In Vitro.

BACKGROUND/AIM: We investigated the anti-proliferative effect of quercetin on liver cancer cell lines. MATERIALS AND METHODS: Thirteen liver cancer cell lines were cultured followed by treatment with varying concentrations of quercetin (0-100 µM) or quercetin and 5-FU, and the cell viability was analysed by the MTT assay. Flow cytometry was also used to examine cell cycle progression after treatment with quercetin. RESULTS: The addition of quercetin resulted in a dose- and time-dependent suppression of cell proliferation. In some cell lines, treatment with quercetin and 5-FU caused an additional or synergistic effect. Most cell lines displayed cell cycle arrest at different phases of the cell cycle. CONCLUSION: Quercetin inhibits the proliferation of liver cancer cells via induction of apoptosis and cell cycle arrest.

Salvage Surgery for Initially Unresectable Locally Advanced Hepatocellular Carcinoma Downstaged by Hepatic Arterial Infusion Chemotherapy.

BACKGROUND/AIM: Recent studies have demonstrated the efficacy of salvage surgery following downstaging of hepatocellular carcinoma (HCC). The aim was to assess the outcomes of salvage surgery after successful downstaging using hepatic arterial infusion chemotherapy (HAIC). PATIENTS AND METHODS: Patients whose diagnosis was unresectable locally advanced HCC and who were resected after conversion to a resectable status by HAIC were included. The overall survival (OS) rate, and disease-free survival (DFS) rate were analyzed by stratifying patients into those with Vp3/4, Vv2/3, and those without major vascular invasion (MVI). RESULTS: Eighteen patients were censored. Among them, six patients had Vp3/4, four patients had Vv2/3, and eight patients had no MVI. The 5-year OS rates of patients with Vp3/4 and those without MVI were 83% and 73%, respectively, whereas those with Vv2/3 had 0% (p<0.001). CONCLUSION: Salvage surgery has the potential to provide excellent outcomes in resectable HCC patients, except for those with Vv2/3.

A case of reactive lymphoid hyperplasia of the liver in a patient with autoimmune hepatitis.

BACKGROUND: Reactive lymphoid hyperplasia (RLH) of the liver is a benign disorder. It is usually observed in the skin, orbit, thyroid, lung, breast, or gastrointestinal tract, but rarely in the liver. Since the first report of RLH of the liver in 1981, only 75 cases have been described in the past literature. Herein, we report a case of RLH of the liver in a patient with autoimmune hepatitis (AIH), which was misdiagnosed as hepatocellular carcinoma (HCC) preoperatively and resected laparoscopically. CASE PRESENTATION: A 43-year-old Japanese woman with autoimmune hepatitis was followed up for 5 years. During her medical checkup, a hypoechoic nodule in segment 6 of the liver was detected. The nodule had been gradually increasing in size for 4 years. Abdominal ultrasound (US) revealed a round, hypoechoic nodule, 12 mm in diameter. Contrast-enhanced computed tomography (CT) demonstrated that the nodule was slightly enhanced in the arterial dominant phase, followed by perinodular enhancement in the portal and late phases. A magnetic resonance imaging (MRI) scan showed low signal intensity on the T1-weighted image (T1WI) and slightly high signal intensity on the T2-weighted image (T2WI). The findings of the Gd-EOB-DTPA-enhanced MRI were similar to those of contrast-enhanced CT. Tumor markers were all within the normal range. The preoperative diagnosis was HCC and a laparoscopic right posterior sectionectomy was performed. Pathological examination revealed that the nodular lesion was infiltrated by small lymphocytes and plasma cells, and germinal centers were present. Immunohistochemistry was positive for B cell and T cell markers, indicating polyclonality. The final diagnosis was RLH of the liver. CONCLUSIONS: The pathogenesis of RLH of the liver remains unknown, and a definitive diagnosis based on imaging findings is extremely difficult. If a small, solitary nodule is found in female patients with AIH, the possibility of RLH of the liver should be considered.

Hand-assisted laparoscopic surgery for Bochdalek hernia in an adult patient with a history of laparotomy: A case report.

INTRODUCTION: Bochdalek hernia (BH) is a congenital diaphragmatic hernia that generally occurs in infants and is rarely seen in adults. Surgical repair of BH is recommended, but the approach for repairing BH should be selected carefully in individual cases. It is well known that hand-assisted laparoscopic surgery (HALS) has the advantage of preserving tactile sensation compared with standard laparoscopic surgery. We describe an adult patient with a history of abdominal incisional hernia who developed BH that was treated safely by HALS. PRESENTATION OF CASE: An 87-year-old woman was admitted to our hospital with nausea. She had a history of right hemicolectomy and repair of an abdominal incisional hernia using mesh at 5 years after hemicolectomy. Chest and abdominal computed tomography revealed herniation of the gastric corpus through the left posterior diaphragm. BH was diagnosed and hernia repair by HALS was selected as the approach because dense adhesions were expected in the abdominal cavity. The operation was performed safely and her postoperative course was uneventful. CONCLUSION: HALS was useful, especially when removing adhesions around the hernial orifice. HALS is a feasible approach for BH and should be considered as one of the options in patients with a history of previous abdominal surgery.

Intrabiliary growth type of metastasis from colon cancer, 12 years after curative colectomy: a case report.

BACKGROUND: Liver is a common location of colorectal metastasis, but intrabiliary growth of liver metastasis is not well recognized. Furthermore, intrabiliary metastasis that discovered over 10 years after excision has rarely been described. CASE PRESENTATION: An 80-year-old man was admitted due to the presence of a liver mass in segment 5 (S5) concomitant with elevated carcinoembryonic antigen (CEA), and carbohydrate antigen (CA) 19-9. He underwent right hemicolectomy for colon cancer 12 years prior. Enhanced computed tomography (CT) showed dilated bile ducts with periductal enhancement in S5; hence, cholangiocarcinoma was suspected. Upon anterior segmentectomy, we observed that the cut surface of the specimen exhibited a yellowish-white tumor within the bile ducts. Histologically, the tumor formed within the papillary process, extended along the lumen, and replaced the normal bile duct epithelium. Immunohistochemical studies showed that the liver tumor and primary colon cancer were negative for cytokeratin (CK) 7 and positive for CK20 and Caudal-type homeobox transcription factor 2 (CDX-2). In addition, both tumors showed a same KRAS mutation. We diagnosed the liver tumor as liver metastasis recurrence from colon cancer. CONCLUSION: Intrabiliary growth type of metastasis (IGM) is difficult to distinguish from cholangiocarcinoma, and sometimes develops long after surgery; thus, careful examination of a patient's history is needed in such cases.

Evaluation of hepatocellular carcinoma spread via the portal system by 3-dimensional mapping.

BACKGROUND/PURPOSE: The pattern of tumor cell spread via the portal system has not been fully clarified in patients with hepatocellular carcinoma (HCC). This study aimed to evaluate the intrahepatic distribution of cancer cells derived from the main tumor by assessing histological portal invasion and/or intrahepatic metastasis (vp/im). METHODS: In 14 patients who underwent anatomical resection of primary solitary HCC ≤ 50 mm in diameter, vp/im were examined pathologically, and the sites of the lesions were reproduced on preoperative 3D-CT images. The number of vp/im and the distance of each lesion from the tumor margin were also determined. RESULTS: The tumor diameter was <30 mm in seven patients (smaller HCCs) and 30-50 mm in seven patients (larger HCCs). 3D mapping revealed that almost all vp/im were localized to the peritumoral area within one cm of the tumor margin in smaller HCCs, whereas vp/im seemed to spread extensively to the feeding 3rd level portal branches in larger HCCs. The number of vp/im was greater in patients with larger HCCs than in those with smaller HCCs. CONCLUSIONS: 3D mapping suggested tumor cells of HCC spread via the portal vein extensively in several cases.

Evaluation of Surgical Procedures for T2 Gallbladder Cancer in Terms of Recurrence and Prognosis.

T2 (tumor invades perimuscular connective tissue; no extension beyond serosa or into liver) gallbladder cancer has generally been treated by S4aS5 subsegmentectomy (S4aS5 HR). We investigated the therapeutic effect of full-thickness cholecystectomy (FC) and gallbladder bed resection (GBR), in terms of tumor location and resection margin (distance from the tumor). At our department we employ the following protocol to determine the extent of resection needed to achieve R0 status: (1) A tumor located in the gallbladder fundus (Gf) or body (Gb) and only on the free peritoneal side was classified as P-type, for which full-thickness cholecystectomy and regional lymph node dissection were performed. (2) A tumor located in Gf or Gb and in contact with the liver bed was classified as H-type, for which gallbladder bed resection and regional lymph node dissection were performed. (3) A tumor located in the gallbladder neck (Gn) was classified as N-type, for which gallbladder bed resection, bile duct resection, and regional lymph node dissection were performed. Twenty-two patients admitted to our department between January 2000 and December 2014 with pT2gallbladder cancers were included in our study. Surgical procedures performed were compared with those specified in our protocol, and patients in whom the extent of resection was greater than that specified in our strategy were evaluated clinicopathologically and in terms of recurrence and the prognosis. Six (27.2%), 7 (31.8%), and 9 (40.9%) patients underwent limited, standard, and extended surgery, respectively. Ten (66.7%) of 15 patients with tumors close to the liver bed underwent cholecystectomy or extended surgery, 7 (85.7%) of 8 patients with tumors close to the bile duct underwent bile duct resection, and 16 (72.7%) of 22 patients underwent regional lymph node dissection. Recurrence at the bile duct resection margin, para-aortic lymph node metastasis, and hepatic metastasis occurred in 2, 1, and 3 patients, respectively. The 3-year survival rates (for patients including those dying of noncancer causes) were 50, 100, and 75% after limited, standard, and extended surgery, respectively. There was a significant difference in the survival rate of patients who underwent standard or extended surgery (P=0.0273). Favorable results were obtained in T2 gallbladder cancer patients without performing S4aS5 subsegmentectomy. Depending on the tumor location, neither full-thickness cholecystectomy nor gallbladder bed resection appeared to pose problems regarding recurrence or prognosis. In conclusion, surgical treatment based on our protocol, which aims to achieve the condition of R0, may result in a sufficient therapeutic effect.

Clinicopathological features of neoplasms with neuroendocrine differentiation occurring in the liver.

BACKGROUND/AIMS: We investigated the clinicopathological features of hepatic neuroendocrine tumours (NET) and neuroendocrine carcinoma (NEC), which remain largely unknown. MATERIAL AND METHODS: We examined 1235 tumours from 1048 patients who had undergone curative hepatectomy for liver neoplasms at Kurume University Hospital. Pathological diagnoses were based on the 2010 WHO Classification of Tumours of the Digestive System. We performed immunostaining for hepatocyte markers (eg, hepatocyte paraffin (HepPar)-1), neuroendocrine markers (eg, chromogranin A (CGA)) and the proliferation marker (Ki-67). RESULTS: There were four cases of NET G2 (0.38%) and five of hepatic malignant tumours with an NEC component (HNEC) (0.48%). HNEC cases were classified into three types, that is, transitional, intermediate and separate types, according to their histological and immunohistochemical features. In the former two types, the NEC component intermingled with the moderately to poorly differentiated hepatocellular carcinoma (HCC) component or intermediate component consisting of tumour cells showing the colocalisation of CGA and HepPar-1. In the separate type, the NEC and poorly differentiated HCC components were present separately, whereas the sarcomatous HCC component was detected in the vicinity of the NEC component. Ki-67 labelling indices of the NET G2, HCC and NEC components of HNEC were 6.8%, 14.9% and 58.9%, respectively. CONCLUSIONS: Primary hepatic NET and NEC are very rare tumours. The NEC component in HNEC showed high proliferative activity and influenced patient prognoses.