Bile Duct Infiltration Research Articles

Combined Resection of Liver and Hilar Bifurcation for Colorectal Liver Metastasis: A Single-Center Experience and Review of the Literature

Introduction: Colorectal liver metastases (CRLM) infiltrating the hilar bifurcation is rarely described. We investigated the outcome of partial hepatectomy combined with resection of the hilar bifurcation. Methods: Data collection for patients who underwent resection for CRLM at our institution was performed prospectively from January 2008 to August 2021. Follow-up ended in August 2023. Patients with and without bile duct infiltration of CRLM were analyzed retrospectively. The primary endpoints were overall (OS) and recurrence-free survival (RFS). Results: A total of 1,156 liver resections were screened. Out of those, 18 were combined resections of the liver and the hilar bifurcation. Bile duct infiltration of CRLM was histologically proven in 5 of 18 cases. Preoperative mild obstructive jaundice occurred in 6 of 18 patients and was treated by drainage. Out of those, only 2 had a confirmed infiltration of the hilar bifurcation by CRLM. The median recurrence-free survival (RFS) was 10 months in those patients with bile duct infiltration compared to 9 months in those with no infiltration (p = 0.503). Conclusion: While CRLM is common, infiltration into the central biliary tract is rare. Tumor invasion of the biliary tree can cause jaundice, but jaundice does not necessarily mean tumor invasion. We have shown that combined resection of the liver and hilar bifurcation for CRLM is safe and infiltration of the bile duct by CRLM did not seem to have a significant effect on RFS or OS.

Histopathological Spectrum of Liver Allograft Biopsies and Association with Clinical and Pathological Parameters in Transplant Patients: A Cross-sectional Study

Introduction: Transplantation is vital for acute and terminal irreversible liver conditions. While imaging and functional measurements are valuable for evaluating post-transplant hepatocellular or biliary issues, liver allograft biopsies are used to determine the underlying causes of these changes. Long-term Immunosuppression (IMS), complex clinical circumstances, and de novo complications present challenges in transplant pathology, necessitating a multidisciplinary approach. Aim: To conduct a histopathological assessment of allograft liver biopsies for differential diagnosis, timing (postoperative day), and prevalence of post-transplantation complications, including identifying the causes of graft damage. Materials and Methods: This retrospective cross-sectional study was conducted between January 2019 and June 2022 at Vayalil Parambath Shamsheer (VPS) Lakeshore Hospital, Kochi, Kerala, India. A total of 45 post-transplant needle biopsy samples were analysed, examining histological characteristics and clinical data extracted from hospital records. Over 3.5 years, 45 post-liver transplant biopsies were performed. All clinical records and biopsy findings were examined using staining, and immunohistochemical analysis was performed. The Banff Working Group’s criteria were used to grade rejection based on a semiquantitative index, the Rejection Activity Index (RAI), into indeterminate (Score 1, 2); mild (Score 3, 4); moderate (Score 5, 6); and severe (>6). The classic histologic findings are characterised by predominant portal-based lesions, including a classical triad of mixed inflammatory cell infiltrates, venous endothelial inflammation, and inflammatory infiltration of bile ducts. Results: Among 38 patients, a total of 45 needle biopsies were performed. The first specimen was collected within a few hours of transplantation, and the final specimen was collected after 770 days. Notably, T-Cell-Mediated Rejection (TCMR) was diagnosed in 9 out of 45 (20.00%) specimens. Other complications included Intrahepatic Cholestasis (IHC) in 11 out of 45 (24.44%) cases, biliary obstruction in 5 out of 45 (11.11%) patients, Herpes Simplex Virus (HSV) hepatitis in 3 out of 45 (6.67%) specimens, Plasma Cell-Rich Rejection (PCRR) in 2 out of 45 (4.44%), and Isolated Central Perivenulitis (ICP), Dengue Haemorrhagic Fever (DHF), and veno-occlusive-like disease in 2 out of 45 (4.44% each) specimens. One patient had ethanolinduced liver injury (1 out of 45, 2.22%). Conclusion: Post-transplant liver biopsies are essential for accurate and timely diagnosis of rejection and other complications, guiding therapeutic interventions. This study offers insights into the types, prevalence, and timing of critical complications following liver transplantation (LTx).

Preoperative skeletal muscle fat infiltration is a strong predictor of poorer survival in gallbladder cancer underwent surgery

Recently, a decrease in skeletal muscle, termed sarcopenia, has been reported to be associated with poorer survival of patients in several types of cancer. However, few studies have investigated the association between sarcopenia and the survival of patients with gallbladder cancer. A total of 88 patients undergoing curative resection for advanced gallbladder cancer were included in this study. The quality of skeletal muscle was assessed by the intramuscular adipose tissue content (IMAC), and the quantity of skeletal muscle was assessed by the psoas muscle index (PMI), measured on preoperative computed tomography. The optimum cutoff values for IMAC and PMI for predicting the overall survival in each sex were determined using a minimum p value approach. Clinicopathological factors, IMAC and PMI were retrospectively analyzed to identify the predictors of overall survival (OS). The cutoff values for IMAC were-0.3 in males and 0.04 in females. The numbers of patients with low IMAC and high IMAC were 42 and 46, respectively. The cutoff values for PMI were 7.3cm2/m2 in males and 5.0cm2/m2 in females. The numbers of patients with low PMI and high PMI were 22 and 66, respectively. A multivariate analysis revealed that pT stage (pT3/4, hazard ratio [HR]=6.72, p=0.004), high IMAC (HR=4.12, p<0.001), Bile duct infiltration (present, HR=2.82, p=0.046), high age (≥72 years old, HR=2.64, p=0.010), major hepatectomy (performed, HR=2.50, p=0.031) and pN1/2 (HR=2.17, p=0.010) as independent prognostic factors. IMAC was independent prognostic factor for resected advanced gallbladder cancer, so the quality of skeletal muscle more strongly predicted survival than the quantity of skeletal muscle.

Intrabiliary metastases in colorectal cancer. A systematic review

Background: Liver metastases emerge in 25-50% patients during colorectal cancer (CRC) and iIntrabiliary growth is present in a small proportion of these patients. Intrabiliary metastases (IBM) include microscopic/macroscopic bile duct invasion with hepatic lesions, intrabiliary lesion without hepatic mass and extrahepatic bile duct lesions. Literature is scarce about IBM, its radiological diagnosis, the most suitable treatment and its prognosis. Material & Methods: A systematic search according PRISMA guidelines without limits was performed. The selected studies included patients with a diagnosis of CRC and associated IBM, either synchronous or metachronous mestastases. Results: Forty studies were selected: 30 case report and 10 case series. The epidemiological data were mostly men in the sixth decade of life. The median time between diagnosis of the primary tumor and hepatic metastases was 46.7 months (range: 0-180). Most CRC metastases are CK7- / CK20 + (Figure 1 shows histological images). Treatment ranged from endoscopic resection to mayor hepatic resections combined with pancreatectomies. When curative surgery was no possible, palliative treatments included biliary prosthesis or no treatment. The survival data are confusing. About prognosis, patients with macroscopic IBM show better survival (5 years: 80%) than microscopic IBM (48%) or without bile duct infiltration (57%). Conclusion: IBM should be considered in all patients with a history of CRC presenting dilatation of the bile duct. It is necessary to standardize the definition of this pathology, since the existing terminology may cause confusion and make it difficult to carry out case studies and case series. Surgery is the only curative treatment, but more studies are needed to determine the most appropriate type of liver resection. Anatomic surgery is defended to obtain free margins of the bile duct, while a more economic surgery increases risk of recurrence.

Intraoperative ultrasound predictors of microinvasion of small hepatocarcinoma (

Background: Small hepatocellular carcinoma (HCC) seems to be curable by surgery or ablation. The presence of microinvasion (MI) such as portal venous, hepatic vein, bile duct infiltration, and/or intrahepatic metastasis is the best indicator of a poor prognosis (1). Previous study showed that intraoperative ultrasound (IOUS) definition of MI-HCC had a high agreement with histological findings (2). Prognoses of patients with MI-HCC were compared according to different treatments: anatomic resection (AR), non-anatomic resection NAR) and laparoscopic thermoablation (LAT). Material & Methods: A total of 174 consecutive patients with single, small HCC with a MI pattern at IOUS examination were evaluated. Among these, we compared the outcomes of the AR group (n = 58), the NAR group (n = 20) and the LAT group (n = 96) performing an analysis of the recurrence patterns during a median follow-up of 35.2 months (range: 2-163). Results: HCC recurrence was recorded in 39 patients (68 %) of the AR group, 15 patients (75 %) of the NAR group and 68 patients (71%) of the LAT group, with no significant differences (p=0.853). The incidences of number of recurrences (solitary/multiple) were similar between the three groups. In addition, the rates of local recurrences in the resection groups was very low (AR: 3.5%; NAR: 5%) in comparison to LAT group (21%; p=0.005). The disease-free survival curves of surgical resection groups are significantly better than that of the LAT group (p=0.0125). Conclusions: Patients with MI-HCC, if it is technically possible, should not be treated by LAT but instead should receive hepatic resection with a wide tumor margin to eradicate MI near the main tumor, even in HCC <3 cm. 1) Yamashita Y et al. Ann Surg Oncol 2012; 19: 2027-34 2) Santambrogio R et al. Liver Intern. 2018; 38: 312-20

Assessment of microinvasive patterns of HCC by IOUS: correlation with pathologic resected specimen

Background: The presence of microinvasion (MI) such as portal venous, hepatic vein, bile duct infiltration or intrahepatic metastasis, is the best indicator of a poor prognosis after hepatic resection (HR) and transplantation (OLT). However, preoperative MI patterns are difficult to detect with the current imaging modality. The primary end-point of the study is to evaluate the ability of Intraoperative ultrasound (IOUS) to depict the same pathological features (PF) of hepatocellular carcinoma (HCC). The secondary end-point is to determine whether IOUS patterns can be used to differentiate histopathologic grade of HCC Methods: Between January 2005 and March 2016, 179 patients were enrolled in this study: the pathologist (blinded to the IOUS findings) was requested to classify the specimen according the same IOUS features and several correlation analyses and multivariate analysis were accomplished Results: IOUS features had a high agreement with the PF in terms of MI pattern, diameter of the tumor and presence of satellites. As regards to hystologic grade, only the microvascular infiltration (p=0.001) and infiltrative HCC aspect (p=0.038) were independent predictors for HCC grading Conclusion: During the liver resection, IOUS examination can identify aggressive patterns and anatomic hepatic resection or partial hepatic resection with a wide tumor margin should be accomplished to eradicate MI HCC. Furthermore, IOUS parameters could estimate the post-OLT risk of tumor recurrence, thus improving the patient selection process

Adjuvant chemotherapy did not improve gallbladder cancer prognosis.

Background: Surgery is standard of gallbladder cancer (GBC) care. Chemotherapy (chemo) is indicated only in locally advanced and metastatic disease. Aim : Ameliorate 03 years disease free survival (DFS) of GBC after R0 surgery and adjuvant chemo. Methods: It’s a prospective randomised study. From January 2010 to March 2013, 83 patients were curativelly resected for GBC. 80 patients were included, 41 patients in surgery groupe and 39 patients surgery and adjuvant chemo. Surgical resection was cholecystectomy bisegmentectomy IVb-V and lymphadenectomy. Chemo regimen consisted in gemcitabin (1250 mg/m2 d1/d8) and cisplatin (70 mg/m2 d1) all 21 d (06 cycles). Results: There were 64 women and 16 males (sex ratio : 0,25), median age was 57. median follow up is 53 months (m). median recurrence delay is 25,8 m. Surgery was R0 in all patients, median lymph nodes number is 12.5. Post operative mortality is 3,61% (03 patients), the morbidity is 40% (32 patients) ; 10.2% major complications (Clavien III- IV). Chemo toxicity concerned 57% in adjuvant chemo group (39 patients). DFS at 3 and 5 y is 67,7% et 63,8 % respectivelly. DFS at 03 and 05 y in chemo is 58,6% and 52,9% versus 73,2% and 67,5% in surgery alone group respectivelly (p=0,125). Multivariate analysis ; age up to 65y, BMI up to 25, number of positive lymph nodes and main bile duct infiltration were recurrence predictive factors. Conclusion: Adjuvant chemo did not improve GBC prognosis. R0 resection is the standard of care and should be reserved for experienced teams.

Cholangiocellular cancer: the state of the problem and ways to improve the results of surgical treatment

To improve the outcomes in patients with resectable biliary cancer. There were 263 procedures for cholangiocellular carcinoma (CCC) for the period 1998—2017. Adjuvant chemotherapy was performed in 102 (38.8%) patients. Extensiveliver resections (78.9%) prevailed for intrahepatic cholangiocellular carcinoma (n=128), 6 (4.7%) patients required vascular resection. Seventy-seven pancreatoduodenectomies were performed for common bile duct cancer, portal vein resection was done in 8 (10.4%) patients. In case of Klatskin tumor (n=58) liver resection combined with bile duct resection (n=52) prevailed. Portal vein resection was done in 16 (27.6%) patients. Postoperative morbidity in patients with intrahepatic CCC was revealed in 68 (53.1%) cases, mortality — in 5 (3.9%) cases. Among patients with Klatskin tumor morbidity was revealed in 51 (87.9%) cases, mortality — in 6 (10.3%) cases. In patients with common bile duct cancer morbidity was revealed in 53 (68.8%) cases, mortality — in 4 (5.2%) cases. In whole cohort median overall survival was 30 months. R0-resection was associated with better long-term results (median 37 months) compared with R1—R2 resection (20 months; p=0.01). Lymph node involvement is associated with significantly worse prognosis (p=0.016), however 5-year survival is observed (25.6%). Adjuvant chemotherapy in R0-resection significantly improved long-term results: median was 46 months (vs. 30 in group without chemotherapy; p=0.02). In intrahepatic CCC patients multiple lesions or mechanical jaundice did not aggravate long-term results. R0-resection including lymphadenectomy, resection of adjacent organs and vessels is advisable for CCC. Isolated bile duct resection should be used as an exception. Adjuvant therapy improved long-term results. Multiple lymph node lesion or bile duct infiltration are not contraindications to surgery in intrahepatic CCC patients.

Pancreaticoduodenectomy with portal vein/superior mesenteric vein resection for patients with pancreatic cancer with venous invasion

With the development of new surgical techniques, pancreaticoduodenectomy (PD) with portal vein or superior mesenteric vein (PV/SMV) resection has been used in the treatment of patients with borderline resectable pancreatic cancer. However, opinions of surgeons differ in the effectiveness of this surgical technique. This study aimed to investigate the effectiveness of this approach in patients with pancreatic cancer. Follow-up visits and retrospective analysis were carried out of 208 patients with pancreatic cancer who had undergone PD (PD group) and PD combined with PV/SMV resection and reconstruction (PDVR group) from June 2009 to May 2013 at our center. Statistical analysis was performed to compare the clinical features, the difference of survival time and risk factors of venous invasion in pancreatic cancer. Factors relating to postoperative survival time of pancreatic cancer were also investigated. In the PDVR group, which consisted of 42 cases, the 1-, 2- and 3-year survival rates were 70%, 41% and 16%, respectively and the median survival time was 20.0 months. Among the 166 patients in the PD group, the 1-, 2- and 3-year survival rates were 80%, 52%, and 12%, respectively with the median survival time of 26.0 months. No significant difference in survival time and R0 resection ratio was found between the two groups. Lumbodorsal pain, tumor with pancreatic capsular invasion and bile duct infiltration were found to be independent risk factors for PV invasion in pancreatic cancer. In addition, non R0 resection, large tumor size (>2 cm) and poorly differentiated tumor were independent risk factors for survival time in post-PD. The tumor has a higher chance of venous invasion if preoperative imagings indicate that it juxtaposes with the vessel. Lumbodorsal pain is the chief complaint. Patients with pancreatic cancer associated with PV involvement should receive PDVR for R0 resection when preoperational assessment shows the chance for eradication.

Predictors for Microinvasion of Small Hepatocellular Carcinoma ≤2 cm

Hepatocellular carcinoma (HCC) ≤ 2 cm in diameter is considered to have a low potential for malignancy. A retrospective review was undertaken of 149 patients with primary solitary HCC ≤ 2 cm who underwent initial hepatic resection between 1994 and 2010. The independent predictors of the microinvasion (MI) such as portal venous, hepatic vein, or bile duct infiltration and/or intrahepatic metastasis were identified by multivariate analysis. Prognosis of patients with HCC ≤ 2 cm accompanied by MI was compared to that of patients with HCC ≤ 2 cm without MI. Forty-three patients with HCC ≤ 2 cm had MI in patients (28.9%). Three independent predictors of the MI were revealed: invasive gross type (simple nodular type with extranodular growth or confluent multinodular type), des-γ-carboxy prothrombin (DCP) >100 mAU/ml, and poorly differentiated. Disease-free survival rates of patients with HCC ≤ 2 cm with MI (3 year 44%) were significantly worse than those for HCC ≤ 2 cm without MI (3 year 72%). This disadvantage of disease-free survival rate of patients with HCC ≤ 2 cm with MI could be dissolved by hepatic resection with a wide tumor margin of ≥ 5 mm (P = 0.04). Even in cases of HCC ≤ 2 cm, patients who are suspected of having invasive gross type tumors in preoperative imaging diagnosis or who have a high DCP level (>100 mAU/ml) are at risk for MI. Therefore, in such patients, hepatic resection with a wide tumor margin should be recommended.

Post Transplantation Lymphoproliferative Disorder (PTLD) Presenting as Biliary Duct Obstruction

After adult liver transplantation (LT), post-transplant lymphoproliferative disorder (PTLD) is an uncommon but serious complication of immunosuppression (IMS) in presence of an acute or latent EBV infection. The clinical pres- entation of this disease is aspecific, and, after LT, it may mimic anastomotic bile duct stricture. We report the cases of 2 adult patients who developed, 3 months and 8 years after OLT, an EBV-associated PTLD with diffuse intrinsic infiltration of bile duct mimicking anastomotic biliary stricture. In the absence of liver or hilar nodes in- volvement, percutaneous biopsies were non contributive and the diagnosis were made by surgical biopsy. After reduction of IMS and Rituximab treatment, both patients are alive without recurrence 5 and 6 years after diagnosis. In conclusion, PTLD is one of the differential diagnosis of biliary tree obstruction after OLT. Diagnosis requires surgical biopsies and treatment consists in IMS reduction and Rituximab.

The standardized surgical approach improves outcome of gallbladder cancer

BackgroundThe objective of this study was to examine the extent of surgical procedures, pathological findings, complications and outcome of patients treated in the last 12 years for gallbladder cancer.MethodsThe impact of a standardized more aggressive approach compared with historical controls of our center with an individual approach was examined. Of 53 patients, 21 underwent resection for cure and 32 for palliation.ResultsOverall hospital mortality was 9% and procedure related mortality was 4%. The standardized approach in UICC stage IIa, IIb and III led to a significantly improved outcome compared to patients with an individual approach (Median survival: 14 vs. 7 months, mean+/-SEM: 26+/-7 vs. 17+/-5 months, p = 0.014). The main differences between the standardized and the individual approach were anatomical vs. atypical liver resection, performance of systematic lymph dissection of the hepaticoduodenal ligament and the resection of the common bile duct.ConclusionAnatomical liver resection, proof for bile duct infiltration and, in case of tumor invasion, radical resection and lymph dissection of the hepaticoduodenal ligament are essential to improve outcome of locally advanced gallbladder cancer.

【表8.3.b.1】深達度 【表8.3.b.2】腫瘍の大きさ 【表8.3.b.3】腫瘍の肉眼的形態 【表8.3.b.4】膵内胆管浸潤 【表8.3.b.5】十二指腸浸潤 【表8.3.b.6】膵前面被膜浸潤 【表8.3.b.7】膵後方組織浸潤 【表8.3.b.8】門脈系静脈浸潤 【表8.3.b.9】動脈浸潤 【表8.3.b.10】神経叢浸潤 【表8.3.b.11】他臓器浸潤 【表8.3.b.12】JPS T因子 【表8.3.b.13】UICC T因子 【図8.3.b.14】JPS T因子ごとにみた内分泌腫瘍の生存率 【図8.3.b.15】UICC T因子ごとにみた内分泌腫瘍の生存率

【表8.3.b.1】深達度 【表8.3.b.2】腫瘍の大きさ 【表8.3.b.3】腫瘍の肉眼的形態 【表8.3.b.4】膵内胆管浸潤 【表8.3.b.5】十二指腸浸潤 【表8.3.b.6】膵前面被膜浸潤 【表8.3.b.7】膵後方組織浸潤 【表8.3.b.8】門脈系静脈浸潤 【表8.3.b.9】動脈浸潤 【表8.3.b.10】神経叢浸潤 【表8.3.b.11】他臓器浸潤 【表8.3.b.12】JPS T因子 【表8.3.b.13】UICC T因子 【図8.3.b.14】JPS T因子ごとにみた内分泌腫瘍の生存率 【図8.3.b.15】UICC T因子ごとにみた内分泌腫瘍の生存率

【表7.3.b.1】深達度 【表7.3.b.2】腫瘍の大きさ 【表7.3.b.3】嚢胞の大きさ 【図7.3.b.4】嚢胞の大きさ分布 【表7.3.b.5】腫瘍の肉眼的形態 【表7.3.b.6】膵内胆管浸潤 【表7.3.b.7】十二指腸浸潤 【表7.3.b.8】膵前面被膜浸潤 【表7.3.b.9】膵後方組織浸潤 【表7.3.b.10】門脈系静脈浸潤 【表7.3.b.11】動脈浸潤 【表7.3.b.12】神経叢浸潤 【表7.3.b.13】他臓器浸潤 【表7.3.b.14】JPS T因子 【表7.3.b.15】UICC T因子 【図7.3.b.16】JPS T因子ごとにみた粘液性嚢胞腫瘍の生存率 【図7.3.b.17】UICC T因子ごとにみた粘液性嚢胞腫瘍の生存率

【表7.3.b.1】深達度 【表7.3.b.2】腫瘍の大きさ 【表7.3.b.3】嚢胞の大きさ 【図7.3.b.4】嚢胞の大きさ分布 【表7.3.b.5】腫瘍の肉眼的形態 【表7.3.b.6】膵内胆管浸潤 【表7.3.b.7】十二指腸浸潤 【表7.3.b.8】膵前面被膜浸潤 【表7.3.b.9】膵後方組織浸潤 【表7.3.b.10】門脈系静脈浸潤 【表7.3.b.11】動脈浸潤 【表7.3.b.12】神経叢浸潤 【表7.3.b.13】他臓器浸潤 【表7.3.b.14】JPS T因子 【表7.3.b.15】UICC T因子 【図7.3.b.16】JPS T因子ごとにみた粘液性嚢胞腫瘍の生存率 【図7.3.b.17】UICC T因子ごとにみた粘液性嚢胞腫瘍の生存率

【表3.3.b.1】深達度 【表3.3.b.2】腫瘍の大きさ 【表3.3.b.3】腫瘍の肉眼的形態 【表3.3.b.4】膵内胆管浸潤 【表3.3.b.5】十二指腸浸潤 【表3.3.b.6】門脈系静脈浸潤 【表3.3.b.7】門脈系静脈浸潤部位（重複あり） 【表3.3.b.8】動脈浸潤 【表3.3.b.9】動脈浸潤部位（重複あり） 【表3.3.b.10】神経叢浸潤 【表3.3.b.11】神経叢浸潤部位（重複あり） 【表3.3.b.12】他臓器浸潤 【表3.3.b.13】他臓器浸潤部位（重複あり）

【表3.3.b.1】深達度 【表3.3.b.2】腫瘍の大きさ 【表3.3.b.3】腫瘍の肉眼的形態 【表3.3.b.4】膵内胆管浸潤 【表3.3.b.5】十二指腸浸潤 【表3.3.b.6】門脈系静脈浸潤 【表3.3.b.7】門脈系静脈浸潤部位（重複あり） 【表3.3.b.8】動脈浸潤 【表3.3.b.9】動脈浸潤部位（重複あり） 【表3.3.b.10】神経叢浸潤 【表3.3.b.11】神経叢浸潤部位（重複あり） 【表3.3.b.12】他臓器浸潤 【表3.3.b.13】他臓器浸潤部位（重複あり）

【表6.3.b.1】深達度 【表6.3.b.2】腫瘍の大きさ 【表6.3.b.3】嚢胞の大きさ 【図6.3.b.4】嚢胞の大きさ分布 【表6.3.b.5】腫瘍の肉眼的形態 【表6.3.b.6】膵内胆管浸潤 【表6.3.b.7】十二指腸浸潤 【表6.3.b.8】膵前面被膜浸潤 【表6.3.b.9】膵後方組織浸潤 【表6.3.b.10】門脈系静脈浸潤 【表6.3.b.11】動脈浸潤 【表6.3.b.12】神経叢浸潤 【表6.3.b.13】他臓器浸潤 【表6.3.b.14】JPS T因子 【表6.3.b.15】UICC T因子 【図6.3.b.16】JPS T因子ごとにみた膵管内腫瘍の生存率 【図6.3.b.17】UICC T因子ごとにみた膵管内腫瘍の生存率

【表6.3.b.1】深達度 【表6.3.b.2】腫瘍の大きさ 【表6.3.b.3】嚢胞の大きさ 【図6.3.b.4】嚢胞の大きさ分布 【表6.3.b.5】腫瘍の肉眼的形態 【表6.3.b.6】膵内胆管浸潤 【表6.3.b.7】十二指腸浸潤 【表6.3.b.8】膵前面被膜浸潤 【表6.3.b.9】膵後方組織浸潤 【表6.3.b.10】門脈系静脈浸潤 【表6.3.b.11】動脈浸潤 【表6.3.b.12】神経叢浸潤 【表6.3.b.13】他臓器浸潤 【表6.3.b.14】JPS T因子 【表6.3.b.15】UICC T因子 【図6.3.b.16】JPS T因子ごとにみた膵管内腫瘍の生存率 【図6.3.b.17】UICC T因子ごとにみた膵管内腫瘍の生存率

【表4.2.c.1】腫瘍占拠部位の比較 【表4.2.c.2】腫瘍の大きさの比較 【表4.2.c.3】膵内胆管浸潤の比較 【表4.2.c.4】十二指腸浸潤の比較 【表4.2.c.5】膵前方被膜浸潤の比較 【表4.2.c.6】膵後方組織浸潤の比較 【表4.2.c.7】門脈系静脈浸潤の比較 【表4.2.c.8】動脈浸潤の比較 【表4.2.c.9】神経叢浸潤の比較 【表4.2.c.10】他臓器浸潤の比較

【表4.2.c.1】腫瘍占拠部位の比較 【表4.2.c.2】腫瘍の大きさの比較 【表4.2.c.3】膵内胆管浸潤の比較 【表4.2.c.4】十二指腸浸潤の比較 【表4.2.c.5】膵前方被膜浸潤の比較 【表4.2.c.6】膵後方組織浸潤の比較 【表4.2.c.7】門脈系静脈浸潤の比較 【表4.2.c.8】動脈浸潤の比較 【表4.2.c.9】神経叢浸潤の比較 【表4.2.c.10】他臓器浸潤の比較

Hepatitic pattern of graft versus host disease in children

Liver involvement by graft-versus-host disease (GVHD) is characterized histologically by bile duct damage, which may be severe. A different pattern, "hepatitic GVHD," has been described in adult patients. This pattern also shows marked lobular hepatitis and hepatocellular damage. We report the development of hepatitic GVHD in six pediatric patients. Clinical information and histologic features of liver biopsy samples were retrospectively reviewed. Patients' ages ranged from 3 to 11 years. Underlying diagnosis, pre-transplant conditioning and GVHD prophylaxis varied. Peripheral blood stem cells were the source of the allograft in four patients, matched sibling in one, and matched-unrelated donor in one. Hepatic GVHD was detected between 149 and 310 days post-transplant. Prior acute GVHD had developed in two patients, and involved the skin and/or gastrointestinal tract. No patients had significant ductopenia. Only one patient had significant lymphocytic infiltration of bile ducts (ductitis). Bile duct epithelial damage and significant portal/periportal inflammation were present in all patients. Lobular necro-inflammation was present in five patients. Five patients improved with immunosuppression and one died with progressive GVHD. This series focuses on hepatitic GVHD in pediatric patients. Clinical and histologic patterns are similar to what has been described in adults. Specific etiology and pathogenesis of this entity remain unclear.

Immune response and liver transplantation

In an article published in the January 2005 issue of Liver Transplantation, Warlé et al. provided an intriguing report on possible correlation between cytokine gene polymorphism and liver graft rejection.1 In brief, the authors suggest that interleukin IL-10 -1082 polymorphism could play a critical role in determining the human liver graft rejection. Two principal evaluations emerge from this study: first, the role of a preferential immune response related to liver transplant, and second, a possible involvement of immunoregulatory T cells such as CD4+CD25+ T lymphocytes. A first key question is if a preferential cytokine network may play an absolute role in causing a liver graft rejection. In our previous paper, we have shown that a proinflammatory cytokine profile was related to liver acute rejection.2 Our study comprised a group of 14 patients with different causes of liver disease treated with the same immunosuppressive regimen of therapy and with the diagnosis of acute cellular rejection based on the presence of at least 2 of the following features: bile duct infiltration and damage, or venous endothelitis of the portal tracts; hepatic artery or portal vein occlusion was excluded by Doppler echography. In our patients we found a statistically significant increase (P < 0.001) of IL-2 level in the liver with respect to peripheral blood. The determination was performed by enzyme linked immunosorbent assay test in day-3 culture supernatants collected by biopsy, processed into small clumps and simple suspensions, and incubated with anti-CD3. Our study showed that differences in the rate of acute rejection may be related to different factors such as different regimens and maintenance of therapy, type of initial cause of liver disease, and type of individual immune response. The individual immune response can be regulated by a specific activity of Treg cells. Recent evidence has implicated regulatory T cells in transplantation tolerance and rejection.3 Treg cells can suppress the immune system by several mechanisms.4 In particular, IL-10 and transforming growth factor β1 (TGF-β1) have been shown to be important mediators of Treg-mediated suppression.5 IL-10 was originally described as a Th2 cytokine cell, yet IL-10 may also have the important role of feedback regulator to control the pathology associated with an overexuberant Th1 response. The source of IL-10 during acute rejection may be Th1, Th2, or regulatory T cells, on the basis of an individual background and pathogen. It is possible that the mechanisms of action of such T lymphocytes may be associated with different pathways related to differences in systemic vs. local inflammation. The molecular mechanism involved in regulation may depend on the level of inflammation accompanying an immune response.6 Finally, we think that the risk factor for acute rejection may not be related, in a stereotyped way, to a specific cytokine profile but, conversely, to individual Treg cells activated during liver transplant. Such cells can influence unrelated aspects of immune homeostasis. Oreste Perrella*, Costanza Sbreglia*, Alessandro Perrella*, Oreste Cuomo , Marco Perrella , * Department of Infectious Diseases and Immunology, Hospital D. Cotugno, Naples, Italy, Liver Unit and Department of Surgery, Hospital A. Cardarelli, Naples, Italy, Institute of Respiratory diseases, Federico II University, Naples, Italy.

Hepatoduodenal ligament invasion by gallbladder carcinoma: histologic patterns and surgical recommendation.

A consensus for the optimal management of hepatoduodenal ligament (HDL) invasion by gallbladder carcinoma has yet to be reached. We retrospectively correlated the patterns of HDL invasion with the surgical outcome. From 1985 to 2000, 59 patients underwent combined resection of the extrahepatic bile duct and gallbladder and contiguous organs if required. Pathologic staging (UICC) was stage II, 4; stage III, 14; stage IVa, 10; and stage IVb, 31. Hepatoduodenal ligament invasion was subdivided into lymph node involvement (LNI) and bile duct infiltration (BDI). Patterns of HDL invasion were compared with bile duct morphology, resectability, and outcome. Bile duct infiltration ( n = 32) caused stenosis of the bile duct in all cases, whereas LNI ( n = 40) caused stenosis in only 4 cases. Resection was complete after extended cholecystectomy ( n = 22) in 36%; 4b/5 segmentectomy ( n = 10) in 90%; major hepatectomy ( n = 2) in 50%; and hepatopancreatoduodenectomy ( n = 17) in 53% of cases. Surgery was curative in 75% of patients without BDI, and was < 30% with BDI. The most common factor preventing curative resection in BDI was perineural invasion around the HDL. Perineural invasion occurred in over 70% of cases at either the cut end of the bile duct or in the margin of dissection. The 3-year survival rates, excluding patients with R2 resection (residual cancer) and death in hospital, were LNI(-)BDI(-) ( n = 8), 65.6%; LNI(+)BDI(-) ( n = 17), 35.3%; LNI(-)BDI(+) ( n = 7), 14.3%; and LNI(+)BDI(+) ( n = 17), 5.9%. There were no 5-year survivors with BDI. In conclusion, perineural invasion in BDI is an important obstacle to complete resection. Hepatopancreatoduodenectomy is a feasible strategy only for LNI(+)BDI(-) disease.