Pancreaticoduodenectomy: impact of the technique on operative outcomes and surgical mortality / Duodenopancreatectomia: impacto da técnica nos resultados operatórios e mortalidade cirúrgica

ABSTRACT Background: Pancreaticoduodenectomy (PD) is a procedure associated with significant morbidity and mortality. Initially described as gastropancreaticoduodenectomy (GPD), the possibility of preservation of the gastric antrum and pylorus was described in the 1970s. Aim: To evaluate the mortality and operative variables of PD with or without pyloric preservation and to correlate them with the adopted technique and surgical indication. Method: Retrospective cohort on data analysis of medical records of individuals who underwent PD from 2012 through 2017. Demographic, anthropometric and operative variables were analyzed and correlated with the adopted technique (GPD vs. PD) and the surgical indication. Results: Of the 87 individuals evaluated, 38 (43.7%) underwent GPD and 49 (53.3%) were submitted to PD. The frequency of GPD (62.5%) was significantly higher among patients with pancreatic neoplasia (p=0.04). The hospital stay was significantly shorter among the individuals submitted to resection due to neoplasias of less aggressive behavior (p=0.04). Surgical mortality was 10.3%, with no difference between GPD and PD. Mortality was significantly higher among individuals undergoing resection for chronic pancreatitis (p=0.001). Conclusion: There were no differences in mortality, surgical time, bleeding or hospitalization time between GPD and PD. Pancreas head neoplasm was associated with a higher indication of GPD. Resection of less aggressive neoplasms was associated with lower morbidity and mortality.

RESUMO Racional : A duodenopancreatectomia (DP) é procedimento associado com significativa morbimortalidade. Inicialmente descrita como gastroduodenopancreatectomia (GDP), a possibilidade de preservação do antro gástrico e piloro foi descrita na década de 1970. Objetivo : Avaliar a mortalidade e variáveis operatórias da DP com ou sem preservação pilórica e correlacioná-las com a técnica adotada e indicação cirúrgica. Método: Estudo de coorte histórica, baseado em análise de dados de registros médicos de indivíduos submetidos à DP entre os anos de 2012 a 2017. Foram analisadas variáveis demográficas, antropométricas e operatórias e correlacionadas com a técnica adotada (GDP vs. DP) e a indicação cirúrgica. Resultados : Dos 87 indivíduos avaliados, 38 (43,7%) foram submetidos à GDP e 49 (53,3%) à DP. A frequência de realização da GDP (62,5%) foi significativamente maior entre os pacientes com neoplasia de pâncreas (p=0,04). O tempo de internação total foi significativamente menor entre os indivíduos submetidos à ressecção por neoplasias de comportamento menos agressivo (p=0,04). A mortalidade cirúrgica foi de 10,3%, não havendo diferença entre GDP e DP. A mortalidade foi significativamente maior entre os indivíduos submetidos à ressecção por pancreatite crônica (p=0,001). Conclusão : Não houve diferenças na morbimortalidade, tempo cirúrgico, sangramento ou tempo de internação entre GDP e DP. A neoplasia de cabeça de pâncreas associou-se mais com indicação de GDP. A ressecção de neoplasias menos agressivas associou-se a menor morbimortalidade.

Expression of epidermal growth factor receptor (EGFR) in cholangiocarcinomas: predictive factors and survival / Expressão do receptor do fator de crescimento epitelial (EGFR) em colangiocarcinomas: fatores preditivos e sobrevida

ABSTRACT Objective: to evaluate the expression of the epithelial growth factor receptor (EGFR) by immunohistochemistry, and to verify its association with prognostic factors and survival of patients operated by cholangiocarcinoma. Methods: we verified the immunohistochemical expression of EGFR in 35 surgical specimens of cholangiocarcinoma (CCA). We obtained survival curves with the Kaplan-Meier method. Results: we found significant EGFR expression in ten (28.6%) of the 35 CCAs, eight with score 3 and two with score 2. Advanced stages (III and IV) presented higher EGFR expression (p=0.07). The clinical characteristics that were most associated with positive EGFR expression were female gender (p=0.06) and absence of comorbidities (p=0.06). Overall survival at 12, 24, 36 and 48 months was 100%, 82.5%, 59% and 44.2%, respectively. The survival of EGFR positive patients at 12, 24, 36 and 48 months was 100%, 75%, 50% and 0%, whereas for negative EGFR patients it was 100%, 87.5%, 65.6% and 65.6%, respectively. Conclusion: EGFR expression occurred in 28.6% of the cases studied and was associated with lower survival.

RESUMO Objetivo: avaliar a expressão do receptor do fator de crescimento epitelial (EGFR) por meio de imuno-histoquímica, e verificar sua associação com fatores prognósticos e com a sobrevida dos pacientes operados por colangiocarcinoma. Métodos: a expressão imuno-histoquímica de EGFR foi verificada em 35 peças cirúrgicas de colangiocarcinomas (CCA). Curvas de sobrevida foram obtidas pelo método de Kaplan-Meier. Resultados: expressão significativa de EGFR foi encontrada em dez (28,6%) de 35 CCA, oito com escore 3 e dois com escore 2. Estágios avançados (III e IV) apresentaram maior expressão de EGFR (p=0,07). As características clínicas que mais estiveram associadas com a expressão positiva de EGFR foram o sexo feminino (p=0,06) e ausência de comorbidades (p=0,06). A sobrevida global aos 12, 24, 36 e 48 meses foi de 100%, 82,5%, 59% e 44,2%, respectivamente. A sobrevida de pacientes EGFR positivos aos 12, 24, 36 e 48 meses foi de 100%, 75%, 50% e 0%, enquanto que para EGFR negativos foi de 100%, 87,5%, 65,6% e 65,6%, respectivamente. Conclusão: a expressão do EGFR ocorreu em 28,6% dos casos estudados e esteve associada a menor sobrevida.

Intrahepatic, Perihilar and Distal Cholangiocarcinoma: Management and Outcomes

Abstract: Introduction and aims. Cholangiocarcinomas are a heterogeneous group of tumors that can be classified into three clinically distinct types of cancers, intrahepatic, perihilar and distal cholangiocarcinoma. The inconsistent use of nomenclature for these cancers has obscured a true knowledge of the epidemiology, natural history and response to therapy of these cancers. Our aims were to define demographic characteristics, management and outcomes of these three distinct cancer types. Materials and methods. A retrospective study of patients enrolled in an institutional cancer registry from 1992 to 2010. Median survival was compared between different treatment modalities over three time periods for the three types of cholangiocarcinoma at different stages of the disease using Kaplan Meyer analysis. Results. 242 patients were identified. All cases were reviewed and classified into intrahepatic (90 patients), distal (48 patients) or perihilar (104 patients) cholangiocarcinomas. These cancers differed in median age of onset, gender distribution, median survival and stage. 13.8% of patients presented with stage I, 5.8% with stage II, 9.6% with stage III, 28% with stage IV, with 41.8% having unknown stage. The overall median survival was 15.8 months, and was 23, 25, 14, and 4.5 months for stages I, II, III, and IV respectively. Surgery improved survival in both early and advanced stages. Multimodality therapies further improved outcomes, particularly for perihilar cholangiocarcinoma. Conclusion. Perihilar, distal and intrahepatic cholangiocarcinoma vary in their presentation, natural history and therapeutic approach to management. A consistently applied classification is essential for meaningful interpretation of studies of these cancers.

Resultados del tratamiento quirúrgico del colangiocarcinoma intrahepático / Intrahepatic cholangiocarcinoma: experience in 30 operated patients

background: Intrahepatic cholangiocarcinoma (ICC) corresponds to 10% of liver primary malignant tumors. Aim: To show the results of surgical treatment of ICC in a biliary surgery center. material and methods: Review of a prospective database of operated patients at a surgical service of a clinical hospital. Thirty operated patients with an ICC, aged 25 to 83 years (20 women), were identified. Results: Twenty six patients had symptoms, 12 of 19 had high levels of CA19-9 and in four the tumor was non resectable. Twenty four patients underwent major hepatectomy and two, a minor hepatectomy. Combined resections were performed in three patients. Lymphadenectomy was performed in 14 patients and five had lymph node metastases. Surgical time was 272 minutes, mean intensive care unit stay was 10 days and mean ventilatory support use was five days. Surgical mortality was 19% and complications appeared in 53% of patients. Tumors were stage I, II, III and IV in 11, 5, 3 and 11 patients respectively. Overall survival was 16 months. Survival in tumors stage I and II was 50% at five years. In stages III and IV, it was 11.2 months. Conclusions: Surgery for ICC has an acceptable mortality and complications rate with a five years survival of 25%.

Introducción: El colangiocarcinoma intrahepático (CCIH), corresponde al segundo cáncer primario hepático, representando alrededor del 10% de los cánceres primarios del hígado; el tratamiento es la hepatectomía. Objetivo: Mostrar los resultados del tratamiento quirúrgico de pacientes con CCIH en Chile en un centro de cirugía hepatobiliar. Pacientes y métodos: Análisis prospectivo de los pacientes con CCIH operados en nuestro centro entre 2005 y 2015. Resultados: 30 pacientes, 20 mujeres (67%), 10 hombres (33%). Edad promedio: 60 años (rango 25-83 ), 26 pacientes sintomáticos (87%), CA19-9 elevado en 12 (63,2%), 4 pacientes (13%) irresecables, 24 pacientes (80%) hepatectomías mayores y 2 resecciones menores. Resecciones combinadas en 3, linfadenectomía en 14 pacientes (47%), metástasis linfonodales en 5 (17%). Tiempo promedio quirúrgico 272 min (rango 45-480). UCI, mediana 10 días, ventilación mecánica mediana 5 días. Hospitalización, mediana 10 días y 7 días postoperatorio. Morbilidad 53%, mortalidad 19%. R0 en 19 pacientes (64%), R1 en 7 pacientes (23%) y R2 en 4 pacientes (13%). Estadio I en 11 pacientes, estadio II en 5 pacientes, estadio III en 3 pacientes, estadio IV en 11 pacientes. Sobrevida general de 16 meses. Sobrevida estadio I 58,4 meses, estadio II 31,1 meses, estadio III 5,9 meses y estadio IV 11,8 meses, p = 0,06. Sobrevida R0 16 meses, R1: 31,1 meses y R2: 9,25 meses, p = 0,53. Sobrevida estadios I y II 50% a 5 años, estadios III-IV 11,2 meses, p < 0,01. Discusión: Este es el primer reporte nacional de una serie importante de pacientes con CCIH, con morbilidad y mortalidad aceptables. Sobrevida de 25% a 5 años.

TGF-ß1 expression is associated with invasion and metastasis of intrahepatic cholangiocarcinoma

BACKGROUND: Transforming growth factor (TGF)-ß is involved in many physiologic processes, it often promotes metastasis, and its high expression is correlated with poor prognosis. In the present study, we analyzed the correlation between transforming growth factor beta 1 (TGF-ß1) expression and prognosis in intrahepatic cholangiocarcinoma RESULTS: We examined the expression of TGF-ß1 in 78 intrahepatic cholangiocarcinomas by immunohistochemistry and correlated the expression with clinicopathological parameters. TGF-ß1 was expressed in 37 of 78 (47.4 %) intrahepatic cholangiocarcinomas. The expression of TGF-ß1 was significantly correlated with lymph node metastasis, distant metastasis, and tumour recurrence. Patients with TGF-ß1-positive tumours had significantly shorter survival time. In a multivariant analysis, the expression of TGF-ß1 and the tumour stage were independent prognostic factors CONCLUSIONS: Our data suggest that expression of TGF-ß1 is a novel prognostic marker for intrahepatic cholangiocarcinoma.

Composite liver tumors: A radiologic-pathologic correlation

Bi-phenotypic neoplasm refers to tumors derived from a common cancer stem cell with unique capability to differentiate histologically into two distinct tumor types. Bi-phenotypic hepatocellular carcinoma-cholangiocarcinoma (HCC-CC), although a rare tumor, is important for clinicians to recognize, since treatment options targeting both elements of the tumor are crucial. Imaging findings of bi-phenotypic HCC-CC are not specific and include features of both HCC and CC. A combination of imaging and immuno-histochemical analysis is usually needed to make the diagnosis.

Prognostic significance of snail expression in hilar cholangiocarcinoma

Many patients with hilar cholangiocarcinoma (HC) have a poor prognosis. Snail, a transcription factor and E-cadherin repressor, is a novel prognostic factor in many cancers. The aim of this study was to evaluate the relationship between snail and E-cadherin protein expression and the prognostic significance of snail expression in HC. We examined the protein expression of snail and E-cadherin in HC tissues from 47 patients (22 males and 25 females, mean age 61.2 years) using immunohistochemistry and RT-PCR. Proliferation rate was also evaluated in the same cases by the MIB1 index. High, low and negative snail protein expression was recorded in 18 (38%), 17 (36%), and 12 (26%) cases, respectively, and 40.4% (19/47) cases showed reduced E-cadherin protein expression in HC samples. No significant correlation was found between snail and E-cadherin protein expression levels (P = 0.056). No significant correlation was found between snail protein expression levels and gender, age, tumor grade, vascular or perineural invasion, nodal metastasis and invasion, or proliferative index. Cancer samples with positive snail protein expression were associated with poor survival compared with the negative expresser groups. Kaplan-Meier curves comparing different snail protein expression levels to survival showed highly significant separation (P < 0.0001, log-rank test). With multivariate analysis, only snail protein expression among all parameters was found to influence survival (P = 0.0003). We suggest that snail expression levels can predict poor survival regardless of pathological features and tumor proliferation. Immunohistochemical detection of snail protein expression levels in routine sections may provide the first biological prognostic marker.

Clinicopathological Characteristics in Combined Hepatocellular-Cholangiocarcinoma: A Single Center Study in Korea

PURPOSE: Combined hepatocellular-cholangiocarcinoma (CHCC) is an uncommon form of cancer, and its clinicopathological features have rarely been reported in detail. This study was undertaken to evaluate the clinicopathological characteristics and prognostic factors of CHCC. MATERIALS AND METHODS: The clinicopathological features of patients diagnosed with CHCC at Severance Hospital between January 1996 and December 2007 were retrospectively studied by comparing them with the features of patients with hepatocellular carcinoma (HCC) or cholangiocarcinoma (CC) who had undergone a hepatic resection during the same period. RESULTS: Forty-three patients diagnosed with CHCC were included in this study (M : F=35 : 8, median age, 55 years). According to the parameters of the American Joint Committee on Cancer staging, there were 6 (14.0%), 9 (20.9%), 25 (58.1%), and 3 (7.0%) patients with stages I, II, III, and IV cancer, respectively. Thirty-two of the 43 patients underwent resection with curative intent. After resection, 27 patients (84.4%) had tumor recurrence during the follow-up period of 18 months (range: 6-106 months), and the median time to recurrence was 13 months. Overall median survival periods after hepatic resection of CHCC, HCC and CC were 34, 103 and 38.9 months, respectively (p<0.001). The median overall survival for all patients with CHCC was 21 months, and the 5-year survival rate was 18.1%. The presence of portal vein thrombosis and distant metastasis were independent prognostic factors of poor survival. CONCLUSION: Even after curative hepatic resection, the presence of a cholangiocellular component appeared to be a poor prognostic indicator in patients with primary liver cancer.

Analysis of Prognostic Factors after Curative Resection for Combined Hepatocellular and Cholangiocarcinoma / 대한소화기학회지

BACKGROUND/AIMS: Combined hepatocellular and cholangiocarcinoma (HCC-CC) is a rare form of primary liver carcinoma which contains characteristics of both hepatocellular carcinoma and cholangiocarcinoma. The aim of this study was to evaluate the prognostic factors of combined HCC-CC after curative resection. METHODS: Between January 1987 and December 2005, pathologically confirmed combined HCC-CC patients who underwent curative resection at Seoul National University Hospital were evaluated. We reviewed the medical records and evaluated the time-to-recurrence (TTR), overall survival (OS) and prognostic factors of combined HCC-CC. RESULTS: A total of 31 patients were evaluated (M:F=27:4; median age, 61 years). According to the American Joint Committee on Cancer system, patients with stage I, II, III(A), III(B) and III(C) at the time of resection were 4, 16, 7, 2 and 2, respectively. Twenty six patients (83.9%) had tumor recurrence during the follow-up period and their median TTR was 5.7 months. Twenty one patients received additional treatment while 5 patients did not. As a result, median OS was 21.6 months and 3 year survival rate was 15.4%. In multivariate analysis, stage III than stage I or II at resection was an independent prognostic factor associated with shortened TTR (p<0.01). Older age (p=0.03), stage III(C) rather than stage I, II, III(A) at time of resection (p=0.02), and Child-Pugh B rather than A (p<0.01) were independent prognostic factors associated with shortened OS. CONCLUSIONS: Even after curative resections, patients with combined HCC-CC show poor prognosis with early recurrence and poor survival. However, surgical treatment should be warranted for relatively young patients in early stage with well preserved liver function.

Review: Analysis of Survival Rate and Prognostic Factors of Intrahepatic Cholangiocarcinoma: 318 Cases in Single Institute / 대한간학회지

No abstract available.

Palliative surgical bypass versus percutaneous transhepatic biliary drainage on unresectable hilar cholangiocarcinoma.

OBJECTIVE: To compare the survival probability of unresectable hilar cholangiocarcinoma patients who have been managed by palliative surgical bypass versus percutaneous transhepatic biliary drainage (PTBD). MATERIAL AND METHOD: A historical (retrospective) cohort study was performed by retrospective and prospective data collection. From January 1, 2000 to December 31, 2002, all unresectable hilar cholangiocarcinoma patients who received only one type of palliative surgical bypass or PTBD in Srinagarind Hospital, Khon Kaen University were included in the present study. The patients were followed until December 31, 2004. Survival analysis was completed for all of the patients. STATISTIC ANALYSIS: Survival analysis was analyzed with the Kaplan-Meier method, Cox regression analysis, and Log-rank test. A p-value of less than 0.05 was considered significant. RESULTS: During the study period, 83 patients were included. Palliative surgical bypass was performed in 42 patients and PTBD was performed in 41 patients. Demographic data, peri-operative complication rate, and late complication rate were comparable. The median survival time of the palliative surgical bypass group was 160 days,(95% CI: 85.33, 234.67) and 82 days (95% CI: 29.76, 134.24)for PTBD group. Comparing survival experience by Log-rank test gave statistical significant diference (p = 0.0276). Hazard ratio was 0.599 (p = 0.03) CONCLUSION: Survival rate of the palliative surgical bypass group was higher than the PTBD group. The survival rate of both groups was comparable to previous reports.

Prognostic Factors after Major Resection for Distal Extrahepatic Cholangiocarcinoma / 대한소화기학회지

BACKGROUND/AIMS: Although diagnosis and surgical treatment for distal common bile duct cancer have enormously advanced, survival is not satisfactory and its prognostic factors are still being debated. Thus, we evaluated the outcomes and prognostic factors after major resection for distal extrahepatic cholangiocarcinoma (dCC). METHODS: One hundred and fifty-four patients who underwent major resection such as pancreaticoduodenectomy for dCC were retrospectively analyzed. We investigated clinical features, postoperative complications, survival, and prognostic factors of dCC. CONCLUSIONS: One hundred and three (66.9%) male and 51 (33.1%) female patients were enrolled and their mean age was 59.6 (31-78) years. Among them, 97 patients (63.0%) underwent Whipple's procedure, 45 (29.2%) pylorus-preserving pancreaticoduodenectomy, 7 (4.5%) total pancreatectomy, and 5 (3.3%) hepatopancreaticoduodenectomy, respectively. Mean follow-up duration was 26.6 (0.4-108.5) months. The postoperative morbidity and mortality were 42.2% and 1.3%, respectively. Five-year survival rate was 32.8% and mean survival duration was 47.2 (39.1-55.3) months. Type of biliary drainage (percutaneous transhepatic biliary drainage), lymph node status (positive), and cellular differentiation (moderate or poor) were significant indicators for death in multivariate analysis of resectable dCC. CONCLUSIONS: Moderate or poor cellular differentiation and lymph node metastasis may be independent poor prognostic factors for resectable dCC.

Comparison of Survival of Advanced Hilar Cholangiocarcinoma after Biliary Drainage Alone versus Photodynamic Therapy with External Drainage / 대한소화기학회지

BACKGROUND/AIMS: Photodynamic therapy (PDT) has a promising effect on non-resectable hilar cholangiocarcinoma. The aim of this study was to compare overall survival of PDT plus biliary drainage versus biliary stent alone in advanced hilar cholangiocarcinoma. METHODS: Twenty patients who were treated with endoscopic biliary drainage alone (Group A) and 27 patients treated with PDT under percutaneous cholangioscopy and additional percutaneous biliary drainage (Group B) were analyzed retrospectively. RESULTS: The mean bilirubin level declined effectively in both group after treatment. One-year survival was 28% in group A, 52% in group B (p<0.05). Median survival time was 288 days in group A, 558 days in group B (p=0.0143). CONCLUSIONS: PDT under percutaneous cholangioscopy seems to be more effective in extending survival than biliary drainage alone in advanced hilar tumor. To investigate whether PDT can increase survival rates, further prospective, randomized study is needed.

Endoscopic management of cholangiocarcinoma.

Cholangiocarcinoma constitutes the second most common primary liver cancer after hepatocellular carcinoma. It is particularly prevalent in regions where liver flukes are hyperendemic. Obstructive jaundice is the most common presentation. To evaluate patients suspected for cholangiocarcinoma, endoscopy is becoming more popular. Endoscopy can provide important information especially cholangiogram and tissue diagnosis. Recently, the role of endoscopy has not only been used for diagnosis but also for treatment. In this article, the roles of endoscopy for diagnosis, therapy, and future modality of treatment for cholangiocarcinoma are provided.

Pancreaticoduodenectomy for periampullary carcinoma.

OBJECTIVES: To assess the morbidity, mortality and 1- and 2-year survival rates, and safety of pancreaticoduodenectomy for periampullary (including pancreatic head) carcinomas in a non-oncology surgical set-up. METHODS: Records of 45 patients undergoing pancreaticoduodenectomies for periampullary cancers between July 1996 and April 2000 were reviewed. These included ampullary (n=23), pancreatic (14) and duodenal (2) adenocarcinomas, lower-end cholangiocarcinoma (5), and ampullary carcinoid (1). Thirty-seven patients underwent the Whipple procedure and 8 underwent the pylorus-preserving modification. RESULTS: The overall mortality rate was 11% and morbidity rate was 46%. Wound infection was the most common postoperative complication. The 1- and 2-year survival rates for periampullary cancers were 61% and 39% and those for pancreatic cancers were 57% and 36%, respectively. CONCLUSION: Pancreaticoduodenectomy for periampullary tumors remains a formidable procedure in our set-up. However, it can be performed safely with low mortality and morbidity rates.

Resection of hepatocellular carcinoma: personal experience with 67 patients and long-term results.

Hepatocellular carcinoma (HCC) is the most common cancer in Thailand. Hepatic resection has been accepted as the only chance for cure. However; very limited information about the operative treatment and survival of HCC in Thailand has been documented. The author reviewed the experiences of surgical treatment of HCC at the National Cancer Institute, Bangkok and reports herein the long term outcome. From January 1986 to January 1996 a total of 884 primary liver cancers admitted in our institute were reviewed. 112 consecutive hepatic resections were performed by the author. 67 of 112 patients were HCC of which clinical features, survival rate and recurrence were studied. Liver cirrhosis was associated in 49 patients (73.1%). HBsAg was positive in 58 patients (86.6%). Preoperative AFP level was more than 400 ng/ml in 35 patients. The resectability for HCC was 11.0 per cent. In 50 of 67 hepatic resection, major hepatic resection were carried out. Postoperative major complications were found in 14 patients (20.9%). Postoperative mortality rate of 5 patients was 7.5 per cent. Survival curve was calculated by Kaplan-Meier with the overall survival rate at 1, 2, 3, 4, 5 years was 63.2 per cent, 28.6 per cent, 21.1 per cent, 14.5 per cent and 11.5 per cent respectively. 1, 3, 5 years survival rate for a tumor less than 5 cm was 91.0 per cent, 57.0 per cent, 49.4 per cent, tumor size of 5-10 cm was 57.5 per cent, 16.0 per cent, 9.0 per cent and tumor size more than 10 cm was 52.2 per cent, 0 per cent, 0 per cent. A significant difference in survival rate was observed by size. Postoperative recurrences were observed in 45 patients (67.2%) and 82.8 per cent of the patients had intrahepatic recurrence within 2 years. Hepatic resection is an appropriate treatment for a tumor less than 10 cm. However, a tumor larger than 10 cm should be considered for multimodality approaches. Intrahepatic recurrence is high and similar to the reports from the Orient. Close follow-up with prompt treatment for recurrence is the important factor to obtain better results.