EUS-guided versus percutaneous biliary access in patients with obstructive jaundice due to gastric cancer

Background

Gastric cancer is sometimes complicated by obstructive jaundice. However, ERCP may be challenging in patients who have advanced gastric cancer, or recurrent gastric cancer after surgical resection that is complicated by obstructive jaundice. In such cases, percutaneous transhepatic biliary drainage (PTBD) is considered. Recently, EUS-guided biliary drainage (EUS-BD) has been developed. We conducted a retrospective study to compare the efficacy of EUS-BD and PTBD in patients with obstructive jaundice due to gastric cancer.

Clinical impact of biliary drainage and jaundice resolution in patients with obstructive metastases at the hilum

OBJECTIVES: For patients presenting with progressive liver or lymph node metastases (LM) causing obstructive jaundice, survival without adequate biliary drainage is very brief. The aim of this study was to assess the impact of endoscopic drainage for biliary obstruction secondary to LM at the hilum on subsequent administration of chemotherapy and on patient outcome. METHODS: Thirty-five patients were studied and underwent insertion of plastic and/or metal stents, endoscopically (80%) or percutaneously and endoscopically (20%), to obtain complete resolution of jaundice. LM originated from colon (n = 16), gastric (n = 5), breast (n = 5), pancreatic (n = 3), and miscellaneous cancers (n = 6). Bile duct strictures were Bismuth type I-II in 13 patients and type III in 22. RESULTS: The overall rate of success (i.e., complete resolution of jaundice) was 86% after a median of three procedures per patient (range, 1-7). Pruritus, jaundice, nausea, abdominal pain, and anorexia improved significantly in 88, 86, 75, 66, and 50% of cases, respectively. Overall median survival was 4 months and was 6.5 versus 1.8 months (p < 0.05) in the groups of patients whose jaundice resolved completely versus incompletely. The type of stricture did not affect survival. Patients with colon and breast cancer who were eligible for second line chemotherapy after optimal drainage had the longest survival (12-16 months). CONCLUSIONS: In our patients with obstructive LM, endoscopic biliary drainage completely resolved jaundice in 86% and improved clinical symptoms and survival, thus enabling these patients to have additional chemotherapy.     

Upper abdominal stop-flow perfusion as a neo and adjuvant hypoxic regional chemotherapy for resectable gastric carcinoma. A prospective randomized clinical trial.

BACKGROUND/AIMS: Gastric cancer remains a disease with a poor and dismal prognosis even after radical surgical resection. The present study attempts to clarify whether neo and adjuvant hypoxic upper abdominal chemotherapy can improve the survival of patients with gastric cancer undergoing radical surgical resection. Patterns of failure after surgery for gastric cancer include peritoneal seeding, resection margin recurrence, and liver metastasis. METHODOLOGY: From October 1995 to February 1999, 58 patients with resectable gastric cancer were randomly assigned to three groups. Hypoxic upper abdominal chemotherapy was carried out using Mitomycin-C, 5-Fluorouracil, Leucovorin, and Farmorubicin, 10 days before surgery, and 20 days following surgery, in Group A (n=20) with or without in Group B (n=19) systemic chemotherapy; the remaining patients (Group C: n=19) had neither neo nor adjuvant treatment. RESULTS: The 4-year survival of Group C patients was 29.2%. Group A patients (surgery plus hypoxic neo and adjuvant chemotherapy and systemic chemotherapy) had a 4-year survival of 45.5% versus a 4-year survival of 39.2% of Group B patients (surgery and hypoxic neo and adjuvant abdominal perfusion). Patients of all stages, histologically confirmed, were included in this study. CONCLUSIONS: Patients suffering from gastric carcinoma have demonstrated statistically improved survival by combining resectional surgery with neo and adjuvant hypoxic upper abdominal perfusion and adjuvant systemic chemotherapy.     

Topical Application of an Anti-tumor Agent Through a PTBD Catheter for Management of an Incurable Malignant Biliary Obstruction —a PTBD Option—

Abstract: The treatment of a 69-year-old woman with obstructive jaundice due to the direct invasion of metustutic lymph nodes by gastric cancer at the porta hepatis is reported. In this case topical infusion chemotherapy via a percutaneous biliary drainage (PTBD) catheter with Cis-Diammine Dichloro-Platinum (CDDP) plus Adriamycin (ADM) was found to be an effective treatment to achieve internal biliary drainage with the aid of a percutuneous transhepatic cholangioscopy. This result, in our opinion, suggests that the topical use of anti-tumor agents via a PTBD catheter might be considered an option for the treatment of patients with incurable malignant biliary obstruction.     

Stent implantation through rendezvous technique of PTBD and ERCP: the treatment of obstructive jaundice

OBJECTIVE: To study the technical method and clinical value of stent implantation through the rendezvous technique of percutaneous transhepatic biliary drainage (PTBD) and endoscopic retrograde cholangiopancreatography (ERCP) in patients with obstructive jaundice. METHODS: Thirty-six patients with obstructive jaundice underwent the rendezvous technique of PTBD and ERCP after initially unsuccessful ERCP. RESULTS: The procedure of 36 cases were all successful. Sixteen cases underwent PTBD drainage from the bile duct through the right lobe approach and in 20 cases the left lobe approach was used. The one-stage procedure involved in the rendezvous technique of PTBD and ERCP was successful in 23 cases, while the other 13 cases underwent PTBD first and then rendezvous ERCP the next time. The serum total bilirubin 4 days later had decreased by 44.75%, and direct bilirubin had decreased by 45.61%. The main complication was infection of the bile duct. CONCLUSION: Stent implantation using the rendezvous technique of PTBD and ERCP is a new and feasible method to treat obstructive jaundice after initially unsuccessful ERCP. This may be of considerable value in clinical practice.     

Safety and efficacy of irreversible electroporation in the treatment of obstructive jaundice in advanced hilar cholangiocarcinoma

Background

Irreversible electroporation (IRE) has successfully been used for palliation of pancreatic and liver cancers due to its ability to ablate tumors without destroying nearby vital structures. To date, it has not been evaluated in patients with advanced hilar cholangiocarcinoma (AHC). This study presents a single-institution experience with IRE for management of obstructive jaundice in AHC.

Hepatic protein synthesis and cytokines in obstructive jaundice]

To clarify the mechanism of the increase of hepatic protein synthesis observed in the obstructive jaundiced rats, hepatocellular protein synthesis (HPS) and secretory protein synthesis (SPS) were estimated in the rats with obstructive jaundice and the contents of the following in the peripheral blood were determined in 21 patients with obstructive jaundice before and two weeks after percutaneous transhepatic biliary drainage (PTBD): interleukin-1 beta (IL-1 beta), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF alpha), endotoxin (Et), acute-phase protein (APP) and negative acute-phase protein (NAPP). The results: (1) HPS and SPS were markedly increased by obstructive jaundice; (2) IL-1 beta and IL-6 were significantly high and were reduced after PTBD; (3) neither TNF alpha nor Et was detected; (4) APP were significantly high and failed to decline after PTBD; (5) NAPP were significantly low and the contents were restored to the normal levels after PTBD. These results suggest that increased hepatic protein synthesis observed in the rats with obstructive jaundice correspond to the increased hepatic production of APP in patients with obstructive jaundice.     

Feasibility of self-expandable metallic stent plus chemotherapy for metastatic gastric cancer with pyloric stenosis

Background and Aim:  Self-expandable metallic stent placement is accepted as palliative therapy for advanced gastric cancer with gastric outlet obstruction, but data are lacking for chemotherapy after self-expandable metallic stent insertion. This study retrospectively compared results between surgery plus chemotherapy and stenting plus chemotherapy for metastatic gastric cancer with pyloric stenosis.
Methods:  Subjects comprised 26 patients who received chemotherapy after surgery or endoscopic stenting for metastatic gastric cancer with pyloric stenosis between April 2000 and December 2007 in four Japanese hospitals. Patients were categorized into two groups: 15 patients who received chemotherapy after surgery for pyloric stenosis (Surgery group); and 11 patients who received chemotherapy after self-expandable metallic stent placement for pyloric stenosis (Stent group).
Results:  Median survival time and median time to treatment failure were 284 days and 226 days in the Surgery group and 337 days and 247 days in the Stent group, respectively. No significant differences were noted between survival and time to treatment failure. No significant differences were found in median oral intake rate (Surgery, 93.1%; Stent, 93.2%) or median hospital stay rate (Surgery, 24.6%; Stent, 23.7%) during survival. Response rate was 45.5% in the Surgery group and 50% in the Stent group, with no significant difference. Likewise, no significant differences were noted between groups for frequencies of toxicity or complications.
Conclusions:  The present results suggest that chemotherapy after stenting is as effective and safe as chemotherapy after surgery. Stents may replace surgery in combination therapy with chemotherapy for metastatic gastric cancer with gastric outlet obstruction.     

Endoscopic ultrasound-guided choledochoduodenostomy for treatment of ampullary cancer

We describe the case of a patient for whom choledochoduodenostomy was performed under endoscopic ultrasound (EUS) guidance as an alternative to percutaneous transhepatic biliary drainage (PTBD) for the treatment of obstructive jaundice. An 82-year-old man with ampullary cancer was considered operable, but he refused surgery. Endoscopic biliary drainage (EBD) with an 8.5-French plastic stent was performed 2 months later because of the development of obstructive jaundice. The EBD stent was occluded 5 months after the stent insertion, and EUS choledochoduodenostomy (EUS-CDS) was performed. Pneumoperitoneum occurred 1 day after the procedure, which resolved with conservative treatment. Six months later, multiple lymph node metastases occurred, and the patient was effectively treated by chemotherapy (S-1). The patient is still alive with a good quality of life more than 2 years after EUS-CDS. We conclude that EUS-CDS is an effective alternative to PTBD or EBD for patients with malignant biliary obstruction, especially due to ampullary cancer.     

Hepatic functional evaluation using the galactose tolerance test in patients with obstructive jaundice

Hepatic functional mass was evaluated in patients with obstructive jaundice using the galactose tolerance test (GaTT), which reflected cytosolic function of hepatocyte. The T-1/2 values as an index on the GaTT were significantly prolonged in patients with obstructive jaundice in comparison with control subjects whether before or after percutaneous transhepatic biliary drainage (PTBD). But in each cases, some showed nearly normal GaTT-T/2 value and others showed severely prolonged value. Patients with obstructive jaundice could be divided into two groups according to the GaTT-T/2 value before PTBD. The decreasing rate of serum bilirubin level "b" after PTBD was significantly fair in the group A patients (good GaTT-T/2 value before PTBD) than the group B (poor GaTT-T/2 value before PTBD) (P less than 0.05). It was that GaTT-T/2 before PTBD which represented hepatic cytosolic functional mass could predict the effect of PTBD in patients with obstructive jaundice.     

Endoscopic biliary drainage for patients with unresectable pancreatic cancer with obstructive jaundice who are to undergo gemcitabine chemotherapy

INTRODUCTION Pancreatic cancer is one of the most intractable mali- gnancies of the digestive tract and has a dismal prognosis. Such cancer in most patients is in an advanced stage when they first visit medical facilities, and management of obstructive ja…     

Peritoneal recurrence of ampullary carcinoma following curative pancreatoduodenectomy

A 72 year-old Japanese man with peritoneal recurrence of carcinoma of the ampulla of Vater after curative pancreatoduodenectomy is presented. He was treated by percutaneous transhepatic biliary drainage (PTBD) for obstructive jaundice. The PTBD catheter dislodged 14 days later. He underwent emergency open peritoneal lavage and external choledochal drainage for diffuse bile peritonitis. Cytologic examination of bile obtained from the T-tube revealed malignant cells. He underwent pancreatoduodenectomy with regional lymph node dissection 2 months later for ampullary carcinoma. Pathologic examination showed a macroscopic protruding, 8 x 7 x 10 mm, papillary adenocarcinoma of the ampulla of Vater. The tumor was classified as stage II with pT2, pN0, and pM0. Eight months later, cytologic examination of ascites demonstrated adenocarcinoma cells. The patient died with peritoneal recurrence 10 months after curative pancreatoduodenectomy.     

Prognosis of gastric cancer patients with node-negative metastasis following curative resection: outcomes of the survival and recurrence

BACKGROUND: The purpose of the present study was to provide valuable prognostic information on lymph node-negative gastric cancer patients following curative resection. METHODS: Data from 112 lymph node-negative gastric cancer patients who underwent curative resection were reviewed to identify the independent factors of overall survival and recurrence. RESULTS: The five-year survival rate of lymph node-negative gastric cancer patients was 85.7%, and recurrence was identified in 25 patients after curative surgery. The five-year survival rate of lymph node-negative gastric cancer patients was higher than that of lymph node-positive gastric cancer patients (P<0.001). Recurrence in lymph node-negative gastric cancer patients was less than that of lymph node-positive gastric cancer patients (P=0.001). The median survival after recurrence of lymph node-negative gastric cancer patients was longer than that of lymph node-positive gastric cancer patients (P=0.021). Using multivariate analyses, the following results were determined for lymph node-negative gastric cancer patients: sex, operative type and the presence of serosal involvement were independent factors of overall survival; and lymphadenectomy, number of dissected nodes and the presence of serosal involvement were independent factors of recurrence. CONCLUSIONS: The prognosis of lymph node-negative gastric cancer patients was better than that of lymph node-positive gastric cancer patients. Male sex, subtotal gastrectomy and nonserosal involvement should be considered to be the favourable predictors of postoperative long-term survival of lymph node-negative gastric cancer patients. Conversely, limited lymphadenectomy, few dissected nodes and serosal involvement should be considered to be risk factors of postoperative recurrence of lymph node-negative gastric cancer patients.     

Surgical palliation in pancreatic head carcinoma and gastric cancer: the role of laparoscopy.

BACKGROUND/AIMS: In all patients with pancreatic and gastric cancer we always make a laparoscopic exploration to complete the staging. Lately we have adopted the following technique for nonresectable cancers of the head of the pancreas: following endoscopic retrograde cholangiography we position a biliary stent to restore bile flow and obtain regression of jaundice, a laparoscopic-assisted gastroentero-anastomosis (GEA) is then performed as an antecolic isoperistaltic side-to-side gastrojejunostomy. Also in case of nonresectable gastric cancer we perform a laparoscopic-assisted gastrojejunostomy. METHODOLOGY: From January 1994-February 1998 we performed a total of 25 laparoscopic assisted gastrojejunostomies. We adopted this minimally invasive technique for 11 out of 20 patients (55%) with nonresectable cancers of the head of the pancreas, 7 men and 4 women, whose median age was 73 (range: 60-89). A video-assisted gastrojejunostomy was also performed in 14 patients out of 28 (50%), 10 men and 3 women, with a median age of 70 (range: 58-76), with nonresectable distal gastric cancers and 1 woman with non-resectable and obstructing duodenal cancer. The operative time of the video-assisted procedure was 35 min (range: 25-40 min). RESULTS: There were no intra-operative complications and no mortality. All the patients had a very satisfactory post-operative course, with only 1 (4%) with post-operative complications (hyperpyrexia in a patient due to an infection of the biliaryendoprosthesis, with precocious regression after replacement of the prosthesis) and minimal post-operative pain. Median post-operative hospital stay was 3 days (range: 2-4). Median survival after operation was 6 months (range: 2-12) for gastric cancer and 9 months (range: 5-15 months) for pancreatic head carcinoma. CONCLUSIONS: We believe that this technique, for the obstructive syndrome of the pylorus and duodenum, offers these patients the best results/trauma ratio. Two currently remaining types of indications for a GEA, namely non-malignant ulcer and unresectable duodenal or antropyloric obstructive cancer.     

肝门区转移癌所致梗阻性黄疸的内镜支架引流治疗临床效果分析

目的探讨内镜治疗肝门区转移癌所致梗阻性黄疸的临床应用价值。方法2006年开始随机选择自愿应用内镜治疗的晚期肝门区转移癌所致梗阻性黄疸患者,应用内镜胆道塑料内支架技术解除胆道梗阻,观察操作成功率、生存期等评价指标。共治疗肝门转移癌梗阻性黄疸患者38例,其中肝癌13例,胆囊癌3例,胃癌14例,食管癌2例,回肠腺癌1例,胰腺癌5例。结果所有患者治疗成功且临床黄疸完全消退,随访生存期92～521d,平均（185．42±104．41）d。随访观察5例患者更换胆道支架,更换时间3～14个月,平均（8．6±4．1）个月,其中支架移位1例,胆泥阻塞2例,肿瘤阻塞2例。结论内镜支架引流术是肝门区转移癌所致梗阻性黄疸的一种有效治疗方法,具有较高的治疗成功率,可以一定程度延长患者的生存期。     

Photodynamic therapy for cancer of the pancreas

BACKGROUND: Few pancreatic cancers are suitable for surgery and few respond to chemoradiation. Photodynamic therapy produces local necrosis of tissue with light after prior administration of a photosensitising agent, and in experimental studies can be tolerated by the pancreas and surrounding normal tissue. AIMS: To undertake a phase I study of photodynamic therapy for cancer of the pancreas. PATIENTS: Sixteen patients with inoperable adenocarcinomas (2.5-6 cm in diameter) localised to the region of the head of the pancreas were studied. All presented with obstructive jaundice which was relieved by biliary stenting prior to further treatment. METHODS: Patients were photosensitised with 0.15 mg/kg meso-tetrahydroxyphenyl chlorin intravenously. Three days later, light was delivered to the cancer percutaneously using fibres positioned under computerised tomographic guidance. Three had subsequent chemotherapy. RESULTS: All patients had substantial tumour necrosis on scans after treatment. Fourteen of 16 left hospital within 10 days. Eleven had a Karnofsky performance status of 100 prior to treatment. In 10 it returned to 100 at one month. Two patients with tumour involving the gastroduodenal artery had significant gastrointestinal bleeds (controlled without surgery). Three patients developed duodenal obstruction during follow up that may have been related to treatment. There was no treatment related mortality. The median survival time after photodynamic therapy was 9.5 months (range 4-30). Seven of 16 patients (44%) were alive one year after photodynamic therapy. CONCLUSIONS: Photodynamic therapy can produce necrosis in pancreatic cancers with an acceptable morbidity although care is required for tumours invading the duodenal wall or involving the gastroduodenal artery. Further studies are indicated to assess its influence on the course of the disease, alone or in combination with chemoradiation.     

Neoadjuvant chemotherapy combining docetaxel, cisplatin and S-1 in gastric cancer with para-aortic lymph node metastases: report of five cases

We report on five patients with a median age of 56 years (range, 53-68 years) who were diagnosed as advanced gastric cancer with para-aortic lymph node metastases, determined by gastrofiberscope and abdominal spiral computed tomography. These patients received intravenous docetaxel (30 mg/m2) and cisplatin (30 mg/m2) on day 1, 15 and oral S-1 (40 mg/m2 bid) on days 1-14 every 4 weeks. After two cycles of neoadjuvant chemotherapy, all patients received total gastrectomy with D2 lymphadenectomy plus para-aortic lymph nodes dissection. No patient revealed hematological or non-hematological toxicities associated with the chemotherapy (more than grade 2). The postoperative courses were uneventful without major surgery-related complications. Pathological complete response was confirmed one patient in primary lesion and three patients in metastatic lymph nodes including para-aortic lymph nodes. All of five patients are alive without recurrence (median: 36 months, 21-46 months). Thus, neoadjuvant chemotherapy described here may be rather promising regimen for advanced gastric cancer with para-aortic lymph node metastases, considering its low grade toxicities and pathological responses.     

Folfirinox chemotherapy prolongs stent patency in patients with malignant biliary obstruction due to unresectable pancreatic cancer

Background: Stent insertion for biliary decompression to relieve jaundice and subsequent biliary infection is necessary for patients with biliary obstruction caused by pancreatic cancer, and it is important to keep the stent patent as long as possible. However, few studies have compared stent patency in terms of chemotherapy in patients with pancreatic cancer. This study aimed to evaluate the differences in stent patency in terms of recently evolving chemotherapy.Methods: Between January 2015 and May 2017, 161 patients with pancreatic cancer who had undergone biliary stent insertion with a metal stent were retrospectively analyzed. The relationship between chemotherapy and stent patency was assessed. Additionally, overall survival according to the treatment, risk factors for stent patency, and long-term adverse events were evaluated.Results: Median stent patency was 42 days for patients with the best supportive care and 217 days for patients with chemotherapy (conventional gemcitabine-based chemotherapy and folfirinox) (P < 0.001). Furthermore, the folfirinox group showed the longest median stent patency and overall survival, with 283 days and 466 days, respectively (P < 0.001) despite higher adverse events rate. Patients who underwent folfirinox chemotherapy after stent insertion had better stent patency in multivariate analysis (HR = 0.26; 95% CI: 0.12–0.60; P = 0.001).Conclusions: Compared with patients who received best supportive care only, patients who underwent chemotherapy after stent insertion had better stent patency. More prolonged stent patency can be expected for patients with folfirinox than conventional gemcitabine-based chemotherapy.     

FOLFOX4方案治疗晚期胃癌40例临床观察

目的观察FOLFOX4方案治疗晚期胃癌的临床疗效及毒副反应。方法40例晚期胃癌患者，给予FOLFOX4方案化疗。即：奥沙利铂（L-OHP）85mg／m^2。静脉点滴，2h，dl；亚叶酸钙（LV）200mg／m^2，静脉点滴，2h，d1，d2；氟尿嘧啶（5-FU）400mg／m^2静脉推注，后600mg／m^2微泵持续静脉滴注22h，d1，d2；每2周重复，4周为1周期。均治疗2周期以上，按WHO标准评价客观疗效和毒副反应。结果全组40例均可评价疗效，其中完全缓解（CR）3例，部分缓解（PR）17例，稳定（SD）13例，进展（PD）7例，总有效率（CR＋PR）50．0％。中位肿瘤进展时间（m）5．7个月，中位生存时间（MST）为9．8个月。毒副反应主要是骨髓抑制，胃肠道反应及外周神经毒性。白细胞下降发生率为75．0％。主要为Ⅰ／Ⅱ度反应，恶心呕吐发生率62．5％，腹泻30．0％。口腔粘膜炎22．5％。L—OHP引起的可逆性周围神经毒性发生率为45．0％，表现为肢端感觉异常，遇冷加重，但患者一般都能耐受。结论FOLFOX4方案治疗国人晚期胃癌的近期疗效较好，毒副反应可以耐受，值得进一步研究应用。     

Factors associated with early recurrence after curative surgery for gastric cancer

AIM: To characterize patterns of gastric cancer recurrence and patient survival and to identify predictors of early recurrence after surgery.METHODS: Clinicopathological data for 417 consecutive patients who underwent curative resection for gastric cancer were retrospectively analyzed. Tumor and node status was reclassified according to the 7th edition of the American Joint Committee on Cancer tumor-node-metastasis classification for carcinoma of the stomach. Survival data came from both the patients' follow-up records and telephone followups.Recurrent gastric cancer was diagnosed based on clinical imaging, gastroscopy with biopsy, and/or cytological examination of ascites, or intraoperative findings in patients who underwent reoperation.Predictors of early recurrence were compared in patients with pT1 and pT2-4a stage tumors. Pearson's χ 2 test and Fisher's exact test were used to compare differences between categorical variables. Survival curves were constructed using the Kaplan-Meier method and compared via the log-rank test. Variables identified as potentially important for early recurrence using univariate analysis were determined by multivariate logistic regression analysis.RESULTS: Of 417 gastric cancer patients, 80(19.2%)were diagnosed with early gastric cancer and the remaining 337(80.8%) were diagnosed with locally advanced gastric cancer. After a median follow-up period of 56 mo, 194 patients(46.5%) experiencedrecurrence. The mean time from curative surgery to recurrence in these 194 patients was 24 ± 18 mo(range, 1-84 mo). Additionally, of these 194 patients,129(66.5%) experienced recurrence within 2 years after surgery. There was no significant difference in recurrence patterns between early and late recurrence(P 0.05 each). For pT1 stage gastric cancer, tumor size(P = 0.011) and pN stage(P = 0.048) were associated with early recurrence of gastric tumors.Patient age, pT stage, pN stage, Lauren histotype,lymphovascular invasion, intraoperative chemotherapy,and postoperative chemotherapy were independent predictors of early recurrence in patients with pT2-4a stage gastric cancer(P 0.05 each).CONCLUSION: Age, pT stage, pN stage, Lauren histotype, lymphovascular invasion, intraoperative chemotherapy, and postoperative chemotherapy are independent factors influencing early recurrence of pT2-4a stage gastric cancer.