[Novel Treatment Strategy Using Trafermin® Consisting of bFGF for Intractable Pancreatic Fistula-A Case Report].

Pancreatic fistula is one of the most critical complication following distal pancreatectomy. We report here a successfully treated case with intractable pancreatic fistula using Trafermin® consisting of basic fibroblast growth factor(bFGF). A 60- year-old man underwent laparoscopic distal pancreatectomy. After surgery, pancreatic fistula was occurred. Pancreatic fistula persisted for 3 months despite of several conservative treatments. After obtaining informed consent, we started to inject 50µg/day of Trafermin® through a drainage tube into the dehiscence of pancreas. Consequently, pancreatic fistula was successfully closed within a week. This technique could be one of the treatment choices for intractable pancreatic fistula following distal pancreatectomy.

Impact of Neoadjuvant Chemotherapy Among Patients with Pancreatic Fistula After Gastrectomy for Advanced Gastric Cancer.

BACKGROUND: Neoadjuvant chemotherapy (NAC) has been widely adopted for patients with advanced gastric cancer; however, the safety of gastrectomy with D2 lymphadenectomy followed by NAC has not yet been evaluated. We retrospectively analyzed the influence of NAC on morbidity and mortality after gastrectomy in patients with advanced gastric cancer. PATIENTS AND METHODS: A series of 364 patients with advanced gastric cancer who underwent gastrectomy without pancreatectomy between January 2008 and December 2010 at eight hospitals registered to the Yokohama Clinical Oncology Group were studied retrospectively. There were 330 patients who underwent surgical treatment immediately after diagnosis (surgery alone group) and 34 patients (NAC group) who first received NAC and then underwent surgical resection. RESULTS: Although there were no significant differences in the morbidity rate between the two groups, postoperative pancreatic fistula was more often observed in NAC patients than in patients of the group treated with surgery alone [5 cases (14.7%) vs. 11 cases (3.3%); p=0.011]. In the univariate analysis, NAC (p=0.029), bursectomy (p<0.001) and operative bleeding (≥300 ml, p=0.002), were significantly correlated with postoperative pancreatic fistula, and NAC [odds ratio (OR)=4.901, 95% confidence interval (CI)=1.455-16.67; p=0.010] and bursectomy (OR=11.2, 95% CI=3.460-37.04; p<0.001) were independent risk factors for postoperative pancreatic fistula by multivariate analysis. The incidence of postoperative pancreatic fistula was 40.0% among patients who underwent gastrectomy with bursectomy followed by NAC. CONCLUSION: The incidence of pancreatic fistula in patients treated with NAC and bursectomy was significantly higher than that in other patients. Bursectomy may be discouraged for the prevention of pancreatic fistula from gastrectomy following NAC.

[Impact of octreotide on pancreatic fistula after pancreaticoduodenectomy: a prospective study].

OBJECTIVE: To investigate the effect of utilizing octreotide during perioperative period on pancreatic fistula after pancreaticoduodenectomy (PD). METHODS: Three hundreds and six patients admitted from January 2010 to October 2014, who prepared to undergo pancreaticoduodenectomy (PD) were randomly divided into octreotide group (147 cases) and control group (159 cases). In octreotide group, octreotide was used in subcutaneous injection instantly after PD, each 8 hours until postoperative 10(th) day, and patients in control group were injected with the same volume of saline. Differences of pancreatic fistula (Grade A, Grade B, Grade C), hospitalization days and treatment cost were compared. χ(2) test, t-test and Fisher exact test were used to analyzed to the data, respectively. RESULTS: No statistical significance (P>0.05) between two groups in the incidence of pancreatic fistula after PD (Grade A: 8.8% vs. 10.2%, Grade B: 2.7% vs. 4.4%, Grade C: 0.7% vs. 1.3%; χ(2)=0.197, 0.700, 0.288; P=0.657, 0.403, 0.591), the length of hospitalization((12.1±1.2)days vs. (13.0±1.2)days)(t=1.711, P=0.104) and treatment cost (79 700±6 700 vs. 77 600±5 200)(t=1.378, P=0.185). When accompanied with high risk factors, such as soft texture of pancreas, pancreatic duct size less than 3 mm, BMI≥25 kg/m(2) and diabetes, compared with control group, octreotide group had the lower incidence rate of pancreatic fistula and clinical correlative pancreatic fistula(all P<0.05) after PD. CONCLUSIONS: Generally, octreotide makes no contribution to reduce the incidence of pancreatic fistula after PD. However, for patients who is accompanied with high risk factors, such as soft texture of pancreas, pancreatic duct size less than 3 mm, BMI≥25 kg/m(2) and diabetes, octreotide can effectively prevent pancreatic fistula after PD.

[Somatostatin and the digestive system. Clinical experiences]. / A szomatosztatin és az emésztorendszer. Klinikai tapasztalatok.

The effect of somatostatin on the gastrointestinal tract is complex; it inhibits the release of gastrointestinal hormones, the exocrine function of the stomach, pancreas and bile, decreases motility and influences absorption as well. Based on these diverse effects there was an increased expectation towards the success of somatostatin therapy in various gastrointestinal disorders. The preconditions for somatostatin treatment was created by the development of long acting somatostatin analogues (octreotide, lanreotide). During the last twenty-five years large trials clarified the role of somatostatin analogues in the treatment of various gastrointestinal diseases. This study summarizes shortly these results. Somatostatin analogue treatment could be effective in various pathological conditions of the gastrointestinal tract, however, this therapeutic modality became a part of the clinical routine only in neuroendocrine tumours and adjuvant treatment of oesophageal variceal bleeding and pancreatic fistulas.

[Efficacy of octreotide in the treatment of chyle fistulas associated with pancreatic disease]. / Eficacia del octreótido en el tratamiento de la fístula quilosa asociada a enfermedades pancreáticas.

INTRODUCTION: A chyle fistula is an uncommon complication following abdominal and pancreatic surgery, particularly in the retroperitoneal compartment. It can also appear as a complication of a severe acute pancreatitis. Medical treatment is the initial approach, but resolution is often slow. Somatostatin or octreotide can help in accelerating the resolution of fistulae. PATIENTS AND METHODS: Patients developing a chyle fistula (output > 100ml/24h, normal amylase levels and triglyceride concentrations above 110mg/dl) associated with pancreatic disorders were treated with oral intake restriction and parenteral nutrition, followed by subcutaneous octreotide 0.1mg/8h. RESULTS: Four female patients from 55 to 80 years old, underwent pancreatic surgery or presented with an acute pancreatitis, were treated. Chyle fistulae ranging from 100 to 2,000ml/24h were treated with octreotide, being resolved within five to seven days. No recurrence has been found in a 2 to 4 years follow up. CONCLUSIONS: We have found that chyle fistula medical treatment is often related to a slow resolution, somatostatin or octreotide administration dramatically reduces its duration. Other previously reported studies have also shown that the quick onset of such treatment can accelerate the whole process, leading to a shorter recovery and lower hospital costs.

[A case of pancreatic and duodenal fistula after total gastrectomy successfully treated with coagulation factor XIII].

Pancreatic fistula( PF) is a challenging postoperative complication. We report a case of PF following gastrectomy successfully treated using intravenous coagulation factor XIII( FXIII).A 78-year-old man with early gastric cancer underwent total gastrectomy with Roux-en-Y reconstruction. PF developed postoperatively, following which, leakage from the duodenal stump was observed. Percutaneous drainage and re-operative surgery were performed. A somatostatin analogue, antibiotic drugs, and gabexate mesilate were administrated along with nutritional support. The pancreatic and duodenal fistula had been producing duodenal juice for over 30 days since the re-operative surgery. As suspected, reduced FXIII activity was confirmed in the patient. After administering FXIII for 5 days, the amount of duodenal juice from the fistula markedly reduced, and the fistula closed immediately afterwards. The results of our study suggest that administration of FXIII could be a reasonable and effective treatment for patients with pancreatic or/and enterocutaneous fistula who are resistant to standard treatments.

[Best time to administer coagulation factor XIII( Fibrogammin P) for postoperative intractable pancreatic fistula following gastrectomy for gastric cancer].

BACKGROUND: Coagulation factor XIII( Fibrogammin P, F XIII) has been used to treat postoperative pancreatic fistulas following gastrectomy for gastric cancer in Japan. However, little is known about the best timing to start this treatment for early recovery. This study was designed to examine the appropriate time to start Fibrogammin P treatment for pancreatic fistulas, based on nutritional and inflammatory parameters. METHOD: We retrospectively examined 27 consecutive patients with Grade B or C pancreatic fistulas as defined by the International Study Group of Pancreatic Fistula( ISGPF) classification who underwent gastrectomy at our institute between 1997 and 2011. We analyzed data on total protein( TP), albumin (Alb), C-reactive protein( CRP), and hemoglobin( Hb) concentrations and white blood cell( WBC) and lymphocyte counts. We used this information to determine laboratory cut-off values that indicate the most advantageous time to start the administration of Fibrogammin P in order to achieve early recovery within 2 weeks. RESULT: When Fibrogammin P administration was based on more than 2 cut-off values such as Alb>2.6 g/dL and Hb>9.0 g/dL and WBC<9,000/µL (p= 0.1563), early cure of pancreatic fistulas was achieved. CONCLUSION: The use of nutritional and inflammatory parameter values to determine the best time to administer Fibrogammin P may shorten the treatment period.

Systematic review and meta-analysis of somatostatin analogues for the treatment of pancreatic fistula.

BACKGROUND: Somatostatin analogues are used for the treatment of pancreatic fistula, with the aim of achieving fistula closure or reduction of output. METHOD: MEDLINE, Embase and Cochrane databases were searched systematically for relevant articles followed by hand-searching of reference lists. Data on patient recruitment, intervention and outcome were extracted and meta-analysis performed where reasonable. RESULTS: Seven randomized clinical trials met the inclusion criteria and included a total of 297 patients with fistulas of the gastrointestinal tract; of these, 102 patients had fistulas of pancreatic origin. Pooling of closure rates showed no significant difference between patients treated with somatostatin analogues compared with controls: odds ratio 1·52 (95 per cent confidence interval 0·88 to 2·61). Owing to inconsistent descriptions, pooling of results was not possible for other endpoints, such as time to fistula closure. CONCLUSION: There is no solid evidence that somatostatin analogues result in a higher closure rate of pancreatic fistula compared with other treatments.

[Novel treatment strategy using Trafermin® consisting of bFGF for intractable pancreatic fistula following gastrectomy for gastric cancer-a case report with literature reviews].

Despite recent perioperative technological advances in gastric cancer, intractable pancreatic fistula is still a major critical complication following gastrectomy and should be specifically targeted in the effort to improve postoperative outcomes. We preliminary report here a successfully treated case with intractable pancreatic fistula using Trafermin® consisting of basic fibroblast growth factor (bFGF). A 67-year-old man underwent laparoscopic proximal gastrectomy with radical lymphadenectomy for early proximal gastric cancer (pT1bN0M0). After surgery, pancreatic fistula was occurred. Pancreatic fistula persisted for three months despite of surgical and several conservative treatments. After obtaining informed consent, we started to inject 50 µg/day of Trafermin® through a drainage tube into the dehiscence of pancreas. Consequently, pancreatic fistula was successfully closed within three weeks. Our novel treatment technique is simple, rapid and not costly. If informed consent was obtained from patients with low risk of recurrences, this technique should be recommended as one of the treatment choices for intractable pancreatic fistula following curative gastrectomy for gastric cancer.

Postoperative pancreatic fistula after cytoreductive surgery and perioperative intraperitoneal chemotherapy: incidence, risk factors, management, and clinical sequelae.

BACKGROUND: Cytoreductive surgery (CRS) and perioperative intraperitoneal chemotherapy (PIC) has improved survival in selected patients with peritoneal carcinomatosis. This study evaluates the morbidity of postoperative pancreatic fistula (PF) within the context of CRS and PIC. METHODS: Two hundred seventy-one consecutive CRS and PIC procedures were evaluated. Diagnosis and classification of postoperative PF were performed according to the international study group on PF criteria. The associations between 8 clinical and 20 treatment-related factors with postoperative PF were determined by univariate and multivariate analysis. The management and clinical sequelae of postoperative PF were discussed. RESULTS: Seventeen patients (6.3%) developed postoperative PF. None of these patients died during their in-hospital stay. Multivariate analysis identified three independent risk factors for PF: transfusion of >or=6 units of blood (P = 0.029), operation duration of >or=9 h (P = 0.035), and splenectomy (P = 0.020). Conservative management of PF was instituted in all 17 patients and was successful in 16 (94%). The overall time to PF closure was 26 (standard deviation 16) days after diagnosis. Although PF did not contribute to procedure-related mortality, it was associated with increased length of hospital stay (P < 0.001). CONCLUSIONS: CRS and PIC presented an acceptable rate of PF that did not increase the procedure-related mortality. However, PF was associated with longer hospital stay. Most patients with PF were treated conservatively and did not require surgical intervention.

Randomized, placebo-controlled, double-blind study of the efficacy of lanreotide 30 mg PR in the treatment of pancreatic and enterocutaneous fistulae.

OBJECTIVE: Continuous intravenous infusion of somatostatin improves the natural course of digestive fistulae. Lanreotide 30 mg PR is a synthetic analogue of somatostatin with pharmacological activity extending to at least 10 days after intramuscular administration. Its effectiveness was assessed in patients with simple externalized digestive fistulae in a randomized, doubleblind, placebo-controlled study. METHODS: Patients demonstrating a reduction of at least 50% of fistula output within 72 hours after a first double-blind intramuscular injection of lanreotide or placebo were considered to be responders (primary end point) and continued the double-blind treatment to a maximum of 6 injections at 10-day intervals. Other endpoints included fistula closure rate and time to closure. Blind was lifted for nonresponders, and those initially on placebo were then treated with open-label lanreotide. RESULTS: Following the first double-blind injection, 35 of 54 patients (64.8%) on lanreotide were responders versus 20 of 53 (37.7%) on placebo, ie, a 3.1 times higher response likelihood on lanreotide compared with placebo (P = 0.006). Group mean reduction of fistula output at 72 hours was 45.1% and 8.9%, respectively (P = 0.005). Lanreotide compared with placebo had no effect on closure rate which averaged 77% but median time to fistula closure was shorter on lanreotide, based on Kaplan-Meier analysis, although no statistical significance was achieved. CONCLUSION: Compared with placebo, intramuscular lanreotide 30 mg PR significantly decreases digestive fistulae output at Day 3 and shortens time to fistula closure by 9 days. ClinicalTrials.gov registration number: NCT00729313.

Pancreaticopleural fistula visualized by computed tomography scan combined with pancreatography.

CONTEXT: We report a case of a pancreaticopleural fistula which was clearly demonstrated by computed tomography (CT) scan following pancreatography and which was successfully treated with endoscopic nasopancreatic drainage combined with octreotide. CASE REPORT: A 52-year-old male was admitted to our hospital for additionally evaluation of bilateral pleural effusion. The pleural fluid amylase level was markedly elevated. Endoscopic retrograde pancreatography showed a cyst in the body of the pancreas and extravasation of contrast medium extending cranially from the cyst. The disease was treated successfully with endoscopic nasopancreatic drainage combined with the administration of octreotide. A pancreaticopleural fistulous route was clearly demonstrated by CT scan following pancreatography through the nasopancreatic drainage tube. CONCLUSIONS: A CT scan following pancreatography was useful in demonstrating a pancreaticopleural fistulous route.

Report of three cases of chronic pancreatic fistulas treated with prolamine as a sclerosing substance following pancreatic resection.

CONTEXT: Pancreatic fistulas are one of the most common and important complications after pancreatic resection and their consequences are a life-threatening event. Thus, they must be treated in the best way and resolved as soon as possible to avoid their morbidity. METHODS: Three cases of pancreatic fistula following pancreatic resection were reported. They were treated with percutaneous embolization using a sclerosing substance, prolamine, injected into the Wirsung duct via drainage catheter. RESULTS: No complications of the technique were revealed and closure of the pancreatic fistula was obtained shortly thereafter. CONCLUSIONS: The technique is safe and simple and can be repeated several times. It allows good results without complications. Finally, it avoids additional surgery allowing a shorter recovery time and a lower risk of morbidity.

Somatostatin versus octreotide in the treatment of patients with gastrointestinal and pancreatic fistulas.

BACKGROUND AND PURPOSE: Gastrointestinal and pancreatic fistulas are characterized as serious complications following abdominal surgery, with a reported incidence of up to 27% and 46%, respectively. Fistula formation results in prolonged hospitalization, increased morbidity/mortality and increased treatment costs. Conservative and surgical approaches are both employed in the management of these fistulas. The purpose of the present study was to assess, evaluate and compare the potential clinical benefit and cost effectiveness of pharmacotherapy (somatostatin versus its analogue octreotide) versus conventional therapy. PATIENTS AND METHODS: Fifty-one patients with gastrointestinal or pancreatic fistulas were randomized to three treatment groups: 19 patients received 6000 IU/day of somatostatin intravenously, 17 received 100 microg of octreotide three times daily subcutaneously and 15 patients received only standard medical treatment. RESULTS: The fistula closure rate was 84% in the somatostatin group, 65% in the octreotide group and 27% in the control group. These differences were of statistical significance (P=0.007). Overall mortality rate was less than 5% and statistically significant differences in mortality among the three groups could not be established. Overall, treatment with somatostatin and octreotide was more cost effective than conventional therapy (control group), and somatostatin was more cost effective than octreotide. The average hospital stay was 21.6 days, 27.0 and 31.5 days for the somatostatin, octreotide and control groups, respectively. CONCLUSIONS: Data suggest that pharmacotherapy reduces the costs involved in fistula management (by reducing hospitalization) and also offers increased spontaneous closure rate. Further prospective studies focusing on the above parameters are needed to demonstrate the clinicoeconomic benefits.

Octreotide does not prevent postoperative pancreatic fistula or mortality following Pancreaticoduodenectomy.

The role of octreotide in preventing pancreatic fistula following pancreaticoduodenectomy (PD) remains controversial. The purpose of our study was to report our experience with octreotide in 266 patients undergoing PD from 1995 to 2002. There were 150 males and 116 females. Patients were divided into two groups. Group 1 did not receive octreotide (N = 61). Group 2 received octreotide (N = 205). The average patient age was 66.2 years in the control group and 63.6 years in the octreotide group. One hundred fifty patients were male and 116 were female. Thirty-day mortality for both groups was 1.9 per cent. The incidence of pancreatic fistula was 12 per cent. Fistula occurrence in the octreotide group was 13 per cent and in the no-octreotide group 8 per cent (P = 0.34). Common complications in the no-octreotide group were pancreatic leak (10%), pancreatic fistula (8%), and delayed gastric emptying (8%). Common complications in the octreotide group were pancreatic leak (18%), pancreatic fistula (13%), intra-abdominal abscess (7%), and arrhythmia or myocardial infarction (7%). The only statistically different variable was the incidence of arrhythmia or myocardial infarction (P = 0.026). Octreotide did not reduce pancreatic fistula, other complications, or mortality. Octreotide may contribute cardiac morbidity. Octreotide cannot be recommended to prevent mortality or postoperative complications after PD.

[Natural history of the pancreatic stump after duodenopancreatectomy of the pancreatic head]. / Histoire naturelle du moignon pancréatique après duodénopancréatectomie céphalique (DPC).

UNLABELLED: Major complications following pancreaticoduodenectomy are thought to be chiefly associated with exocrine secretion of the pancreatic remnant which is not well known. This work aims to assess the exocrine secretion of the pancreatic remnant within the early post-operative period. PATIENTS AND METHODS: Seventy-five patients undergoing pancreaticoduodenectomy for presumed tumour were included in a prospective multicentre study. A tube was inserted in the pancreatic duct at the time of construction of the pancreatic anastomosis. Peripancreatic drainage was routinely used. Pancreatic juice and peripancreatic drainage fluid were collected and measured and pancreatic enzyme monitored. For 7 days patients received total parenteral nutrition and continuous infusion of randomly Somatostatin 14 (S-14) at a dose of 6 mg/24 h (days 1-6) and 3 mg/24 h (day 7) or matching placebo. Pancreatic fistula was defined as a daily drainage of more than 100 cc of amylase-rich fluid after day 3, persisting after day 12 or associated with symptoms or needing specific treatment. RESULTS: Daily output of pancreatic juice was low during the first postoperative day and then increased gradually until day 5. A high enzyme concentration was observed in pancreatic juice on the first post-operative day. S-14 infusion resulted in a significant decrease of both pancreatic fistula rate and enzyme concentration in peripancreatic fluid. CONCLUSIONS: During the first postoperative days, the outflow of the exocrine secretion of the pancreatic remnant is low but contains a high enzyme concentration with significant leaks within the peripancreatic area. S-14 infusion results in a decrease of pancreatic juice leaks from the pancreatic remnant.

[Management of postoperative pancreatic fistula resistant to octreotide therapy]. / Postepowanie z pooperacyjnymi przetokami trzustkowymi opornymi na leczenie oktreotydem.

Pancreatic fistula is a rare postoperative complication, usually occurring after pancreatic surgery. Majority of them heal spontaneously, some patients require somatostatin/octreotide treatment. The authors have presented 11 patients with postoperative pancreatic fistula, in whom octreotide therapy in dose of 0.1 mg t.i.d./10 days has been ineffective. The causes of pancreatic fistula have been as follows: necrosectomy of the infected pancreatic necrosis--5 patients, distal pancreatic resection--2 patients, insulinoma enucleation--2 patients, gastrectomy with partial pancreatectomy--2 patients. In 9 patients endoscopic stenting of the main pancreatic duct has been performed. In remained 2 patients after Roux-en-Y gastrectomy the endoscopic access to Vater papilla has been impossible and the patients have received one intramuscular injection of long acting somatostatin analogue. In 8 of 9 patients with pancreatic stenting and in two patients after gastrectomy the fistula has been closed within the period of 6-17 days. In one patient after the necrosectomy the prosthesis implacement has been ineffective. This patient has been successfully treated with two additional injections of long acting somatostatin analogue (one injection/14 days). Authors have concluded that endoscopic pancreatic stenting has been an effective method of treatment of the postoperative pancreatic fistula, resistant to octreotide therapy. In some cases, additional administration of long acting somatostatin analogue has been necessary.