Non-surgical treatment for afferent loop syndrome in recurrent. gastric cancer complicated by peritoneal carcinomatosis.

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1 Clinical case Annals of Oncology 13: , 2002 DOI: /annonc/mdf212 Non-surgical treatment for afferent loop syndrome in recurrent gastric cancer complicated by peritoneal carcinomatosis: percutaneous transhepatic duodenal drainage followed by 24-hour infusion of high-dose fluorouracil and leucovorin K.-D. Lee 1,T.-W.Liu 1,C.-W.Wu 2,C.-M.Tiu 3,J.M.Liu 1, T.-R. Chung 1,J.-Y.Chang 1, J. Whang-Peng 1 &L.-T.Chen 1,4 * 1 Division of Cancer Research, National Health Research Institutes, Taipei; Departments of 2 Surgery and 3 Radiology, Taipei Veterans General Hospital, Taipei; 4 Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan, Republic of China Received 14 January 2002; revised 6 February 2002; accepted 11 March 2002 Afferent loop syndrome (ALS) is a debilitating complication of recurrent gastric cancer. Surgical intervention is usually not feasible in the face of poor general performance, presence of advanced peritoneal carcinomatosis and limited survival of the patients. Non-surgical approaches include internal drainage by stenting at the stenotic or anastomotic site and external drainage via the percutaneous routes. Percutaneous transhepatic duodenal drainage (PTDD) has been shown to provide effective palliation for ALS, but long-term catheterization is usually inevitable. We hereby present two cases of recurrent gastric cancer whose ALS was successfully treated with PTDD followed by weekly 24-h infusion of high-dose 5-fluorouracil and leucovorin (HDFL). PTDD rapidly ameliorated the incapacitating symptoms of ALS, and the effective, low-toxicity chemotherapy subsequently led to tumor regression, restoration of bowel patency and removal of the drainage tube. At present, both patients have remained ALS-free and drainage-free for 16 and 17 months, respectively. Our results indicate that this non-surgical approach with PTDD followed by weekly HDFL could serve as a safe and effective treatment for ALS in recurrent gastric cancer complicated by peritoneal carcinomatosis. Key words: afferent loop syndrome, high-dose 5-fluorouracil/leucovorin, percutaneous transhepatic duodenal drainage Introduction Gastric cancer is the second leading cause of cancer death around the world [1]. Most patients present initially with locally advanced or metastatic disease; one-third of the patients are amenable to curative resection; however, many of them will succumb to tumor relapse even after radical surgery. Afferent loop syndrome (ALS) is a rare manifestation of recurrent gastric cancer [2]. Symptoms of ALS include postprandial upper-quadrant pain, nausea and bilious vomiting. These disabling symptoms usually make oral intake impossible, and result in rapid deterioration in the general condition and impairment of quality of life. Surgical conversion, such as the Roux-en-Y procedure, has been shown to provide effective palliation for ALS resulting from benign complications *Correspondence to: Dr L.-T. Chen, A191 Ward, Taipei Veterans General Hospital, 201 Shih-Pai Road, Sec. 2, Taipei 112, Taiwan, Republic of China. Fax: ; Tel: ; leochen@nhri.org.tw after subtotal gastrectomy with Billroth II anastomosis, such as stricture of the anastomosis, adhesion, stomal ulceration, and rarely, remnant gastric cancer [3, 4]. However, ALS secondary to recurrent gastric cancer is a distinct entity. Attempted surgery, such as Roux-en-Y or enteroenterostomy of Braun s procedure between the proximal afferent and the efferent loop to bypass the obstruction, is usually impossible because of recurrent tumor mass at the anastomotic site and/or extensive mesenteric carcinomatosis resulting in bowel loop fixation. The poor general condition at presentation and the dismal outcome of patients further preclude surgical intervention. Non-surgical treatment is a more reasonable approach. Various external or internal drainage procedures have been used to palliate this frustrating syndrome. Our previous report [5] has described that percutaneous transhepatic duodenal drainage (PTDD) could provide effective palliation in patients with recurrent gastric cancer complicated by ALS and secondary obstructive jaundice. However, without effective systemic therapy, prolonged catheterization is mandatory in such patients. Weekly 24-h infusion of high-dose 5-fluorouracil 2002 European Society for Medical Oncology

2 1152 (5-FU) and leucovorin (LV) (HDFL) is an active regimen with low-toxicity profiles and can be safely applied even in advanced gastric cancer patients whose general condition is unfavorable [6, 7]. We describe two cases of ALS in association with recurrent gastric cancer and peritoneal carcinomatosis in whom the combination of PTDD and 24-h infusion of HDFL therapy led to long-term ALS relapse-free and drainage-free survival. Case reports Case 1 In March 1999, a 73-year-old male was diagnosed with adenocarcinoma of the gastric fundus. He received a radical total gastrectomy, end-to-side esophagojejunostomy, Roux-en-Y jejunojejunostomy, splenectomy and distal pancreatectomy. Pathological examination revealed poorly differentiated adenocarcinoma cells penetrating through the gastric serosa and directly invading into the pancreas. Two of 22 dissected lymph nodes were found to harbor metastatic cancer cells; post-operative staging was IV [T4N1M0; American Joint Committee on Cancer (AJCC) 1997] and adjuvant chemotherapy was not given. In July 2000, the patient presented to our clinic with the chief complaints of epigastric pain, fever, jaundice and the presence of tea-colored urine for 1 week. At hospitalization, he was feverish, emaciated and jaundiced, with pale conjuctiva and icteric sclera. The results of laboratory tests were as follows: white blood cell count, 17500/mm 3 ;hemoglobulin, 10.5 g/dl; platelets, /mm 3 ; albumin, 2.7 g/dl; total/direct bilirubin, 8.1/5.2 mg/dl; alanine aminotransferase (ALT), 58 U/l; aspartate aminotransferase (AST), 69 U/l; lactate dehydrogenase, 322 U/l; alkaline phosphatase (Alk-P), 391 U/l; γ-glutamyltransferase (γ-gt), 301 U/l; and CA19.9, 104 U/ml. Abdominal computed tomography (CT) scan showed prominent dilatation of the duodenal loop, common bile duct (CBD) and bilateral intrahepatic ducts (IHDs), a small amount of ascites and multiple lymphadenopathies over mesentery and superior mesenteric artery axis. Afferent loop obstruction with secondary obstructive jaundice resulting from recurrent gastric carcinoma was diagnosed. As a result of his poor general condition and the presence of peritoneal carcinomatosis, surgical intervention was impossible. Therefore, a sono-guided PTDD procedure was carried out by inserting an 8.3 French (Fr), 32 side-hole pigtail catheter via the dilated left IHD and, under fluoroscopy, the catheter tip was advanced into the distended duodenum. His abdominal pain was promptly relieved and his bilirubin, transaminase, Alk-P and γ-gt levels returned to normal within 2 weeks following the procedure. One week later, he suffered from a recurrence of the epigastric pain and obstructive jaundice because of kinking of his PTDD catheter. After resolution of the above symptoms by PTDD revision, he received weekly 24-h infusions of 5-FU 2600 mg/m 2 and LV 300 mg/m 2 (HDFL) admixed in 500 ml of normal saline and given via a central venous catheter. After 7 weeks of chemotherapy, the daily amount of bowel juice drainage from PTDD was markedly reduced to <10 ml. A Tc 99m cholescintigraphy performed while his PTDD was being temporarily clamped showed mild dilatation of the IHDs and CBD without delayed retention of the isotope tracer in the afferent loop. Therefore, an expandable metallic biliary stent was implanted into the CBD and his PTDD catheter was removed. After an additional 5 months of HDFL treatment, his CA19.9 dropped to 12 U/ml and follow-up CT scan showed Figure 1. Abdominal CT scan in case 2 showing gastric cancer recurrence with afferent loop and gall bladder distension, common bile duct dilatation and left side hydronephrosis. The intrahepatic ducts were not dilated.

3 1153 complete regression of the recurrent tumors at anastomotic site, lymphadenopathy and mesenteric carcinomatosis. His chemotherapy was then changed to oral tegafur/uracil (UFUR ; TTY Biopharm, Taiwan). Four months later, an abdominal CT scan disclosed peritoneal recurrence. He was then salvaged using chemotherapy incorporating biweekly oxaliplatin and a simplified 46-h infusion of 5-FU/LV. At latest presentation, he remains ALS-free for 16 months. Case 2 A 47-year-old man received a radical total gastrectomy with an end-to-side esophagojejunostomy, Roux-en-Y jejunojejunostomy and pancreaticosplenectomy in August Pathology showed moderately to poorly differentiated gastric adenocarcinoma penetrating gastric serosa and invading into the spleen; three of six dissected lymph nodes harbored metastases. Post-operative staging was IV (T4 N1 M0; AJCC 1997). He received post-operative adjuvant chemotherapy with weekly 24-h infusions of 5-FU 850 mg/m 2 and LV 85 mg/m 2, and bolus injections of mitomycin-c 3 mg for 20 courses. Two and a half years later, he suffered from repeated attacks of severe post-prandial epigastric pain and bilious vomiting after meals. On admission, a palpable distended bowel loop with severe tenderness located in the epigastrium and right upper quadrant was found. Laboratory test results were as follows: amylase, 833 U/l; lipase 2, 726 U/l; serum bilirubin, 0.7 mg/dl; ALT, 67 U/l; AST, 64 U/l; γ-gt, 35 U/l; blood urea nitrogen, 15 mg/dl; and creatinine, 1.6 mg/dl. Abdominal ultrasound and CT scan (Figure 1) showed marked swelling of the pancreas with dilated pancreatic ducts, distension of the duodenal loop, and left hydronephrosis and hydroureter caused by confluent lymphadenopathies in the retroperitoneum. There was no IHD dilatation. The serum level of carcinoembryonic antigen (CEA) was 422 U/l. Tc 99m cholescintigraphy showed a prominent afferent loop with tracer retention at 4 h after injection (Figure 3A). Afferent loop syndrome with acute pancreatitis was impressed. Due to poor performance status, surgical intervention was not considered; the patient was referred to the oncologists for palliative treatment. A double-j stent was placed to relieve his hydronephrosis. PTDD via the left intrahepatic duct was unsuccessful because of non-dilated IHDs. Instead, a percutaneous drainage tube was inserted into the gall bladder (PTGBD) to temporarily relieve the pressure of his distal biliary tract. However, his ALS-associated symptoms were not improved. Three days later, transcholecystic cholangiography (Figure 2A) was performed via the PTGBD tube as an alternative for continuous opacification of the biliary trees to guide the insertion of a 10 Fr, 32 side-hole pigtail catheter via the right IHD with its tip being advanced into the afferent loop (Figure 2B). Immediately after PTDD, he had normal food intake without any attack of epigastric pain. Amylase and lipase levels gradually returned to normal range. Two weeks after the PTDD procedure, chemotherapy Figure 2. A percutaneous transcholecystic drainage tube (PTGBD) was inserted into the gall bladder in case 2. Transcholecystic cholangiography was done via the PTGBD for continuous opacification of the biliary trees (A) to guide the insertion of a 10 French, 32 side-hole pigtail catheter via the right intrahepatic duct with its tip being advanced into the afferent loop (B). consisting of a weekly 24-h infusion of HDFL was given. After 9 weeks of chemotherapy, the amount of bowel content drained from the PTDD was gradually reduced. Tc 99m cholescintigraphy revealed normal transit of radioactive tracer from the biliary system to the jejunum (Figure 3B). His PTDD was clamped for 2 weeks and the patients remained asymptomatic. Despite CEA being still high (120 U/l), PTDD was removed. He continuously received weekly 5-FU/LV for 1 year until tumor progression. His chemotherapy was changed to biweekly oxaliplatin with 46-h infusion of FU/LV. His ALS

4 1154 of flexible covered metallic stents has become a popular procedure to palliate postoperative gastrointestinal malignant strictures, including ALS [10 12]. Compared with internal drainage with stenting, the use of PTDD has the advantage of being more economical and less likely to be complicated by symptom recurrence resulting from multiple intestinal strictures; however, it has the disadvantage of carrying an external drainage catheter and is more prone to fluid and electrolyte imbalances. Nevertheless, with the incorporation of an effective systemic therapy, long-term catheterization can be avoided in patients with PTDD, as occurred in our patients. Recurrent gastric cancer patients presenting as ALS in association with peritoneal carcinomatosis usually survive <3 months after palliative drainage procedures if no other adjuvant treatment is given [11, 12]. Systemic chemotherapy has been rather disappointing for peritoneal carcinomatosis resulting from gastric cancer [13 15]. Weekly 24-h infusion of HDFL has recently been shown to be an active regimen with a low toxicity profile for advanced gastric cancer patients with a poor general condition [6, 7]. The response rate of weekly HDFL was 33 48% and 18% for first-line chemotherapy and salvage treatment, respectively [6, 16, 17]. In addition, the weekly HDFL-based regimen was found to be active in patients with malignant ascites and in patients with complete bowel obstruction [18, 19]. Both our patients attained good response to weekly HDFL that led to restoration of bowel patency and prolonged (>15 months) catheter-free survival. This observation suggests that weekly HDFL in combination with PTDD is an effective, non-surgical treatment for patients with recurrent gastric cancer complicated by ALS and advanced peritoneal carcinomatosis. Figure 3. Tc 99m -cholescintigraphy (A) before treatment in case 2 showing the retention of radioactive tracer in a dilated afferent loop (arrows) from 1 to 4 h after injection. After percutaneous transhepatic duodenal drainage and 9 weeks of systemic chemotherapy with high-dose 5-FU/LV, the afferent loop was not visible in the cholescintigraphy (B), indicating a normal transit of tracer through the afferent loop. and pancreatitis have not recurred for 17 months at the time of this report. Discussion In the presence of extensive mesenteric carcinomatosis and poor general condition, non-surgical approaches with various external or internal drainage procedures have become the favorite modality to palliate ALS in association with recurrent gastric cancer. Percutaneous bowel and/or gall bladder drainage is associated with the risk of intraperitoneal leakage [8]; such complications can be avoided by percutaneous transhepatic procedures, such as PTDD [5, 9]. Recently, insertion References 1. Fuchs CS, Mayer RJ. Gastric carcinoma. N Engl J Med 1995; 33: Gale ME, Gerzof SG, Kiser LC et al. CT appearance of afferent loop obstruction. AJR Am J Roentgenol 1982; 138: Herrington JL Jr. Roux-en-Y diversion as an alternate method of reconstruction of the alimentary tract after primary resection of the stomach. Surg Gynecol Obstet 1976; 43: Miranda R, Steffes B, O Leary JP et al. Surgical treatment of the postgastrectomy dumping syndrome. Am J Surg 1980; 139: Yao NS, Wu CW, Tiu CM et al. Percutaneous transhepatic duodenal drainage as an alternative approach in afferent loop obstruction with secondary obstructive jaundice in recurrent gastric cancer. Cardiovasc Intervent Radiol 1998; 21: Hsu CH, Yeh KH, Chen LT et al. Weekly 24-hour infusion of highdose 5-fluorouracil and leucovorin in the treatment of advanced gastric cancer: an effective and low-toxic regimen for patients with poor general condition. Oncology 1997; 54: Yeh KH, Cheng AL. Gastric cancer associated with acute disseminated intravascular coagulation: successful initial treatment with weekly 24-hour infusion of high-dose 5-fluorouracil and leucovorin. Br J Haematol 1998; 100:

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