Quality of Life in Patients with Esophagojejunal Anastomosis after Total Gastrectomy for Cancer

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1 Quality of life after total gastrectomy for cancer Quality of Life in Patients with Esophagojejunal Anastomosis after Total Gastrectomy for Cancer Rãzvn Scurtu, Nicoleta Groza, Ovidiu Oþel, Alcora Goia, Gheorghe Funariu 1 st Surgical Clinic, University of Medicine and Pharmacy, Cluj-Napoca Abstract Objective. To analyze the influence of the esophagojejunostomy type (Roux-en-Y end-to-end or end-to-side, omega, manual or mechanic), of the associated resections and postoperative complications, on patients Quality of Life (QoL) after total gastrectomy for cancer. Methods. From 1997 to 2004, 63 patients underwent a total gastrectomy for cancer. Patients were invited to fill a questionnaire with 14 treatment-specific related symptoms at 3, and respectively, 12 months postoperatively. The present study comprises 39 patients, all without cancer recurrence, who completed all required items. Results. The QoL was not influenced by the patients age and gender, associated resections or by the esophagojejunostomy type. Anastomotic fistula significantly influenced patients appetite at 3 months (p=0.013). At 12 months postoperatively there was a significant difference between the patients body weight when end-to-end anastomosis was compared to end-to-side anastomosis (p=0.023). The patients QoL improved in a significant manner at 12 months postoperatively, compared to their QoL at 3 months. Conclusions. After total gastrectomy for cancer, patients QoL is not significantly influenced by the type of the esophagojejunostomy. The end-to-end esojejunal anastomosis seems to have a less deleterious effect on the postoperative weight loss. Anastomotic fistula remains the only complication with some influence on patients QoL in the first postoperative months. Key words Quality of life - total gastrectomy - esojejunal anastomosis Romanian Journal of Gastroenterology December 2005 Vol.14 No.4, Address for correspondence: Gheorghe Funariu, MD, PhD 1 st Surgical Clinic 1-3 Clinicilor Street Cluj-Napoca, Romania rrscurtu@yahoo.com Rezumat Obiectiv. Scopul acestui studiu este de a analiza influenþa diferitelor tipuri de anastomoze eso-jejunale (ansa în Y a la Roux termino-terminalã, termino-lateralã, ansa în omega, anastomoze mecanice sau manuale) asupra calitãþii vieþii (CV) la pacienþii cu gastrectomie totalã. Metodã. Intre 1997 si 2004 s-au efectuat 63 gastrectomii totale pentru cancer. In postoperator la 3 si respectiv 12 luni pacienþilor le-a fost adresat spre completare un chestionar cu 14 întrebãri privind simptome specifice dupã gastrectomia totalã. Prezentul studiu include 39 pacienþi fãrã semne de recidivã, care au completat integral chestionarul. Rezultate. Calitatea vieþii nu a fost influenþatã de tipul de anastomozã eso-jejunalã, de vârsta sau sexul pacienþilor, nici de rezecþiile asociate gastrectomiei. Prezenþa fistulei anastomotice a influenþat semnificativ apetitul pacienþilor la 3 luni postoperator (p=0,013). La 12 luni postoperator, diferenþa între greutatea corporalã a pacienþilor cu esojejunostomie termino-terminalã ºi cea a celor cu esojejunostomie termino-lateralã a fost semnificativã (p=0,023). Toþi pacienþii au prezentat o ameliorare semnificativã în timp a CV. Concluzii. Calitatea vieþii pacienþilor cu gastrectomie totalã nu este influenþatã de tipul de anastomozã eso-jejunalã. Totuºi ansa în Y a la Roux montatã în termino-terminal are un efect benefic asupra evoluþiei greutãþii pacienþilor comparativ cu anastomozele termino-laterale. Fistula anastomoticã este singura complicaþie care influenþeazã semnificativ CV, dar numai în primele luni postoperator. Introduction Radical surgery offers the only possibility for cure in patients with gastric cancer. Total gastrectomy is the option of choice for tumors located in the middle or proximal part of the stomach (1). Many reconstructive procedures have been developed in the efforts to resolve patients complaints and to improve their nutritional condition after total gastrectomy. However, the Roux-en-Y esophagojejunostomy (R-Y) remains the most commonly used type of reconstruction

2 368 following total gastrectomy (2). Roux-en-Y esophagojejunostomy can be done in an end-to-end or an end-to side fashion, using stitches or mechanical devices. Quality of life (QoL) is a multidimensional construct comprising functioning and well-being, emotional, physical and social aspects and perceived symptom burden of the disease and side effects of treatment. After potentially curative treatment, debilitating problems such as malnutrition, fatigue and postprandial symptoms frequently occur. Several studies compared various methods of digestive reconstruction following total gastrectomy and their influence on the postoperative QoL but focused especially on the usefulness of the gastric pouches (3-5). Other studies assessed the influence of the extent of lymphadenectomy on patients QoL (6,7). Reports concerning the influence of the type of the esophagojejunostomy on the QoL and furthermore, comparing manual and mechanical anastomosis, are lacking. This study was undertaken to compare subjective and functional results of different reconstruction procedures after total gastrectomy for cancer: R-Y end-to-end, R-Y end-toside, omega loop, manual and mechanical esophagojejunostomy. Subjects and methods Between July 1997 and July 2004, 63 patients underwent a total gastrectomy for cancer in our department. All patients were included, after their informed consent, in a prospective study in order to analyze the impact of the digestive reconstruction type on the postoperative outcome. The operative technique has already been described elsewhere (8). Patients were closely followed-up and data were updated by personal contacts with patients during follow-up visits, letters and phone calls to referring physicians and general practitioners, and by phone calls to the patients or their families. QoL was assessed by measuring the treatment of specific symptoms according to the Korenaga et al (9) questionnaire modified by Wu et al (10). All patients were invited to fill a 14 item questionnaire (Table I) at 3 and respectively 12 months postoperatively. High scores reflect a better QoL. Patients who did not fill all items at 3, respectively 12 months after surgery, or in whom recurrence was suspected, were not included in this study. Thirty nine patients completed all items. All patients were disease free one year after surgery. The patients median age was 65 years (range 43-77). There were 11 females (28.2%) and 28 males (71.8%). Thirty-five patients underwent total gastrectomy for gastric adenocarcinoma (89.7%), 3 patients for gastric lymphoma (7.6%) and one presented with a voluminous malignant stromal tumor (2.7%). The TNM postoperative staging, according to the AJCC Cancer Staging Manual (12), of patients with gastric adenocarcinoma was as follows: stage I 4 patients (10.2%), stage II 12 patients (30.7%), stage IIIA 12 patients (30.7%), 3 patients stage IIIB (8%) and 4 patients (10.2%) stage IV Table I Korenaga s score Symptoms Scurtu et al Score Appetite Good 2 Fair 1 Poor 0 Consistency of food Normal 2 Soft 1 Liquid 0 Volume of food Increased 2 Unchanged 1 Decreased 0 Frequency of eating 3 times times 1 > 6 times 0 Eating time <30 minutes minutes 1 >60 minutes 0 Postprandial abdominal fullness Heartburn Diarrhoea Constipation Insomnia Body weight Increased or unchanged 3 Decreased <5kg kg 1 >10 kg 0 Swallowing problem Vomiting Dizziness respectively. Total gastrectomy was indicated in all patients because of the primary tumor location: gastric body and antrum in 4 patients, gastric body in 13, gastric and fornix in 7 and a tumor located to the cardia in 11. Digestive continuity was realized by R-Y esophagojejunostomy in 38 patients and by an omega loop anastomosis in one patient.

3 Quality of life after total gastrectomy for cancer 369 Table II QOL at 3 months after total gastrectomy No. Symptoms Anastomoses (score) End-to-end End-to-side Manual Mechanical Stapler diameter (score) <28 mm >28 mm Appetite Consistency of food Volume of food Frequency of eating Eating time Postprandial abdominal fullness Heartburn Diarrhea Constipation Insomnia Body weight Swallowing problem Vomiting Dizziness 0.957(0.638) 0.867(0.743) 0.727(0.647) 1(0.667) 1.087(0.668) 1.2(0.562) 1.273(0.647) 1.107(0.629) 0.261(0.449) 0.467(0.516) 0.455(0.522) 0.286(0.460) 0.696(0.470) 0.400(0.507) 0.273(0.467) 0.679(0.476) 1(0.309) (0.258) 1.1(0.316) 0.964(0.331) 0.217(0.422) 0.200(0.414) 0.091(0.302) 0.250(0.441) 0.913(0.515) 1.200(414) 1.273(0.467) 0.893(0.497) 1.091(0.526) 1.200(0.561) 1.100(0.568) 1.143(0.525) 0.826(0.388) 0.667(0.488) 0.818(0.405) 0.750(0.441) 0.739(0.541) 0.800(0.775) 0.636(0.674) 0.821(0.612) 1.217(0.600) 1.200(0.561) 1.273(0.647) 1.179(0.548) 1.609(0.499) 1.533(0.516) 1.364(0.505) 1.643(0.488) 1.435(0.590) 1.467(0.516) 1.545(0.522) 1.429(0.573) 1.739(0.541) 1.800(0.414) 1.727(0.467) 1.786(0.499) 0.867(0.516) 1.154(0.801) 1.267(0.594) 1.308(0.480) 0.267(0.458) 0.308(0.480) 0.733(0.458) 0.615(0.506) 0.867(0.352) 1.077(0.277) 0.133(0.352) 0.385(0.506) 0.867(0.516) 0.923(0.494) 1.067(0.458) 1.231(0.599) 0.800(0.414) 0.692(0.480) 0.933(0.594) 0.692(0.630) 1.467(0.516) 0.846(0.376) 1.667(0.488) 1.615(0.506) 1.400(0.632) 1.462(0.519) 1.933(0.258) 1.615(0.650) Values are expressed as mean± standard deviation Table III QOL at 12 months after total gastrectomy No. Symptoms Anastomoses Stapler diameter (score) (score) End-to-end End-to-side Manual Mechanical <28 mm >28 mm Appetite Consistency of food Volume of food Frequency of eating Eating time Postprandial abdominal fullness Heartburn Diarrhea Constipation Insomnia Body weight Swallowing problem Vomiting Dizziness 1.391(0.656) 1.333(0.617) 1.545(0.688) 1.286(0.600) 1.267(0.594) 1.308(0.630) 1.565(0.507) 1.733(0.458) 1.727(0.467) 1.607(0.497) 1.467(0.594) 1.709(0.439) 0.957(0.209) 0.800(0.414) 0.727(0.467) 0.929(0.262) 0.867(0.352) 1(0.0) 1.087(0.417) 1.0(0.378) 1.0(0.447) 1.071(0.378) 1.067(0.258) 1.077(0.277) 1.217(0.422) 1.933(2.549) 2.182(2.960) 1.214(0.418) 1.133(0.352) 1.308(0.480) 1.087(0.288) 1.200(0.414) 1.091(0.302) 1.143(0.356) 1.133(0.352) 1.154(0.376) 1.435(0.507) 1.333(0.488) 1.182(0.405) 1.429(0.573) 1.400(0.632) 1.462(0.519) 1.609(0.499) 1.333(0.617) 1.455(0.688) 1.536(0.508) 1.533(0.516) 1.538(0.519) 1.087(0.417) 0.867(0.352) 1.0(0.0) 1.0(0.471) 1.133(0.352) 0.846(0.555) 1.087(0.668) 1.333(0.617) 1.273(0.647) 1.143(0.651) 1.267(0.594) 1.0(0.707) 1.870(0.344) 1.800(0.414) 1.909(0.302) 1.821(0.390) 1.800(0.414) 1.846(0.376) 1.826(0.388) 1.933(0.258) 1.909(0.302) 1.857(0.356) 1.867(0.352) 1.846(0.376) 1.739(0.449) 1.667(0.488) 1.636(0.505) 1.714(0.460) 1.667(0.488) 1.769(0.439) 1.913(0.288) 1.933(0.258) 2.00(0.0) 1.893(0.315) 1.867(0.352) 1.923(0.277) Values are expressed as mean± standard deviation p T-T/ Mechanical/ <28/>28 T-L Manual mm p T-T/ Mechanical/ <28/>28 T-L Manual mm

4 370 Twenty-eight anastomoses were performed using mechanical suture devices (71.7%) and 11 were performed manually (28.3%). In 8 patients (20.5%), associated resections had to be performed in order to achieve R0 resections: 7 splenopancreatectomies and 1 colon resection followed by immediate colon anastomosis. We analyzed the influence of the esojejunal anastomosis type (end-to-end or end-to-side R-Y, omega, manual or mechanic), of the stapler diameter (for the mechanically performed anastomosis), as well as of the associated resections and of the postoperative complications, especially of the anastomotic fistula, on the QoL after total gastrectomy at 3 and 12 months respectively. Values are expressed as mean ± standard deviation. The t-test, Mann-Whitney U test and Wilcoxon test were appropriately used. A value of p < 0.05 was considered statistically significant. All analyses were performed with the Statview Software (Abacus Concepts, Inc., Berkeley, California). Results Eleven patients (28.2%) developed postoperative complications. There were 5 anastomotic fistulas (12.8%), all in patients with Roux-en-Y esophagojejunostomy; 2 fistulas (5.1%) occurred in patients with end-to-end anastomosis and 3 (7.7%) after end-to-side anastomosis. Three fistulas (7.7%) occurred after manual anastomosis and 2 (5.1%) after mechanical anastomosis. Two patients (5.1%) developed intra-abdominal collections without any evidence of anastomotic or dudodenal fistula and were conservatively managed. One patient developed a duodenal fistula, two patients had postoperative pancreatic fistulas and another one developed bronchopneumonia. All these patients recovered under conservative treatment. The mean postoperative weight loss was 6.2 kg (ranges ). The QoL was not influenced by the age and gender of the patients, or by the associated resections. At 3 months after total gastrectomy, none of the 14 investigated symptoms was significantly influenced by the different types of esophagojejunostomy (end-to-end versus end-to-side and mechanical versus manual) or by the stapler diameter when mechanical anastomosis were performed (Table II). At 12 months postoperatively the global QoL was not influenced by any of the studied parameters (Table III). However, the patients body weight was significantly influenced by the end-to-end anastomosis compared to endto-side anastomosis (p=0.023). Patients with end-to-side anastomosis lost more weight (mean 6.7 kg) compared to those having an end-to-end anastomosis (mean 4.9 kg) (p=0.023). The global QoL at 3 and 12 months postgastrectomy in patients with postoperative complications did not differ from that recorded in patients with uneventful postoperative course, resulting in a non significant p for all the 14 analyzed Scurtu et al items. However, when only the presence of the anastomotic fistula was analyzed, we found a significant influence on patients appetite at 3 months postoperatively, when compared to patients without fistula (p=0.013) (Table IV). Table IV Influence of the anastomotic fistula on patients appetite at 3 months postoperatively Patients (n=39) Appetite (score) p Anastomotic fistula Yes (n=5) 0.200± No (n=34) 1.059±0.600 Values are expressed as mean± standard deviation The patients QoL improved at 12 months postoperatively in a significant manner compared with the QoL at 3 months (Table V). Only two items (vomiting and dizziness) showed no significant amelioration in time. On the other hand, a significant improvement (p=0.0001) was recorded for the volume of the ingested food, frequency of eating, postprandial abdominal fullness and patients body weight between the two studied periods. The only patient with omega type reconstruction presented significant postoperative heartburn (score= 0), with no improvement in time. This patient was included in the group of end-to side anastomosis for statistical purposes, since the other 13 studied parameters did not differ from those recorded in patients with R-Y esophagojejunostomy. Table V Evolution in time of QoL No. Parameters p 1 Appetite Consitency of food Volume of food Frequency of eating Eating time Postprandial abdominal fullness Heartburn Diarrhea Constipation Insomnia Body weight Swallowing problem Vomiting Dizziness Discussion During the last decade the QoL concept has became an important and a widely accepted measure of outcome in addition to traditional end-points such as survival, diseasefree survival or postoperative morbidity (12). Therefore, in surgery, knowledge of postoperative QoL should to be taken into consideration for clinical decision making regarding therapy (13). QoL assessement in patients undergoing surgery for cancer of the stomach is still a matter of debate. A variety of instruments have been used to measure QoL ranging from

5 Quality of life after total gastrectomy for cancer physician based measures of nutrition to symptom scores and more recently to generic instruments specific to patients with gastric cancer (14-16). Korenaga et al (9) developed in 1992 a questionnaire to measure treatment specific symptoms after gastrectomy for cancer, a questionnaire modified in 1997 by Wu (10). We decided to use the same instrument in order to assess the QoL of our patients since at the beginning of the present study there was no validated standardized-module specific for patients with gastric cancer. In fact, only in 2004, Blazeby et al. demonstrated the validity of the EORTC QLQ-STO 22, a questionnaire module designed to assess QoL in patients with gastric cancer (17). Diaz de Liano et al showed no relationship between any postoperative major complication and QoL after gastrectomy (6). The present study supports this conclusion since only the appetite at 3 months after surgery was significantly reduced when anastomotic fistula occurred, while none of the other 13 studied items were influenced and no other recorded complication had any significant effect on the patients QoL. The relatively high anastomotic fistula rate (12.8%) reported in the present series might be partially explained by a more thorough follow-up of patients with postoperative complications resulting in better completed questionnaires. In the present study, 8 patients (21.5%) underwent associated resections of adjacent organs. There were 7 distal splenopancreatectomies and one partial colectomy. Patients with or without associated resections had no significant differences between their global QoL. A similar conclusion was reported by Thybusch-Bernhardt et al in their series (7). Several studies showed a significant weight loss in patients undergoing total gastrectomy (18-20). The mean reported weight loss was around 6 kg. In the present series the mean weight loss was 6.2 kg (ranges ). Patients with end-to-side anastomosis lost more of their weight (mean 6.7 kg) compared to those having an end-to-end anastomosis (mean 4.9 kg). This is the first study which mentions a certain influence of the esophagojejunostomy type on the postoperative weight loss after total gastrectomy. Previous reports showed that only subtotal gastrectomy or in the case of total gastrectomy, digestive reconstruction with a gastric pouch favourably influence postoperative weight loss (4,5,18,19). Zieren et al (21) demonstrated that QoL after gastrectomy improves progressively during the first 6 months after surgery in patients without tumor recurrence. Our results confirm this trend since we recorded a significant improvement, at 12 months postoperatively, for 12 of the 14 studied items as compared with the findings at 3 months after surgery. Conclusions Patients QoL after total gastrectomy for cancer is not significantly influenced by the type of the esophagojejunostomy. However, at 12 months postoperatively, the end-to-end esojejunal anastomosis has a less deleterious effect on patients postoperative weight loss. Anastomotic fistula remains the most frequent postoperative complication and the only complication with some influence on patients QoL in the first postoperative months. References Barbarisi A, Parisi V, Parmeggiani U et al. Impact of surgical treatment on quality of life of patients with gastrointestinal tumors. Ann Oncol 2001;12 Suppl 3: S Espat NJ, Karpeh M. Reconstruction following total gastrectomy: a review and summary of the randomized prospective clinical trials. Surg Oncol 1998;7: Adachi S, Inagawa S, Enomoto T et al. Subjective and functional results after total gastrectomy: prospective study for longterm comparison of reconstruction procedures. Gastric Cancer 2003; 6: Nozoe T, Anai H, Sugimachi K. 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