Ampullary carcinoma: Treatment and prognosis

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Ampullary carcinoma: Treatment and prognosis Authors David P Ryan, MD Harvey Mamon, MD, PhD Carlos Fernandez-del Castillo, MD Disclosures All topics are updated as new evidence becomes available and our peer review process is complete. Literature review current through: Oct 2013. | This topic last updated: Nov 8, 2013. INTRODUCTION — Periampullary tumors are neoplasms that arise in the vicinity of the ampulla of Vater. Neoplasms that arise in this site can originate from the pancreas, duodenum, distal common bile duct (CBD), or the structures of the ampullary complex. The ampulla of Vater is formed by the duodenal aspect of the sphincter of Oddi muscle, which surrounds the confluence of the distal CBD and main pancreatic duct as well as the papilla of Vater, a mucosal papillary mound at the distal insertion of these ducts on the medial wall of the duodenum (figure 1). Ampullary carcinomas are defined as those that arise within the ampullary complex, distal to the confluence of the distal common bile duct and the pancreatic duct (figure 2). It can be difficult to distinguish a primary ampullary carcinoma from other periampullary tumors preoperatively. However, true ampullary cancers have a better prognosis than periampullary malignancies of pancreatic or bile duct origin. Resectability rates are higher, and five-year survival rates are approximately 30 to 50 percent in patients with limited lymph node involvement. In contrast, fewer than 10 percent of patients with completely resected nodepositive pancreatic cancer are alive at two years. Thus, an aggressive approach to diagnosis and treatment of periampullary tumors is needed to ensure that patients with these comparatively favorable cancers are treated optimally. This topic review will cover the treatment and prognosis of ampullary carcinomas. The epidemiology, biologic behavior, clinical manifestations, diagnosis and staging are covered separately. (See "Ampullary carcinoma: Epidemiology, clinical manifestations, diagnosis and staging".) TREATMENT FOR LOCALIZED DISEASE — The only potentially curative treatment for ampullary carcinoma is surgical resection. Complete tumor resection with negative margins (R0 resection) is a prerequisite for cure. Pancreaticoduodenectomy — Pancreaticoduodenectomy (Whipple operation) is considered the standard approach for ampullary cancer (figure 3). This can be done as a pylorus-preserving procedure or as a conventional pancreaticoduodenectomy, which includes an antrectomy (figure 4). Although some authors claim advantages of a pylorus-preserving procedure because of a shorter operative time and less intraoperative blood loss [1], this is based on European variations of the technique which require creation of a Roux-en-Y to anastomose separately the gastric from the pancreatic and biliary anastomosis. Otherwise, there are no differences in long-term survival, and some series have shown higher incidence of delayed gastric emptying with the pylorus preservation. The impact of a pylorus-preserving procedure on long-term gastrointestinal function is less certain. Some studies suggest an improved nutritional state (as reflected by faster weight gain in the first postoperative year), but results have been inconsistent. (See "Pancreaticoduodenectomy (Whipple procedure): Techniques" and "Surgery in the treatment of exocrine pancreatic cancer and prognosis", section on 'Pancreaticoduodenectomy'.) Surgical outcomes from pancreaticoduodenectomy for ampullary cancer have improved over time. In contemporary
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Section Editor Kenneth K Tanabe, MD

Deputy Editor Diane MF Savarese, MD

Ampullary carcinoma: Treatment and prognosis

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single-institution series, rates of potentially curative resection have increased from approximately 80 to over 90 percent [2-6]. Long-term survival is possible after pancreaticoduodenectomy, even for patients with lymph node metastases or invasion beyond the duodenal wall (T3 disease, (table 1)). (See 'Prognosis' below.) Although pancreaticoduodenectomy has been associated with high perioperative morbidity and mortality rates in the past, contemporary series show that in experienced hands, perioperative (30-day) mortality rates are between 0 and 5 percent [2-10]. Perioperative morbidity rates are between 20 and 40 percent, with the most common problems being pneumonia, intraabdominal infection, anastomotic (pancreatic) leak, and delayed gastric emptying [11,12]. (See 'Complications' below.) These improved outcomes have been attributed to better operative technique and postoperative care. One of the most important reasons for this is the greater experience of a limited number of surgeons who perform the procedure regularly in high-volume institutions [13-15]. Good outcomes have been described even in patients older than 80 years in such centers. However, even within high-volume hospitals, operative mortality rates from pancreaticoduodenectomy vary considerably depending upon the experience of the individual surgeon [16]. Preoperative biliary drainage — The most common presenting symptom of ampullary carcinoma is obstructive jaundice (80 percent) caused by compression of the distal bile duct by the tumor. (See "Ampullary carcinoma: Epidemiology, clinical manifestations, diagnosis and staging".) The role of preoperative biliary drainage in patients with periampullary tumors is controversial. Because obstructive jaundice can impair hepatic, renal, and immune function, it was hoped that preoperative relief of jaundice would correct these defects and decrease postoperative morbidity and mortality rates from pancreaticoduodenectomy. However, the available data from randomized trials of preoperative drainage versus no drainage are conflicting. Furthermore, three meta-analyses examining the benefit of preoperative biliary drainage for patients with obstructive jaundice have come to different conclusions, with one finding neither an adverse nor a favorable impact of preoperative stenting on the incidence of postoperative morbidity or mortality, another finding an overall adverse impact of stenting on the postoperative complication rate, and the third, significantly fewer postoperative complications in the stented group but no impact on postsurgical mortality. (See "Pancreaticoduodenectomy (Whipple procedure): Techniques" and "Surgery in the treatment of exocrine pancreatic cancer and prognosis".) In the specific setting of ampullary cancer, the benefit of preoperative biliary drainage was addressed in a retrospective series of 82 patients undergoing potentially curative surgery at a single hospital in Singapore; 35 were drained preoperatively and 47 were not [17]. Preoperative drainage was associated with a significantly reduced incidence of postoperative wound infection (3 versus 26 percent), but there was no favorable impact on other postoperative complications or survival. Uncertainty as to the benefit of preoperative drainage has led to differing approaches. Some surgeons routinely decompress jaundiced patients with an endoscopically placed stent prior to surgery. However, others reserve biliary decompression for selected patients in whom surgery will be delayed or those with debilitating pruritus or a clinical picture of cholangitis with fever and leucocytosis. In practice, the majority of patients who present with obstructive jaundice will have been stented by a gastroenterologist before the diagnosis is established and it is known whether or not the patient is a surgical candidate; the surgeon usually has little influence on the decision. For those who are not stented, our preference is to proceed with ERCP and stenting only when there is high grade jaundice (>15 mg/dl of bilirubin) and surgery will not take place within the following week. The prognostic implication of obstructive jaundice at presentation on prognosis is discussed below. (See 'Obstructive jaundice' below.) Complications — The most frequent treatment-related complication of pancreaticoduodenectomy is pancreatic fistula, and the rates are higher for patients with ampullary cancer than for pancreas cancer because the pancreatic parenchyma is typically normal in ampullary carcinoma. Other complications include delayed gastric emptying,

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and postoperative diabetes as a result of pancreatic resection. Intraoperatively. In contrast. Early. sepsis. Tis. in other series. eight cases were converted from ampullectomy to pancreaticoduodenectomy because of disease extent or a frozen-section finding of invasive tumor. ampullectomy does not accomplish removal of the regional lymph nodes. (See "Treatment of ampullary adenomas". while local ampullary excision could be considered for high-risk patients with well-differentiated T1 ampullary cancers that are less than 6 mm based on endoscopic ultrasound (EUS). However. and only one was alive at last follow-up. in which most of the patients were considered high-risk candidates for surgery [2. This has generated interest in less aggressive surgical options. (See "Pancreaticoduodenectomy (Whipple procedure): Techniques". T1) well differentiated ampullary cancers without angiolymphatic invasion [35]. a more aggressive surgical approach is preferred by most surgeons for invasive tumors. 45 percent of patients with pathologically confirmed T1 invasive ampullary adenocarcinomas had lymph node metastases [38]. Furthermore. seven recurred. In the aggregate. Because of the low rate of nodal metastases (less than 4 percent in most series). and photodynamic therapy. bile leaks. at least in the setting of invasive disease [11. of the 91 patients undergoing pancreaticoduodenectomy during the same time period for invasive adenocarcinoma.2 cm) that was thought to represent a benign adenoma after a preoperative biopsy [31]. Recommendations for management of ampullary carcinoma are not included in published guidelines from either the National Comprehensive Cancer Network (NCCN) [39] or the European Society for Medical Oncology (ESMO) [40].34-37].) Endoscopic papillectomy has been attempted in early stage (Tis. However. 21:47 hemorrhage. The literature on these techniques in the setting of ampullary carcinoma is limited to single-case reports and small series. range 0. A major concern is the inferior cancer-specific survival following local resection of small ampullary invasive carcinomas in the analysis from Sloan-Kettering described above [35].uptodate. Eight of the 29 patients treated by ampullectomy alone had invasive tumor on the final histology. (table 1)) [28. 68 were still alive at the end of the study period.Ampullary carcinoma: Treatment and prognosis 14/11/13. Comparison of these studies with each other is limited by different eligibility criteria for ampullectomy and the fact that the extent of surgery (eg. and few had carcinomas. 49 without recurrence. ● Endoscopic snare resection (papillectomy) is an effective means of treating ampullary adenomas. as long as the patient is a reasonable candidate for pancreaticoduodenectomy. In our view. Experience with this approach is limited to small published series. but at the expense of higher recurrence rates and inferior survival. the majority of the patients reported in these series had ampullary adenomas. such as local resection or ampullectomy for selected patients.) Local resection — Many patients with ampullary cancer are elderly and have significant comorbidities. The largest series included 37 patients who were planned for ampullectomy rather than pancreaticoduodenectomy at Memorial Sloan-Kettering Cancer Center because of significant comorbidity or a small ampullary lesion (median 1. including well-differentiated T1 lesions. some have suggested that local resection is a reasonable approach for well-differentiated small (<6 mm) tumors that do not penetrate through the ampullary musculature (ie. Thus. the available data indicate that local resection is associated with lower morbidity than pancreaticoduodenectomy. Nd:YAG laser ablation.23. low-grade tumors — In contrast to pancreaticoduodenectomy. T1.5 cm. "ampullectomy" versus "local resection") has not always been clearly specified. local resection (ampullectomy with lymph node sampling) is a reasonable alternative to pancreaticoduodenectomy for selected patients with noninvasive (pTis) tumors (table 1).29-33].com/contents/ampullary-carcinoma-treatment-…duodenectomy&selectedTitle=3%7E47&view=print&displayedView=full Página 3 de 24 .21. acceptance of this method for definitive treatment is hampered http://www. Minimally-invasive nonsurgical therapies — Minimally invasive nonsurgical therapies for ampullary carcinoma include endoscopic snare resection.18-28]. if the patient can tolerate this approach. pancreaticoduodenectomy is preferred for any invasive adenocarcinoma.4 to 4. However.

Summary — While potentially curative in the setting of ampullary adenomas. stratified according to surgical stage (table 1) was as follows [11]: ● Stage I – 84 percent ● Stage II – 70 percent ● Stage III – 27 percent ● Stage IV – 0 percent About two-thirds of patients surviving five years after pancreaticoduodenectomy for ampullary carcinoma are also alive at 10 years [57].41-44]. and from 17 to 50 percent for node-positive disease [2. photodynamic therapy (PDT) eradicates local tumor with less surrounding tissue destruction. In one such series of 12 patients with ampullary cancer. section on 'Epidemiology and biologic behavior'. Five-year overall survival in one retrospective single-institution series. 21:47 by the inadequacy of biopsy in terms of correct pathologic characterization of the lesion (and therefore its risk of harboring lymph node metastases) and the inability to predict successful.) http://www.18.30.4. all three modalities of nonsurgical treatment provide palliative rather than curative benefit for patients with ampullary carcinoma. (See "Ampullary carcinoma: Epidemiology. margin-negative endoscopic resection [20.com/contents/ampullary-carcinoma-treatment-…duodenectomy&selectedTitle=3%7E47&view=print&displayedView=full Página 4 de 24 .uptodate. PROGNOSIS — The outcome of resected ampullary cancer depends upon the extent of local invasion. Photofrin®). PDT uses a photosensitizing drug (a hematoporphyrin derivative. Irradiation with visible light via a light-transmitting catheter (light-guide) placed through an endoscope and targeted at the tumor energizes the photosensitizing molecule within the tumor and catalyzes oxygen free-radical generation leading to cell death [46].) In the largest series of PDT involving 10 patients with ampullary cancer.48-50]. diagnosis and staging".7-11. duodenal obstruction was relieved in one. ● Compared with laser ablation. Five-year survival rates following pancreaticoduodenectomy range from 64 to 80 percent for patients with node-negative disease. Tumor bulk was greatly reduced in four additional patients. The major side effect of PDT is prolonged cutaneous photosensitivity after the procedure. Epidemiology and End Results) database between 1988 and 2003 are presented in the table (table 2) [50]. (See "Photodynamic therapy for ablation of Barrett's esophagus".Ampullary carcinoma: Treatment and prognosis 14/11/13. As an example.29. Outcomes tend to be somewhat worse in population-based analyses. Endoscopic debulking has been used mainly preoperatively to permit stent insertion and decompression of the biliary tree. which is disproportionately retained by malignant tissue after intravenous administration. clinical manifestations. status of the surgical margins. requiring the patient to avoid sunlight and wear appropriate clothing to protect the skin for several weeks after treatment.11. These methods are appropriate only for patients who are not operative candidates and those who refuse surgery. and the presence or absence of nodal metastases [5. while little effect was observed in the remaining three. ● Laser ablation offers the potential for control of local tumor growth in patients who are unfit for more aggressive therapy. It is unclear whether this represents a true difference in biology or earlier presentation of ampullary cancers due to earlier biliary obstruction. particularly for those with nodepositive disease. remission was achieved for 8 to 12 months in three who had small tumors confined to the ampulla [47].13. These survival data are better than similar presentations for pancreatic cancer. The controversy surrounding the need for preoperative biliary decompression is discussed above (see 'Preoperative biliary drainage' above). five-year survival rates stratified by stage at presentation from a series of 1301 patients with ampullary cancer reported to the National Cancer Institute SEER (Surveillance. and the longest survival was 36 months (median 21 months) [45].51-56].

More recent data suggest that adenocarcinomas of the ampulla of Vater can be subdivided according to histologic subtype and immunohistochemical staining pattern into distinct subsets with differing biologic behavior. More evidence on the influence of histomolecular phenotypes in ampullary cancer is needed before conclusions can be drawn [68].55.69-71]: ● In a report of 66 patients undergoing resection for an ampullary cancer. among patients with nodal metastases. and 46 from Verona.uptodate. with some suggesting no difference. Australia. ● Patients with a node-positive. is also of prognostic importance [6. In contrast. is unclear. The median number of resected nodes was 16.Ampullary carcinoma: Treatment and prognosis 14/11/13. adjuvant therapy recommendations for patients with ampullary cancer follow guidelines established for pancreatic cancer rather than intestinal cancer. The impact of adjuvant therapy on outcomes according to histomolecular phenotype could not be addressed in the study since only a minority of patients (64 of 208) in all three cohorts received adjuvant chemotherapy. The incidence of positive margins is low (3 percent in one series [6]). the available data are conflicting. Histology — In addition to depth of tumor invasion (the T stage.9. (table 1)) and nodal status. However. MUC1-negative).com/contents/ampullary-carcinoma-treatment-…duodenectomy&selectedTitle=3%7E47&view=print&displayedView=full Página 5 de 24 .18. Italy. none of the 15 patients with three or more involved nodes remained alive beyond 28 months. MUC1 positive) had a significantly worse outcome than did those with an intestinal phenotype (CDX-positive.60. ● The number of involved nodes divided by the total number of examined nodes is referred to as the lymph node ratio (LNR). pancreaticobiliary phenotype had a poor prognosis (five-year survival 20 percent). high-grade histology and positive surgical margins are associated with a worse prognosis [2. node-negative pancreaticobiliary phenotype) had an intermediate prognosis (five-year survival 47 percent). median survival 16 versus 116 months [67]. At present.) Nodal metastases — The presence of nodal involvement portends a worse prognosis. and others. Five-year survival was also predicted by the LNR: http://www. a worse prognosis for the pancreaticobiliary type [65-67]. particularly when compared to the incidence of positive margins in resected pancreatic adenocarcinoma (40 percent in the same series). 21:47 Prognostic factors — The following sections will summarize the available data on predictors of recurrence. those with a histomolecular pancreaticobiliary phenotype (CDX-negative. Whether there is a correlation between prognosis and morphologic type (ie. The results were comparable in two additional independent cohorts of 90 patients from Glasgow. non-pancreaticobiliary phenotype. (See 'Adjuvant therapy' below.11. When histomolecular phenotype was combined with the lymph node status. particularly with regard to adjuvant therapy.58-64]. the number of affected nodes. and it was not randomly assigned. Scotland. and patients with 16 or more examined nodes had a significantly lower recurrence rate and better five-year survival (81 versus 45 percent) than patients whose pathology material contained 16 or fewer nodes. One study evaluated the utility of using the LNR for predicting recurrence and survival in 90 patients who underwent resection of ampullary carcinoma [69]. three subsets of ampullary adenocarcinomas emerged with significantly different survival outcomes: ● Patients with a node-negative. particularly compared to the total number of examined nodes. ● The remaining patients (node-positive.54. intestinal versus pancreaticobiliary) is unclear. non-pancreaticobiliary histomolecular phenotype tumor had an excellent prognosis (five-year survival 88 percent).6. In a retrospective study of a cohort of 72 patients treated for ampullary adenocarcinoma in Sydney. five-year survival rates were similar among the 13 patients with two or fewer positive lymph nodes and the 38 with node-negative disease (approximately 50 percent) [60]. Whether and how this information could be used to individualize treatment decisions.

respectively. The most common site of distant spread is the liver. clinical manifestations. respectively. the optimal cutoff levels of CA 19-9 to stratify risk for disease recurrence was >150 units/mL in non-jaundiced patients and >300 units/mL in the presence of cholestasis [76]. In one study. although others note a predominance of distant metastases [52.76]. patients who required intraoperative transfusion of more than three units of red blood cell units had worse outcomes than those requiring less blood [75]. lymph node metastasis was the sole risk factor for distant recurrence. These data could be interpreted as demonstrating that early detection of ampullary carcinoma prior to the onset of obstructive jaundice is associated with a better oncologic outcome. diagnosis and staging".uptodate. 29 of 125 patients who underwent definitive surgery for an ampullary cancer received adjuvant RT with concurrent 5FU. A prospective.) Patterns of recurrence — In many series. whether there is a role for extended lymphadenectomy) are unclear.2 to ≤0. Therefore.4 – 0 percent In contrast to other GI tumor sites. requiring more intraoperative dissection) than those who do not require transfusion. (See "Ampullary carcinoma: Epidemiology.2 – 49 percent • LNR >0. and the risk factors for locoregional recurrence were the presence of pancreatic invasion and tumor size. The median time to recurrence was 11. The implications of these data on the extent of lymph node dissection (ie. The role of preoperative biliary drainage in patients who present with obstructive jaundice is addressed above (see 'Preoperative biliary drainage' above). five. suggesting the need for effective adjuvant therapy.Ampullary carcinoma: Treatment and prognosis 14/11/13.com/contents/ampullary-carcinoma-treatment-…duodenectomy&selectedTitle=3%7E47&view=print&displayedView=full Página 6 de 24 .77]. 21:47 • LNR = 0 – 75 percent • LNR >0 to ≤0. and do not routinely perform extended lymphadenectomy in these patients.63]. The risk factors for locoregional and distant recurrence are slightly different. In multivariate analysis. The authors concluded that the added morbidity of extended lymphadenectomy could not be justified by the better oncologic outcomes.4 months.and ten-year survival rates were 70 and 49 percent. lymph node status emerged as http://www. ADJUVANT THERAPY — Despite the high rate of potentially curative resections in contemporary series. In one study. In one of the largest reports from the Mayo Clinic. There are few published data to guide the use of adjuvant therapy in patients with resected ampullary cancer. Obstructive jaundice — Patients who present with obstructive jaundice tend to have a worse prognosis. randomized study of 62 patients who underwent resection of ampullary carcinoma found no difference in the five-year survival in the group undergoing standard versus extended lymphadenectomy (56 versus 60 percent) [73]. but other sites include peritoneum.4 – 38 percent • LNR >0.52. In contrast. in patients who were jaundiced at presentation [74]. Intraoperative blood transfusion — In a systematic review.78-83]. recurrences are about evenly split between locoregional recurrence and distant spread [10. Chemoradiotherapy — Benefit from postoperative chemoradiotherapy in patients with completely resected disease has been suggested in several uncontrolled series [58.77]. the number of lymph nodes does not influence N stage (table 1) [72]. This was shown in a series of 127 patients who underwent pancreaticoduodenectomy with regional lymphadenectomy for ampullary carcinoma [10]. in patients who did not present with obstructive jaundice versus 34 and 29 percent. supraclavicular lymph nodes and lung [10. while the remainder received no adjuvant therapy [78]. However. We agree with this conclusion. bone. The surgeon and pathologist should aim to dissect and analyze at least 12 lymph nodes. more than one-half of patients die from recurrent disease. Tumor marker elevation — Elevated preoperative levels of the serum tumor markers CA 19-9 and CEA are associated with a poorer prognosis relative to individuals with normal values [52. the independent contribution of intraoperative blood transfusion to outcomes remains uncertain. patients who require transfusion tend to be sicker as a group (or their tumors are more advanced. section on 'Serum tumor markers'. Both pancreatic invasion and lymph node involvement were significant predictors of inferior survival.

and 11 percent in the control group. 95% CI 0.uptodate. or single agent gemcitabine (1000 mg/m2 weekly for three of every four weeks for six months) [87]. daily for five days. we suggest that these patients be managed in a manner similar to the approach used for resected pancreatic cancer. Overall survival rates at one. HR 0. and there were more serious adverse effects in the FU group as well.57-1.77.) Chemotherapy alone — The benefit of adjuvant chemotherapy for resected ampullary adenocarcinomas was directly studied in the international ESPAC-3 trial.) http://www.98) and for gemcitabine alone (HR 0. section on 'EORTC study'.11).75. 35 other) were randomly assigned to one of three arms: observation alone. Summary — The results of clinical trials are not definitive.89] and the lack of data from randomized trials proving a survival advantage. leucovorinmodulated 5-FU (six courses of leucovorin 20 mg/m2 IV bolus followed by 5-FU 425 mg/m2. For the 104 periampullary cancers (which included cancers of the ampulla.86. and 59 percent had node-positive disease.57-0. the median survival in the FU/leucovorin group was 57. the 24 patients who received adjuvant therapy survived significantly longer than the 30 who did not receive it. even for those who have the intestinal histomolecular phenotype. there was no difference in the two-year survival rate (67 versus 63 percent) or in the incidence of locoregional recurrence in the treated patients compared to controls. The only other randomized trial that addressed the benefit of adjuvant chemotherapy was a multicenter randomized trial from Japan that compared surgery with and without postoperative chemotherapy (two courses of mitomycin C plus infusional 5-FU. Posthoc analysis did not show differential treatment responsiveness based upon histologic subtype. In a trial from the EORTC. once per month). Although of a greater magnitude.com/contents/ampullary-carcinoma-treatment-…duodenectomy&selectedTitle=3%7E47&view=print&displayedView=full Página 7 de 24 . and there is no consensus regarding the optimal management of patients after resection of an ampullary cancer. other retrospective comparisons [84. On the other hand. 95% CI 0.8 months. However. followed by prolonged oral administration of 5-FU until tumor progression) in 508 patients with pancreaticobiliary tract cancer (56 with ampullary cancer) [88]. the difference in median survival between gemcitabine-treated and observed patients was still not statistically significant (median 46 versus 35 months. but not in those with ampullary cancer (five-year survival 28 versus 34 percent in the chemotherapy and control groups. 95% CI 0. but grade 3 or 4 stomatitis (11 versus 0 percent) and diarrhea (14 versus 4 percent) were significantly more common with leucovorin-modulated FU. those treated with gemcitabine had a median survival that was almost twice as long as those in the observation group (median 71 versus 41 months). when the analysis was restricted to patients with ampullary cancer. and five years in the adjuvant therapy group were 91. The use of adjuvant chemotherapy was associated with a potentially meaningful overall survival advantage but it was not statistically significant (median 43 versus 35 months. in which 428 patients with periampullary malignancies (297 ampullary. citing the more favorable prognosis of ampullary as compared to other biliary tract cancers [59.510. 95% CI 0.66 to 1. Recommendations for management of ampullary carcinoma are not included in published guidelines from either the NCCN [39] or ESMO [40]. Many clinicians do not recommend adjuvant chemoradiotherapy or chemotherapy for resected ampullary cancers. compared to 66.70. A complete (R0) resection was achieved in 84 percent of patients.Ampullary carcinoma: Treatment and prognosis 14/11/13. There was no difference in overall survival between the chemotherapy arms. Furthermore. (See "Adjuvant and neoadjuvant therapy for exocrine pancreatic cancer". 22. 54. However. A significant survival benefit for adjuvant chemotherapy was seen in the patients with gallbladder cancer (5-year survival 26 versus 14 percent). HR 0. Within the high-risk node-positive subgroup (n = 54). in secondary multivariate analysis adjusting for predefined prognostic variables. respectively). 218 patients with resected pancreatic or other periampullary cancers were randomly assigned to postoperative RT (40 Gy in split courses) plus concurrent 5-FU (25 mg/kg per day by continuous infusion) or observation [86]. 96 bile duct. and the only phase III randomized trial that included a substantial number of patients with ampullary carcinoma have failed to show a benefit for postoperative chemoradiotherapy. three.85]. there was a statistically significant survival benefit for any chemotherapy (HR for death 0. distal common bile duct or duodenum). 21:47 the only significant predictor of outcome.97).05). and 48 percent. (See 'Histology' above.

) Initial 5-FU-based chemoradiotherapy followed by four months of gemcitabine alone is an acceptable alternative.uptodate.) POSTTREATMENT SURVEILLANCE — Posttreatment surveillance to detect recurrent or persistent disease is performed at regular intervals. as we do in patients with pancreatic adenocarcinoma. although they represented a small minority [93]. There was a significant survival advantage to the combination both in terms of progression-free and overall survival. The utility of periodic CT scan of the abdomen is unclear. although this approach remains unproven for resected ampullary tumors. (See "Systemic therapy for advanced http://www.Ampullary carcinoma: Treatment and prognosis 14/11/13. the optimal way to sequence 5-FU-based chemoradiotherapy and gemcitabine alone is unclear. (See "Adjuvant and neoadjuvant therapy for exocrine pancreatic cancer". (See "Treatment of ampullary adenomas". Patients with ampullary cancer were included in the ABC trial of gemcitabine with and without cisplatin. particularly because of recent advances in treatment of advanced disease. and starting three to five weeks later. 21:47 The approach differs in Europe and in the United States. section on 'Unresectable or metastatic disease' and "Systemic therapy for advanced cholangiocarcinoma" and "Chemotherapy for advanced exocrine pancreatic cancer". largely because of the rarity of this disease. Many clinicians follow patients every six months for five years and annually thereafter. However. most European clinicians use chemotherapy alone after resection of either a pancreatic or ampullary cancer. (See "Treatment of localized cholangiocarcinoma: Surgical management and adjuvant therapy".) There is no consensus on the best management for patients with advanced ampullary carcinoma. and serum tumor markers (typically CEA and CA 19-9). which showed that 5FU-containing chemotherapy (but not chemoradiotherapy) prolongs survival in resected pancreatic cancer. Follow-up visits usually include history and clinical examination. followed by chemoradiotherapy with concurrent infusional 5-FU (250 mg/m2 daily). treating these patients more like those with advanced pancreatic cancer or small bowel adenocarcinoma [94]. which consists of three weekly doses of gemcitabine alone (1000 mg/m2 per week). which suggests a potentially clinically meaningful but statistically insignificant improvement in overall with adjuvant gemcitabine or leucovorin-modulated 5-FU [87]. although the optimal surveillance strategy is undefined [39]. An acceptable regimen is that used in RTOG 9704. although others disagree. or more commonly. We treat all patients with resected ampullary cancer stage IB or higher (table 1) like we do those with resected pancreatic adenocarcinoma using concurrent chemoradiotherapy with infusional 5-FU. (See "Treatment of small bowel neoplasms". or pancreatic origin is particularly important for the selection of the treatment approach. Given the risk for distant recurrence and the results from RTOG 9704 [92]. the distinction as to whether periampullary tumors are of intestinal. (See "Adjuvant and neoadjuvant therapy for exocrine pancreatic cancer". then annually for an additional three to five years. and the report of the ESPAC-3 trial. biliary. ampullary plus biliary tract cancers. results of the German CONKO trial [91] showing a survival benefit from adjuvant gemcitabine in the same patient population. pancreatic and ampullary adenocarcinomas. an approach used for resected extrahepatic cholangiocarcinoma. NCCN guidelines are not available. Based upon the ESPAC-1 trial [90].com/contents/ampullary-carcinoma-treatment-…duodenectomy&selectedTitle=3%7E47&view=print&displayedView=full Página 8 de 24 . A reasonable approach is surveillance endoscopy every six months for two years.) The American approach differs with regard to chemoradiotherapy. we also add a course of gemcitabine adjuvant chemotherapy to chemoradiotherapy.) As with pancreatic cancer. While the need for endoscopic surveillance is universally accepted. section on '5-FU plus irinotecan and/or oxaliplatin'. compared to gemcitabine alone. three months of single agent gemcitabine (1000 mg/m2 weekly for three of every four weeks) [92]. Many consider this to represent the standard regimen for advanced ampullary as well as biliary tract cancers. most published recommendations are similar to those reported after local resection of ampullary adenomas. (See "Adjuvant and neoadjuvant therapy for exocrine pancreatic cancer". as is concurrent 5-FU-based chemoradiotherapy alone. combined with those from the German CONKO trial [91]. Much of the data on chemotherapy for advanced ampullary cancer are in combined series that include patients with small bowel.) CHEMOTHERAPY FOR ADVANCED DISEASE — Limited data exist to guide physicians in the choice of chemotherapy.

uptodate. a more aggressive surgical approach is preferred for patients who are candidates for pancreaticoduodenectomy because of better outcomes. (See 'Pancreaticoduodenectomy' above.) The approach differs in Europe and in the United States: ● Based upon the ESPAC-1 trial. section on 'Unresectable or metastatic disease'.com/contents/ampullary-carcinoma-treatment-…duodenectomy&selectedTitle=3%7E47&view=print&displayedView=full Página 9 de 24 . (table 1)) (Grade 2B). The following represents our approach to patients with resected ampullary tumors: • Eligible patients should be encouraged to enroll in clinical trials evaluating the potential benefits of chemotherapy and/or chemoradiotherapy as well as new therapies.Ampullary carcinoma: Treatment and prognosis 14/11/13. Resectability rates are higher. We offer adjuvant therapy to all patients with resected ampullary cancer stage IB or higher (table 1). However. photodynamic therapy) provide palliative rather than curative benefit for patients with ampullary carcinoma. (See 'Minimally-invasive nonsurgical therapies' above.) Adjuvant therapy — There is no consensus regarding the optimal management of patients after resection of an ampullary adenocarcinoma. suggesting a potentially clinically meaningful but statistically insignificant improvement in overall survival with adjuvant gemcitabine or leucovorin-modulated 5-FU in ampullary cancer. (See 'Introduction' above and "Ampullary carcinoma: Epidemiology. endoscopic snare resection.) SUMMARY AND RECOMMENDATIONS — It can be difficult to distinguish a primary ampullary carcinoma from other periampullary tumors (mainly pancreatic carcinoma or distal cholangiocarcinoma) preoperatively. we prefer infusional 5-FU. true ampullary cancers have a better prognosis than pancreatic head cancers or distal cholangiocarcinomas. Thus. Ampullectomy is also a reasonable approach for poor surgical candidates who have a well-differentiated T1 tumor that is less than 6 mm in size (based upon endoscopic ultrasound [EUS]). clinical manifestations. which showed that 5-FU-containing chemotherapy (but not chemoradiotherapy) prolongs survival in resected pancreatic cancer. (See 'Local resection' above. we suggest a combination of concurrent chemoradiotherapy and chemotherapy for patients with resected ampullary cancers stage IB or higher (table 1) rather than observation alone (Grade 2C). including our group. and a preliminary report of the ESPAC-3 trial. There are scant data to guide adjuvant treatment decisions. and we use gemcitabine alone for the chemotherapy portion. • Off-protocol. treat these patients in a similar manner as those with resected pancreatic head adenocarcinomas. (See 'Adjuvant therapy' above. These methods should be restricted to patients who are not operative candidates and those who refuse surgery. and the true benefit of such therapy remains uncertain. many clinicians. laser ablation. Nevertheless.) ● We suggest local ampullary excision rather than pancreaticoduodenectomy for patients with noninvasive ampullary tumors (pTis. During the concurrent chemoradiotherapy portion. the German CONKO trial showing a survival benefit from adjuvant gemcitabine in the same patient population. and five-year survival rates are 30 to 50 percent in selected patients with limited lymph node involvement. most European clinicians use chemotherapy alone after resection of an ampullary neoplasm. an aggressive approach to diagnosis and treatment of periampullary tumors is needed to ensure that patients with these comparatively favorable cancers are treated optimally. diagnosis and staging". section on 'Gemcitabine plus cisplatin' and "Chemotherapy for advanced exocrine pancreatic cancer" and "Treatment of small bowel neoplasms". 21:47 cholangiocarcinoma".) ● The American approach more often includes chemoradiotherapy as well as adjuvant chemotherapy. (See "Adjuvant and neoadjuvant therapy for exocrine pancreatic cancer". However.) ● Nonsurgical treatment modalities (ie. http://www.) Primary treatment ● We recommend pancreaticoduodenectomy rather than local resection for most patients with invasive ampullary carcinomas (Grade 1B).

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Is postoperative adjuvant chemotherapy useful for gallbladder carcinoma? A phase III multicenter prospective randomized controlled trial in patients with resected pancreaticobiliary carcinoma. Balachandran P. et al. Sikora SS. Wang Q. et al. 75:436. Kim K. Chie EK. 77. Byrd DR. et al. et al. J Gastrointest Surg 2008. Compton CC. Chakravarthy A. 69. Int J Radiat Oncol Biol Phys 2000. Palta M. Balachandran P. 100:19. Kulig J. Ford JM. http://www. Amano H. Chang DK. et al. Arroyo GF. Eur J Surg Oncol 2005. Prognostic relevance of lymph node ratio and number of resected nodes after curative resection of ampulla of Vater carcinoma. Wolfgang CL. 76. Smith RA. p. Kapoor S. 31:158. Springer. part 2: randomized controlled trial evaluating survival. Broadwater G. 7th. Falconi M. Mehta VK. Sutton R. 19:1535. Cox TF. Sikora SS. J Clin Oncol 2013. 82. 86. Intraoperative allogeneic red blood cell transfusion in ampullary cancer outcome after curative pancreatoduodenectomy: a clinical study and meta-analysis. J Gastrointest Surg 2007. Bhatia S. Yeo CJ.uptodate. 68. 75. Role of adjuvant chemoradiation therapy in adenocarcinomas of the ampulla of vater. 40:162. and location of metastatic nodes. et al. morbidity. Ann Surg Oncol 2012. et al. Adjuvant chemo-radiotherapy in ampullary cancers. Pancreaticoduodenectomy with or without distal gastrectomy and extended retroperitoneal lymphadenectomy for periampullary adenocarcinoma. 83. Clinicopathologic features of ampullary carcinoma without jaundice.235. Intensified adjuvant combined modality therapy for resected periampullary adenocarcinoma: acceptable toxicity and suggestion of improved 1-year disease-free survival. American Joint Committee on Cancer Staging Manual. 92:244. 31:1348. 73. Radiother Oncol 2009. Lymph node involvement in ampullary cancer: the importance of the number. 79. J Surg Oncol 2009. et al. New York 2010. et al. Sierzega M. 89. 70. Miller RC. 74. Lillemoe KD. Trends in survival after surgery for cholangiocarcinoma: a 30-year population-based SEER database analysis. Ann Surg 1999. Shirai Y. 308:147. JAMA 2012. Yeo CJ. et al. Sahmoud T. et al. Yasuda H. Role of adjuvant chemoradiotherapy for ampulla of Vater cancer. Patel P. Number of positive lymph nodes independently affects long-term survival after resection in patients with ampullary carcinoma. Arch Surg 2001. Abrams RA. Domínguez I. Neoptolemos JP.Ampullary carcinoma: Treatment and prognosis 14/11/13. Hsu CC. Takada T. Edge SB. 31:3842. Johns AL. Ghaneh P. Jang JY. Hu ZQ. et al. Wakai T. Klinkenbijl JH. Histomolecular phenotypes and outcome in adenocarcinoma of the ampulla of vater. et al. Egawa N. Rana V. 70:735. Moore MJ. 236:355. Winter JM. Haddock MG. Pawlik TM. 15:3178. and mortality. Zhou J. Nathan H. 230:776. World J Surg 2008. Yao HS. 32:2038. Jeekel J. 12:1422. ratio. et al. 136:65. et al. 80. Ann Surg 2002. 71. 33:346. Sakata J. Adjuvant radiotherapy and 5-fluorouracil after curative resection of cancer of the pancreas and periampullary region: phase III trial of the EORTC gastrointestinal tract cancer cooperative group. Cancer 2002. Cameron JL. Effect of adjuvant chemotherapy with fluorouracil plus folinic acid or gemcitabine vs observation on survival in patients with resected periampullary adenocarcinoma: the ESPAC-3 periampullary cancer randomized trial. Dimri K. Pancreas 2006. et al (Eds). et al. 88. J Clin Gastroenterol 2006. Int J Radiat Oncol Biol Phys 2009. Krishnan S. Long-term survival and recurrence patterns in ampullary cancer. et al. et al. 78. Kamisawa T. Adjuvant chemoradiation versus surgery alone for adenocarcinoma of the ampulla of Vater. Tu Y. J Clin Oncol 2013. Crippa S. Fisher GA. 32:390. Evans DB. Histomolecular phenotypes of adenocarcinoma of the ampulla of vater: more evidence is required. et al. Jamieson NB. 87. Int J Radiat Oncol Biol Phys 2008. 95:1685. 81. 85. Int J Radiat Oncol Biol Phys 2006. Adjuvant chemoradiotherapy for "unfavorable" carcinoma of the ampulla of Vater: preliminary report. Carcinoma of the ampulla of Vater: patterns of failure following resection and benefit of chemoradiotherapy. Nowak K.com/contents/ampullary-carcinoma-treatment-…uodenectomy&selectedTitle=3%7E47&view=print&displayedView=full Página 13 de 24 . et al. 84. 21:47 67. Wang WJ. 72. Ann Surg Oncol 2008. 66:514. Eur J Surg Oncol 2007. Prognosis of resected ampullary adenocarcinoma by preoperative serum CA19-9 levels and platelet-lymphocyte ratio. 48:1089. 11:1488. Adjuvant therapy for ampullary carcinomas: the Mayo Clinic experience.

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known as the sphincter choledochus (or sphincter of Boyden). keeps resistance to bile flow high.uptodate. and thereby permits filling of the gallbladder during fasting and prevents retrograde reflux of duodenal contents into the biliary tree. A separate structure.com/contents/ampullary-carcinoma-treatment-…uodenectomy&selectedTitle=3%7E47&view=print&displayedView=full Página 15 de 24 . called the sphincter pancreaticus. 21:47 GRAPHICS Sphincter of Oddi in relation to the ampulla of Vater Diagram of the anatomy of the sphincter of Oddi and ampulla of Vater. The muscle fibers of the sphincter pancreaticus are interlocked with those of the sphincter choledochus in a figure eight pattern. A circular aggregate of muscle fibers.Ampullary carcinoma: Treatment and prognosis 14/11/13. http://www. encircles the distal pancreatic duct. The muscle fibers of the spincter of Oddi surround the intraduodenal segment of the common bile duct and the ampulla of Vater.

uptodate.Ampullary carcinoma: Treatment and prognosis 14/11/13. 21:47 Locations ampullary tumors http://www.com/contents/ampullary-carcinoma-treatment-…uodenectomy&selectedTitle=3%7E47&view=print&displayedView=full Página 16 de 24 .

21:47 Conventional pancreaticoduodenectomy (Whipple procedure) http://www.com/contents/ampullary-carcinoma-treatment-…uodenectomy&selectedTitle=3%7E47&view=print&displayedView=full Página 17 de 24 .Ampullary carcinoma: Treatment and prognosis 14/11/13.uptodate.

Ampullary carcinoma: Treatment and prognosis 14/11/13.uptodate. 21:47 Pylorus-preserving pancreaticoduodenectomy http://www.com/contents/ampullary-carcinoma-treatment-…uodenectomy&selectedTitle=3%7E47&view=print&displayedView=full Página 18 de 24 .

uptodate. 21:47 TNM staging for ampullary carcinoma Primary tumor (T) TX T0 Tis T1 T2 T3 T4 Primary tumor cannot be assessed No evidence of primary tumor Carcinoma in situ Tumor limited to the ampulla of Vater or sphincter of Oddi Tumor invades duodenal wall Tumor invades pancreas Tumor invades peripancreatic soft tissues or other adjacent organs or structures other than pancreas Regional lymph nodes (N) NX N0 N1 Regional lymph nodes cannot be assessed No regional lymph node metastasis Regional lymph node metastasis Distant metastasis (M) M0 M1 No distant metastasis Distant metastasis Anatomic stage/prognostic groups Stage 0 Stage IA Stage IB Stage IIA Stage IIB Tis T1 T2 T3 T1 T2 T3 Stage III Stage IV T4 Any T N0 N0 N0 N0 N1 N1 N1 Any N Any N M0 M0 M0 M0 M0 M0 M0 M0 M1 Note: cTNM is the clinical classification. Inc.com/contents/ampullary-carcinoma-treatment-…uodenectomy&selectedTitle=3%7E47&view=print&displayedView=full Página 19 de 24 . Chicago. Used with the permission of the American Joint Committee on Cancer (AJCC). Illinois. http://www.Ampullary carcinoma: Treatment and prognosis 14/11/13. The original source for this material is the AJCC Cancer Staging Manual. Seventh Edition (2010) published by Springer New York. pTNM is the pathologic classification.

Ampullary carcinoma: Treatment and prognosis 14/11/13.uptodate. http://www. Modified from: O'Connell. Ann Surg Oncol 2008. CSS: cause-specific survival. et al.com/contents/ampullary-carcinoma-treatment-…uodenectomy&selectedTitle=3%7E47&view=print&displayedView=full Página 20 de 24 . Epidemiology and End Results database of the National Cancer Institute. * SEER: Surveillance. 21:47 Five-year survival in a series of 1301 patients with ampullary cancer reported to the SEER* registry between 1988 and 2003 Stage at presentation Ia Ib IIa IIb III IV N stage N0 N1 518 749 48 21 59 28 N 218 255 252 483 38 15 60 57 30 22 27 0 Five-year survival percent OS 74 66 41 30 34 0 CSS OS: overall survival. 15:1820.

21:47 Gemcitabine for nonmetastatic pancreatic and biliary cancer [1] Cycle length: 4 weeks.25 percent of patients receiving gemcitabine.com/contents/ampullary-carcinoma-treatment-…uodenectomy&selectedTitle=3%7E47&view=print&displayedView=full Página 21 de 24 . • Assess basic metabolic panel (including serum creatinine) and liver function prior to each cycle and otherwise as indicated during treatment.000/mm 3 and ≥50.000 cells/mm 3[1]. dose should be recalculated for all drugs. http://www. Monitoring parameters: • CBC with differential and platelet count weekly during treatment. Discontinue gemcitabine immediately and permanently. There is insufficient information from clinical studies to allow clear dose recommendations in these patients.Ampullary carcinoma: Treatment and prognosis 14/11/13. or the platelets decrease to <100. • Pulmonary toxicity: A variety of manifestations of pulmonary toxicity have been reported. with or without renal failure or central nervous system findings. Administration schedule Weekly for three weeks followed by one week of rest. Pretreatment considerations: • Emesis risk: LOW.uptodate. Refer to UpToDate topic on "Chemotherapy hepatotoxicity and dose modification in patients with liver disease". If there is a change in body weight of at least 10 percent. Discontinue gemcitabine immediately and permanently. During therapy. but these are seldom of clinical significance. Consider diagnosis if the patient develops hemolysis and severe thrombocytopenia. The US FDA approved product information recommends holding gemcitabine for an absolute neutrophil count <500 cells/mm 3 or platelets <50.000/mm 3[2]. • Hemolytic-uremic syndrome (HUS): In clinical trials. Refer to UpToDate topic on "Prevention and treatment of chemotherapyinduced nausea and vomiting". Refer to UpToDate topic on "Use of granulocyte colony stimulating factors in patients with chemotherapy-induced neutropenia". HUS was reported in 0. Suggested dose alterations for toxicity: • Myelotoxicity: This regimen should not be initiated unless the white blood cell count is >3500 cells/mm 3 and platelets are ≥100. Drug Gemcitabine Dose and route 1000 mg/m 2 IV Administration Dilute in 100 mL normal saline (concentration no greater than 40 mg/mL) and administer over 30 minutes. Refer to UpToDate topic on "Pulmonary toxicity associated with antineoplastic therapy: Cytotoxic agents". the dose of gemcitabine should be decreased by 25 percent if the absolute neutrophil count decreases to <1000 cells/mm 3 but ≥500 cells/mm 3.000/mm 3[2]. Refer to UpToDate topic on "Causes of thrombotic thrombocytopenic purpura-hemolytic uremic syndrome in adults". • Dose adjustment for baseline liver or renal dysfunction: A lower starting dose may be needed for patients with liver impairment. • Infection prophylaxis: Primary prophylaxis with granulocyte colony stimulating factors not indicated (risk of neutropenic fever <1 percent). • Hepatotoxicity: Gemcitabine is commonly associated with a transient rise in serum transaminases.

21:47 This table is provided as an example of how to administer this regimen. et al. Gemzar (gemcitabine hydrochloride). Oettle H. The clinician is expected to use his or her independent medical judgment in the context of individual circumstances to make adjustments.nih. http://www. 2011). References: 1. 297:267. there may be other acceptable methods. US FDA approved manufacturer's package insert. JAMA 2007. accessed on November 28.com/contents/ampullary-carcinoma-treatment-…uodenectomy&selectedTitle=3%7E47&view=print&displayedView=full Página 22 de 24 . IV: intravenous.Ampullary carcinoma: Treatment and prognosis 14/11/13. This regimen must be administered by a clinician trained in the use of chemotherapy.gov.nlm. as necessary. 2. (Available online at dailymed.uptodate. CBC: complete blood count. US National Library of Medicine.

then 4 weeks. The US FDA approved product information recommends holding gemcitabine for an absolute neutrophil count <500 cells/mm 3 or platelets <50.000/mm 3 and ≥50. Refer to UpToDate topic on "Use of granulocyte colony stimulating factors in patients with chemotherapy-induced neutropenia". Discontinue gemcitabine immediately and permanently. or the platelets decrease to <100. Consider diagnosis if the patient develops hemolysis and severe thrombocytopenia.uptodate. the dose of gemcitabine should be decreased by 25 percent if the absolute neutrophil count decreases to <1000 cells/mm 3 but ≥500 cells/mm 3. • Dose adjustment for baseline liver or renal dysfunction: A lower starting dose may be needed for patients with liver impairment. There is insufficient information from clinical studies to allow clear dose recommendations in these patients. http://www.Ampullary carcinoma: Treatment and prognosis 14/11/13. but these are seldom of clinical significance. Drug Gemcitabine* Dose and route 1000 mg/m 2 IV Administration Dilute in 100 mL normal saline (concentration no greater than 40 mg/mL) and administer over 30 to 60 minutes. • Hemolytic-uremic syndrome (HUS): In clinical trials. 21:47 Gemcitabine for metastatic pancreatic and biliary tract cancer [1] Cycle length: 8 weeks for first cycle. Monitoring parameters: • CBC with differential and platelet count weekly during treatment.25 percent of patients receiving gemcitabine. During therapy. • Infection prophylaxis: Primary prophylaxis with granulocyte colony stimulating factors not indicated (incidence of neutropenic fever <1 percent [1-4]). Suggested dose alterations for toxicity: • Myelotoxicity: This regimen should not be initiated unless the white blood cell count is greater than 3500 cells/mm 3 and platelets are greater than or equal to 100. Administration schedule Weekly for seven weeks followed by one week of rest in the first cycle. Pretreatment considerations: • Emesis risk: LOW.000/mm 3[5].com/contents/ampullary-carcinoma-treatment-…uodenectomy&selectedTitle=3%7E47&view=print&displayedView=full Página 23 de 24 . HUS was reported in 0. • Hepatotoxicity: Gemcitabine is commonly associated with a transient rise in serum transaminases. with or without renal failure or central nervous system findings. • Assess basic metabolic panel (including serum creatinine) and liver function tests prior to each cycle and otherwise as indicated during treatment.000/mm 3[5]. Refer to UpToDate topic on "Prevention and treatment of chemotherapyinduced nausea and vomiting".000 cells/mm 3[1]. then weekly for three weeks followed by one week of rest in all subsequent cycles. Refer to UpToDate topic on "Causes of thrombotic thrombocytopenic purpura-hemolytic uremic syndrome in adults". Refer to UpToDate topic on "Chemotherapy hepatotoxicity and dose modification in patients with liver disease".

Br J Cancer 2006. 21:47 • Pulmonary toxicity: A variety of manifestations of pulmonary toxicity have been reported.nih. IV: intravenous. Oettle H. Ann Oncol 2005. accessed on November 28. a dose of 1250 mg/m2 after the first cycle. but not exceeding. Gemzar (gemcitabine hydrochloride). Stathopoulos GP. US FDA approved manufacturer's package insert. provided the absolute neutrophil count and platelets exceed 1500 cells/mm3 and 100. Burris HA. Herrmann R. Discontinue gemcitabine immediately and permanently. et al.nlm.000/mm3. CBC: complete blood count. (Available online at dailymed. the gemcitabine dose could be increased by 25 percent up to.uptodate. respectively. US National Library of Medicine. The clinician is expected to use his or her independent medical judgment in the context of individual circumstances to make adjustments.gov.com/contents/ampullary-carcinoma-treatment-…uodenectomy&selectedTitle=3%7E47&view=print&displayedView=full Página 24 de 24 . References: 1. there may be other acceptable methods. 3. 16:1639. 15:2403. 4. This regimen must be administered by a clinician trained in the use of chemotherapy. http://www. If there is a change in body weight of at least 10 percent. 95:587. J Clin Oncol 1997. as necessary. et al. This table is provided as an example of how to administer this regimen. J Clin Oncol 2007. dose should be recalculated for all drugs. ​ * In the original protocol.Ampullary carcinoma: Treatment and prognosis 14/11/13. 2011). 5. 2. et al. 25:2212. Refer to UpToDate topic on "Pulmonary toxicity associated with antineoplastic therapy: Cytotoxic agents". et al. and nonhematologic toxicity was less than or equal to WHO Grade 1[1].