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Is local excision of pT1-ampullary carcinomas justified?
European Journal of Surgical Oncology 1996; 22:366-371
Is local excision of pTl-ampullary carcinomas justified? P. Klein*, B. Reingruber, S. Kastl*, O. Dworakt and W. Hohenberger* *Department of Surgery, Friedrich-Alexander University, Erlangen-Nfirnberg, and t Division of Clinical Pathology, Department of Surgery, Friedrich-Alexander-University, Erlangen-Nfirnberg, Germany
We propose that local excision of carcinomas of the ampulla of Yater is justifiable under the following conditions: when the tumour is limited to the ampulla of Vater as diagnosed by pre-operative endoluminal sonography (uTl) and UICC-staging (pT1); and when it is graded G1 or G2 and there is no lymphatic infiltration and the turnout is completely resected 010). Under these conditions peri-operative morbidity and mortality were significantly reduced compared with more extensive surgery. There was no local recurrence of tumour in our study and long-term survival rates were comparable with Whipple's procedure. This implies that lymphatic spread is limited in localized disease and the feasibility of the proposed procedure may therefore be analogous to localized resections in other malignant tumours, e.g. carcinoma of the rectum.
Key words: carcinoma; ampulla of Vater; excision; pancreatoduodenectomy.
Introduction Carcinomas arising within the ampulla of Vater are rare but constitute a definite pathological entity. This is reflected in better prognosis of ampullary carcinomas compared with carcinomas originating from the head of the pancreas or from the biliary tract. Local excision of tumours of the papilla was first described by Halsted in 1898) Since 1935 Whipple's procedure 2 or other modifications of pancreatoduodenectomy 3 have been regarded as the surgical standard for malignant tumours. Local tumour excision is seen as an alternative, limited to benign lesions or elderly patients or patients in poor medical condition, and unfit for extensive surgery.~ Interestingly, the reports on these high-risk patients with defined early stage (pTl) (Fig. 1), locally excised low grade (Gl/2) carcinomas, showed substantially reduced complication rates and survival figures similar, and in some series even better ~ than those of pancreatoduodenectomy. Studies of local resection ofpT1 carcinomas of the ampulla of Vater are mainly episodic and unbiased trials with sufficiently large numbers of comparable cases are still lacking because pancreatoduodenectomy is considered standard procedure for all radically operable carcinomas of the ampulla of Vater. We present here our series of 35 patients with pT1 (G 1-3) carcinoma of the ampulla of Vater, the largest series ever to compare partial pancreatectomy directly with local excision for this tumour entity and stage. Here, too, Whipple's procedure has been the procedure of choice and was performed in 26 cases. Local excision of the ampulla was performed in nine patients, with encouraging results. Patients and methods
of Surgery, University Hospital, Erlangen, Germany. The follow-up period was between 3 and 16 years and a mean of 8.9 years for all 19 patients still alive (partial pancreatoduodenectomy: 15 patients; range, 4-16 years; mean, 9.1 years; local excision: four patients; range, 3-16 years; mean, 8.3 years). In a non-randomized study, prospective in terms of histopathological data recruitment, all 35 patients were reviewed retrospectively. Patients selected for local excision either had the pre-operative diagnosis of ampullary adenoma (and in the case of an intra- or post-operative finding of carcinoma would have undergone Whipple's procedure) or had been unfit for extensive surgery for medical reasons. Otherwise Whipple's procedure was the standard surgical treatment. On 21 patients primary Whipple's procedure was performed. In 14 patients a local excision of the papilla was carried out. Five of these patients (Table 1) had the local excision converted to partial pancreatoduodenectomy (n = 26). Nine patients had exclusive local excision. There were 23 (66%) men and 12 (34%) women included in the study, local excision was performed on five men and four women. The median age of all patients was 64 years (range: 41-84 years) with a highly significant statistical difference between the two groups (P<0.001). Patients on whom local tumour excision was performed (n=9) were 11 years older on average (69.7 years; range: 65-84 years) than the more extensively operated on (n=26) group (58.4 years; range: 41-73 years). This was mainly due to the fact that local excision was performed in patients judged medically unfit for Whipple's procedure by the examining surgeons and anaesthetists.
Patients
Clinicalpresentation
Between 1970 and 1992, 35 patients were operated on for a pT1 carcinoma of the ampulla of Vater at the Department
All our patients had been clinically symptomatic at the time of surgery. The predominant symptom was jaundice (69%),
0748-7983/961040366+ 06 $12.00•0
© 1996 W.B. SaundersCompany Limited
Local excision of p Tl-ampullary carcinomas
367
Tumour limited to the ampulla of Vater
Fig. 1. UICC: (p)TI-carcinoma of the ampulla of Vater?
Table I. Patients converted
from local excision to partial pancreatoduodenectomy
Patient (and age)
Staging and grading after local excision
RS (54 years)
pTI G2 RI
Comments
Unfit for extented surgery; haemorrhage after local excision; delayed Whipple's procedure; no residual tumour, no lymph node metastasis Permanent histology; pTI G2 R0 TP (41 years) carcinoma G2; Whipple's procedure after 7 days: no residual tumour, no lymph node metastasis Whipple's procedure FK(56 years) pTl G1 R0 performed immediately after frozen section: no residual tumour, no lymph node metastasis Inadequate operation RM(66 years) pTl GI R2 elsewhere; referred for Whipple's procedure: Carcinoma GI R0, no lymph node metastasis EE (56 years) frozen Seclion: Familial polyposis; Whipple's procedure 4 days after local Adenoma perm. histology excision: no residual tumour, no lymph node metastasis pTl GI R0
computed tomography has been used routinely since 1983, ~° and, used more infrequently, oesophagogastroduodenoscopy and endo-luminal sonography (since 1992). Pre-operative biopsies were available in 26 cases (74%).
Operative procedures 1. Whipple's procedure and other modifications of pancreatoduodenectomy have been described in detail by GALL. 3In our series Whipple's procedure was performed on 25 patients, lymphatic dissection on 17 (or 68%; 100% since 1985), one patient was treated by total pancreatoduodenectomy. 2. Local excision was performed in patients with the tentative diagnosis of ampullary adenoma or in elderly carcinoma patients of poor general condition. After mobilization the duodenum was incised longitudinally, opposite the papilla. The peri-sphincteric duodenal mucosa was then electrodissected, the ampulla excised completely, taking a full thickness of the duodenal wall together with the terminal segments of both the pancreatic and common bile ducts. A 'neopapilla' was created at the posterior wall of the duodenum into which the orifices of the bile and pancreatic ducts were implanted.
Statistics 48% of the patients presented with pain; weight loss (29%), pyrexia (17%) and pruritis (8.6%) were less common.
Survival rates were calculated according to the Kaplan-Meier method, and for analysis of difference the log-rank test was used.
blvestigations Since 1970, the beginning of our study period, investigation routines, especially the use of imaging techniques, have changed. Various diagnostic measures have therefore been used to establish the pre-operative diagnosis. Abdominal ultrasound and ERCP have been used in 31 cases (88%),
Results
Of 26 biopsies that were obtained pre-operatively, 13 were diagnosed as carcinoma (50%). In the frozen section examination, 24 of 26 (92%) specimens were correctly
P. Klein et al.
368
Table 2. UICC-staging and histopathological grading9 in the
100 h
=
pancreatoduodenectomy and local excision groups UICC
pT I/R0 pT I/R 1
Grading
GI G2 G3 G3
Local excision
5 3 -I
Partial pancreatoduodenectomy 14 9 3 --
1 .............
i °°
rj diagnosed as carcinoma. In one case of familial polyposis an adenoma was identified and the diagnosis corrected to GIcarcinoma by subsequent full histological evidence. In another patient intraoperative diagnosis was indeterminate and the lesion was later found to be a G2-carcinoma. Both patients underwent Whipple's procedure 4 and 7 days after local excision had been performed. The then resected specimens were found to be free of tumour, and showed no lymphatic metastases.
/
o
i
I
I
12
2,1
36
i
48
i
60 72 Months
i
I
84
96
I
lO8 12o
Fig. 2. Survival after local resection ( , n=9) vs partial pancreatoduodenectomy (. . . . , n=25) of pTl carcinomas of the ampulla of Vater, operative mortality included.
measures and he died of tumour progression 8 months after surgery.
StaghTg and grading Only non-metastatic pTl carcinomas were considered in our series. Of the nine locally resected tumours, eight were graded GI or G2. In one patient the turnout was found to be G3 and the resection margins showed microscopic tumour involvement (RI). In the pancreatoduodenectomy group, three (11%) of 26 tumours were graded as G3, and all 26 cases were R0 resections (Table 2).
L),mphatic spread In the partial pancreatoduodenectomy group lymphatic metastases were found in two patients (7.7%; G2 N 1; G3 N 1). Excluding G3 tumours and focusing on all Grade 1 and 2/ pTl tumours examined in our study (n=247, only one G2 tumour was found to have caused regional lymphatic metastases (N I ; 4.2%7 by the time of surgery.
Mortality Tun?our recul'rellCe
There were no deaths related to surgery in the local tumour excision group, two patients (7.7'/,,) died as a consequence of partial pancreatoduodenectomy, one with ileus I0 weeks post-operatively, and one with anastomotic dehiscence 6 weeks post-operatively. There were two tumour-related deaths in the local excision group (G3 RI: 8 months postoperatively; G1 R 0 : 6 4 months) and two tumour-related deaths in the partial pancreatoduodenectomy group (GI R0: 67 months; G3 R0:74 months).
Concerning tumour recurrence and related mortality in all R0 cases ( n = 34), there were three pTl/R0 cases where the tumour recurred, one ofwhich had a G3 grading. In the local excision group, one Gl tumour recurred and the patient died 64 months after surgery. The other two recurrences were in the partial pancreatoduodenectomy group (G3/NI and G l / N l 7, with a survival of 74 and 67 months, respectively.
Survival Morbidity In the local tumour excision group there was a complication rate of 22% (pancreatitis, n = 1; subphrenic abscess, n = 1). For pancreatoduodenectomy, morbidity was higher (35%; subphrenic abscesses, s7= 3; pancreatic fistulae, n = 4; biliary fistula, n = 1; ileus, n = 17.
In the local excision group, four patients are still alive today, after 16, 9, 5 and 3 years without tumour recurrence (see Fig. 2). The survival curve of patients of this group from the fourth year post-operatively resembled the natural death rate," with 17= 5 patients alive. Four patients (44%) survived 5 years or more. Five-year overall survival in the partial pancreatoduodenectomy group was 73% (n-- 19 of 26).
Resectability Whereas all tumours could be entirely removed in the pancreatoduodenal resection group, there was one G3 tumour in the local excision group which had penetrated into lymphatic vessels (LI) and where the resection margins were not free of tumour (R 1). This patient's poor overall condition (hemiparesis, insulin-dependent diabetes, myocardial infarction, cachexia) precluded any further operative
Discussion
Although usually vague and non-specific, the prodromal symptoms of neoplastic growth of the ampulla of Vater set in early and these lesions are more likely to be diagnosed at an early stage. Diagnostic advances, especially in computed tomography
Local exc&ion of p Tl-ampullary carcinomas and endoscopic ultrasound, increase the reliability of preoperative diagnosis and tumour staging, as well as postoperative follow-up. EUS, a method introduced to our patients in 1992, has become a useful tool in determining the extent and depth of invasion t2 and it further increases the likelihood of detecting existing T l-lesions. Frozen section has proven useful in distinguishing adenoma from carcinoma. In one case (GI) a false-negative (4%) diagnosis was made in our series; in another case, diagnosis was indeterminate and a carcinoma (G2) was found on permanent histology (both patients underwent subsequent Whipple's procedure, where no remaining tumour could be found). However, several frozen sections may be necessary for diagnosis. More difficult, and to some degree subjective, is the conventional grading (G 1-3) of malignant tumours in frozen section, the distinction between GI and G2 tumours particularly depends on the experience of the pathologist. More reproducible in frozen section is the distinction between low and high grade tumour, as proposed by UICC. ~3 Unfortunately, in our material, one G2 tumour, resected by a Whipple's procedure, showed multiple microscopic metastases in regional lymph nodes which would have most certainly remained undetected if a local excision had been carried out. Therefore, frozen sections of suspicious lymph nodes may be helpful for intraoperative staging and planning, but negative findings should not be overvalued. A further histological feature of interest in determination of invasiveness is the infiltration of lymphatic vessels. However, the diagnosis may be difficult and depends on the tissue excised. The ampulla has a distinct pattern of lymphatic drainage and in contrast to pancreatic tumours with a diffuse lymphatic spread, tumours of the ampulla tend to involve a single group of lymph nodes, even in advanced disease/~ These morphological features make the ampullary lesions a distinct clinical entity yielding a substantially superior prognosis, unless confused with the far more frequent heterogeneous 'periampullary lesions'. ~5 Correspondingly, Bittner ~ showed that in ampullary carcinomas of stage pTl, irrespective of the tumour grade and exact site of the carcinoma, only one of 15 examined groups of lymph nodes was involved (6.7%) correlating well with 7.7% in our study. This implies that the risk of a prognostically relevant metastatic spread lies within the same range as the average mortality figures for partial pancreatoduodenectomy. ~7 The principle of performing partial pancreatoduodenectomy for a confirmed carcinoma of the ampulla of Vater has been advocated by most authors since the 1970s, 4'6'18 even though this procedure has never been compared with the local ampullary excision in controlled prospective trials on classified tumour subgroups. Of all ampullary carcinomas, 5-year survival after partial pancreatoduodenectomy is around 40"/o in most reports (n=24; 7 n=2319). For local excisions the sizes of the case series are smaller and are subjected to an unfavourable preselection in many instances. Therefore, the figures seem to be more variable and range from 9% (n = 1419) to 440/0 (n = 84), the latter notably being the largest documented study to date without pre-selection of poor-risk patients (Table 3). When Makipour (n = 82°) explained that in selected older
369
patients with localized tumours, ampullectomy provided results equal to, or better than, a pancreatoduodenal resection this was at a time when mortality from Whipple's procedure was still high. As mortality from this method was substantially decreasing even in elderly patients -'t and now ranges from well below 5% in large operative centres, the most viable justification for limiting surgery to local excision has become disputable, s In our department Whipple's procedure has so far been indicated for all carcinomas of this region whenever a curative intention was feasible. The mortality rate in our series was at an overall 7.7% and at 3.9% for operations performed after 1978. The post-operative morbidity of Whipple's procedure, however, remains high, at 35% even today. Local excision has been justified only in cases of old age and poor condition. Accordingly, in the present series, patients on whom excision of the papilla had been performed (n = 9), were of a significantly higher age (mean: 69.7 vs 58.4 years) on average. Interestingly, despite unfavourable pre-selection in this group there was nil mortality, with a lower complication rate (22%). If applied to a younger age group, the substantially less impaired quality of life would have to be also considered in favour of the local resection. Without tumour staging, Knox, 7 presenting his series of 25 locally resected cases with nil operative mortality, vaguely stated that there does appear to be a group of patients with ampullary carcinomas who are adequately treated by a local excision. In 1991 Koch ~7presented his series of four patients, where ampullary carcinomas, macroscopically invisible and undetected by frozen section, were discovered postoperatively by full histology (pTl G1 NO). These 'occult' carcinomatous formations within adenomas did not recur for the observed 1-8 post-operative years and the performed local resections were regarded curative. This experience prompted the author to advocate abstinence from pancreatoduodenal resection in those cases provided regular and frequent followup investigations were carried out. Increasing numbers of reported local excisions of ampullary carcinomas, ~'~7 although still mainly episodic in themselves, show that ifpatients had been grouped according to Gand T-classifications, survival rates in the well-differentiated (GI/2) and early stage (pTl NO M0) subgroups would be equal to those of pancreatoduodenectomy. Likewise, Mori, ~7 with his histopathological findings on n = 5 stage I patients who had undergone Whipple's procedure, stated that local excision may have been reasonable in these cases. The results o four series indicate, that, if limited to patients with well or moderately differentiated (i.e. 'low risk' according to UICC) and completely resectable ampullary carcinomas of the earliest stage and without lymphatic invasion, local excision seems to produce survival rates similar to those of Whipple's procedure, although mortality and complication figures are markedly lower with local excision. Controversy remains over T1-G3-1esions, which might not always be detected via frozen section. Unlike in local resection of Ti carcinoma of the rectum where a major operation would follow in a case of local irresectability, a G3ampullary carcinoma missed on frozen section would entail
370
P Klein et al.
Table 3. Compiled data on locally resected ampullary carcinomas
Author
Year
Patients
Staging
Grading
Tumour-related death (years)
Akwari~ Tudor2~ Robertson4
1977 1984 1986 1986 1989 1990
pTI ? ~ ? (R0) pT 1 ?
? GI GI G3 ? GI ?
I; 5; 15
Knox7 Delcorej5 Gertsch'~
4 I 4 2 25 1 5
Kochz7 Erlangen
1991 1995
4 9
pTl pTl pT1
GI GI/2 G3
a re-laparotomy and a Whipple's procedure. However, there was not a single such case in our series, and two patients in whom Whipple's procedure was added to a prior local excision had well (G l) and moderately (G2) differentiated carcinomas showing no residual tumour in the pancreatoduodenal specimens. In summary, if tumour-specific therapy of ampullary lesions was intended, our proposals for the following conditions would be: 1. With a pre-operative diagnosis of adenoma or TI N0carcinoma of the ampulla o fVater, local resection is indicated; if intraoperative findings show T>I or N>0 or 'high-grade' tumour, the procedure would have to be extended to partial pancreatoduodenectomy. 2. If, post-operatively, an adenoma or a tentative T1 NO carcinoma had to be reclassified by full histological evidence as T>I, N>0, or ifa poorly differentiated Tl-G3-carcinoma was found, partial pancreatoduodenectomy would subsequently need to be performed. Any lymphatic metastasis or lymphatic infiltration detected pre-, intra, or post-operatively would, for reasons of radicality, necessitate immediate or subsequent pancreatoduodenectomy and precludes local resection. Ifthe patient was unfit for extensive surgery, local excision would be the procedure of choice, unless palliative measures (e.g. endoluminal laser treatment; stent placement) were preferred. There should be regular and frequent follow-up of locally excised carcinoma patients at least every 3-months for the first 2 years and every 6 months until completion of the 5year follow-up period. If these checks are adhered to, the combination of endoscopic and endosonographic procedures should facilitate early detection of any tumour recurrence and provide reasonable safety, acknowledging that even by using all of the indicated diagnostic and therapeutic measures, lymphatic metastases cannot be definitely excluded. In our pT1 Gl/2 tumours, a lymphatic metastasis was present in one of 24 (4.3°/'0)patients. At present, however, this risk seems to be equal or lower than the mortality of Whipple's procedure in our as well as in published series. 5.7 We must also accept that in our study, like in studies of most other large centres, numbers of this rare tumour entity are as yet too small to reach a definite conclusion. The possibility of combining cases of other studies is limited by the lack of comparability. Minimal criteria should therefore
4; 5 0, 3; 0, 7
Unrelated death (years)
6
Aliveafter years 2 18 1
5 year survival 51%
5 0, 6
2; 4; 4
9 all alive after 1-3 years 1; 4; 5; 8 3; 5; 9; 16
be met in the uniform evaluation ofcarcinomas of the ampulla of Vater. Special attention should be drawn to a careful and complete histological processing of the resected specimen, whereby lymphatic invasion should be excluded. Staging according to UICC, histology and grading should be provided in any case, as should values for mortality, morbidity, survival and tumour recurrence. Additionally, values for quality of life would be desirable. Until further evidence becomes available, it should be concluded that a local tumour excision of carcinoma of the ampulla of Vater is justifiable under the following conditions: If the tumour is confined to the ampulla (pT 1) and is graded Gl/2 according to U1CC. If there is no evidence of lymphatic penetration and if the tumour has been resected completely (R0-resection, UICC). With figures for survival equal to those of pancreatoduodenectomy and with lower complication and mortality rates despite a worse initial medical status and higher age, local recurrence could be avoided. Long periods of post-operative survival suggest a low probability of lymphatic spread as seen in similar limited procedures elsewhere.
References
I. Halsted WS. Contributions to the surgery of the bile passages, especiallyof the common bileduct. Boston Med Surg J 1899;141: 645-54. 2. Whipple AO, Parsons WB, Mullins CR. Treatment ofcarcinoma of the ampulla of Vater. Ann Surg 1935; 102: 763-79. 3. Gall FP, Hermanek P, Gebhardt C, Meier H. Erweiterte Resektion der Pankreas- und periampull/iran Karzinome: Regionale,totale und partielle Duodenopankreatektomie. Leber Magen Darrn 1981; 11: 179-84. 4. Robertson JFR, Imrie CW, Hole DJ, Carter DC, Blumgart LH. Management of periampullary carcinoma. Br J Surg 1987; 74: 816-9. 5. Tarazi RY, Hermann RE, Vogt DP, et al. Results of surgical treatment of periampullary tumours: a thirty-five year experience. Surgery 1986;100:716-23. 6. Wise L, Pizzimbono C, Dehner L. Periampullary cancer. Am J Surg 1976; 131: 141-8. 7. Knox RA, Kingston RD. Carcinoma ofthe ampulla ofVater. Br JSurg 1986;73: 72-3. 8. Schlippert W, Lucke D, Anuras S, Christensen J. Carcinoma of the papilla of Vater. Am J Surg 1978; 135: 763-70. 9. Spiessl B, et al (eds). TNM-Atlas: lllustrated Guide to the TNMI pTNM-Classification of Malignant Tumours (3rd edn). Berlin, Heidelberg: Springer, 1989: 120.
Local excision o f pTl-ampullary carcinomas 10. Hohenberger W, Zirngibl H, Gall FP. Pancreatic and periampular carcinoma. In: Veronesi U, Amesio B, Burn I, Denis L, Mazzeo F (eds) Surgical Oncology. A European handbook. Berlin, Heidelberg, New York, London, Paris, Tokyo, Hong Kong: Springer, 1989: 578-621. I I. Bundesminister ftir Gesundheit; Lebenserwartung in Jahren im Alter X. In: Der Bundesminister ftlr Gesundheit, ed. Daten des Gesundheitswesens. Baden-Baden, Nosmos: 1991: 23. 12. Farouk M, Niotis M, Branum GD, Cotton PB, Meyers WC. Indications for and the technique of local resection of tumours of the papilla of Vater. Arch Surg 1991; 126: 650--2. 13. Hermanek E Henson DE, Hutter RVP, Sobin LH (eds). TNM Supplement. A Commentary on Uniform Use. Berlin, Heidelberg: Springer, 1993. 14. Cubilla AL, Fortner J, Fitzgerald PJ. Lymph node involvement in carcinoma of the head of the pancreas area. Cancer 1978; 41: 880-7. 15. Delcore R Jr, Connor CS, Thomas JH, Friesen SR, Hermreck AS. Significance of tumour spread in adenocarcinoma of the ampulla of Vater. Am JSurg 1989; 158: 593-6. 16. Bittner R, Roscher R, Sail F, Dopfer H-P, Sch/51zelE, Beger HG. Der Einflul3 von Tumorgr613e und Lymphknotenstatus auf die Prognose des Pankreascarcinoms. Chirurg 1989; 60: 240-5. 17. Koch B, Hildebrand U, Schtider G, Seitz G, Feifel G.
18. 19. 20. 21.
22. 23. 24.
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Eingeschrlinkte Radikalit~t beim okkulten Karzinom der Papilla Vateri. Langenbecks Arch Chir 1991; 376: 195-8. Mori K, Ikei S, Yamane T, Yamaguchi Y, Katsumori T, Shibata Y, Arai T. Pathologic factors influencing survival of carcinoma of the ampulla ofVater. EurJSurg Onco11990; 16: 183-8. Sellner F, Jelinek R. Die Wandlung der Wertigkeit der PapiUenextirpation beim Papillencarcinom. Chirurg 1984; 55: 809-12. Makipour H, Cooperman A, Danzi JT, Farmer RG. Carcinoma of the ampulla of Vater: Review of 38 cases with emphasis on treatment and prognostic factors. Ann Surg 1975; 183: 341--4. Hannoun L, Christophe M, Ribeiro J, Nordlinger B, Elriwini M, Tiret E, Parc R. A report of forty-four instances of pancreaticoduodenal resection in patients more than seventy years of age. Surg Gyn Obst 1993; 177: 556--60. Akwari OE, van Heerden JA, Adson MA, Baggenstoss AH. Radical pancreatoduodenectomy for cancer of the papilla of Vater Arch Surg 1977; 112: 451-6. Tudor RG. Long term survival following local resection of carcinoma of ampulla of Vater. Br JSurg 1984; 71: 271. Gertsch P, Baer HU, Lerut A, Blumgart LH. Technik der Papilloduodenektomie. Langenbecks Arch Chir 1990; 375: 246-50.
A cceptedfor publication 19 April 1996
Is local excision of pTl-ampullary carcinomas justified? P. Klein*, B. Reingruber, S. Kastl*, O. Dworakt and W. Hohenberger* *Department of Surgery, Friedrich-Alexander University, Erlangen-Nfirnberg, and t Division of Clinical Pathology, Department of Surgery, Friedrich-Alexander-University, Erlangen-Nfirnberg, Germany
We propose that local excision of carcinomas of the ampulla of Yater is justifiable under the following conditions: when the tumour is limited to the ampulla of Vater as diagnosed by pre-operative endoluminal sonography (uTl) and UICC-staging (pT1); and when it is graded G1 or G2 and there is no lymphatic infiltration and the turnout is completely resected 010). Under these conditions peri-operative morbidity and mortality were significantly reduced compared with more extensive surgery. There was no local recurrence of tumour in our study and long-term survival rates were comparable with Whipple's procedure. This implies that lymphatic spread is limited in localized disease and the feasibility of the proposed procedure may therefore be analogous to localized resections in other malignant tumours, e.g. carcinoma of the rectum.
Key words: carcinoma; ampulla of Vater; excision; pancreatoduodenectomy.
Introduction Carcinomas arising within the ampulla of Vater are rare but constitute a definite pathological entity. This is reflected in better prognosis of ampullary carcinomas compared with carcinomas originating from the head of the pancreas or from the biliary tract. Local excision of tumours of the papilla was first described by Halsted in 1898) Since 1935 Whipple's procedure 2 or other modifications of pancreatoduodenectomy 3 have been regarded as the surgical standard for malignant tumours. Local tumour excision is seen as an alternative, limited to benign lesions or elderly patients or patients in poor medical condition, and unfit for extensive surgery.~ Interestingly, the reports on these high-risk patients with defined early stage (pTl) (Fig. 1), locally excised low grade (Gl/2) carcinomas, showed substantially reduced complication rates and survival figures similar, and in some series even better ~ than those of pancreatoduodenectomy. Studies of local resection ofpT1 carcinomas of the ampulla of Vater are mainly episodic and unbiased trials with sufficiently large numbers of comparable cases are still lacking because pancreatoduodenectomy is considered standard procedure for all radically operable carcinomas of the ampulla of Vater. We present here our series of 35 patients with pT1 (G 1-3) carcinoma of the ampulla of Vater, the largest series ever to compare partial pancreatectomy directly with local excision for this tumour entity and stage. Here, too, Whipple's procedure has been the procedure of choice and was performed in 26 cases. Local excision of the ampulla was performed in nine patients, with encouraging results. Patients and methods
of Surgery, University Hospital, Erlangen, Germany. The follow-up period was between 3 and 16 years and a mean of 8.9 years for all 19 patients still alive (partial pancreatoduodenectomy: 15 patients; range, 4-16 years; mean, 9.1 years; local excision: four patients; range, 3-16 years; mean, 8.3 years). In a non-randomized study, prospective in terms of histopathological data recruitment, all 35 patients were reviewed retrospectively. Patients selected for local excision either had the pre-operative diagnosis of ampullary adenoma (and in the case of an intra- or post-operative finding of carcinoma would have undergone Whipple's procedure) or had been unfit for extensive surgery for medical reasons. Otherwise Whipple's procedure was the standard surgical treatment. On 21 patients primary Whipple's procedure was performed. In 14 patients a local excision of the papilla was carried out. Five of these patients (Table 1) had the local excision converted to partial pancreatoduodenectomy (n = 26). Nine patients had exclusive local excision. There were 23 (66%) men and 12 (34%) women included in the study, local excision was performed on five men and four women. The median age of all patients was 64 years (range: 41-84 years) with a highly significant statistical difference between the two groups (P<0.001). Patients on whom local tumour excision was performed (n=9) were 11 years older on average (69.7 years; range: 65-84 years) than the more extensively operated on (n=26) group (58.4 years; range: 41-73 years). This was mainly due to the fact that local excision was performed in patients judged medically unfit for Whipple's procedure by the examining surgeons and anaesthetists.
Patients
Clinicalpresentation
Between 1970 and 1992, 35 patients were operated on for a pT1 carcinoma of the ampulla of Vater at the Department
All our patients had been clinically symptomatic at the time of surgery. The predominant symptom was jaundice (69%),
0748-7983/961040366+ 06 $12.00•0
© 1996 W.B. SaundersCompany Limited
Local excision of p Tl-ampullary carcinomas
367
Tumour limited to the ampulla of Vater
Fig. 1. UICC: (p)TI-carcinoma of the ampulla of Vater?
Table I. Patients converted
from local excision to partial pancreatoduodenectomy
Patient (and age)
Staging and grading after local excision
RS (54 years)
pTI G2 RI
Comments
Unfit for extented surgery; haemorrhage after local excision; delayed Whipple's procedure; no residual tumour, no lymph node metastasis Permanent histology; pTI G2 R0 TP (41 years) carcinoma G2; Whipple's procedure after 7 days: no residual tumour, no lymph node metastasis Whipple's procedure FK(56 years) pTl G1 R0 performed immediately after frozen section: no residual tumour, no lymph node metastasis Inadequate operation RM(66 years) pTl GI R2 elsewhere; referred for Whipple's procedure: Carcinoma GI R0, no lymph node metastasis EE (56 years) frozen Seclion: Familial polyposis; Whipple's procedure 4 days after local Adenoma perm. histology excision: no residual tumour, no lymph node metastasis pTl GI R0
computed tomography has been used routinely since 1983, ~° and, used more infrequently, oesophagogastroduodenoscopy and endo-luminal sonography (since 1992). Pre-operative biopsies were available in 26 cases (74%).
Operative procedures 1. Whipple's procedure and other modifications of pancreatoduodenectomy have been described in detail by GALL. 3In our series Whipple's procedure was performed on 25 patients, lymphatic dissection on 17 (or 68%; 100% since 1985), one patient was treated by total pancreatoduodenectomy. 2. Local excision was performed in patients with the tentative diagnosis of ampullary adenoma or in elderly carcinoma patients of poor general condition. After mobilization the duodenum was incised longitudinally, opposite the papilla. The peri-sphincteric duodenal mucosa was then electrodissected, the ampulla excised completely, taking a full thickness of the duodenal wall together with the terminal segments of both the pancreatic and common bile ducts. A 'neopapilla' was created at the posterior wall of the duodenum into which the orifices of the bile and pancreatic ducts were implanted.
Statistics 48% of the patients presented with pain; weight loss (29%), pyrexia (17%) and pruritis (8.6%) were less common.
Survival rates were calculated according to the Kaplan-Meier method, and for analysis of difference the log-rank test was used.
blvestigations Since 1970, the beginning of our study period, investigation routines, especially the use of imaging techniques, have changed. Various diagnostic measures have therefore been used to establish the pre-operative diagnosis. Abdominal ultrasound and ERCP have been used in 31 cases (88%),
Results
Of 26 biopsies that were obtained pre-operatively, 13 were diagnosed as carcinoma (50%). In the frozen section examination, 24 of 26 (92%) specimens were correctly
P. Klein et al.
368
Table 2. UICC-staging and histopathological grading9 in the
100 h
=
pancreatoduodenectomy and local excision groups UICC
pT I/R0 pT I/R 1
Grading
GI G2 G3 G3
Local excision
5 3 -I
Partial pancreatoduodenectomy 14 9 3 --
1 .............
i °°
rj diagnosed as carcinoma. In one case of familial polyposis an adenoma was identified and the diagnosis corrected to GIcarcinoma by subsequent full histological evidence. In another patient intraoperative diagnosis was indeterminate and the lesion was later found to be a G2-carcinoma. Both patients underwent Whipple's procedure 4 and 7 days after local excision had been performed. The then resected specimens were found to be free of tumour, and showed no lymphatic metastases.
/
o
i
I
I
12
2,1
36
i
48
i
60 72 Months
i
I
84
96
I
lO8 12o
Fig. 2. Survival after local resection ( , n=9) vs partial pancreatoduodenectomy (. . . . , n=25) of pTl carcinomas of the ampulla of Vater, operative mortality included.
measures and he died of tumour progression 8 months after surgery.
StaghTg and grading Only non-metastatic pTl carcinomas were considered in our series. Of the nine locally resected tumours, eight were graded GI or G2. In one patient the turnout was found to be G3 and the resection margins showed microscopic tumour involvement (RI). In the pancreatoduodenectomy group, three (11%) of 26 tumours were graded as G3, and all 26 cases were R0 resections (Table 2).
L),mphatic spread In the partial pancreatoduodenectomy group lymphatic metastases were found in two patients (7.7%; G2 N 1; G3 N 1). Excluding G3 tumours and focusing on all Grade 1 and 2/ pTl tumours examined in our study (n=247, only one G2 tumour was found to have caused regional lymphatic metastases (N I ; 4.2%7 by the time of surgery.
Mortality Tun?our recul'rellCe
There were no deaths related to surgery in the local tumour excision group, two patients (7.7'/,,) died as a consequence of partial pancreatoduodenectomy, one with ileus I0 weeks post-operatively, and one with anastomotic dehiscence 6 weeks post-operatively. There were two tumour-related deaths in the local excision group (G3 RI: 8 months postoperatively; G1 R 0 : 6 4 months) and two tumour-related deaths in the partial pancreatoduodenectomy group (GI R0: 67 months; G3 R0:74 months).
Concerning tumour recurrence and related mortality in all R0 cases ( n = 34), there were three pTl/R0 cases where the tumour recurred, one ofwhich had a G3 grading. In the local excision group, one Gl tumour recurred and the patient died 64 months after surgery. The other two recurrences were in the partial pancreatoduodenectomy group (G3/NI and G l / N l 7, with a survival of 74 and 67 months, respectively.
Survival Morbidity In the local tumour excision group there was a complication rate of 22% (pancreatitis, n = 1; subphrenic abscess, n = 1). For pancreatoduodenectomy, morbidity was higher (35%; subphrenic abscesses, s7= 3; pancreatic fistulae, n = 4; biliary fistula, n = 1; ileus, n = 17.
In the local excision group, four patients are still alive today, after 16, 9, 5 and 3 years without tumour recurrence (see Fig. 2). The survival curve of patients of this group from the fourth year post-operatively resembled the natural death rate," with 17= 5 patients alive. Four patients (44%) survived 5 years or more. Five-year overall survival in the partial pancreatoduodenectomy group was 73% (n-- 19 of 26).
Resectability Whereas all tumours could be entirely removed in the pancreatoduodenal resection group, there was one G3 tumour in the local excision group which had penetrated into lymphatic vessels (LI) and where the resection margins were not free of tumour (R 1). This patient's poor overall condition (hemiparesis, insulin-dependent diabetes, myocardial infarction, cachexia) precluded any further operative
Discussion
Although usually vague and non-specific, the prodromal symptoms of neoplastic growth of the ampulla of Vater set in early and these lesions are more likely to be diagnosed at an early stage. Diagnostic advances, especially in computed tomography
Local exc&ion of p Tl-ampullary carcinomas and endoscopic ultrasound, increase the reliability of preoperative diagnosis and tumour staging, as well as postoperative follow-up. EUS, a method introduced to our patients in 1992, has become a useful tool in determining the extent and depth of invasion t2 and it further increases the likelihood of detecting existing T l-lesions. Frozen section has proven useful in distinguishing adenoma from carcinoma. In one case (GI) a false-negative (4%) diagnosis was made in our series; in another case, diagnosis was indeterminate and a carcinoma (G2) was found on permanent histology (both patients underwent subsequent Whipple's procedure, where no remaining tumour could be found). However, several frozen sections may be necessary for diagnosis. More difficult, and to some degree subjective, is the conventional grading (G 1-3) of malignant tumours in frozen section, the distinction between GI and G2 tumours particularly depends on the experience of the pathologist. More reproducible in frozen section is the distinction between low and high grade tumour, as proposed by UICC. ~3 Unfortunately, in our material, one G2 tumour, resected by a Whipple's procedure, showed multiple microscopic metastases in regional lymph nodes which would have most certainly remained undetected if a local excision had been carried out. Therefore, frozen sections of suspicious lymph nodes may be helpful for intraoperative staging and planning, but negative findings should not be overvalued. A further histological feature of interest in determination of invasiveness is the infiltration of lymphatic vessels. However, the diagnosis may be difficult and depends on the tissue excised. The ampulla has a distinct pattern of lymphatic drainage and in contrast to pancreatic tumours with a diffuse lymphatic spread, tumours of the ampulla tend to involve a single group of lymph nodes, even in advanced disease/~ These morphological features make the ampullary lesions a distinct clinical entity yielding a substantially superior prognosis, unless confused with the far more frequent heterogeneous 'periampullary lesions'. ~5 Correspondingly, Bittner ~ showed that in ampullary carcinomas of stage pTl, irrespective of the tumour grade and exact site of the carcinoma, only one of 15 examined groups of lymph nodes was involved (6.7%) correlating well with 7.7% in our study. This implies that the risk of a prognostically relevant metastatic spread lies within the same range as the average mortality figures for partial pancreatoduodenectomy. ~7 The principle of performing partial pancreatoduodenectomy for a confirmed carcinoma of the ampulla of Vater has been advocated by most authors since the 1970s, 4'6'18 even though this procedure has never been compared with the local ampullary excision in controlled prospective trials on classified tumour subgroups. Of all ampullary carcinomas, 5-year survival after partial pancreatoduodenectomy is around 40"/o in most reports (n=24; 7 n=2319). For local excisions the sizes of the case series are smaller and are subjected to an unfavourable preselection in many instances. Therefore, the figures seem to be more variable and range from 9% (n = 1419) to 440/0 (n = 84), the latter notably being the largest documented study to date without pre-selection of poor-risk patients (Table 3). When Makipour (n = 82°) explained that in selected older
369
patients with localized tumours, ampullectomy provided results equal to, or better than, a pancreatoduodenal resection this was at a time when mortality from Whipple's procedure was still high. As mortality from this method was substantially decreasing even in elderly patients -'t and now ranges from well below 5% in large operative centres, the most viable justification for limiting surgery to local excision has become disputable, s In our department Whipple's procedure has so far been indicated for all carcinomas of this region whenever a curative intention was feasible. The mortality rate in our series was at an overall 7.7% and at 3.9% for operations performed after 1978. The post-operative morbidity of Whipple's procedure, however, remains high, at 35% even today. Local excision has been justified only in cases of old age and poor condition. Accordingly, in the present series, patients on whom excision of the papilla had been performed (n = 9), were of a significantly higher age (mean: 69.7 vs 58.4 years) on average. Interestingly, despite unfavourable pre-selection in this group there was nil mortality, with a lower complication rate (22%). If applied to a younger age group, the substantially less impaired quality of life would have to be also considered in favour of the local resection. Without tumour staging, Knox, 7 presenting his series of 25 locally resected cases with nil operative mortality, vaguely stated that there does appear to be a group of patients with ampullary carcinomas who are adequately treated by a local excision. In 1991 Koch ~7presented his series of four patients, where ampullary carcinomas, macroscopically invisible and undetected by frozen section, were discovered postoperatively by full histology (pTl G1 NO). These 'occult' carcinomatous formations within adenomas did not recur for the observed 1-8 post-operative years and the performed local resections were regarded curative. This experience prompted the author to advocate abstinence from pancreatoduodenal resection in those cases provided regular and frequent followup investigations were carried out. Increasing numbers of reported local excisions of ampullary carcinomas, ~'~7 although still mainly episodic in themselves, show that ifpatients had been grouped according to Gand T-classifications, survival rates in the well-differentiated (GI/2) and early stage (pTl NO M0) subgroups would be equal to those of pancreatoduodenectomy. Likewise, Mori, ~7 with his histopathological findings on n = 5 stage I patients who had undergone Whipple's procedure, stated that local excision may have been reasonable in these cases. The results o four series indicate, that, if limited to patients with well or moderately differentiated (i.e. 'low risk' according to UICC) and completely resectable ampullary carcinomas of the earliest stage and without lymphatic invasion, local excision seems to produce survival rates similar to those of Whipple's procedure, although mortality and complication figures are markedly lower with local excision. Controversy remains over T1-G3-1esions, which might not always be detected via frozen section. Unlike in local resection of Ti carcinoma of the rectum where a major operation would follow in a case of local irresectability, a G3ampullary carcinoma missed on frozen section would entail
370
P Klein et al.
Table 3. Compiled data on locally resected ampullary carcinomas
Author
Year
Patients
Staging
Grading
Tumour-related death (years)
Akwari~ Tudor2~ Robertson4
1977 1984 1986 1986 1989 1990
pTI ? ~ ? (R0) pT 1 ?
? GI GI G3 ? GI ?
I; 5; 15
Knox7 Delcorej5 Gertsch'~
4 I 4 2 25 1 5
Kochz7 Erlangen
1991 1995
4 9
pTl pTl pT1
GI GI/2 G3
a re-laparotomy and a Whipple's procedure. However, there was not a single such case in our series, and two patients in whom Whipple's procedure was added to a prior local excision had well (G l) and moderately (G2) differentiated carcinomas showing no residual tumour in the pancreatoduodenal specimens. In summary, if tumour-specific therapy of ampullary lesions was intended, our proposals for the following conditions would be: 1. With a pre-operative diagnosis of adenoma or TI N0carcinoma of the ampulla o fVater, local resection is indicated; if intraoperative findings show T>I or N>0 or 'high-grade' tumour, the procedure would have to be extended to partial pancreatoduodenectomy. 2. If, post-operatively, an adenoma or a tentative T1 NO carcinoma had to be reclassified by full histological evidence as T>I, N>0, or ifa poorly differentiated Tl-G3-carcinoma was found, partial pancreatoduodenectomy would subsequently need to be performed. Any lymphatic metastasis or lymphatic infiltration detected pre-, intra, or post-operatively would, for reasons of radicality, necessitate immediate or subsequent pancreatoduodenectomy and precludes local resection. Ifthe patient was unfit for extensive surgery, local excision would be the procedure of choice, unless palliative measures (e.g. endoluminal laser treatment; stent placement) were preferred. There should be regular and frequent follow-up of locally excised carcinoma patients at least every 3-months for the first 2 years and every 6 months until completion of the 5year follow-up period. If these checks are adhered to, the combination of endoscopic and endosonographic procedures should facilitate early detection of any tumour recurrence and provide reasonable safety, acknowledging that even by using all of the indicated diagnostic and therapeutic measures, lymphatic metastases cannot be definitely excluded. In our pT1 Gl/2 tumours, a lymphatic metastasis was present in one of 24 (4.3°/'0)patients. At present, however, this risk seems to be equal or lower than the mortality of Whipple's procedure in our as well as in published series. 5.7 We must also accept that in our study, like in studies of most other large centres, numbers of this rare tumour entity are as yet too small to reach a definite conclusion. The possibility of combining cases of other studies is limited by the lack of comparability. Minimal criteria should therefore
4; 5 0, 3; 0, 7
Unrelated death (years)
6
Aliveafter years 2 18 1
5 year survival 51%
5 0, 6
2; 4; 4
9 all alive after 1-3 years 1; 4; 5; 8 3; 5; 9; 16
be met in the uniform evaluation ofcarcinomas of the ampulla of Vater. Special attention should be drawn to a careful and complete histological processing of the resected specimen, whereby lymphatic invasion should be excluded. Staging according to UICC, histology and grading should be provided in any case, as should values for mortality, morbidity, survival and tumour recurrence. Additionally, values for quality of life would be desirable. Until further evidence becomes available, it should be concluded that a local tumour excision of carcinoma of the ampulla of Vater is justifiable under the following conditions: If the tumour is confined to the ampulla (pT 1) and is graded Gl/2 according to U1CC. If there is no evidence of lymphatic penetration and if the tumour has been resected completely (R0-resection, UICC). With figures for survival equal to those of pancreatoduodenectomy and with lower complication and mortality rates despite a worse initial medical status and higher age, local recurrence could be avoided. Long periods of post-operative survival suggest a low probability of lymphatic spread as seen in similar limited procedures elsewhere.
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A cceptedfor publication 19 April 1996