ročník 11,2003 č.4
Klinika

Pancreas carcinoma and chronic pancreatitis. Diagnostic dilemmas from surgical aspect

Oláh, A.

Dept. of Surgery, Petz Aladár Teaching Hospital
Győr, Hungary

Attempts to improve long-term survival

Although pancreatic resection for ductal adenocarcinoma is a much safer procedure than 20 years ago with an operative mortality less than 5% in high-volume centers, this achievements are overshadowed by the fact that long-term survival following resection continues to be low. Only 5 - 10 % of resected patients live beyond 5 years after surgery with curative intent, with median survivals of 12 to 18 months. However, survival data are limited, in part, because survival is largely reported as Kaplan-Meier estimates (1).
Efforts to improve surgical treatment have led to the development of more radical procedures, as total pancreatectomy, routinly performed portal vein resection or radical extended pancreatectomy and lymphadenectomy.
Several studies were unable to show any difference between the classic Whipple procedure and the pylorus-preserving resection for the treatment of carcinoma, so the removal of the distal stomach seems an unnecessary procedure The total pancreatectomy did not have any impact on long-term survival in comparison to standard pancreatoduodenectomy.
Most patients following curative resection have residual micrometastasis. The fact, that the pancreatic bed is the sole site of recurrence in 30% of the cases and is a component of intraabdominal recurrence in 38-86% makes the concept of "extended" resection logical (2). Radical resection of lymph nodes and peripancreatic soft tissues, as currently developed in several centers in Japan, suggest improved outcome. On the other hand, the current prospective, randomized trials in the United States fail to show this benefit (1, 3). At present the data do not permit adequate evaluation in terms of conclusions.
The portal vein resection obviously increases the resectability rate. However, there are almost no long-term survivor. The patients likely to benefit the most from portal vein resection are those with inflammatory adherence to the vein wall who would otherwise undergo only a palliative procedure (4).

Future perspectives

It is clear that in vast majority of pancreatic cancers operative treatment alone at the time of diagnosis is inadequate. Further improvements in survival should be sought at the areas of earlier diagnosis. In cases of tumors smaller than 1 cm almost 60 % 5-year survival could be achieved (5). Unfortunately, these "minute tumors" are unable to detected by conventional imaging techniques. Endoscopic ultrasonography has shown promising results in identifying cancers smaller than 2 cm. The newly developed "pancreatoscopy" can detect early ductal epithelial changes or abnormalities. Mutations in the K-ras oncogene might be useful method in screening of high risk population. Combination of these methods may increase the rate of early cancers still in really curable stadium (1).

Cancer and chronic pancreatitis

On the other hand, it is important to identify the high-risk population for development of pancreatic cancer. The association between chronic pancreatitis and pancreatic cancer is a well-known phenomenon. Epidemiological studies indicate that patients with chronic pancreatitis have a 3 - 15 times risk of developing pancreatic carcinoma compared with a control population. Löwenfels represented a 1.8% and 4.0% risk of cancer for chronic pancreatitis patients at 10 and 20 years, respectively (6). Almost 40% of patients with hereditary pancreatitis develop cancer by age 70 (7).
In an Italian review four of nine patients surviving beyond 5 year were submitted to surgery with a preoperative diagnosis of chronic pancreatitis (8). The indication for resection because of inability to rule out malignancy might be 10 - 20 % in different series.
Based on these facts it should be important to resect all suspicious pancreatic head mass, which can be solid (ductal adenocarcinoma, chronic pancreatitis, endocrine tumor) or cystic lesion (cystic neoplasm, true cyst).

Preoperative histology

There is no doubt that, if easily achievable, preoperative histological confirmation of the diagnosis of malignancy is advantageous.
The need for surgical intervention is often determined by the presence or absence of jaundice or duodenal obstruction. In a patient with obstructive symptoms secondary to a pancreatic head mass, resection may be a choice of treatment regardless of the certain diagnosis. In these cases the preoperative histological confirmation is not essential before surgical intervention.
By contrast, the management of a relatively asymptomatic tumor of the body or tail, or the non-operative treatment of an advanced case, is dependent on accurate diagnosis. It is important for an honest discussion on prognosis with the patient or relatives, also. So, the need for confirmed diagnosis is inversely proportional to the resectability of the lesion.
Cystic lesions are easily identified by CT or MRI, although even fine-needle aspiration biopsy cannot sufficiently differentiate between malignant and benign cystic tumors, and it fails in about 30 %. Rapid tumor enhancement and specific biochemical features may suggest an endocrine tumor. The vast majority of malignant head tumors are ductal carcinomas (80 -90 %), which are almost always solid masses in radiologic imaging studies. Although nonductal tumors are also often solid, cystic components demonstrated radiographically in an isolated pancreatic mass suggests a nonductal tumor, which has a far better prognosis with a 5-year survival of 30 % to 50 % (9, 10).
The first step in a case of a suspected pancreatic head cancer is the staging of the disease and the evaluation of the fitness of the patient. In unresectable cases (advanced tumor or distant metastases), histological confirmation and non-operative procedure (stenting) is the optimal choice of treatment.
Various imaging techniques may suggest the diagnosis or the potential for resectability (US, CT, MRI, angiography, endosonography), but even with all of the cytological techniques (brush cytology during ERCP, percutaneous FNA or core biopsy) in 15 - 20 % of the cases impossible to differentiate between cancer and chronic pancreatitis (9, 11). It means that in practice in one in five patients with a suspected pancreatic carcinoma may have no confirmed diagnosis having completed a staging protocol (12).
The reported sensitivity of percutaneous FNA cytology for diagnosing malignancy varies between 55 % and 97 %. As false positive results are exceptional, the specificity in most studies is 100 % (13, 14). The occurence of false negative results means a great limitation of the method, because a negative result should not influence the decision-making if the clinical suspicion of cancer is high and the mass seems to be resectable. The preoperative histological confirmation adds also little in patients in whom exploration is planned anyway, even for palliation of gastric outlet obstruction. Based on these arguments percutaneous FNA cytology is recommended only for advanced cases where nonoperative palliation is feasible.

Intraoperative dilemmas

Therefore the case of a suspected malignant tumor of the head of the pancreas is a fairly common problem faced by surgeons. What can we do with a pancreatic head mass intraoperatively without previous cytologic or histologic verification? When must we strive to establish definite diagnosis at all costs, and how can we achieve it?
The intraoperative FNA cytology is the most common method. The sensitivity is 70 % to 100 % by reported series, most often it is around 90 %. Tissue biopsy of pancreatic lesions can be done as incisional or wedge biopsies or by use of Trucut needles. The sensitivity of pancreatic biopsy for histological evaluation has been reported to be 83 - 92 %. False positive results are extremely rare. The reported rate of complications related to the biopsy varies from 0 % to 10 % and the mortality rate from 0 % to 4 % (13).
The reason that the sensitivity of intraoperative tissue biopsies are not better than FNA cytologies is the surgeon's fear of complications. Cautious wedge biopsies, obtaining too superficial specimens, can result false negative reports, because pancreatic cancer often is surrounded by a large rim of pancreatitis. Therefore, needle biopsy is recommended for mass located deep in the head of pancreas, reserving tissue biopsy only for superficial lesions.
When should pancreatic biopsies be done? If pathological confirmation will alter our decision about resection, all efforts should be made to confirm the diagnosis. In the case of a mass lesion with obstructive symptoms cytology does not alter the need for surgical decompression, and some kind of resection is a reasonable treatment option. Moreover, the inflammatory head mass is a special clinical entity. It has always a higher pain score and higher risk of developing pancreatic cancer. Based on these data resection remains a valuable form of treatment for painful or complicated chronic inflammatory head mass; so if the tumor seems to be resectable it should be resected, when the surgical team can perform it with an acceptable low mortality rate.
The most questionable cases are those patients, who have a descrete mass lesion in the pancreatic head without any obstructive symptoms. It may be also a chance finding as a suspected pancreatic cancer. On the other hand, an asymptomatic focal mass secondary to chronic pancreatitis may require no surgical treatment. In these cases accurate biopsy should be done. If the biopsy is positive, resection may be done. However, if the biopsy is negative, the abdomen should be closed and further diagnostic tests done. Evaluating the result of an intraoperative cytologic or histologic examination, we have to take into consideration that a benign result by itself never excludes the presence of a malignancy.
Differentiation between chronic pancreatitis and carcinoma is difficult, even intraoperatively. Intraoperative biopsy has a false negative rate of about 10 % for detecting pancreatic cancer (10). These results show that a nihilistic approach in the case of pancreatic head mass with suspected but unproved malignancy is not justified. Pancreatoduodenectomy should be performed for any tumor even without histologic confirmation if an experienced pancreatic surgeon cannot exclude pancreatic carcinoma.

References

  1. Tsiotos GG, Farnell MB, Sarr MG: Are the results of pancreatectomy for pancreatic cancer improving? World J Surg, 1999, 23 : 913
  2. Sperti C, Pasquali C, Piccoli A, Pedrazzoli S: Recurrence after resection for ductal adenocarcinoma of the pancreas.World J Surg 1997, 21 : 195
  3. Yeo CJ, Cameron JL, Lillemoe KD et al: Pancreaticoduodenectomy with or without distal gastrectomy and extended retroperitoneal lymphadenectomy for periampullary adenocarcinoma, part 2: randomized controlled trial evaluating survival, morbidity and mortality. Ann Surg 2002, 236 : 355
  4. Shibata C, Kobari M, Tsuchiya T et al: Pancreatectomy combined with superior mesenteric-portal vein resection for adenocarcinoma of pancreas. World J Surg 2001, 25 : 1002
  5. Ishikawa O, Ohigashi H et al: Minute carcinoma of the pancreas measuring 1 cm or less in diameter - Collective review of Japanese case reports.Hepato.Gastroenterology 1999, 46 : 8
  6. Löwenfels AB, Maisonneuve P, Cavallini G et al: Pancreatitis and the risk of pancreatic cancer. N Engl J Med 1993, 328 : 1433
  7. Löwenfels AB, Maisonneuve P, DiMagno EP et al: Hereditary pancreatitis and the risk of pancreatic cancer. J Nat Cancer Inst 1997, 89 : 442
  8. Sperti C, Pasquali C, Piccoli A, Pedrazzoli S: Survival after resection for ductal adenocarcinoma of the pancreas. Br J Surg 1996, 83 : 625
  9. Böttger TC, Junginger T: Treatment of tumors of the pancreatic head with suspected but unproved malignancy: is a nihilistic approach justified? World J Surg 1999, 23 : 158
  10. Thompson JS, Murayama KM, Edney JA et al: Pancreaticoduodenectomy for suspected but unproven malignancy. Am J Surg 1994, 169 : 571
  11. Yamaguchi K, Chijiiwa K, Saiki S et al: "Mass-forming" pancreatitis masquerades as pancreatic carcinoma. Int J Pancreatol 1996, 20 : 27
  12. Carter CR, Imrie CW: Is histological diagnosis essential before resection of suspected pancreatic carcinoma? In: Pancreatic disease. Ed. by Johnson CD, Imrie CW. Springer-Verlag London Ltd, 1999.
  13. Ihse I, Axelson J, Dawiskiba S et al: Pancreatic biopsy: Why? When? How? World J Surg 1999, 23 : 896
  14. Nakamura R, Machado R, Amikura K et al: Role of fine needle aspiration cytology and endoscopic biopsy in the preoperative assessment of pancreatic and peripancreatic malignancies. Int J Pancreatol 1994, 16 : 17

Addresse for correspondence:

Professor Attila Oláh, MD, PhD.
Dept. of Surgery, Petz Aladár Teaching Hospital
Győr, Hungary