Short-term outcome of pylorus-preserving pancreaticoduodenectomy for pancreatic carcinoma

Short-term outcome of pylorus-preserving pancreaticoduodenectomy for pancreatic carcinoma

Hamed Rashad, MD; Mohamed A Mansour,MD; Ahmed  Zeidan,MD; Hussein  G El-Gohary, MD; Ashraf M Abd elkader, MD

Department of General Surgery, Benha University, Benha, Egypt.

Abstract

Objectives: To illustrate immediate  and  short-term outcome  of pylorus-preserving

pancreaticoduodenectomy (PPPD) as a surgical modality for patients having pancreatic carcinoma.

Patients & methods: The study included 23 patients; 13 males and 10females with mean age of 66.3±4 years. All patients underwent clinical evaluation, laboratory assessment and CT or MRI examination. Primary outcome measures included frequency of leakage, fistula, intra­ abdominal fluid collection/abscess, delayed gastric emptying and/or postoperative bleeding. Secondary outcome measures included operation time, blood loss, required blood replacement, status of resection margins, number and status of removed lymph nodes, general morbidity, duration of  ICU  and  postoperative (PO)  hospital stay  and  PO  overall   mortality.

Results: No intraoperative complications or mortality were recorded. Site of tumor origin was pancreatic in 15 patients and ampullary in 8 patients. Nine tumors were poorly differentiated. Mean tumor diameter was 2.4±0.4 em.Surgical margin showed microscopic infiltration in two patients. Perineural and vascular invasions were detected in 13 and 10 patients, respectively. Seventeen patients had positive lymph node metastases in the resection specimen. Mean number of resected lymph nodes was 17±1.8. Mean ICU stay duration was 2.4±0.8 days. One patient developed acute myocardial infarction on the 2nd PO day. The frequency of fiStula development was 13.6%; one patient had intra-abdominal collection and underwent CT guided drainage. Four patients (18.2%) developed wound infection and 6 patients had delayed gastric emptying for total PO morbidity rate of 59.1%. Mean PO hospital stay was 10.6±1.9 days with an immediate PO survival rate of95.7%. Mean duration of follow-up was 31.1±9.1 months with

2-year survival rate of82.6%, 3-year survival rate of39.1% and 4-year survival rate of 13%.

Conclusion: PPPD could be considered as a safe, feasible and effective surgical modality for patients having pancreatic tumors with controllable PO morbidity and PO survival for >4 years in 13%.

Key words: Pancreatic carcinoma, pylorus-preserving pancreaticoduodenectomy, morbidity, survival.

Introduction:

Pancreatic cancer is the fourth leading cause of cancer death in men and the fifth in women, accounting for4.8% and 5.5% of cancer deaths in men and women, respectively. The aggressive biology of these tumors and the high local recurrence rate in combination with the early metastatic spread lead to 5-year survival rates between  II% and 2I%  after resection.!.2

Surgical resection by  means of pancreaticoduodenectomy provides the only

chance of cure for patients with periampullary and pancreatic carcinoma. Advances in surgical technique have reduced the operative mortality rate to below 5% in high-volume centers. Nevertheless, operative morbidity remains high, occasionally approaching 30% to 40%, most often including pancreatic fistula, intra­ abdominal abscesses, sepsis, and delayed gastric emptying.3

The classic  Whipple  operation is the standard basic surgical procedure performed predominantly  for   the   treatment  of

periampullary and pancreatic head cancer. The classic Whipple operation consists of an en bloc removal of the pancreatic head, the duodenum, the common bile duct, the gall bladder, and the distal portion of the stomach together with the adjacent lymph-nodes.Classic Whipple operation can  lead  to  specific complications such as early and late dumping, postoperative weight loss and postoperative reflux.4,5

Pylorus preserving pancreaticoduodenectomy {PPPD) represents an important advance  in the history of pancreatic surgery. The operation can be performed with a low operative mortality and morbidity, is technically easier thanthe standard Whipple resection, and it minimizes the long­ term physiological disturbance to the patient. Clinical and experimental evidence has substantiated the view that preservation of the pylorus reduces the incidence of marginal anastomotic ulceration following pancreatectomy. Multiple meta-analyses documented that in the absence of relevant differences in mortality, morbidity, PPPD does not compromise the long-term survival in patients with periampullary cancers, and seems to be as effective as the classic Whipple as a surgical modality for management of periampullary cancer.6-8

The present study aimed to illustrate the immediate and short-term outcome of pylorus­ preserving pancreaticoduodenectomy{PPPD) as a surgical  modality  for patients  having pancreatic carcinoma.

Patients and methods:

The current study was conducted at General Surgery Department, Benha  University Hospital since June 2007 till March 2012 so as to allow 2-year follow-up period for the last case operated on. After obtaining written fully informed patients' consent, all  patients

presenting were admitted at General Surgery

ward for clinical evaluation, laboratory assessment and underwent CT or MRI examination for  assuring the  diagnosis.

Operative procedure:

Upon opening of the abdomen, liver was carefully  inspected and  palpated for  any metastatic disease.  Pancreatic tumor  was

palpated and its mobility was assessed, if it is respectable, duodenum and head of pancreas were  mobilized and  the  tumor  was  then bimanually palpated. Then, mobilization of the second and third parts of duodenum was commenced and continued until the superior mesenteric vein comes into view as it crosses the duodenum. The stomach was mobilized and  the  right  gastro-epiploic vein  was meticulously dissected and ligated between ligatures  just before its termination  in the superior mesenteric vein below the neck of the pancreas. All tributaries passing from the head of pancreas and uncinate process to the superior mesenteric vein were divided between ligatures. Cholecystectomy was performed and common bile duct (CBD) and lower hepatic ducts were mobilized and CBD was divided just above the entry  of the cystic  duct. Jejunum was mobilized and ligament of Treitz was incised to free the duodenojujenal flexme and proximal jejunum was divided. Then, neck of pancreas was divided, pancreatic duct was cannulated with fine catheter passed into jejunum prior to end-to-side pancreaticojujenal  anastomosis which was conducted and the other end of the catheter was gotten out through separate jejunal stab.Then CBD was anastomosed end-to-side to  jejunum   and  proximal  jejunum   was anastomosed to the pylorus. After assuring hemostasis, abdominal cavity was drained and abdomen  was    closed,  Figure(l-4).

Outcome items:

a. Primary outcome measures are defined as

PO pancreatic associated morbidity (disease specific) and included leakage of pancreatic anastomosis/pancreatic fistula, intra­ abdominal fluid collection/abscess, biliary leakage  and/or  postoperative  bleeding. Delayed gastric emptying defined as the persistent need for a nasogastric tube for longer than 10 days was also recorded.

b.   Secondary  outcome measures  included

operation time, blood loss, required blood replacement, status of resection margins, number and status of removed lymph nodes, duration of ICU stay, general morbidity including postoperative gastrointestinal bleeding, shock, sepsis; duration ofhospital stay and postoperative overall mortality.

Figure(1):Showed duodenumis kocherized; inforiorvenacava (IVC) anddilated common bile   duct   (CBD)   were  also   shown.

Figure(3):The view afterthe Jstcutshowing the proximal pylorus and the distal endof the Jst part of the duodenum (D).

Results:

The study included 23 patients; 13 males

and 10 females with mean age of 66.3±4; range: 58-72 years. Fifteen patients had additional co-morbidities with diabetes mellitus was the commonest.  Patients' detailed enrollment data are shown in Table(l). All

Table (1): Ptltients' enroUment dma.

Figure (2): Showed sling suspension of the dilated  common   bile   duct   (CBD).

Figure (4): The view after completion of excision showing the proximal pylorus and distally the small intestine (S Int.) which was cut for anastomosis.

patients bad PPPD with a meanoperative time of 4±0.8; range:3-5 hours. Mean blood loss was 640±115; range:400-800 ml.All patients required blood transfusion with a mean number of used units was 2.8±0.7; range: 2-3 units Table(2). No intraoperative complications or mortality was recorded.

Data are presented as mean±SD & numbers; ranges and percentages are in parenthesis.          -

Table (1): Operative data.

Data are presented as mean±SD & numbers,· ranges and percentages are in parenthesis.

The site of tumor origin was pancreatic in

15 patients (65.2%) and ampullary in 8 patients (34.8%). Mean tumor diameter was 2.4±0.4; range: 1.5-3 em. Nine tumors were poorly differentiated (39.1%). Surgical margin showed microscopic  infiltration in two patients; one patient had carcinoma involving the margin at the level of the uncinate  process adjacent to the superior mesenteric vein and the other had

a positive microscopic margin at the pancreatic neck?body transection site. Thirteen patients (56.5%) showed perineural invasion and 10 patients (43.5%) showed vascular invasion. Seventeen patients (73.9%) had histologically positive lymph node metastases in the resection specimen, and  the  mean  total  number of resected lymph nodes was 17±1.8; range: 15-

20 node, Table(3).

Table (3): Pathological data of excised specimens.

Data are presented as mean±SD & numbers; ranges and percentages are in parenthesis.

All  patients passed the  immediate postoperative period at surgical ICU for a mean duration of 2.4±0.8; range:  1-4  days.  One patient developed acute myocardial infarction on the 2nd postoperative day; he was cardiac patient and had previous coronary artery bypass surgery one year prior to diagnosis of pancreatic cancer. Unfortunately, this patient died on the

4th postoperative day because of development of cardiogenic shock that failed to respond to treatment, Table(4).

During hospital  stay three patients (13%) developed fistula; the leaking fluid was biliary and CT examination of these patients identified intra-abdominal collection in only one patient and had CT guided collection drainage. All of the  three patients received conservative

Table (4): Postoperative data.

treatment and well-responded to it without the need for re-operation. Four patients (17.4%) developed wound infection that responded to conservative treatment in three of them, but the 4th patient was diabetic and infection was flared up, this patient received intensive insulin therapy and wound was drained, after control of  diabetes wound healing proceeded uneventfully without the need for re-suturing. Six patients (26.1%) developed delayed gastric emptying for a mean duration of 12.2±1.2; range: 11-14  days. Total PO morbidity  rate was 59.1% of patients who remained alive till discharge. Twenty-two patients were discharged alive for an immediate PO survival rate of95.7% after a mean PO hospital stay of

10.6±1.9; range: 8-15 days, Table(4).

Data are presented as mean±SD & numbers; ranges and percentages are in parenthesis.

Throughout mean duration of follow-up of

31.1±9.1; range: 6-43 months; 3 patients died for a follow-up survival rate of 87% and a total survival rate  of  82.6%. Nineteen patients completed their follow-up for >2 years (2-year

survival rate of 82.6%), 9 patients completed their follow-up for >3 years (3-year survival rate of 39.1%) and 3 patients completed their follow-up for >4 years (4-year survival rate of

13%), Figure(5).

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23

22

21

20

19

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11

16

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Figure (5): Number of survivals recorded througlwut follow-up period.

Dileuuion:

Concerning the primaly outcome ofPPPD,

immediate PO morbidity was reported in t3 patients for afrequency of 59.1%;tbn::epatimts (13.6%) developed biliary fistula., 4 patients (18.2%) developed wound infection and 6 patients (27.2%)developed DGE.InhaDdwith these figures of PO morbidity, K.wok et aV re.IJOited that post-cperati.ve moroidity rate was SS%and included intra-abdominal collections (17%),major hemonbage (l0.7%), pancreatic anastomotic le;Wsge (9%) and delayed gastric emptying (22%).Zureikat et aLto reported an overall  complications rate   of   SO%.

Six patients had delayed gastric emptying for a frequency of27.3% and mean duration

of hospital stay for such morbidity ofabout 12 days.  Multiple  studies tried  to  explore underlying  factors and propose  lines for

prevemionandlormanagement ofOOE. Malleo

et af.ll  reported DGE frequency of 13.8%

among their series of 260 patients underwent PPPD and found abdominal collections, pancreatic fistulae and sepsis were associated

with clinically relevant DGE, but pancreatic andbiliary fistulawere independeotriskfiu:tors for development of DGE. Kurahara et af.t2 reported an incidem:e ofDGE of34.8% with PPPD  and  13%  with  subtotal stomach preserving pancreaticoduodenectomy with significantly shorter duration of hospital stay. Kawai  et  al.13 found  pylorus-resecting

pm;reaticoduodeectomy significantly reduces the incidence ofDGE compared with PPPD. Gangavatikcr et af.l4 evaluated the effect of ante<:olic versus retrocolic reconstruction on DGE and found no significant difference in the incidence of DGE in the antecolic vs.the retrocolic group (34.4% vs. 27.8%) and concluded that the incidence ofDGE does not appear to be related to the method of reconstruction.

No patient developed pancreatic fistula, this could be attributed to the applied procedural modification in the form of extracorporeal

pancn:atic drainage through a catheter passed throughtbe pancreatic duct prior to anastomosis of pancreatic stump to the jejunum , then was extracted  through  a  distant  jejunal  stab Sllll'OUDded by purse stringsuture and the distal end of the catheter was extracted through a separate skin stab, so all efflux of pancreatic duct was drained out of the jejunum, giving time for anastomotic line healing andprotecting it from exposure to pancreatic enzymes. In hand with the personal trials for avoiding pancreatic fistula, Mita et af.ls found the use of TachoComb fibrin adhesive as a sealing method     in       duct-to-mucosa pancreaticojujeunostomy is safe, reliable for the prevention of pancreatic fistula, and shows promise  for  all  types of  reconstruction following  pancreaticoduodenectomy.

The obtained results illustrated the reasibility

Ain-Sham:sJ SllTg2012;S(J):SJJ-540

and safety ofPPPD with reasonable operative time  and intraoperative blood loss  and hospitalization  time. In hand with these data; Tani et al.16 evaluated the outcomes of PD and PPPD  for pancreatic cancer  and found  that surgical outcomes and  incidence of postoperative complications suggest that PPPD is  an  appropriate surgical procedure for pancreatic adenocarcinoma with significantly better  cause-specific survival of the  PPPD patients  than that of the PD patients. Also, Alsaif17 documented that in the context  of operative factors like blood loss and operation time, complications such as  DGE  and anastomotic leaks, and the impact on quality of life and survival, PPPD was found to be at least  as good as classic  PD, if not better in some aspects.  In support  of feasibility and safety, various studies tried it for management of unusual types of cases; Souzaki et ai.IS presented a case of a 6-year-old female with advanced pancreatoblastoma treated successfully  by   PPPD after  induction chemotherapy, radiation  and  stem cell transplantation. Fragulidis et ai.19 presented a case of PPPD for pancreatic head cancer, 13 years after a transhiatal esophagectomy, sparing the gastric  tube and the right gastroepiploic artery and vein and concluded  that PPPD is less time-consuming and less invasive, since no further  reconstruction of the alimentary tract or  the  vascular system is  applied.

Throughout mean duration of follow-up of

31.1±9.1; the 2-year survival rate was 82.6%, the 3-year survival rate was 39.1% and the 4- year survival rate of 13%. These figures are coincident  with that presented in literature; Chakravarty et al.2o reported that the overall

1- and  3-year survival rates  of patients undergoing PD/PPPD were 50.0% and 16.7%, and 44.4% and 12.2%, respectively.However, the reported survival duration was longer than that reported by Peros et al.21 who documented that  major pancreatic resections can  be performed  safely, with acceptable  morbidity and mortality and good long-term results, even in middle-volume centers with median survival for the whole group of patients of 17 months. These data also go in hand with that previously reported in reviews of randomized controlled studies which  showed that postoperative mortality was not significantly different after

both types of operations, but quality  of life was reported to be in favor of the pylorus­ preserving  Whipple  operation.6-8,22

The reported results and review of literature allowed to  conclude that  PPPD  could  be considered as a safe, feasible and effective surgical modality for patients having pancreatic tumors  with controllable PO morbidity and PO survival for >4 years in 13%.

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