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Epidemiology, Diagnosis and Management of Pancreatic Cancer in 4 Hospitals in Yaoundé And Douala (Cameroon)

Article Information

Jean Paul Engbang1,2*, Christian Beugheum Chasim3, Franck Moise Abenelang1, Marcelin Ngowe Ngowe1,4

1Faculty of Medicine and Pharmaceutical Sciences, The University of Douala, Douala-Cameroon

2Douala Laquintinie Hospital, Douala-Cameroon

3Douala General Hospital, Douala-Cameroon

4Faculty of Medicine and Biomedical Sciences, The University de Yaounde I, Yaoundé-Cameroon

*Corresponding Author: Jean Paul Engbang, Faculty of Medicine and Pharmaceutical Sciences, The University of Douala, Douala-Cameroon

Received: 11 March 2021; Accepted: 17 March 2021; Published: 31 March 2021

Citation: Jean Paul Engbang, Christian Chasim Beugheum, Franck Moise Abenelang, Marcelin Ngowe Ngowe. Epidemiology, Diagnosis and Management of Pancreatic Cancer in 4 Hospitals in Yaoundé And Douala (Cameroon). Journal of Surgery and Research 4 (2021): 167-181.

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Abstract

Introduction: Pancreatic cancer is a public health problem because of its poor prognosis. Most of the factors related to the prognosis of this cancer are negative and pessimistic. Therefore, our work is to estimate the overall survival of our patients and to establish the prognostic factors associated to survival.

Materials and Methods: This was a cohort study with retrospective data collection method, carried out from January 1, 2010 to December 31, 2019 i.e. a period of 10 years. The research took place in General hospitals of Yaounde and Douala; at Yaounde University Teaching Hospital and at Laquintinie. We obtained ethical clearance from the Institutional Review Board of the University of Douala. We included records of patients with pancreatic cancer of at least 12 months follow-up after diagnosis.

Results: We had a total of 94 cases of pancreatic cancer during our study. Mean age at diagnosis was 56.5 ±12.3 years, the most represented age group was 50-59 years (48.9%), with sex ratio of 1.6 in favor of men. Median consultation time was 6 months. The most common stage of diagnosis was stage IV of the TNM classification.

Conclusion: At the end of our study, it appeared that survival associated to pancreatic cancer remains low, in fact the median overall survival was 25 months. All prognostic factors found in our study were factors of poor prognosis which were: consultation time >3 months; high serum creatinine level and the occurrence of metastases.

Keywords

Pancreatic cancer, Prognostic factors, Survival, Therapy, Cameroon

Pancreatic cancer articles; Prognostic factors articles; Survival articles; Therapy articles; Cameroon articles

Article Details

1. Introduction

Cancer refers to an uncontrolled proliferation of abnormal cells [1]. These cells can metastasize through the blood or lymphatic route [2]. In 2018 global mortality from all cancers, for all ages and for both sexes was around ten million deaths; after lung cancer (18.2%), digestive cancers, in particular colorectal (9.2%) and gastric (8.2%) cancers are the major causes of death across the world [3]. Pancreatic cancer was responsible for four hundred and fifty-nine thousand new cases and nearly four hundred and fifty thousand deaths in 2018, ranking it the 7th leading cause of cancer death in the world and justifying the challenge it represents today [4], becoming in recent years a real global health problem [5, 6]. Indeed, in North America the mortality associated with pancreatic cancer was 6.5/100,000 inhabitants, classifying it as the 3rd cause of death in the United States [7]. In France, mortality was higher (7.3%) in women [8]. According to the WHO, by 2030, five hundred thousand new cases are expected in developing countries, this also means that at least four hundred and eighty thousand deaths from this cancer are predicted [5]. In Africa, a study shows that the mortality is 7% and is higher than the incidence [9]. Moreover, according to the WHO, in Africa in 2018, sixteen thousand new cases of pancreatic cancer were noted against fifteen thousand five hundred deaths [3]. The prevalence of pancreatic cancer is 0.7% with a death rate associated with pancreatic cancer of 87% during hospitalization in Togo [10]. Cholestatic jaundice, abdominal pain and deteriotion of general condition are the most frequent complaints of patients [10]. The most widely used surgical treatment is a palliative surgery (bilio-digestive bypass) versus curative surgery (Cephalic Duodenopancreatectomy and Splenopancreatectomy) [11]. Concerning chemotherapy, gemcitabine, folfirinox and capecitabine are the chemotherapy molecules in mono or poly chemotherapy [11, 12]. In Cameroon, this cancer has a prevalence of 1.16% of cancers for survival below 5% [13-15]. Very few studies concerning the different aspects of pancreatic cancer management have been carried out in Cameroon, which is why we thought of doing this multicenter study on this subject.

2. Materials and Methods

This was a retrospective descriptive study of histologically proven malignant tumors of pancreas, diagnosed from January 1, 2010 to December 31, 2019. The research took place in departments of surgery, gastro-enterology and oncology of General hospitals of Yaounde and Douala; at Yaounde University Teaching Hospital and at Laquintinie. Patients for whom the diagnosis was confirmed by histology were included in the study. We collected, from register of those departements, socio-demographic, clinical, paraclinical, therapeutic data and those relating to the evolution of patients operated on for gastric pathologies. All these data entered in a pre-tested data sheet. Data were registered and processed using Statistical Package for Social Sciences (SPSS) software version 23.0.

3. Results

3.1 Epidemiological characteristics and medical history

As shown in table 1, our studied population had a mean age at diagnosis of 56.5±12.3 years with extremes ranging from 17 to 87 years. Patients aged between 50 and 59 years were the most represented at 48.9% (46 cases).

Men were in the majority. We had 58 men (62%) for a sex ratio of 1.6.

Patients were mostly alcohol and tobacco users at 71.3% and 52.1%, respectively. While familial diabetes returned to first position at 46.8% among family history.

Variable

N

%

Age

Oct-19

1

1.1

20-29

1

1.1

30-39

4

4.3

40-49

9

9.6

50-59

46

48.9

60-69

23

24.5

70-79

4

4.3

≥80

6

6.4

Gender

Male

58

61.7

Female

36

38.3

Comorbidities

Diabetes

30

31.9

Chronic pancreatitis

9

9.6

Pancreatic tumor

3

3.2

Acute pancreatitis

8

8.5

Chronic hepatopathy

10

10.6

Other cancer

2

2.1

Hemoglobin electrophoresis

4

4.3

Hemoglobin electrophoresis

4

4.3

Family history

Diabetes

29

30.9

Chronic pancreatitis

5

5.3

Pancreatic cancer

3

3.2

Breast cancer

10

10.6

Ovarian cancer

3

3.2

Colorectal cancer

12

12.8

Toxicological history

Alcoholic intake

67

71.3

Smoking history

49

52.1

Table 1: General characteristics and medical history of patients

3.2 Clinical signs

The frequent reasons for consultation were cholestatic jaundice and abdominal pain represented at 78.8% (74 cases) each (table 2). The patients seen in consultation mainly presented the grade IV deterioration in general condition according to the WHO classification; or 47.9% (45 cases) of the patients examined. Overweight patients accounted for 42.6% (40 patients) of the sample (table 2). About 4 out of 5 patients presented with scleral jaundice on physical examination. And almost 1 in 4 patients presented with edema during physical examination.

Symptoms/Signs

n

%

Functional signs

Cholestatic jaundice

74

78.8

Abdominal pains

74

78.8

Weight loss

35

37.2

Vomiting

35

37.2

Constipation

29

30.9

Diarrhea

3

3.2

Abdominal bloating

5

5.3

Leg swelling

2

2.1

General signs

WHO general condition

AGC stade 0

11

11.7

AGC stade I

10

10.6

AGC stade II

14

14.9

AGC stade III

14

14.9

AGC stade IV

45

47.9

Température

Normothermy

84

89.4

Hyperthermia (T°≥37,8°C)

10

10.6

Physical signs

Sclera

Icterics

74

78.7

Anicteric

20

21.3

Presence of abdominal mass

23

24.5

Edemato-ascitic signs

22

23.4

Lower limb(s)

12

12.8

Ascites

1

1.1

Ascites + lower limb(s)

8

8.5

Hydrops

1

1.1

AGC-Alteration of General Condition

Table 2: Symptoms and physical signs of the study population.

3.3 Paraclinical signs

3.3.1 Biological data: According to table 3, CA 19-9 was achieved in 48 patients (51.1% of the sample), came back high in 39 of them (81.3%). Of the 20 (21.3% of the sample) patients for whom lipase results were available, 10 had a high rate (50.0%).7 out of 10 patients had high amylasemia. Sixteen patients (17.0% of the sample) achieving total bilirubin, all of them had predominantly conjugated hyper bilirubinemia. We found that 87 (92.5% of the sample) patients had kidney workup and 31 of them had high creatinine. Of the 91 (96.8% of the sample) patients who achieved the rhesus blood group, just below 30% of these were of O blood group and were the most represented in our study; on the other hand, all were rhesus positive.

Variables

Effective (n=94)

Percentage (%)

Tumor marker

CA 19-9

48

51.1

≥ 37 UI/ml

39

81.3

ACE

7

7.4

> 5 µg/l

3

42.9

AFP

6

6.4

≥ 10 ng/ml

1

16.7

Enzymes

Lipasemia

20

21.3

> 60 UI/L

10

50

Amylasemia

10

10.6

> 45 UI/l

7

70

Hepatic check

Total bilirubin

16

17.0

> 12 mg/l

16

100

Direct bilirubin

16

17.0

> 2 mg/l

16

100

Renal check

87

92.5%

Urea

> 0.45 g/l

10

11.5

Creatinine

> 13 mg/l

31

35.6

Hepatic cytolysis

78

82.9

Presence

68

87.2

Absence

10

12.8

Nutrionation assessment

Albumin

10

10.6

< 40 g/l

2

20

≥ 40 g/l

8

80

ABO blood group

91

96.8

O

27

29.6

A

21

23.1

B

21

23.1

AB

22

24.2

Rhesus

91

+

91

100

ACE: Carcinoembryonic Antigen; AFP: Alpha Foeto-Protein; CA 19-9: Carbohydrate Antigen 19-9

Table 3: Distribution of patients according to biological signs

3.4. Imaging signs

3.4.1. Diagnostic radiological workup: Abdominal ultrasound was the first-line examination and in 47 patients (50.0%), it revealed a mass most often located at the cephalo-isthmic level (43 cases; 91.5%). While the CT scan found a pancreatic abdominal mass in 45 patients (47.8%), it identified a cephalo-isthmic mass in 8 out of 10 patients (table 4).

In total, the tumor was usually localized in just over 4 out of 5 patients at the cephalo-isthmic level of the pancreas.

The majority (46.7% of patients with ductal dilation) presented with diffuse dilation of the bilio-pancreatic ducts.

Variables

Effective (n=94)

Percentages (%)

Localization of pancreatic mass

Abdominal ultrasound (n=47)

Céphalo-isthmic

43

91.5

Corporealocaudal

4

8.5

Abdominal CT scan (n=45)

Céphalo-isthmic

36

80.0

Corporealocaudal

9

20.0

MRI (n=2)

Céphalo-isthmic

1

50

Corporealocaudal

1

50

Ductal dilations (n=75)

Choledochus

6

8.0

Secondary biliary tree

2

2.6

Wirsung

1

1.3

Santorini

0

0

CA

12

16.0

CAW

14

18.7

CAWS

35

46.7

Other combination

5

6.7

MRI: Magnetic Resonance Imaging; CA: Choledochus + secondary biliary tree; CAW : CA + Wirsung ; CAWS : CAW + Santorini

Table 4: Distribution of patients according to diagnostical imaging results.

3.5 Extension assessment and staging

As represented in table 5, metastases were present in 65 patients (nearly 7 out of 10) in our sample and were predominantly lymph node (n = 63; 96.9%). CT revealed metastasis in 57.6% (37 cases) of our sample. MRI was rarely performed. We could only find the charts of 5 patients in whom the results of the chest x-ray were available, and these showed interstitial lung disease (3 cases) and were normal in 2. The most common TNM stage at diagnosis is stage IV in 51.1% (48 cases).

Variables

Effective (n=94)

Percentages (%)

Presence of métastases

65

69.2

Ultrasound (n=26)

Ganglionic

26

100

Hépatic

10

38.5

Pulmonary

0

0

CT TAP (n=37)

Ganglionic

37

100

Hépatic

22

59.4

Pulmonary

16

43.2

MRI TAP (n=2)

Ganglionic

2

100

Hépatic

1

50

Pulmonary

1

50

Stade TNM

Stade IA

15

16

Stade IB

10

10.6

Stade IIA

4

1.1

Stade IIB

12

12.8

Stade III

5

3.2

Stade IV

48

51.1

TAP: Thoraco-Abdomino-Pelvic

Table 5: Distribution according to extension assessment and staging

3.6 Histopathology

Analysis of the surgical specimen was performed in 75 patients (79.5%). The most common histologic type is pancreatic ductal adenocarcinoma at 80.7% (78 cases). Low-grade differentiation of the tumor was most often seen in 59 patients (75.6%). In the end, the histological diagnosis was made in 78 patients (82.9%). In our patients under 30 years of age we were not able to objectify the histologic type asserting pancreatic cancer.

Variables

Effectifs (n=94)

Pourcentages (%)

Sample

Surgical specimen

75

79.8

Histological type

Pancreatic ductal adenocarcinoma

63

84

Acini carcinoma

1

1.3

Acini cystadenocarcinoma

2

2.7

Pancreatoblastoma

8

10.7

Solid pseudo papillary tumor

1

1.3

Degree of differentiation

75

79.8

Undifferentiated

13

17.3

Low grade differentiation

58

77.3

Well differentiated

4

5.3

Table 6: Distribution according to histopathology

3.7 Treatment

3.7.1 Types of treatment: The most commonly performed surgical procedure was bilio-digestive bypass in almost 4 out of 5 of those who had surgery. Gemcitabine monotherapy was the most widely used (32 patients; 43.2%) as chemotherapy in our study (table 7).

Variables

Effective (n=94)

Percentages (%)

Surgical treatment

87

92.6

Cephalic duodenopancreatectomy

12

13.8

Left splenopancreatectomy

6

6.9

Median pancreatectomy

0

0

Total pancreatectomy

0

0

Bilio-digestive bypass

69

79.3

Medical treatment

74

78.7

Exclusive gemcitabine

32

43.2

Gemcitabine+Erlotinib

4

5.4

Gemcitabine+oxaliplatin

8

10.8

Gemcitabine+Cysplatin

1

1.4

Folfirinox

25

33.8

Gemcitabine+ Paclitaxel

13

17.6

Table 7: Distribution according to treatment modalities

3.7.2 Treatment according to stage: As shown in table 8, Bilio-digestive derivation associated with chemotherapy (most often exclusive gemcitabine in 29 patients) was most often adopted as a management protocol (46 cases, 51.1%) for patients with stage IV cancer.

Therapies

Stage

Effective (n=94)

Percentages (%)

Exlusive excisional surgery

IA

4

4.3

Resection + adjuvant chemotherapy

IA

2

2.1

IB

1

1.1

IIB

5

5.3

Neoadjuvant chemotherapy + excision

IB

2

2.1

IIB

4

4.3

BDD + Chemotherapy

IA

6

6.4

IB

4

4.3

IIA

1

1.1

IIB

3

3.2

III

3

3.2

IV

46

48.9

Exlusive BDD

IA

4

4.3

IB

2

2.1

Exlusive chemotherapy

IV

7

7.4

BDD: Bilio-Digestive Derivation

Table 8: Types of treatment according to stage

3.8 Evolution

3.8.1 Response to therapy: We have 10 patients (10.6% of the sample) who had good control of the progression of their pancreatic cancer after a median follow-up time of 18 months and more. We initially had 63 patients (67.0%) with lymph node involvement and 48 patients (51.1%) with distant metastases at the time of diagnosis (table 9)

Variables

Effective (n=94)

Percentages (%)

Situation before the treatment

Invaded lymph nodes

65

69.1

Distant metastases

48

51.1

After the treatment (t≥12moths)

Full remission

10

10.6

Locoregional recurrences

12

12.7

Secondary metastases

21

22.3

Table 9: Distribution according to the response to the treatment.

3.9 Locoregional invasion after treatment

The median occurrence time of locoregional recurrence was 13.1 months. The lymph nodes of the celiac plexus were most often affected. Chemotherapy was most often used in case of recurrence and as a first-line (table 10).

Variables

Modalities

Effective (n=12)

Percentages (%)

Occurrence delay

12 months

7

58.3

18 months

3

25.0

24 months

1

8.3

30 months

1

8.3

Occurrence site

Mesenteric lymph nodes

3

25.0

Celiac lymph nodes

8

66.7

Other lymph nodes

1

8.3

Treatment initiated

Abstention

3

25.0

Chemotherapy

9

75.0

Table 10: Distribution according to the occurrence of locoregional metastatases.

3.10 Occurrence of distant metastases after the treatment

The median time to secondary onset of metastases was 12.7 months. Most often they occurred in the liver or simultaneously in the liver and lungs (8 cases; 38.1% each).

Exlusive chemotherapy gemcitabine or folfirinox was often used for cases of metastasis. In addition, we have a patient lost to follow-up after 18 months of follow-up.

Variables

Modalités

Effectifs (n=21)

Pourcentages (%)

Occurrence delay

12 months

14

66.7

18 months

6

28.6

24 months

1

4.7

Occurrence site

Liver

8

38.1

Lungs

5

23.8

Liver + Lungs

8

38.1

Other

0

0

Treatment initiated

Lost view

1

4.7

Chemotherapy

20

95.3

Table 11: Occurrence of distant metastatases after therapy

3.11 Complications

As shown in table 12, the main complications of pancreatic cancer were diabetes (in 76.6%) and compression of the main bile duct (63.8%).

Gastroparesis was the most common surgical complication (5.3%), while chemotherapy mainly induced renal toxicity (14.9%).

Variables

Effective (n=94)

Percentages (%)

Complications related to the disease

82

87.2

Acute pancreatitis

13

13.8

Pseudo cyst of the pancreas

3

3.2

Compression of the bile ducts

60

63.8

Exocrine pancreatis insufficiency

25

26.6

Diabetes/hyperglycemia

72

76.6

Infections

10

13.5

Induced immunosuppression

3

3.2

Thromboembolism

3

3.2

Surgical complications

10

10.6

Gastro paresis

5

5,3

Pancreatic fistula

1

1.1

Gastrointestinal bleeding

2

2.1

Abscess of the abdominal wall

2

2.1

Complications of chemotherapy

28

29.8

Renal toxicity

14

14.9

Table 12: Distribution according to occurrence of complications

4. Discussion

The mean age at diagnosis was 56.5 ± 12.3 years, with extremes ranging from 17 to 87 years. Ntagirabiri et al in Burundi in 2012 had an average age of 50.3 years [16]. In Burkina Faso, Koura et al who found in 2020 an average of 56.4 years [17] while in Algeria, Sellam et al in 2015 who found an average of 62.2 years [18]. These data confirm that pancreatic cancer is said to be “age-dependent” with the elderly as a preferential target.

Our study finds that the sex ratio is 1.6 in favor of men. These findings are similar to those of Rawla et al in the United States in 2019, who found a sex ratio of 1.5 [7]; and Bouvier et al. in France in 2017 who found a sex ratio of 1.4 [19]. These data confirm that males are the most affected by pancreatic cancer.

According to our study, patients with average socioeconomic status are the most affected, followed by those with an affluent standard of living. This does not agree with the results of the study conducted by Bryere et al in France in 2019, which found a higher incidence in patients with a very low standard of living rather than in the less poor [20]. And neither does it agree with the data of Ouédraogo S et al. in 2018 which found that digestive cancers in general (including pancreatic cancer) had as a target population patients with less than 1 US dollar of daily income (defining the socioeconomic level of patients in their study) [6]. Our findings could be explained by the fact that people at a low (or even very low) socioeconomic level are hardly diagnosed with pancreatic cancer because they do not have enough means to go to the hospital at the onset of symptoms.

During our study, we found a median consultation time of around 6 months with extremes ranging from 0 to 52 months. While most of our patients coming to consult were already at the metastasis stage, in our study we found a median time to onset of metastases of 0 days. Our consultation time is similar to that found by Alegbeyele et al in Nigeria in 2019, who found a median consultation time of 25 weeks, or around 6 months [21]. This is because in Cameroon, we first resort to traditional therapies as a first-line treatment. Patients won't get to the hospital until when the later have not been effective, thus the delay in diagnosis and the diagnosis at a late stage (metastasis stage).

In our personal study, patients consuming alcohol were the most represented (71.3%), followed by patients consuming tobacco (52.1%). El Fatihi in his research in Morocco in 2019 found that diabetes (29.6%) and tobacco (26.1%) were the most frequent [11], while El Mir found that tobacco was the most important risk factor and attributed to it was 20% of pancreatic tumors [12]. We can justify that because in Cameroon alcohol consumption begins at an early age and is taken disorderly in large quantities. If alcohol has not yet demonstrated its role in the genesis of pancreatic cancer; it can in the long run lead to chronic pancreatitis and even according to the study by Mandengue et al. [22] alcohol is associated with obesity which are both (chronic pancreatitis and obesity) risk factors establishing the occurrence of pancreatic cancer.

We found that cholestatic jaundice and abdominal pain (78% each) were the most frequent complaints of patients, followed by vomiting and weight loss (37.2% each). Zertiti S found in 2018 in Morocco that the most frequent signs were jaundice (81%), abdominal pain (78%) and pruritus (38%) [23]. Aaouidi in 2019, still in Morocco, found that abdominal pain was the most frequent complaint (60%), followed by vomiting and jaundice (20% each) [24]. While Bouglouga O et al instead found in 2015 a deterioration of the general condition (97%), abdominal pain (87%) and jaundice (80%) as being the frequent reasons for consultation [10]. The most frequent signs are similar. We could explain it by the fact that in general the tumor is localized at the level of the head of the pancreas; which will therefore combine signs such as jaundice, pruritus, abdominal pain or a change in general condition, weight loss and vomiting.

We discovered that the majority of patients (56.4%) were diagnosed with stage IV pancreatic cancer against 26.6% for stage I. Sellam, et al in their study found 26.2% of cases were diagnosed at stage M1, followed respectively by stages T4 (21.8%) and T3 (21.2%); on the other hand Aomari et al found 80% of patients with visceral metastatic extension [18, 25]. We can cite three reasons for this: the insidious or silent evolutionary nature of pancreatic cancer; the nonspecific nature of its clinical expression, which from the outset did not lead to making this diagnosis; and finally we can say that the patient generally comes to the hospital long after the revelation of the disease for various reasons such as lack of financial means or simple negligence.

The most widely used surgical treatment during our study was palliative surgery, in particular bilio-digestive bypass (79%) versus curative surgery, which represented 21% (Cephalic Duodenopancreatectomy at 14% and Splenopancreatectomy at 7%). El Fatihi had also found that 31% of his patients underwent palliative surgery (choledoco-duodenal diversion with cholecystectomy, duodeno-jejunal diversion, gastro-jejunal and bilio-digestive diversion...) against 21% who had undergone surgery for curative purposes (DPC, SPG) [11]. Meanwhile El Mir in his research found rather that palliative surgery (bilio-digestive bypass) was 31% against curative surgery at 57.9% (CPD with lymph node dissection) [12]. We could justify our data by the fact that in our study, the majority of our patients were diagnosed with stage IV cancer. Stage IV is that of distant metastases and contraindicates any tumor resection; therefore the only possible alternative is palliative surgery, including bilio-digestive bypass.

Gemcitabine was the chemotherapy molecule most used in mono (42.3%) or poly chemotherapy in our study, followed by Folfirinox (33%). El Mir also found that Gemcitabine is more used for neo-adjuvant chemotherapy and in combination with Capecitabine in case of adjuvant chemotherapy [12]. El Fatihi finds similar data concerning Gemcitabine, which is very often used in pancreatic cancer in combination or alone [11]. Gemcitabine would therefore still be widely used to date and more often preferred to other molecules in monotherapy or in combination, probably because Gemcitabine had better median overall survival and better progression-free survival compared to survival associated with other molecules; when used in combination, there is a survival gain of several months or even years.

5. Conclusion

The mean age at diagnosis of our patients with pancreatic cancer was 56.5 ± 12.3 years and the male sex was predominant with a sex ratio of 1.6. The frequent risk factor in our study was 71.3% alcohol consumption; the most frequent functional signs were cholestatic jaundice and abdominal pain at 78.8% each. The diagnosis was most often made at stage IV of the TNM classification in 56.4% of cases and the most common histologic type was pancreatic ductal adenocarcinoma in 67.0% of cases. In 79% of cases a bilio-digestive diversion was performed among those who had undergone a surgical intervention; while gemcitabine was used more in our study. The most common cancer-related complication was diabetes (76.6%); nearly 3 out of 4 patients had died.

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