Advertisement

SN Comprehensive Clinical Medicine

, Volume 1, Issue 2, pp 104–112 | Cite as

Treatment of Insulinomas with Minimally Invasive Physical Procedure. Literature Review

  • Stanislav V. Berelavichus
  • Andrey G. Kriger
  • Rimma S. Dugarova
  • Ayrat R. KaldarovEmail author
Surgery
  • 197 Downloads
Part of the following topical collections:
  1. Topical Collection on Surgery

Abstract

Insulinoma is the most common functioning pancreatic neuroendocrine tumor with the development of the organic hyperinsulinism and the severe hypoglycemia. Insulinoma can be treated radically only by surgical removal. In cases when the surgery may cause severe complications with the high risk of mortality, the physical non-surgical methods can be used. The world literature review using PubMed, MedScape, and Cochrane databases was performed. Keywords “insulinoma” + “physical methods” were used including every type of the method. One hundred fifty-two articles in English devoted to different physical methods of treatment of neuroendocrine tumors were found. Twenty-seven papers with the description of the minimally invasive treatment of insulinomas were found among them. There were data about the different methods revealed such as radiofrequency ablation, microwave ablation, cryodestruction, laser ablation, irreversible electroporation, photodynamic therapy, high-intensity focused ultrasound, Cyberknife, and tumor alcoholization. Literature search showed that there are a few papers about the description of the self-experience of each method, but there are no papers with the full compartment of advantages and disadvantages of each method of treatment. Each method was used because of its availability in the hospital or department. Contemporary statement of the physical mini-invasive method of insulinomas treatment requires investigations with the full randomized trials. These researches can identify the points to use one or another physical method and to choose the most right way to treat patients with hormonal-producing pancreatic neuroendocrine tumors.

Keywords

Insulinoma Neuroendocrine tumor Pancreas Miniinvasive surgery Physical treatment 

Introduction

Insulinoma is a hormone-secreting tumor of the pancreas that is characterized by a borderline malignant potential. Frequency of occurrence is 1–2 per 1,000,000 people per year [1, 2, 3]. Hypoglycemic syndrome is a severe complication of insulinoma. It can even lead to hypoglycemic coma. Insulinoma, unlike ductal adenocarcinoma, has no expensive periphery growth potential and does not cause pancreatic hypertension nor atrophy of the pancreatic parenchyma. Thereby, there is a high risk of postoperative complications such as severe pancreatitis, external pancreatic fistula, and erosive bleeding. [4, 5]. The development of minimally invasive treatment is an alternative to resection methods.

Radiofrequency ablation, cryodestruction, ultrasonic, microwave and laser ablation, photodynamic therapy, irreversible electroporation, Cyberknife, and ethanol destruction are used in the treatment of pancreatic tumors.

Materials and Methods

While looking through the literature at the beginning of 2017, 152 articles devoted to different physical methods of treatment of neuroendocrine tumors were found. Twenty-seven methods of minimally invasive treatment of insulinomas were found among them [1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51].

Results

The data analyses showed that until now, there has been no study presenting all the advantages and disadvantages of minimally invasive physical methods of insulinoma treatment. Data on basic techniques of minimally invasive non-resectional methods are given below.

Radiofrequency Ablation

The first heating of the biological substance was carried out by the French physicist A. d’Arsonval in 1891 [6]. He showed that a flow of waves with a frequency of over 10 kHz heats tissues without pain or muscle contractions. His experiments became the basis for electrosurgery. At the beginning of the twentieth century, radiofrequency coagulation for the treatment of tumors of different localizations started to spread.

The first application of radiofrequency ablation under endoscopic ultrasonic control was described by S. Nahum Goldberg in 1999 in an experiment upon animals [7]. There were many adverse events and a high mortality rate in this experiment (30 and 54%). Ultimately, the length of the active electrode was adapted to the size of the expected pancreatic lesion.

In 2014, S. Fegrachi published meta-analyses on the usage of radiofrequency ablation in the treatment of pancreatic tumors [8]. In this publication, five research projects are described. One hundred fifty-eight patients with locally advanced cancers of the pancreas are represented (Table. 1). All patients underwent radiofrequency ablation. The median survival rate in patients with the third stage of locally advanced pancreatic cancer was between 20 and 33 months. This data correlates positively with the results of radical surgical treatment followed by adjuvant chemotherapy. [8]. In the study by V. Singh in 2011, life expectancy ranged between 9 and 36 months [9].
Table 1

Efficacy and safety of RFA in treatment of pancreatic tumors

Authors, years

N patients

Locally advanced pancreatic cancer

Metastases

Quantity

Complications

Complications associated with RFA

Mortality

Median survival, months

Girelli, 2011

100

100 (100%)

1–2

26%

15%

3%

20

Singh 57, 2011

10

10 (100%)

10%

10%

0%

9–36

Spiliotis, 2007

12

8 (66%)

4 (34%)

1–3

25%

16%

0%

33

Wu, 2006

16

11 (69%)

5 (31%)

2–5

43%

37%

19%

Matsui 58, 2000

20

9 (45%)

11 (55%)

1–15

10%

10%

5%

3

Summary

158 (100%)

138 (87%)

20 (13%)

     

In most cases, more than one RFA procedure was needed, firstly, because the volume of the coagulum was too small and could not include the whole lesion, and secondly, because of tumor tissue resistance. Complications associated with RFA ranged between 10 and 37%. The main types of complications reported included pancreatic fistula, gastrointestinal bleeding, portal vein thrombosis, and acute pancreatitis. The mortality rate was about 19%.

Common complications were in the range from 10 to 40%. The types varied widely and included pneumonia, peritoneal abscess, acute renal failure, ascites, hepatic failure, diphtheria colitis, hemoperitoneum, fluid congestions in the abdomen, gastric ulcers, and cholelithiasis.

Many of the complications arose as a result of the duodenum, biliary tree, or peri-pancreatic vasculature. Many authors report that RFA causes inadvertent damage to structures adjacent to the zone of ablation, such as the normal pancreas, that increases the risk of acute pancreatitis and pancreatic fistulas.

In the reviewed studies, the main safety factors in preventing complications are described. The allowable limit of heating of the coagulation antenna should not exceed 90 °С, the distance between the antenna’s “tip” and the vessels should be more than 5 mm, and the distance between the “tip” and the duodenum should be more than 10 mm.

The first open RFA on pancreatic insulinoma was described by D.A. Litvak in 2003 [10]. In 2009, S. Limmer was the first to carry out a transcutaneous RFA on an insulinoma that was located on the front surface of the pancreatic tail in an 80-year-old patient with severe comorbidities. Within 7 months of the procedure, no hypoglycemia was registered [11].

Microwave Ablation

The largest experiment with microwave ablation on pancreatic cancer was presented in 2007 by N. J. Lygidakis [12] (Table 2). MVA was carried out in 15 cases of 15 patients with locally advanced pancreatic tumors which were found to be unresectable. The mean diameter was 6 cm (4; 8); patients with distant metastasis were not included in the study. In six patients (40%), postoperative pancreatitis type A according to ISGPF was seen. Median survival was 22 months.
Table 2

MWA of pancreatic adenocarcinoma

Author

N patients

Lesion size

Complications

Median survival (months)

Mortality

Lygidakis

15

60 mm

6 (40%)-pancreatitis

22

0%

Carrafiello

10

32 mm

2 (20%)-pancreatitis

9.2

0%

Carrafiello G. described 10 cases of pancreatic head cancer treated with MWA [13]. Five underwent transcutaneous microwave ablation, five laparotomy access. The median diameter of the tumors was 32 mm (20–43 mm). There were no significant differences found between the groups. Median survival was 9.2 months (3; 16). Postoperative complications were observed in two patients (20%), according to Clavien-Dindo I degree in one, III—two (postnecrotic cyst was drained by puncture, and pseudoaneurysm of the gastroduodenal artery was treated through endovascular access).

In 2015, O.T. Chen (USA) presented the first successful results of transcutaneous MWA in the treatment of pancreatic insulinoma in a 60-year-old with unresectable lung cancer. The patient was discharged within 48 h without complications. There was no relapse of hypoglycemia registered within 3 months of observation [14].

In Russia, transcutaneous MWA for pancreatic insulinomas were carried out and described by A. Chernousov in 2015. An 81-year-old patient entered the clinic with signs of organic hyperinsulinism and severe comorbidities. A neuroendocrine tumor was found in the pancreatic head and was 21 × 10 mm in size. The pancreatic duct was 5 mm from the lesion. The postoperative period was without complications, and on the 7th day, the patient was discharged. An endarterectomy was carried out after 3 weeks for vital indications. In the postoperative period, the patient died of acute myocardial infarction. There was no hypoglycemia registered during the observation period. [15].

Cryodestruction

In 1970, Richard S. Myer described the cryodestruction technique in experimental treatment on animals’ pancreases. [16]. For 20 years, this method was used as a treatment of pancreatic carcinomas in men [17]. In a review in 2012, Zhen Tao studied the safety and efficacy of cryosurgery in local advanced pancreatic tumors [18]. In his article, he analyzed five studies that included the necessary criteria to evaluate the method (Table 3). Acute pancreatitis followed by delayed gastric empty was the most frequent postoperative complication. The system’s immune reaction caused by the focal thermal ablation is described by the authors, but the mechanism of pancreatitis has still not been well examined.
Table 3

Efficacy and safety of cryodestruction in the treatment of pancreatic tumors

Authors

N

1 year survival

Reduce of pain syndrome

Median survival

Gastrostasis

Pancreatic fistula

Biliary fistula

Gastrointestinal bleeding

Kovach

9

66.7% (6/9)

0

0

Li

44

57.5%

89.7% (34/38)

14

40.9% (18/44)

6.8% (3/44)

6.8% (3/44)

0

Wu

15

63.6%

13.4

0

0

1

0

Yi

8

100% (5/5)

25% (2/8)

0

1

Xu

38

16

0

0

In 2016, Mirko D’Onofrio and coauthors completed their review on cryodestruction in the treatment of pancreatic tumors [19] with the J. Li study [20]. Two insulin-producing tumors in genetically proven familial multiple endocrine neoplasia type 1 were treated with percutaneous cryodestruction.

Laser Ablation

Nowadays, lasers are used to treat primary and secondary hepatic lesions. Opportunities for its use in pancreatology are being studied in experiments on animals. [21]. The first use of laser ablation in vivo was described by F. Di Matteo in 2014. [22]. A laser ablation of 9 mm nonfunctional neuroendocrine tumor of pancreas isthmus under endoscopic ultrasound guidance was performed on a 46-year-old woman. In the anamnesis was a distal pancreatic resection due to the NET of the pancreas tail, and she refused a total pancreatectomy. No complications occurred after the procedure. The 12-month follow-up CT scan showed a reduction of the ablated area from 18 to 9 mm.

Irreversible electroporation ablation

One of the newest methods of tumor ablation. This method is based on the electromagnetic field created by an alternating current. The electromagnetic field damages the cell membrane and causes necrosis of the cell. Four studies have been published to date (Table 4) [23, 24, 25]. The only case of percutaneous electroporation was presented in an article in 2012 [24]. Fourteen patients with unresectable adenocarcinomas of the pancreas were described in this study. Radical surgical procedures were carried out after several procedures of IRE. Post-procedural follow-ups were held between 11 and 14 months. In the early postoperative period, there were no deaths, but after 2, 4, and 5 months, three patients died from the progress of the main disease with initial distant metastases.
Table 4

Irreversible electroporation ablation in treatment of pancreatic tumors

Authors

N patients

Quantity of common complications

Complications associated with the procedure

Total mortality

Post-procedure deaths

Median survival, months

Laparotomy

 Martin et al.20

54

32

1

20.2

 Philips et al.21

49

1

 Martin et al.22

29

9

4

1

1

Percutaneous

 Narayana et al.23

14

3

1

3

0

6-month survival 78%

Total

144

44 (30%)

5 (3%)

5 (3%)

2 (1.3%)

 

Two duodenal fistulas, a pancreatic fistula, a bile fistula, and a thrombosis of the portal vena are the complications associated with IRE, which occurred in 3% of cases.

R. Martin reported that the standard treatment of unresectable adenocarcinomas accompanied with IRE may extend the period of survival by 9 months (from 11 to 20.2 months) [24, 25].

Photodynamic Therapy

In 2002, A. Bown first described photodynamic therapy for cancer of the pancreas. [26]. Sixteen patients with inoperable adenocarcinomas of the pancreas were studied. All had obstructive jaundice, which was relieved by biliary stenting prior to further treatment. The median survival time after photodynamic therapy was 9.5 months. Seven of the 16 patients (44%) died 1 year after photodynamic therapy (Table 5). In the early postoperative period, two (12.5%) patients had gastrointestinal bleeding due to the involvement of the gastroduodenal artery. This was controlled without surgery.
Table 5

Photodynamic therapy for tumors of the pancreas

Authors

N patients

Photosensitizer

Number of fibers in the antenna

Number of ablations

Outcome

Complications

Bown

16

mTH-PC

Mono

1

Tumor necrosis in 16/16.

Median survival 9.5 months

GI bleeding in 2/16. Controlled without surgery

Huggett

13 + 2

Verteporfin

Mono (13)

Multy (2)

1

Tumor necrosis in 15/15

When multi-wire sensor is used on CT scan a clinically non-significant peripancreatic inflammation is registered.

Patients were kept in a darkened room for at least 1 week after the treatment to avoid photosensitivity reactions. This was the main flaw of this procedure.

High-Intensity Focused Ultrasound (HIFU)

Many studies and series of usages of HIFU are performed nowadays. (Table 6). This treatment leads to full tumor necrosis and a small percentage of specific complications [27, 28, 29, 30, 31, 32, 33, 34].
Table 6

High-intensity focus ultrasound treatment (HIFU) of pancreas

Authors

N of patients

Study model

Outcome and survival

Complications

Wang27

224

Advanced pancreatic ductal adenocarcinoma

No messages

Anorexia, nausea, bloating in 4.5%

Xiong28

89

Unresectable PDAC

Median survival 26 months (stage II), 11.2 months (III), 5.4 months (IV)

Superficial skin burns in 3.4%, asymptomatic pseudocysts in 1.1%

Sung29

46

III or IV stage PDAC

Median survival 12.4 months

Minor complications (abdominal pain, fever, and nausea) 57%

Major complications (pancreatic fistula, gastric ulcer, and skin burns) 10.2%

Xie30

41

1. HIFU alone

2. HIFU combination with gencitabin

Reduction of pain syndrome

1.66.7%

2.76.6%

Absent

Gao et al. 31

39

Local PDAC

Median survival 11 months

Survival of more than 1 year in 30.8% pain syndrome reduced in 79.5%

Absent

Zhao et al.32

37

Gencitabin and HIFU were used in the 2nd phase of the local PDAC

Total survival 12.6 months

Pain syndrome reduced in 78.6%

Neutropenia 16.2%, thrombocytopenia 5.4%, and nausea 8%

Vetshev P.S. et al.33

16

Unresectable PDAC

Median survival

18 months

Idiopathic hyperthermia 5 (31%), III stage burn 1 (6%), reactive pancreatitis 2 (12%), and perforation of the duodenum 1 (6%)

In 2013, К. Wang and coauthors presented a large study that described a retrospective analysis of HIFU in 224 patients with advanced pancreatic carcinoma [27]. The mean age was 60 years old (28–85 years old). In 86 patients, the 3rd stage was present (38%), and in 138, the 4th stage (62%). The tumor was located in the pancreatic head in 47 cases (21%), and in the body and tail, in 177 cases (79%). Ultimately, the length of the active electrode was adapted to the size of the lesion. The procedure was carried out with the JC system that is based on high-intensity focused ultrasound waves which cause hypothermia and coagulation necrosis. The procedure was carried out under real-time ultrasound imaging. There were no severe complications such as hollow organ perforation or bleeding. These results demonstrate the safety of the application of HIFU.

The largest Russian HIFU experience for pancreatic carcinoma was presented by P. Vetshev [35]. Eighteen HIFU were carried out between 2009 and 2014 upon 16 patients. The mean tumor size was 3.5 ± 1.5 cm. Tumors were found in the head of the pancreas in eight (50%), in the body in seven (44%), and in the tail of one (6%). After HIFU, in all cases, decreased tumor sizes were observed, though in one case it fully disappeared. In five cases, idiopathic hyperthermia occurred, and in one, 3rd stage burning; in two, reactive pancreatitis and in one, duodenum perforation was the main complications. There was no mortality in the early postoperative period. Seven patients died within 3 months and 2 years because of the generalization of the illness. The median survival after HIFU in patients with unresectable tumor of the pancreas was 18 months. HIFU has some restrictions despite the positive results. Most restrictions are due to the absence of the acoustic window (constitutional features of the patient, scars of the anterior abdominal wall, colostomy, soldered loops, or previous operation). Destructions cannot be done in cases of tumor invasion into the stomach and/or duodenum wall. The other restriction is mechanical jaundice aggravating the clinical symptoms and leading to minimally invasive procedures that prologues the preparation period before the HIFU (percutaneous external and external internal biliary excretion, extrahepatic ducts stenting).

Cyberknife

A method of treatment used on a well-defined fixed target. It requires the patient to be fixed in a tight and quite painful position. Cyberknife can follow changes in body position and correct the irradiation direction immediately and automatically. Albert C. Kong was the first to use Cyberknife for pancreatic cancer treatment in the first phase. In the postoperative period, pain syndrome and increased body mass were observed in 100% of cases [36]. D. Schellenberg has continued the II phase [37] (Table 7).
Table 7

Radiosurgery for the pancreatic adenocarcinomas

Author

N patients

Mean age

Localization

Stage of the illness

Mean dose (gray)

Combination with chemotherapy

Complications

Effects of the procedure

Median survival

Mortality

Shellenberg35

20

63

II–III, 20

25

+

1 (5%), pain syndrome

18 (90%), nausea

1 (5%), perforations of duodenum

3 (15%), gastric ulcer

2 patients are alive.

Disease progression, 19. Median time before progression, 9.2 months. Only 1 did not have relapse for 25 months

11.8 мес.

Ze36

20

54

13, head

7, body and tail

II, 7

III, 13

40

6 (30%), granulocytopenia

7 (35%), nausea and vomiting

18 (90%), abolition of anesthetics

6 (30%), full response 9 (45%), partial

3 (15%), without effect

1 (5%), tumor progress

7 months. (3; 11)

1 (5%)

Lischalk37

20

64

9 head

11 body, tail

II, 6 (30%)

III, 2 (10%)

IV, 12 (60%)

30

+

2 (10%), cancer progress

13.6 months. (9,7; 16,7)

2 (10%)

Song38

59

62

40 head

19

body, tail

III–IV, 59

45

36 (61%), nausea, vomiting, and diarrhea

1 (1.7%), intestinal obstruction

8 (13.6%), full remission

31 (52.5%), partial remission

12 (20.3%), stable follow up

8 (13.6%), progression

12, 5 мес. (3.2; 48.7)

Hoyer39

22

61

III–IV, 22

42

5 (22%), mucositis, gastric, and duodenal ulcers

8 of 12 (66%) improvement of condition, decrease of pain syndrome.

Median time before progress, 4.8 months. 1 (5%) was alive after 12 months

5.7 months

Zeng40

24

III, 19

IV, 5

45 Гр

9 (37.5%), III class acute toxicity

11 of 14 (78.6%) decrease of the pain syndrome.

Median follow up 35.8 months (14.2; 72.7).

35.8 (14.2; 72.7)

Su41

25

63

20 head

5 body, tail

III, 9 (36%)

IV, 16 (64%)

43.3

Neoadjuvant, 2

6 (24%), nausea, vomiting, and malaise

13 of 20 (65%), pain syndrome decrease.

Total survival within the first year, 37%, within the second year—18%.

11 months (2; 25)

Didolkar42

85

66

57, head

28, body and tail

25.5

+

12 (14.1%), duodenitis

11 (12.9%), gastritis

3 (3.5%), diarrhea

1 (1.2%), renal failure

Total, partial response on the treatment with stabilization of the process in 78 patients for 3–36 months with the median of 8 months. The pain syndrome decreased

18.6 months from diagnosis

8.52 months after the treatment

The results of the studies of stereotaxis radiosurgery for the treatment of patients with local and locally advanced carcinomas show that median survival is within the range from 5.7 to 35.8 months. The choice of the patients to undergo the Cyberknife depended on different types of chemotherapy at various stages of the disease. The median survival increases when combined stereotactic surgery and specific chemotherapy are being used.

Cristiano Huscher, in 2012, was the first to describe the usage of the Cyberknife in organic hyperinsulinism due to a pancreatic tumor in a 44-year-old patient in 2008. There have been no signs of hypoglycemia observed up to the present time [38].

Alcoholization

Alcoholization with ethanol is not a physical but a chemical technique in the treatment of tumors. Nevertheless, we have included this method in our review as one of the non-resectional technologies.

C. Jurgensen, in 2006, reported on a successful treatment of pancreatic insulinoma with a 95% ethanol injection under US control [39]. In 2013, three insulinomas located in the pancreatic head, body, and tail were treated with one-time alcoholization under US control by M. J. Lee. The patient was 26 years old and had MEN I. There is an increased interest in using ethanol in NET for pancreas treatment (Table 8). It is reported as being successful in 100% cases [41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51]. Postoperative pancreatitis occurred in 7 of 45 patients. A severe postoperative pancreatitis that was followed by a laparoscopic necrotomy is described in one patient. Hematoma of omentum bag and pancreatic duct stricture was registered in two cases as late complications. Ethanol destruction carried out under US control is a safe and effective method in the treatment of insulinomas though the long-term results are still not rated. There are no data on ethanol ablation found in Russia.
Table 8

Ethanol ablation of the pancreatic tumors

Author

Year

Number of patients

Complications

Outcome

Jurgensen et al.44

2009

1 (insulinoma)

No

Recovery

Muscatiello, Deprez et al.45,46

2008

2 (3 nonfunctional NET)

1, pancreatitis; 1, hematoma of the omentum bag

Recovery

Vlegaar et al.47

2011

1 (insulinoma)

No

Recovery

Levy-Schnack et al.48, 49

2012

8 (insulinomas)

2, pancreatitis, pseudocyst

Recovery

Lee et al.50

2013

1 (insulinoma)

No

Recovery

Bor-Qin-Paik et al.51–53

2014

11 (insulinomas)

No

Recovery

Yang D et al.54

2015

4 (insulinomas)

No

Recovery

Park et al.55

2015

11 (10, nonfunct. NET; 4, insulinomas)

3, acute pancreatitis

1, abdominal pain

4, incomplete effect in cases of insulinomas

Paik et al.56

2016

8 (2, SPPT; 3, insulinoma; 1, gastrinoma; 2, nonfunction.NET)

2, abdominal pain; 1, acute pancreatitis; 1, hyperthermia

2, ineffective,

6, persistent remission

Total

 

45 patients with 46 pancreatic tumors

  

Discussion

This review has shown a vast interest in minimally invasive physical and chemical methods in the treatment of pancreatic tumors. At the same time, there is no protocol for their use despite the wide range of procedures. Thus, the only indication for the minimally invasive treatment of the NEP is the equipment in the clinic. It is of great importance to work out the guidelines for using minimally invasive physical and chemical destruction of NEP (insulinomas) of the pancreas based on their localization, the size and character of the lesion, the distance from the pancreatic duct, the consistency of the pancreas, and so on. Therefore, studies on this theme should be continued.

Notes

Compliance with Ethical Standards

Conflict of Interest

The authors declare no conflicts of interest.

References

  1. 1.
    Modlin IM, Champaneria MC, Chan AK, Kidd M. A three-decade analysis of 3,911 small intestinal neuroendocrine tumors: the rapid pace of no progress. Am J Gastroenterol. 2007;102(7):1464–73.  https://doi.org/10.1111/j.1572-0241.2007.01185.x.CrossRefPubMedGoogle Scholar
  2. 2.
    Modlin IM, Lye KD, Kidd M. A 5-decade analysis of 13,715 carcinoid tumors. Cancer. 2003;97(4):934–59.  https://doi.org/10.1002/cncr.11105.CrossRefPubMedGoogle Scholar
  3. 3.
    Hauso O, Gustafsson BI, Kidd M, Waldum HL, Drozdov I, Chan AK, et al. Neuroendocrine tumor epidemiology: contrasting Norway and North America. Cancer. 2008;113(10):2655–64.  https://doi.org/10.1002/cncr.23883.CrossRefPubMedGoogle Scholar
  4. 4.
    Kriger AG, Akhtanin EA, Zemskov VM. Risk factors and prevention of postoperative pancreatitis at resection procedures of the pancreas. Khirurgiya. 2016;7:4–10.  https://doi.org/10.17116/hirurgia201674-10.CrossRefGoogle Scholar
  5. 5.
    Abbott DE, Tzeng CW, McMillan MT, Callery MP, Kent TS, Christein JD, Behrman SW, Schauer DP, Hanseman DJ, Eckman MH, Vollmer CM. Pancreas fistula risk prediction: implications for hospital costs and payments. HPB (Oxford). 2016.  https://doi.org/10.1016/j.hpb.2016.10.016
  6. 6.
    Siperstein AE, Gitomirski А. History and technological aspects of radiofrequency thermоablation. Cancer. 2000;6:293–303.Google Scholar
  7. 7.
    Goldberg SN, Mallery S, Gazelle GS, Brugge WR. EUS-guided radiofrequency ablation in the pancreas: results in a porcine model. Gastrointest Endosc. 1999;50(3):392–401.CrossRefGoogle Scholar
  8. 8.
    Fegrachi S, Besselink MG, van Santvoort HC, van Hillegersberg R, Molenaar IQ. Radiofrequency ablation for unresectable locally advanced pancreatic cancer: a systematic review. HPB (Oxford). 2014;16(2):119–23.  https://doi.org/10.1111/hpb.12097 Review.CrossRefGoogle Scholar
  9. 9.
    Singh V, Varshney S, Sewkani A, Varshney R, Deshpande G, Shaji P, et al. Radiofrequency ablation of unresectable pancreatic carcinoma: 10-year experience from single centre. Pancreatology. 2011;11(Suppl. 1):52.Google Scholar
  10. 10.
    Litvak DA, Bleicher RJ, Bilchik AJ. Radiofrequency ablation of a refractory unresectable insulinoma of the pancreas. Contemp Surg. 2003;59:229–32.Google Scholar
  11. 11.
    Limmer S, Huppert PE, Juette V, Lenhart A, Welte M, Wietholtz H. Radiofrequency ablation of solitary pancreatic insulinoma in a patient with episodes of severe hypoglycemia. Eur J Gastroenterol Hepatol. 2009;21(9):1097–101.CrossRefGoogle Scholar
  12. 12.
    Lygidakis NJ, Sharma SK, Papastratis P, Zivanovic V, Kefalourous H, Koshariya M, et al. Microwave ablation in locally advanced pancreatic carcinoma–a new look. Hepatogastroenterology. 2007;54(77):1305–10.PubMedGoogle Scholar
  13. 13.
    Carrafiello G, Ierardi AM, Fontana F, Petrillo M, Floridi C, Lucchina N, et al. Microwave ablation of pancreatic head cancer: safety and efficacy. J Vasc Interv Radiol. 2013;24:1513–20.  https://doi.org/10.1016/j.jvir.2013.07.005.CrossRefPubMedGoogle Scholar
  14. 14.
    Chen OT, Dojki FK, Weber SM, Hinshaw JL. Percutaneous microwave ablation of an Insulinoma in a patient with refractory symptomatic hypoglycemia. J Gastrointest Surg. 2015;19(7):1378–81.  https://doi.org/10.1007/s11605-015-2831-2.CrossRefPubMedGoogle Scholar
  15. 15.
    Chernousov AF, Egorov AV, Musaev GK. Percutaneous microwave ablation of insulin-producing tumor of the pancreas. Khirurgiya. 2015;12:107–10.  https://doi.org/10.17116/hirurgia201512107-110.CrossRefGoogle Scholar
  16. 16.
    Myers RS, Hammond WG, Ketcham AS. Cryosurgery of primate pancreas. Cancer. 1970;25:411–4.  https://doi.org/10.1002/1097-0142(197002)25:2<411::AID-CNCR2820250220>3.0.CO;2-7.CrossRefPubMedGoogle Scholar
  17. 17.
    Patiutko II, Barkanov AI, Kholikov TK, Lagoshnyĭ AT. The combined treatment of locally disseminated pancreatic cancer using cryosurgery. Vopr Onkol. 1991;37:695–700.PubMedGoogle Scholar
  18. 18.
    Tao Z, Tang Y, Li B, Yuan Z, Liu FH. Safety and effectiveness of cryosurgery on advanced pancreatic cancer: a systematic review. Pancreas. 2012;41(5):809–11.  https://doi.org/10.1097/MPA.0b013e318243a503 Review.CrossRefPubMedGoogle Scholar
  19. 19.
    D'Onofrio M, Ciaravino V, De Robertis R, Barbi E, Salvia R, Girelli R, et al. Percutaneous ablation of pancreatic cancer. World J Gastroenterol. 2016;22(44):9661–73.CrossRefGoogle Scholar
  20. 20.
    Li J, Zhang C, Chen J, Yao F, Zeng J, Huang L, et al. Two case reports of pilot percutaneous cryosurgery in familial multiple endocrine neoplasia type 1. Pancreas. 2013;42(2):353–7.  https://doi.org/10.1097/MPA.0b013e318258f233.CrossRefPubMedGoogle Scholar
  21. 21.
    Di Matteo F, Martino M, Rea R, et al. EUS-guided Nd: YAG laser ablation of normal pancreatic tissue: a pilot study in a pig model. Gastrointest Endosc. 2010;72:358–63.CrossRefGoogle Scholar
  22. 22.
    Di Matteo F, Picconi F, Martino M, Pandolfi M, Pacella CM, Schena E, et al. Endoscopic ultrasound-guided Nd: YAG laser ablation of recurrent pancreatic neuroendocrine tumor: a promising revolution? Endoscopy. 2014;46(Suppl 1 UCTN):E380–1.  https://doi.org/10.1055/s-0034-1377376.CrossRefPubMedGoogle Scholar
  23. 23.
    Martin RCII, McFarland K, Ellis S, Velanovich V. Irreversible electroporation in locally advanced pancreatic cancer: potential improved overall survival. Ann Surg Oncol. 2013;20(Suppl 3):S443–9.CrossRefGoogle Scholar
  24. 24.
    Philips P, Hays D, Martin RC. Irreversible electroporation ablation (IRE) of unresectable soft tissue tumours: learning curve evaluation in the first 150 patients treated. PLoS One. 2013;8:e 76260.CrossRefGoogle Scholar
  25. 25.
    Martin RC II, McFarland K, Ellis S, Velanovich V. Irreversible electroporation therapy in the management of locally advanced pancreatic adenocarcinoma. J Am Coll Surg. 2012;215:361–9.CrossRefGoogle Scholar
  26. 26.
    Bown SG, Rogowska AZ, Whitelaw DE, Lees WR, Lovat LB, Ripley P, et al. Photodynamic therapy for cancer of the pancreas. Gut. 2002;50:549–57.CrossRefGoogle Scholar
  27. 27.
    Huggett MT, Jermyn M, Gillams A, Illing R, Mosse S, Novelli M, et al. Phase I/II study of verteporfin photodynamic therapy in locally advanced pancreatic cancer. Br J Cancer. 2014;110:1698–704.CrossRefGoogle Scholar
  28. 28.
    Huggett MT, Jermyn M, Gillams A, Mosse S, Kent E, Bown SG, et al. Photodynamic therapy for locally advanced pancreatic cancer (VERTPAC study): final clinical results. Pancreatology. 2013;13:e2–3.CrossRefGoogle Scholar
  29. 29.
    Wang K, Zhu H, Meng Z, Chen Z, Lin J, Shen Y, et al. Safety evaluation of high-intensity focused ultrasound in patients with pancreatic cancer. Onkologie. 2013;36:88–92.  https://doi.org/10.1159/000348530.CrossRefPubMedGoogle Scholar
  30. 30.
    Xiong LL, Hwang JH, Huang XB, Yao SS, He CJ, Ge XH, et al. Early clinical experience using high intensity focused ultrasound for palliation of inoperable pancreatic cancer. JOP. 2009;10:123–9.PubMedGoogle Scholar
  31. 31.
    Sung HY, Jung SE, Cho SH, Zhou K, Han JY, Han ST, et al. Long-term outcome of high-intensity focused ultrasound in advanced pancreatic cancer. Pancreas. 2011;40:1080–6.  https://doi.org/10.1097/MPA.0b013e31821fde24.CrossRefPubMedGoogle Scholar
  32. 32.
    Xie DR, Chen D, Teng H. A multicenter non-randomized clinical study of high intensity focused ultrasound in treating patients with local advanced pancreatic carcinoma. Zhongguo Zhong Liu Linchuang. 2003;30:630–4.Google Scholar
  33. 33.
    Gao HF, Wang K, Meng ZQ, Chen Z, Lin JH, Zhou ZH, et al. High intensity focused ultrasound treatment for patients with local advanced pancreatic cancer. Hepato-Gastroenterology. 2013;60(128):1906–10.PubMedGoogle Scholar
  34. 34.
    Zhao H, Yang G, Wang D, Yu X, Zhang Y, Zhu J, et al. Concurrent gemcitabine and high-intensity focused ultrasound therapy in patients with locally advanced pancreatic cancer. Anti-Cancer Drugs. 2010;21:447–52.  https://doi.org/10.1097/CAD.0b013e32833641a7.CrossRefPubMedGoogle Scholar
  35. 35.
    Karpov OE, Vetshev PS, Bruslik SV, Sviridova TI, Sarzhevsky VO, Sudilovskaya VV, et al. Ultrasound ablation (HIFU) in the treatment of malignant tumors of the pancreas. Vestn Khirurgicheskoi Gastroenterol. 2014;3-4:10–6.Google Scholar
  36. 36.
    Koong AC, Le QT, Ho A, Fong B, Fisher G, Cho C, et al. Phase I study of stereotactic radiosurgery in patients with locally advanced pancreatic cancer. Int J Radiat Oncol Biol Phys. 2004;58(4):1017–21.CrossRefGoogle Scholar
  37. 37.
    Schellenberg D, Kim J, Christman-Skieller C, Chun CL, Columbo LA, Ford JM, et al. Single-fraction stereotactic body radiation therapy and sequential gemcitabine for the treatment of locally advanced pancreatic cancer. Int J Radiat Oncol Biol Phys. 2011;81(1):181–8.  https://doi.org/10.1016/j.ijrobp.2010.05.006.CrossRefPubMedGoogle Scholar
  38. 38.
    Huscher CG, Mingoli A, Sgarzini G, Mereu A, Gasperi M. Image-guided robotic radiosurgery (CyberKnife) for pancreatic insulinoma: is laparoscopy becoming old? Surg Innov. 2012;19(1):NP14–7.  https://doi.org/10.1177/1553350611418990.CrossRefPubMedGoogle Scholar
  39. 39.
    Jürgensen C, Schuppan D, Neser F, Ernstberger J, Junghans U, Stölzel U. EUS-guided alcohol ablation of an insulinoma. Gastrointest Endosc. 2006;63(7):1059–62.CrossRefGoogle Scholar
  40. 40.
    Muscatiello N, Salcuni A, Macarini L, Cignarelli M, Prencipe S, di Maso M, et al. Treatment of a pancreatic endocrine tumor by ethanol injection guided by endoscopic ultrasound. Endoscopy. 2008;40(Suppl 2):E258–9.  https://doi.org/10.1055/s-2007-966962.CrossRefPubMedGoogle Scholar
  41. 41.
    Deprez PH, Claessens A, Borbath I, Gigot JF, Maiter D. Successful endoscopic ultrasound-guided ethanol ablation of a sporadic insulinoma. Acta Gastroenterol Belg. 2008;71:333–7.PubMedGoogle Scholar
  42. 42.
    Vleggaar FP, Bij de Vaate EA, Valk GD, Leguit RJ, Siersema PD. Endoscopic ultrasound-guided ethanol ablation of a symptomatic sporadic insulinoma. Endoscopy. 2011;43(Suppl 2 UCTN):E328–9.  https://doi.org/10.1055/s-0030-1256775.CrossRefPubMedGoogle Scholar
  43. 43.
    Levy MJ, Thompson GB, Topazian MD, Callstrom MR, Grant CS, Vella A. US-guided ethanol ablation of insulinomas: a new treatment option. Gastrointest Endosc. 2012;75:200–6.  https://doi.org/10.1016/j.gie.2011.09.019.CrossRefPubMedGoogle Scholar
  44. 44.
    Schnack C, Hansen CØ, Beck-Nielsen H, Mortensen PM. Treatment of insulinomas with alcoholic ablation. Ugeskr Laeger. 2012;174:501–2.PubMedGoogle Scholar
  45. 45.
    Lee MJ, Jung CH, Jang JE, Hwang JY, Park DH, Park TS, et al. Successful endoscopic ultrasound-guided ethanol ablation of multiple insulinomas accompanied with multiple endocrine neoplasia type 1. Intern Med J. 2013;43(8):948–50.  https://doi.org/10.1111/imj.12208.CrossRefPubMedGoogle Scholar
  46. 46.
    Bor R, Farkas K, Bálint A, Molnár T, Nagy F, Valkusz Z, et al. Endoscopic ultrasound-guided ethanol ablation: an alternative option for the treatment of pancreatic insulinoma. Orv Hetil. 2014;155:1647–51.  https://doi.org/10.1556/OH.2014.30012.CrossRefPubMedGoogle Scholar
  47. 47.
    Qin SY, Lu XP, Jiang HX. EUS-guided ethanol ablation of insulinomas: case series and literature review. Medicine (Baltimore). 2014;93:e85.  https://doi.org/10.1097/MD.0000000000000085.CrossRefGoogle Scholar
  48. 48.
    Paik WH, Seo DW, Dhir VK, Wang HPO. Mo1373 EUS-guided ethanol ablation of small solid pancreatic neoplasm. Gastrointest Endosc. 2014;79(Suppl 5):AB413.  https://doi.org/10.1016/j.gie.2014.02.550.CrossRefGoogle Scholar
  49. 49.
    Yang D, Inabnet WB 3rd, Sarpel U, DiMaio CJ. EUS-guided ethanol ablation of symptomatic pancreatic insulinomas. Gastrointest Endosc. 2015;82(6):1127.  https://doi.org/10.1016/j.gie.2015.06.030.CrossRefPubMedGoogle Scholar
  50. 50.
    Park do H, Choi JH, Oh D, Lee SS, Seo DW, Lee SK, et al. Endoscopic ultrasonography-guided ethanol ablation for small pancreatic neuroendocrine tumors: results of a pilot study. Clin Endoscrinol. 2015;48:158–64.  https://doi.org/10.5946/ce.2015.48.2.158.CrossRefGoogle Scholar
  51. 51.
    Paik WH, Seo DW, Dhir V, Wang HP. Safety and efficacy of EUS-guided ethanol ablation for treating small solid pancreatic neoplasm. Medicine (Baltimore). 2016;95(4):e2538.  https://doi.org/10.1097/MD.0000000000002538.CrossRefGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2018

Authors and Affiliations

  1. 1.A.V. Vishnevsky Institute of SurgeryMinistry of Health, RussiaMoscowRussian Federation
  2. 2.Abdominal Surgery DepartmentA.V. Vishnevsky Institute of SurgeryMoscowRussian Federation
  3. 3.Abdominal Surgery DepartmentA.V. Vishnevsky Institute of SurgeryMoscowRussian Federation
  4. 4.Abdominal Surgery DepartmentA.V. Vishnevsky Institute of SurgeryMoscowRussian Federation
  5. 5.Abdominal Surgery DepartmentA.V. Vishnevsky Institute of SurgeryMoscow RegionRussian Federation

Personalised recommendations