Neoplasms of the Appendix

Abstract

Background

Neoplasms of the vermiform appendix are rare. They comprise a heterogeneous group of entities requiring different kinds of treatment.

Methods

This review is based on publications retrieved by a selective literature search in the PubMed, Embase, and Cochrane databases.

Results

0.5% of all tumors of the gastrointestinal tract arise in the appendix. Their treatment depends on their histopathological classification and tumor stage. The mucosal epithelium gives rise to adenomas, sessile serrated lesions, adenocarcinomas, goblet-cell adenocarcinomas, and mucinous neoplasms. Neuroendocrine neoplasms originate in neuroectodermal tissue. Adenomas of the appendix can usually be definitively treated by appendectomy. Mucinous neoplasms, depending on their tumor stage, may require additional cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemoperfusion (HIPEC). Adenocarcinomas and goblet-cell adenocarcinomas can metastasize via the lymphatic vessels and the bloodstream and should therefore be treated by oncological right hemicolectomy. Approximately 80% of neuroendocrine tumors are less than 1 cm in diameter when diagnosed and can therefore be adequately treated by appendectomy; right hemicolectomy is recommended if the patient has risk factors for metastasis via the lymphatic vessels. Systemic chemotherapy has not been shown to be beneficial for appendiceal neoplasms in prospective, randomized trials; it is recommended for adenocarcinomas and goblet-cell adenocarcinomas of stage III or higher, in analogy to the treatment of colorectal carcinoma.

cme plus

This article has been certified by the North Rhine Academy for Continuing Medical Education. The deadline for submissions is 6.August 2024.

Participation in the CME certification program is possible only over the internet: cme.aerzteblatt.de.

Every year more than 100,000 appendectomies are carried out in Germany (1, 2). in 0.9–1.7% of patients, a neoplasm is detected during the histopathologic work-up (3, 4). Neoplasms of the appendix account for only about 0.5% of all gastrointestinal neoplasms (3, 4), but they form a heterogeneous group that requires specific therapy depending on what the entity is. Often, tumors of the appendix are adequately treated by just the appendectomy. In other cases, metastasized tumors lead to ascites, compression related disruptions of the gastrointestinal passage, and abdominal pain. The primary operation is often carried out while still unaware of the tumor, which means that after the histopathology result is obtained, appropriate action will have to be taken.

Before an appendectomy, most patients undergo ultrasound scanning to verify the diagnosis; computed tomography (CT) scanning is done in 17% (5). But even CT imaging rarely allows for a reliable preoperative diagnosis of a neoplasm of the appendix (6, 7).

This article provides an overview of the most common neoplasms of the appendix and the specific therapeutic recommendations. Primary hematolymphoid, mesenchymal, or melanocytic tumors of the appendix are rare—as are metastases—and are not the subject of this article (8). The therapeutic recommendations are based on registry studies, retrospective evaluations, or case series. Because these tumors are so rare it has not been possible to date to undertake randomized controlled trials of the individual tumor entities.

The Table shows the classification of neoplasms of the appendix according to histologic origin on the basis of the most recent WHO Classification of Tumours—Digestive System Tumours published in 2019 (9).

Table. Classification of neoplasias of the appendix (according to WHO 2019) (9).

Appendix neoplasms		Prevalence
Sessile serrated lesions and adenomas		4/3 597* (10, 11)
Mucinous neoplasms	Low-grade mucinous neoplasm of the appendix (LAMN)High-grade mucinous neoplasm of the appendix (HAMN)	476/171 341* (10, 11, 40)
Adenocarcinomas	Non-mucinous adenocarcinoma (NOS, “not otherwise specified”) Mucinous adenocarcinoma Signet ring cell adenocarcinoma Undifferentiated carcinoma	366/171 341* (10, 11, 40)
Goblet cell adenocarcinoma		n/a
Neuroendocrine neoplasms	Neuroendocrine tumors (NET)Neuroendocrine carcinomas (NEC) Mixed neuroendocrine/non-neuroendocrine neoplasms (MiNEN)	0.2–0.3/100 000 persons (34)

* Appendectomy specimens

Adenomas and sessile serrated lesions

Adenomas and sessile serrated lesions (SSL) of the appendix are very rare and mainly incidental findings. Two studies that retrospective analyzed specimens obtained from >3500 appendectomies found 116 neoplasms, of which four were adenomas or SSL (10, 11). The characteristic seen on histology is a saw-tooth architecture. Most SSLs are free from dysplasia, but low-grade or high-grade dysplasias can occur. Bigger lesions can cause appendicitis by obstructing the appendix lumen (9). Lesions in the region of the appendix ostium can be detected on colonoscopy.

As with colorectal adenomas it should be evaluated whether endoscopic ablation is possible. With an R0 resection rate of 93% in a retrospective multicenter study, endoscopic full-thickness resection is promising, but 17% of patients develop appendicitis after the intervention (12). If endoscopic ablation is not possible, minimally invasive appendectomy should be carried out, if needed with resection of the cecal pole.

After total resection no further therapy is required (9). Follow-up care should be provided according to the recommendations of the National Disease Management (S3) Guideline “Colorectal cancer” (13).

Mucinous neoplasms

This category includes low grade mucinous neoplasms of the appendix (LAMN) and high-grade mucinous neoplasms of the appendix (HAMN), which are characterized by dysplastic, mucogenic epithelia, extracellular mucus deposits, and displacing, but not tissue invasive, growth. If they perforate peritoneal mucus deposits may be the result. If the latter are acellular the term used to describe them is peritoneal mucinosis. If tumor cells are found in addition, the entity is a Pseudomyxoma peritonei (PMP) (9, 14).

Low-grade mucinous neoplasms of the appendix

LAMN cause distension of the appendix and display low-grade atypias, whereas high-grade atypias, signet ring cells, or invasive tumor growth are excluded (Figure 1a and 1b). The are classified as grade 1 tumors (9) and occur frequently in the 5th-7th decades of life. They affect mainly the female sex. LAMN are diagnosed in 0.13% of appendectomies; notable underdiagnosis can be assumed (15). The TNM (tumor, node, metastasis) classification has a peculiarity in that tumor categories pT1 and pT2 for LAMN are not assigned, as expansion into the smooth muscle layer is categorized as herniation (16) (eTable 1).

Figure 1:

Aspects of low-grade mucinous neoplasms of the appendix (LAMN)

a) Histologic image of LAMN, HE staining; typical lamina propria replaced by villous proliferation of mucinous, mildly atypical epithelia that border on fibrosed connective tissue

b) Computed tomography (CT) scan LAMN (arrow) without any indication of Pseudomyxoma peritonei (PMP)

c) Intraoperative finding of Pseudomyxoma peritonei with mucin deposits on the hepatic capsule as well as on the lesser and greater omentum

eTable 1. TNM classification and UICC stages of low-grade mucinous neoplasms of the appendix.

Primary tumor
pTis:	Tumor limited to the appendix with acellular mucin or mucinous epithelium, which can extend into the smooth muscle layer
pT1	Not given for LAMN
pT2	Not given for LAMN
pT3	Tumor invasion of the subserosa or mesoappendix
pT4	Tumor has perforated the visceral peritoneum, including mucinous peritoneal tumor spread or acellular mucin beyond serosa of the appendix or mesoappendix and/or infiltrated other organs/structures
pT4a:	Tumor has perforated the visceral peritoneum, including mucinous peritoneal tumor spread within the right lower quadrant
pT4b:	Tumor has infiltrated (directly) other organs/structures
N-Status	n/a
Distant metastases
M0	No distant metastases
M1 – M1a – M1b – M1c	Distant metastases present Intraperitoneal acellular mucin Intraperitoneal metastases, including mucinous epithelial cells Non-peritoneal metastases
UICC/ AJCC stage
0	pTis
IIA	pT3
IIB	pT4a
IIC	pT4b
IVA	Every T
IVA	Every T
IVC	Every T

M, distant metastases; p, pathology; T, primary stage;

UICC, Union internationale contre le cancer;

LAMN, low-grade mucinous neoplasm of the appendix

If no total resection has been done during appendectomy, and if no perforation, PMP, or mucinosis are present, appendectomy alone suffices by way of treatment. If mucin has been extensively disseminated into the abdominal cavity (Figure 1c), cytoreductive surgery with hyperthermic intraperitoneal chemoperfusion (HIPEC) is recommended (17– 19). In HIPEC, after the surgical cytoreduction has been completed, cytotoxic solution heated to 42–43°C is infused through large-lumen abdominal drainages and left to circulate for 30–90 minutes. Anesthesia is stopped only afterwards.

Cytoreduction aims to remove the entire tumor load/burden. Subsequent HIPEC aims to kill off residual tumor cells (20).

The decisive factor in order to evaluate the recurrence risk and thus the prognosis is the cellularity of the mucins confirmed in the abdominal cavity. If mucinosis is acellular the probability of recurrence is lower and progression-free survival significantly higher than in PMP. A retrospective evaluation of 121 patients described in spite of completed cytoreduction a significantly shorter progression-free survival in patients with cellular mucin (98% versus 69.8 %; p=0.002) (21). Therapeutic recommendations are shown in (Figure 2).

Figure 2.

Flow chart of recommended therapy of low-grade mucinous neoplasms of the appendix.

HAMN, high-grade mucinous neoplasms; HIPEC hyperthermic intraperitoneal chemoperfusion; LAMN, low-grade mucinous neoplasms; PMP, Pseudomyxoma peritonei

No benefit of adjuvant or perioperative systemic chemotherapy has been shown for LAMN to date. What was found instead was a negative effect of the total and progression-free survival on neoadjuvant chemotherapy (22, 23). Prospective randomized trials in this area are lacking.

After resection, follow-up treatment should be undertaken, in the form of CT imaging and measuring of tumor markers (CEA, CA 19–9, and CA 125), so as to detect any recurrence as early as possible (4, 17, 24). A suggested follow-up care scheme entails abdominal sectional imaging every six months for a time period of five years (preferably magnetic resonance imaging) and simultaneous measuring of the tumor markers.

In early tumor stages without perforation the recurrence risk or the probability for developing a PMP are significantly lower than in the scenario of a perforated appendix or a finding of PMP during the primary operation (23).

High-grade mucinous neoplasms of the appendix

HAMN was first defined in the 5th edition of the WHO Classification of Tumours—Digestive System Tumours and equates to a grade 2 neoplasm (9). In contrast to LAMN, focal high-grade dysplasias are present. LAMN as a rule triggers low-grade PMP (G1), whereas HAMN leads in more cases to a high-grade PMP (G2), which is associated with a worse prognosis (25). The PSOGI (Peritoneal Surface Oncology Group International) guidelines published in 2021 recommend in non-perforated HAMN without an morphologic indication of a PMP on imaging appendectomy alone, and in case of perforation or peritoneal spread, right hemicolectomy and a cytoreductive operation using HIPEC. Overall, as these tumors are so rare, data are even scarcer than for LAMN and recommendations are based on case series (9).

Adenocarcinomas of the appendix

Adenocarcinomas are malignant glandular neoplasms with invasive growth. Distinction is made between non-mucinous adenocarcinoma (NOS, “not otherwise specified”), mucinous adenocarcinoma, signet ring cell adenocarcinoma, and undifferentiated cancers (eTable 2). Non-mucinous adenocarcinomas are graded in analogy to colorectal cancers; a two-grade system is used (low-grade: previously G1 or G2, high-grade: previously G3). Conventional mucinous adenocarcinomas are assigned a grade 2, and confirmation of signet ring cells results in a grade 3 (9).

eTable 2. TNM classification and UICC tumor stages of adenocarcinomas and goblet cell carcinomas of the appendix.

Primary tumor
pT0	No tumor detected
pTis	Carcinoma in situ
pT1	Infiltration of submucosa
pT2	Infiltration of smooth muscle layer
pT3	Infiltration of subserosa
pT4a	Tumor growth into visceral peritoneum
pT4b	Infiltration of neighboring organs
Lymph nodes
N0	No lymph nodes affected
N1	1–3 regional lymph nodes involved
N2	≥ 4 regional lymph nodes involved
Distant metastases
M0	No distant metastases
M1	Distant metastases present
UICC/AJCC stage
0	Tis	N0	M0
I	T1–2	N0	M0
II	T3–4	N0	M0
III	Every T stage	N1–2	M0
IV	Every T stage	Every N stage	M1

M, distant metastases; N, lymph node metastases;

p, pathology; T, primary stage; UICC, Union internationale contre le cancer;

LAMN, low-grade mucinous neoplasms of the appendix

A mucinous adenocarcinoma is present if >50% of the tumor surface consists of extracellular mucin. To be classified as a signet ring cell carcinoma, >50% of the tumor needs to consist of signet cells. If the respective proportions are <50%, the term used is that of adenocarcinoma with extracellular mucus secretion or a signet ring cell containing adenocarcinoma. Undifferentiated cancers show—except for epithelial marker expression—no further histologic, immunohistochemical, or molecular indicators of the tissue of origin (9).

If adenocarcinomas of the appendix are diagnosed as an incidental finding after appendectomy, the T category is already determined in the histology work-up and therapy can be set out on this basis. In completely resected pTis tumors, appendectomy is sufficient. In totally resected pT1 tumors and in the absence of risk factors, appendectomy may also suffice. In pT1 tumors in combination with risk factors (G3 differentiation, angioinvasion, or R1 resection) and in higher-grade tumors than pT2, oncologic right hemicolectomy with systematic lymphadenectomy should be carried out (26).

The data regarding adjuvant chemotherapy are inconclusive because of the lack of prospectively randomized trials (27– 29), and the current PSOGI guidelines make a “can” recommendation for adjuvant chemotherapy after cytoreduction has been carried out (23).

Studies of palliative chemotherapy are scarce. If patients have not had a successful complete cytoreduction, no unanimous recommendation for additive or palliative chemotherapy is given (23). In routine clinical practice, adjuvant systemic therapy is given in accordance with the national disease management guideline “Colorectal Carcinoma” for not G1-differentiated adenocarcinomas of the appendix depending on established risk factors (especially positive nodal status) (13, 30). Palliative systemic therapy at (symptomatic) stage IV is also guided by the treatment of colorectal carcinoma; the use of biologicals (anti-VEGF or anti-EGFR antibodies depending on the RAS/BRAF mutation status) has to date not been validated for adenocarcinomas of the appendix. Mutation analysis of the tumors can, however, provide indications for responsiveness to systemic therapy and predict the disease course (31).

Goblet cell adenocarcinoma of the appendix

Goblet cell adenocarcinoma of the appendix has a mostly tubular structure, resembles crypt epithelium, and consists of goblet-like mucus secreting cells, intermixed with endocrine cells and cells that are similar to Paneth cells. It was first described as a separate tumor entity in the 2019 WHO classification. In terms of histology, distinction is made between low-grade (tubular and grouped tumor cell architecture) and high-grade growth patterns (loss of tubular or grouped architecture). The classification of goblet cell adenocarcinoma requires by definition at least focal low-grade growth. There are three grades, depending on the proportion of low-grade to high-grade tumor components (low-grade proportion: G1:>75%, G2: 50–75%, G3: <25%) (9). The TNM or UICC (Union internationale contre le cancer) classification is in line with that of adenocarcinomas of the appendix (eTable 2) (16).

Goblet cell adenocarcinomas account for 10–23% of primary neoplasms of the appendix (32, 33). The mean age at diagnosis is in the 6th decade of life, and both sexes are affected equally (26).

A meta-analysis that analyzed data from 1225 patients found that if confirmation of distant metastases was lacking, most of the patients had undergone right hemicolectomy in addition to appendectomy. In patients whose tumors were category pT3 or pT4 this led to a small but significant increase in 5-year survival (82% versus 85.4%; p=0.028), but this did not apply for patients in tumor categories pT1 and pT2. A positive effect of adjuvant chemotherapy was seen for tumor stage III and higher (33). If tumors are diagnosed only once they have metastasized, most studies recommend palliative chemotherapy, in keeping with the treatment of colorectal cancer (34). In tumors that have metastasized exclusively into the peritoneum the guideline recommends cytoreductive operation using the HIPEC regimen (34). Retrospective studies including small patient populations, which were included in the meta-analysis mentioned above, showed in selected patients (“peritoneal cancer index” [PCI] <20%, total resection) improved survival as a result of cytoreduction using HIPEC (33).

The 5-year survival rate has been described as 100% in stage I, 76% in stage II, 22% in stage III, and as 14% in stage IV (35).

Neuroendocrine neoplasms of the appendix

Neuroendocrine neoplasms (NEN) are epithelial tumors with a neuroendocrine differentiation. They include neuroendocrine tumors (NET) and neuroendocrine carcinomas (NEC). After the mucinous neoplasms (LAMN and HAMN), neuroendocrine (carcinoid) tumors are the most common tumors of the appendix, whereas NEC are rarities. NET consist of uniform cells with characteristically finely stippled chromatin and organoid architecture. By definition they are well differentiated and depending on the rate of mitosis and the Ki-67 marker index, distinction is made between low-grade (G1), intermediate-grade (G2), and high-grade (G3) tumors. Compared with NET, NEC usually have a lost organoid architecture and in many cases necroses. NEC are highly proliferative and per se poorly differentiated tumors.

Mixed neuroendocrine non-neuroendocrine neoplasms (MiNEN) of the appendix are rare. The defining factor for the diagnosis is for each tumor component to account for at least 30% of the tumor and is unequivocally identifiable morphologically and immunohistochemically. A combination of NEC and adenocarcinoma is most common. The TNM classification is in line with that of adenocarcinoma of the appendix (9) (eTable 2).

The incidence of NET has been described as 0.2–0.3/100,000 (34). The appendix is the fifth most common location for NET after the small bowel, rectum, pancreas, and stomach (36). In contrast to other tumors of the appendix, national and international guidelines exist for the diagnostic evaluation, therapy, and follow-up of NET of the appendix (34, 37).

The tumor category of NET is determined on the basis of tumor size (eTable 3). At the time of diagnosis most NET are <1 cm (pT1a, 80%), 15% are 1–2 cm (pT1b), and about 5% are >2cm (pT2) (34). Yao et al. described that distant metastases were found in 12% of patients, whereas 60% had local tumor disease and 28% had regional metastases (lymph node metastases or continually extensive growth) (38).

eTable 3. UICC/TNM classification and ENETS classification of neuroendocrine neoplasms of the appendix.

Primary tumor
	UICC	ENETS
T1	T1a: Tumor diameter ≤ 1 cm T1b: Tumor diameter > 1 to ≤ 2 cm	Tumor diameter ≤ 1 cm, invasion of smooth muscle layer
T2	Tumor diameter > 2 cm to ≤ 4 cm, with/without infiltration of the cecum	Tumor diameter ≤ 2 cm and < 3 mm invasion oif subserosa/mesoappendix
T3	Tumor diameter > 4 cm or infiltration of the ileum	Tumor diameter > 2 cm or > 3 mm invasion of subserosa/mesoappendix
T4	Tumor perforation or infiltration of neighboring organs	Invasion of the peritoneum or neighboring organs
Lymph node
N0	No lymph node involvement
N1	Lymph nodes involved
Distant metastases
M0	No distant metastases
M1	Distant metastases present
UICC/AJCC stage
I	T1	N0
II	T2–3	N0
III	T4	N0
	Every T stage	N1
IV	Every T stage	Every N stage

M, distant metastases; N, lymph node metastases; p, pathology; T, primary stage;

UICC, Union internationale contre le cancer; LAMN, low-grade mucinous neoplasm of the appendix

Established risk factors for the development of lymph node metastases and therefore associated with a higher risk of recurrence are tumor size (>2 cm), R1 resection, angioinvasion, infiltration of the mesoappendix >3 mm, and Ki-67 antigen >2% (34).

Current guidelines recommend appendectomy alone if the tumor size is <2 cm and risk factors are lacking. In tumors <2 cm in the presence of risk factors, ileocecal resection/right hemicolectomy should be carried out, including the lymphatic drainage areas of the ileocolic artery and vein. In tumors >2 cm, oncologic right hemicolectomy is recommended.

The question of the need for oncologic hemicolectomy has been investigated in a recently published retrospective multicenter study. The researchers studied 278 patients with 1–2 cm sized NET of the appendix to establish whether oncologic hemicolectomy improved long-term survival. No significant difference was seen for overall survival in the two groups (hazard ratio 0.88; 95% confidence interval: [0.44; 1.75]); p=0.71). The authors concluded that possible lymph node metastases are irrelevant in this selective patient population (39). If resectable distant metastases are found, these should be resected. In irresectable distant metastases resection of the primary can be considered so as to prevent possible complications (ileus, mesenteric ischemia). In well differentiated irresectable and asymptomatic tumors an “watch and wait” strategy can be considered versus medication treatment. In poorly differentiated or symptomatic well differentiated tumors, medication treatment should be initiated (34). The therapy of NET is shown in Figure 3.

Figure 3.

Flow chart of therapy for neuroendocrine tumors of the appendix

*Risk factors: R1 resection, angioinvasion, infiltration of mesoappendix > 3 mm and KI-67 > 2 %;

NET, neuroendocrine tumor

The prognosis in well differentiated NET in the absence of distant metastases is excellent; Yao et al reported a survival period of more than 360 months. In the presence of distant metastases the median survival was 27 months (38).

As the risk of recurrence or metastasis in small in totally resected and well differentiated small tumors, no follow-up is recommended in tumors <1 cm. For tumors in combination with risk factors, follow-up using magnetic resonance imaging, CT, or positron emission tomography-CT is recommended for a period of 10–15 years (34, 37).

Conclusions

In order to avoid overtreatment or undertreatment of patients, knowledge of the histologic classification of neoplasms of the appendix is a fundamental prerequisite. For many neoplasms of the appendix—such as adenomas, LAMN, and most NET—appendectomy suffices, and adenomas as well as some NET do not require follow-up. Especially for slow-growing tumors such as LAMN, long term follow-up is crucial, in order to identify Pseudomyxoma peritonei at an early stage.

As neoplasms of the appendix are altogether rare, high quality randomized controlled trials are lacking, which makes treating these patients an even bigger challenge.

Questions on the article in issue 31–32/2023: Neoplasms of the Appendix.

The submission deadline is 6 August 2024. Only one answer is possible per question. Please select the answer that is most appropriate.

Question 1

What percentage of all tumors of the gastrointestinal tract is located in the appendix?

1.  0.1 %

2.  0.5 %

3.  5.0 %

4. 15.0 %

5. 25.0 %

Question 2

Which neoplasm is associated with/accompanied by sawtoothlike tissue architectures?

1. Adenoma

2. Adenocarcinomas

3. Mucinous neoplasms

4. Neuroendocrine neoplasms

5. Goblet cell adenocarcinoma

Question 3

For which of the following neoplasms of the appendix can perforation result in Pseudomyxoma peritonei?

1. Sessile serrated lesion

2. Adenocarcinoma

3. Mucinous neoplasm

4. Goblet cell carcinoma

5. Neuroendocrine neoplasm

Question 4

Which of the following morphologic signs indicate a grade 3 adenocarcinoma of the appendix?

1. Signet ring cells

2. Staple cells

3. Goblet cells

4. Sickle cells

5. Spindle cells

Question 5

In which setting is the term mucinous adenocarcinoma used?

1. If at least 10 % of the tumor surface is covered in intracellular mucin.

2. If intracellular mucin is present in at least 50 % of tumor cells.

3. If a maximum of 50 % of the tumor surface is covered in mucin.

4. If more than half of the tumor surface consists of extracellular mucin.

5. If the entire tumor surface is covered by extracellular mucin

Question 6

In which of the following T categories does appendectomy suffice as a therapeutic measure in adenocarcinoma?

1. pT1

2. pTis

3. pT2

4. pT4

5. pT4b

Question 7

Which therapy is recommended for grade 1/grade 2 neuroendocrine tumors of the appendix that measure > 2 cm but have no distant metastases?

1. Appendectomy without follow-up

2. Appendectomy with follow-up

3. Right hemicolectomy with follow-up

4. Appendectomy and medication treatment

5. Watch-and-wait strategy

Question 8

What does the abbreviation MiNEN in the text stand for?

1. “Mixed neuroendocrine-non-neuroendocrine neoplasm”

2. “Malignant intestinal neuroendocrine neoplasm”

3. “Mixed intestinal non-neuroendocrine neoplasm”

4. “Malignant intestinal non-endocrine neoplasm”

5. “Mesenteric infiltration of non-endocrine neoplasm”

Question 9

Which mean survival interval/period is reported in the text for patients with well differentiated neuroendocrine appendix tumors without distant metastases?

1. 5 years

2. 10 years

3. 20 years

4. 30 years

5. 40 years

Question 10

Which procedure is mentioned in the text under the acronym HIPEC ?

1. Hypothermic intraperitoneal chemoperfusion

2. Hypobaric intraperitoneal chemoperfusion

3. Hypothermic intraoperative chemoablation

4. Hemilateral intraperitoneal chemoablation

5. Hyperthermic intraperitoneal chemoperfusion