Appendiceal Neoplasms

Abstract

Primary appendiceal neoplasms are rare and most commonly diagnosed incidentally, upon histological analysis of the appendectomy specimen. The timing and circumstances of the diagnosis, tumor histology, staging, required resection margin, and probability of nodal disease are factors of consideration to determine the further management of such patients. In many instances further surgery is indicated. The tumors are classified as epithelial (mucinous and non-mucinous), non-epithelial (carcinoids and others), or mixed tumors (goblet cell carcinoid). Epithelial tumors represent the most common appendiceal tumors. Apart from direct invasive growth, lymphogenous and hematogenous spread, particularly mucin-producing lesions, can result in a mucocele, perforate, and thus lead to dissemination of tumor cells and mucin into the peritoneal cavity to form pseudomyxoma peritonei. For localized disease, the goal is to achieve a curative R0 resection either by appendectomy alone or by a formal right hemicolectomy. Metastatic disease requires an individualized approach weighing systemic chemotherapy against cytoreductive surgery with HIPEC in select cases. Neuroendocrine tumors (carcinoids) are non-epithelial and often hormone-active argentaffin/argyrophilic tumors that derive from the dispersed enterochromaffin cells of the gastrointestinal tract and can metastasize to regional lymph nodes and distant organs. The aggressiveness of the surgical approach depends on the tumor size as the most important parameter of the primary tumor staging, the location of the tumor, and the presence or absence of regional or distant metastases.

FormalPara Key Concepts

• Although appendectomy for appendicitis is the most commonly performed emergency operation performed by general surgeons, primary neoplasms of the vermiform appendix are rare, and each individual general surgeon will have limited experience in the management of such lesions.

• Most primary neoplasms of the appendix are not associated with specific signs or symptoms and are incidentally diagnosed after pathological analysis of the appendectomy specimen or detected incidentally on computed tomography (CT) for other indications.

• Primary neoplasms of the appendix can generally be divided into epithelial, non-epithelial, and mixed lesions. Epithelial lesions include adenoma and adenocarcinoma. Non-epithelial tumors include neuroendocrine tumors (carcinoids), lymphoma, leiomyoma, leiomyosarcoma, and other even rarer rarities. Goblet cell carcinoids are mixed lesions with features of carcinoid as well as mucinous adenocarcinoma.

• Epithelial tumors, and specifically mucinous adenocarcinomas, are the most common primary appendiceal neoplasms.

• Pseudomyxoma peritonei is the result of a perforation and peritoneal dissemination of a mucin-producing epithelial neoplasm, most commonly originating from the appendix or the ovaries. In select patients, cytoreductive surgery with HIPEC should be considered.

• A mucocele is a morphologic cystic manifestation of an epithelial appendiceal neoplasm. Perforation leads to pseudomyxoma peritonei. Therefore, intact removal en bloc is of utmost importance.

• Appendiceal carcinoids are rarely associated with carcinoid syndrome or multicentricity.

• The newest tumor staging guidelines distinguish appendiceal tumors from colon cancer and separate between epithelial and non-epithelial lesions.

• The extent of surgical resection depends on the cell type, the preoperative staging, the ability to achieve negative resection margins, and the probability of nodal disease.

• Surgery is the primary treatment for localized disease, whereas its role in metastatic disease needs to be individually analyzed and weighed against systemic chemotherapy.

Introduction

• Appendectomy is the most frequent emergency operation performed by general surgeons with close to 300,000 performed in the United States annually.

• On comparably rare occasion, the pathology of the appendectomy specimen incidentally reveals an appendiceal neoplasm (“incidentaloma ”), which sometimes is recognized even before or at least during surgery, but more often only after the patient has already been discharged from the hospital.

• Paradoxically and despite the fact that abdominal surgeons at all levels are very frequently involved in treating appendiceal pathology, appendiceal neoplasms are quite infrequent but may cause rather complex intellectual, management, and technical challenges in subsequent surgical interventions (Table 37.1).

Table 37.1 Clinical scenarios depending on the type and timing of diagnosis of appendiceal neoplasms

Epidemiology

• Primary neoplasms of the appendix have an incidence of 0.12 cases per 1,000,000 person-years and are found in 0.9–1.4% of appendectomy specimens.

• They can be asymptomatic, be associated with appendicitis, or cause noninflammatory symptoms.

• Preoperative diagnosis based on symptoms, imaging, and laboratory results is extremely rare.

• Even intraoperatively, less than 50% appendiceal neoplasms are recognized as such.

• A retrospective cohort analysis of the Surveillance, Epidemiology, and End Results database suggested that the incidence of appendiceal neoplasms has increased significantly in the past few decades from 0.63 to 0.97 per 100,000 population.

  • It is unclear though whether this is a true increase or a simple reflection of higher awareness and reclassification as a separate entity. The increase appears to have affected all histological subtypes in an equal fashion (Table 37.2).

• Historically, carcinoid tumors were considered the most frequent neoplasms originating within the appendix, although more recent publications demonstrate that epithelial neoplasms are more frequent and represent 58% of malignant appendiceal tumors.

• At the time of diagnosis, a total of 74% of appendiceal cancer cases have already spread and developed regional or distant metastases in 39% and 35%, respectively.

Table 37.2 Reported incidence over time of appendiceal neoplasms in SEER database

Anatomical Pathology and Staging

• The literature unfortunately has for a long time shown little consistency and used a variety of nomenclatures, classification systems, and descriptive terms when referring to appendiceal neoplasms. Many synonyms for lesions of such rarity undoubtedly have led to confounding terminology.

• From an anatomical point of view, the appendix in essence has a smaller diameter but otherwise a similar layered wall structure as the rest of the large intestine; however there is a higher representation of immunological tissue components (GALT, gut-associated lymphoid tissue).

• The appendix does not participate in processing of intestinal contents but produces 2–3 mL of mucin per day and may participate in immunological functions.

• The arterial blood supply originates from the appendicular artery which branches off the ileocolic artery; the venous drainage is via the superior mesenteric vein to the portal vein system; the lymphatic drainage follows the vascular structures and due to variability may parallel the ileocolic, right colic, and right branch of the middle colic artery.

• Appendiceal neoplasms should be categorized according to the tissue of origin as well as the pattern of growth, expansion, and spreading (Table 37.3).

Table 37.3 Tumor classifications and manifestations

Epithelial Neoplasms

• Epithelial neoplasms are divided into mucinous and non-mucinous neoplasms.

• Mucinous neoplasms of the appendix are classified according to the grade and aggressiveness of the tumor.

  • Descriptively, these lesions characteristically can form mucoceles of the appendix, a morphologic term describing the dilation of the appendix with intraluminal accumulation of mucoid material (Fig. 37.1).

  • The obstruction can either be caused by the epithelial neoplasm itself, an independent tumor, or a benign process (retention cysts, mucosal hyperplasia).

  • Rupture of a mucocele results in peritoneal spillage and spread of mucin and – depending on the malignant potential of the lesion – of cellular elements, which are the basis for mucinosis, pseudomyxoma peritonei, and carcinomatosis.

• Low-grade appendiceal mucinous neoplasms (LAMNs) are well-differentiated neoplasms that morphologically resemble adenomas.

• LAMN has become the neutral term for a number of entities such as appendiceal villous or serrated adenoma, cystadenoma, borderline tumor of the appendix, and mucinous tumors of uncertain malignant potential.

• These lesions which tend to grow slowly and grossly are characterized by a well-defined structure, cystic dilation, and mucinous content.

• The appendiceal wall is fibrotic and – as a sign of chronicity – may sometimes contain calcifications.

• Gross rupture (spontaneously or as a result of surgical manipulation) may be evident as mucin extruding onto the serosal surface or seeding of more distant peritoneal surfaces as evidenced by the presence of mucin lakes.

• Prognosis of LAMN depends on the presence or absence of epithelial cells outside the appendix.

  • Tumors confined to the appendix generally have an excellent prognosis.

  • However, LAMN may proliferate outside the appendix in a malignant fashion, producing pseudomyxoma peritonei and/or distant metastases.

• Pseudomyxoma peritonei (PMP) derived from perforation of a LAMN is characterized by abundant extracellular mucin, hyalinized fibrotic stroma, and harboring scant strips of low-grade mucinous epithelium.

  • The term is not strictly limited to appendiceal neoplasms, but the condition can result from other tumor origins such as ovaries, gallbladder, and others.

• The prognosis of a ruptured LAMN is dependent on the amount and cellularity of mucin deposits, and recurrence rates increase when epithelial cells are present in the mucin.

• Most instances of PMP resulting from LAMN remain confined to the right lower quadrant. Even if the spread of PMP goes beyond the immediate vicinity, the lesion may pursue an indolent but progressive course.

• The superordinate term “PMP” has been categorized into disseminated peritoneal adenomucinosis (DPAM) and peritoneal mucinous (adeno)carcinomatosis (PMAC or PMCA) .

  • The former reflects a low-grade pseudomyxoma arising from LAMNs, whereas the latter indicates peritoneal carcinomatosis.

  • DPAM lesions contain scarce strips of low-grade mucinous epithelium with mild atypia and no significant mitotic activity; these low-grade lesions usually cover but do not infiltrate the surface of the organs to which they adhere.

• Appendiceal adenocarcinoma is also divided into mucinous and non-mucinous types.

• Mucinous adenocarcinoma of the appendix is characterized by a destructive growth pattern with tumor invasion of the appendiceal wall beyond the muscularis mucosae; infiltrating pools of mucin harbor cytologically malignant glandular epithelium arranged in strips, clusters, and complex proliferations.

• Mucinous adenocarcinoma due to the increasing pressure of accumulating mucin is prone to rupture, spreading and seeding into the peritoneal cavity, leading to formation of pseudomyxoma peritonei.

• Mucinous tumors spread along peritoneal surfaces, even in the absence of lymph node metastases. Peritoneal mucinous (adeno)carcinomatosis (PMAC/PMCA) results from secondary peritoneal proliferation of appendiceal or intestinal mucinous adenocarcinoma nests that lead to invasion of parenchymal and visceral organs and the omentum and potentially trigger secondary lymph node metastases at those sites.

• Non-mucinous adenocarcinomas behave similarly to colonic adenocarcinomas, infiltrating the appendiceal wall and metastasizing to regional lymph nodes and the liver.

• Non-mucinous adenocarcinomas show a spectrum of morphological features of the invasive component.

  • In some cases the tumor is identical to colonic adenocarcinoma with malignant (pseudo-)glandular formations, increased stratification, and disorganization (compared to the regular columnar epithelium).

  • In other cases, the malignant glands are tubular in shape, lined by cuboidal epithelium, associated with modest amount of extracellular mucin.

• Signet ring cell carcinoma is a rare but aggressive subentity of mucinous adenocarcinoma, characterized by dissolute growth and infiltration of mucin-containing cancer cells (signet rings); it almost never remains confined and may display an infiltrative growth below intact appearing mucosal surfaces as well as a rapid dissemination within the peritoneal cavity.

• Signet ring cell carcinoma is typically associated with a poor prognosis.

• Prognosis of appendiceal adenocarcinomas – similar to colon cancer – is primarily determined by the stage, but within stage IV also depends on the histological subtype and grading as well as the route of dissemination.

• Within each stage and histological subtype, poor differentiation is associated with unfavorable outcomes.

• Mucinous adenocarcinomas have a markedly worse outcome (reduced cancer-specific survival) than non-mucinous adenocarcinomas of the appendix (Table 37.4).

• This observation, which was based on published data analysis of the National Cancer Database (NCDB) , was recently implemented into the current staging guidelines by the American Joint Committee on Cancer (AJCC) .

  • Appendiceal carcinomas for the first time are classified separately from colonic adenocarcinoma, and distinction is made between mucinous and non-mucinous types; histologic grading for mucinous tumors is considered of particular importance for metastatic tumors (Table 37.5).

Fig. 37.1

Appendiceal mucocele : the computed tomography shows the cystic enlargement at the base of the appendix (asterisk, panels A and B), as well as the moderately enlarged appendix (in-between arrows, panel C)

Table 37.4 Cancer-specific survival for appendiceal adenocarcinoma stratified by stage and grade

Table 37.5 TNM staging by AJCC for appendiceal adenocarcinoma

Neuroendocrine Appendiceal Lesions /Carcinoid Tumors

• The WHO classification utilizes the terms “neuroendocrine tumor ” (NET), “neuroendocrine carcinoma” (NEC), and “mixed adeno-neuroendocrine carcinomas ” (MANEC).

  • Synonyms for NET include carcinoid tumors and well-differentiated endocrine tumors/carcinoma.

  • Synonyms for NEC are poorly differentiated endocrine carcinoma and small cell/large cell endocrine carcinoma.

  • Goblet cell carcinoids (now called carcinomas) are MANEC.

• Carcinoids or carcinoid tumors represent neuroendocrine tumors grade 1 and are derived from a variety of dispersed neuroendocrine cells (formerly labeled as amine precursor uptake and decarboxylation cells, APUD cells). These cells and the resulting tumors are not only found in the appendix but in the entire gastrointestinal tract and other organs and are therefore addressed more comprehensively in the next chapter.

• Nonetheless, appendiceal carcinoids are only extremely rarely associated with multicentricity, and there is no known association with multiple endocrine neoplasia (MEN syndrome) .

• On gross examination, carcinoid tumors of the appendix are yellow-tan firm nodules. 75% are located at the tip, 15% in the mid-appendix, and 10% at the base of the organ.

• At the time of diagnosis, the majority (80%) are less than 1 cm, 14% measure between 1 and 2 cm, and 6% are greater than 2 cm in size.

• Histologically, carcinoids are characterized by submucosal uniform cell conglomerates with a nested or insular pattern. The cytoplasm has a modestly eosinophilic, fine granularity, and the nuclei show the classic endocrine “salt-and-pepper” chromatin pattern.

• Ki67 is used to determine the proliferative capacity of the tumor for grading according to the current WHO classification.

• AJCC staging for carcinoids is based on tumor size as it correlates with the incidence of metastases and represents the most important prognostic parameter, whereas the depth of invasion, lymphatic, perineural, or serosal invasion, lacks prognostic power (Table 37.6).

  • Lymph node metastases are rare for lesions of less than 10 mm diameter but occur in 20–30% of patients with carcinoids greater than 2 cm in size (Table 37.7); distant metastases are comparably rare in appendiceal carcinoids.

• Five-year survival rates for patients with local, regional, and distant metastatic disease are 95%, 81%, and 31%, respectively.

Table 37.6 TNM staging (by AJCC and ENETS) for neuroendocrine appendiceal tumors

Table 37.7 Impact of appendiceal carcinoid size on lymph node metastasis and survival

Goblet Cell Carcinoids

• This term may add confusion to the classification of appendiceal lesions. It is considered a hybrid between epithelial and neuroendocrine tumors and is also referred to as mucinous adeno-neuroendocrine carcinoma.

• These tumors have a mean age of presentation in the fifth decade and behave more like adenocarcinoma than carcinoid.

• Clinically, goblet cell carcinoids in the middle third of the appendix may in fact cause appendicitis.

• At surgical exploration, 10% or more of the tumors are found to have already widespread metastatic disease; two-thirds of goblet cell carcinoids are incidental findings on appendectomy and ileocecectomy specimens.

• Five-year survival rates are worse than for regular carcinoids and for stages I, II, III, and IV were 100%, 76%, 22%, and 14%, respectively, i.e., range from 50% to 80% for locoregional disease to less than 20% for patients with distant metastases.

Clinical Features

• Appendiceal epithelial neoplasms are notorious for the absence of any specific signs or symptoms, especially at early stages.

• The complicating factor is that they escape detection by routine screening efforts such as colonoscopy.

• If a tumor is concentric and causes obstruction of the lumen, clinical symptomatology of appendicitis may ensue.

  • Red flags in patients with signs of “appendicitis ” should include any age above 50, family history of colorectal cancer or inflammatory bowel disease, prolonged history, or anemia.

• At later stages, epithelial appendiceal neoplasms may present as a localized abdominal or pelvic mass, bowel obstruction, or progressive, painless, abdominal distention when large volumes of mucin accumulate in the peritoneal cavity (pseudomyxoma peritonei).

• Even hormone-active tumors such as carcinoids remain silent and are only incidentally detected.

  • Since they are frequently located at the tip of the appendix, they may not even trigger appendicitis.

  • Carcinoid syndrome is extremely rare (less than 5%) and requires the presence of significant metastatic disease to allow these substances to escape the hepatic first-pass effect and be released into the systemic circulation.

• Given the incredible variability of clinical circumstances under which an appendiceal neoplasm may be diagnosed, clinicians will have to develop concepts and algorithms to optimize and standardize their management (Table 37.1).

Diagnostic Procedures

• Clinical examination is expectedly unreliable in detecting, confirming, or ruling out an appendiceal neoplasm.

• Tumor markers are limited and include non-specific carcinoembryonic antigen (CEA) for epithelial lesions or 5-HIAA metabolites in the urine for carcinoids. Neither marker is suited for screening or as a negative predictive test.

• Cross-sectional imaging (CT, MRI) is of greatest value in evaluating a suspected appendiceal neoplasm.

• Tumors of sufficient size can be demonstrated as a moderately enhancing soft tissue mass or a cystic dilatation of the appendix beyond 15 mm, which should raise suspicion if noted as an incidental finding.

• Bowel displacement is an indirect sign of a pathological extraluminal process and is best visualized by adequate opacification of the terminal ileum and cecum by means of intraluminal contrast and differs from an abscess by the lack of inflammatory signs.

• Features of a mucocele include well-encapsulated and smooth lesions in the right lower quadrant with regular wall and low attenuation that depends on the amount of mucin in the tissue and the center of the lesion.

• The presence of punctate, curvilinear calcifications in a right lower quadrant cystic lesion is highly suggestive of a mucocele: they develop as a dystrophic response to a chronic inflammatory process.

• Pseudomyxoma peritonei is characterized by low-attenuation ascites and serosal implants which when not obvious are best seen as scalloping of the liver contour, at peritoneal reflections, or the pouch of Douglas (Fig. 37.2).

• For treatment strategy and prognosis, it is important to quantify areas affected by PMP. The peritoneal carcinomatosis index (PCI) is a summary score with a maximum of 39 points from nine abdominal squares and four small bowel segments, whereby each area is scored between 0 and 3 when deposits are >5 cm.

• Positron emission tomography (PET ) scan may have a role for detection or monitoring of systemic metastatic disease but is notoriously ineffective in assessing pseudomyxoma peritonei.

• Since most carcinoids are surgical/pathological incidentalomas, most diagnostic investigations are performed after the initial operation.

• For the majority of incidentally diagnosed, well-differentiated appendiceal neuroendocrine tumors of <10 mm, no postoperative diagnostic procedure is necessary.

• After complete resection of 10–20 mm lesions, a single CT or MRI to rule out lymph node and distant metastases is recommended, but without level I evidence.

• For lesions >20 mm, CT and/or MRI of the abdomen is recommended; in addition a PET scan or a somatostatin receptor scan in combination with SPECT/CT (or somatostatin receptor PET with three-phase CT scan) may be considered to detect or rule out distant tumor spread.

• Appendiceal neoplasms typically evade detection by colonoscopy. Occasionally, a protrusion of the appendiceal orifice or release of mucoid material may be recognized (Fig. 37.3).

  • However, colonic evaluation (colonoscopy, CT colonography) is recommended prior to any elective intervention for a suspected or proven appendiceal neoplasm, because both epithelial and neuroendocrine tumors may be multicentric and/or be associated with synchronous lesions in up to 10–20%.

Fig. 37.2

Pseudomyxoma peritonei : the computed tomography in a coronal view (panel A) and axial view (panel B) of a patient with massive deposits of low-attenuation mucin throughout the entire abdomen with scalloping of the liver contour and widening of the spaces between the compressed bowel loops

Fig. 37.3

Colonoscopic appearance : even though appendiceal neoplasms frequently escape endoscopic detection, they occasionally lead to an extramucosal protrusion (asterisk) of the appendiceal orifice into the cecal lumen. ICV ileocecal valve

Medical Management

• Management of localized appendiceal neoplasms is primarily surgical.

• Nonsurgical modalities come into play for locally advanced or metastatic lesions as well as for primarily systemic neoplasms such as leukemia or lymphoma.

• Adjuvant and palliative systemic chemotherapy are still largely based on 5-fluorouracil and typically combined with other conventional agents (oxaliplatin and others) or biological drugs such as bevacizumab.

• Somatostatin is being used for metastatic and particularly symptomatic carcinoid tumors.

• Radiation treatment is not part of routine management of any appendiceal tumor and is reserved for special circumstances on an individualized basis.

Surgical Treatment of Appendiceal Lesions

• Surgery is the primary treatment for localized disease with the goal to achieve a curative R0 resection; in metastatic disease, the role of surgery needs to be individually analyzed and weighed against systemic chemotherapy or best palliative care.

• Surgical decision-making should therefore take five questions into consideration as also alluded to in the previously listed clinical scenarios:

  • 1. Has the primary tumor already been removed?

  • 2. Was the clinical situation associated with possible tumor spillage?

  • 3. For a given tumor, what entails an adequate margin?

  • 4. What is the probability of nodal involvement?

  • 5. In case of locally advanced or metastatic disease, is aggressive surgical intervention superior to conservative management?

• Depending on the answers, there are four possible surgical responses (Table 37.8): (a) appendectomy only, (b) hemicolectomy or completion hemicolectomy, (c) cytoreductive surgery and peritonectomy with or without HIPEC, or (d) conservative management.

Table 37.8 Operations performed for appendiceal neoplasms

Appendectomy

• Appendectomy alone should be reserved for premalignant lesions, carcinoma in situ (Tis), or carcinoids of less than 1 cm diameter provided that a sufficient margin can be obtained.

• Carcinoids of 1–2 cm represent a gray zone but may be associated with a higher than previously reported incidence of nodal disease, suggesting that appendectomy may not suffice.

• An appendiceal mucocele requires careful dissection to avoid perforation of the lesion.

  • If the case is approached laparoscopically, placement of the whole appendix/cecum into a specimen bag prior to starting the dissection may be a strategy to avoid rupture and spillage or conversion to a laparotomy.

Right Hemicolectomy

• For non-perforated appendiceal adenocarcinoma , carcinoids larger than 2 cm, and any of the previously mentioned lesions with unfavorable features or whose margins are insufficient with an appendectomy alone, an oncological right hemicolectomy with a mesocolic lymph node dissection is indicated.

  • Oncological resection for adenocarcinoma achieves better 5-year survival rates than appendectomy alone.

• The incidence of lymph node metastases in appendiceal carcinoid tumors increases with size of the tumor (Table 37.7).

• There is a controversy regarding the surgical management of patients in which perforation of a mucinous appendiceal neoplasm has occurred resulting in pseudomyxoma peritonei .

• Some argue that a right hemicolectomy is not necessary in this situation as the outcome is determined by the peritoneal disease rather than the lymph nodes.

Cytoreductive Surgery and HIPEC

• In cases of advanced peritoneal dissemination, cytoreductive surgery with HIPEC is performed in selected cases.

• If pseudomyxoma peritonei is unexpectedly encountered during an operative exploration, the patient would be best served by careful retrieval and cytological analysis of any mucinous fluid present and referral to a specialized center with expertise in cytoreductive surgery and HIPEC. Minimization of surgical manipulation and mobilization of intra-abdominal viscera will facilitate the subsequent cytoreductive surgery performed later.

• The mainstay of surgical treatment for disseminated peritoneal disease is the arduous operative task of cytoreductive surgery and heated intraperitoneal chemotherapy (HIPEC) (Fig. 37.4).

• In retrospective series, this surgical modality has demonstrated favorable results in carefully selected patients but at the same time was associated with a substantial morbidity and mortality; in addition, most series note that incomplete cytoreduction was unable to achieve a relevant benefit as the recurrence rates were very high.

• It seems rather obvious that the outcomes depend on the extent of the initial disease whereby a number of authors recommended to limit cytoreductive surgery and HIPEC to patients with a PCI of less than (16-)20.

• In reviewing the evidence supporting the use of cytoreduction and HIPEC, it should be noted that the literature on the technique and outcomes continues to have significant limitations.

  • Most series are retrospective and inconsistent in regard to inclusion criteria, extent of disease, concomitant treatment, protocols, and follow-up. Selection bias is inherent to their study designs.

  • Favorable results of prior trials have been challenged by availability of more aggressive systemic chemotherapy regimens, the latter of which parenthetically has been found to increase the risk of complications after HIPEC.

  • Most importantly, however, there is a lack of prospective randomized data on direct comparison of HIPEC and cytoreductive surgery with modern systemic chemotherapy alone.

  • A heated debate continues as to whether HIPEC should be considered the standard of care or still an experimental approach.

• In preparation for cytoreductive surgery and HIPEC, adequate staging and quantitative assessment using the PCI , colonic clearance, aggressive hydration, and bowel cleansing are essential.

  • Considerations include provisions for stomas, timely prophylactic vaccination for splenectomy (against pneumococcus, meningococcus, and H. influenzae), and placement of a gastrostomy tube and feeding jejunostomy tube.

• Cytoreductive surgery aims at removing or reducing all visible tumor implants to less than 2 mm in size as only complete cytoreduction allows for adequate drug penetration into residual tumor deposits.

  • It typically includes omentectomy and stripping of all parietal peritoneal surfaces, including the subdiaphragmatic spaces and the paracolic recesses (peritonectomy).

  • However, it may also involve aggressive multi-organ resection including tumor-involved bowel (colon, small bowel) or other organs (gallbladder, spleen, uterus/ovaries, and others), or the posterior rectus sheath may be removed.

  • For the HIPEC phase of the procedure, a number of open or closed techniques have been reported.

    • We have typically used the closed technique to minimize heat dissipation, spillage of perfusate, and safety hazard to health personnel.

    • The incision is temporarily closed to the size of a gel port through which large-bore afferent and efferent cannulas are placed to the peritoneal cavity.

    • The heated chemotherapeutic drugs are circulated throughout the abdominal cavity via pumps and heat exchangers (heart-lung machine).

    • The most frequently used drug is mitomycin-c , which is administered for a duration of 60–120 min at a temperature of 41–43° C.

    • Reconstructions and anastomoses are to be performed after the hyperthermic perfusion phase.

• Cytoreductive surgery and HIPEC are associated with formidable morbidity that may exceed 50% (Table 37.9).

  • Apart from myelosuppression and nephrotoxicity with intensified diuresis, complications include sepsis, respiratory failure, ileus, anastomotic leak, abscess, enterocutaneous fistula, acute renal failure, thromboembolic events, and in the long run formation of hostile adhesions.

  • The mortality rates in initial reports were approximately 10% but could be reduced significantly in more recent series (Table 37.9).

• In the majority of reports, PCI score, PMCA tumor type, and completeness of cytoreduction were significant prognostic factors. Perioperative or neoadjuvant chemotherapy is currently a matter of debate and is not routinely used.

Fig. 37.4

Hyperthermic intraperitoneal chemotherapy (HIPEC). (Courtesy of Eric K. Johnson, MD)

Table 37.9 Selected series on cytoreductive surgery and HIPEC for appendiceal neoplasms