Pancreatic cystic neoplasms

Pancreatic cystic neoplasms comprise a heterogeneous group of lesions characterised by cystic components within the pancreatic parenchyma, with a broad spectrum of biological behaviour ranging from clearly benign forms to entities with variable potential for malignant transformation. Over recent decades, these lesions have acquired increasing clinical relevance because of the widespread use of high-resolution imaging techniques, which has led to a substantial rise in incidental diagnoses among asymptomatic individuals undergoing radiological examinations for other indications.

From histopathological and clinical perspectives, pancreatic cystic neoplasms include entities that differ in cellular origin, morphology, anatomical distribution and oncological risk. The principal types include mucinous tumours, characterised by variable malignant potential, and serous lesions, which generally behave benignly. Borderline forms and rare neoplasms also occur, each with specific biological features and management implications. Correct lesion characterisation is essential because management strategies range from simple longitudinal surveillance to surgical resection.

The natural history of pancreatic cystic neoplasms is heterogeneous and depends on histological type, size, location and the presence of risk features. Many lesions remain stable for years, whereas others show slow but continuous progression towards malignancy. Diagnosis and staging require an integrated approach combining morphological imaging, endoscopic assessment with sampling of cyst contents and, in selected cases, biochemical and molecular analyses. Management is typically multidisciplinary and aims to balance oncological risk against the morbidity of invasive procedures.

The epidemiology of pancreatic cystic neoplasms is strongly influenced by the increasing use of imaging techniques such as computed tomography and magnetic resonance imaging, which has produced a marked rise in diagnoses, often in the absence of symptoms. Observational studies indicate that pancreatic cystic lesions can be found in a substantial proportion of the adult population, with prevalence increasing progressively with age. Only some of these lesions, however, are true neoplasms with clinically relevant significance.

Demographically, many pancreatic cystic neoplasms show preferential distributions by sex and age. Some forms, particularly mucinous lesions, are more frequently diagnosed in middle-aged women, whereas other entities have a more balanced distribution. Advanced age is associated with a greater likelihood of detecting cystic lesions, but not necessarily with a proportional increase in the risk of malignancy.

Specific risk factors for the development of pancreatic cystic neoplasms have not been defined unequivocally. Unlike ductal adenocarcinoma, there is no strong and consistent association with smoking or alcohol consumption, although these factors may indirectly influence risk through the development of chronic pancreatic disease. In some settings, an association has been observed with chronic inflammatory conditions of the pancreas, which can complicate the differential diagnosis with pseudocysts.

Genetic factors and predisposing inherited conditions have an important role. Some genetic syndromes are associated with an increased risk of specific pancreatic cystic neoplasms, often together with other systemic manifestations. In these patients, lesions may be multiple and present at a younger age than in the general population, making dedicated surveillance necessary.

Biologically, pancreatic cystic neoplasms arise through abnormal differentiation of the ductal epithelium or other cellular compartments, with production of mucin or serous fluid and formation of cystic cavities. In mucinous lesions, the progressive accumulation of genetic alterations may promote transition to dysplastic and invasive forms, whereas serous lesions generally retain an indolent course.

Taken together, these elements define an epidemiological setting in which pancreatic cystic neoplasms are increasingly identified and their clinical impact is determined mainly by the ability to distinguish low-risk lesions from those with malignant potential. This distinction is essential for establishing management strategies proportionate to individual risk.

There are no population screening programmes for pancreatic cystic neoplasms because most lesions are identified incidentally and only a limited proportion carries a significant risk of malignant progression. The absence of simple, sufficiently specific tests and the risk of overdiagnosis make systematic screening unjustified in the general population.

Clinical management is based mainly on surveillance of identified lesions, with the aim of monitoring their evolution over time and detecting signs of malignant transformation at an early stage. Surveillance is indicated particularly for cystic neoplasms with oncological potential when immediate criteria for surgical resection are absent. The monitoring strategy is tailored according to lesion type, size, location and the presence of suspicious radiological features.

The imaging methods most commonly used during follow-up are magnetic resonance imaging with cholangiopancreatography and endoscopic ultrasonography. MRI provides a non-invasive assessment that can be repeated over time, whereas endoscopic ultrasonography offers more detailed characterisation of the cyst wall and permits fluid sampling for cytological and biochemical analyses when required. Integration of these techniques improves diagnostic accuracy and risk stratification.

In individuals with inherited genetic syndromes associated with an increased risk of pancreatic neoplasms, surveillance may begin earlier and be conducted more intensively. In these settings, identification and monitoring of cystic lesions form part of structured long-term surveillance programmes aimed at early diagnosis of clinically relevant neoplastic transformation.

In recent years, innovative approaches have been proposed to refine the management of pancreatic cystic neoplasms, including cyst-fluid biomarkers and targeted molecular analyses. These tools may provide additional information on a lesion’s biological potential, but they are not yet sufficiently standardised for widespread routine use and remain largely confined to specialist centres.

Overall, the absence of population screening makes personalised surveillance, based on integrated assessment of clinical, radiological and biological factors, central to management. The objective is to prevent progression to invasive forms while avoiding excessive treatment in patients with indolent lesions.

Pancreatic cystic neoplasms are a heterogeneous group of lesions characterised by cystic cavities lined by neoplastic epithelium, with biological behaviour ranging from entirely benign forms to lesions with malignant potential and true invasive neoplasms. Their biology reflects origin from different cellular compartments of the exocrine pancreas, particularly the ductal epithelium and, less frequently, mucinous or serous epithelial cells with distinct differentiation programmes.

Pathogenetically, pancreatic cystic neoplasms develop through mechanisms that differ from those of conventional ductal adenocarcinoma. In many cases, the process begins with a focal alteration of the ductal or glandular epithelium, which acquires aberrant secretory activity and causes progressive formation of cystic cavities. Persistent proliferative stimuli and accumulation of genetic and epigenetic alterations may, in some types, lead to progression from dysplasia to carcinoma through a well-recognised sequence.

From a genetic perspective, molecular profiles differ significantly according to the type of cystic neoplasm. Mucinous neoplasms, including IPMNs and mucinous cystic neoplasms, frequently harbour activating KRAS mutations as an early event, sometimes accompanied by GNAS alterations, which are particularly characteristic of IPMNs and affect cyclic-AMP-mediated signalling. With dysplastic progression, mutations of TP53, SMAD4 and CDKN2A emerge, similarly to invasive pancreatic ductal adenocarcinoma.

Serous cystic neoplasms, by contrast, show a distinct molecular profile, generally lacking KRAS mutations and characterised by alterations of the VHL gene, especially in settings associated with von Hippel–Lindau syndrome. These lesions have low genomic instability and typically benign biological behaviour, consistent with the absence of genetic driver events for malignant transformation.

In addition to genetic mutations, epigenetic alterations contribute to the cystic phenotype. Changes in DNA methylation and chromatin affect the expression of genes involved in mucin secretion, cell polarity and maintenance of epithelial architecture. In mucinous lesions, these changes promote abundant mucin production and progression towards high-grade dysplasia.

The microenvironment of pancreatic cystic neoplasms is generally less desmoplastic than that of invasive ductal adenocarcinoma. In forms with advanced dysplasia or malignant transformation, however, progressive stromal remodelling occurs, with fibroblast activation, neoangiogenesis and the development of a chronic inflammatory infiltrate. These elements accompany the transition to more aggressive biological behaviour.

The principal biological categories include:

• serous cystic neoplasms, which generally behave benignly;
• mucinous cystic neoplasms, with potential for malignant transformation;
• intraductal papillary mucinous neoplasms, characterised by dysplasia–carcinoma progression;
• rare cystic neoplasms, including solid pseudopapillary variants with a cystic component.

Histologically, serous cystic neoplasms consist of small cysts lined by clear cuboidal epithelium rich in glycogen, often arranged in a microcystic pattern. Mucinous cystic neoplasms instead contain larger cavities lined by mucin-secreting columnar epithelium and are characterised by ovarian-type stroma, a distinctive diagnostic feature. IPMNs show papillary proliferation of ductal epithelium with mucin production and variable grades of dysplasia.

Immunohistochemistry supports characterisation: expression of mucins such as MUC1, MUC2 and MUC5AC helps distinguish mucinous subtypes, whereas markers such as CK7 and CK19 confirm ductal origin. Assessment of the grade of dysplasia and any stromal invasion is the key step in defining biological risk.

Overall, pancreatic cystic neoplasms form a biological continuum ranging from benign lesions to direct precursors of pancreatic adenocarcinoma, determined by the interaction between specific genetic alterations, epigenetic regulation and progressive stromal remodelling.

The clinical manifestations of pancreatic cystic neoplasms are extremely variable and depend on lesion type, size, location and possible involvement of the main or secondary pancreatic ducts. A large proportion of these lesions is asymptomatic and is identified incidentally during imaging performed for other clinical indications.

When present, symptoms are often non-specific. Dull or intermittent abdominal pain in the epigastric or hypochondriac region is one of the most common manifestations and is related to capsular distension or compression of adjacent structures. Pain may radiate posteriorly and tends to be more frequent in large lesions or those located in the body and tail of the pancreas.

Neoplasms involving the main pancreatic duct, particularly main-duct IPMNs, may obstruct pancreatic-juice outflow and cause episodes of recurrent acute pancreatitis or chronic pancreatitis. In these cases, the clinical picture is dominated by acute abdominal pain, nausea, vomiting and elevated pancreatic enzymes, with progressive deterioration of pancreatic function.

In lesions located in the pancreatic head, compression of the common bile duct may cause obstructive jaundice, dark urine, pale stools and pruritus. This scenario is more typical of large mucinous neoplasms or IPMNs and often represents the clinical sign that leads to diagnosis.

Clinical presentation varies according to type:

• serous neoplasms: frequently asymptomatic or associated with mild pain;
• mucinous neoplasms: pain, a palpable mass and risk of progression;
• main-duct IPMNs: recurrent pancreatitis, jaundice and a higher risk of malignancy;
• branch-duct IPMNs: often incidental, with late symptoms.

As they enlarge, some cystic neoplasms may cause a sensation of an abdominal mass, early satiety, nausea or compression of adjacent gastrointestinal structures. In rare cases, cyst rupture or infection of cyst contents may cause acute pain and fever, producing an acute abdominal presentation.

Malignant transformation or the presence of an invasive component is associated with more evident systemic signs, such as weight loss, fatigue and rapid worsening of symptoms. At these stages, manifestations related to metastatic spread may occur, similarly to invasive pancreatic adenocarcinoma.

Physical findings are often minimal or absent. In advanced cases, abdominal tenderness, jaundice and signs of nutritional impairment may be detected. The overall clinical picture is one of lesions with variable behaviour, in which persistent pancreatic symptoms or the onset of alarm features always require thorough diagnostic evaluation.

The diagnostic assessment of pancreatic cystic neoplasms begins with clinical suspicion or, more frequently, with an incidental finding on imaging performed for other indications. The diagnostic strategy follows a rational sequence aimed first at correctly characterising the cystic lesion, then distinguishing benign forms, lesions with malignant potential and already malignant neoplasms, and finally defining disease extent in advanced cases, without yet introducing formal staging. Symptoms, when present, include vague or persistent abdominal pain, recurrent acute pancreatitis, obstructive jaundice, weight loss or new-onset diabetes, but a substantial proportion of patients is asymptomatic. The initial objective is therefore to avoid underdiagnosis of high-risk lesions and overtreatment of indolent lesions.

Laboratory tests have a supportive role and cannot establish a definitive diagnosis. Serum markers, including CA 19-9, may be normal or moderately elevated and do not reliably distinguish among different cystic entities. Abnormal pancreatic enzymes or cholestatic indices may be present in cases complicated by pancreatitis or biliary compression. Biochemical findings must therefore be interpreted as ancillary elements within a broader clinical and radiological context.

Imaging is the cornerstone of diagnostic assessment. Contrast-enhanced computed tomography provides an initial evaluation of the lesion, defining its size, location, relationship with the main pancreatic duct and the presence of calcifications or mural nodules. Magnetic resonance imaging with magnetic resonance cholangiopancreatography (MRCP), however, is considered the reference examination for characterising cystic neoplasms because of its superior resolution in delineating communication with the ductal system, wall morphology and cyst contents. MRI also helps distinguish patterns suggestive of specific entities, such as mucinous or serous neoplasms.

Endoscopic ultrasonography (EUS) has a central role when imaging does not permit definitive characterisation or when signs of possible malignancy are present. EUS allows detailed assessment of cyst walls, any mural nodules or endoluminal projections, and the peripancreatic tissues. During the procedure, aspiration of cyst contents may be performed for biochemical, cytological and molecular analysis of the fluid.

Cyst-fluid analysis provides useful information for lesion classification. Measurement of intracystic CEA helps distinguish mucinous from non-mucinous lesions, whereas amylase levels may suggest communication with the ductal system. Cytology has limited sensitivity but, when positive, permits a diagnosis of malignancy. In selected centres, molecular analysis of cyst fluid can identify mutations associated with specific neoplasms and supplement the diagnostic picture.

The definitive diagnosis of pancreatic cystic neoplasms is based on integration of clinical, radiological and endoscopic findings. Histopathologically, when tissue is available, the different entities show distinctive features. Mucinous neoplasms have mucin-secreting epithelium with variable dysplasia, whereas serous neoplasms are characterised by glycogen-rich cuboidal cells. When stromal invasion is documented, a diagnosis of carcinoma associated with a cystic neoplasm is made.

According to the principal international guidelines, adequate assessment of a pancreatic cystic neoplasm requires a minimum set of clinical, imaging and endoscopic information to guide management; these elements are not formal “diagnostic criteria” but are essential requirements for reliable evaluation:

Elements required for diagnostic assessment of pancreatic cystic neoplasms

• Identification of a pancreatic cystic lesion by CT or MRI.
• Detailed morphological characterisation with MRI and MRCP.
• Assessment of risk features or suspected malignancy.
• Use of endoscopic ultrasonography with aspiration of cyst contents when indicated.
• Multidisciplinary integration of clinical, radiological and endoscopic data.

The differential diagnosis includes pancreatic pseudocysts, typically associated with acute or chronic pancreatitis, and other non-neoplastic cystic lesions. Distinction is based on clinical history, radiological appearance and biochemical analysis of cyst fluid. Solid neoplasms with cystic degeneration and pancreatic metastases must also be considered because they have different characteristics and therapeutic implications.

Once diagnostic characterisation is complete, subsequent investigations focus on identifying any evidence of invasion or advanced disease. Computed tomography assesses vascular involvement and the presence of metastases, whereas 18F-FDG PET may be used in selected cases to clarify equivocal findings or suspected malignant transformation.

In summary, diagnostic assessment of pancreatic cystic neoplasms follows a structured sequence: incidental or clinical identification; CT and especially MRI with MRCP; endoscopic ultrasonography with fluid analysis when indicated; and multidisciplinary integration to define the nature and risk of the lesion.

Staging of pancreatic cystic neoplasms has clinical significance mainly in forms with malignant transformation or an associated invasive carcinoma. In benign lesions or those with low-grade dysplasia, formal staging is replaced by assessment of the risk of progression. When invasion is present, the reference system is the AJCC/UICC TNM classification applied to pancreatic carcinoma.

Clinical staging is based on integration of computed tomography and magnetic resonance imaging findings, which permit assessment of local extent, involvement of vascular structures and the presence of distant metastases. In carcinoma associated with a cystic neoplasm, staging follows the same principles used for pancreatic adenocarcinoma, with particular attention to vascular relationships and nodal status.

Prognostically, the fundamental distinction is between non-invasive lesions and lesions with invasive carcinoma. Non-invasive cystic neoplasms that are appropriately selected and monitored or surgically treated generally have a favourable prognosis. By contrast, stromal invasion causes a marked deterioration in outcome, bringing biological behaviour closer to that of malignant pancreatic neoplasms.

Conceptually, the principal prognostic categories may be summarised as follows:

Prognostic categories in pancreatic cystic neoplasms

• Non-invasive lesions: no carcinoma, with an excellent prognosis after resection or with appropriate surveillance.
• Lesions with advanced dysplasia: high risk of progression, with surgery indicated in selected patients.
• Associated invasive carcinoma: prognosis depends on TNM stage and resectability.

When a surgical specimen is available, pathological staging permits more accurate prognostic assessment based on the extent of invasion, resection-margin status and any lymph-node involvement. Complete resection of a non-invasive cystic neoplasm is associated with high long-term survival.

Survival curves show a marked difference between non-invasive and invasive forms. Long-term survival is excellent in the former, whereas outcome in the latter is strongly determined by stage at diagnosis and the feasibility of radical resection.

In addition to stage, several additional prognostic factors influence clinical evolution, including lesion size, mural nodules, dilatation of the main pancreatic duct and the patient’s general condition. Age, performance status and comorbidities influence both treatment choice and overall prognosis.

Overall, prognostic assessment of pancreatic cystic neoplasms is an integrated process combining morphological, biological and clinical characteristics. Outcome is favourable in non-invasive forms, whereas in forms with an associated carcinoma the prognosis becomes similar to that of malignant pancreatic neoplasms and remains strongly dependent on stage and resectability.

Treatment of pancreatic cystic neoplasms requires an individualised, risk-stratified approach because these lesions encompass biologically diverse entities ranging from entirely benign forms to neoplasms with variable malignant potential and frankly invasive lesions. Management should be entrusted to a multidisciplinary team with specific expertise in pancreatic disease, capable of integrating clinical, radiological, endoscopic and, when available, cytological and molecular data.

The first decision point is the distinction between lesions suitable for active surveillance and those requiring surgical treatment. This assessment is based on cyst size, morphological characteristics, involvement of the main pancreatic duct, the presence of mural nodules, symptoms and individual risk factors, including patient age and comorbidities.

In forms with a low risk of malignant transformation, such as many serous cystic neoplasms and some small mucinous neoplasms without suspicious features, clinical and radiological surveillance is the preferred approach. This strategy avoids unnecessary surgery, which carries appreciable morbidity, while maintaining longitudinal monitoring to detect any evidence of biological evolution.

Surgery is indicated for lesions with a high risk of malignancy or features suggesting neoplastic transformation. In particular, surgical treatment is recommended for mucinous neoplasms with mural nodules, significant dilatation of the main pancreatic duct, rapid growth, symptoms attributable to the lesion or suspicious cytology. Main-duct and mixed-type IPMNs also represent a clear surgical indication in most cases.

The type of operation depends on the location of the lesion. Neoplasms of the pancreatic head are treated by pancreaticoduodenectomy, whereas lesions of the body and tail generally undergo distal pancreatectomy, with or without spleen preservation in selected cases. The objective is complete resection with clear margins, combined with adequate lymphadenectomy when malignancy is suspected or confirmed.

In multifocal lesions, particularly IPMNs, the surgical strategy may be complex. In selected cases, segmental resection with surveillance of the pancreatic remnant may be indicated, whereas total pancreatectomy is reserved for exceptional situations because of its major impact on quality of life through the inevitable development of diabetes and severe exocrine pancreatic insufficiency.

Cystic neoplasms already associated with an invasive component are treated according to the principles governing malignant pancreatic neoplasms, with radical surgery followed, when indicated, by adjuvant treatment according to histology and stage. In these cases, management extends beyond simple cystic disease and enters structured oncological pathways.

Assessment of operative risk is an essential component of treatment. Pancreatic surgery carries potentially severe complications, including pancreatic fistula, delayed gastric emptying and infection. The surgical indication must therefore always result from careful balancing of the risk of neoplastic progression against procedural risk, especially in older patients or those with substantial comorbidities.

At every stage, integration of nutritional and metabolic support is crucial, particularly in patients undergoing extensive resections. Prevention and treatment of exocrine pancreatic insufficiency and glycaemic abnormalities are integral to overall therapeutic management.

Follow-up and post-treatment surveillance are central to the clinical management of pancreatic cystic neoplasms because of the possibility of late progression, recurrence or development of new lesions in the residual pancreatic parenchyma. The methods and duration of follow-up depend on histological type, treatment received and the individual risk profile.

In patients managed with active surveillance, follow-up is primarily radiological. Magnetic resonance imaging with cholangiopancreatography is the reference examination because it provides detailed assessment of cyst contents, septa, mural nodules and the main pancreatic duct without exposure to ionising radiation. The frequency of examinations is tailored according to the lesion’s initial size and stability over time.

During surveillance, attention focuses on identifying alarm features, such as rapid growth, the appearance of mural nodules, changes in the pancreatic duct or the onset of symptoms. When such findings occur, the diagnostic and therapeutic pathway is reassessed and surgery may become necessary.

In patients who undergo surgical resection for a non-invasive cystic neoplasm, follow-up aims to monitor the pancreatic remnant. This is particularly important in IPMNs, which carry a meaningful risk of metachronous lesions. Radiological surveillance is generally continued over the long term, even in the absence of disease.

When a cystic neoplasm contains or develops an invasive component, follow-up follows the principles used for malignant pancreatic neoplasms, with closer clinical and radiological assessments, particularly during the first years after treatment when the risk of recurrence is highest.

Management of functional sequelae is a fundamental component of follow-up. After pancreatic surgery, patients must be monitored for exocrine pancreatic insufficiency and secondary diabetes, with dynamic adjustment of enzyme-replacement and metabolic therapy. Periodic nutritional monitoring is essential to prevent malnutrition and loss of muscle mass.

Follow-up is generally prolonged and often indefinite in forms with potential for multifocality or late transformation. In patients with stable low-risk lesions, the intervals between examinations may be gradually lengthened while maintaining structured surveillance.

In summary, follow-up of pancreatic cystic neoplasms is not a merely formal review but a continuous process integrating radiological surveillance, clinical assessment and functional management, with the aim of preventing malignant evolution and preserving long-term quality of life.

Long-term quality-of-life considerations are central to management of pancreatic cystic neoplasms, particularly given the frequent incidental diagnosis and the lengthy courses of surveillance or postoperative follow-up. Even without neoplastic progression, the psychological and functional impact of the condition may significantly affect daily life, making continuous, structured assessment of quality of life necessary.

One relevant domain is the burden of long-term surveillance. In patients undergoing periodic radiological follow-up, uncertainty regarding the risk of malignant transformation may cause persistent anxiety, anticipatory stress and difficulty planning personal and working life. Repeated investigations over time impose a psychological burden that requires appropriate clinical communication and continuous information support.

In surgically treated patients, exocrine and endocrine pancreatic function substantially influences quality of life. Exocrine pancreatic insufficiency may manifest with steatorrhoea, diarrhoea and malabsorption, whereas loss of endocrine function may lead to pancreatogenic diabetes. These conditions require lasting lifestyle adaptations, continuous metabolic monitoring and individualised nutritional support.

Nutrition and body composition are important determinants of long-term well-being. Unintentional weight loss, reduced muscle mass and nutritional deficiencies may develop gradually, especially after extensive pancreatic resections. Maintaining adequate nutritional status is essential to preserve functional capacity, independence and overall quality of life.

Chronic abdominal pain, although not constant, may persist in some patients because of surgical sequelae, fibrosis or postoperative anatomical changes. This symptom may limit physical activity and interfere with sleep, requiring an integrated approach to pain control.

The psychological and psychosocial domain is particularly important. Awareness of living with a lesion that has neoplastic potential, even when risk is low, may cause anxiety, somatic hypervigilance and reduced perceived health. In patients who have undergone surgery, bodily and functional changes may affect self-image and social relationships. Structured psychological support and clear, continuous communication with the treating team promote better long-term adaptation.

Overall, long-term quality of life in pancreatic cystic neoplasms depends on the healthcare system’s ability to provide integrated care that combines clinical and imaging surveillance with management of functional, nutritional and psychological sequelae. Quality of life is therefore a primary clinical outcome that should be considered alongside oncological risk in decision-making and follow-up.

Complications of pancreatic cystic neoplasms arise from the interaction between the biological characteristics of the lesion, neoplastic progression and the therapeutic strategies adopted, producing a heterogeneous clinical picture that requires long-term monitoring. Although many lesions follow an indolent course, some may undergo malignant transformation or cause clinically relevant local complications.

Local progression may compress adjacent structures, causing abdominal pain, obstructive jaundice or digestive symptoms. When the lesion communicates with the main pancreatic duct, obstruction of outflow may promote episodes of acute or chronic pancreatitis with progressive impairment of pancreatic function.

A major complication is malignant transformation, the risk of which varies according to cystic-neoplasm type, lesion size and the presence of risk features. Progression to invasive carcinoma radically changes the prognosis and requires prompt treatment.

Pancreatic surgery, indicated when risk features or malignant transformation are present, is associated with appreciable morbidity. The principal complications include postoperative pancreatic fistula, intra-abdominal infection, haemorrhage and delayed gastric emptying. In the long term, exocrine and endocrine pancreatic insufficiency are common sequelae with a significant impact on quality of life.

Invasive diagnostic procedures, such as endoscopic ultrasound-guided fine-needle aspiration, carry specific risks that are generally low but not negligible. Pancreatitis, bleeding and infection may complicate these procedures, particularly in patients with comorbidities or anatomical abnormalities.

Systemically, deterioration of nutritional status, infection and, more rarely, thromboembolic events may complicate the clinical course, especially in patients undergoing major surgery. Progressive functional decline requires a comprehensive approach integrating symptom control, nutritional support and, when indicated, palliative care.

Management of complications is based on structured prevention, including appropriate selection of patients for surveillance or surgery, adequate clinical and imaging monitoring, and early recognition of signs of progression or complication. Integration of multidisciplinary expertise reduces morbidity, improves quality of life and optimises long-term outcomes.