A careful pain assessment allows the clinician to accurately identify the generators of each pain syndrome and target their therapy correctly [3]. A helpful mnemonic to use is PQRST, shown in Table 13.2.

The most common pain syndromes in pancreatic cancer will be reviewed here, organized by location of disease. Tumors located in the head of the pancreas can cause a visceral epigastric pain syndrome, often described as boring through to the back; sensory innervation from the entire upper abdomen is transmitted through the celiac plexus. When tumor invades the celiac plexus itself, a neuropathic pain syndrome, classically belt-like, radiating from the epigastrium around to the mid-back or vice versa, is common. Liver metastases, when peripheral and either stretching or involving the highly innervated liver capsule, cause an inflammatory visceral pain syndrome; subdiaphragmatic lesions can result in referred pain to the R shoulder. Bulky retroperitoneal lymphadenopathy can cause a visceral back pain syndrome which is classically relieved by hunching forwards; the position shifts the retroperitoneal capsule, which is highly innervated, off of the lymph nodes. Peritoneal carcinomatosis can cause either an inflammatory, diffuse peritoneal pain when nodules invade the peritoneum, or a visceral, cramping pain due to partial small bowel obstruction by tumor deposits. Finally, invasion of the duodenum or gastric wall by tumor can cause an epigastric nociceptive pain syndrome, exacerbated by eating, as gastric juices flood the ulcerated area.

Weight loss in pancreatic cancer can be due to one or more syndromes which often overlap. Syndromes which impact caloric intake or absorption of nutrients can often be reversed or significantly improved with good symptom management.

Pancreatic insufficiency is common with tumors located in the head of the pancreas and presents with abdominal cramping, flatulence, urgency to defecate, and weight loss. Steatorrhea, the most singular symptom of this constellation, does not develop until lipase concentrations fall below 10% of normal, so a high clinical suspicion for this syndrome is warranted [4].

Early satiety can be due to benign causes of gastroparesis (autonomic dysfunction, medications, prior gastrointestinal surgery, or celiac plexus neurolysis) or malignant gastroparesis: in one study, 60% of patients with pancreatic cancer and without gastroduodenal invasion or obstruction experienced abnormally delayed gastric emptying [5]. In the absence of obstruction, which is ruled out by upper gastrointestinal endoscopy or radiographic series, the pathophysiology of gastroparesis in pancreatic cancer patients is due to disruption of the vagus nerve or enteric neural tissues by micrometastases, paraneoplastic antineuronal antibodies, or production of inhibitory neurotransmitters by the tumor [6]. Nonobstructing malignant gastroparesis is diagnosed by gastric emptying scintigraphy.

Anorexia can be the result of severe fatigue, poorly controlled nausea, pain, or depression, xerostomia, stomatitis, or dysgeusia.

In contrast to the weight loss syndromes above, cancer-related anorexia-cachexia syndrome (CACS) cannot be reversed when intake or absorption is improved. The European Palliative Care Research Collaborative defines CACS as a multifactorial syndrome defined by an ongoing loss of skeletal muscle mass (with or without loss of fat mass) that cannot be fully reversed by conventional nutritional support and leads to progressive functional impairment [7]. The pathophysiology is characterized by a negative protein and energy balance driven by a variable combination of reduced food intake and abnormal metabolism (EPCRC). Its prevalence in advanced, unresectable pancreatic cancer patients is 60–80%, and in one study, it was associated with a median survival of 21 weeks [8]. Fearon et al. have proposed a three-factor classification to diagnose cachexia, requiring the presence of at least two of three factors: weight loss >10%, low food intake (≤1500 kcal/day), and systemic inflammation (CRP > 10 mg/mL) [9].

Patients with pancreatic cancer are more likely to experience mood disorders (anxiety, depression, or a mixed state) than patients with other cancer diagnoses: Prevalence rates for combined mood disorders in recent studies ranged from 36 to 57% [10, 11], and undertreatment of these conditions impacts patients’ quality of life. In addition to the mood-specific symptoms of anxiety or depression, an untreated mood disorder can masquerade as, or intensify the experience of, other cancer-related symptoms, such as pain, dyspnea, nausea, and anorexia, and can lead to reductions in performance status, thereby potentially interfering with patients’ ability to tolerate chemotherapy.

Screening for depression in the cancer population is challenging because many of the physical symptoms of depression (fatigue, weight loss, insomnia or hypersomnia, and poor concentration) can result from the cancer process itself. Therefore, experts recommend the use of psychological symptoms instead [12]. It is also important to distinguish depression from preparatory grief, which is a normal part of incurable cancer patients’ preparation for death, and features rumination about the past, intermittent withdrawal from family/friends, and times of sadness, crying, or anxiety [13]. Table 13.3 compares these diagnostic criteria to one another. Consider the diagnosis of adjustment disorder when a patient has depressed symptoms but none of the above criteria are met [14]. Finally, some statements of apparent suicidality (e.g., “I wish I were dead”) can be clues to poorly controlled symptoms (i.e., pain) and should be explored before assuming they relate to depression.

Symptoms of anxiety can be related to medical illness; the clinician should be mindful of possible medication side effects (corticosteroids, some antidepressants, psychostimulants) or withdrawal symptoms (alcohol, opioids, benzodiazepines, clonidine, antidepressants, gabapentin, and corticosteroids), as well as undertreated symptoms (dyspnea, pain), and treat these appropriately. When anxiety is a predominant and limiting symptom and the previous etiologies are not present, the clinician should take a psychiatric history, inquiring about prior episodes of anxiety or depression, PTSD, alcohol, or drug use, prior or current treatment with a mental health professional, or past psychiatric hospitalizations. In addition, the clinician should assess for the presence of panic attacks (pounding heart, sweating, trembling, shortness of breath or choking, dizzy/lightheaded, fear of losing control, or derealization), or lifelong phobias. Patients who screen positive for any of the above elements should be referred to a psychiatry or palliative care practitioner.

The primary tools used to palliate the symptoms of advanced pancreatic cancer are symptom-based medications and procedures, which will be described below. Palliative chemotherapy is appropriate for patients with adequate functional status (ECOG ≥ 2), and even in the absence of objective response, single agent gemcitabine improved clinical benefit response (pain, weight loss, and functional status) [15]. Finally, early integration of palliative care consultants, when available, improves clinical and quality of life outcomes and may improve survival [16]. As a result, early referral to palliative care is now part of ASCO clinical practice guidelines for advanced pancreatic cancer [17].