Pancreaticoduodenectomy is one of the major procedures for periampullary malignancy and benign diseases. However, the high rate of postoperative complications hinders the rehabilitation and increases medical cost. Other than improving surgical techniques, identifying susceptible patients and refining support strategy seems crucial. In the present study, we found preoperative skeletal muscle index and density as well as age were prognostic factors affecting postoperative complications. More importantly, through sub-group analysis, the IPNT and APD were independent determinants for complications in patients with lower SMI. These results may provide a practical strategy for distinguishing PD patients of high risk and tailored nutritional therapy.
Previously, Martin et al demonstrated skeletal muscle depletion was a powerful prognostic factor for survival in cancer patients . In critical patients, muscle wasting was prevalent and profound. Up to 60–70% critical patients had muscle wasting at ICU admission , and 20% of skeletal muscle reduction was found in ICU patients within first 10 days . Both the quantity and quality of skeletal muscle affected the course and outcome of the disease [2, 3]. In our present study, preoperative muscle depletion was found in 40.75% subjects who would undergo PD. The reported incidence rate of sarcopenia in PD patients varied a lot from 24.2%  to 75.5% [7, 23], which may due to different population and cut-off value. Pancreatic and periampullary cancer patients were always malnourished at admission. It was necessary to have a thorough and accurate evaluation on the nutritional status. To date, CT was a widely used method for measuring skeletal muscle conditions due to its accuracy , and other approaches included bioelectrical impedance analysis and ultrasound. In our univariable analysis, VATA/SMA ratio appeared to be a significant factor affecting postoperative morbidity (RR 1.23, 95%CI 1.07–1.56, P = 0.012). This was in accordance with previous studies. David et al have shown high visceral adipose tissue was associated with increased infection rate (OR: 2.4) in pancreatic cancer patients. Moreover, longer survival was observed in patients with high muscle attenuation combined with low visceral adipose tissue (P = 0.011) . In cancer patients underwent PD, Sandini et al had shown a high visceral adipose tissue-to-skeletal muscle ratio significantly increased major complication with OR reaching 3.20 . From a prospective study with 284 patients undergoing PD, researchers demonstrated sarcopenic obesity was the only independent predictor for POPF (OR 2.65, 95% CI 1.43–4.93) . In addition, females tend to have higher rate of sarcopenic obesity (BMI > 25) than males (38% vs. 12%) in patients with resectable PDAC and those patients showed higher incidence of major complications (P < 0.001) . Adipose tissue does have some merits, such as energy storage, harm protection, warm keeping. Being a double-edge sword, fat may also play a bad character under some conditions. Excessive visceral fat could handicap the surgical operation, increasing the intraoperative risk. As an endocrine organ, unbalanced adipokines and cytokines may promote postoperative inflammation and develop insulin resistance .
In the multivariable regression, we found preoperative L3 level muscle index and density were predictive of postoperative complications. Here, higher muscle density was significantly related reduced complications (OR = 0.85, 95%CI 0.64–1.03, p = 0.029). The result was in line with other studies. Amini et al reported higher risk of morbidity and complication was observed in patients with sarcopenia after curative resection for pancreatic adenocarcinoma . Recently, both Nicolas and Minji et al have demonstrated mean muscle attenuation could be a promising parameter to predict complications and POPF after PD [6, 7]. In addition to short-term results, long-term outcome also seems to relate to skeletal muscle conditions. Elisabeth et al have shown sarcopenia negatively impacted overall survival in resectable PDCA patients (14 vs. 20 months) . However, several studies demonstrated the amount of muscle mass was not predictive of major complication or morbidity after pancreatic surgery [22, 26]. We considered the disagreement may relate to different methods, cut-off values and etiology.
Lower skeletal muscle area and density probably mean lower protein reserve and myosteatosis. In aging and tumor patients, the muscle depletion may be caused by insufficient intake and ensuing proteolysis, which occurred long before admission. Study has shown the serum albumin concentration correlated well with skeletal mass in critical patients . Decreased albumin always indicated poor nutrition status and even leaded to tissue edema, which may hamper surgical procedure and healing. Reduced muscle density was a reflection of alteration in muscle composition within muscle fibers, as fluid surcharge and fat accumulation . In several researches of oncology, including melanoma, adrenocortical carcinoma, renal cell carcinoma, muscle density was found to be an independent prognostic factor of survival [29–31]. An inverse association between muscle attenuation and triglyceride content has been established in healthy adults , and it was shown IMAT correlated with muscle density . Myosteatosis may involve insulin resistance, inflammation, mitochondrial damage and oxidative stress . These metabolic changes would further cause a fuel utilization shift from lipids to glucose in muscle, leading to muscle protein depletion and reduced capacity .
Of particular interesting, our subgroup analysis revealed that delayed initiation of supplementary parental nutrition (SPN) was associated with higher complications in low SMI patients undergoing PD (OR 1.89, 95% CI 1.43–2.49, p = 0.032). It was widely recognized that early enteral feeding was preferred in major surgery and critical patients [11, 12, 19]. However, enteral feeding always accompanied with abdominal distention, nausea, vomiting and underfeeding, especially among patients receiving major upper gastrointestinal surgery. According to ASPEN guideline, PN should be delayed for 5–7 days in the postoperative ICU patients, who may partly represent PD subjects . However, the rationale resources it based on were largely from clinical studies conducted more than twenty years ago [13, 34, 35], which may differ from current PN pattern including preparation technology and hypocaloric feeding. Actually, in a recent multicenter RCT comparing EN and PN, no difference in mortality, infectious complication rate, and hospital length of stay was observed in critical patients . In malnourished patients, PN resulted in a significantly lower mortality with a tendency towards lower rates of infection . The timing of starting PN has long been debated in critical and surgical patients [11, 12, 19, 38]. Our present study, to our knowledge, for the first time demonstrated only in low SMI patients, early PN was beneficial for reduced complication. This result was in line with Heidegger’s research, which found in malnourished patients and those with special risks SPN should be considered on day 4 after ICU admission . Indeed, many studies have yielded negative results on early PN support in critical and surgical patients [38, 40]. However, a recent Cochrane meta-analysis could not draw a clear conclusion as whether early or late SPN was better in critical patients due to low-quality evidence . The heterogeneity and different baseline nutrition status may have impacted the results. ESPEN guideline suggested PN should be considered in high nutrition risk or malnourished patients [12, 19]. But, no clear prescription was provided as a lack of integrating studies. Since skeletal muscle was a crucial indicator for nutrition status and affected patients outcome both in short and long term [2, 3, 21], we tested whether it could differentiate the efficiency of parental nutrition support in PD patients. The present results may help identify those patients who may benefit early PN support and provide some evidence for early SPN in sarcopenic patients.
Some mechanism researches have shown early PN may suppress muscle cell autophagy and associated with muscle weakness [42, 43]. In addition, increased amount of adipose tissue within the muscle compartments was observed in critical patients receiving early PN . However, these outcomes did not mean worse endpoints. Perhaps, it may just represent a metabolic process. Anyhow, early nutrition support and sufficient protein supply can ensure necessary substrates in malnourished patients, even though it may not affect muscle wasting.
Here we also have shown higher protein supply was a protective factor for postoperative complication in low SMI patients (OR 0.76, 95%CI 0.53–0.89, p = 0.021). This result was supported by previous observational researches [44, 45], which demonstrated higher protein delivery was associated with improved survival. Benefits of high protein delivery were also found in RCT trials. Ferrie et al shown higher level of amino acids supply (1.1 g/kg vs o.9 g/kg) was associated with improved patients focused outcomes, such as handgrip strength and muscle mass, despite without differences in mortality . Doig et al found higher intravenous amino acid therapy was related to improvement in renal function . Ishibashi et al shown higher protein intake (> 1.5 g/kg/d) was associated with less total body protein loss. Mechanistic studies have shown a 3-h high level (1 g/kg/d) amino acid infusion was able to improve protein balance from negative to positive in critical patients . Sundstrom et al also reported a supplemental intravenous amino acid infusion sustained a positive protein balance for 24 h . Current guidelines recommend adequate protein supply (≥ 1.2 or 1.3 g/kg/d) in critical patients, but few data exists as to major surgery patients . Therefore, sufficient protein supply appears beneficial in surgical patients, but high quality evidence is needed.
Our study did have some limitations that should be addressed. First, the patient population underwent PD procedure was due to various reasons from trauma, benign disease to cancer. This heterogeneity may reduce the quality of evidence to guide clinical case. Second, we only analyzed the relationship between preoperative skeletal muscle and short-term postoperative complications. The extent of muscle wasting after surgery was not documented, which may also influence the short and long-term outcomes. Thus, dynamic courses of skeletal muscle conditions and its impact on prognosis as well as nutrition support should be examined in the future. Third, the patients who received late PN may have more severe conditions, such as hemodynamic instability, which may add bias to the analysis.