Patient selection and the volume effect in pancreatic surgery: unequal benefits?

Background

The volume effect in pancreatic surgery is well established. Regionalization to high-volume centres has been proposed. The effect of this proposal on practice patterns is unknown.

Methods

Retrospective review of pancreatectomy patients in the Nationwide Inpatient Sample 2004–2011. Inpatient mortality and complication rates were calculated. Patients were stratified by annual centre pancreatic resection volume (low <5, medium 5–18, high >18). Multivariable regression model evaluated predictors of resection at a high-volume centre.

Results

In total, 129 609 patients underwent a pancreatectomy. The crude inpatient mortality rate was 4.3%. 36.0% experienced complications. 66.5% underwent a resection at high-volume centres. In 2004, low-, medium- and high-volume centres resected 16.3%, 24.5% and 59.2% of patients, compared with 7.6%, 19.3% and 73.1% in 2011. High-volume centres had lower mortality (P < 0.001), fewer complications (P < 0.001) and a shorter median length of stay (P < 0.001). Patients at non-high-volume centres had more comorbidities (P = 0.001), lower rates of private insurance (P < 0.001) and more non-elective admissions (P < 0.001).

Discussion

In spite of a shift to high-volume hospitals, a substantial cohort still receives a resection outside of these centres. Patients receiving non-high-volume care demonstrate less favourable comorbidities, insurance and urgency of operation. The implications are twofold: already disadvantaged patients may not benefit from the high-volume effect; and patients predisposed to do well may contribute to observed superior outcomes at high-volume centres.     

Rankings versus reality in pancreatic cancer surgery: a real-world comparison

Background

Patients are increasingly confronted with systems for rating hospitals. However, the correlations between publicized ratings and actual outcomes after pancreatectomy are unknown.

Methods

The Massachusetts Division of Health Care Finance and Policy Hospital Inpatient Discharge Database was queried to identify pancreatic cancer resections carried out during 2005–2009. Hospitals performing fewer than 10 pancreatic resections in the 5-year period were excluded. Primary outcomes included mortality, complications, median length of stay (LoS) and a composite outcomes score (COS) combining primary outcomes. Ranks were determined and compared for: (i) volume, and (ii) ratings identified from consumer-directed hospital ratings including the US News & World Report (USN), Consumer Reports, Healthgrades and Hospital Compare. An inter-rater reliability analysis was performed and correlation coefficients (r) between outcomes and ratings, and between rating systems were calculated.

Results

Eleven hospitals in which a total of 804 pancreatectomies were conducted were identified. Surgical volume correlated with overall outcome, but was not the strongest indicator. The highest correlation referred to that between USN rank and overall outcome. Mortality was most strongly correlated with Healthgrades ratings (r = 0.50); however, Healthgrades ratings demonstrated poorer correlations with all other outcomes. Consumer Reports ratings showed inverse correlations.

Conclusions

The plethora of publicly available hospital ratings systems demonstrates heterogeneity. Volume remains a good but imperfect indicator of surgical outcomes. Further systematic investigation into which measures predict quality outcomes in pancreatic cancer surgery will benefit both patients and providers.     

Early oral feeding after pancreatoduodenectomy enhances recovery without increasing morbidity

Objective

The aim of this study was to evaluate whether a change in the routine feeding strategy applied after pancreatoduodenectomy (PD) from nasojejunal tube (NJT) feeding to early oral feeding improved clinical outcomes.

Methods

An observational cohort study was performed in 102 consecutive patients undergoing PD. In period 1 (n = 51, historical controls), the routine postoperative feeding strategy was NJT feeding. This was changed to a protocol of early oral feeding with on-demand NJT feeding in period 2 (n = 51, consecutive prospective cohort). The primary outcome was time to resumption of adequate oral intake.

Results

The baseline characteristics of study subjects in both periods were comparable. In period 1, 98% (n = 50) of patients received NJT feeding, whereas in period 2, 53% (n = 27) of patients did so [for delayed gastric empting (DGE) (n = 20) or preoperative malnutrition (n = 7)]. The time to resumption of adequate oral intake significantly decreased from 12 days in period 1 to 9 days in period 2 (P = 0.015), and the length of hospital stay shortened from 18 days in period 1 to 13 days in period 2 (P = 0.015). Overall, there were no differences in the incidences of complications of Clavien–Dindo Grade III or higher, DGE, pancreatic fistula, postoperative haemorrhage and mortality between the two periods.

Conclusions

The introduction of an early oral feeding strategy after PD reduced the time to resumption of adequate oral intake and length of hospital stay without negatively impacting postoperative morbidity.     

Treatment sequencing strategy for hepatic epithelioid haemangioendothelioma

Background

The biology of hepatic epithelial haemangioendothelioma (HEHE) is variable, lying intermediate to haemangioma and angiosarcoma. Treatments vary owing to the rarity of the disease and frequent misdiagnosis.

Methods

Between 1989 and 2013, patients retrospectively identified with HEHE from a single academic cancer centre were analysed to evaluate clinicopathological factors and initial treatment regimens associated with survival.

Results

Fifty patients with confirmed HEHE had a median follow-up of 51 months (range 1–322). There was no difference in 5-year survival between patients presenting with unilateral compared with bilateral hepatic disease (51.4% versus 80.7%, respectively; P = 0.1), localized compared with metastatic disease (69% versus 78.3%, respectively; P = 0.7) or an initial treatment regimen of Surgery, Chemotherapy/Embolization or Observation alone (83.3% versus 71.3% versus 72.4%, respectively; P = 0.9). However, 5-year survival for patients treated with chemotherapy at any point during their disease course was decreased compared with those who did not receive any chemotherapy (43.6% versus 82.9%, respectively; P = 0.02) and was predictive of a decreased overall survival on univariate analysis [HR 3.1 (CI 0.9–10.7), P = 0.02].

Conclusions

HEHE frequently follows an indolent course, suggesting that immediate treatment may not be the optimal strategy. Initial observation to assess disease behaviour may better stratify treatment options, reserving surgery for those who remain resectable/transplantable. Prospective cooperative trials or registries may confirm this strategy.     

Glecaprevir/pibrentasvir for patients with chronic hepatitis C virus infection and severe renal impairment

Data are limited regarding the real‐world effectiveness and safety of glecaprevir/pibrentasvir (GLE/PIB) in patients with chronic hepatitis C virus (HCV) infection and severe renal impairment (RI). We aimed to evaluate the performance of GLE/PIB in patients with chronic kidney disease (CKD) stage 4 or 5 in Taiwan. 108 chronic HCV patients with CKD stage 4 (n = 32) or 5 (n = 76) receiving GLE/PIB for 8‐12 weeks were retrospectively recruited at 4 academic centres in Taiwan. The effectiveness was determined by sustained virologic response at off‐therapy week 12 (SVR₁₂) for evaluable (EP) and per‐protocol populations (PP). The safety profiles were also assessed. By EP and PP analyses, the SVR₁₂ rate was 99.1% (107 of 108 patients; 95% confidence interval (CI): 94.9%‐99.8%) and 100% (107 of 107 patients; 95% CI: 96.5%‐100%). The SVR₁₂ rates were 100% (95% CI: 89.3%‐100%) and 98.7% (95% CI: 92.9%‐99.8%) in patients with CKD stage 4 and 5, respectively. One patient, who declined off‐therapy follow‐up after permanently discontinuing GLE/PIB at on‐treatment week 9 due to scheduled cardiac surgery, had nonvirologic failure. Sixteen (14.8%) patients had serious adverse events (AEs), which were judged not related to GLE/PIB. The three most common AEs were pruritus (19.4%), fatigue (15.7%) and nausea (13.9%). None had ≥3‐fold upper limit of normal for total bilirubin and alanine aminotransferase levels. None of the 9 patients with hepatitis B virus (HBV) coinfection developed HBV‐associated hepatitis. In conclusion, GLE/PIB for 8‐12 weeks is effective and well‐tolerated in HCV patients with severe RI.     

TREM-1 Promotes Survival during Klebsiella pneumoniae Liver Abscess in Mice

Klebsiella pneumoniae liver abscess (KPLA) is prevalent in East Asia. Liver abscess can develop after translocation of K. pneumoniae from a patient''s bowel into the liver via the portal circulation. TREM-1 (triggering receptor expressed on myeloid cells 1) amplifies inflammatory signaling during infection, but its role in KPLA is poorly understood. We used an animal study to characterize the role of TREM-1 in KPLA. We compared survival rates, bacterial burdens in tissues, inflammatory cytokine levels, and histology findings between wild-type and Trem-1 knockout (KO) mice after oral inoculation of capsular type K1 K. pneumoniae. Translocation of K. pneumoniae to mesenteric lymph nodes and liver was examined, and intestinal permeability, antimicrobial peptide expression, and the clearance of K. pneumoniae in the small intestine were determined. In the absence of TREM-1, KPLA model mice showed increased K. pneumoniae dissemination, enhanced liver and systemic inflammation, and reduced survival. Impaired bacterial clearance in the small intestine causes enhanced K. pneumoniae translocation, which renders Trem-1 KO mice more susceptible to K. pneumoniae oral infection. In conclusion, TREM-1-mediated bacterial clearance in the small intestine is an important immune response against K. pneumoniae. TREM-1 deficiency enhances K. pneumoniae translocation in the small intestine and increases mortality rates in mice with KPLA.     

Fe-vacancy order and superconductivity in tetragonal β-Fe1-xSe

Several superconducting transition temperatures in the range of 30–46 K were reported in the recently discovered intercalated FeSe system (A_1-xFe_2-ySe₂, A = K, Rb, Cs, Tl). Although the superconducting phases were not yet conclusively decided, more than one magnetic phase with particular orders of iron vacancy and/or potassium vacancy were identified, and some were argued to be the parent phase. Here we show the discovery of the presence and ordering of iron vacancy in nonintercalated FeSe (PbO-type tetragonal β-Fe_1-xSe). Three types of iron-vacancy order were found through analytical electron microscopy, and one was identified to be nonsuperconducting and magnetic at low temperature. This discovery suggests that the rich-phases found in A_1-xFe_2-ySe₂ are not exclusive in Fe-Se and related superconductors. In addition, the magnetic β-Fe_1-xSe phases with particular iron-vacancy orders are more likely to be the parent phase of the FeSe superconducting system instead of the previously assigned β-Fe_1+δTe.The iron pnictide superconductors have opened the door to a new way to obtain superconductivity at very high temperatures. β-Fe_1+δSe is remarkable among those superconductors in that it contains the essential electronic and structural constituents required for superconductivity without the conceptual complexity seen in other systems (1). Previous studies showed that the superconducting property of β-Fe_1+δSe made under high-temperature thermodynamic conditions is very sensitive to stoichiometry (1, 2). In the Fe-Se binary phase diagram (2–4), the PbO-type tetragonal structure (the β phase) only stabilized at the Fe-rich side (δ = 0.01–0.04), whereas bulk superconductivity was observed in samples with δ close to 0.01 (5). McQueen et al. showed no superconductivity for samples with δ = 0.03 (5). On the other hand, the fact that only one superconducting phase has been reported in FeSe, unlike the other Fe-As–based superconductors that exhibit clear doping dependence of superconductivity and the absence of superconductivity in FeTe, led to the suggestion that FeTe is the nonsuperconducting parent compound of FeSe (6). Thus, the phase diagram derived from this picture shows very different features compared with other Fe-As–based superconductors (6, 7). In this work, we use low-temperature synthesis methods to prepare β-Fe_1-xSe for a wide range of compositions, which allows for the determination for the composition-dependent electronic behavior for this important superconducting system.The recent discovered alkali/alkaline-intercalated iron selenide (A_1-xFe_2-ySe₂) superconductors with rich superconducting phases, where A = K, Rb, Cs, Tl, attracted great attention not only due to its high superconducting transition temperature (T_c, up to 46 K) (8), but also because of their dissimilar characteristics compared with other iron-based superconductors, especially its seemingly intrinsic multiphase nature and the presence of iron vacancies and orders in the nonsuperconducting regime (9–13). The most frequently observed Fe-vacancy order in A_1-xFe_2-ySe₂ is the × × 1 superstructure, which yields a phase of A_0.8Fe_1.6Se₂ (or A₂Fe₄Se₅). Scanning tunneling microscopy (STM) (11, 14, 15) and transport studies (12, 13, 16, 17) showed that A₂Fe₄Se₅ is an antiferromagnetic (AFM) insulator. Neutron scattering measurements (9) revealed a blocked checkerboard AFM with magnetic moments along the c axis for A₂Fe₄Se₅, ordered at a temperature as high as >500 K, with an unexpected large ordered magnetic moment of ∼3.3 μ_B/Fe at 10 K. Experiments have further shown that the type of vacancy and magnetic orders is highly sensitive to the stoichiometry (x and y) of A_1-xFe_2-ySe₂. Reports have shown the existence of other Fe-vacancy order with the forms × × 1 (10), × 2 × 1 (13, 18), and × × 1 (19). However, the magnetic properties such as the type and transition temperature of the magnetic order are far less studied compared with that of the K₂Fe₄Se₅ phase. In addition, there were also results showing in K_1-xFe_2-ySe₂ samples with a typical T_c = 31 K and additional superconducting phase with T_c = 44 K (20), whereas no clear identification of the new phases was available.The complexity of phases and phase separation during crystal preparation in A_1-xFe_2-ySe₂ make it difficult to conclusively verify the phase-property relationship, even for the superconducting phases. β-Fe_1+δSe, on the other hand, has the simplest structure among all iron-based superconductor families. Several surprising results related to the Fe-Se system appeared in the literature during the last few years, including the enhancement of T_c to about 40 K under high pressure (21–23) and the intriguing extremely high T_c (with a superconducting energy gap of ∼20 meV) in molecular beam epitaxy (MBE)-grown single-layer FeSe (24–26). We also demonstrated the presence of a superconducting-like feature with T_c close to 40 K in samples of nano-dimensional form (27). Therefore, it is quite natural to ask whether the presence of the complex phases observed in A_1-xFe_2-ySe₂ compounds and Fe-vacancy order exist in samples without alkaline metals. Here we present the first discovery of iron vacancies and three types of vacancy orders in tetragonal β-Fe_1-xSe, characterized by analytical transmission electron microscopy (TEM). Our observations imply that an unprecedented phase diagram should be considered in the Fe-Se superconductors.