Pediatr Transplantation 2014: 18: 875–881
© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd
Pediatric Transplantation DOI: 10.1111/petr.12360
Surgical consultation and intervention during pediatric hematopoietic stem cell transplantation Madenci AL, Lehmann LE, Weldon CB. (2014) Surgical consultation and intervention during pediatric hematopoietic stem cell transplantation. Pediatr Transplant, 18: 875–881. DOI: 10.1111/petr. 12360. Abstract: Children undergoing HSCT are at risk for complications due to immune system impairment, toxicity from prior therapies and conditioning regimens, and long-term use of indwelling catheters. These problems may require assessment by the surgical team. We sought to characterize the role of surgical consultation during primary hospital stay for HSCT. We retrospectively reviewed the records of consecutive patients undergoing HSCT between September 2010 and September 2012. One hundred and seventy-three patients underwent 189 HSCTs. General surgery consultations occurred during 33% (n = 62) of primary hospitalizations for HSCT, with a total of 85 consults. Sixtythree (73%) consults resulted in an intervention in the operating room or at the bedside. The majority of consults were for CVL issues (59%, n = 50), followed by abdominal complaints (16%, n = 14). Patients requiring surgical consultation had significantly higher in-hospital mortality (16% vs. 2%, p < 0.01) and 100-day TRM (10% vs. 2%, p < 0.01), compared with those not requiring consultation. Patients undergoing HSCT often require surgical consultation, most commonly for line-related issues. Surgical consultation heralded an increased risk of in-hospital and 100-day TRM. Issues among this high-risk cohort of children who have undergone HSCT must be familiar to the general surgeon and oncologist alike.
HSCT is an important and increasingly used treatment modality for children with an array of malignant and benign diseases (1, 2). However, HSCT carries an attendant risk of complications, due to transplantation-specific factors as well as underlying disease. TRM in children ranges from 5% (autograft) (3) to 15–40% (high-risk allograft) (4) due to toxicity from prior therapies, the conditioning regimen, complications arising from altered immune function, long-term indwelling Abbreviations: BM, bone marrow; CLABSI, central lineassociated bloodstream infections; CVL, central venous line; ECMO, extracorporeal membrane oxygenation; GVHD, graft-versus-host disease; HD, hemodialysis; HSCT, hematopoietic stem cell transplantation; IQR, interquartile range; PBSC, peripheral blood stem cell; TRM, transplant-related mortality.
Arin L. Madenci1,2, Leslie E. Lehmann3,4 and Christopher B. Weldon1,4 1
Department of Surgery, Boston Children’s Hospital and Harvard Medical School, Boston, MA, USA, 2 Department of Surgery, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA, 3Division of Hematology/Oncology, Department of Medicine, Boston Children’s Hospital and Harvard Medical School, Boston, MA, USA, 4Department of Pediatric Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA, USA
Key words: hematopoietic stem cell transplantation – referral and consultation – interdisciplinary communication – pediatrics – health services – central venous catheters Christopher B. Weldon, MD, PhD, Department of Surgery, 300 Longwood Avenue, Fegan 3, Boston, MA 02115, USA Tel.: +1 617 355 4503 Fax: +1 617 730 0752 E-mail: [email protected] Accepted for publication 14 August 2014
catheters, and multiple drug use (5). While it is known that patients receiving HSCT are at risk of complications requiring surgical evaluation, the incidence, causes, and outcomes of surgical problems have not been previously reported in depth. Among adults, approximately 10% of HSCT recipients have been reported to require surgical consultation, most commonly for cholecystitis, abdominal pain, and central line complications (6). Those consulted patients had a 13% in-hospital mortality rate. Among children undergoing HSCT, the data are sparse. A recent retrospective review of pediatric HSCT recipients by Lieber et al. reported a 10% rate of unplanned surgery (consultation rate not reported) due to transplant-related complications and 50% mortality among such patients (7). 875
Madenci et al.
To enhance awareness of issues requiring surgical expertise in this medically complex population and to facilitate coordination of care between transplant physicians and surgeons, we reviewed our institutional experience with pediatric patients admitted for HSCT. We report here on the incidence of surgical consultation, the outcomes of such evaluations, and subsequent interventions. Furthermore, we assessed whether patients undergoing surgical consultation were at increased risk of mortality. Patients and methods This is an institutional review board-approved single-institution study of consecutive pediatric patients undergoing HSCT between September 2010 and September 2012. We acquired demographic, transplant, and outcomes data from a security-protected, prospectively captured database. Surgical consult information was obtained retrospectively. We tabulated patient demographics, disease leading to transplantation, and donor source. Our primary outcome was indication for general surgery consultation during the primary hospital admission. Secondary end-points were in-hospital mortality, 100-day TRM, and overall mortality. Although some patients were hospitalized multiple times, each death was counted only once. One-hundred-day TRM was defined as death related to transplantation occurring ≤100 days after HSCT. Nonparametric statistical tests were used when appropriate.
Results Patient cohort
One hundred and seventy-three patients underwent 189 HSCTs, of which 65% (n = 123) were allogeneic transplants. Median (IQR) age at the time of HSCT was six (1–13) yr. Among allogeneic recipients, the donor source was most commonly BM (85%, n = 105). Of these, 46 patients (37%) had a matched family donor, most commonly a sibling (n = 44). All but one was fully matched. Among the 77 (63%) matched unrelated donors, 57 (74%) were fully matched. Indication for allogeneic transplant was most commonly leukemia (55%, n = 67), while the remainder were largely for immunodeficiencies (11%, n = 14) and benign hematologic disorders (13%, n = 16). Three patients with lymphoma underwent allogeneic transplantation. Among autologous recipients, the donor source was almost always mobilized PBSCs (99%, n = 65). The majority of autologous transplants were performed for solid tumors (95%, n = 63). One patient underwent autologous transplant for acute promyelocytic leukemia. Overall median (IQR) length of hospital stay was 36 (29–44) days. In-hospital mortality was 7% (n = 13). Further 876
Table 1. Characteristics of pediatric HSCT patients Variable*
Overall
Number (%) Age, yr Characteristics of allogeneic recipients Diagnosis (%-allogeneic) Leukemia Benign hematologic disorders Immune deficiency MDS Aplastic anemia Solid tumor Fanconi anemia Other Donor source (%-allogeneic) BM Cord BM/Cord Matched family donor (%-allogeneic) Characteristics of autologous recipients Diagnosis (%-autologous) Solid tumor Immune deficiency (gene therapy) Leukemia Donor source (%-autologous) PBSC BM
189 (100.0) 7 (3–15) 123 (65) 67 (55) 16 (13) 14 (11) 10 (8) 5 (4) 3 (2) 2 (2) 6 (5) 105 (85) 17 (14) 1 (1) 46 (37) 66 (35) 63 (95) 2 (3) 1 (1) 65 (99) 1 (1)
MDS, myelodysplasia. *Reported as number (%) or median (IQR).
details surrounding the characteristics of transplant admissions are reported in Table 1. Consultations
General surgery consultations occurred during 33% (n = 62) of primary hospitalizations for HSCT, with a total of 85 consults (mode = 1, maximum = 8). Consultations occurred at a median (IQR) of 24 (15–40) days following admission. Of the 85 surgical consultations, 73% (n = 63) resulted in operative or bedside intervention. The most common reason for surgical consultation was CVL complication (59% of consultations, n = 50). Among these consultations, nearly half (45%, n = 22) were for line removal for suspected infection. The majority of positive cultures revealed Gram-negative rods (27%, n = 6), followed by Streptococcus viridans (23%, n = 5). Three patients had Staphylococcus species, two patients had Candida species, and one patient had Granulicatella species. Five patients had no positive cultures identified. In all cases of suspected infection, the indication for consult was line removal, which occurred in 86% (19/22) of cases. All three patients with suspected infection for whom lines were not removed had negative blood cultures. Two patients with nega-
Surgical consultation in pediatric HSCT
tive cultures did have CVLs removed due to persistent fevers and suspected infection. The remainder of surgery consults for CVL issues were for removal of non-required lines (16%, n = 8), external breaks (14.0%, n = 7), malposition (12.0%, n = 6), non-functioning CVL (10.0%, n = 5), therapeutic access (2.0%, n = 1), and exposed suture (2.0%, n = 1). The one patient who required therapeutic access for extracorporeal photopheresis survived. Of CVL-related consults, 84% resulted in intervention, including eight bedside and 35 operative interventions. There were no complications from CVL removal at the bedside (n = 2) or in the operating room (n = 29). Among 23 consults for CVL infection, 21 lines were removed (91%), including three (13%) at the bedside and 18 (78%) in the operating room. Among seven consults for external breaks, all were repaired (four bedside, three in the operating room). The second most common reason for consult was for abdominal complaints (16%, n = 14). The abdominal issues included distension (57%, n = 8), evaluation for GVHD with requested biopsy (14%, n = 2), gastrointestinal hemorrhage (14%, n = 2), and gallbladder issues (14%, n = 2). Among the eight patients with distension, consultations included concern for ascites (n = 3), small bowel obstruction (n = 1), adynamic ileus (n = 1), compartment syndrome (n = 1), distension with enteral feeds (n = 1), and infectious colitis (n = 1). Of all abdominalrelated consults, only two (14%) resulted in intervention. One patient underwent bedside paracentesis for evaluation of possible infectious ascites with no infectious cause identified. This patient expired two months post-operatively with multisystem organ failure. One patient with presumed septic shock from suspected infectious colitis underwent exploratory laparotomy and subtotal colectomy. The surgical pathology for the total abdominal colectomy showed no evidence of colitis, GVHD, or ischemia. The patient ultimately expired due to underlying cor pulmonale, the extent of which had not been previously appreciated prior to surgery. Other indications for surgery consult included evaluation for lung biopsy (6%, n = 5), lymph node biopsy (1%, n = 1), enteral access (6%, n = 5), HD access (6%, n = 5), surgical site infection (3%, n = 3), thoracocentesis (1%, n = 1), and ECMO cannulation (1%, n = 1). Of the five lung biopsies performed (video-assisted thoracoscopic surgery, n = 3; open surgery, n = 2), two were negative for studies and cultures, one revealed alveolar hemorrhage, one
revealed bronchiolitis obliterans organizing pneumonia, and one revealed idiopathic interstitial pneumonitis. Results from the lung biopsy changed clinical management of two patients who initiated steroid treatment after diagnosis with bronchiolitis obliterans organizing pneumonia and alveolar hemorrhage. The one lymph node biopsy revealed myeloid sarcoma and led to redirection of treatment goals to palliation. Five patients required consults regarding access for or discontinuation of HD, of whom four patients expired. One surviving patient was consulted for HD catheter removal following conclusion of dialysis requirements for acute renal failure due to hemolytic-uremic syndrome and carboplatin toxicity. Among three surgical site infections, one patient had erythema at the former implantable venous access device site which was treated with broad spectrum antibiotics. Ultrasound was negative for fluid collection and no further intervention was taken. The second patient presented for consult with tenderness to palpation at the former neuroblastoma resection site due to a palpable suture beneath the skin. Given the absence of fevers, erythema, cellulitis, and skin breakdown, the patient was observed. The third patient presented for consultation with fevers and erythema at the liver transplant surgical site. Ultrasound showed the transplanted liver parenchyma within normal limits and the absence of fluid collections. The erythema was demarcated and empiric antibiotic coverage was broadened. One patient underwent thoracocentesis for a pleural effusion which was a culture-negative transudate. One patient required ECMO for pulseless electrical activity due to respiratory failure and ultimately expired. Details of indications for surgical consultation are presented in Table 2. Predictors of consultation
Table 3 reports factors associated with surgical consultation. No factor, including donor transplant type (allograft vs. autograft; p = 0.23) and matched family donor (vs. matched unrelated donor, p = 0.83), was associated with need for surgical consultation. There was likewise no association between any factor and likelihood of surgical intervention, as displayed in Table 4. Outcomes
Overall outcomes are reported in Table 5. Overall, in-hospital, and 100-day transplant-related mortalities were 16% (n = 27), 7% (n = 13), and 5% (n = 9), respectively. Compared with patients who did not have issues requiring surgical con877
Madenci et al. Table 2. Indication for surgical consultation during pediatric HSCT
Table 4. Characteristics of pediatric HSCT patients who did and did not undergo surgical intervention
Indication for consult (n = 85)
Number (%)
CVL issues Infection Removal of non-required line External break Malposition Non-functioning Therapeutic access Exposed suture Abdominal pathology Distension GVHD Hemorrhage Gallbladder Need for biopsy Lung Lymph node Enteral access issues HD access Surgical site infection ECMO cannulation Thoracocentesis
50 (59) 22 (44) 8 (16) 7 (14) 6 (12) 5 (10) 1 (2) 1 (2) 14 (16) 8 (57) 2 (14) 2 (14) 2 (14) 6 (7) 5 (83) 1 (17) 5 (6) 5 (6) 3 (3) 1 (1) 1 (1)
Variable*
Table 3. Characteristics of pediatric HSCT patients who did and did not undergo surgical consultation
Variable* Number (%) Age Characteristics of allogeneic recipients Diagnosis (%-allogeneic) Leukemia Benign hematologic disorders Immune deficiency MDS Aplastic anemia Solid tumor Fanconi anemia Other Donor source (%-allogeneic) BM Cord BM/Cord Matched family donor (%-allogeneic) Characteristics of autologous recipients Diagnosis (%-autologous) Solid tumor Immune deficiency Leukemia Donor source (%-autologous) PBSC BM
Surgical consult
No surgical consult
62 (33) 7 (3–14) 44 (71)
127 (67) 7 (3–16) 79 (62)
22 (50) 8 (18) 5 (11) 3 (7) 2 (5) 1 (2) 0 (0) 3 (7)
45 (57) 8 (10) 9 (11) 7 (9) 3 (4) 2 (3) 2 (3) 3 (3)
36 (82) 7 (16) 1 (2) 17 (39) 18 (29)
69 (87) 10 (13) 0 (0) 29 (37) 98 (38)
17 (94) 0 (0) 1 (6)
46 (96) 2 (4) 0 (0)
18 (100) 0 (0)
47 (98) 1 (2)
No surgical intervention
45 (24) 7 (2–14) 31 (69)
144 (76) 7 (3–15) 92 (64)
15 (48) 7 (23) 3 (10) 2 (7) 2 (7) 0 (0) 0 (0) 2 (7)
52 (57) 9 (10) 11 (12) 8 (9) 3 (3) 3 (3) 3 (3) 4 (4)
25 (81) 5 (16) 1 (3) 13 (42) 14 (31)
80 (87) 12 (13) 0 (0) 33 (36) 52 (36)
13 (93) 0 (0) 1 (7)
50 (96) 2 (4) 0 (0)
14 (100) 0 (0)
51 (98) 1 (2)
p
0.97 0.54 0.60
0.29
0.67 0.54 0.25
>0.99
MDS, myelodysplasia. *Reported as number (%) or median (IQR).
p
0.55 0.23 0.87
0.32
0.83 0.23 0.33
>0.99
MDS, myelodysplasia. *Reported as number (%) or median (IQR).
sultation, patients requiring surgical consultation had significantly longer lengths of stay (median, IQR 43, 34–62 vs. 33, 26–41 days, p < 0.01) as well as higher in-hospital mortality (16% vs. 2%, 878
Number (%) Age Characteristics of allogeneic recipients Diagnosis (%-allogeneic) Leukemia Benign hematologic disorders Immune deficiency MDS Aplastic anemia Solid tumor Fanconi anemia Other Donor source (%-allogeneic) BM Cord BM/Cord Matched family donor (%-allogeneic) Characteristics of autologous recipients Diagnosis (%-autologous) Solid tumor Immune deficiency Leukemia Donor source (%-autologous) PBSC BM
Surgical intervention
p < 0.01 and 100-day TRM [10% vs. 2%, p = 0.03]). Surgical consultation was not associated with significantly increased overall mortality (20% vs. 12%, p = 0.18). Requiring surgical intervention was significantly associated with increased in-hospital mortality (18% vs. 3%, p < 0.01) and 100-day TRM (11% vs. 3%, p = 0.04), but not overall mortality (22% vs. 12%, p = 0.09). Furthermore, in-hospital mortality varied with type of consult, ranging from 2% (3/127) in the no consult group to 7% (3/42) in the group with CVL issues to 39% (7/18) in the non-CVL surgical consult group (p < 0.01). Of 13 patients who expired during the primary hospital admission, the cause of death was multisystem organ failure in 11 patients (with underlying infection in three of these patients) and progression of underlying disease in two patients. One patient developed recurrent acute myelogenous leukemia that presented with leukemic infiltrates in the soft tissue and rapidly progressed to respiratory failure. The second patient had progression of neuroblastoma that led to difficulty swallowing and ultimately respiratory failure. One-hundred-day TRM was due to multisystem organ failure in all nine patients, with underlying infection documented in four of these patients,
Surgical consultation in pediatric HSCT Table 5. Outcomes of pediatric HSCT patients following surgical consultation and intervention Variable*
Surgical consult
No surgical consult
p
Surgical intervention
No surgical intervention
p
Number (%) Length of stay, days†,‡ Mortality In-hospital mortality†,‡ 100-day TRM†,‡ Overall mortality
61 (32) 43 (34–62)
128 (68) 33 (26–41)
© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd
Pediatric Transplantation DOI: 10.1111/petr.12360
Surgical consultation and intervention during pediatric hematopoietic stem cell transplantation Madenci AL, Lehmann LE, Weldon CB. (2014) Surgical consultation and intervention during pediatric hematopoietic stem cell transplantation. Pediatr Transplant, 18: 875–881. DOI: 10.1111/petr. 12360. Abstract: Children undergoing HSCT are at risk for complications due to immune system impairment, toxicity from prior therapies and conditioning regimens, and long-term use of indwelling catheters. These problems may require assessment by the surgical team. We sought to characterize the role of surgical consultation during primary hospital stay for HSCT. We retrospectively reviewed the records of consecutive patients undergoing HSCT between September 2010 and September 2012. One hundred and seventy-three patients underwent 189 HSCTs. General surgery consultations occurred during 33% (n = 62) of primary hospitalizations for HSCT, with a total of 85 consults. Sixtythree (73%) consults resulted in an intervention in the operating room or at the bedside. The majority of consults were for CVL issues (59%, n = 50), followed by abdominal complaints (16%, n = 14). Patients requiring surgical consultation had significantly higher in-hospital mortality (16% vs. 2%, p < 0.01) and 100-day TRM (10% vs. 2%, p < 0.01), compared with those not requiring consultation. Patients undergoing HSCT often require surgical consultation, most commonly for line-related issues. Surgical consultation heralded an increased risk of in-hospital and 100-day TRM. Issues among this high-risk cohort of children who have undergone HSCT must be familiar to the general surgeon and oncologist alike.
HSCT is an important and increasingly used treatment modality for children with an array of malignant and benign diseases (1, 2). However, HSCT carries an attendant risk of complications, due to transplantation-specific factors as well as underlying disease. TRM in children ranges from 5% (autograft) (3) to 15–40% (high-risk allograft) (4) due to toxicity from prior therapies, the conditioning regimen, complications arising from altered immune function, long-term indwelling Abbreviations: BM, bone marrow; CLABSI, central lineassociated bloodstream infections; CVL, central venous line; ECMO, extracorporeal membrane oxygenation; GVHD, graft-versus-host disease; HD, hemodialysis; HSCT, hematopoietic stem cell transplantation; IQR, interquartile range; PBSC, peripheral blood stem cell; TRM, transplant-related mortality.
Arin L. Madenci1,2, Leslie E. Lehmann3,4 and Christopher B. Weldon1,4 1
Department of Surgery, Boston Children’s Hospital and Harvard Medical School, Boston, MA, USA, 2 Department of Surgery, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA, 3Division of Hematology/Oncology, Department of Medicine, Boston Children’s Hospital and Harvard Medical School, Boston, MA, USA, 4Department of Pediatric Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA, USA
Key words: hematopoietic stem cell transplantation – referral and consultation – interdisciplinary communication – pediatrics – health services – central venous catheters Christopher B. Weldon, MD, PhD, Department of Surgery, 300 Longwood Avenue, Fegan 3, Boston, MA 02115, USA Tel.: +1 617 355 4503 Fax: +1 617 730 0752 E-mail: [email protected] Accepted for publication 14 August 2014
catheters, and multiple drug use (5). While it is known that patients receiving HSCT are at risk of complications requiring surgical evaluation, the incidence, causes, and outcomes of surgical problems have not been previously reported in depth. Among adults, approximately 10% of HSCT recipients have been reported to require surgical consultation, most commonly for cholecystitis, abdominal pain, and central line complications (6). Those consulted patients had a 13% in-hospital mortality rate. Among children undergoing HSCT, the data are sparse. A recent retrospective review of pediatric HSCT recipients by Lieber et al. reported a 10% rate of unplanned surgery (consultation rate not reported) due to transplant-related complications and 50% mortality among such patients (7). 875
Madenci et al.
To enhance awareness of issues requiring surgical expertise in this medically complex population and to facilitate coordination of care between transplant physicians and surgeons, we reviewed our institutional experience with pediatric patients admitted for HSCT. We report here on the incidence of surgical consultation, the outcomes of such evaluations, and subsequent interventions. Furthermore, we assessed whether patients undergoing surgical consultation were at increased risk of mortality. Patients and methods This is an institutional review board-approved single-institution study of consecutive pediatric patients undergoing HSCT between September 2010 and September 2012. We acquired demographic, transplant, and outcomes data from a security-protected, prospectively captured database. Surgical consult information was obtained retrospectively. We tabulated patient demographics, disease leading to transplantation, and donor source. Our primary outcome was indication for general surgery consultation during the primary hospital admission. Secondary end-points were in-hospital mortality, 100-day TRM, and overall mortality. Although some patients were hospitalized multiple times, each death was counted only once. One-hundred-day TRM was defined as death related to transplantation occurring ≤100 days after HSCT. Nonparametric statistical tests were used when appropriate.
Results Patient cohort
One hundred and seventy-three patients underwent 189 HSCTs, of which 65% (n = 123) were allogeneic transplants. Median (IQR) age at the time of HSCT was six (1–13) yr. Among allogeneic recipients, the donor source was most commonly BM (85%, n = 105). Of these, 46 patients (37%) had a matched family donor, most commonly a sibling (n = 44). All but one was fully matched. Among the 77 (63%) matched unrelated donors, 57 (74%) were fully matched. Indication for allogeneic transplant was most commonly leukemia (55%, n = 67), while the remainder were largely for immunodeficiencies (11%, n = 14) and benign hematologic disorders (13%, n = 16). Three patients with lymphoma underwent allogeneic transplantation. Among autologous recipients, the donor source was almost always mobilized PBSCs (99%, n = 65). The majority of autologous transplants were performed for solid tumors (95%, n = 63). One patient underwent autologous transplant for acute promyelocytic leukemia. Overall median (IQR) length of hospital stay was 36 (29–44) days. In-hospital mortality was 7% (n = 13). Further 876
Table 1. Characteristics of pediatric HSCT patients Variable*
Overall
Number (%) Age, yr Characteristics of allogeneic recipients Diagnosis (%-allogeneic) Leukemia Benign hematologic disorders Immune deficiency MDS Aplastic anemia Solid tumor Fanconi anemia Other Donor source (%-allogeneic) BM Cord BM/Cord Matched family donor (%-allogeneic) Characteristics of autologous recipients Diagnosis (%-autologous) Solid tumor Immune deficiency (gene therapy) Leukemia Donor source (%-autologous) PBSC BM
189 (100.0) 7 (3–15) 123 (65) 67 (55) 16 (13) 14 (11) 10 (8) 5 (4) 3 (2) 2 (2) 6 (5) 105 (85) 17 (14) 1 (1) 46 (37) 66 (35) 63 (95) 2 (3) 1 (1) 65 (99) 1 (1)
MDS, myelodysplasia. *Reported as number (%) or median (IQR).
details surrounding the characteristics of transplant admissions are reported in Table 1. Consultations
General surgery consultations occurred during 33% (n = 62) of primary hospitalizations for HSCT, with a total of 85 consults (mode = 1, maximum = 8). Consultations occurred at a median (IQR) of 24 (15–40) days following admission. Of the 85 surgical consultations, 73% (n = 63) resulted in operative or bedside intervention. The most common reason for surgical consultation was CVL complication (59% of consultations, n = 50). Among these consultations, nearly half (45%, n = 22) were for line removal for suspected infection. The majority of positive cultures revealed Gram-negative rods (27%, n = 6), followed by Streptococcus viridans (23%, n = 5). Three patients had Staphylococcus species, two patients had Candida species, and one patient had Granulicatella species. Five patients had no positive cultures identified. In all cases of suspected infection, the indication for consult was line removal, which occurred in 86% (19/22) of cases. All three patients with suspected infection for whom lines were not removed had negative blood cultures. Two patients with nega-
Surgical consultation in pediatric HSCT
tive cultures did have CVLs removed due to persistent fevers and suspected infection. The remainder of surgery consults for CVL issues were for removal of non-required lines (16%, n = 8), external breaks (14.0%, n = 7), malposition (12.0%, n = 6), non-functioning CVL (10.0%, n = 5), therapeutic access (2.0%, n = 1), and exposed suture (2.0%, n = 1). The one patient who required therapeutic access for extracorporeal photopheresis survived. Of CVL-related consults, 84% resulted in intervention, including eight bedside and 35 operative interventions. There were no complications from CVL removal at the bedside (n = 2) or in the operating room (n = 29). Among 23 consults for CVL infection, 21 lines were removed (91%), including three (13%) at the bedside and 18 (78%) in the operating room. Among seven consults for external breaks, all were repaired (four bedside, three in the operating room). The second most common reason for consult was for abdominal complaints (16%, n = 14). The abdominal issues included distension (57%, n = 8), evaluation for GVHD with requested biopsy (14%, n = 2), gastrointestinal hemorrhage (14%, n = 2), and gallbladder issues (14%, n = 2). Among the eight patients with distension, consultations included concern for ascites (n = 3), small bowel obstruction (n = 1), adynamic ileus (n = 1), compartment syndrome (n = 1), distension with enteral feeds (n = 1), and infectious colitis (n = 1). Of all abdominalrelated consults, only two (14%) resulted in intervention. One patient underwent bedside paracentesis for evaluation of possible infectious ascites with no infectious cause identified. This patient expired two months post-operatively with multisystem organ failure. One patient with presumed septic shock from suspected infectious colitis underwent exploratory laparotomy and subtotal colectomy. The surgical pathology for the total abdominal colectomy showed no evidence of colitis, GVHD, or ischemia. The patient ultimately expired due to underlying cor pulmonale, the extent of which had not been previously appreciated prior to surgery. Other indications for surgery consult included evaluation for lung biopsy (6%, n = 5), lymph node biopsy (1%, n = 1), enteral access (6%, n = 5), HD access (6%, n = 5), surgical site infection (3%, n = 3), thoracocentesis (1%, n = 1), and ECMO cannulation (1%, n = 1). Of the five lung biopsies performed (video-assisted thoracoscopic surgery, n = 3; open surgery, n = 2), two were negative for studies and cultures, one revealed alveolar hemorrhage, one
revealed bronchiolitis obliterans organizing pneumonia, and one revealed idiopathic interstitial pneumonitis. Results from the lung biopsy changed clinical management of two patients who initiated steroid treatment after diagnosis with bronchiolitis obliterans organizing pneumonia and alveolar hemorrhage. The one lymph node biopsy revealed myeloid sarcoma and led to redirection of treatment goals to palliation. Five patients required consults regarding access for or discontinuation of HD, of whom four patients expired. One surviving patient was consulted for HD catheter removal following conclusion of dialysis requirements for acute renal failure due to hemolytic-uremic syndrome and carboplatin toxicity. Among three surgical site infections, one patient had erythema at the former implantable venous access device site which was treated with broad spectrum antibiotics. Ultrasound was negative for fluid collection and no further intervention was taken. The second patient presented for consult with tenderness to palpation at the former neuroblastoma resection site due to a palpable suture beneath the skin. Given the absence of fevers, erythema, cellulitis, and skin breakdown, the patient was observed. The third patient presented for consultation with fevers and erythema at the liver transplant surgical site. Ultrasound showed the transplanted liver parenchyma within normal limits and the absence of fluid collections. The erythema was demarcated and empiric antibiotic coverage was broadened. One patient underwent thoracocentesis for a pleural effusion which was a culture-negative transudate. One patient required ECMO for pulseless electrical activity due to respiratory failure and ultimately expired. Details of indications for surgical consultation are presented in Table 2. Predictors of consultation
Table 3 reports factors associated with surgical consultation. No factor, including donor transplant type (allograft vs. autograft; p = 0.23) and matched family donor (vs. matched unrelated donor, p = 0.83), was associated with need for surgical consultation. There was likewise no association between any factor and likelihood of surgical intervention, as displayed in Table 4. Outcomes
Overall outcomes are reported in Table 5. Overall, in-hospital, and 100-day transplant-related mortalities were 16% (n = 27), 7% (n = 13), and 5% (n = 9), respectively. Compared with patients who did not have issues requiring surgical con877
Madenci et al. Table 2. Indication for surgical consultation during pediatric HSCT
Table 4. Characteristics of pediatric HSCT patients who did and did not undergo surgical intervention
Indication for consult (n = 85)
Number (%)
CVL issues Infection Removal of non-required line External break Malposition Non-functioning Therapeutic access Exposed suture Abdominal pathology Distension GVHD Hemorrhage Gallbladder Need for biopsy Lung Lymph node Enteral access issues HD access Surgical site infection ECMO cannulation Thoracocentesis
50 (59) 22 (44) 8 (16) 7 (14) 6 (12) 5 (10) 1 (2) 1 (2) 14 (16) 8 (57) 2 (14) 2 (14) 2 (14) 6 (7) 5 (83) 1 (17) 5 (6) 5 (6) 3 (3) 1 (1) 1 (1)
Variable*
Table 3. Characteristics of pediatric HSCT patients who did and did not undergo surgical consultation
Variable* Number (%) Age Characteristics of allogeneic recipients Diagnosis (%-allogeneic) Leukemia Benign hematologic disorders Immune deficiency MDS Aplastic anemia Solid tumor Fanconi anemia Other Donor source (%-allogeneic) BM Cord BM/Cord Matched family donor (%-allogeneic) Characteristics of autologous recipients Diagnosis (%-autologous) Solid tumor Immune deficiency Leukemia Donor source (%-autologous) PBSC BM
Surgical consult
No surgical consult
62 (33) 7 (3–14) 44 (71)
127 (67) 7 (3–16) 79 (62)
22 (50) 8 (18) 5 (11) 3 (7) 2 (5) 1 (2) 0 (0) 3 (7)
45 (57) 8 (10) 9 (11) 7 (9) 3 (4) 2 (3) 2 (3) 3 (3)
36 (82) 7 (16) 1 (2) 17 (39) 18 (29)
69 (87) 10 (13) 0 (0) 29 (37) 98 (38)
17 (94) 0 (0) 1 (6)
46 (96) 2 (4) 0 (0)
18 (100) 0 (0)
47 (98) 1 (2)
No surgical intervention
45 (24) 7 (2–14) 31 (69)
144 (76) 7 (3–15) 92 (64)
15 (48) 7 (23) 3 (10) 2 (7) 2 (7) 0 (0) 0 (0) 2 (7)
52 (57) 9 (10) 11 (12) 8 (9) 3 (3) 3 (3) 3 (3) 4 (4)
25 (81) 5 (16) 1 (3) 13 (42) 14 (31)
80 (87) 12 (13) 0 (0) 33 (36) 52 (36)
13 (93) 0 (0) 1 (7)
50 (96) 2 (4) 0 (0)
14 (100) 0 (0)
51 (98) 1 (2)
p
0.97 0.54 0.60
0.29
0.67 0.54 0.25
>0.99
MDS, myelodysplasia. *Reported as number (%) or median (IQR).
p
0.55 0.23 0.87
0.32
0.83 0.23 0.33
>0.99
MDS, myelodysplasia. *Reported as number (%) or median (IQR).
sultation, patients requiring surgical consultation had significantly longer lengths of stay (median, IQR 43, 34–62 vs. 33, 26–41 days, p < 0.01) as well as higher in-hospital mortality (16% vs. 2%, 878
Number (%) Age Characteristics of allogeneic recipients Diagnosis (%-allogeneic) Leukemia Benign hematologic disorders Immune deficiency MDS Aplastic anemia Solid tumor Fanconi anemia Other Donor source (%-allogeneic) BM Cord BM/Cord Matched family donor (%-allogeneic) Characteristics of autologous recipients Diagnosis (%-autologous) Solid tumor Immune deficiency Leukemia Donor source (%-autologous) PBSC BM
Surgical intervention
p < 0.01 and 100-day TRM [10% vs. 2%, p = 0.03]). Surgical consultation was not associated with significantly increased overall mortality (20% vs. 12%, p = 0.18). Requiring surgical intervention was significantly associated with increased in-hospital mortality (18% vs. 3%, p < 0.01) and 100-day TRM (11% vs. 3%, p = 0.04), but not overall mortality (22% vs. 12%, p = 0.09). Furthermore, in-hospital mortality varied with type of consult, ranging from 2% (3/127) in the no consult group to 7% (3/42) in the group with CVL issues to 39% (7/18) in the non-CVL surgical consult group (p < 0.01). Of 13 patients who expired during the primary hospital admission, the cause of death was multisystem organ failure in 11 patients (with underlying infection in three of these patients) and progression of underlying disease in two patients. One patient developed recurrent acute myelogenous leukemia that presented with leukemic infiltrates in the soft tissue and rapidly progressed to respiratory failure. The second patient had progression of neuroblastoma that led to difficulty swallowing and ultimately respiratory failure. One-hundred-day TRM was due to multisystem organ failure in all nine patients, with underlying infection documented in four of these patients,
Surgical consultation in pediatric HSCT Table 5. Outcomes of pediatric HSCT patients following surgical consultation and intervention Variable*
Surgical consult
No surgical consult
p
Surgical intervention
No surgical intervention
p
Number (%) Length of stay, days†,‡ Mortality In-hospital mortality†,‡ 100-day TRM†,‡ Overall mortality
61 (32) 43 (34–62)
128 (68) 33 (26–41)
