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Diverticulitis in immunodeficient patients: our experience ... · OR 6281 inglés Diverticulitis in...
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Title:Diverticulitis in immunodeficient patients: our experiencein the management of high-risk patients
Authors:Javier Serrano González, José Luis Lucena de la Poza, LauraRomán García de León, Jesús Gabriel García Schiever, NedaFarhangmehr Setayeshi, Pablo Calvo Espino, Arsenio SánchezMovilla, Victor Sánchez Turrión
DOI: 10.17235/reed.2019.6281/2019Link: PubMed (Epub ahead of print)
Please cite this article as:Serrano González Javier, Lucena de la Poza José Luis, RománGarcía de León Laura, García Schiever Jesús Gabriel,Farhangmehr Setayeshi Neda, Calvo Espino Pablo, SánchezMovilla Arsenio, Sánchez Turrión Victor. Diverticulitis inimmunodeficient patients: our experience in themanagement of high-risk patients. Rev Esp Enferm Dig 2019.doi: 10.17235/reed.2019.6281/2019.
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OR 6281 inglés
Diverticulitis in immunodeficient patients: our experience in the management of
high-risk patients
Javier Serrano González1, José Luis Lucena de la Poza1, Laura Román García de León1,
Jesús Gabriel García Schiever2, Neda Farhangmehr Setayeshi3, Pablo Calvo Espino1,
Arsenio Sánchez Movilla1 and Víctor Sánchez Turrión1
1General Surgery and Digestive Diseases Service. Hospital Puerta de Hierro
Majadahonda. Majadahonda, Madrid. Spain. 2General Surgery and Digestive Diseases
Service. Hospital General Universitario de Ciudad Real. Ciudad Real, Spain. 3General
Surgery and Digestive Diseases Service. Colchester General Hospital. Colchester,
United Kingdom
*This study was partially presented in the XXX National Surgery Congress, Madrid,
2014.
Received: 21/3/2019
Accepted: 4/7/2019
Correspondence: Javier Serrano González. General Surgery and Digestive Diseases
Service. Hospital Universitario Puerta de Hierro Majadahonda. C/ Manuel de Falla, 1.
28222 Majadahonda, Madrid. Spain
e-mail: [email protected]
ABSTRACT
Introduction: acute diverticulitis is a very prevalent disease. The need for a more
aggressive management in immunodeficient patients has not been established. We
present the results of our unit with immunodeficient patients diagnosed with acute
diverticulitis and their follow-up.
Objectives: to assess the possibility that a conservative management in this group is as
valid as in the immunocompetent population.
Methods: a retrospective analysis study was performed in our hospital. Forty
immunodeficient patients (transplant, corticoid treatment, dialysis, oncologic, HIV
patients) diagnosed with acute diverticulitis were analyzed. The patients were
managed with a surgical or non-surgical treatment according to their status on
admission. The main analyzed items were the severity of the acute episode and the
need for surgical treatment compared to the cause of immunodeficiency. Other
studied variables included follow-up results and recurrences.
Results: thirty-two of the 40 patients studied received a non-surgical treatment during
the acute episode, eight required emergency surgery (seven had a Hartmann
procedure and one underwent a colon resection and anastomosis). Transplant patients
and those between 40 and 50 years old proved to be higher risk groups. Three patients
subsequently required elective surgery due to complications. Twenty-four patients had
uneventful recoveries.
Conclusions: the frequency of complicated acute diverticulitis is higher in
immunodeficient patients than that of the general population. Non-surgical treatment
seems to be as safe as in immunocompetent patients. Younger and transplanted
patients were higher risk groups for severe acute diverticulitis that required a more
aggressive management initially.
Keywords: Diverticulitis. Colon. Immunodeficiency.
INTRODUCTION
Diverticular disease is defined as the presence of diverticula or pseudodiverticula in
the colonic wall. In Western countries, it is mostly located in the sigmoid colon
followed by the descending colon. The prevalence is influenced by life habits,
especially high-fat, high-protein and low-fiber diets. This has also been observed in
Asian countries, where customs are becoming more similar to those of Western
countries during the last few decades (1,2). Up to 80% of the population over 70 years
old have diverticula (3,4) and around 25% of these cases will develop at least one
episode of acute diverticulitis (AD) during their lifetime (5).
Patients with conditions that compromise their immunological competence are more
and more common in our daily practice as oncologic patients, chronic kidney disease
(CKD) under dialysis and transplant patients, among others. Several studies describe a
more aggressive evolution of recurrent episodes of AD in immunodeficient patients
(ID) (6,7), with a higher ratio of complicated disease than immunocompetent patients
(IC). They require a more active management of the disease due to the risk of more
aggressive episodes, and elective surgical treatment is indicated after the first episode
of non-complicated AD (8-10).
The goal of this study was to analyze the results of the ID patients treated in our
hospital for AD, and to design the best care strategy for these cases.
MATERIALS AND METHODS
An observational retrospective and descriptive study was performed of ID patients
diagnosed with AD, treated in a tertiary hospital between 2008 and 2016. This study
was approved by the Ethics Committee for Clinical Research in our hospital.
Immunodeficient patients were considered as those with chronic corticoid treatment,
solid organ transplant, hematologic neoplasm, solid organ tumor, chronic kidney
disease under dialysis and those with HIV infection. The patients included in the study
were diagnosed with AD after a clinical and analytical evaluation and an
abdominopelvic computed tomography (CT) scan (11,12). ID patients admitted with a
diagnosis of AD but without available data for a proper analysis were excluded from
the study.
The analyzed data included: age at the time of diagnosis, gender, severity of the
disease (using the Modified Hinchey Classification), cause of immunodeficiency (13),
risk factors for a poor outcome (RFPO) (diabetes mellitus, chronic kidney disease
without dialysis, high blood pressure, smoking habit or dyslipidemia) (14-16),
treatment (medical vs surgical), days of admission, need for surgical treatment during
follow-up, complications during hospital stay and recurrences.
Medical treatment consisted of nil per os (NPO), intravenous fluids, wide spectrum
antibiotics and intravenous analgesia (17). Antibiotic treatment for admitted patients
was performed using intravenous piperacilin/tazobactam 4/0.5 g every six hours,
adjusting the dosage to kidney function when necessary. Tigecyclin + ciprofloxacin
were used in patients with an allergy. This treatment continued for at least five days,
followed by oral amoxicillin/clavulanic acid for another 5-7 days (ciprofloxacin +
metronidazole in allergic patients). Emergency surgical treatment (EST) was performed
in patients with generalized peritonitis (stages III and IV of the Hinchey Classification)
or in the case of septic shock. Surgical procedures included the Hartmann procedure or
resection via primary anastomosis; the decision was made by the responsible surgeon
based on their experience, local contamination and the patient’s status and stability (
18-20). Elective colonic resection was indicated in a few cases after conservative
management of the acute episode, depending on the severity of the first episode and
the appearance of subsequent relapses (21). After discharge, the patients underwent
at least a six-month follow-up, with clinical, analytical and radiologic tests. A
colonoscopy was also performed if this had not been performed during the five years
prior to the first episode of AD.
Statistical analysis
Quantitative variables were expressed as absolute values and qualitative variables
were expressed as absolute values and percentages. Statistical analysis was performed
using the IBM® SPSS® Statistics 20 program. The Student’s t test was used to compare
quantitative variables, assuming a p < 0.05 as statistically significant. Chi-squared test
contingency tables were used to analyze qualitative variables. These tables are useful
when analyzing the relationship between two categorical variables, on which only a
nominal measurement can be made. Thus, it is possible to assess the existence of
statistical significant differences between corrected typified residues (CTR). Residues
are the differences between the observed and the expected frequencies in each box of
the table; they are used to understand the association between the compared
elements. CTR have a normal distribution, with a mean of 0 and a standard deviation
of 1. With these tools and a confidence level of 0.95, statistical significant differences
were found when studying the CTR and these differences were statistically significant
when the residues where outside of the interval (-1.96; 1.96). The positive or negative
result of this residue shows the direct or inverse relationship between the categories.
RESULTS
During the study period, 578 patients were analyzed and all were admitted to our unit
after being diagnosed with AD. Forty-six patients of these were analyzed and six were
excluded due to insufficient data (Fig. 1). Of the 40 analyzed patients (6.9% of the total
patients admitted with AD), 21 were male (52%) and 19 female (48%) with an average
age of 63 years old, ranging from 43 to 85 years old.
Among the different causes for ID, the cohort was divided in 14 patients (35%) who
had previously received a transplant: six had a kidney transplant (43% of all patients
with a transplant), five bi-pulmonary (36%), two liver (14%) and one heart (7%); four
patients (10%) had a chronic kidney disease with dialysis and six (15%) had
hematologic neoplasms; two had acute myeloid leukemia (33%), one prolymphocytic
leukemia (17%), one multiple myeloma, one B lymphoma and one T lymphoma; eight
patients (20%) were actively receiving treatment for a solid tumor; six patients (15%)
were receiving treatment with corticoids, including one with systemic erythematosus
lupus, one with Sjögren’s syndrome, one for psoriasic arthropaty, two cases of
rheumathoid arthritis and one case of polychondritis; and two patients (5%) had an
active HIV infection.
Among the RFPO, ten patients had high blood pressure (25%), five were diabetic
(12.5%), four were active smokers (10%), two were dyslipidemic (5%) and two had
chronic kidney disease without dialysis (CKDWOD, 5%). Ten patients had no risk factors
that could predict a poor outcome of the disease.
According to the results of the CT scan performed for every patient in the Emergency
Ward, 26 cases (65%) developed a non-complicated AD (Hinchey stage Ia); three
patients (7.5%) were classified as stage Ib, four patients (10%) as stage II, two patients
(5%) had a stage III and five cases (12.5%) had a stage IV AD. One of the cases was
diagnosed with a right AD (patient with a kidney transplant, stage Ia) and the rest were
diagnosed with AD of the descending or sigmoid colon. All received treatment in our
hospital except one, who refused to be admitted.
Of all the patients in our study, 32 (80%) initially received conservative treatment and
eight (20%) required EST (six had undergone a previous transplant and two were
oncologic patients). Resection of the affected colonic segment with a colostomy was
performed in all cases, except for one case in which a resection and primary
anastomosis was performed. With regard to the severity of the AD cases that required
EST, one patient (12%) was a stage II, two were stage III (25%) and five patients (63%)
were classified as a stage IV. All patients diagnosed with a stage III or stage IV AD were
treated with EST (Table 1).
Three of the patients who initially received a non-surgical management (NSM) with
antibiotics underwent surgical treatment during the first year of follow-up after the
acute episode. Sigmoidectomy and primary anastomosis were performed in two cases,
one with CKD and a stage II AD with persistent rectorrhagia after the acute episode,
and the other patient underwent chronic corticoid treatment and had persistent
subocclusive episodes after the initial episode was resolved. Another patient with
stage II AD and lymphoma underwent a Hartmann’s procedure.
The average time of admission was 14.5 ± 20 days (4-115), with a median stay of eight
days. Treatment with antibiotics was continued for an average of 17.3 ± 11.1 days (7-
68), with a median of 14.5 days. Twenty-four of the patients (60% of the total) had an
uneventful hospital stay. Among the patients who received NSM, the complications
registered were one respiratory infection (2.5%), five patients (12.5%) relapsed at least
once after being discharged (there were no complicated AD in any of the readmitted
patients) and one patient died (2.5%) (this patient had acute myeloid leukemia and
was admitted with a stage Ia AD). Among those who received EST, complications
included one paralytic ileus (2.5%), one surgical wound infection (2.5%), one intra-
abdominal abscess that required percutaneous drainage (2.5%) and one patient who
required a second surgery (2.5%) due to a dehiscence of the primary anastomosis. In
the second group, one patient (2.5%) who had a pulmonary adenocarcinoma with
brain metastases and underwent a Hartmann's procedure died.
Age and gender
Of the patients who required an EST, 50% were male and 50% were female. The
average age of the patients with EST was 54 years old; the average age in the NSM
group was 65 years old (p = 0.013). When the patients were divided into age groups
(Fig. 2), the group aged 40-50 years was found to have a higher risk of being diagnosed
with stage II (CTR = 3.3) and stage IV (CTR = 2) AD, and a lower tendency of having
stage Ia disease (CTR = -3.3). Furthermore, there were significant differences in this
age group regarding surgical treatment, as EST was more frequently required than
NSM (CTR = 2.4). In addition, eleven out of the 12 cases (91%) older than 70 years of
age were diagnosed of with stage Ia AD (CTR = 2.3).
Cause of immunodeficiency
Patients with hematologic neoplasms, chronic corticoid treatment and CKD had higher
rates of stage Ia AD (100%, 83% and 75%, respectively). Meanwhile, the percentage of
patients with a previous transplant diagnosed with stage Ia non-complicated AD was
43% (CTR = -2.2). These patients had a higher risk of being diagnosed with stage IV AD
(80% of all patients with stage IV AD, CTR = 2.3) (Fig. 3). Regarding the need for an EST,
six patients (75%) had undergone a transplant, which amounted to 43% of the patients
in this group (CTR = 2.7). There were no statistically significant differences with regard
to the relationship between the transplanted organ and the severity of the disease or
the treatment received.
Risk factors for poor outcome of AD
There was a significant association in the CKDWOD group that favored EST (CTR = 2.9).
Both patients with this condition (100%) received an EST.
Recurrences
There were no statistically significant differences in any of the analyzed subgroups (p =
0.4).
DISCUSSION
According to previous studies, ID patients tend to have a more aggressive first episode
of AD, with higher mortality rates compared to IC patients (22). In our study, the
percentage of complicated AD was 35%, which is higher than the rate described in the
scientific literature for IC patients (12% according to the study of Fung et al. and 25%
as reported by Weizman et al.) (23,24). Patients with previous solid organ transplants
have a higher risk of a complicated AD and for the requirement of EST. A correlation
was observed between the younger age groups and a more severe presentation. The
opposite was also observed between more moderate presentations and the older age
groups.
In our experience, NSM with antibiotics, which was the treatment initially used in 80%
of our patients, showed satisfactory results and surgical treatment due to poor
progress was not required in any case. Twenty per cent required EST and Hartmann’s
procedure was the safest technique (25) (88% of the cases with initial EST) in the
context of severe intra-abdominal infection, patients with anastomosis dehiscence risk
factors and, occasionally, in patients with septic shock that required vasoactive drugs
during surgery. There were no cases of laparoscopic drainage and lavage. The
percentage of patients that required surgery was higher than for IC patients who
needed EST (20% vs 7-10%) (26-28). Among the RFPO for AD, the group with CKD
without dialysis had a higher risk of EST, in spite of the small sample size. No other
RFPO were found to be responsible for a higher risk of requiring initial EST, including
DM.
There was a global mortality of 5% during the acute episode for IC patients, which is
higher than in previously reported studies (29). The recurrence rate of 12.5% was
similar to that described in the literature for IC patients (around 10% in the first year)
(30). This percentage seems to be higher in patients with chronic corticoid treatment.
There is still controversy in the literature regarding patient management after an acute
episode has been resolved, with no clear guidelines to determine if elective surgical
treatment is indicated and when (31,32). There is evidence that colonic resection and
primary anastomosis is the preferred procedure when elective surgery is performed
(33,34).
Our study has some limitations. First, this was a retrospective study with a limited
number of patients and therefore, it is more difficult to obtain statistically significant
differences. Thus, further studies with larger sample sizes are needed. Furthermore,
this study was performed following the modified Hinchey classification for AD,
although other more modern classifications could have been used such as those
proposed by Sartelli et al. (35) or Mora et al. (modified Neff classification) (36).
Anyway, we believe our results are equivalent, considering uncomplicated AD
Hinchey’s stage Ia (Sartelli’s “uncomplicated”, modified Neff’s “stage 0”). A higher
proportion of complicated presentations would have required surgical treatment
(Hinchey’s stages Ib-IV, Sartelli’s complicated stages 1-4 and modified Neff’s stages 1-
4).
CONCLUSIONS
There are proportionally more complicated AD in ID patients than in the general
population. However, NST seems to be as safe as in IC patients, with the same
indications for surgical treatment in both groups. Recurrence rates are also similar,
which we believe does not justify performing surgery outside the actual guidelines for
the general population. Younger patients and those with a history of solid organ
transplants are the main groups with a higher risk of developing more severe episodes
that might require a more aggressive management when diagnosed.
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Table 1. Comparison between medical treatment vs emergency surgical treatment
Medical treatment Emergency surgical treatment
17 male
15 female
Sex 4 male
4 female
65 years old Average age 54 years old
11 days Average time of
admission
31 days
Hinchey
26 Ia 0
3 Ib 0
3 II 1
0 III 2
0 IV 5
Cause for immunosuppression
8 Transplant 6
6 Solid tumor 2
6 Corticoid therapy 0
6 Hematologic tumor 0
4 CKD 0
2 HIV 0
Patient’s progress
22 No complications 1
5 Recurrences 0
1 Deaths 1
Fig. 1. Management of the patients in our study.
Fig. 2. Emergency surgical treatment in the different age groups.
Fig. 3. Association between the cause of immunodeficiency and the severity of acute
diverticulitis.