Introduction
Jejunal adenocarcinoma constitutes an infrequent subtype of small bowel adenocarcinoma,
an already rare type of cancer that accounts for 3% of all gastrointestinal malignancies
and that presents with an estimated 11,000 new cases annually in the United States.[1]
[2] The clinical presentation is usually unspecific, with the main reported symptom
being an intermittent, cramping abdominal pain in up to 71.7% of patients, which is
particularly present in distal lesions. Most cases are detected in advanced stages
as a result of a delay in diagnosis due to the uncharacteristic symptomatology and
to the anatomic location of the disease. Management strategies remain controversial,
with a surgical approach being the first line of treatment, and the benefit of chemotherapeutic
agents remains unclear.[3]
The coronavirus disease 2019 (COVID-19) is an infectious disease caused by severe
acute respiratory syndrome coronavirus 2. Throughout the year of 2020, it has become
a global health issue, with an estimated 12,964,809 cases and 570,288 deaths reported
to the World Health Organization (WHO) by mid-July.[4] Although it was initially mainly associated with respiratory symptoms, organic affection
became more noticeable as the amount of cases increased exponentially, with gastrointestinal
and thrombotic manifestations shown to be present in a significant percentage of patients.[5]
The authors present the case of a patient with a perforated jejunal adenocarcinoma,
who was found to be COVID-19-positive, which may have influenced such a rare presentation.
Case Report
A 71-year-old female patient arrived at our unit after 6 days of constipation, accompanied
by abdominal pain. On the 3rd day of her clinical course, she presented with a complete intestinal obstruction.
She had previous history of systemic arterial hypertension, depression, and gastrointestinal
bleeding as well as a 10-year history of intermittent abdominal pain. Her only previous
surgeries included a cesarean section and cervical and lumbar laminectomies.
The patient was checked into our hospital for conservative management of her intestinal
obstruction with intestinal decompression and fluid therapy. X-rays and laboratory
studies were ordered, showing hydro-air levels in the small bowel, free abdominal
fluid, and leukocytosis (33,000 per mm3) with neutrophilia (90.2%). The rest of her
blood tests showed no significant abnormalities.
On physical examination, she presented with diffuse abdominal pain, reduced peristalsis,
positive Blumberg sign and an increase in muscle resistance along the midline, particularly
at the mesogastric level. No respiratory symptoms were present, and she had proper
saturation levels without oxygen support.
The patient underwent an exploratory laparotomy due to suspicion of abdominal sepsis
secondary to a strangulated small bowel loop. The procedure evidenced a purulent,
fibrinous material covering multiple small bowel loops, thus causing them to adhere
to each other, as well as a punctate lesion in the jejunum with low output leakage
of intestinal content. A 51-centimeter jejunal segment was resected and an intestinal
end-to-end hand-sewn anastomosis was performed ([Fig. 1]).
Fig. 1 Trans surgical findings. Fibrinopurulent plaques adhered to small bowel loops (white arrows) after the initial
adhesions had been excised. A punctiform perforation can be observed (black arrow),
with intestinal material leakage.
On her first postoperative day, a central venous catheter was placed, and parenteral
nutrition was initiated. The patient continued with an appropriate postsurgical evolution
until the 3rd postoperative day, when she developed a dry cough and began exhibiting lower oxygen
saturation levels. Chest x-rays were taken on alternate days due to COVID-19 suspicion,
and a reverse transcription-polymerase chain reaction (RT-PCR) test was ordered ([Fig. 2]). She continued to show a favorable evolution, requiring only one to two liters
of oxygen per minute to achieve adequate saturation levels, and initiating liquid
enteral feeding on her 6th postoperative day. The RT-PCR test showed a positive result for COVID-19 infection.
The patient remained in the hospital for 2 more days, and then requested a voluntary
discharge. She continued her recovery and isolation in her home, with telephonic check-ups
confirming a satisfactory evolution 1 month after her surgery.
Fig. 2 Chest x-rays during the second and fourth postsurgical days. Chest x-rays taken during the second (A) and fourth (B) postsurgical days. The initial
x-ray was ordered to check for the correct placement of the central venous catheter.
The second x-ray was ordered to monitor the respiratory symptoms referred by the patient.
Slight peripheral interstitial affection can be observed.
The anatomopathological report showed a 2.5 × 2 × 2-centimeters lesion, identified
as a moderately differentiated adenocarcinoma that ranged from the visceral peritoneum
to the serosa, with negative surgical margins (stage T4N0MX) ([Fig. 3]).
Fig. 3 Anatomopathological examination of the resected jejunum. A stricture can be observed at the site of the tumoral lesion (white arrow), with
the perforation being evident in the antimesenteric border (black arrow).
Discussion
Small bowel cancer is a rare phenomenon, even though the small intestine represents
∼ 75% of the length and over 90% of the surface area of the alimentary tract. In the
United States, there are ∼ 11,110 new cases and 1,700 patient deaths from small bowel
cancer annually, representing ∼ 0.6% of their annual load of new cancer cases, and < 3%
of all gastrointestinal malignancies. It has an approximate incidence of 2.4 per 100,000
inhabitants, an apparent predominance for black males and a median age at diagnosis
of between 55 and 66 years old.[1]
[6] Of these types of tumors, only 13.2 to 31% of cases seem to affect the jejunum,
with the duodenum acting as the main location in most patients (between 48 and 73.6%
of cases).[3]
For a long time, adenocarcinomas were the most common histological type of malignant
neoplasm affecting the small bowel, with up to 45% of cases; nevertheless, over the
last 2 decades, neuroendocrine tumors have increased their incidence, becoming the
main type of small bowel cancer in current times (44% versus 33% of cases). Adenocarcinomas
are mainly found in the duodenum, with neuroendocrine tumors mainly affecting the
ileum, and no particular histological subtype proclivity being currently described
for the jejunum.[7]
The lower incidence associated with this pathology when compared with other gastrointestinal
tract cancers is hypothesized to be secondary to the rapid transit of chymus through
the small intestine, which allows for a shorter exposure to carcinogens and less irritation
of the mucosa. Another theory exposes that a smaller bacterial load, when compared
with the more distal portions of the alimentary tract, leads to less carcinogens forming
from bile acid breakdown by the intestinal microbiota.[8] Another hypothesis includes a larger amount of immunoglobulin-A due to the prevalence
of intestinal lymphoid tissue, and the enormous self-renewing capacity of the intestinal
epithelium, which is able to completely replace itself in 4 to 5 days.[9]
Some modifiable and nonmodifiable risk factors for small intestine adenocarcinoma
have been identified; of these, several have an obvious overlap with risk factors
associated with colorectal cancer. Some of the modifiable risk factors are alcohol,
smoking, refined carbohydrates, red meat, and smoked foods. Nonmodifiable risk factors
include familial adenomatous polyposis, Lynch syndrome, Peutz-Jeghers syndrome, Crohn’s
disease, and both hereditary colorectal nonpolyposis as well as the antecedent of
non-hereditary colorectal cancer.[6]
[10]
Another similarity with colorectal cancer is that most small intestine adenocarcinomas
also seem to arise from adenomas through a sequence of specific genetic changes. Some
of these changes include mutations in the p53 tumor suppressor gene and in the Kirsten
rat sarcoma (KRAS) oncogene, which have been implicated in up to 50% of cases, as
well as mutations in the adenomatous polyposis coli tumor suppressor gene, present
in ∼ 10% of cases.[11]
The presenting clinical picture for these tumors is usually vague, particularly in
its early stages, being either asymptomatic or having a predominance of nonspecific
abdominal discomfort or pain, which may be accompanied by weight loss, anemia, vomiting,
and nausea as the disease progresses, eventually leading to obstruction and/or perforation
of the bowel. Due to this, the diagnosis is usually delayed and takes place during
surgical intervention or at advanced stages of the disease, worsening the prognosis
for the patient.[8]
[10]
Finding and locating tumors in the small intestine, particularly in the jejunum and
in the ileum, is a current challenge. The barium series technique has a sensitivity
of ∼ 60%, while computed tomography (CT) and magnetic resonance imaging (MRI) have
reported different degrees of sensitivity according to tumor location and disease
stage, ranging from 47 to 80%. Standard endoscopic techniques are generally useless
in jejunal adenocarcinoma, due to their limitation in exploring < 40% of the small
bowel. The wireless endoscopic capsule allows for imaging of the entire length of
the small intestine, but it does not allow the user to take biopsies of the imaged
tissues. The accuracy has increased with the use of CT enterography/enteroclysis,
achieving an approximate sensibility of 84.7 to 92.7% in different series. As previously
mentioned, the operating room plays a key role in the diagnosis in up to 85% of cases.[3]
[8]
[10]
[12] After the diagnosis, French guidelines recommend performing a thoraco-abdomino-pelvic
tomographic scan to detect possible distant metastases, as well as both upper and
lower endoscopy to look for other tumors that may suggest a predisposing genetic syndrome.
Carcinoembryonic antigen (CEA) and carbohydrate antigen 19.9 (CA 19.9) should be measured
at baseline, as these tumor markers may have a prognostic value, particularly in advanced
disease.[13]
Due to its rare incidence, an adequate treatment strategy for jejunal adenocarcinoma
remains controversial. Early, localized disease is best treated with a complete surgical
resection (R0) of the primary tumor, as well as of locoregional lymph nodes.[14] As previously mentioned, guidelines for a standardized approach are not currently
available, but the literature recommends a wide resection, removing both the mesentery
and lymphatics up to the superior mesenteric vessels, with a minimum of 12 lymph nodes
obtained for pathologic evaluation. As previously mentioned, this recommendations
stem mainly from current knowledge of the appropriate management of colorectal cancer.[8]
[12] Surgical intervention is generally needed even in advanced stages, due to the high
risk of obstruction or bleeding, which can usually be the first manifestation of an
otherwise clinically silent or nonspecific presentation.[1]
[9]
The role of chemotherapy in the management of both localized and disseminated disease
has been a matter of debate in recent years. No standard chemotherapy regimen exists
to date, but adjuvant treatment for metastatic adenocarcinoma is usually carried out
with 5-Fluorouracil as the sole agent, this choice being also extrapolated from the
current management options for colon adenocarcinoma.[12] Capecitabine and oxaliplatin (CAPOX), folinic acid/5-FU/oxaliplatin (FOLFOX), and
folinic acid/5-FU/irinotecan (FOLFIRI) are promising therapeutic options, but more
randomized clinical trials are needed to evaluate the efficacy of these treatment
methods, as well as that of chemotherapy itself for this rare type of malignancy.[10]
The currently accepted staging system for small bowel adenocarcinomas is the tumor,
node, metastasis (TNM) system of the combined American Joint Committee on Cancer/Union
for International Cancer Control. Its most recent edition revised the definitions
of the T stage, with T1, T2, T3, and T4 representing a tumor that invades up to the
submucosa (T1), the muscularis propia (T2), the subserosa or mesentery (T3), and that
perforates the visceral peritoneum or invades neighboring structures (T4), respectively.
The definition of node disease was revised as well, with N1 disease including up to
two positive nodes and N2 more than two. Stage I includes T1 and T2 tumors without
positive nodes or metastatic disease, stage II involves T3 and T4 tumors without nodes
or metastases. Positive nodes are defined as stage III, with stage IV being reserved
for patients with metastatic disease.[15] Most reported cases are diagnosed at advanced stages, with up to 40% of patients
presenting with positive nodes and 35 to 50% of patients presenting with metastatic
disease.[1]
[9]
Only 31.9% of small intestine tumors are detected in localized stages of invasion.
Survival rates are generally lower for jejunal disease when compared to its duodenal
counterpart due to its location aiding in the delay of diagnosis in some of the reported
series, while others argue that a jejunal location actually adds to a more favorable
prognosis.[16]
[17] Five-year survival for adenocarcinomas is dependent on disease stage at diagnosis;
no specific values are currently available for jejunal adenocarcinoma as a single
entity, but small intestine adenocarcinomas are associated with a 85.2% 5-year relative
survival for localized disease, 76.2% for regional disease, 42.2% for distant disease,
and 51.5% for patients with an undefined stage.[16]
Recurrence is high, presenting in between 40 and 60% of cases, even after surgery
with complete resection. The relapse pattern observed for this type of adenocarcinomas
seems to be predominantly systemic. Poor prognostic factors described by Ahmed et
al. include the male gender, age > 55 years old, black race, higher stage at diagnosis,
intestinal locations other than the jejunum, poorly differentiated tumors or positive
margins after resection.[13] Positive prognostic factors include an earlier age at diagnosis, lymphadenectomy
with > 12 local nodes, and perhaps even marriage. It is worth mentioning that the
study by Xie et al. did not find significant differences in prognosis regarding gender,
race, or intestinal location of the tumor.[6]
Coronavirus disease 2019 is an infectious disease caused by the severe acute respiratory
syndrome coronavirus 2, which has managed to become a global health issue, with an
estimated 12,964,809 cases and 570,288 deaths reported to the WHO by mid-July.[4] While initially thought to only affect the airways, symptoms of organic affection
became apparent as the number of cases increased. This phenomenon may be explained
by the fact that SARS-CoV-2 binds to its target cells through angiotensin-converting
enzyme 2 receptors, which are expressed by epithelial cells in the lungs, the gastrointestinal
tract and blood vessels.[18] Gastrointestinal symptoms may be the first manifestations of COVID-19, preceding
any respiratory affection; their frequency varies amongst recent studies, from 3.0
to 39.6% of cases.[19] The most common manifestation is diarrhea, which appeared as the initial symptom
of illness in up to 19.4% of patients.[18] Controversy remains regarding whether gastrointestinal manifestations may impact
prognosis for the better or the worse, and more studies need to be carried out. Nonetheless,
gastrointestinal manifestations have led to an increase in COVID-19 diagnosis in previously
unsuspected patients, since the virus may be found in stool samples long after it
stops being present in the pharynx. Pathological examination of the stomach and bowels
of COVID-19 patients have demonstrated different degrees of degeneration, necrosis,
and detachment of the mucosal epithelium.[5]
[18]
[19]
The mortality amongst postsurgical patients who are found to be COVID-19-positive
ranges from 19.5 to 38.5% of cases, with complications being 13 times more likely
amongst these patients. The most commonly referred complications include pulmonary
(pneumonia and acute respiratory failure, p < 0.001), hemorrhagic (need for blood transfusion, p = 0.79), and thrombotic manifestations (peripheral and arterial thrombosis, p = 0.004).[20]
