Добавил:
Sekretar
kiopkiopkiop18@yandex.ru
t.me/Prokururor I Вовсе не секретарь, но почту проверяю
Опубликованный материал нарушает ваши авторские права? Сообщите нам.
Вуз:
Предмет:
Файл:Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_917_Библиотеки_им_академика_М_И_Перельмана.pdf
12 Unexpected Findings at Appendectomy
171
appendectomy by utilizing a stapler, endo-loops, or suture ligating the stump. Care
should be taken to avoid narrowing the small bowel lumen from which the diverticulum arose. In general, diverticulectomy can safely be performed with a laparoscopic approach. Routine exteriorization of the bowel for direct palpation is an
option that may avoid laparotomy but is not, in general, required [3]. In some
instances, small bowel resection may be necessary either due to the amount of
inammation and involvement of the associated small bowel or because of anatomic
concerns. Diverticulectomy alone is sufcient for clearing all heterotopic tissue that
may be present while also decreasing postoperative complications compared to segmental small bowel resection [4].
When diverticulectomy for inamed Meckel’s is performed, it may still be reasonable to perform a prophylactic appendectomy as it adds minimal morbidity to
the procedure and has the potential to prevent later pathology. There is virtually no
literature to guide this decision. However, whether to perform a prophylactic diverticulectomy in the setting of appendicitis is discussed in the literature. The rationale
includes a small risk of becoming symptomatic and a very low risk of malignancy.
The overall risk of symptoms from a Meckel’s ranges from 4 to 16%, and an estimated morbidity from the procedure ranges from 0 to 6% [1]. It is impossible to
make a strong management recommendation in the absence of evidence. However,
a reasonable approach may be to remove a Meckel’s with features that may represent a higher risk of becoming symptomatic, namely, those in male patients, those
under age 50years, diverticular length greater than 2cm, and those with heterotopic
tissue felt on palpation [5].
Cecal Diverticulitis
Cecal diverticulitis is a relatively rare problem that accounts for approximately 3%
of all diverticulitis. Compared to appendicitis, it is also very rare (0.4–2.1% compared to ~7%). Given the association between the cecum and the appendix, diagnostic uncertainty based on clinical signs and symptoms as well as imaging ndings is
understandable. Up to 70% of patients diagnosed with this problem in the operating
room had a preoperative diagnosis of appendicitis on imaging [6]. The classic presentation is a patient with right lower quadrant pain, tenderness on examination, and
fever. Leukocytosis is common as is an inammatory reaction in the right lower
quadrant on imaging. Authors that attempt to differentiate suggest that the course of
cecal diverticulitis may be more indolent than appendicitis, and the pain does not
begin in the epigastrium [7]. Unlike left-sided diverticuli, cecal diverticuli tend to be
true diverticuli consisting of all layers of the bowel wall though traditional false
diverticuli may also occur. They are seen more frequently in men of Asian descent,
and the true diverticuli are considered a congenital phenomenon.
When it is diagnosed preoperatively, cecal diverticulitis may be managed nonoperatively in the majority of cases similarly to left-sided diverticulitis. Surgical treatment of this entity includes right hemicolectomy, ileocecal resection, or simple
diverticulectomy or inversion of the diverticulum [6, 8]. When diagnosed
172
E. Steinhagen and G. M. Nash
intraoperatively, recommendations are based on a grading system: Grade I describes a
protruding, easily identiable cecal diverticuli, grade II is an inamed cecal mass,
grade III is a localized abscess or stula, and grade IV represents a free perforation
[9]. In cases of grade I cecal diverticulitis, simple diverticulectomy and appendectomy
are recommended. For grades II–IV, the suggested treatment is ileocecectomy or right
hemicolectomy [10]. In practice, cecal diverticulitis may be impossible to distinguish
from a mass intraoperatively, and in those cases, an oncologic right hemicolectomy is
the prudent choice. In some clinical scenarios, it may be the most prudent option to
simply terminate the procedure and treat the diverticulitis with antibiotics until the
diverticulum can be denitively addressed in the elective setting.
Sigmoid Diverticulitis
A redundant sigmoid may lie in the midline, in the pelvis, or even in the right lower
quadrant. Inammation of the sigmoid colon may appear similar to appendicitis on
clinical history, physical exam, and laboratory evaluations. On CT scan, inammatory changes may appear in the right lower quadrant, and the appendix may also
appear thickened or secondarily inamed. In this situation, the appendiceal inammation is due to proximity rather than inherent pathology. There is often a serositis
on direct observation. In this situation, appendectomy is not indicated, but consideration for removal to prevent future complications can be considered. Treatment of
complicated sigmoid diverticulitis is discussed in Chap. 28.
Epiploic Appendagitis
Inammation of an epiploic appendage may partially mimic appendicitis clinically
with acute onset right lower quadrant pain that is progressive. However, patients are
usually afebrile and without leukocytosis, nausea, or vomiting. The right colon is
the third most common site for appendagitis, following the sigmoid and descending
colon. The etiology of epiploic appendagitis is torsion of the appendage causing
venous occlusion that can result in ischemia, thrombosis, or infarction. It is benign
and self-limited, requiring no specic treatment. Patients typically improve with
oral anti-inammatory medications over 4–7 days. Rarely, an inamed epiploic
appendage will become infected and develop into an abscess, cause a bowel obstruction, or act as a lead point for intussusception.
On imaging, it should be feasible to differentiate this entity from appendicitis;
the patient should have a normal appendix, and on CT scan there is inammatory
inltration of the fat around the offending epiploic appendage. There is a characteristic central lucency [11]. With ultrasound, an inamed epiploic appendage will
appear as an oval, non-compressible mass with no central ow on Doppler when the
probe is placed over the point of maximal tenderness [12]. In cases of severe inammation, it could appear that the inammation is surrounding the appendix and can
lead to diagnostic confusion.
12 Unexpected Findings at Appendectomy
173
Given the widespread use of imaging, this is a diagnosis that is typically not
made in the operating room at this point. However, if imaging is not utilized or not
available and it is found in the context of a normal appendix, the appendix should
not be removed. There is no evidence whether it is necessary to remove the offending epiploic appendage once identied.
Crohn’s Disease
On laparoscopy, features of Crohn’s disease may be visualized including creeping
fat, thickened mesentery, inamed bowel, abscess, and strictures. When these are
found, it must rst be determined if there is a perforation. If there is a bowel perforation, an appropriate resection should be performed with or without a stoma depending on patient and surgeon factors. When there is no perforation and particularly
when the diagnosis has not previously been made, no resection should be performed.
The remainder of the bowel should be carefully examined to determine the extent of
the disease. Areas of inammation, mesenteric thickening, and creeping fat should
be noted. Strictures are also a common nding and may or may not be associated
with proximal bowel dilation depending on the severity. The position and distance
between abnormal segments should be documented. Following the operation, a
careful history should be taken with the new diagnosis in mind, and patients should
be seen by a gastroenterologist to direct further workup and treatment.
While certainly it is possible for a patient with a new diagnosis of Crohn’s disease to have appendicitis as well, it is somewhat rare to have two simultaneous
problems. The commonly taught adage to remove the appendix if the base and
cecum are normal and to leave it if they are not is a reasonable approach despite no
specic evidence in either direction. The goal of this approach is to reduce diagnostic confusion in the future between a Crohn’s are and appendicitis. The appendix,
however, should not be removed if the cecal inammation involves the base of the
appendix given the risk of postoperative stump leak. Given the availability of imaging, this is less important, but since the morbidity of the appendectomy is minimal,
it is still appropriate.
Gynecologic Pathology
Many gynecologic and obstetric conditions may mimic the clinical signs and symptoms of appendicitis. Even on imaging, some entities may demonstrate right lower
quadrant inammatory changes. Therefore, if the appendix is normal on laparoscopy, the pelvis should be carefully evaluated. Diagnoses such as tubo-ovarian
abscess, pelvic inammatory disease, ovarian torsion, ruptured ectopic pregnancy,
ovarian cyst, hydrosalpinx, or even severely symptomatic endometriosis may mimic
appendicitis.
Whenever possible, the assistance of a gynecologist should be utilized in dealing
with these entities. If that is not feasible, any infection or sepsis should be drained;
174
E. Steinhagen and G. M. Nash
nonviable tissue should be removed with the goal of preserving both ovaries and
fallopian tubes whenever possible.
Pelvic inammatory disease (PID) is a usually polymicrobial infection of the
upper part of the female reproductive system (uterus, fallopian tubes, ovaries).
Symptoms include pain, fever, and vaginal discharge. The pain may be pelvic or
lower abdominal. On exam, cervical motion tenderness and adnexal tenderness may
be noted. There is typically mucopurulent cervicitis. The most frequently implicated organisms are Neisseria gonorrhoeae or Chlamydia trachomatis, but polymicrobial infection with a number of other bacteria is also common [13, 14]. The
diagnosis is often made clinically and based on physical exam and therefore requires
a high degree of suspicion. Tubo-ovarian abscess is a late complication of pelvic
inammatory disease. If the abscess ruptures, it can result in peritonitis and sepsis.
The abscess is often visible on ultrasound or cross-sectional imaging such as CT
scan but on the right side could appear similar to appendicitis if the inammation is
extensive and the appendix lays in the pelvis. On laparoscopy, there may be a conned abscess. In addition, inammatory changes consistent with Fitz-Hugh-Curtis
perihepatitis may be seen. PID is usually treated with antibiotics alone. When tuboovarian abscess requires surgery, operative therapy may include either drainage or
salpingo-oophorectomy.
Ovarian torsion occurs when the ovary rotates on its vascular pedicle and the
vessels are occluded. This leads to unilateral pain and is often associated with nausea and vomiting. It may be more common in the setting of ovarian masses or cysts.
When suspected, the diagnosis can often be made with Doppler sonography that
demonstrates a loss of blood ow to the affected ovary. When diagnosed preoperatively on imaging, a gynecologist should be consulted. When found incidentally in
the operating room, the treatment for ovarian torsion is surgical detorsion and pexy;
if the ovary is necrotic or nonviable, it should be removed.
Ectopic pregnancy occurs when the embryo implants outside of the uterine cavity. The fallopian tube is the most common site of implantation [15]. Common
symptoms are abdominal/pelvic pain associated with vaginal bleeding in the setting
of a positive pregnancy test. Nauseas and vomiting are less frequent. Most women
present between 4 and 8weeks after the last menstrual period [16]. On ultrasound,
there is no evidence of intrauterine pregnancy. When diagnosed early, medical management with methotrexate and serial laboratory monitoring is often feasible.
Ruptured ectopic pregnancy, however, is a surgical emergency because of the risks
for severe bleeding and hemorrhagic shock. When possible, consultation to gynecology should be made prior to going to the operating room. In the operating room,
the affected fallopian tube is incised, and the contents are removed; alternatively,
salpingectomy may be required. The ovary should be preserved when possible.
Appendiceal Mass
The other occasional unexpected intraoperative nding during appendectomy is an
appendiceal mass or mucocele (dilated mucin-lled appendix), which occurs in less
than 2% of appendectomy specimens [17]. Recent database studies suggest that the
12 Unexpected Findings at Appendectomy
Box 12.2 Appendiceal Neoplasms
175
Epithelial neoplasms
• Adenocarcinoma (mucinous and non-mucinous)
• Low-grade mucinous appendiceal neoplasm (LMAN)
• Signet ring carcinoma
• Goblet cell carcinoma
1
Non-epithelial neoplasms
• Carcinoid tumor
• Lymphoma
• Leiomyoma
• Leiomyosarcoma
incidence of appendiceal tumors may be increasing from 0.63 to 0.97 per 100,000
persons; however, this may be a consequence of more selective appendectomy or
more thorough pathologic evaluation [18, 19]. While many appendiceal neoplasms
are not identied until the pathologist is examining the specimen, when noted in the
operating room, an appendiceal mass requires thoughtful treatment about how to
proceed.
Appendiceal neoplasms may be broadly classied into epithelial and nonepithelial tumors (Box 12.2). Epithelial tumors include mucinous or non-mucinous
adenocarcinoma, low-grade appendiceal mucinous neoplasm, and signet ring carcinomas. Non-epithelial neoplasms include carcinoid tumors, lymphomas, leiomyomas, and leiomyosarcomas. Goblet cell carcinoids are mixed epithelial and
non-epithelial neoplasms but with an adenocarcinoma phenotype. An additional
feature common to epithelial tumors is associated mucin in the peritoneal cavity.
When there is large-volume mucinous ascites, the clinical syndrome is referred to as
pseudomyxoma peritonei; however, this is rarely an unexpected nding.
Nevertheless, smaller areas of mucinous peritoneal implants, which were not identied on imaging, may be seen during surgery and should be evaluated for if there is
a suspicion for an appendiceal neoplasm at exploration.
It is not always feasible to conrm malignancy at the time of surgery, even if
there is mucin present on the serosa of the appendix or on the nearby or remote
peritoneal surfaces. However, it is important to note whether the mass is at the tip of
the appendix or at the base. The remainder of the peritoneal cavity must also be
carefully surveyed to look for mucin or nodular lesions on the peritoneum, mesentery, or other organs.
1
Mixed epithelial and non-epithelial neoplasms but with an adenocarcinoma phenotype.
176
Fig. 12.1 Peritoneal
implant
E. Steinhagen and G. M. Nash
In general, the surgical approach to an unexpected appendiceal mass during a
laparoscopy for presumed appendicitis should be as follows:
• Carefully inspect the pelvis, ovaries, both hemidiaphragms, liver, omentum,
mesentery, and bowel serosa at the beginning of the operation accompanied by
photo documentation and extensive sampling of suspicious or indeterminate
peritoneal lesions in four quadrants (Fig.12.1). These should be sent for perma-
nent rather than frozen section as it may not be truly representative due to tumor
heterogeneity. If it is not the practice of your hospital to routinely section the
entire appendix, ensure that this is requested for this patient.
• When peritoneal disease is seen, avoid laparoscopic ports or incisions in the
rectus muscle and keep in the midline if possible as incisional metastases may
occur and are more difcult to manage off the midline.
• The goal of surgery in this setting is to address urgent symptoms/conditions
related to the mass such as appendicitis or bowel obstruction. However, it is pru-
dent to limit surgery to appendectomy and biopsy of peritoneal disease whenever
possible as right colectomy, hysterectomy, or any organ resection may be unnec-
essary, in the setting of a benign mass, or may complicate future management, in
the setting of malignancy [20].
• There is no absolute contraindication to laparoscopy for appendiceal tumors, and
surgical approach should depend on surgeon experience. The tumor should not
be directly grasped to avoid rupture.
• If the patient has not had completed cross-sectional imaging of abdomen and
pelvis prior to surgery, this should be performed if malignancy is identied on
nal pathology. If preoperative ultrasound is suspicious for an appendiceal mass
in the setting of appendicitis, obtaining cross-sectional imaging preoperatively
may assist in decision-making.
12 Unexpected Findings at Appendectomy
Fig. 12.2 Ruptured
low-grade appendiceal
mucinous neoplasm
(LAMN) with peritoneal
mucin
177
Appendiceal adenocarcinoma is a rare cancer with an estimated incidence of 2.6
per one million per year. These tumors are thought to arise from adenomas and are
most commonly mucinous or intestinal type though some harbor a variety of elements. Mechanical rupture of these tumors does not necessarily lead to peritoneal
metastases, and many will have established metastases prior to symptoms of rupture
[21]. The typical pattern of metastasis is to the parietal and visceral peritoneum
rather than along lymphatics, particularly in low-grade primary tumors [22].
However, the intestinal type is thought to progress along the adenoma to carcinoma
sequence and is comparable to colon cancer, yet solid organ metastases are not common as initial site of metastatic disease [21]. Signet ring cell appendiceal adenocarcinoma is a particularly rare subset of mucinous adenocarcinoma. It is rarely
conned at diagnosis and may inltrate below mucosal surfaces. Unfortunately, the
majority of appendiceal cancers may have spread at the time of diagnosis, though
estimates vary greatly by series [17, 23–25]. Mucin may be found throughout the
abdomen and easily visualized in more advanced cases (Fig.12.2); in other situations, there may be small mucin deposits which are subtle and are only seen after
meticulous inspection. For the low-grade lesions, right hemicolectomy typically
does not play a role in staging as lymph node positivity rate may be as low as 5%;
however, in higher-grade primary tumors, lymph nodes have been shown to be predictive of recurrence [22, 23]. As a result, given the uncertain nature of the disease
at time of index surgery and the more extensive treatment that will likely be required
particularly for many appendiceal cancers, right colectomy is best reserved for an
elective operation after appropriate pathology review and patient counseling.
A low-grade appendiceal mucinous neoplasm (LAMN) is a well-differentiated
tumor which grows slowly and tends to have a brotic, sometimes calcied appendiceal wall and is commonly described as a mucocele by radiologist; however, it is
important to note that mucocele is not a pathologic diagnosis (Fig.12.3). LAMNs
may extrude mucin on the nearby serosal surfaces. When a mucinous lesion is suspected, it is important to avoid directly grasping it as it may rupture and increase the
risk of subsequent recurrence within the peritoneal cavity if the mucin harbors neoplastic epithelium.
178
Fig. 12.3 Intact
low-grade appendiceal
mucinous neoplasm
(LAMN) opened for
pathologic examination
E. Steinhagen and G. M. Nash
When LAMNs are conned to the mucosa of the appendix, as proven by complete sectioning of the appendix and careful examination of the peritoneum by
imaging and during surgery, appendectomy with negative margins is curative, and
no specic follow-up is necessary. However, when there is intramural or extraappendiceal mucin present, further follow-up and, possibly, treatment are necessary.
When the mucin is acellular and seen within the wall of the appendix or conned to
the serosa of the appendix or periappendicular tissue, the entity is referred to as
LAMN of uncertain malignant potential (UMP) and is associated with a 5% risk of
subsequent recurrence. However, cellular mucin carries a higher risk of recurrence,
and consideration of subsequent treatment at a specialty center should be given [26,
27]. Simple appendectomy is typically sufcient for diagnostic and therapeutic pur-
pose for LAMN and LAMN/UMP.However, partial cecectomy or ileocecectomy is
occasionally necessary to clear the margin for neoplastic tissue. Formal right colectomy is unnecessary as the initial treatment as most mucinous neoplasms seen on
preoperative imaging do not harbor invasive cancer and are not at risk for lymph
node metastases. Baseline serum tumor markers including CEA, CA-125, and
CA19-9 may be useful for monitoring LAMN/UMP and can be drawn pre- and
postoperatively if a LAMN is suspected. There are no formal guidelines for surveillance of LAMN/UMP; however, imaging and serum markers more frequently than
once a year appear unnecessary given the low risk of recurrence and indolent course
for those who recur.
While denitive management of appendiceal carcinoma may ultimately include
right hemicolectomy and/or intraperitoneal chemotherapy (IPC), the most appropriate course of action upon recognizing this unexpected nding is to remove the
appendix, biopsy suspected metastatic disease, and close without additional organ
resection. Neither the surgeon nor the patient may be prepared for a more signicant
undertaking. If the next step in a patient’s treatment involves systemic chemotherapy or cytoreductive surgery, a more extensive operation may delay initiation of that
treatment. A right hemicolectomy alone does not provide any survival advantage
over appendectomy alone in stage IV disease nor does it particularly help with
12 Unexpected Findings at Appendectomy
Fig. 12.4 Neoendocrine
tumor (NET) on CT
179
staging in many cases [22, 28]. Furthermore, studies have suggested improved efcacy of IPC with a lower prior surgical score which is calculated based on extent of
previous surgery [29]. Therefore, while it is certainly appropriate to remove the
appendix and perform any other necessary biopsies, a more extensive right hemicolectomy is not warranted in most cases.
Carcinoid tumors, also known as neuroendocrine tumors (NET), of the appendix
have an incidence of 0.15 per 100,000 per year (Fig.12.4) [30, 31]. Approximately
75% occur at the tip of the appendix, 15% in the mid-appendix, and 10% at the base.
Size is one of the critical features of staging for carcinoid tumor; fortunately the
majority are less than 1cm at the time of removal, and only 6% are more than 2cm
[32]. With increasing size, penetration of the appendiceal wall and inltration of the
mesoappendix become more likely. However, size is the most signicant predictor of
prognosis, rather than depth of invasion and lymphatic or perineural invasion. In a
carcinoid <1cm in size, lymph node metastases are rare. In tumors over 2cm, the risk
is approximately 20–30% [33]. Distant metastasis for appendiceal carcinoid is rare at
diagnosis. In general, denitive management of non-metastatic appendiceal carcinoids >2cm, those at the base or with positive margins, or those with adverse histologic features or radiologic evidence or locoregional nodal involvement is right
hemicolectomy, though it is important to note that there are no data to address the
benet of this intervention. Nevertheless, pathologic diagnosis must be made; therefore, appendectomy alone is the rst treatment. Once the diagnosis of appendiceal
NET is made, workup including cross-sectional imaging should be performed.
Octreotide scans and serum markers are unnecessary in the absence of symptoms
consistent with metastatic disease, such as carcinoid syndrome. Staging right colectomy is recommended for tumors greater than 2 cm, and no specic follow-up is
necessary for tumors less than 1.5cm. The management of tumors between 1.5 and
2cm after appendectomy remains controversial. The two largest series of appendiceal
NET report no cases of lymph node metastases in patients with <2cm tumors; however, there are only seven patients reported in case series with lymph node metastases
and tumors <2cm. [34–36] Though small bowel NET is associated with synchronous
additional small bowel lesions, this has not been described in appendiceal NET.
180
E. Steinhagen and G. M. Nash
Conclusions
When intraoperative ndings do not match up to preoperative expectations, a
thoughtful approach is required. The remainder of the abdomen must be examined
if the appendix is normal to identify the etiology of the patients’ symptoms. An
abnormality that likely explains the clinical picture should be appropriately
addressed; others such as epiploic appendicitis and some presentations of Crohn’s
disease do not require any intervention. The impulse to intervene because the operation is underway should be tempered by careful judgement about what might have
been done differently if the correct diagnosis was apparent and the potential for
harm. When a mass or mucin is encountered, the operation should be limited to
appendectomy and biopsies to denitively stage the patient whenever possible.
Patients will benet from denitive pathology and preoperative planning if any further intervention is considered.
References
1. Sagar J, Kumar V, Shah DK. Meckel’s diverticulum: a systematic review. J R Soc Med.
2006;99(10):501–5.
2. Levack MM, Fiedler AG, Kaafarani H, King DR.Perforation of a mesenteric Meckel’s diver-
ticulum. J Surg Case Rep. 2018;2018(6):rjy126.
3. Ezekian B, Leraas HJ, Englum BR, Gilmore BF, Reed C, Fitzgerald TN, etal. Outcomes of
laparoscopic resection of Meckel’s diverticulum are equivalent to open laparotomy. J Pediatr
Surg. 2019;54(3):507–10.
4. Robinson JR, Correa H, Brinkman AS, Lovvorn HN. Optimizing surgical resection of the
bleeding Meckel diverticulum in children. J Pediatr Surg. 2017;52(10):1610–5.
5. Park JJ, Wolff BG, Tollefson MK, Walsh EE, Larson DR.Meckel diverticulum: the Mayo
Clinic experience with 1476 patients (1950-2002). Ann Surg. 2005;241(3):529–33.
6. Fang J-F, Chen R-J, Lin B-C, Hsu Y-B, Kao J-L, Chen M-F.Aggressive resection is indicated
for cecal diverticulitis. Am J Surg. 2003;185(2):135–40.
7. Koshy RM, Abusabeib A, Al-Mudares S, Khairat M, Toro A, Di Carlo I.Intraoperative diag-
nosis of solitary cecal diverticulum not requiring surgery: is appendectomy indicated? World J
Emerg Surg. 2016;11(1):1.
8. Connolly D, McGookin R, Gidwani A, Brown M.Inamed solitary caecal diverticulum– it is
not appendicitis, what should I do? Ann R Coll Surg Engl. 2006;88(7):672–4.
9. Cecal diverticulitis. In: Welch JP, Cohen JL, Sardella WV, Vignati PV, editors. Diverticular
disease, management of the difcult surgical case. Baltimore: Williams and Watkins;
1998:428–441.
10. Hall J, Hammerich K, Roberts P.New paradigms in the management of diverticular disease.
Curr Probl Surg. 2010;47(9):680–735.
11. Singh AK, Gervais DA, Hahn PF, Sagar P, Mueller PR, Novelline RA. Acute epiploic
appendagitis and its mimics. Radiographics. 2005;25(6):1521–34.
12. Mollà E, Ripollés T, Martínez MJ, Morote V, Roselló-Sastre E.Primary epiploic appendagitis:
US and CT ndings. Eur Radiol. 1998;8(3):435–8.
13. Mitchell C, Prabhu M.Pelvic inammatory Disease. Infect Dis Clin N Am. 2013;27(4):793–809.
14. Sharma H, Tal R, Clark N, Segars J. Microbiota and pelvic inammatory disease. Semin
Reprod Med. 2014;32(01):043–9.
15. Mausner Geffen E, Slywotzky C, Bennett G.Pitfalls and tips in the diagnosis of ectopic preg-
nancy. Abdom Radiol. 2017;42(5):1524–42.