KEY WORDS
Laryngectomy - pharyngeal reconstruction - pharyngocutaneous fistula
INTRODUCTION
Advanced laryngeal and hypopharyngeal cancer often require a TL as part of their multimodal
treatment. In certain instances, a part or whole of the pharynx will need to be resected
to ensure oncological margins. In the era of organ preservation chemoradiotherapy,
the surgeon is often faced with salvage resections with its attendant complications.
Pharyngeal reconstruction is required to enable oral feeding and voice rehabilitation
with a tracheo-oesophageal puncture. This study was performed to determine the outcomes
following pharyngeal reconstruction in TL and to determine the predictors of pharyngocutaneous
fistula (PCF) and swallowing dysfunction.
MATERIALS AND METHODS
From a prospectively maintained database of patients treated at Amrita Institute of
Medical Sciences, Kochi, we identified 57 patients who underwent pharyngeal reconstruction
following TL between 2003 and 2010. Information extracted from this database included
patient demographics, prior treatment history, tumour details, surgical details, post-operative
course of events, details of radiotherapy and follow-up details. The outcomes regarding
speech, swallowing, fistula and stricture were noted.
Statistical analysis
Descriptive variables were summarised. Univariate analysis was performed using Pearson
bivariate correlation coefficient, to assess determinants of fistula and dysphagia.
Multivariate analysis was performed with logistic regression analysis. P < 0.05 was considered statistically significant. Statistical analysis was done using
SPSS version 22 (IBM Corp, Armonk, NY).
RESULTS
Patient characteristics
A total of 57 (M = 44 and F = 13) patients underwent pharyngeal reconstruction following
TL. The median age of patients was 55 years (range 42–72 years). The median follow-up
was 22 months (range 6–60 months). Patient and treatment characteristics are shown
in [Table 1].
Table 1
Patient and treatment characteristics
|
Characteristics
|
Number of patients (%)
|
|
PMMC: Pectoralis major myocutaneous flap, ALT: Anterolateral thigh-free flap
|
|
Age (years)
|
|
|
≥60
|
22 (39)
|
|
<60
|
35 (61)
|
|
Sex
|
|
|
Male
|
44 (77)
|
|
Female
|
13 (23)
|
|
Site involved
|
|
|
Hypopharynx
|
29 (51)
|
|
Larynx
|
22 (39)
|
|
Oropharynx
|
5 (9)
|
|
Thyroid
|
1 (1)
|
|
Prior treatment
|
|
|
None
|
26 (46)
|
|
Chemoradiotherapy
|
10 (18)
|
|
Radiotherapy
|
9 (16)
|
|
Surgery + chemoradiotherapy
|
7 (12)
|
|
Surgery + radiotherapy
|
4 (7)
|
|
Induction chemotherapy
|
1 (1)
|
|
Defect
|
|
|
Circumferential
|
31 (54)
|
|
Partial
|
26 (46)
|
|
Flap used
|
|
|
PMMC patch
|
24 (42)
|
|
PMMC tubed
|
5 (9)
|
|
ALT patch
|
6 (10)
|
|
ALT tubed
|
2 (4)
|
|
Gastric pull-up
|
13 (23)
|
|
Jejunal-free flap
|
7 (12)
|
Tumour and prior treatment characteristics
The sites involved by tumour included hypopharynx in 29 patients, larynx in 22 patients,
oropharynx (posterior pharyngeal wall extending to the larynx) in 5 patients and thyroid
gland with extensive laryngeal involvement in 1 patient.
Thirty-one patients (54%) had prior treatment; chemoradiotherapy in 10 patients, radiotherapy
in 9 patients, surgery with adjuvant chemoradiotherapy in 7 patients, surgery with
adjuvant radiotherapy in 4 patients and induction chemotherapy in 1 patient. Those
who received previous radiotherapy or chemoradiotherapy had recurrent or residual
disease after treatment requiring surgery, while those who previously underwent TL
with primary closure and developed pharyngeal recurrences.
Surgical technique employed
All patients underwent a standard technique of closure. In patients in whom a cutaneous
flap was used, an interrupted suturing in two layers with 3-0 vicryl was employed.
The first layer of closure was a dermis-to-dermis approximation and the second layer
was a muscle-to-muscle or fascia-to-fascia approximation of the flap. Proximally,
the flap was spatulated, while distally a lock-and-key figure was used for approximation.
In the cases of visceral flaps, the flap was sutured to the end of the defect with
interrupted prolene sutures.
Nature of defect and choice of flap
Following tumour resection, 31 patients (54%) had circumferential pharyngeal defects
and 26 patients (46%) had partial pharyngeal defects. The flaps used in our series
included pectoralis major myocutaneous (PMMC) patch in 24 patients (42%), tubed PMMC
flap in 5 patients (9%) [[Figures 1]
[2]
[3]], tubed anterolateral thigh (ALT)-free flap in 6 patients (11%) and ALT-free flap
patch in 2 patients (5%), gastric pull-up in 12 patients (21%) and free jejunal flap
in 7 patients (12%) [[Figure 1]].
Figure 1: Pharyngeal reconstruction performed with jejunal-free flap
Figure 2: Pharyngeal reconstruction with a pectoralis major myocutaneous flap being tubed
Figure 3: Our institutional algorithm for laryngopharyngeal reconstruction. PMMC: Pectoralis
major myocutaneous flap, RFFF: Radial forearm-free flap, ALT: Anterolateral thigh
flap
Our protocol for pharyngeal reconstruction is shown in [Figure 3]. For patients having a patch defect, the PMMC flap is preferred in a vessel-depleted
neck or in a salvage setting post-radiotherapy, where the vascularised muscle bulk
has been shown to prevent PCF.[[1]] Otherwise, a radial forearm-free flap is used as it is thin and pliable, allowing
deglutition. When mucosal and skin defects are present, the PMMC is used for similar
indications as for patch defects, with the external surface of the flap covered with
a split skin graft. When free flap reconstructions are suitable, depending on the
patient's habitus, a radial forearm free flap or anterolateral thigh free flap are
used; the goal is to have a thin pliable conduit. For circumferential defects where
the lower end is accessible in the neck for anastomoses, PMMC is used again in salvage
settings, in a vessel-depleted neck or in patients unfit for prolonged anaesthesia.
The ALT is another suitable option for circumferential reconstruction if the thigh
skin is not too thick or hairy; in either of these situations, a radial forearm is
used. The jejunal-free flap can also be used; enteric flaps are associated with better
swallowing outcomes than skin-lined flaps,[[2]] however, their harvest requires expertise and their tolerance to ischaemia is very
limited and hence, considerable microsurgical expertise needs to be acquired before
attempting them. For circumferential defects where the lower end is not easily accessible
in the neck for a tension-free anastomosis, a gastric pull-up is preferred. In our
institution, the jejunal flap is the choice for patients with circumferential defects
with good surgical fitness, while ALT is the choice for patients who are less fit,
in whom the additional morbidity of a laparoscopic harvest should be avoided. Gastric
pull-up is used only when the lower resection stump is not available for anastomosis
in the neck.
Pharyngocutaneous fistula
Post-operative PCF was seen in 20 patients (37%), of which 15 of these patients were
managed conservatively and 5 required surgical intervention in the form of a second
flap reconstruction (PMMC flap in three and radial forearm-free flap in two).
Our protocol for assessment of pharyngeal integrity after reconstruction was videofluoroscopy
with a modified barium swallow on the 14th post-operative day. Those without leaks were started on oral alimentation, while
those with leaks were continued on nasogastric alimentation. For patients with minor
leaks, conservative management was administered with nasogastric alimentation, high
protein diet and wound care, with reassessment after 2 weeks. For those with significant
leaks or those with more than 1 month of conservative management after the initial
diagnosis of PCF, surgical correction was performed. We were unable to identify any
predictors of persistent PCF requiring surgical correction.
The most common site of leak was in between the suture line (80%) with the remaining
occurring at either the proximal or distal circumferential suture line in tubed repairs
(20%). Complications following pharyngeal reconstruction are shown in [Table 2], with the leak rate of individual flaps as shown.
Table 2
Complications following pharyngeal reconstruction
|
Complications
|
Number of patients (%)
|
|
PMMC: Pectoralis major myocutaneous flap, ALT: Anterolateral thigh-free flap
|
|
Fistula
|
|
|
PMMC patch
|
12/24 (50)
|
|
PMMC tubed
|
3/5 (60)
|
|
ALT patch
|
1/2 (50)
|
|
ALT tube
|
1/6 (16)
|
|
Gastric pull-up
|
2/12 (16)
|
|
Jejunal-free flap
|
1/6 (16)
|
|
Pharyngeal stricture
|
|
|
PMMC patch
|
4/24 (16)
|
|
PMMC tubed
|
0
|
|
ALT patch
|
0
|
|
ALT tubed
|
0
|
|
Gastric pull-up
|
0
|
|
Jejunal-free flap
|
4/6 (66)
|
|
Swallowing dysfunction
|
|
|
PMMC patch
|
5/24 (21)
|
|
PMMC tubed
|
1/5 (20)
|
|
ALT patch
|
1/2 (50)
|
|
ALT tubed
|
4/6 (66)
|
|
Gastric pull-up
|
4/12 (33)
|
|
Jejunal-free flap
|
1/6 (16)
|
When we performed a univariate analysis for the determinants of PCF [[Figure 3]], the only significant predictor of fistula was the presence of a partial pharyngeal
defect; those with partial pharyngeal defects were associated with a fistula in 54%,
while those with circumferential defects were associated with a fistula in 31%. However,
on multivariate analysis, this was not significant; it is likely to have been confounded
by factors like choice of flap and patient factors that could not be adequately adjusted
for.
Swallowing dysfunction
Full oral alimentation was restored by the 1st month in 7, in the 2nd month by 13 patients and in the 3rd month by nine patients; 40% of patients were on full oral alimentation within 3 months
after surgery. Another ten patients (18%) had oral alimentation restored between 6
and 12 months following surgery.
The reasons for dysphagia in these patients were strictures, the presence of pseudodiverticuli
or reduced propulsion in the neopharynx. Eight patients (15%) developed pharyngeal
strictures of which five were dilated successfully. The remaining patients underwent
a feeding procedure in the form of a percutaneous endoscopic gastrostomy or feeding
jejunostomy.
At last follow-up, 99 patients (72%) were on full oral alimentation. On univariate
analysis, the only predictor of poor swallowing was hypopharyngeal involvement by
tumour (pharynx vs. larynx, P = 0.046), as shown in [Table 3]. None of the characteristics, such as age and the nature of defect or the nature
of flap used, were found to impact post-operative dysphagia [[Table 4]].
Table 3
Patient characteristics associated with fistula
|
Characteristic
|
Without fistula
|
With fistula
|
P value on univariate analysis
|
P value on multivariate analysis
|
|
*Statistically significant
|
|
Age (years)
|
|
|
|
|
|
<60
|
23
|
12
|
0.872
|
-
|
|
≥60
|
14
|
8
|
|
|
|
Sex
|
|
|
|
|
|
Male
|
27
|
17
|
0.302
|
-
|
|
Female
|
10
|
3
|
|
|
|
Site
|
|
|
|
|
|
Pharyngeal
|
21
|
13
|
0.624
|
-
|
|
Laryngeal
|
15
|
7
|
|
|
|
Pharyngeal defect
|
|
|
|
|
|
Circumferential
|
24
|
7
|
0.006*
|
Not significant
|
|
Partial
|
9
|
13
|
|
|
|
Flap used
|
|
|
|
|
|
Regional
|
26
|
16
|
0.425
|
-
|
|
Free
|
11
|
4
|
|
|
Table 4
Patient characteristics associated with swallowing dysfunction
|
Characteristic
|
Without swallowing dysfunction
|
With swallowing dysfunction
|
P value on univariate analysis
|
P value on multivariate analysis
|
|
*Statistically significant
|
|
Age (years)
|
|
|
|
|
|
<60
|
26
|
9
|
0.617
|
-
|
|
≥60
|
15
|
7
|
|
|
|
Sex
|
|
|
|
|
|
Male
|
32
|
12
|
0.805
|
-
|
|
Female
|
9
|
4
|
|
|
|
Pharyngeal defect
|
|
|
|
|
|
Circumferential
|
23
|
8
|
0.677
|
-
|
|
Partial
|
18
|
8
|
|
|
|
Site
|
|
|
|
|
|
Pharyngeal
|
21
|
13
|
0.046*
|
0.003*
|
|
Laryngeal
|
19
|
3
|
|
|
|
Flap used
|
|
|
|
|
|
Regional
|
30
|
12
|
0.413
|
-
|
|
Free
|
9
|
6
|
|
|
Speech outcomes
Tracheo-oesophageal puncture and prosthesis insertion were done in 20 patients (35%).
Those with enteric flaps or persistent PCF did not undergo prosthesis placement in
the primary setting. Of these 20 patients, 17 (85%) developed satisfactory speech.
Of those who did not receive tracheo-oesophageal punctures, rehabilitation was offered
with electrolarynx.
Mortality
Three patients (5%) died in the post-operative period. Of these, one was due to acute
coronary syndrome in the perioperative period and two were following PCF, leading
to sepsis. Of the 20 patients developing PCF, the mortality rate was 10%.
DISCUSSION
Pharyngeal reconstruction remains a continuous challenge post-ablation for head-and-neck
cancer. With the increasing use of organ preservation protocols in the treatment of
laryngeal and hypopharyngeal cancers, surgery is often performed in a salvage setting.
These results often results in extensive defects and significant local toxicity resulting
in a higher local complication rate following surgery.
A large series that those receiving previous chemoradiotherapy have a significantly
higher incidence of wound complications (45% vs. 25%) and PCF rate (32% vs. 12%) when
compared to those undergoing surgery without any previous therapy.[[3]] This was reflected in our cohort of patients, with over half of the patients having
received previous treatment and a PCF rate of around 37%. However, when we analysed
for determinants of fistula, the only predictor was a partial defect when compared
with a circumferential defect (54% vs. 31%), which was significant on univariate analysis
but not significant on multivariate analysis, as shown in [Table 3]. These findings, however, are consistent with similar series in the literature.[[4]] It is important to note that three quarters of the patients with PCF were managed
successfully with conservative management, which suggests that repeated surgical intervention
may be ill-advised, especially when poor wound healing is a result of previous radiotherapy.
Our surgical technique of closure was standardised for all cases. We utilised interrupted
suturing in two layers with 3-0 vicryl. Proximally, the flap was spatulated, while
distally a lock-and-key figure was used for approximation. The ideal technique of
closure and the resultant fistula rates have been intensely debated. One of the first
articles to address this was by Su and Chiang[[5]] who advocated placement of the T-shaped suture line posteriorly. Cho et al.[[6]] suggested a modification to the flap design, by overlapping of the vertical suture
line with de-epithelialised skin, using a two-layered closure and triangular flaps
at the distal anastomotic site (to reduce anastomotic stricture). Although no consensus
has been reached, it is important to remember the principles of closure; the approximation
needs to be watertight with just adequate approximation so as to not compromise the
vascularity of the suture line. In addition, in cases with extensive defects where
fistula is likely, it is important to isolate the carotid vessels from the repair
and potential area of leak to prevent life-threatening haemorrhage.
The choice of flap for reconstruction is often determined by the extent of the defect,
technical expertise and patient fitness. Our institutional protocol was as discussed
earlier; however, modifications are needed according to patient fitness and body habitus.
For patients unfit for prolonged anaesthesia, regional flaps are used. The bulk of
individual flaps needs to be assessed on a patient before taking a decision on choice
of flap.
Swallowing dysfunction was another important end-point of our study. A successful
pharyngeal reconstruction entails complete oral alimentation without dysphagia. At
last follow-up, 72% of our cohort was on full oral alimentation, with 40% achieving
this within the first 3 months following surgery. Videofluoroscopic assessments are
crucial in these patients; it is estimated that up to 50% of patients suffer from
dysphagia following laryngectomy that adversely impacts their quality of life.[[4]] Continuous assessment by a swallowing therapist leads to early identification and
treatment in many of these cases. In our cohort, patients with hypopharyngeal disease
had a significantly higher incidence of dysphagia. This is understandable as flap
reconstructions do not contribute to propulsion of the bolus and the loss of intrinsic
pharyngeal mucosa is likely to correlate with poor propulsion in the neopharynx.[[7]]
Speech rehabilitation with tracheo-oesophageal puncture and prosthesis insertion was
done in a little over a third of patients, with a majority of them functioning well.
In gastric pull-up and jejunal flaps, the puncture has been shown to be successful,
but the voice quality is often poor with a gurgling quality when compared to skin-lined
flaps.[[6]] The decision of primary versus secondary tracheo-oesophageal is controversial,
however, if the patient is likely to have a PCF, the puncture is deferred till complete
healing. For patients in whom prosthesis placement is unsuccessful or ill-advised,
electrolarynx remains a viable method of speech rehabilitation.
CONCLUSION
Pharyngeal reconstruction following TL is feasible with good results. Majority of
the patients, who swallow, regain acceptable swallowing function within 3 months.
Most of the early post-operative fistulae can be managed conservatively. The incidence
of stricture formation is low, and these are often amenable to dilatation. Patients
with pharyngeal disease have poorer swallowing outcomes and higher rates of fistula.
Financial support and sponsorship
Nil.
