The Results of Revision Surgery for Interdigital Neuromas
January 1st, 2003
Emmanouil D Stamatis, M.D
Mark S Myerson, M.D
Abstract
In a six year period (January 1996-January 2001), we re-explored 60 interspaces (49 patients, 49 feet) due to recurrent or unresolved symptoms after previous procedure for interdigital neuroma excision. Ten patients underwent excision of a primary neuroma from an adjacent interspace, while nineteen underwent concomitant forefoot surgery. The average duration of follow-up was 39.7 months (range, 6 to 79 months). The final follow-up evaluation included review of medical records, radiographs, clinical assessment and a questionnaire regarding subjective satisfaction rate, pain level, footwear and activity restrictions. Fifteen patients (30.7%) were completely satisfied, thirteen (26.5%) satisfied with minor reservations, ten (20.4%) satisfied with major reservations and eleven (22.4%) dissatisfied with the postoperative outcome. Twenty-eight of the forty-nine patients (57.2%) had no or mild pain, twenty-nine patients (59.2%) had moderate or severe footwear restrictions, and eight patients (16.3%) had moderate activity restrictions.
Intraoperative findings, simultaneous surgery to adjacent interspaces, concomitant forefoot surgery and previous attempts at re-exploration did no influence the final outcome. Persistent or recurrent symptoms after nerve transection present a challenging problem for both the surgeon and the patient. Thorough preoperative discussion must be undertaken with the patient, providing the average rates of failure and the increased likelihood of footwear and activity restrictions.
Introduction
There are numerous published reports on the etiology of interdigital neuritis (Morton’s neuroma), but most recent studies strongly support that it is a form of entrapment neuropathy (16, 18, 23, 31). Although non-operative measures may provide satisfactory results to some patients (3, 17), the surgical treatment seems to provide more predictable results and lasting pain relief.
Despite a few reports on release of the transverse metatarsal ligament (12, 15, 28), as an alternative to neurectomy, the later remains the most commonly used procedure for the treatment of interdigital neuritis through a plantar (2, 20, 26, 30) or a dorsal approach (2, 3, 5, 6, 8, 14, 21, 25, 35).
The reported results on the outcome after neurectomy are rather conflicting, with a reported failure rate of 2% to 14% (2, 3, 5, 8, 14, 20, 21, 25, 26, 35).
The treatment of the later group of patients with recurrent or unresolved symptoms after previous neuroma excision is a rather disquieting problem. There are only a few reports regarding the rate of failure after re-exploration of a painful interspace. The reported failure rate after such a revision surgery varies from 8% to 80% (4, 5, 19, 25, 27). In addition, even if there is significant pain improvement, the reported rates of footwear and activity restrictions range from 50% to 85% and from 20% to 55%, respectively (4, 19, 25).
The purpose of the current retrospective study was to evaluate the outcome of our consecutive series of patients who underwent revision surgery due to unresolved or recurrent symptoms after an initial procedure or procedures for interdigital neuroma excision. We were particularly interested in the overall outcome after revision surgery regarding postoperative pain level, activity and footwear restrictions. We were also interested in whether the exploration of two adjacent interspaces, the intraoperative findings, the concomitant forefoot surgery and the previous attempts at re-exploration have an influence on the final outcome.
Materials and Methods
In a six year period (January 1996- January 2002), 57 patients (57 feet) underwent revision surgery due to unresolved or recurrent symptoms after an initial procedure or procedures for interdigital neuroma excision. Of the 57 patients, 8 patients were lost to the final follow-up: 3 patients were contacted but declined to participate, and 5 patients had moved from the area and could not be located. The remaining 49 patients (49 feet) were successfully conducted and seen at our institution for the final follow-up.
There were 41 female and 8 male who had an average age of 55.1 years (range, 30 to 78 years) at the time of the revision procedure. There were 22 right feet and 27 left feet. This group of patients had previously undergone excision of 64 interdigital neuromas. 34 patients had undergone excision of a single neuroma and 15 patients had undergone simultaneous or sequential excision of two neuromas in adjacent interspaces in the same foot. The initial neurectom-y (-ies) had been performed at our institution in 5 patients and at a different institution in 44 patients.
From the 64 previously explored interspaces, 60 were re-explored because of severe recurrent or unresolved symptoms. In 38 patients one interspace was re-explored (34 with previous excision of a single neuroma and 4 with previous excision of two adjacent neuromas), and in 11 patients both previously operated interspaces in the same foot were re-explored. Ten of the 34 patients with a previous single interspace initial neurectomy were found to have another primary neuroma at an adjacent interspace, which was contributing symptoms in addition to those of the previously involved interspace. This neuroma was excised at the same time with the re-exploration of the previously operated interspace (Tables I-IV).
Seven (7) of the 38 patients with a single interspace re-exploration had undergone one previous attempt of re-exploration prior entering the study (Six at a different and one at our institution). One of the 11 patients with two interspaces re-explored at the same time had undergone two previous attempts of re-explorations at a different institution while another one had undergone three previous attempts of re-explorations at a different institution.
Nineteen (19) of the 49 patients were found to have concomitant forefoot pathology which was contributing symptoms in addition to those from the involved interspaces, and they were treated accordingly at the same time of interspace(s) re-exploration. The indications for surgery in this group of patients were: two patients with isolated hallux valgus deformity, one with recurrent hallux valgus deformity, one with hallux valgus deformity and concomitant instability of the 2nd metatarsophalangeal (MTP) joint, seven with isolated 2nd MTP instability, two with 2nd and 3rd MTP instability, two with intractable plantar keratosis (IPK) under the 4th metatarsal head, one with IPK under the 2nd-3rd-4th metatarsal heads, one with bunionette deformity, one with 2nd-3rd-4th hammertoe deformity and one with 3rd MTP synovial cyst.
Preoperative assessment
All patients with recurrent or unresolved symptoms after previous neurectomy were carefully evaluated before re-exploration of any interspace. All patients had undergone previous unsuccessful non-operative treatment with shoe and activity modifications, metatarsal pads and/or other types of orthotics, nonsteroidal anti-inflammatory medication and local injections with steroids. In all patients, the symptoms were not much different from those of a primary neuroma with the majority of them complaining for diffuse, poorly defined forefoot pain which was exacerbated by the foot wear. Pain was occasionally reported radiating to the toes or even to the calf.
Detailed history, meticulous clinical assessment and radiographic evaluation were mandatory to identify the main source of pain. Even if there was pain in the previously explored interspaces and clinical evidence of recurrent pathology, the whole forefoot area was carefully scrutinized. Care was taken to identify other sources of pain different than the previously explored interspace such as lesser toe metatarsophalangeal joint pathology (synovitis, synovial cyst, Freiberg disease, and instability), presence of other neuromas at the adjacent interspaces, metatarsal stress fractures, hallux or lesser toes deformities with subsequent stress transfer, painful previous surgical scars, and painful iatrogenic superficial neuromas. Care was also taken to ascertain that there was no proximal pathology mimicking or contributing to the forefoot symptoms, such as tarsal tunnel syndrome and lumbar radiculopathy. In addition, and especially in high risk patients (e.g. diabetics) diffuse nerve pathology such as peripheral neuropathy and reflex sympathetic dystrophy was ruled out.
When the differential diagnosis was not clear or when there was evidence of concomitant pathology contributing symptoms to those of the previously explored interspace, sequential injections with local anesthetic to the painful areas were proved extremely useful to confirm the diagnosis. Diagnostic injections were used in 16 (32.6%) patients.
In addition, the use of ultrasonography at our institution (24) for the diagnosis of recurrent or adjacent primary neuromas significantly improved the accuracy of preoperative diagnosis in 14 (28.5%) patients.
Standard weight-bearing radiographs were evaluated for any significant forefoot pathology. A radiographic indication of instability of a lesser metatarsophalangeal joint was medial deviation of the joint of >5° (7).
The use of MRI was limited, since the reports on its efficacy in demonstrating a neuroma are rather conflicting (13, 29).
An extensive discussion was performed with all patients preoperatively in order to identify their psychological back-up and their expectations from the revision surgery
Surgical approach
All procedures were performed by the senior author (MSM). Forty-seven patients underwent re-exploration of the involved interspaces through a dorsal incision and two through a transverse plantar incision placed proximal to the weight bearing area of the forefoot. Three of the forty-seven patients had undergone the previous neurectomy through a plantar incision, while the two patients with the plantar re-exploration at our institution, had undergone the previous neurectomy through a dorsal incision.
For the dorsal approach, the previous incision was utilized or a new was made (in case of previous plantar approach) over the involved interspace extending from its distal aspect up to approximately three cm proximally. When additional pathology of the adjacent MTP joints had to be addressed, a more extensive incision was utilized extending over the MTP joint.
The skin incision was then deepened through the subcutaneous tissues. After the superficial bleeders were cauterized, taking care to protect any cutaneous nerves, a Weitlander retractor was inserted into the incision and then the interosseous space was perforated with a rongeur. A small laminar spreader was then inserted into the interosseous space between the metatarsals which were placed under tension. A Senn retractor was then inserted distally, and this exposed the deep transverse metatarsal ligament, which had partly or completely reformed from scar tissue. Careful probing of the under surface of the ligament was performed in a proximal direction with a clamp and it was then released with a Metzenbaum scissors. In several occasions the interdigital nerve was found intact or transected at the level of zone I (under the deep transverse metatarsal ligament) as this was described by Amis et al (1). This was documented in the operative note and all the later nerves were also considered intact, since their main trunk was left in the interspace.
In other occasions, and despite previous adequate, more proximal, resection, a stump neuroma had been formed, and this was consistently found adherent to the under surface or the lateral aspect of the adjacent metatarsal neck. This was documented in the operative note as a stump neuroma.
A small clamp was then utilized and the nerve elevated into the incision. The intact nerve or the stump neuroma was then carefully dissected off the surrounding soft tissue scar, and all the remaining small plantar cutaneous branches were then cut as they branched from the main trunk of the nerve. The nerve was then completely elevated and traced proximally. The transaction was performed proximally as far as possible in the interosseus musculature. All specimens were sent for pathological examination.
The transverse plantar approach (4) was utilized in two cases, where there were clinical findings (severe plantar tenderness, positive Tinel sign) of a plantarly adherent stump neuroma, at a quite proximal location in the interspace. In these cases the plantar exposure offered adequate visualization of the nerve, which would clearly be difficult through a dorsal approach.
All the primary neuromas which were detected in any adjacent interspaces were also excised through a dorsal approach.
The patients were allowed to walk with weight-bearing as tolerated, in a postoperative shoe. The postoperative protocol in the presence of additional forefoot surgery was individualized depending on the procedure.
Concomitant procedures
All MTP instabilities were addressed with dorsal MTP capsular release, and flexor digitorum longus tendon transfer to the extensor hood. In two cases a distal oblique metatarsal osteotomy (Weil) was additionally utilized in order to address increased metatarsal length. All the hallux valgus deformities but the recurrent were treated with a distal Chevron osteotomy. The recurrent deformity was treated with a Ludloff shaft metatarsal osteotomy and distal soft tissue release. All the isolated IPK lesions were addressed with a DuVries plantar condylectomy, while the IPK lesion under several metatarsophalangeal joints was addressed with distal dorsiflexion metatarsal osteotomies. The hammertoe deformities were addressed with proximal inter-phalangeal resection arthroplasty. A synovial cyst was removed from an MTP joint and a bunionette deformity was corrected with an oblique fifth metatarsal osteotomy.
Last follow-up assessment
The current study had received approval by the internal review board (IRB), and informed consent form was obtained from all patients. The first author (EDS), who was not directly involved in the procedures, conducted the review. All of the patients’ medical records, including preoperative and postoperative chart notes and radiographs, operative reports, and pathology reports were reviewed.
All patients were asked to define their pain level, restrictions in footwear, and restrictions in activity. The pain level scale was: 4 (no pain); 3 (mild pain); 2 (moderate pain) and 1(severe pain). The footwear restrictions scale was: 1 (no restrictions, able to wear any kind of shoes, any time); 2 (mild restrictions, able to wear narrow fashion shoes-such as high heels- occasionally, for moderate time); 3 (moderate restrictions, able to wear only flat, wide shoes) and 4 (major restrictions, able to wear only wide athletic type of shoes or slippers). The activity restrictions scale was: 1 (no restrictions for any kind of activities); 2 (mild restrictions, impairment of strenuous activities only, such as long distance run or aerobic exercise); 3 (moderate restrictions, such as impairment of prolonged ability for walking or standing) and 4 (severe restrictions, impairment of daily activities).
Patients were asked to subjectively rate their overall satisfaction after surgery. The satisfaction rate scale which was used, it was a slightly modified scale of that reported by Johnson et al (19). According to this scale the patient was: 1, completely satisfied (no pain, no restrictions in activity and no or mild restrictions in footwear); 2, satisfied with minor reservations (mild pain, no or mild restrictions in activity and mild or moderate restrictions in footwear); 3, satisfied with major reservations (moderate pain, mild or moderate restrictions in activity and moderate restrictions in footwear) and 4, dissatisfied (severe pain, moderate or severe restrictions in activity and moderate or severe restrictions in footwear).
The patients were also asked if there was need for pads or other types of orthotics in addition to any footwear modifications.
Clinical assessment was performed and last follow-up radiographs were reviewed. Clinical assessment included: Inspection of the plantar aspect of the foot for the detection of intractable plantar keratosis (callosity) or fat-pad atrophy; Palpation of the explored interspaces (primary and revised) and the adjacent lesser MTP joints; Percussion over the explored interspaces and surgical scars; Drawer test (32) of lesser MTP joints for the detection of instability; Sensory examination of the involved web spaces and comparison of the findings with the subjective sensation of numbness. All radiographs were reviewed for any evidence of osseous or joint pathology, especially lesser MTP instability.
The forty-nine patients were separated in four groups depending on the type of surgery they had undergone. Thus, in Group I (Table I) the patients had only undergone re-exploration of one or two interspaces; in Group II (Table II) the patients had undergone re-exploration of an interspace and a primary neuroma excision from an adjacent interspace; in Group III (Table III) the patients hade undergone re-exploration of one or two interspaces and concomitant forefoot surgery and in Group IV (Table IV) the patients had undergone re-exploration of an interspace, a primary neuroma excision from an adjacent interspace and concomitant forefoot surgery.
In all patients who underwent concomitant forefoot surgery we did not assign a score according to AOFAS scales. Kitaoka et al (22) stated that in the presence of nerve disorders these scales have limited application. This happens because any nerve pathology may affect grading pain severity. Additionally, previous reports (8, 25) have demonstrated that even isolated neuroma surgery significantly affects the footwear and activity level and a significant number of the involved interspaces remain tender. Instead we preferred to describe any complications from these concomitant surgeries which contributed to less favorable outcome.
Data collection and descriptive statistics were performed with Microsoft Excel (Microsoft Corp, Bellevue, WA). Statistical analysis was performed with a chi-square test in order to compare: the postoperative outcome of patients between different groups; the postoperative outcome of surgeries with different intraoperative findings (intact nerve or stump neuroma); the postoperative outcome of surgery in one interspace or two adjacent interspaces (two recurrent neuromas or one recurrent and one primary); the postoperative outcome of the patients with and without previous attempts of re-exploration; and the postoperative outcome of patients with and without concomitant forefoot surgery. The significance was set at p<0.05.
Results
The average duration of postoperative follow-up was 39.7 months (range, 6 to 79 months). The average time between the previous procedure (initial procedure or last attempt), different than the last re-exploration, and the recurrence of symptoms was 13.6 months (range, 0 to 110 months). The average time between the previous procedure (initial procedure or last attempt) and revision surgery at our institution was 27.8 months (range, 3 to 140 months). Twenty four patients (49%) reported that their symptoms never resolved after the previous procedure. Nineteen of them were found to have (during the re-exploration at our institution) an intact or quite distally transected nerve while five of them were found to have a stump neuroma.
The distribution of the sixty re-explored web spaces was: twenty-six (43.4%) 2nd interspaces; thirty-three (55%) 3rd interspaces and one (1.6%) 4th interspace. Five (50%) of the ten primary neuromas occurred in the 2nd interspace, while four (40%) occurred in the 3rd and one (10%) in the 4th interspace.
During the re-exploration of the sixty interspaces we identified thirty-two (53.3%) intact or quite distally transacted nerves, twenty-seven (45%) stump neuromas, while in one (1.7%) interspace the only intraoperative finding was a synovial cyst from an adjacent lesser MTP joint. Pathology reports confirmed the intraoperative findings in all cases.
Fifteen patients (30.7%) were completely satisfied, thirteen (26.5%) satisfied with minor reservations, ten (20.4%) satisfied with major reservations and eleven (22.4%) dissatisfied with the postoperative outcome. Fifteen patients (30.7%) had no pain, thirteen patients (26.5%) had mild pain, eleven patients (22.4%) had moderate pain and ten patients (20.4%) had severe pain. One of the patients with moderate pain stated that in fact was dissatisfied because of severe footwear restrictions (Case 6 in Table II). Eleven patients (22.4%) reported the need for metatarsal pads or orthotics in addition to footwear modifications.
Seven patients (14.3%) had no footwear restrictions, thirteen patients (26.5%) had mild restrictions, twenty-one (42.9%) had moderate and eight (16.3%) severe footwear restrictions.
Nineteen patients (38.8%) had no activity restrictions, twenty-two (44.9%) had mild restrictions, eight (16.3%) moderate restrictions and none reported severe restrictions interfering with daily activities. Two patients reported mild restrictions of their activities despite they had stated that the level of their pain was severe (Case 8 in Table III and case 24 in Table I).
The re-explored or primary explored interspaces were tender on palpation in thirty-five of the forty-nine patients (71%), and twenty-six (53%) were aware of that. Tenderness on palpation of the re-explored web spaces was not necessarily associated with less favourable outcome (Tables I-IV).
The objective findings of the sensory examination revealed no patients with normal sensation between the digits. Thirty patients (61.2%) had numbness in the plantar aspect of the involved web spaces. In this later group were included the eleven patients who had undergone re-exploration of two interspaces and the ten patients who had undergone re-exploration of one interspace and concomitant resection of a primary neuroma from an adjacent web space. Thirty-two patients (65.3%) had subjective sensation of numbness but it was reported as vexing by three of them. Interestingly five of the patients with two operated adjacent interspaces did not report subjective sensation of numbness (Tables (I-IV).
There were nine patients (18.3%) who had tenderness on palpation of ten lesser metatarsophalangeal joints. Five of these joints (four patients) had a positive drawer test while three of them (two patients) had also had radiographic evidence of instability. The later three joints had been treated for instability at the same time with the revision neuroma surgery. On another one tender joint a distal metatarsal dorsiflexion osteotomy had been performed at the same time with the revision neuroma surgery.
Intractable plantar keratosis was detected under fourteen lesser metatarsophalangeal joints. Nine of them were asymptomatic and the remaining five were associated with tenderness and/or signs of metatarsophalangeal instability. Fat pat atrophy was not detected on any patients.
There were two patients with subjective complaints for scar tenderness. In fact one of them reported severe dissatisfaction with the previous plantar incision which had been preformed at a different institution. The other patient was dissatisfied with the dorsal incision which had been performed at our institution, and a positive Tinel sign was also present over the scar.
A positive nerve percussion test (Tinel) over the explored interspaces was found in twenty-one patients (42.8%), but it could not be associated with the satisfaction rate.
Complications occurred in six patients (12.2%). Two developed Reflex Sympathetic Dystrophy (RSD) which required further treatment with lumbar sympathetic blocks. Two patients had recurrent instability of three lesser metatarsophalangeal joints which had been treated for instability at the same time with the revision neuroma surgery, but only the patient with the isolated unstable joint was symptomatic. The later patient denied a revision procedure for the failed forefoot surgery. One patient had a recurrent hallux valgus deformity which did not adversely affect the satisfaction rate. One patient developed a superficial wound infection which was successfully treated with local wound care and oral antibiotics.
A detailed evaluation of the eleven dissatisfied patient revealed that: Four had severe pain in the re-explored interspace(s) and severe footwear restrictions; two severe pain in the re-explored interspace(s); two sever pain in the re-explored interspace(s), severe footwear restrictions and vexing subjective sensation of numbness; one had moderate pain in the re-explored interspace, severe footwear restrictions, vexing subjective sensation of numbness and a positive Tinel sign over the dorsal scar; one had severe pain due to instability of a lesser metatarsophalangeal joint; and one had severe pain (metatarsalgia) and severe footwear restrictions after previous distal metatarsal dorsiflexion osteotomy.
The postoperative outcome of patients between different groups regarding satisfaction rate, pain level, footwear and activity restrictions was not statistically different with p values of 0.627, 0.350, 0.964 and 0.882, respectively.
The intraoperative findings (intact nerve versus stump neuroma) did not affect the subjective satisfaction rate, the pain level, the footwear and activity restrictions (p values of 0.181, 0.098, 0.352 and 0.101, respectively).
The postoperative outcome of surgery in one interspace or two adjacent interspaces (two recurrent neuromas or one recurrent and one primary) was not statistically different. The p values for the satisfaction rate, pain level, footwear and activity restrictions were 0.478, 0.661, 0.966 and 0.704 respectively.
The postoperative outcome of the patients with and without previous attempts of re-exploration was also not statistically different. The p values for the satisfaction rate, pain level, footwear and activity restrictions were 0.565, 0.519, 0.587 and 0.761, respectively.
Finally, the postoperative outcome of the patients with or without concomitant forefoot surgery was not statistically different. The p values for the satisfaction rate, pain level, footwear and activity restrictions were 0.514, 0.347, 0.733 and 0.802, respectively.
Discussion
Several reports have demonstrated that persistent or recurrent symptoms with a concomitant, relatively high dissatisfaction rate are rather common after resection of an interdigital nerve for interdigital neuritis (Morton’s neuroma). The most commonly reported causes of recurrent or persistent symptoms are: inadequate resection of the nerve (19); formation of a transaction neuroma which is attached to an area of movement, friction, pressure or tension (25, 34); inadequate preoperative assessment of other sources of pain which contribute symptoms stimulating those of interdigital neuritis (4).
In an effort to address this problem several studies have prompted the following proposals: A plantar approach which might enhance adequate visualization of the digital nerve at its most proximal location in the interspace (2,20,26,30); Adequate transaction of the small plantarly directed nerves that branch from the interdigital nerve and might preclude retraction of the transacted nerve out of the weight bearing area (1, 25); Release of the transverse metatarsal ligament alone or in combination with neurolysis which should not lead to formation of a transaction neuroma (12, 15, 28); Intermuscular transposition of the transacted nerve which might eliminate the neurotropic predilection of the transected nerve to grow toward the cut surface of the distal portion of the nerve (6, 9, 10).
By reviewing the literature regarding the relatively high failure rate after resection of an interdigital nerve, the reasonable questions that arise are: How one should treat the patients with recurrent or unresolved symptoms and what the expected outcome is. The literature is spare and the majority of the studies report on re-exploration of the involved interspaces and repeated nerve transaction (4, 19, 25). The failure rates of these techniques are rather high demonstrating that treatment of persistent pain after an interdigital nerve resection is a disquieting problem. Of interest are a few studies reporting on implantation of the proximal stump into muscle (11, 34) or bone (27). The results from these two studies are rather conflicting though with reported failure rates of 0% and 11.5%, respectively.
In our series, we utilized a dorsal approach for re-exploration of the involved interspace and a nerve transection at a quite proximal location. Our results demonstrated that the dorsal approach provides relatively similar outcome to that after a plantar approach (19). The overall dissatisfaction rate is relatively similar or slightly higher to those reported in other studies (4, 19, 25). Based on our results we also demonstrated that inadequate initial nerve resection is a common cause of persistent symptoms. The later has been also reported by Johnson et al (19). We anecdotally report that a significant percentage of patients with inadequate initial nerve resection had had a rather small dorsal incision, which clearly did not allow for adequate visualization.
Based on our results we also demonstrated that additional sources of pain, such as primary neuromas in adjacent interspaces, may contribute symptoms to those from the involved interspaces. The later was also supported by Beskin et al (4), who reported a 16.6% incidence of adjacent primary neuroma.
Previous reports have cautioned against simultaneous adjacent interspace exploration, stating that occurrence of two neuromas in the same foot is rare and that the expected outcome is worse (5, 8, 14, 33). In our series the patients with isolated interspace surgery compared to the patients who had two interspaces explored at the same time, did not have statistically different outcome. The later was also supported by Benedetti et al (2). Concomitant forefoot surgery and intraoperative finding did not influence the final outcome. Finally, previous attempts of re-exploration did not also affect the final outcome as it has also been reported by Johnson et al (19).
Persistent or recurrent symptoms after nerve transection present a challenging problem for both the surgeon and the patient. Thorough preoperative discussion must be undertaken with the patient, providing the average rates of failure and the increased likelihood of footwear and activity restrictions. The surgical treatment options are similar to those available for a primary neuroma, although the results from transposition techniques (11, 27, 34) may suggest that their further investigation and application could provide improved outcome comparing to that of the traditional techniques.
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