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Neodymium-YAG Laser Treatment of Intrabronchial Lesions
clinical invastiaatilns Neodymium-VAG Laser Treatment of lntrabronchial Lesions* A New Mapping Technique via the Flexible Flberoptlc Bronchoscope Lee Roy Joyner, Jr., M.D.;t Antti G. Maran, M.D., F.C.C.P.; Robert Sarama, M.D.; and Albin Yakaboski We report the results of the treatment of 45 patients (38 with
malignant and seven with benign disease) with intrabronchiallesions using the neodymium-YAG laser via the fteDble &beroptic bronchoscope. Multiple treatment sessions were used with treatment intervals varying from four days to four weeks. Additional debridement procedures were also necessary in select cases. (There was total of 109 treatments in 45 patients~ Over 70 percent (81 of 109) of all treatments were clone without intubation and with sedation techniques, and topical lidocaine application similar to that used in standard &beroptic bronchoscopy. Laser treatment of the less edenme segmental lesion resulted in very meaning£ul palliation and laser therapy need not be reserved for extensive central disease only. In our judgment, this can most safely be done ith the exception of chemotherapy for oat cell W carcinoma, the outcome in the treatment oflung cancer has not appreciably improved in over two decades. 1 From the day of diagnosis, 75 percent of all patients are inoperable and one-half of the remaining 25 percent will develop progressive disease in spite of For editorial comment, see page 416 surgery...3 Vigorous early detection programs have raised as many gloomy questions regarding health care cost, continued need for extensive resection, multicentricity, and new metachronous primaries as problems solved. u A practical hematoporphyrin marker with subsequent therapeutic potential is not yet available and would likely also have only limited potential. 8 •7 The present reality remains that "palliation is the only game in town" for over 80 percent of all lung cancer victims. To date, endoscopic neodymium-YAG laser phototherapy has been limited primarily to central malignant lesions in the trachea or main bronchi in the •From the St. Francis Hospital, Monroe, Louisiana.
t Assistant Professor of Medicine, Louisiana State University School
of Medicine, S~rt. Manuscript received June 26; revision accepted November 2. Reprint requem: Dr. Joyner, 401 Hall Street, Monroe, Louidana
71201
418
with a "real time, intrabronchial mapping technique." The Mill Rose (W-22-13) transbronchial needle was used intraoperatively to perforate blind intrabronchial obstructions. Renogra&n (Ren-M-60 M) was then band injected to locate and 8uoroscopically visualize the postobstructive bronchial remnant. Precise laser penetration into the postobstructive remnant was then possible by following the same pathway. 'l1lis technique greatly extended our ability to safely perforate segmental and even blind central obstructing lesioos. In our judgment, without a "real time intrabronchial mapping technique,,. wscular and bronchial perforations would be more likely when treating the more distal lobar and segmental obstructions.
relatively advanced state. a.ro In fact, most lung cancers occur in the lobar or proximal segmental bronchi rather than occur centrally. 8 •11 It is very difficult to gain insight from available material regarding treatment techniques, ie, laser energy settings, operative time, number of treatments required, optimal time between retreatments, hazards, etc. In our experience, many lobar and segmental lesions which could be visualized with the flexible fiberoptic bronchoscope could not be effected by laser therapy because of the subsequent loss of degree of flexion with passage of the stiff quartz light guides now available. By "over tightening" of the cable of the fiberscope (BITR Olympus), we were able to treat even upper lobe apical segmental lesions completely. This report details the results, complications, and techniques used in the neodymium-VAG laser phototherapy of 38 patients with inoperable lung cancer, two-thirds of whom had endoscopic disease limited to lobar or segmental sites. In each case, an associated condition existed that in our judgment could best be palliated with laser phototherapy. The results of seven benign cases are also included. MATERIALS AND METHODS
All patients in this series were evaluated by the pulmonary section
guide. The transbronchial aspirating retractable biopsy needle (Wang model W-222-13) was used fur intraoperative bronchograms. Renografin (Reno-M-60) was used as contrast when the transbronchial needle was employed intraoperatively, and dilute Dionosil was used fur more detailed bronchial visualization once an obstruction had been perfOrated. A Phillips fluoroscopic C-arm was used intraoperatively fur real time fluoroscopy on command. The C-arm viewing monitor hook-up was altered so that the real time fluo-
FIGURE 1. Diagram of real time intrabronchial mapping technique. (Upper). Under direct vision, the Wang transbronchial needle is advanced at suspected site ofbronchial communication across the intrabronchial obstructing process. With the stilet in place the depth of initial needle penetration is varied with anticipated axial length of intrabronchial obstruction. (Lower). Small amounts ofRenografin is hand injected, typically under considerable pressure, until the postobstructive bronchial remnant is localized. Laser penetration fOllowing the same pathway is then straightfOrward. of the Northeast Medical Specialty Clinic between October of 1982 and February of 1984. With the exception of one patient, all cancer victims were classified as non.resectable surgically by extent of disease or due to poor overall general health considerations. A single patient received laser phototherapy fur drainage of a pneumonia prior to subsequent successful pneumonectomy. This was an MMB (Messerschmitt-Bolkow-Bohm) sponsored FDA protocol approved study conducted at St. Francis Medical Center in Monroe, Louisiana. The Institutional Review Committee of this institution also gave approval and patients were fully infOrmed of the nature, intent, and risk factors involved. An extensive FDA approved infOrmed consent furm was signed by each patient. Equipment
Laser treatments were perfOrmed in an operating room designed exclusively fur laser work. Patients who \vere not intubated were given supplemental oxygen via a 25 percent to 45 percent Ventimask altered to accommodate transnasal fiberoptic bronchoscopy. A fiberscope (B1TR Olympus) was modified by "over tightening" the flexion cable so that a flexion of 180 degrees was possible with the laser quartz light guide in place. The fiberscope was used fur endoscopic photography and the microvideo camera (Circon) was used fur video documentation befure and after all treatments. The neodymium yttrium alUininum garnet (YAG) (Endolase, model K621101) and quartz light guide were used as a source of laser energy. Helium, due to its low potential fur supporting combustion, was used as the gas source in the treatment field via the quartz light
FIGURE 2. Injection sequence as seen on the C-arm fluoroscopy intraoperatively with "alveologram effect." (Top). Wang needle (BmtJU arrow) used to hand inject Renografin into anterior segment of LUL beyond the obstructing LUL neoplasm. LUL alveologram produced with no defi{lite bronchus visualized. (Center) . After laser crater developed into anterior segment ofLUL, repeat Wang needle injection shows somewhat indistinct (large arrow) outline of proximal postobstructive bronchus (the lingulae bronchogram below is a result of retrograde flow of renografin into the uninvolved lingulae segment). (Bottom). LUL anterior segment "Dionosil bronchogram" taken at debridement session lOur days later-LUL anterior segment opened widely with laser and in excellent condition in spite of previous obstructing carcinoma. CHEST I 87 I 4 I APRIL, 1985
419
TYPI OF LISION
PATIENTS PIBCENT
Squamou Cell
28
75
Luoe Cell
4
11
O.tC.ll
3
1
Metulatic and Othero
3
1
DISTRIBUTION OF LESIONS
Bronch...
.NUMBER
PIBCENT
Trachea and Main Stem
14
33
Sevemental
29
67
FIGURE 3. Intrabronchiallocation of malignant lesions and cell types. roscopic image was displayed on the VCR as well as on the standard C-arm monitor. This allowed fOr a permanent three-fOurths-inch VCR record of all fluoroscopic procedures. The technique used fOr real time intrabronchial mapping was as follows: Once a blind intrabronchial obstruction was encountered, the transbronchial needle was used to perfOrate the tumor (Fig 1). A few milliliters (2 to 10) of contrast were then hand injected while C-arm fluoroscopy allowed visualization. This procedure was repeated at different sites until the postobstructive bronchial lung remnant was found. The laser light guide was then immediately positioned at this site and an initial laser crater developed. The transbronchial needle was then passed through the crater to reconfirm an on-line course into the bronchial remnant before final laser penetration. Once laser perfOration was effected, a larger polyethylene catheter was advanced distally and dilute Dionosil was band injected. This resulted in a much higher quality segmental bronchogram which was used to access the condition of the postobstructive bronchus and to determine iffunctional lung tissue existed distally (Fig 2).
Photo Documentation of Lesion and Result Guidelines All lesions were photographed utilizing instant prints, 35 mm slides and rolling video. The degree of airway obstruction was then estimated based on pictorial review befOre and after each laser treatment. In each case, there was also a primary associated condition, ie, obstructive pneumonia, hemoptysis, atelectasis, dyspnea on exertion, etc, for which laser application had been selected (18ble I). Overall results were considered excellent if25 percent or less residual obstruction existed after final laser treatment plus the resolution of the primary associated condition. Results were considered good if greater than 25 percent residual obstruction was present, but there was still resolution of the primary associated condition. Results were considered poor if there was failure to influence the primary associated condition, regardless of the degree of residual airway obstruction. 7}n1e
of Anesthesia
Eighty-one of the 109 laser treatments were done with topical lidocaine anesthesia and sedation. Ten milliliters of 4 percent lidocaine was nebulized orally and an additional 5 to 10 ml placed directly into the larynx at the time of bronchoscopy. Glycopyrrolate (Robinul), 0.2 ml, and appropriate amounts ofdiazepam (Valium) and meperidine (Demerol) were given intravenously to maintain light sedation. Patients were still able to fOllow commands and cough when so instructed. Some patients complained later of the stench of burning tissue but experienced no other ill-effects. Oxygenation was supplemented with a Ventimask system. 1\venty-eight of106 treatments were given with general anesthesia and oral tracheal intubation. After sedation with diazepam, ketamine was used as a hypnotic and pancuronium bromide used to 420
produce paralysis. The lowest possible Fl<>t to maintain an arterial Po2 of65 or greater was given. At no time was the laser administered in an oxygen atmosphere greater than 40 percent. Arterial blood gas values were obtained frequently intraoperatively regardless of the anesthesia method used. Ventilation was temporarily a problem only in the three cases of lase!'-induced massive hemorrhage who subsequently recovered. In each case, Pco2 levels in the 70 to 90 range with acute respiratory acidosis occurred immediately fOllowing hemorrhage. As aspirated blood clots were removed endoscopically, the Pco2 levels reverted to normal rapidly. 1\w of the three patients were intubated at the time of hemorrhage. All treatments were perfOrmed in a setting where anesthesia and thoracic surgical consultation were instantly available ifneeded.
REsuus Central Malignant Lesions
There was a total ofl4lesions in 11 patients in either the trachea or mainstem bronchi (Fig 3). In all of those where the degree of obstruction was critical, the primary associated condition was dyspnea on exertion. Several also had distal infections (Table 1). Results were excellent in five, good in fum; and poor in two (excellent+ good= 80 percent). All patients with associated mediastinal disease at the time of treatment died within fuur months of laser phototherapy from progressive disease (8 of 11). The three patients with disease limited to the central airway without evidence of mediastinal metastasis had excellent long-term results. The endoscopic appearance and subsequent outcome was somewhat unexpected. Extensive submucosal disease resulting in complete airway obstruction responded to laser phototherapy and actually required less total laser energy than comparable intrabronchial tumors. Even when a submucosal process extended distally 5 to 8 em, a completely patent airway was possible with repeat laser treatments (Fig 4). Frequent debridement was mandatory fOllowing treatment of this type of submucosal disease. Within 24 to 48 hours, the treatment site was filled with a gel of necrotic tumor coagulum. This material could be easily cleared with suction; however, reaccumulation for several days occurred as necrotic tumor continued to Nd-VAG L.u« Thlalment ollntrabronchlall.aslons
(Joyner et Ill)
FIGURE 4. Demonstration of the ability to successfully treat a submucosal cancer process obstructing the right main bronchus. (Top). A 56-year-old man with a pinpoint orifice to the right main stem bronchus due to a recurrent squamous cell carcinoma after maximum radiation therapy. Endoscopically, all disease is submucosal; however, laser phototherapy was still given to an area extending several millimeters circumferentially from this pinpoint opening. (Center) . Four days later, the treatment site is covered with a gelatinous material which can be easily removed with suction via the flexible fiberscope. Three additional laser treatments are given after debridement at weekly intervals. General anesthesia was used only fur the initial treatment session. (Bottom). Final result is a widely patent right main bronchus with associated resolution of right lung atelectasis. Death occurred five months later from cardiac metastasis without recurrent atelectasis.
weep from the laser-affected bronchial walls. Repeat debridement was therefore required. Large, bulky central bronchial tumors were extremely demanding with regard to physician time required, and total laser energy necessary to relieve the obstruction. Extensive endobronchial debridement of charred particles with forceps also extended the time required for treatment. Endotracheal in tuba-
FIGURE 5. Demonstration of both the abi1ity to manage pulmonary hemorrhage with the laser and the rationale for treating "asymptomatic" segmental lesions in select cases. (Upper). A small nodular squamous cell carcinoma with surrounding hemorrhage arising from the apical posterior segment of the left upper lobe. A normal appearing lingulae segment is seen below. This lesion occurred as the only manifestation of carcinoma in an 82-year-old man with massive hemoptysis, This lesion could not be treated with the standard BlTR fiberscope due to the angulation required. Using the BlTR with the "overtightened cable," photocoagulation was used to promptly control hemorrhage (a ten-minute procedure without general anesthesia). Due to severe chronic congestive heart feai1ure, surgery was not a viable consideration and this patient refused external radiation. Laser photovaporization was used one week later to ablate all visible cancer and create a deep crater into the apical posterior segment. Four months later, a third laser treatment was given to ablate a single small recurrent nodule. (Lower). This photograph shows treatment site 11 months later-there is no visible cancer and all biopsies and brushings are negative. Laser therapy was the only treatment given. Death occurred three months later from a ruptured aortic aneurysm-autopsy not granted.
tion was routinely used for this type of lesion because of time considerations and because of the need frequently to change fiberscopes fur debridement purposes. There was a single complication in the central malignant obstructive group. Pulmonary artery perfOration occurred during a fOurth treatment session in a patient with extensive right main bronchial obstruction. This oecurred before the development of an adequate intrabronchial mapping technique. CHEST I 87 I 4 I APRIL, 1985
421
7. Renogra&n bronchogram of postobstructive bronchial remnant. (Upper) . Wang needle (arrow) used to perfOrate inferior lingulae segment "blind obstruction" (see photos Case 1). Bronchogram as seen on C-Arm fluoroscopy early in hand injection sequence. (Lower). Bronchial outline becomes quite obvious later in injection sequence. There is no alveolarization (even after several minutes) of Renografin in this case. Postobstructive dilatation of lingulae bronchus is not as severe as these magnified photos suggest. FIGURE
6. Value of laser treatment in recurrent segmental obstructions of the lingulae segment of the LUL after prior maximum radiation treatment. (Thp). A 62-year-old man with squamous cell carcinoma occluding the left upper division with an obstructed left upper lobe and lingula. A positive main carinallymph node needle aspirate prevented surgical consideration. Initial treatment consisted of laser photovaporization of 80 percent of visible intrabronchial cancer fOllowed by external radiation (6000 rads). Pneumonia and atelectasis of the LUL and lingulae initially resolved. (Center). Six months later, there is now "blind obstruction" of both lingulae subsegments with a patent LUL above. The chest x-ray film shows an abscess in the lingulae associated with a 13.5 kg weight loss and prolonged symptoms of infection. (Bottom) . The Wang needle Renografin bronchogram technique was used to successfully locate both lingulae subsegments with successful laser perfOration and drainage of a bacterial abscess. There is a marked clinical response, all weight is regained, and the patients functional status is excellent fOr an additional year. 1Wo treatments at monthly intervals resulted in near normal lingulae subsegments, as shown in this photograph. Death occurred from liver metastasis not associated with further chest infection. FIGURE
Lobar and Segmental Malignant Lesions There was a total of29lesions in 27 patients localized to lobar and segmental sites (Fig 3). The most frequently associated condition was infection, ie, postob422
structive pneumonia in 18, and lung abscess in two. There were seven patients with significant hemoptysis with the bleeding site localized to the surface of a lobar or segmental malignancy. Results were excellent in 19 (70 percent), good in five (19 percent), (excellent+ good= 89 percent), and poor in three (11 percent). There were three serious episodes of laser-induced hemorrhage from what appeared to be superficial bronchial arteries or tumor neovascularization. Though temporarily life threatening, all three patients recovered without sequelae. There was a single pulmonary artery perfOration resulting in instantaneous death in a patient with endoscopic disease limited to the lingula. The only other complication was a postlaser-treatment pneumonia in a previously uninvolved pulmonary segment which responded to conventional treatment. Six of seven patients with significant hemoptysis had no further hemorrhage after a single laser photocoagulation procedure. When the site of bleeding was easily accessible and Was, indeed, originating from the surface of an intrabronchial malignancy, instant control of
Table 1-Maligraant Laiona Residual Location
rl
Primary Assoc
Condition
Patient
SeJIAge
Lesion
I
7
M/54 M/76 M/81 M/68 M/46 M/61 M/63
RMB RLL LUL LUL LUL RUL RUULUL
8 9 10 ll 1.2 13 14 15 16
F/61 M/76 F/65 M/59 M/65 M/60 M/64 M/66 M/55
17 18 19 20 21 22
Previous Therapy
None R
75 100 75 100 100
1/30(
30 25 25 50 25 30
Pn. resolwd •Rx liilure Pn. resolwd Rx liilure
Obst Pn. Obst Pn.
RIC None
100 100
None Surg.
111.41 1/0.11
50 25
Pn. resolwd Pn. resolved
LUL
Hemop.
None
80
None
310.41
0
M/64
RMB
OOFJPn.
RIC
100
None
3119K
20
M/68 M/63 M/53 M/65 M/52 M/72 M/67 M/23 M/67 M/62 M/64 M/81
LLL
Hemop. Pn. Hemop. Pn. Hemop. Pn. Pn. DOE Pn.IDOE Pn. Pn.IDOE Pn.
R RIC None R Laser R (larynx) None SIRIC None None RIC None
60 50 15 100 20
None
RLL T RMB T RLLILLL RUL RMBILMB RMB RLL RMBILMB Lingula
110.6K 314.5( 31301
60 0 0 20 0 10 40 SIW50110 15 20 15
None None None
23
24
M/66 M/56
LUL LUL
25
M/80
26
rr
38
D-4 mo. (Prog Dis) A-7 mo. A-12 mo. D-1 mo. (Prog Dis) A-ll mo. D-1 mo. brain mebl PD A-10 mo. A-7 mo. wlleft pneumonectomy D-7 mo. rup abel
111.21 W0.41 W0.51 110.1K W0.7I
Hemop. Obst Avs. Obst Pn. DOE/Pn. Obst Pn. DOEIPn.
~
Hemorr. resolved
R R R None R R
LUL RLL RUL LMB RLL RMB
34
D-4 mo. (cor art mets) A-10 mo. ~ mo. (Prog Dis) A-ll mo. A-12 mo. D-2 mo. (MI) A-i mo.
0 25 75 25 0 0 25 10 30
M/56 M/64 M/59 M/63 M/66 M/66
35 36
DOEIPn. resolwd Pn.resolwd Hemop. resolved Pn. resolwd Pn. resolwd Hemop. resolwd Hemop. resolwd (BAB) Pn. 6: Abs. resolwd Pn. resolwd (BAB) •Rx liilure Pn. resolwd (BAB) Pn. resolved Pn.resolved Pn. resolved Hemorr. resolwd DOFJPn. resolwd
41201 51251 110.6( 51201 fil301 &140( W1.61 &1201 51321
R None
29
Current Status
R R None None None R None None R
Obst Pn/Abs Obst Pn. Obst Pn. Obst Pn. Obst Pn. Obst Pn. Obst Pn. Hemop. DOE/Pn/Cougb
30 31 32 33
Final Outcome
0 0 30 0 0 40 20
RUL RUL LUL LUL LUL LUL LUL RLL RMB
28
( )
5115( f/61 11111 110.61 4/20( 110.41 41381
R None R R None None None
6
.
'Jioeatment
None R None None R None R
DOE/Pn. Obst Pn. Hemop. Obst Pn. Obst Pn. Hemop. Hemop.
2 3 4 5
Subse- No. 'Jioeatmenbl quent Total Joules Initially Therapy Used
.. obst
Airway Obst Last Laser
R R None R R None
100 75 100 100 100 90 90
75 100
A-10 mo. D-ll mo. (Prog Dis) D-10 mo. (Prog Dis) D-10 mo. (Prog Dis) D-9 (Prog Dis) A..Smo. A-4 mo. D-12 mo. (Prog Dis) D-4 mo. Pmg Cal
bleed
T (liacbea) R (Radiation)
K (10.e3) Abs (Abscess)
S (Surgery)
D (Dead) A (Alive)
c (Chemotherapy)
c
95
100 100 100 100 60 40
c
90
90
100 l()()/8(W50
c
None R None R R None
c
100 60
R
90
c
100
None
Pmg Dis (Progressive Disease)
M1 RMB RLL
(Myocardiallnlirction) (Right Main Bronchus) (Right Lower Lobe)
bleeding could be easily effected (Fig 5). Once an intrabronchial mapping technique was developed, blind lobar or segmental obstructions were not treated unless the postobstructive bronchial remnant could be easily localized or unless the fOrceps would pass easily through the tumor distally into an obvious patent bronchial remnant. There were no
1/26(
110.81 110.8( W0.61 W28K 11161 110.6( 11381 110.71
RUL (Right Upper Lobe) LUL (Left Upper Lobe) LMB (Left Main Bronchus) LLL (Uit Lower Lobe) BAB (Broncbial Artery Bleed)
Abs. resolved
!Jemop'I.esion
resolved Laser death sec. Mlhemorr. Hemorr. resolved Pn. resolved
J...esi9n smaller
Pn. resolved Hemop. resolwd Pn. resolved Pn. resolwd DOE impTOYed Pn. resolwd Pn. resolved DOE resolved Fa!al bemorr. (laser death) DOE
aneury
D-2 mo. nwslbleed D-3 mo. (Prog Dis) D-4 mo. (Prog Dis) A-4 mo. A-2 mo. A-2 mo. A-2 mo. A-3mo. A-2mo. A-2mo. A-3mo. A-1 mo. D (Dyspnea Oil Exertion)
Obst Pn. (Obstructi\'1! Pneumonia)
Hemop. (Hemoptysis) Ca (Carcinoma)
complications when these guidelines were fOllowed in segmental and lobar lesions. Though ten of these 27 patients have subsequently died, only two had significant morbidity related to recurrent airway obstruction. Relief of obstructive pneumonia and resolution of atelectasis could be sustained fur several months with laser phototherapy CHEST I 87 I 4 I APRIL. 1985
423
Table !-Benign Lesioru* 1YPe
Patient
Sex/Age
1
F/68
2
F/59
3
M/64
4
F/85
5
Fns
6
M/37
1
Fno
and Location of Lesion Necrotizing granulomatrachea Granulation tissue lingulae Adenoma (carcinoid) Adenoma (carcinoid) LUL Granulation tissue RUL Subglottic stenosis, web-type trachea Subglottic stenosis diffuse typetrachea
Percent Presenting Symptoms
No. '&eatment/
Airway Obstruction
Total
Final Outcome
Current Status
BefOre Laser
After Laser
Joules Used
75
25
310.91(
DOE resolved
A-9mo
100
25
310.91(
Hemop resolved
A-13mo
DOE/Hemop
75
0
211.61(
A-12mo
Hemop
20
0
110.51(
DOE/Hemop resolved Hemop resolved
Cough/Pn
50
10
111.41(
DOE
85
10
4/401(
DOE
90
20
31401(
DOE
Hemop
Cough/Pn resolved DOE resolved
DOE resolved
A-ll mo
A-12 mo A-13 mo
A-4mo
•see 'lllble 1 fOr abbreviations. as the only treatment used in this group (Fig 6). Benign Lesions 'Ii'eatment of benign lesions proved to be very gratifying. Results were excellent in every case. There were no complications in this group (Table 2). Both bronchial adenomas reported in this series were relatively small and responded completely to laser thermal necrosis. These lesions tended to involute readily with relatively small total laser energy required. Intraoperative hemorrhage was much less of a problem than with carcinomas of the same size. The fOllow-up period is too short to judge rate or extent of recurrence, though neither lesion has recurred at six and eight months, respectively. Granulation tissue, on the other hand, hemorrhaged more than comparable obstructions by carcinomas. This bleeding resulted in prolonged treatment sessions and tended to occur in spite of numerous preventive laser maneuvers. The final outcome, however, was excellent. The web-type subglottic stenosis in this series responded in an excellent fashion to laser thermal necrosis. Bleeding was minimal because of the avascular composition; however, maximum vaporizing setting was required, and total laser energy requirement was large. DISCUSSION
The majority of the patients in this series were derived from those routinely encountered in a non-
medical center based, private pulmonary specialty practice. The lesions fur palliation in this group are similar to those seen daily by most practicing pulmonary specialists. The hospital stay was two days or less fur 34 of the 45 patients. The total cost to the patient was much less than surgery and comparable to or less than for radiation or chemotherapy. The results of palliation were instant, and in many cases, lasting in relative terms. The physician time spent was not excessive once experience was gained. Infection distal to an obstructed bronchus was our most frequent indication fur treatment in lobar and segmental disease. In each case, the clinical course had failed to resolve or had recurred promptly in spite of maximal conventional therapy. Resolution of infection occurred promptly fOllowing laser phototherapy, if tumor perfOration were effected. There was no evidence that edema or other factors associated with laser phototherapy adversely affected outcome. To the contrary, prompt defervescence of fever and clinical improvement were the rule. The almost universally poor outcome of lung abscess distal to an unresectable obstructing carcinoma is well documented. Ill In both lung abscesses in this series, abscess drainage occurred intraoperatively, and the subsequent clinical course was that of a nonobstructed lung abscess. Laser phototherapy was also used to facilitate drainage of an obstructing pneumonia with associated septic shock in one patient who subsequently underwent successful left pneumonectomy (case 24, Table 1). Nd-VAG "-'ll8elment ollntrablonc:hlal L.eelona (Joyner et Ill)
It was frequently necessary to perfOrm at least a single bronchoscopic procedure three to five days after laser therapy to remove obstructing debris, even when the treated segment was completely patent at the conclusion of the initial laser treatment. This aspect of treatment was greatly facilitated by the use of Fogarty arterial embolectomy catheters. Once debridement of the visible particulate matter with forceps was complete, No. 4 to No. 6 Fogarty arterial embolectomy catheters were advanced distally several centimeters into the previously obstructed segment using the large channel flexible fiberscope. Dilute Renografin in saline was then used to inflate the balloon gently. The catheter was then slowly withdrawn with successive balloon inflations and deflations proximally. This resulted in both removal of distal debris and segmental dilatation to improve subsequent patency. Because of the dilute nature of the Renografin, rapid alveolarization frequently occurred when used intraoperatively via needle injection. This led to two unique problems. On some occasions, a definite bronchus was never visualized due to the rapid silhouetting effect of the alveolarized contrast material (Fig 2). A segmental alveologram, however, proved to be equally as safe a marker as actual visualization of the postobstructed bronchus, ie, safe perfOration was always possible ifa segmental alveologram corresponding to the appropriate segmental anatomy were used as evidence of bronchial perfOration with the transbronchial needle. The second problem was due to persistence of the alveolarized Renografin for 24 to 48 hours after treatment. This resulted in a gas exchange abnormality similar to an equal volume pneumonia. In this setting, Dionosil was dense enough to allow for adequate bronchograms regardless of the amount of renografin previously used. There was no untoward effect from the subsequent use of laser, even when small quantities of Renografin or dionosil were visible in the treatment field. This technique greatly improved our ability to penetrate lobar and segmental obstructing lesions safely. In attempting to locate the postobstructive remnant, one would occasionally see direct injections of Renografin into pulmonary arteries in the same vicinity at disconcertingly short distances from the treatment site. The use oflaser blindly in this setting would be unacceptably treacherous. Pulmonary hemorrhage proved to be the only major complication in this series. There were three distinct types of hemorrhage, each with a different prognosis. Hemorrhage from the substances of an intrabronchial tumor never proved to be a major problem. Though temporarily brisk, the application of topical epinephrine plus dispatch in the use of laser coagulation controlled and prevented airway compromise from this type ofhemorrhage. Bronchial artery hemorrhage was a somewhat unex-
pected complication and truly tested the mettle of the endoscopist. The three such episodes occurred while treating less extensive endoscopic disease at the lobar level. Relatively low power settings were employed at the time ofhemorrhage (30 to 50 W), and even in retrospect, there was nothing unique about intent or method of therapy to forebode impending hemorrhage. This phenomenon is not observed with repeat laser hits to the normal bronchial wall at various power settings in experimental animals13.14 and may be uniquely related to the relatively superficial location and longitudinal course of the human bronchial aJ'o tery. 15 Because of the rate of blood show, it was impossible to consider laser photocoagulation to stop this type ofhemorrhage. In each case, the hemorrhage ceased spontaneously after two to five minutes. Considerable effurt was then required to re-establish adequate ventilation and clear the airway of clots. All three patients survived the hemorrhage without further bleeding, even after several months. Pulmonary artery perfOration was the third type of hemorrhage encountered. Both episodes of pulmonary artery perfOration in this series occurred while treating the bronchial wall with low vaporizing power settings (40 to 60 W) in an area not previously documented fluoroscopically with contrast to align directly with an obstructed bronchial remnant. The intraoperative use of contrast material should further minimize this risk. With the use of a real time intrabronchial mapping technique, we have developed the following treatment scheme for intrabronchiallesions:
Central Obstructions (Trachea ofMainstem Bronchus) Vaporizing power settings were safe in our hands when directed down the known channel ofa major central airway. The axial length of tumor involvement and the condition of the distal bronchus and lung can be assessed to some degree by the initial use of contrast (renografin or dilute Dionosil) before laser treatment. Sixty to 100 W of power at 0.5 to 1.0 second pulses produce rapid photovaporization with the establishment of a central lumen. We elect to terminate the first laser treatment once the airway caliber is 60 to 70 pe~ cent of normal. Four to seven days later, the second laser treatment is given. It is easier at this time, after debridement, to determine more prudently the extent of viable cancer remaining. Further widening of the airway caliber is then straightforward by careful ci~ cumferential use of laser photovaporization. In mainstem lesions, no attempt is made to perfOrate lobar segments unless clear visualization ofdistal bronchial rami is certain with the intraoperative use of contrast as described (Fig 7). The only anatomic situation in which laser treatment was consistently of no benefit was that where the CHEST I 87 I 4 I APRIL, 11186
421
cancer process occupied the entire axial length of the main bronchus. Even after successfully removing the majority of the intrabronchial component of cancer, unless one could then visualize the origin of several normal appearing distal bronchial segments beyond the carcinoma, no significant palliation resulted. This was true even if two to three distal segments were temporarily patent to the passage of biopsy forceps and/or contrast.
treatment. A single debridement session is usually adequate. We would suggest that a No. 6 to No. 7 Fogarty catheter be placed routinely in the proximal main bronchus befOre proceeding with laser treatment in segmental disease. In the event of sudden bronchial artery hemorrhage, immediate isolation of the bleeding segment or bronchus is insured by balloon inflation even ifdirect visualization is obscured by blood.
Lobar and Segmental Lesions
Laser Treatment Concomitant with Radiation Therapy
At the lobar level, the initial treatment plan is determined by the extent of lobar bronchial obstruction. H a portion of the lobar bronchus is patent, there is little difficulty in cancer demarcation. 'freatment with relatively low laser power settings (25 to 40 W) can be used to extend safely the treatment field to the segmental level. If the lobar bronchus is completely obstructed, an intrabronchial mapping procedure is employed initially to perforate the cancer. If this cannot be done with the biopsy furceps, then the transbronchial needle is used. Employing this technique, again treatment can be extended to the segmental level with 25 to 40 W delivered in .5 to 1.0 second pulses. To manage residual airway obstruction at the segmental level, the transbronchial needle with contrast is employed, and no further treatment is given unless distal subsegments are clearly demonstrated fluoroscopically. In the case of distal infection, every effi>rt is made to open all major segments involved roentgenographically with the infectious process at the time of the first treatment. We round it safe to use vaporizing laser power settings to perforate segmental obstructions (60 to 80 W), once distal rami were located. Patency of the more distal subsegments was then documented by either passing biopsy furceps with fluoroscopic visualization and/or by the use of segmental Dionosil bronchography (Fig 2). At the time of initial laser treatment, obstructed main segments were opened widely to a "normal" caliber such that distal subsegments were easily visible. No attempt was made to vaporize any cancer component lying between bronchial orifices at the segmental or subsegmentallevel. 'freatment was applied only to further increase the caliber of visible narrowed air channels. The charred, freshly laser treated bronchial surface is rapidly coated with mucus and tumor debris. One frequently finds well-fOrmed mucus plugs and laser debris completely occluding the airway at the treatment site two to fuur days later. This material is tightly adherent to the lasered surface, and prolonged bronchial obstruction with recurrence of obstructive symptoms occur unless debridement is done. This phenomenon occurred so frequently that we routinely repeat bronchoscopy fuur to seven days after initial laser
This protocol has been extended to allow fur the combination of laser therapy and conventional radiation therapy in inoperable lung cancer patients. Patients who are not judged to need urgent, immediate laser palliation are entered into a double blind protocol. In one group, laser is used initially to eliminate as much of the intrabronchial cancer component as can be done safely. Conventional radiation therapy is then given to the same site and to other areas as judged necessary by the radiotherapist. One or two months fOllowing the completion of radiation therapy, bronchoscopy is repeated and the initial treatment site re-
FIGURE 8. Apparent synergistic effect of laser and radiation. (Upper). A 74-yeaN)ld loWman had right main bronchus completely occluded (squamous cell carcinoma). View of main carina with an open left bronchus and no visible right bronchus. An intraoperative bronchogram was used to locate the right main bronchial channel which also demonstrated uninvolved RULand RLL distally (ie, short axial length of malignant process). Laser photovaporization was used to effect perfOration into right main bronchus with immediate relief of severe dyspnea. (Lower). View of main carina three months later fOllowing radiotherapy and the single laser treatment. Patient is still alive 13 months later with a single recurrent nodule on the right lateral tracheal wall successfully treated with laser.
examined and rephotographed. The second group receives only radiation with repeat intrabronchial examination at the same time interval. It is our intent to determine if initial laser treatment enhances the intrabronchial effect of radiation therapy, and to determine if there are fewer subsequent intrabronchial airway complications with combination therapy (Fig 8). Early results suggest combination therapy may have great merit. ACKNOWLEDGMENT: The invaluable assistance of Gloria Wheeler in the preparation ofthis manuscript is deeply appreciated. The support of the Sisters and Sur&ical Staff at Sl Francis Medical Center is also greatly appreciated. IDustrative support by Mr. Henry Saam was invaluable. REFERENCES 1 Carr Dl; Rosenow III. Bronchogenic carcinoma. Basics of RD. 1977; 5:5 2 Ferguson TB. Symposium on lung cancer. Chest 1971; 624-650 3 Perez C1; Corti DL, Vincent RG. Patterns of tumor recurrence after definitive irradiation of inoperable non-oat cell carcinoma of the lung. Int J Radiat Oncol Bioi Phys 1980; 6:987-94 4 Fontana R. Early diagnosis of lung cancer. Am Rev Respir Dis
1977; 116:399-402 5 Sanderson DR, Fontana RS, Woolner LB, Bematz PE, Payne
WS. Bronchoscopic localization of radiographically occult lung cancer. Chest 1974; 65:608-12 6 Doiron DR, Profio E, Vincent RG, Dougherty TJ. Fluorescence bronchoscopy tOr detection oflung cancer. Chest 1979; 76:27-32 7 Hayata Y, Kato H, Konab C, Ono J, 18kizawa N. Photoradiation in treatment of lung cancer. Chest 1982; 81:269-76 8 Dumon JF, Reboud E, Garbe L, Aucomte F. Merle B. 'lreatment of transbronchial lesions by laser photoresection. 1982;
81:278-84 9 McDougall JD, Cortese ED. Nd-YAG laser therapy of malignant airway obstructions: Mayo Clinic Prec 1983; 58:35-49 10 Toty L, Personne C, Colchen A. Voursch G. Bronchoscopic management of tracheal lesions using the Nd-YAG laser. Thorax 1981; 36:175-78
11 Mountain CF. Lung cancer clinical diagnosis and treatment. New York: Grune & Stratton, 1977 12 Finegold SM. Lung abscess and necrotizing pneumonJa. In:
Fishman AP, Pulmonary disease and disorders. New York: McGraw Hill, 1980; 110:1202-08 13 Hayakawa K, Oho K, Yuji M. Photodynamic effects of laser surgery on the trachea and bronchi of mongrel dogs. Second World Congress tOr Bronchoscopy, Dusseldorf: W Ger, 1980; 74 14 Iwasaki M, Konishi 1; Murata N, Maruyama W. Wada 1; et al. Effects of argon and YAG lasers on canine esophagus. Proc Third lnt Cong Laser Surg III, 1979; 86-90 15 Cortese D, McDougall Jr. Will laser therapy help your lung cancer patient. J Resp Dis 1984; 45-55
CHEST I 87 I 4 I APRIL, 11186
4rt
malignant and seven with benign disease) with intrabronchiallesions using the neodymium-YAG laser via the fteDble &beroptic bronchoscope. Multiple treatment sessions were used with treatment intervals varying from four days to four weeks. Additional debridement procedures were also necessary in select cases. (There was total of 109 treatments in 45 patients~ Over 70 percent (81 of 109) of all treatments were clone without intubation and with sedation techniques, and topical lidocaine application similar to that used in standard &beroptic bronchoscopy. Laser treatment of the less edenme segmental lesion resulted in very meaning£ul palliation and laser therapy need not be reserved for extensive central disease only. In our judgment, this can most safely be done ith the exception of chemotherapy for oat cell W carcinoma, the outcome in the treatment oflung cancer has not appreciably improved in over two decades. 1 From the day of diagnosis, 75 percent of all patients are inoperable and one-half of the remaining 25 percent will develop progressive disease in spite of For editorial comment, see page 416 surgery...3 Vigorous early detection programs have raised as many gloomy questions regarding health care cost, continued need for extensive resection, multicentricity, and new metachronous primaries as problems solved. u A practical hematoporphyrin marker with subsequent therapeutic potential is not yet available and would likely also have only limited potential. 8 •7 The present reality remains that "palliation is the only game in town" for over 80 percent of all lung cancer victims. To date, endoscopic neodymium-YAG laser phototherapy has been limited primarily to central malignant lesions in the trachea or main bronchi in the •From the St. Francis Hospital, Monroe, Louisiana.
t Assistant Professor of Medicine, Louisiana State University School
of Medicine, S~rt. Manuscript received June 26; revision accepted November 2. Reprint requem: Dr. Joyner, 401 Hall Street, Monroe, Louidana
71201
418
with a "real time, intrabronchial mapping technique." The Mill Rose (W-22-13) transbronchial needle was used intraoperatively to perforate blind intrabronchial obstructions. Renogra&n (Ren-M-60 M) was then band injected to locate and 8uoroscopically visualize the postobstructive bronchial remnant. Precise laser penetration into the postobstructive remnant was then possible by following the same pathway. 'l1lis technique greatly extended our ability to safely perforate segmental and even blind central obstructing lesioos. In our judgment, without a "real time intrabronchial mapping technique,,. wscular and bronchial perforations would be more likely when treating the more distal lobar and segmental obstructions.
relatively advanced state. a.ro In fact, most lung cancers occur in the lobar or proximal segmental bronchi rather than occur centrally. 8 •11 It is very difficult to gain insight from available material regarding treatment techniques, ie, laser energy settings, operative time, number of treatments required, optimal time between retreatments, hazards, etc. In our experience, many lobar and segmental lesions which could be visualized with the flexible fiberoptic bronchoscope could not be effected by laser therapy because of the subsequent loss of degree of flexion with passage of the stiff quartz light guides now available. By "over tightening" of the cable of the fiberscope (BITR Olympus), we were able to treat even upper lobe apical segmental lesions completely. This report details the results, complications, and techniques used in the neodymium-VAG laser phototherapy of 38 patients with inoperable lung cancer, two-thirds of whom had endoscopic disease limited to lobar or segmental sites. In each case, an associated condition existed that in our judgment could best be palliated with laser phototherapy. The results of seven benign cases are also included. MATERIALS AND METHODS
All patients in this series were evaluated by the pulmonary section
guide. The transbronchial aspirating retractable biopsy needle (Wang model W-222-13) was used fur intraoperative bronchograms. Renografin (Reno-M-60) was used as contrast when the transbronchial needle was employed intraoperatively, and dilute Dionosil was used fur more detailed bronchial visualization once an obstruction had been perfOrated. A Phillips fluoroscopic C-arm was used intraoperatively fur real time fluoroscopy on command. The C-arm viewing monitor hook-up was altered so that the real time fluo-
FIGURE 1. Diagram of real time intrabronchial mapping technique. (Upper). Under direct vision, the Wang transbronchial needle is advanced at suspected site ofbronchial communication across the intrabronchial obstructing process. With the stilet in place the depth of initial needle penetration is varied with anticipated axial length of intrabronchial obstruction. (Lower). Small amounts ofRenografin is hand injected, typically under considerable pressure, until the postobstructive bronchial remnant is localized. Laser penetration fOllowing the same pathway is then straightfOrward. of the Northeast Medical Specialty Clinic between October of 1982 and February of 1984. With the exception of one patient, all cancer victims were classified as non.resectable surgically by extent of disease or due to poor overall general health considerations. A single patient received laser phototherapy fur drainage of a pneumonia prior to subsequent successful pneumonectomy. This was an MMB (Messerschmitt-Bolkow-Bohm) sponsored FDA protocol approved study conducted at St. Francis Medical Center in Monroe, Louisiana. The Institutional Review Committee of this institution also gave approval and patients were fully infOrmed of the nature, intent, and risk factors involved. An extensive FDA approved infOrmed consent furm was signed by each patient. Equipment
Laser treatments were perfOrmed in an operating room designed exclusively fur laser work. Patients who \vere not intubated were given supplemental oxygen via a 25 percent to 45 percent Ventimask altered to accommodate transnasal fiberoptic bronchoscopy. A fiberscope (B1TR Olympus) was modified by "over tightening" the flexion cable so that a flexion of 180 degrees was possible with the laser quartz light guide in place. The fiberscope was used fur endoscopic photography and the microvideo camera (Circon) was used fur video documentation befure and after all treatments. The neodymium yttrium alUininum garnet (YAG) (Endolase, model K621101) and quartz light guide were used as a source of laser energy. Helium, due to its low potential fur supporting combustion, was used as the gas source in the treatment field via the quartz light
FIGURE 2. Injection sequence as seen on the C-arm fluoroscopy intraoperatively with "alveologram effect." (Top). Wang needle (BmtJU arrow) used to hand inject Renografin into anterior segment of LUL beyond the obstructing LUL neoplasm. LUL alveologram produced with no defi{lite bronchus visualized. (Center) . After laser crater developed into anterior segment ofLUL, repeat Wang needle injection shows somewhat indistinct (large arrow) outline of proximal postobstructive bronchus (the lingulae bronchogram below is a result of retrograde flow of renografin into the uninvolved lingulae segment). (Bottom). LUL anterior segment "Dionosil bronchogram" taken at debridement session lOur days later-LUL anterior segment opened widely with laser and in excellent condition in spite of previous obstructing carcinoma. CHEST I 87 I 4 I APRIL, 1985
419
TYPI OF LISION
PATIENTS PIBCENT
Squamou Cell
28
75
Luoe Cell
4
11
O.tC.ll
3
1
Metulatic and Othero
3
1
DISTRIBUTION OF LESIONS
Bronch...
.NUMBER
PIBCENT
Trachea and Main Stem
14
33
Sevemental
29
67
FIGURE 3. Intrabronchiallocation of malignant lesions and cell types. roscopic image was displayed on the VCR as well as on the standard C-arm monitor. This allowed fOr a permanent three-fOurths-inch VCR record of all fluoroscopic procedures. The technique used fOr real time intrabronchial mapping was as follows: Once a blind intrabronchial obstruction was encountered, the transbronchial needle was used to perfOrate the tumor (Fig 1). A few milliliters (2 to 10) of contrast were then hand injected while C-arm fluoroscopy allowed visualization. This procedure was repeated at different sites until the postobstructive bronchial lung remnant was found. The laser light guide was then immediately positioned at this site and an initial laser crater developed. The transbronchial needle was then passed through the crater to reconfirm an on-line course into the bronchial remnant before final laser penetration. Once laser perfOration was effected, a larger polyethylene catheter was advanced distally and dilute Dionosil was band injected. This resulted in a much higher quality segmental bronchogram which was used to access the condition of the postobstructive bronchus and to determine iffunctional lung tissue existed distally (Fig 2).
Photo Documentation of Lesion and Result Guidelines All lesions were photographed utilizing instant prints, 35 mm slides and rolling video. The degree of airway obstruction was then estimated based on pictorial review befOre and after each laser treatment. In each case, there was also a primary associated condition, ie, obstructive pneumonia, hemoptysis, atelectasis, dyspnea on exertion, etc, for which laser application had been selected (18ble I). Overall results were considered excellent if25 percent or less residual obstruction existed after final laser treatment plus the resolution of the primary associated condition. Results were considered good if greater than 25 percent residual obstruction was present, but there was still resolution of the primary associated condition. Results were considered poor if there was failure to influence the primary associated condition, regardless of the degree of residual airway obstruction. 7}n1e
of Anesthesia
Eighty-one of the 109 laser treatments were done with topical lidocaine anesthesia and sedation. Ten milliliters of 4 percent lidocaine was nebulized orally and an additional 5 to 10 ml placed directly into the larynx at the time of bronchoscopy. Glycopyrrolate (Robinul), 0.2 ml, and appropriate amounts ofdiazepam (Valium) and meperidine (Demerol) were given intravenously to maintain light sedation. Patients were still able to fOllow commands and cough when so instructed. Some patients complained later of the stench of burning tissue but experienced no other ill-effects. Oxygenation was supplemented with a Ventimask system. 1\venty-eight of106 treatments were given with general anesthesia and oral tracheal intubation. After sedation with diazepam, ketamine was used as a hypnotic and pancuronium bromide used to 420
produce paralysis. The lowest possible Fl<>t to maintain an arterial Po2 of65 or greater was given. At no time was the laser administered in an oxygen atmosphere greater than 40 percent. Arterial blood gas values were obtained frequently intraoperatively regardless of the anesthesia method used. Ventilation was temporarily a problem only in the three cases of lase!'-induced massive hemorrhage who subsequently recovered. In each case, Pco2 levels in the 70 to 90 range with acute respiratory acidosis occurred immediately fOllowing hemorrhage. As aspirated blood clots were removed endoscopically, the Pco2 levels reverted to normal rapidly. 1\w of the three patients were intubated at the time of hemorrhage. All treatments were perfOrmed in a setting where anesthesia and thoracic surgical consultation were instantly available ifneeded.
REsuus Central Malignant Lesions
There was a total ofl4lesions in 11 patients in either the trachea or mainstem bronchi (Fig 3). In all of those where the degree of obstruction was critical, the primary associated condition was dyspnea on exertion. Several also had distal infections (Table 1). Results were excellent in five, good in fum; and poor in two (excellent+ good= 80 percent). All patients with associated mediastinal disease at the time of treatment died within fuur months of laser phototherapy from progressive disease (8 of 11). The three patients with disease limited to the central airway without evidence of mediastinal metastasis had excellent long-term results. The endoscopic appearance and subsequent outcome was somewhat unexpected. Extensive submucosal disease resulting in complete airway obstruction responded to laser phototherapy and actually required less total laser energy than comparable intrabronchial tumors. Even when a submucosal process extended distally 5 to 8 em, a completely patent airway was possible with repeat laser treatments (Fig 4). Frequent debridement was mandatory fOllowing treatment of this type of submucosal disease. Within 24 to 48 hours, the treatment site was filled with a gel of necrotic tumor coagulum. This material could be easily cleared with suction; however, reaccumulation for several days occurred as necrotic tumor continued to Nd-VAG L.u« Thlalment ollntrabronchlall.aslons
(Joyner et Ill)
FIGURE 4. Demonstration of the ability to successfully treat a submucosal cancer process obstructing the right main bronchus. (Top). A 56-year-old man with a pinpoint orifice to the right main stem bronchus due to a recurrent squamous cell carcinoma after maximum radiation therapy. Endoscopically, all disease is submucosal; however, laser phototherapy was still given to an area extending several millimeters circumferentially from this pinpoint opening. (Center) . Four days later, the treatment site is covered with a gelatinous material which can be easily removed with suction via the flexible fiberscope. Three additional laser treatments are given after debridement at weekly intervals. General anesthesia was used only fur the initial treatment session. (Bottom). Final result is a widely patent right main bronchus with associated resolution of right lung atelectasis. Death occurred five months later from cardiac metastasis without recurrent atelectasis.
weep from the laser-affected bronchial walls. Repeat debridement was therefore required. Large, bulky central bronchial tumors were extremely demanding with regard to physician time required, and total laser energy necessary to relieve the obstruction. Extensive endobronchial debridement of charred particles with forceps also extended the time required for treatment. Endotracheal in tuba-
FIGURE 5. Demonstration of both the abi1ity to manage pulmonary hemorrhage with the laser and the rationale for treating "asymptomatic" segmental lesions in select cases. (Upper). A small nodular squamous cell carcinoma with surrounding hemorrhage arising from the apical posterior segment of the left upper lobe. A normal appearing lingulae segment is seen below. This lesion occurred as the only manifestation of carcinoma in an 82-year-old man with massive hemoptysis, This lesion could not be treated with the standard BlTR fiberscope due to the angulation required. Using the BlTR with the "overtightened cable," photocoagulation was used to promptly control hemorrhage (a ten-minute procedure without general anesthesia). Due to severe chronic congestive heart feai1ure, surgery was not a viable consideration and this patient refused external radiation. Laser photovaporization was used one week later to ablate all visible cancer and create a deep crater into the apical posterior segment. Four months later, a third laser treatment was given to ablate a single small recurrent nodule. (Lower). This photograph shows treatment site 11 months later-there is no visible cancer and all biopsies and brushings are negative. Laser therapy was the only treatment given. Death occurred three months later from a ruptured aortic aneurysm-autopsy not granted.
tion was routinely used for this type of lesion because of time considerations and because of the need frequently to change fiberscopes fur debridement purposes. There was a single complication in the central malignant obstructive group. Pulmonary artery perfOration occurred during a fOurth treatment session in a patient with extensive right main bronchial obstruction. This oecurred before the development of an adequate intrabronchial mapping technique. CHEST I 87 I 4 I APRIL, 1985
421
7. Renogra&n bronchogram of postobstructive bronchial remnant. (Upper) . Wang needle (arrow) used to perfOrate inferior lingulae segment "blind obstruction" (see photos Case 1). Bronchogram as seen on C-Arm fluoroscopy early in hand injection sequence. (Lower). Bronchial outline becomes quite obvious later in injection sequence. There is no alveolarization (even after several minutes) of Renografin in this case. Postobstructive dilatation of lingulae bronchus is not as severe as these magnified photos suggest. FIGURE
6. Value of laser treatment in recurrent segmental obstructions of the lingulae segment of the LUL after prior maximum radiation treatment. (Thp). A 62-year-old man with squamous cell carcinoma occluding the left upper division with an obstructed left upper lobe and lingula. A positive main carinallymph node needle aspirate prevented surgical consideration. Initial treatment consisted of laser photovaporization of 80 percent of visible intrabronchial cancer fOllowed by external radiation (6000 rads). Pneumonia and atelectasis of the LUL and lingulae initially resolved. (Center). Six months later, there is now "blind obstruction" of both lingulae subsegments with a patent LUL above. The chest x-ray film shows an abscess in the lingulae associated with a 13.5 kg weight loss and prolonged symptoms of infection. (Bottom) . The Wang needle Renografin bronchogram technique was used to successfully locate both lingulae subsegments with successful laser perfOration and drainage of a bacterial abscess. There is a marked clinical response, all weight is regained, and the patients functional status is excellent fOr an additional year. 1Wo treatments at monthly intervals resulted in near normal lingulae subsegments, as shown in this photograph. Death occurred from liver metastasis not associated with further chest infection. FIGURE
Lobar and Segmental Malignant Lesions There was a total of29lesions in 27 patients localized to lobar and segmental sites (Fig 3). The most frequently associated condition was infection, ie, postob422
structive pneumonia in 18, and lung abscess in two. There were seven patients with significant hemoptysis with the bleeding site localized to the surface of a lobar or segmental malignancy. Results were excellent in 19 (70 percent), good in five (19 percent), (excellent+ good= 89 percent), and poor in three (11 percent). There were three serious episodes of laser-induced hemorrhage from what appeared to be superficial bronchial arteries or tumor neovascularization. Though temporarily life threatening, all three patients recovered without sequelae. There was a single pulmonary artery perfOration resulting in instantaneous death in a patient with endoscopic disease limited to the lingula. The only other complication was a postlaser-treatment pneumonia in a previously uninvolved pulmonary segment which responded to conventional treatment. Six of seven patients with significant hemoptysis had no further hemorrhage after a single laser photocoagulation procedure. When the site of bleeding was easily accessible and Was, indeed, originating from the surface of an intrabronchial malignancy, instant control of
Table 1-Maligraant Laiona Residual Location
rl
Primary Assoc
Condition
Patient
SeJIAge
Lesion
I
7
M/54 M/76 M/81 M/68 M/46 M/61 M/63
RMB RLL LUL LUL LUL RUL RUULUL
8 9 10 ll 1.2 13 14 15 16
F/61 M/76 F/65 M/59 M/65 M/60 M/64 M/66 M/55
17 18 19 20 21 22
Previous Therapy
None R
75 100 75 100 100
1/30(
30 25 25 50 25 30
Pn. resolwd •Rx liilure Pn. resolwd Rx liilure
Obst Pn. Obst Pn.
RIC None
100 100
None Surg.
111.41 1/0.11
50 25
Pn. resolwd Pn. resolved
LUL
Hemop.
None
80
None
310.41
0
M/64
RMB
OOFJPn.
RIC
100
None
3119K
20
M/68 M/63 M/53 M/65 M/52 M/72 M/67 M/23 M/67 M/62 M/64 M/81
LLL
Hemop. Pn. Hemop. Pn. Hemop. Pn. Pn. DOE Pn.IDOE Pn. Pn.IDOE Pn.
R RIC None R Laser R (larynx) None SIRIC None None RIC None
60 50 15 100 20
None
RLL T RMB T RLLILLL RUL RMBILMB RMB RLL RMBILMB Lingula
110.6K 314.5( 31301
60 0 0 20 0 10 40 SIW50110 15 20 15
None None None
23
24
M/66 M/56
LUL LUL
25
M/80
26
rr
38
D-4 mo. (Prog Dis) A-7 mo. A-12 mo. D-1 mo. (Prog Dis) A-ll mo. D-1 mo. brain mebl PD A-10 mo. A-7 mo. wlleft pneumonectomy D-7 mo. rup abel
111.21 W0.41 W0.51 110.1K W0.7I
Hemop. Obst Avs. Obst Pn. DOE/Pn. Obst Pn. DOEIPn.
~
Hemorr. resolved
R R R None R R
LUL RLL RUL LMB RLL RMB
34
D-4 mo. (cor art mets) A-10 mo. ~ mo. (Prog Dis) A-ll mo. A-12 mo. D-2 mo. (MI) A-i mo.
0 25 75 25 0 0 25 10 30
M/56 M/64 M/59 M/63 M/66 M/66
35 36
DOEIPn. resolwd Pn.resolwd Hemop. resolved Pn. resolwd Pn. resolwd Hemop. resolwd Hemop. resolwd (BAB) Pn. 6: Abs. resolwd Pn. resolwd (BAB) •Rx liilure Pn. resolwd (BAB) Pn. resolved Pn.resolved Pn. resolved Hemorr. resolwd DOFJPn. resolwd
41201 51251 110.6( 51201 fil301 &140( W1.61 &1201 51321
R None
29
Current Status
R R None None None R None None R
Obst Pn/Abs Obst Pn. Obst Pn. Obst Pn. Obst Pn. Obst Pn. Obst Pn. Hemop. DOE/Pn/Cougb
30 31 32 33
Final Outcome
0 0 30 0 0 40 20
RUL RUL LUL LUL LUL LUL LUL RLL RMB
28
( )
5115( f/61 11111 110.61 4/20( 110.41 41381
R None R R None None None
6
.
'Jioeatment
None R None None R None R
DOE/Pn. Obst Pn. Hemop. Obst Pn. Obst Pn. Hemop. Hemop.
2 3 4 5
Subse- No. 'Jioeatmenbl quent Total Joules Initially Therapy Used
.. obst
Airway Obst Last Laser
R R None R R None
100 75 100 100 100 90 90
75 100
A-10 mo. D-ll mo. (Prog Dis) D-10 mo. (Prog Dis) D-10 mo. (Prog Dis) D-9 (Prog Dis) A..Smo. A-4 mo. D-12 mo. (Prog Dis) D-4 mo. Pmg Cal
bleed
T (liacbea) R (Radiation)
K (10.e3) Abs (Abscess)
S (Surgery)
D (Dead) A (Alive)
c (Chemotherapy)
c
95
100 100 100 100 60 40
c
90
90
100 l()()/8(W50
c
None R None R R None
c
100 60
R
90
c
100
None
Pmg Dis (Progressive Disease)
M1 RMB RLL
(Myocardiallnlirction) (Right Main Bronchus) (Right Lower Lobe)
bleeding could be easily effected (Fig 5). Once an intrabronchial mapping technique was developed, blind lobar or segmental obstructions were not treated unless the postobstructive bronchial remnant could be easily localized or unless the fOrceps would pass easily through the tumor distally into an obvious patent bronchial remnant. There were no
1/26(
110.81 110.8( W0.61 W28K 11161 110.6( 11381 110.71
RUL (Right Upper Lobe) LUL (Left Upper Lobe) LMB (Left Main Bronchus) LLL (Uit Lower Lobe) BAB (Broncbial Artery Bleed)
Abs. resolved
!Jemop'I.esion
resolved Laser death sec. Mlhemorr. Hemorr. resolved Pn. resolved
J...esi9n smaller
Pn. resolved Hemop. resolwd Pn. resolved Pn. resolwd DOE impTOYed Pn. resolwd Pn. resolved DOE resolved Fa!al bemorr. (laser death) DOE
aneury
D-2 mo. nwslbleed D-3 mo. (Prog Dis) D-4 mo. (Prog Dis) A-4 mo. A-2 mo. A-2 mo. A-2 mo. A-3mo. A-2mo. A-2mo. A-3mo. A-1 mo. D (Dyspnea Oil Exertion)
Obst Pn. (Obstructi\'1! Pneumonia)
Hemop. (Hemoptysis) Ca (Carcinoma)
complications when these guidelines were fOllowed in segmental and lobar lesions. Though ten of these 27 patients have subsequently died, only two had significant morbidity related to recurrent airway obstruction. Relief of obstructive pneumonia and resolution of atelectasis could be sustained fur several months with laser phototherapy CHEST I 87 I 4 I APRIL. 1985
423
Table !-Benign Lesioru* 1YPe
Patient
Sex/Age
1
F/68
2
F/59
3
M/64
4
F/85
5
Fns
6
M/37
1
Fno
and Location of Lesion Necrotizing granulomatrachea Granulation tissue lingulae Adenoma (carcinoid) Adenoma (carcinoid) LUL Granulation tissue RUL Subglottic stenosis, web-type trachea Subglottic stenosis diffuse typetrachea
Percent Presenting Symptoms
No. '&eatment/
Airway Obstruction
Total
Final Outcome
Current Status
BefOre Laser
After Laser
Joules Used
75
25
310.91(
DOE resolved
A-9mo
100
25
310.91(
Hemop resolved
A-13mo
DOE/Hemop
75
0
211.61(
A-12mo
Hemop
20
0
110.51(
DOE/Hemop resolved Hemop resolved
Cough/Pn
50
10
111.41(
DOE
85
10
4/401(
DOE
90
20
31401(
DOE
Hemop
Cough/Pn resolved DOE resolved
DOE resolved
A-ll mo
A-12 mo A-13 mo
A-4mo
•see 'lllble 1 fOr abbreviations. as the only treatment used in this group (Fig 6). Benign Lesions 'Ii'eatment of benign lesions proved to be very gratifying. Results were excellent in every case. There were no complications in this group (Table 2). Both bronchial adenomas reported in this series were relatively small and responded completely to laser thermal necrosis. These lesions tended to involute readily with relatively small total laser energy required. Intraoperative hemorrhage was much less of a problem than with carcinomas of the same size. The fOllow-up period is too short to judge rate or extent of recurrence, though neither lesion has recurred at six and eight months, respectively. Granulation tissue, on the other hand, hemorrhaged more than comparable obstructions by carcinomas. This bleeding resulted in prolonged treatment sessions and tended to occur in spite of numerous preventive laser maneuvers. The final outcome, however, was excellent. The web-type subglottic stenosis in this series responded in an excellent fashion to laser thermal necrosis. Bleeding was minimal because of the avascular composition; however, maximum vaporizing setting was required, and total laser energy requirement was large. DISCUSSION
The majority of the patients in this series were derived from those routinely encountered in a non-
medical center based, private pulmonary specialty practice. The lesions fur palliation in this group are similar to those seen daily by most practicing pulmonary specialists. The hospital stay was two days or less fur 34 of the 45 patients. The total cost to the patient was much less than surgery and comparable to or less than for radiation or chemotherapy. The results of palliation were instant, and in many cases, lasting in relative terms. The physician time spent was not excessive once experience was gained. Infection distal to an obstructed bronchus was our most frequent indication fur treatment in lobar and segmental disease. In each case, the clinical course had failed to resolve or had recurred promptly in spite of maximal conventional therapy. Resolution of infection occurred promptly fOllowing laser phototherapy, if tumor perfOration were effected. There was no evidence that edema or other factors associated with laser phototherapy adversely affected outcome. To the contrary, prompt defervescence of fever and clinical improvement were the rule. The almost universally poor outcome of lung abscess distal to an unresectable obstructing carcinoma is well documented. Ill In both lung abscesses in this series, abscess drainage occurred intraoperatively, and the subsequent clinical course was that of a nonobstructed lung abscess. Laser phototherapy was also used to facilitate drainage of an obstructing pneumonia with associated septic shock in one patient who subsequently underwent successful left pneumonectomy (case 24, Table 1). Nd-VAG "-'ll8elment ollntrablonc:hlal L.eelona (Joyner et Ill)
It was frequently necessary to perfOrm at least a single bronchoscopic procedure three to five days after laser therapy to remove obstructing debris, even when the treated segment was completely patent at the conclusion of the initial laser treatment. This aspect of treatment was greatly facilitated by the use of Fogarty arterial embolectomy catheters. Once debridement of the visible particulate matter with forceps was complete, No. 4 to No. 6 Fogarty arterial embolectomy catheters were advanced distally several centimeters into the previously obstructed segment using the large channel flexible fiberscope. Dilute Renografin in saline was then used to inflate the balloon gently. The catheter was then slowly withdrawn with successive balloon inflations and deflations proximally. This resulted in both removal of distal debris and segmental dilatation to improve subsequent patency. Because of the dilute nature of the Renografin, rapid alveolarization frequently occurred when used intraoperatively via needle injection. This led to two unique problems. On some occasions, a definite bronchus was never visualized due to the rapid silhouetting effect of the alveolarized contrast material (Fig 2). A segmental alveologram, however, proved to be equally as safe a marker as actual visualization of the postobstructed bronchus, ie, safe perfOration was always possible ifa segmental alveologram corresponding to the appropriate segmental anatomy were used as evidence of bronchial perfOration with the transbronchial needle. The second problem was due to persistence of the alveolarized Renografin for 24 to 48 hours after treatment. This resulted in a gas exchange abnormality similar to an equal volume pneumonia. In this setting, Dionosil was dense enough to allow for adequate bronchograms regardless of the amount of renografin previously used. There was no untoward effect from the subsequent use of laser, even when small quantities of Renografin or dionosil were visible in the treatment field. This technique greatly improved our ability to penetrate lobar and segmental obstructing lesions safely. In attempting to locate the postobstructive remnant, one would occasionally see direct injections of Renografin into pulmonary arteries in the same vicinity at disconcertingly short distances from the treatment site. The use oflaser blindly in this setting would be unacceptably treacherous. Pulmonary hemorrhage proved to be the only major complication in this series. There were three distinct types of hemorrhage, each with a different prognosis. Hemorrhage from the substances of an intrabronchial tumor never proved to be a major problem. Though temporarily brisk, the application of topical epinephrine plus dispatch in the use of laser coagulation controlled and prevented airway compromise from this type ofhemorrhage. Bronchial artery hemorrhage was a somewhat unex-
pected complication and truly tested the mettle of the endoscopist. The three such episodes occurred while treating less extensive endoscopic disease at the lobar level. Relatively low power settings were employed at the time ofhemorrhage (30 to 50 W), and even in retrospect, there was nothing unique about intent or method of therapy to forebode impending hemorrhage. This phenomenon is not observed with repeat laser hits to the normal bronchial wall at various power settings in experimental animals13.14 and may be uniquely related to the relatively superficial location and longitudinal course of the human bronchial aJ'o tery. 15 Because of the rate of blood show, it was impossible to consider laser photocoagulation to stop this type ofhemorrhage. In each case, the hemorrhage ceased spontaneously after two to five minutes. Considerable effurt was then required to re-establish adequate ventilation and clear the airway of clots. All three patients survived the hemorrhage without further bleeding, even after several months. Pulmonary artery perfOration was the third type of hemorrhage encountered. Both episodes of pulmonary artery perfOration in this series occurred while treating the bronchial wall with low vaporizing power settings (40 to 60 W) in an area not previously documented fluoroscopically with contrast to align directly with an obstructed bronchial remnant. The intraoperative use of contrast material should further minimize this risk. With the use of a real time intrabronchial mapping technique, we have developed the following treatment scheme for intrabronchiallesions:
Central Obstructions (Trachea ofMainstem Bronchus) Vaporizing power settings were safe in our hands when directed down the known channel ofa major central airway. The axial length of tumor involvement and the condition of the distal bronchus and lung can be assessed to some degree by the initial use of contrast (renografin or dilute Dionosil) before laser treatment. Sixty to 100 W of power at 0.5 to 1.0 second pulses produce rapid photovaporization with the establishment of a central lumen. We elect to terminate the first laser treatment once the airway caliber is 60 to 70 pe~ cent of normal. Four to seven days later, the second laser treatment is given. It is easier at this time, after debridement, to determine more prudently the extent of viable cancer remaining. Further widening of the airway caliber is then straightforward by careful ci~ cumferential use of laser photovaporization. In mainstem lesions, no attempt is made to perfOrate lobar segments unless clear visualization ofdistal bronchial rami is certain with the intraoperative use of contrast as described (Fig 7). The only anatomic situation in which laser treatment was consistently of no benefit was that where the CHEST I 87 I 4 I APRIL, 11186
421
cancer process occupied the entire axial length of the main bronchus. Even after successfully removing the majority of the intrabronchial component of cancer, unless one could then visualize the origin of several normal appearing distal bronchial segments beyond the carcinoma, no significant palliation resulted. This was true even if two to three distal segments were temporarily patent to the passage of biopsy forceps and/or contrast.
treatment. A single debridement session is usually adequate. We would suggest that a No. 6 to No. 7 Fogarty catheter be placed routinely in the proximal main bronchus befOre proceeding with laser treatment in segmental disease. In the event of sudden bronchial artery hemorrhage, immediate isolation of the bleeding segment or bronchus is insured by balloon inflation even ifdirect visualization is obscured by blood.
Lobar and Segmental Lesions
Laser Treatment Concomitant with Radiation Therapy
At the lobar level, the initial treatment plan is determined by the extent of lobar bronchial obstruction. H a portion of the lobar bronchus is patent, there is little difficulty in cancer demarcation. 'freatment with relatively low laser power settings (25 to 40 W) can be used to extend safely the treatment field to the segmental level. If the lobar bronchus is completely obstructed, an intrabronchial mapping procedure is employed initially to perforate the cancer. If this cannot be done with the biopsy furceps, then the transbronchial needle is used. Employing this technique, again treatment can be extended to the segmental level with 25 to 40 W delivered in .5 to 1.0 second pulses. To manage residual airway obstruction at the segmental level, the transbronchial needle with contrast is employed, and no further treatment is given unless distal subsegments are clearly demonstrated fluoroscopically. In the case of distal infection, every effi>rt is made to open all major segments involved roentgenographically with the infectious process at the time of the first treatment. We round it safe to use vaporizing laser power settings to perforate segmental obstructions (60 to 80 W), once distal rami were located. Patency of the more distal subsegments was then documented by either passing biopsy furceps with fluoroscopic visualization and/or by the use of segmental Dionosil bronchography (Fig 2). At the time of initial laser treatment, obstructed main segments were opened widely to a "normal" caliber such that distal subsegments were easily visible. No attempt was made to vaporize any cancer component lying between bronchial orifices at the segmental or subsegmentallevel. 'freatment was applied only to further increase the caliber of visible narrowed air channels. The charred, freshly laser treated bronchial surface is rapidly coated with mucus and tumor debris. One frequently finds well-fOrmed mucus plugs and laser debris completely occluding the airway at the treatment site two to fuur days later. This material is tightly adherent to the lasered surface, and prolonged bronchial obstruction with recurrence of obstructive symptoms occur unless debridement is done. This phenomenon occurred so frequently that we routinely repeat bronchoscopy fuur to seven days after initial laser
This protocol has been extended to allow fur the combination of laser therapy and conventional radiation therapy in inoperable lung cancer patients. Patients who are not judged to need urgent, immediate laser palliation are entered into a double blind protocol. In one group, laser is used initially to eliminate as much of the intrabronchial cancer component as can be done safely. Conventional radiation therapy is then given to the same site and to other areas as judged necessary by the radiotherapist. One or two months fOllowing the completion of radiation therapy, bronchoscopy is repeated and the initial treatment site re-
FIGURE 8. Apparent synergistic effect of laser and radiation. (Upper). A 74-yeaN)ld loWman had right main bronchus completely occluded (squamous cell carcinoma). View of main carina with an open left bronchus and no visible right bronchus. An intraoperative bronchogram was used to locate the right main bronchial channel which also demonstrated uninvolved RULand RLL distally (ie, short axial length of malignant process). Laser photovaporization was used to effect perfOration into right main bronchus with immediate relief of severe dyspnea. (Lower). View of main carina three months later fOllowing radiotherapy and the single laser treatment. Patient is still alive 13 months later with a single recurrent nodule on the right lateral tracheal wall successfully treated with laser.
examined and rephotographed. The second group receives only radiation with repeat intrabronchial examination at the same time interval. It is our intent to determine if initial laser treatment enhances the intrabronchial effect of radiation therapy, and to determine if there are fewer subsequent intrabronchial airway complications with combination therapy (Fig 8). Early results suggest combination therapy may have great merit. ACKNOWLEDGMENT: The invaluable assistance of Gloria Wheeler in the preparation ofthis manuscript is deeply appreciated. The support of the Sisters and Sur&ical Staff at Sl Francis Medical Center is also greatly appreciated. IDustrative support by Mr. Henry Saam was invaluable. REFERENCES 1 Carr Dl; Rosenow III. Bronchogenic carcinoma. Basics of RD. 1977; 5:5 2 Ferguson TB. Symposium on lung cancer. Chest 1971; 624-650 3 Perez C1; Corti DL, Vincent RG. Patterns of tumor recurrence after definitive irradiation of inoperable non-oat cell carcinoma of the lung. Int J Radiat Oncol Bioi Phys 1980; 6:987-94 4 Fontana R. Early diagnosis of lung cancer. Am Rev Respir Dis
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11 Mountain CF. Lung cancer clinical diagnosis and treatment. New York: Grune & Stratton, 1977 12 Finegold SM. Lung abscess and necrotizing pneumonJa. In:
Fishman AP, Pulmonary disease and disorders. New York: McGraw Hill, 1980; 110:1202-08 13 Hayakawa K, Oho K, Yuji M. Photodynamic effects of laser surgery on the trachea and bronchi of mongrel dogs. Second World Congress tOr Bronchoscopy, Dusseldorf: W Ger, 1980; 74 14 Iwasaki M, Konishi 1; Murata N, Maruyama W. Wada 1; et al. Effects of argon and YAG lasers on canine esophagus. Proc Third lnt Cong Laser Surg III, 1979; 86-90 15 Cortese D, McDougall Jr. Will laser therapy help your lung cancer patient. J Resp Dis 1984; 45-55
CHEST I 87 I 4 I APRIL, 11186
4rt