Bronchoplastic and Bronchovascular Procedures of the Tracheobronchial Tree in the Management of Primary Lung Cancer

of all branches 8 times, including vertebral artery once; resection of subclavian artery followed by PrFE bypass 3 times); (2) brachial plexus was freed from tumor in 18 patients: Tl (18 patients), C8 (10 patients~ C7 (4 patients~ C6 up to C4 (1 patient); (3) other structures, ·such as subclavian vein, vertebral artery, phrenic nerve, scalene muscles could not have been either safely freed from tumor or resected with suf&cient tumo...&ee margin without the cervical approach. Nine patients bad a wedge resection of the tumor using an automatic stapler, 14 patients had lobectomy, and 1 patient bad pneumonectomy. Operative mortality was 4.1'11, 19 among the 23 survivors bad postoperative radiotherapy, 2 of those with associated chemotherapy. Although longterm survival was poor (32'11 at 24 months), surgery provided a satisfactory and long-term relief of pain; 4 patients are alive without evidence of recurrence at 8, 17, 26, and 96 months. Even though long-term survival is poor, surgery is still the best treatment of pain in Pancoast syndrome. In some cases in our series, surgery, even deemed palliative, together with postoperative radiation therapy, bas provided long-term painless and disease-free survival. CoNCLUSION

While surgery remains the best treatment ofbronchogenic carcinoma, new surgical techniques, ie, carinal reconstruction, prosthetic replacement of SVC, and combined approach of superior sulcus tumors, can be applied to T3-T4 tumors; the operative mortality is I~ it provides satisfactory relief of symptoms, and gives much better results than surgery of N2 tumors. REFERENCES 1 Dartevelle PC, JCbahfe

J,

Cbapelier A, et al. 'Ii'acheal sleeve

pneumonectomy for bronchogenic carcinoma: report of 55 cases. Ann Thone Surg 1988; 46:68-72 2 Merlier M, Rojas A, Gbarbi N, et al. Uniflcation of criteria. ln: Delarue NC, Escbapasse H, eds. International Trends in General Thoracic Surgery. Philadelphia: WB Saunders, 1985:27-36 3 DesJauriers

J,

Bronchoplaatlc and Bronchovaacular Procedures of the Tracheobronchlallhle In the Management of Primary Lung

Cancer*

T.uguo Narulr., M.D., F.C.C.P

rice Thomas performed the &rst sleeve lobectomy in a P case of bronchial adenoma in 1947 and Allison• the &rst 1

bronchovascular procedure for bronchial carcinoma in 1952. Paulson and S})aw4 reported 9 cases of bronchoplasty for lung carcinoma in 1955 as a compromise operation for patients whose pulmonary reserve was inadequate to permit pneumonectomy. After these initial reports many otheW17 were published. Paulson and associates' reported 54 cases ofbronchoplasty performed in 1970, 8'11 of total lung cancer resection cases. Further, Jensik and associates• reported 57 cases of bronchoplasty indicated for lung cancer cases in 1972. Bronchoplasty was already common in the US in these years.

In Japan bronchoplasty was reported for only 4 cases of lung cancer among the total 55 cases of bronchoplasty performed up to 1960. In 1968, the data collected for reported bronchoplasty in Japan were .still only 7 cases of lung cancer of the total 77 cases of bronchoplasty performed.11 However, eventually the number of lung cancer cases for which bronchoplasty bad been indicated increased. According to the total data collected .in 1983, 11 there were 929 lung cancer cases for which bronchoplasty applied, out of a total of 1,568 cases with indications for bronchoplasty. Since then this operative procedure is highly respected and is used increasingly nationwide. Although there was broad application of this procedure, the number of central type of early stage lung cancer cases establishment of early detection system and advancement achieved in diagnostic technique, bronchoplasty is widely applied as a standard operative procedure, especially for central, early stage lung cancer.

Beaulieu M, B6oaz6ra A, McClish A. Sleeve

INDICATIONS

pneumonectomy for bronchogenic carcinoma. Ann Thone Surg 1978; 28:465

4 Dartevelle P, Cbapelier A, Nav~as, et al. &placement of the superior vena cava with Fl'FE grafts combined with resection of

mediastinal-pulmonary malignant tumors. J Thone Cardiovasc Surg 1987; 94:361-66 5 Dartevelle P, Levasseur P, Rojas-Minnda A. Eurese par voie combin~ cervico-thoraclque des tumeurs responsables de syndrome de Pancoast et 1bbias. Nouv Presse Med 1981; 10:1051-54

The objectives of bronchoplastic and bronchovascular procedures for selected cases oflung cancer are preservation of lung tissue, improvement of curability, and extension of operative indication. The procedures are indicated in the following circumstances: (I) tumor invasion from the lobar to the main bronchus; (2) pneumonectomy is not applicable for reasons of pulmonary function and others, but curable by this mode of operation; (3) curable by this mode of operation, even in cases of reserve of cardiopulmonary function; (4) preferable when tumor is limited to one lobe (applicable to any lobe); (5) when tumor invasion is within the range of reconstruction; (6) applicable even ifunilateral mediastinal lymph node metastases are present; (7) preferable for squamous cell *From the Department of Surgery, National Cancer Center Hospital, 'lbitto, Japan, D ------1.. fro

SupPOrteil in part by a Cnmt-in-Aid for Cancer .._..,.. the Japanese Ministry of Health and Welfare.

~~:Dr.

l Tau/qff ~.

m

Norulr., Nollonol Caner Cml«' HOiplfGI, l-

Clwo-lcu, 7bir,v, }trptm 104

CHEST I 98 I 1 I JULY, 19811 I Supplemlnt

538

carcinoma and low-grade malignancy; (8) preferable for central lung cancer in early stage. This procedure should be indicated regardless of ages of patients or sites of cancer, but the principle is to select the procedure that secures curability. Being strictly a local treatment, bronchoplasty is preferable for squamous cell carcinoma or low-grade malignant tumor. Even in metastasis extended to mediastinal lymph nodes, relatively better end results could be expected when cases for which curative operation could be feasible; therefore, this procedure is clearly indicated for such cases, particularly squamous cell carcinoma. When carcinomatous infiltration is extended to the pulmonary artery, if preservation oflung tissue is considered possible, sleeve resection the bronchus as well as the pulmonary artery should be performed. DECISION AND EXTENT OF RANGE TO BE REsECTED

For operative determination on range of cancerous invasion in bronchus required to judge whether this procedure is appropriate or not, major subjects are the change on the surface of bronchial mucous membrane observed by endoscopy and the extent of invasion of bronchial epithelium as well as bronchial wall, identified by CT scan, tomography, etc. However, as modes of cancer spread within the bronchus are difficult to identify, in many cases the accurate extent of the invasion is very difficult to confirm. For extent of cancerous invasion of surface of bronchial mucosa, it is appropriate to depend on transbronchoscopical biopsy. It is most important to carry out pathologic examination on bronchial stumps during the operation in every case. When results are positive, additional resection or the second best treatment should be applied. VENTILATION SYSTEM

Intratracheal anesthesia was given to each patient. For ventilation during bronchoplastic surgery, the hospital used double-lumen orotracheal tubes (Robertsham), in which a silicon spiral is built in, or Bronchocath. In the left sided lung cancer cases, when bronchoplasty has to be performed after thoracotomy with intubation indicated using the ordinary intratracheal tube with a single cuff, operation is conducted blocking the left main bronchus temporarily with Naruke System Balloon (Koken Co). As suturing is completed, within 20 minutes after the dissection of the bronchus, it is generally not necessary to conduct ventilation for ipsilateral residual lung from the operating field by insertion of tube. OPERATIVE PROCEDURES

In bronchoplastic surgery for lung cancer, various different procedures are applied according to and along with sites where cancer is located. Bronchoplastic procedures usually consist of sleeve resection of the main bronchus, combined with upper lobectomy and an end-to-end anastomosis of the bronchus. The order of the operation is as follows: the patient is placed in the lateral position and the posterolateral skin incision is used. A sufficient length of the skin incision is recommended to obtain a good operative field. The fifth rib is removed and the fourth rib partially resected. The chest wall is opened through the fifth rib bed. Ligation and dissection of the 54S

pulmonary vein, mediastinal lymph node dissection, and ligation and dissection of pulmonary artery are carried out. On the right side, the azygos vein is resected. When dissection of the azygos vein is performed, it is done at the side of the superior vena cava to prepare it for use as a cover of the site of the suture line. The pulmonary ligament must be cut so that the lung can be mobilized upward. After placing stay sutures of 3-0 TI-Cron at the proximal portion of bronchus and distal side of bronchus, the bronchus is resected. Although the location of the cancer can be determined preoperatively, pathologic examination of the bronchial stump should be made intraoperatively. End-to-end anastomosis is delayed until the report of the pathologic examination is available. When the cancerous infiltration is identified in a bronchial stump, additional resection is carried out. Simple interrupted sutures of absorbable sutures of atraumatic needles (4-0 Dexon-S, Dexon-plus, Vicryl, Maxon, or PDS) are inserted through the submucosa without pulling the suture out in the lumen of mucosa. The knots are tied on the outside of the bronchial wall. For the membranous portion, full-thickness sutures should be used. Several suture materials have been used over the years for the bronchial anastomosis. Since 1976, Dexon, a synthetic absorbable suture, has been used, and recently synthetic absorbable monofilament suture, Maxon (polyglyconate) or PDS (polydioxanone) are being used. In performing bronchial suture, it is important to keep the mucosal surface smooth. The membranous portion is done in a final stage of anastomosis to adjust the caliber of the anastomotic lumen. In principle, lapping around the anastomosis is not performed. In bronchovascular procedures, after bronchial anastomosis has been done, the pulmonary artery is anastomosed. Prior to the arterial anastomosis, the position of anastomosed artery should be estimated cautiously to prevent distortion or bending of the artery anastomosed. A fi.beroptic bronchoscope check of the anastomosed area of the bronchus should be made after its completion. Careful attention must be given to the removal ofbronchial secretion with the fi.beroptic bronchoscope during the early postoperative period. Regular bronchoscopic section is necessary in the early postoperative period. RESULTS

From 1965 to 1987, bronchoplastic procedures were performed on 111 Japanese patients with primary lung cancer. Of these Illcases, sleeve lobectomy was performed in 91 cases, including 19 cases in which sleeve lobectomy was done with concomitant resection of the pulmonary artery, and 20 wedge resection cases including 1 case in which wedge resection combined with resection of the pulmonary artery. Age and sex distribution in these 111 cases ranged from 25-76 years, with 103 male and 8 female subjects. These cases are classified by histologic types as 84 cases of squamous cell carcinoma, 13 cases of adenocarcinoma, 5 cases oflarge cell carcinoma, 3 cases ofadenosquamous cell carcinoma, 2 cases of double cancer, 1 unclassified case, 2 cases of carcinoid and 1 case of mucoepidemoid. In terms of pathologic stage, there were 18 cases in stage 1, 19 in stage 2, 62 in stage 3A, 7 in stage 3B, and 5 in stage 4. 5th World Cclrl'-1ce on Lung Cencer

Among 72 cases in which sleeve lobectomy bad been performed, 9 cases bad postoperative complications. Of these 9, 4 cases bad suture granulation, and pneumonectomy was carried out for 2 cases, while 2 cases died of bleeding due to bronchovascular fistula, bronchial fistula, and 2 cases of pneumonia. Suture granulation occurred in 1 of 19 cases in which wedge resection bad been conducted. There was 1 case of pulmonary infarction for which 20 combined bronchoplasty and pulmonary artery dissections were performed. The patient was treated with completion pneumonectomy. One patient died within 30 days after operation. The operative death rate was 0.9%. All cases of complication were in early stages, and they rarely occur. The 5-year survival rates by stages of disease are 54.4% for stage 1, 62.4% for stage 2, 39.2% for stage 3A, 0 for stage 3B, and 0 for stage 4. In 78 cases for which curative operation was performed the survival rate was 52.5%. When the relation between extent of lymph node metastasis and prognosis is reviewed, there were 50.0% in pNO cases, 45.9% in pN1, 32.5% in pN2, and 0% in pN3 cases. There were 20 cases eligible for which combined resection of the pulmonary artery. Of a total of 20 cases, there were 16 cases of squamous cell carcinoma, 2 of adenosquamous cell carcinoma, and 2 of adenocarcinoma. The results, including hospital deaths from bronchoplasty, lobectomy, and pneumonectomy, were 40.5% for bronchoplastic cases, and 43.3% for lobectomy cases, and 23.9% for pneumonectomy case. Many reports describe end results of cases for which bronchoplastic procedures and bronchovascular procedures were done.e.a.u.w.- Operative mortality of bronchoplastic procedures were 0-and 11.4%. Anastomotic stricture rates were 0-17.0%, while the rate of bronchial fistula was 1-11.4% and that oflocal recurrence 2-51%. As to operative mortality ofbronchovascular procedures, Toomes and VogtMoykopfl reported 17% among 88 cases and 11.1% in 36 cases with angioplastic procedure only. Many reports described a 30% 5-year survival rate. It is evident that operative curability depends on the extent of lymph node metastasis as well as histologic status in prognosis. CONCLUSION

Bronchoplasty has been conducted in a total of 111 lung cancer cases, including 18 cases in stage 1, 19 in stage 2, 62 in stage 3A, 7 in stage 3B and 5 in stage 1, while bronchovascular procedure was indicated in 20 of the 111 cases. The 5-year survival rate of the 111 cases for which bronchoplasty bad been performed was 40.5% including 1 operative death; while 5-year survival rate of 20 cases for which bronchovascular procedure was performed was 24.0%; and 78 cases for which curative operation was conducted resulted in the 5-year survival rate of52.5%. The 5-year survival rates per N factor were 50.0% for NO, 45.9% for N1, 32.5% for N2, and 0% for N3. Points to be considered for prevention against complication are cautious suture technique including appropriate selection of suture materials, skillful and experienced assistants for the operation, and postoperative good sputum expectoration by bronchofiberscopy. To preserve pulmonary function, enhance curability, and extend the scope of operative indication, these procedures

are particularly applicable for selected cases of squamous cell carcinoma or low-grade malignancy. REFERENCES 1 Price TC. Conservative resection of the bronchial tree. J R Coli Surg Edin 1956; 1:169-71 2 Allison OR. Course of thoracic surgery in Groningen, 1954. Cited in ref 3. 3 Toomes H. Vogt-Moykopf I. Conservative resection for lung cancer: international trends in general thoracic surgery 1. In: Delarue N, Eschapasse H, eds. Lung cancer. Philadelphia: WB Saunders, 1985; 88-99 4 Paulson DL, Shaw RR. Bronchial anastomoses and bronchoplastic procedures in the interest of preservation oflung tissue. J Thorac Cardiovasc Surg 1955; 29:283 5 Matthes TH. Uber Moglichkeiten von Lungenteil· und Bronchusresktionen mit End-zu-End Anastomose bei ausgenwahlten Fallen von Bronchiallcarzinomen. Thoraxchir 1959; 4:48-54 6 Jhonston JB, Jones PH. The treatment of bronchial carcinoma by lobectomy and sleeve resection of the main bronchus. Thorax 1959; 14:48-54 7 Price TC. Lobectomy with sleeve resection. Thorax 1960; 15:90-

11

8 Paulson DL, Urschel JC, McNamara JJ, Show RR. Bronchoplastic procedures for bronchogenic carcinoma. J Thorac Cardiovasc Surg 1970; 59:38-48 9 Jensik RJ, Faber LP, Milloy FJ, Amot JJ. Sleeve lobectomy for carcinoma, a ten year experience. J Thorac Cardiovasc Surg 1972; 64:400-12 10 Naruke T, Yoneyama T, Ogata T, Suemasu K. Bronchoplastic procedure for lung cancer. J Thorac Cardiovasc Surg 1977; 73:927-35 11 Bennet F\Y, Smith AR. A twenty-year analysis of the results of sleeve resection for primary bronchogenic carcinoma. Thorac Cardiovasc Surg 1978; 76:840-45 12 ~isel RD. Cooper JD, Delarue NC, Theman TE, Todd TRJ, Pearson Gl. Sleeve lobectomy for carcinoma of the lung. J Thorac Cardiovasc Surg 1979; 78:839-49 13 Ungar J, Gyeney J, Scherer E, Szarvas J. Sleeve lobectomy: an alternative to pneumonectomy in the treatment of bronchial carcinoma. J Thorac Cardiovasc Surg 1981; 29:41 14 Vogt-Moykopf I, Abel U, Heinrich ST, Toomes H, Wesch H. Organsparende Operationsverfahren beim Bronchialbrzinom, Ergebnisse. Langenbecks Arch Chir 1981; 355:117 15 Belli L, Memi A, Beati CA. Bronchoplastic procedures and pulmonary artery reconstruction in the treatment of bronchogenic cancer. J Thorac Cardiovasc Surg 1985; 90:167-71 16 Deslaruies J, Gaulin P, Beaulieu M, et al. Long term clinical and functional results of sleeve lobectomy for primary lung cancer. J Thorac Cardiovasc Surg 1986; 91:871-79 17 Frist WH, Mathisen OJ, Hilgenberg Ad, et al. Bronchial sleeve resection with and without pulmonary resection. J Thorac Cardiovasc Surg 1987; 93:350-57 18 Dotal Y. Present status of bronchoplasty. Lung Heart 1960; 4:315-22 19 Maeda M, Nanjyo S, Nakamura K, Nakamoto K, 1lu:la H, Naruke T. Statistical survey of tracheobronchoplasty in Japan. J Japan Soc Bronchol1986; 8:346-55 20 Rees GM, Paneth M. Lobectomy with sleeve resection in the treatment ofbronchial tumours. Thorax 1970; 25:160-64 21 Shaw KM, Luke DA. Lobectomy with sleeve resection of the bronchus for malignant disease of the lung and the influence of the suture material for bronchial repair. J Thorac Cardiovasc Surg 1979; 27:325 22 Van den Bosch JMM, Bergstein PGM, Laros CD, Gelissen HJ, Schaepken van Riemst ALEWS, Wagenaar SS. Lobectomy with sleeve resection in the treatment of tumors of the bronchus. CHEST I 98 I 1 I JULY. 1989 I Supplement

55S

Chest 1981; 90:154-57 23 Narub T, Suemasu JC. Bronchoplastic surgery fOr lung cancer mel the results. Jpn J Surg 1983; 13:165-7! !4 Belli L, Meroni A, Ronclinara C, Beati CA. Bronchoplastic procedures and pulmonary artery reconstruction in the treat-

ment of bronchopnic cancer. J Tborac Cardiovasc Surg 1985; 90:167-71 !5 Sartori F, Binda R, Spreafico C, Calabro F, 8ea F, Nistri R, et al. Sleeve lobectomy in the treatment of bronchogenic carcinoma. lnt Surg 1986; 71:!33-36

Innovative Chemotherapy

and pericardial involvement. Other occasionally utilized sites include intrathoracic, intrasplenic and intravenous inoculations. The recently described technique of intrabronchial inoculation o&'ers a unique orthotopic model for studying the biology of peripheral airway tumors. 4 While nude mouse xenografts ofl'er useful biologic tools, as weD as a method for propagation of human tumor cells, they are impractical as a method for selection of individualized therapy. Part of the reason is the lengthy and highly variable latent period before the appearance of grossly detectable tumor growth, especiaUy after inoculation of fresh tumor material. Fbr these reasons, considerable interest has been generated in the subrenal capsule assay,• originally described by Bogden. In this assay, tumor tissues are xenografted into the subrenal capsule of either immunosuppressed or immunocompetent mice. Tumor growth is evaluated after a short time, frequently 6 days. Thus, the assay, theoretically, may be used to select individualized therapy. In an extensive study of the assay with non-SCLC (NSCLC) by Theni et aJe utilizing immunocompetent mice, they found the method to be totaUy inappropriate. Many of the specimens contained large foci of necrosis or hemorrhage, and grafts that appeared to contain macroscopic tumor failed to contain tumor on microscopic examination. While this method may be suitable to test ceO lines, it does not appear to be practical for fresh lung cancer tumor tissues.

Xenografts and In vitro Drug Sensitivity Testing Atlj F.

Gadar, M.D. •

O

ver 150,000 cases of lung cancer occur in the USA annually, nearly 90'l' of whom will die of their disease with a median Jife expectancy of less than 1 year. Obviously, we need both new drugs as weD as new therapeutic concepts. While the latter ideas are discussed by other conbibutors to this issue, this report will focus on the use of animal and cell culture models for the selection of individualized chemotherapy as weD as for the identification of new therapeutic agents. ANIMAL MODELS

Animal models have been utilized extensively for screening new agents, as weD as for attempts at selecting individualized therapies. While earlier models focused on the use of electively immunosuppressed rodents or xenografting into immunologicaUy privileged sites such as hamster cheek pouch, recent eft'orts have widely utilized athymic nude mice. A large number and variety of human lung cancers have been xenografted, with reported success rates usually or interest, the take rate of small in the range of~. cell lung cancer (SCLC) is higher in male nude mice than in females, 1 perhaps reSecting the worse prognosis of this disease in men. Many of these xenografts retain the morphologic and biological characteristics of the original tumors. The usual site of transplantation is subcutaneous, and approximately 1()1-1()1 cells are required for a successful take. However, subcutaneous human xenografts seldom invade surrounding tissues or metastasize to distant locations. This is not due to loss of tumorigenicity, but reSects retention of some host defenses by the athymic mouse, including natural killer ceO activity. Thus, longevity of the host animal cannot be utilized as an end-point of drug eflicacy. These &ndings have led to a search for other potential transplantation sites having specialned applications.l.3 \1\e and others have utilized intracranial and intraperitoneal inoculations. The former results in higher take rates and rapid fatality. I or interest, the intracranial tumOrs selectively locate in meningeal and venbicular sites. Thus, it represents a useful model of meningeal carcinomatosis. While only a few tumors can be transplanted intraperitoneaUy, widespread dissemination may result, with frequent involvement of pleural and pericardial spaces.• Thus, these inoculation routes may provide useful models for pleural *National Cancer Institute and Naval Hospital, Bethesda. ~rlnt reqtiBifl: Dr CGzcltar, NCI NtiOJI A(edical Oncology Brt~nch, Bldg 8, Bm 5101, NtJOIIl H~. IJBII&ud4 J0814-5105

-

IN VITRO DRUG 5ENS11lVITY TES11NG Selection of individualized chemotherapy based on In vUro drug sensitivity testing (DST) has been a goal of clinicians for more than 3 decades. Despite intense interest and research, and the de\lelopment of multiple assay methods, this goal has remained theoretic for the most part. In applying such procedures, the following points must be carefuDy considered: How do you test?; What do you test?; How do you interpret and apply the data?; and (most important of all~ What is its clinical relevance? While a detailed discussion of these points is beyond the scope of this report, certain aspects will be considered, in particular those that impact on lung cancer. A large number of assay end points have been utilized for DST. These include clonogenic assays, and those that measure ceO proliferation and ceO kiD. Other assays are based on the measurement of early tumor ceO damage, and include dye exclusion, enzyme assays, DNA replication, protein determinations, and the previously mentioned subrenal capsule assay. The multitude of techniques suggests that no single technique is satisfactory for all situations. Ever since its application for DST,1 the human tumor clonogenic assay has remained the gold standard for predictive tests. However, its general application has been hampered by many problems, both theoretic and practical.1 The