Abstract

M

S

−K

, K

M

−M

,

K

G

, M

N

, A

A

Multifactorial Analysis of Respiratory Complications

in Patients After Subtotal Esophagectomy

Because of Cancer

Wieloczynnikowa analiza powikłań ze strony układu oddechowego

u chorych poddanych subtotalnej resekcji przełyku z powodu raka

1 _{Department and Clinic of Gastrointestinal and General Surgery, Silesian Piasts University of Medicine}

in Wrocław, Poland

2 _{Department and Division of Family Medicine, Silesian Piasts University of Medicine in Wrocław, Poland}

Adv Clin Exp Med 2006, 15, 5, 817–826 ISSN 1230−025X

ORIGINAL PAPERS

© Copyright by Silesian Piasts University of Medicine in Wrocław

Abstract

Background.Esophageal resection performed by a conventional method or using less invasive techniques is usu− ally associated with a number of postoperative complications. Among these, respiratory complications constitute one of the major groups.

Objectives. Analysis of respiratory complications in patients after transthoracic esophagectomy because of cancer. Material and Methods.The retrospective analysis involved 32 patients. The parameters age, sex, and tumor loca− tion, stage, and histopathology were assessed. The condition of the patients’ nutrition was evaluated on the basis of BMI. Respiratory function prior to surgery was assessed by spirometric and gasometric tests. Hemoglobin level, leukocyte count including the percentage of lymphocytes, and total serum protein were assessed prior to and 1, 3, 5, and 7 days after surgery.

Results.The patients were divided into three groups according to respiratory complications: I (n = 13) without complication, II (n = 10) with non−life−threatening complications, and III (n = 9) with severe complications. Overall mortality was 9.4%. The respiratory complications correlated with the observed preoperative decreased values of the spirometric tests and pO2and increased pCO2. Spirometry was normal in group I patients and significantly

decreased in group III (p< 0.05). Decreases in total serum protein on successive days after surgery were highest in group III patients and this was statistically significant in relation to group I (p< 0.05). The level of lymphocytes showed a downward trend in all groups, but only in group III patients was it below 1000/mm3_.

Conclusions.Impaired pulmonary function is a significant risk factor for respiratory complications after transtho− racic esophagectomy. The decreases in serum lymphocyte levels as well as total serum protein in successive post− operative days are also considered unfavorable prognostic factors (Adv Clin Exp Med 2006, 15, 5, 817–826).

Key words:esophageal cancer, esophagectomy, respiratory complications.

Streszczenie

Wprowadzenie. Zabiegi resekcyjne przełyku, wykonywane sposobem konwencjonalnym lub z wykorzystaniem technik mniej inwazyjnych, są obarczone pokaźnym odsetkiem różnorakich powikłań pooperacyjnych. Wśród nich powikłania pochodzące z układu oddechowego zajmują istotną pozycję.

Cel pracy. Analiza powikłań dotyczących układu oddechowego wśród chorych po przezklatkowym wycięciu prze− łyku z powodu raka.

Materiał i metody.Retrospektywną analizą objęto grupę 32 chorych. Ocenie poddano wiek i płeć chorych, umiej− scowienie guza, stopień zaawansowania i postać histologiczną. Stan odżywienia pacjentów analizowano na pod− stawie BMI. Wydolność oddechową przed operacją oceniano na podstawie wskaźników spirometrycznych i gazo− metrycznych. Analizowano również stężenie hemoglobiny, liczbę leukocytów, w tym odsetek limfocytów oraz stę− żenie białka całkowitego w surowicy przed operacją i w 1., 3., 5. i 7. dobie pooperacyjnej.

Among the various malignancies of the alimen− tary canal, cancer of the thoracic segment of the esophagus has one of the poorest prognoses [1]. The clinical symptoms develop relatively late, most commonly when the disease has already reached an advanced clinical stage. The anatomy of the esoph− agus, and especially the lack of serous membrane as well as the exceptionally rich lymphatic network, predispose to a quick spread of the malignancy. Patients not exceeding stage III of the disease according to the UICC (Union Internationale Contre le Cancer) classification [2] are qualified for esophagectomy. Esophageal resection performed by a conventional method or using less invasive tech− niques is usually associated with a number of post− operative complications. Among these, respiratory complications constitute one of the major groups and their incidence, according to various authors, may range from 3–5% to 20% [3–6].

An analysis of the prevalence of esophageal cancer shows that the disease most commonly involves people between 60 and 70 years of age in whom the efficiency of the respiratory system has been compromised to various extents by past or chronic respiratory conditions, which in an obvi− ous way affects the development of postsurgical respiratory complications [5–7]. Malnutrition of the patients resulting from dysphagia is another factor significantly affecting the incidence of post− surgical complications [8].

Basic accessory investigations performed before the operation in patients with esophageal cancer include endoscopic evaluation of the esoph− agus and the bronchial tree combined with biopsies taken for histopathological examination, radiologi− cal assessment of the esophagus with the use of contrast medium, ultrasound examination of the neck and abdomen, as well as intraesophageal ultra− sound examination and, more recently, positron tomography and intraesophageal ultrasonography accompanied by thin−needle biopsy of the mediasti− nal lymph nodes [1, 6, 9]. Preoperative evaluation of respiratory efficiency is primarily based on gaso− metric and spirometric examinations [3, 10].

Esophageal resection using conventional meth− ods is associated with the necessity of opening the thorax, abdominal cavity, and the neck and is surgi− cally extremely invasive, which obviously creates a significant burden to the patient. However, only radical surgery with extensive lymphadenectomy offers any chances for prolonged survival [3, 4].

It seems that correct preoperative evaluation of the tumor stage and respiratory system efficien− cy as well as the general condition and nutritional status of the patient qualified for esophageal resec− tion significantly affect the incidence of peri− and postoperative complications.

The aim of the study was to evaluate the inci− dence and kind of respiratory system complica− tions in patients submitted to esophagectomy due to tumor in the thoracic part.

Material and Methods

From January 2001 to December 2004 a total of 212 patients with esophageal tumor were treated at the clinic. Of these, 32 patients with stage III of the disease according to the UICC classification were qualified for surgical treatment. The remaining 180 patients with stage IV tumors received palliative treatment instead of resection of the esophagus.

The retrospective analysis involved the group of 32 patients treated by esophagectomy. The study group included 5 women and 27 men aged 43 to 76 years (median: 57). Esophageal resection was performed under general anesthesia with the right thoracic approach in all the patients. The tho− racic esophagus and posterior mediastinal lymph nodes were resected in one block, and the pleural cavity was drained. Next the abdominal portion of the esophagus as well as the cardiac orifice of the stomach with perigastric lymph nodes (in the region of the fundus of the stomach and along the left gastric artery) were resected by the peritoneal approach and an alimentation gastric fistula was performed. The cervical esophagus was isolated through an incision along the left sternocleidomas−

wikłaniami. Śmiertelność wynosiła 9,4%. Wystąpienie powikłań oddechowych w okresie pooperacyjnym korelo− wało z obniżonymi w badaniach przedoperacyjnych wynikami zarówno testów spirometrycznych oraz wartościa− mi pO2, jak i podwyższonymi stężeniami pCO2 we krwi żylnej. U pacjentów z grupy I spirometria była prawidło−

wa, a wśród pacjentów z grupy III średnie wartości tych wskaźników były istotnie obniżone (p < 0,05). Stężenie białka całkowitego w surowicy w kolejnych dniach pooperacyjnych było najmniejsze w grupie III i było istotne statystycznie w porównaniu z grupą I (p < 0,05). Liczba limfocytów wykazywała tendencję spadkową we wszyst− kich grupach, ale tylko wśród pacjentów z grupy III jej wartości wynosiły poniżej 1000/mm3_.

Wnioski.Zaburzenie funkcji układu oddechowego, stwierdzane w badaniach przedoperacyjnych, jest znaczącym czynnikiem ryzyka wystąpienia powikłań po przezklatkowym wycięciu przełyku. Zarówno spadek liczby limfocy− tów, jak i stężenia białka całkowitego w surowicy w kolejnych dniach pooperacyjnych można rozważać jako nie− korzystny czynnik prognostyczny (Adv Clin Exp Med 2006, 15, 5, 817–826).

toid muscle and the salivary fistula was performed by the cervical approach. In the postoperative peri− od, intensive breathing exercises were carried out for which the patients had already been prepared before surgery. In patients requiring respiratory assistance, careful hygiene of the bronchial tree was maintained in the postoperative period.

The investigations were based on multifactori− al analysis involving the evaluation of certain para− meters before and after the operation and their cor− relation with respiratory complications observed after the procedure. The analysis included the patients’ age and sex, location of the tumor, stage of the disease according to the UICC, histology and histological grading of the tumor, duration of the surgery, as well as the nutritional status of the patients as expressed by their BMIs (Body Mass Indexes). Respiratory efficiency prior to surgery was evaluated on the basis of spirometric tests (VC: vital capacity, FVC: forced expiratory vital capacity, FEV1: forced expiratory volume in 1 sec−

ond, FEV1%VC: Tiffeneau−index, PEF: peak expi−

ratory flow) and venous blood gasometry (blood pH, pO2: partial oxygen pressure, pCO2: partial

pressure of carbon dioxide, BE: base excess). Moreover, certain laboratory parameters, such as hemoglobin, WBC (white blood cells) including the level of lymphocytes, and total serum protein, were evaluated. The same parameters were investi− gated 1, 3, 5, and 7 days after surgery.

The patients were divided into three groups according to the kind and character of respiratory complications: group I included patients who did not develop any complications, group II patients with non−life−threatening complications (atelecta− sis in the lower lobes, fluid in the pleural cavity not requiring puncture, minor inflammatory focus in one lung), and group III contained patients who developed life−threatening complications (signifi− cant atelectasis, fluid in the pleural cavity above the level of the fifth rib, massive inflammatory changes, pneumothorax on the left side, respirato− ry insufficiency).

Evaluation of statistical significance for para− meters with distributions differing from normal was performed by means of the non−parametric Fisher−Snedecor test.

Results

Among the 32 patients submitted to eso− phagectomy due to tumor, the percentage of men who developed complications (84.4%) was much higher than of women. The tumor was most com− monly localized in the upper or middle thoracic part of the esophagus (68.8%), while, histological−

ly, 81.3% of cases developed squamous cell carci− noma. The histological grading identified 28.1% grade I, 37.5% grade II, and 34.4% grade III tumors. Most of our patients were in stages IIA, IIB, and III of the disease (total: 90.7%). The medi− an duration of surgery was six hours (Table 1).

Uneventful postoperative course (group I) was observed in 13 (40.6%) patients, non−life−threaten− ing complications (group II) occurred in 10 (31.3%) patients, while 9 (28.1%) patients devel− oped severe respiratory complications which resulted in three deaths. The mortality rate was 9.4% (Table 2).

The findings of preoperative spirometric examinations (VC, FVC, FEV1, FEV1%VC, and

PEF) were normal in group I, had borderline val− ues in group II, and were significantly decreased in group III patients, this difference being statistical− ly significant in relation to the findings in group I patients (p < 0.05) (Table 3). Analysis of indi− vidual findings revealed that ventilation distur− bances in one patient suffering from pneumoco− niosis were of restrictive nature, while in the remaining patients they were of a mixed, restric− tive−obturative kind. Normal nutritional status was found in 50.0% of the patients, while a further 31.3% demonstrated undernourishment to various degrees (Table 4).

Gasometric parameters prior to surgery are presented in Table 5, while pO2and pCO2levels in

successive postoperative days are presented in Figs. 1 and 2. Mean pO2levels in groups II and III

were below the norm (70 mm Hg). Patients in group III had the lowest levels, which differed sta− tistically from group I (p< 0.05). No statistically significant difference was revealed on successive days.

below 1000/mm3_{, and it remained low until the}

seventh day after the operation (Fig. 6).

Discussion

Carcinoma of the esophagus is the fifth most prevalent tumor among gastrointestinal cancers and it usually affects middle−aged and older men. The tumor is most commonly localized in the upper and middle thoracic part of the esophagus [1, 3]. In European countries, squamous cell carcinoma rep− resents the most common histological form [6].

In the investigated group of patients, the men to women ratio was 5.4 to 1 and the mean age was 57 years. The tumor involved the upper or middle thoracic part of the esophagus in the majority of the patients (68.8%), while in 31.2% of cases it

was localized in the supradiaphragmatic part of the esophagus. Squamous cell carcinoma accounted for 81.3% of cases, while adenocarcinoma was diagnosed in 18.7% of cases. Histological grading identified 21 grade I or grade II tumors (65.6%) and 11 grade III tumors (34.4%). Our observations are consistent with those of the majority of European authors. Bonavina et al. [6], in a collec− tive review of observations from 17 European cen− ters, reported that in a group of 12,761 patients with esophageal or cardiac orifice tumor, squa− mous cell carcinoma accounted for 76.3% and adenocarcinoma for 23.7% of cases. Resection surgery was possible only in about 50% of patients with squamous cell carcinoma. Schneiden et al. [11] remarks that the incidence of esophageal tumor has been constant for years; however, its incidence among women has been increasing

Table 1. Characteristics of the investigated patients

Tabela 1.Charakterystyka badanych chorych

Parameter Group I Group II Group III Total

(Wskaźnik) (Grupa I) (Grupa II) (Grupa III) (Razem)

Number (Liczba) 13 (40.6%) 10 (31.3%) 9 (28.1%) 32

Sex (Płeć) female (żeńska) 2 2 1 5 (15.6%)

male (męska) 11 8 8 27 (84.4%)

Age (Wiek) median (mediana) 57 54 64 57

mean± SD (średnia ± SD) 57.4± 9.26 53.6± 7.32 61.22± 10.39 57.3± 9.25 Location of the tumor in the esophagus

(Umiejscowienie guza w przełyku)

upper third (1/3 górna) 1 2 3 6 (18.8%)

mid third (1/3 środkowa) 9 5 2 16 (50.0%)

lower third (1/3 dolna) 3 3 4 10 (31.2%)

Histopathology (Histologia)

squamous cell carcinoma (rak płaskonabłonkowy) 10 8 8 26 (81.3%)

adenocarcinoma (rak gruczołowy) 3 2 1 6 (18.7%)

Degree of tumor differentiation

(Stopień zróżnicowania) I 6 1 2 9 (28.1%)

II 3 6 3 12 (37.5%)

III 4 3 4 11 (34.4%)

Preoperative assessment of disease stage according to UICC

(Przedoperacyjny stopień zaawansowania wg UICC)

I 1 1 (3.1%)

IIA 4 4 3 11 (34.4%)

IIB 2 2 2 6 (18.7%)

III 7 3 4 14 (43.8%)

Duration of the operation – hours

(Czas operacji – godz.) median (mediana) 6 6 7 6

mean± SD (średnia ± SD) 6.35± 1.47 6.55± 1.42 6.72± 1.42 6.47± 1.4 Accompanying or past chronic respiratory disorders 2 (bronchial 3 (pneumoco− 5 (15.6%) (Współistniejące lub przebyte przewlekłe choroby asthma, tuber− niosis, tuber−

układu oddechowego) culosis) culosis,

COPD) Mean± SD – mean ± standard deviation; COPD – chronic obturative pulmonary disease.

slowly but steadily. In his report the men to women ratio was 3 to 1. Our investigations did not confirm this trend. Slightly different observations from ours are presented in American literature.

The last decade demonstrated a significant increase in the rate of patients with adenocarcino− ma [1]. The reasons for this phenomenon are unclear. As remarked by Wild et al. [12], it may be

Table 2. Types of complications

Tabela 2.Rodzaje powikłań

Type of complication Group I Group II Group III

(Rodzaj powikłania) (Grupa I) (Grupa II) (Grupa III)

n = 13 n = 10 n = 9

No complications 13

(Bez powikłań)

Atelectasis in lower lobes 7

(Niedodma w dolnych płatach)

Fluid in pleural cavity not requiring puncture 6 (Płyn w jamie opłucnowej niewymagający punkcji)

Minor inflammatory foci in one lung 5

(Drobne ognisko zapalne w jednym płucu)

Significant atelectasis 2

(Masywna niedodma)

Fluid above the 5th rib 4

(Płyn powyżej 5. żebra)

Massive inflammatory changes 3

(Rozległe zmiany zapalne)

Left−side pneumothorax 3

(Lewostronna odma)

Respiratory failure 4

(Niewydolność oddechowa)

Death 3 (Zgon)

Table 3. Preoperative spirometric parameters

Tabela 3.Przedoperacyjne wskaźniki spirometryczne

Feature – % of normal values Group I Group II Group III (Wskaźnik – % wartości należnej) (Grupa I) (Grupa II) (Grupa III)

VC* Me 102 87.5 76.6

Mean± SD 106.3± 12.4 85.5± 8.69 74.4± 20.89

FVC* Me 110 90.1 80.4

Mean± SD 113.6± 9.29 91.5± 11.87 77.1± 15.69

FEV1* Me 119 97.1 61.9

Mean± SD 119.6± 8.76 98.7± 12.32 60.5± 9.34

FEV1%VC Me 108 106.5 84.3

Mean± SD 107.6± 5.1 105.1± 6.05 82.2± 17.16

PEF* Me 68.4 70.4 31.5

Mean± SD 70.3± 13.84 80.3± 22.67 33.5± 8.19 Group I vs. Group III p < 0.05.

VC – vital capacity.

FVC – forced expiratory vital capacity. FEV1– forced expiratory volume in 1 second.

FEV1%VC – Tiffeneau−index.

PEF – peak expiratory flow. Me – median.

Mean± SD – mean ± standard deviation.

Grupa I vs. grupa II, p < 0,05. VC – pojemność życiowa.

FVC – natężona pojemność życiowa. FEV1– natężona pojemność wydechowa

pierwszosekundowa.

FEV1%VC – współczynnik Tiffeneau.

PEF – szczytowy przepływ wydechowy. Me – mediana.

possible that gastroesophageal reflux is a potent risk factor both for tumor and for a precancerous state, such as Barrett’s esophagus. Similar sugges− tions were put forward by Turcotte et al. [13], who stressed that Barrett’s esophagus may be one, although not the only one, of the reasons of the observed increase in the incidence of adenocarci− noma of the esophagus.

The review of literature shows that a signifi− cant number of patients are in advanced stage of the disease when they are first diagnosed and pal− liative therapy remains the only option they can be offered. In the study by Quint et al. [14] as many as 18% of patients had remote metastases at the time of diagnosis. The analysis of our material demonstrates a similar trend. Of 212 patients referred for surgical treatment, 84.9% were in

stage IV of the disease on admission to the hospi− tal. The majority of the 32 patients qualified for esophagectomy (96.8%) were in stages IIA, IIB, or III of the disease. We had only one patient in stage I. Leading American and Japanese centers report much more favorable results in diagnosing early forms of esophageal cancer, which is the effect of wide−scale screening tests for subjects with high risk factors for the disease [1, 4].

Radical resection of the esophagus, regardless of the surgical approach, is burdened with a high rate of postsurgical complications of the respirato− ry system [3–5, 7]. The conventionally applied radical methods are highly invasive to the chest and mediastinum, which results in significant hypofunction of the respiratory system in the post− operative period. Ikeguchi et al. [15], comparing

Table 4. Preoperative nutritional condition of the patients

Tabela 4.Przedoperacyjna ocena stopnia odżywienia

BMI (kg/m2_{) Group I Group II Group III Total}

(Grupa I) (Grupa II) (Grupa III) (Razem)

n = 13 n = 10 n = 9

< 17 severe undernourishment 1 1 (3.1%)

(ciężkie niedożywienie)

17–17.9 undernourishment 1 2 3 6 (18.8%)

(niedożywienie)

18–19.9 presumptive undernourishment 2 1 3 (9.4%)

(podejrzenie niedożywienia)

20–24.9 normal 7 4 5 16 (50.0%)

(norma)

25–29.9 overweight 2 4 6 (18.7%)

(nadwaga) BMI – Body Mass Index. BMI – wskaźnik masy ciała.

Table 5. Preoperative gasometric parameters

Tabela 5.Przedoperacyjne wskaźniki gazometryczne

Parameter Group I Group II Group III

(Wskaźnik) (Grupa I) (Grupa II) (Grupa III)

pH Me 7.419 7.418 7.402

Mean± SD 7.41± 0.02 7.419± 0.32 7.397± 0.047

pO2 (mm Hg)* Me 74.5 69.85 64.4

Mean± SD 74.8± 8.0 69.28± 6.6 63.95± 6.73

pCO2 (mm Hg) Me 39.7 39.45 40.7

Mean± SD 38.42± 4.36 38.9± 3.3 40.47± 2.65

BE (mEq/l) Me 1.2 1.15 1.3

Mean± SD 0.68± 3.31 0.92± 2.6 0.33± 2.64 Group I vs. Group III, p < 0.05.

Me – median.

Mean± SD – Mean ± standard deviation. Grupa I vs. grupa III, p < 0,05.

Me – mediana.

0 10 20 30 40 50 60 70 80

prior to surgery przed operacją 1 day 1. doba 3 day 3. doba 5 day 5. doba 7 day 7. doba Group I/Grupa I Group II/Grupa II Group III/Grupa III pO

(mm Hg) 2

*

Fig. 1. Median partial pressure of oxygen (mm Hg) in groups I, II, and III prior to surgery and at 1, 3, 5, and 7 postoperative days (* group I vs. group III, p < 0.05)

Ryc. 1. Mediany ciśnienia parcjalnego tlenu w gru− pach I, II i III przed operacją oraz w 1., 3., 5. i 7. dobie pooperacyjnej (* grupa I vs. grupa III, p < 0.05)

0 10 20 30 40 50

prior to surgery przed operacją 1 day 1. doba 3 day 3. doba 5 day 5. doba 7 day 7. doba Group I/Grupa I Group II/Grupa II Group III/Grupa III pO

(mm Hg) 2

NS

Fig. 2. Median partial pressure of carbon dioxide (mm Hg) in groups I, II, and III prior to surgery and at 1, 3, 5, and 7 postoperative days (NS – not significant)

Ryc. 2. Mediany ciśnienia parcjalnego dwutlenku węgla w grupach I, II i III przed operacją oraz w 1., 3., 5. i 7. dobie pooperacyjnej (NS – nieistotne statystycznie) 0 10 20 30 40 50 60 70 80

prior to surgery przed operacją 1 day 1. doba 3 day 3. doba 5 day 5. doba 7 day 7. doba Group I/Grupa I Group II/Grupa II Group III/Grupa III serum protein białko w surowicy (g/l) *

Fig. 3. Median serum protein level (g/l) in groups I, II, and III prior to surgery and at 1, 3, 5, and 7 postopera− tive days (* group I vs. group III, p < 0.05)

Ryc. 3. Mediany stężenia białka w surowicy (g/l) w grupach I, II i III przed operacją oraz w 1., 3., 5. i 7. dobie pooperacyjnej (* grupa I vs. grupa III, p < 0.05)

0 2 4 6 8 10 12 14 16

prior to surgery przed operacją 1 day 1. doba 3 day 3. doba 5 day 5. doba 7 day 7. doba Group I/Grupa I Group II/Grupa II Group III/Grupa III serum hemoglobin hemoglobina w surowicy (g/dl) NS

Fig. 4. Median serum hemoglobin levels (g/dl) in groups I, II, and III prior to surgery and at 1, 3, 5, and 7 postoperative days (NS – not significant)

Ryc. 4. Mediany stężenia hemoglobiny w surowicy (g/dl) w grupach I, II i III przed operacją oraz w 1., 3., 5. i 7. dobie pooperacyjnej (NS – nieistotne statystycznie)

0 2000 4000 6000 8000 10000 12000

prior to surgery przed operacją 1 day 1. doba 3 day 3. doba 5 day 5. doba 7 day 7. doba Group I/Grupa I Group II/Grupa II Group III/Grupa III serum

leukocytes leukocyty w surowicy (mm )–3

NS

Fig. 5. Median serum leukocytes levels (/mm3_{) in}

groups I, II, and III prior to surgery and at 1, 3, 5, and 7 postoperative days (NS – not significant)

Ryc. 5. Mediany liczby leukocytów w surowicy (mm–3₎

w grupach I, II i III przed operacją oraz w 1., 3., 5. i 7. dobie pooperacyjnej (NS – nieistotne statystycznie)

0 500 1000 1500 2000 2500 3000

prior to surgery przed operacją 1 day 1. doba 3 day 3. doba 5 day 5. doba 7 day 7. doba Group I/Grupa I Group II/Grupa II Group III/Grupa III serum

lymphocytes limfocyty w surowicy (mm )–3

Fig. 6.Median serum lymphocytes levels in groups I, II, and III prior to surgery and at 1, 3, 5, and 7 postop− erative days

two groups of patients, i.e. after open esophagec− tomy and after the transhiatal procedure, found that significant impairment of the respiratory func− tion in patients after open esophagectomy persists for more than 6 months after surgery (VC and FEV1were 78% and 72% of the preoperative lev−

els, respectively). In contrast, the incidence of res− piratory complications after open esophagectomy and the transhiatal procedure did not differ signif− icantly. However, data from less invasive surgical modalities, especially the thoracoscopic method, presented by other authors are not uniform. Osugi et al. [4] reported a marked decrease in the inci− dence of complications after the thoracoscopic method which reached 5%, but the procedure had to be performed by an experienced and well− trained surgeon. The report by Fukunagi et al. [16] seems to confirm the superiority of less invasive procedures in comparison with open thoracotomy. They demonstrated that the levels of proinflamma− tory cytokines are significantly lower following the thoracoscopic procedure in comparison with the conventional method. Similar observations concerning mini−thoracotomy/laparotomy are pre− sented by Narumiya et al. [17]. However, other authors do not share these opinions [18, 19]. Some suggest that radical lymphadenectomy is possible only at open thoracotomy, others that thoracoscop− ic methods prolong significantly the time of the surgery, while still others do not see any differ− ences in the incidence of complications following conventional and less invasive modalities of treat− ment such as transhiatal esophagectomy [4, 18–20]. Our investigations did not resolve the question, as the transthoracic operation was the preferred surgical method. It seems that the final answer should be expected after a multi−center study on a large population using various surgical modalities and taking into account remote survival rates.

The review of literature concerning risk fac− tors for respiratory complications in patients after esophagectomy indicates that the main risk factors include age over 65 years, low body mass, as well as coexisting chronic disorders in other systems [5, 7, 8]. Moreover, independent risk factors include abnormal preoperative spirometric and gasometric findings, which point to hypofunction of the respiratory system [20].

In the study group, severe respiratory compli− cations occurred in 28.1% of the patients and the associated mortality rate was 9.4%. These obser− vations are similar to the results presented by Marmuse et al. [7], where severe respiratory com− plications affected 36% of patients after esophagectomy with chronic obstructive pul− monary disease and the associated mortality rate

was 10%. It is worth noting that the authors used transhiatal esophagectomy, which is considered a significantly less invasive modality than our open approach. Griffin et al. [3], in their study on 228 patients with subtotal resection of the esopha− gus by means of the Ivor Lewis method, observed severe respiratory complications in 17% of the operated patients. The complications closely cor− related with low values of preoperative spiromet− ric tests. Similar observations have been reported by other authors [10, 20]. Avendano et al. [10] demonstrated that FEV1 above 65% of the norm

indicated the possibility of pulmonary complica− tions. In the material of the present study, the severe respiratory complications observed in group III corresponded to preoperatively decreased results of spirometric examinations (VC, FVC, FEV1, FEV1%VC, PEF). The differ−

ence was statistically significant in relation to the findings in group I patients (p < 0.05). Group III patients also revealed statistically significant (p< 0.05) decreases in pO2and increases in pCO2prior

to the surgery in comparison with patients without pulmonary complications (group I). On the other hand, the mean findings of other preoperative tests (Hb, leukocyte and lymphocyte count, total serum protein concentration) were within the norm and did not show any statistically significant differ− ences in either of the groups. Various degrees of malnutrition in the preoperative period were found in 31.3% of the patients and no statistical differ− ences were found between the study groups.

The examinations on successive postoperative days revealed a statistically significant decrease (p< 0.05) in total serum protein levels in group III patients compared with group I patients. Moreover, group III patients demonstrated a sig− nificant decrease in lymphocyte count to mean levels below 1000/mm3 _{which was observed as}

long as seven days after the procedure and may be considered an unfavorable prognostic factor.

tive period always seem useful, as they may improve the patient’s techniques of spontaneous deep breathing, coughing up, and ventilation with expiratory resistance. In case of obturative disor− ders, individually tailored preoperative physio− therapy and pharmacotherapy may significantly improve the respiratory activities.

In the face of a malignant, evidently life− threatening disease, it is difficult to define general systemic contraindications for surgical treatment; however, it should be stressed that preoperative evaluation of the risk factors may affect the choice of the optimal time and modality of the operation and determine the postoperative management of the patient.

Acknowledgments. The authors thank Maria Zagrodnik of the Medical University Language Department for linguistic assistance.

References

[1] Vazquez−Sequeiros E, Wiersema MJ, Clain JE, Norton ID, Levy MJ, Romero Y, Salomao D, Dierkhising R, Zinsmeister AR:Impact of lymph node staging on therapy of esophageal carcinoma. Gastroenterology 2003, 125, 1626–1635.

[2] Sobin LH, Hermanek P, Hutter RV: TNM classification of malignant tumors. A comparison between the new (1987) and the old editions. Cancer 1988, 61, 2310–2314.

[3] Griffin SM, Shaw IH, Dresner SM:Early complications after Ivor Lewis subtotal esophagectomy with two−field lymphadenectomy: risk factors and management. J Am Coll Surg 2002, 194, 285–297.

[4] Osugi H, Takemura M, Higashino M, Takada N, Lee S, Kinoshita H: A comparison of video−assisted thora− coscopic oesophagectomy and radical lymph node dissection for squamous cell cancer of the oesophagus with open operation. Br J Surg 2003, 90, 108–113.

[5] Bonavina L, Incarbone R, Saino G, Clesi P, Peracchia A:Clinical outcome and survival after esophagectomy for carcinoma in elderly patients. Dis Esophagus 2003, 16, 90–93.

[6] Bonavina L:Early oesophageal cancer: results of a European multicentre survey. Br J Surg 1995, 82, 98–101. [7] Marmuse JP, Maillochaud JH:Respiratory morbidity and mortality following transhiatal esophagectomy in

patients with severe chronic obstructive pulmonary disease. Ann Chir 1999, 53, 23–28.

[8] Kunisaki C, Shimada H, Nomura M, Matsuda G, Otsuka Y, Ono H, Akiyama H:Immunonutrition risk fac− tors of respiratory complications after esophagectomy. Nutrition 2004, 20, 364–367.

[9] Flamen P, Lerut A, Van Cutsen E, De Wever W, Peeters M, Stroobants S, Dupont P, Bormans G, Hiele M, De Leyn P, Van Raemdonck W, Coosemans W, Ectors N, Haustermans K, Mortelmans L: Utility of positron emission tomography for staging of patients with potentially operable esophageal carcinoma. J Clin Oncol 2000, 18, 3202–3210.

[10] Avendano CE, Flume PA, Silvestri GA, King LB, Reed CE:Pulmonary complications after esophagectomy. Ann Thorac Surg 2002, 73, 922–926.

[11] Schneiden R, Pescatore P, Capesius C:Oesophageal intraepithelial and invasive neoplasia of squamous cell type: epidemiology and outcome in Luxemburg, 1980–2001. Acta Gastroenterol Belg 2005, 68, 302–307. [12] Wild CP, Hardie LJ:Reflux, Barrett’s oesophagus and adenocarcinoma: burning questions. Nat Rev Cancer

2003, 3, 676–683.

[13] Turcotte S, Duranceau A:Gastroesophageal reflux and cancer. Thorac Surg Clin 2005, 15, 341–352.

[14] Quint LE, Hepburn LM, Francis IR, Whyte RI, Orringer MB: Incidence and distribution of distant metastases from newly diagnosed esophageal carcinoma. Cancer 1995, 76, 1120–1125.

[15] Ikeguchi M, Maeta M, Kaibara N:Respiratory function after esophagectomy for patients with esophageal can− cer. Hepatogastroenterology 2002, 49, 1284–1286.

[16] Fukunaga T, Kidokoro A, Fukunaga A, Nagakari K, Suda M, Yoshikawa S: Kinetics of cytokines and PMN−E in thoracoscopic esophagectomy. Surg Endosc 2001, 15, 1484–1487.

[17] Narumiya K, Nakamura T, Ide H, Takasaki K:Comparison of extended esophagectomy through mini−thora− cotomy/laparotomy with conventional thoracotomy/laparotomy for esophageal cancer. Jpn J Thorac Cardiovasc Surg 2005, 53, 413–419.

[18] Peracchia A, Rosati R, Fumagalli U, Bona S, Chella B:Thoracoscopic esophagectomy: are there benefits? Semin Surg Oncol 1997, 13, 259–262.

[19] Rentz J, Bull D, Harpole D, Bailey S, Neumayer L, Pappas T, Krasnicka B, Henderson W, Daley J, Khuri S: Transthoracic versus transhiatal esophagectomy: a prospective study of 945 patients. J Thorac Cardiovasc Surg 2003, 125, 1114–1120.

Address for correspondence:

Department and Clinic of Gastrointestinal and General Surgery, Silesian Piasts University of Medicine

ul. Traugutta 57/59 50−417 Wrocław Poland

Conflict of interest: None declared

Received: 21.04.2006 Revised: 12.07.2006 Accepted: 21.09.2006

Praca wpłynęła do Redakcji: 21.04.2006 r. Po recenzji: 12.07.2006 r.