- Email: [email protected]
Quantitative assessment of the free jejunal graft perfusion
j o u r n a l o f s u r g i c a l r e s e a r c h 1 9 4 ( 2 0 1 5 ) 3 9 4 e3 9 9
Available online at www.sciencedirect.com
ScienceDirect journal homepage: www.JournalofSurgicalResearch.com
Quantitative assessment of the free jejunal graft perfusion Kinji Kamiya, MD, PhD,a Naoki Unno, MD, PhD, FACS,a,* Shinichiro Miyazaki, MD, PhD,a Masaki Sano, MD, PhD,a Hirotoshi Kikuchi, MD, PhD,a Yoshihiro Hiramatsu, MD, PhD,a Manabu Ohta, MD, PhD,a Takashi Yamatodani, MD, PhD,b Hiroyuki Mineta, MD, PhD,b and Hiroyuki Konno, MD, PhD, FACSa a b
Second Department of Surgery, Hamamatsu University School of Medicine, Hamamatsu, Japan Department of Otolaryngology/Head and Neck Surgery, Hamamatsu University School of Medicine, Hamamatsu, Japan
article info
abstract
Article history:
Background: Reconstruction with free jejunal graft (FJG) is often performed for patients with
Received 12 May 2014
hypopharyngeal or cervical esophageal cancer. During reconstruction with an FJG after
Received in revised form
pharyngoesophagectomy, it is critical to intraoperatively detect venous anastomotic failure
16 October 2014
and subsequent venous malperfusion to avoid postoperative FJG necrosis. This study in-
Accepted 30 October 2014
troduces a novel method for assessing blood perfusion in FJGs by using indocyanine green
Available online 5 November 2014
(ICG) fluorescence angiography. Methods: We used ICG fluorescence angiography to quantitatively assess FJG blood perfusion in
Keywords:
archived fluorescence video files from 26 patients who had undergone FJG transfer. A software
Indocyanine green
program “ROIs”, was used to create a time-fluorescence intensity curve. We retrospectively
Fluorescence angiography
measured the maximum fluorescence intensity at the terminal ileum and the duration (T1/
Free jejunal graft
2max) between when the intensity began rising and when it reached half of the maximum.
Pharyngoesophagectomy
Results: Among the 26 patients, 5 patients suffered venous anastomotic failure. In three of
Esophageal cancer
these cases, anastomosis was corrected intraoperatively; the other two patients underwent a second FJG transfer. Retrospective assessment showed that the mean T1/2max at the FJG serosae was significantly longer in these five patients than that in FJGs with good blood perfusion. Our analysis revealed that a T1/2max >9.6 s may be a good indicator of FJG venous malperfusion. Conclusions: Quantitative analysis of ICG fluorescence angiography proved useful for detecting venous anastomotic failure of FJG, and may help to reduce vascular problems in FJG reconstruction. ª 2015 Elsevier Inc. All rights reserved.
1.
Introduction
In radical surgery for hypopharyngeal and cervical esophageal cancer, reconstruction after pharyngolaryngoesophagectomy
is performed using a skin flap, colon, or jejunal graft. Of these methods, free jejunal graft (FJG) transplantation is most widely performed [1e4]. However, the procedure is complex, requiring both microvascular and intestinal anastomoses, and
* Corresponding author. Second Department of Surgery, Hamamatsu University School of Medicine, 1-20-1, Handayama, Higashi-ku, Hamamatsu 431 3192, Japan. Tel.: þ81 53 435 2279; fax: þ81 53 435 2273. E-mail address: [email protected] (N. Unno). 0022-4804/$ e see front matter ª 2015 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.jss.2014.10.049
395
j o u r n a l o f s u r g i c a l r e s e a r c h 1 9 4 ( 2 0 1 5 ) 3 9 4 e3 9 9
the success of the reconstruction is primarily dependent on the FJG blood flow. Although microvascular techniques are becoming more advanced, the anastomoses of the jejunal blood vessels to the cervical vessels are often challenging. Failure of vascular anastomosis causes FJG necrosis. To avoid this, FJG blood flow should be intraoperatively assessed. Conventionally, surgeons judge the FJG blood flow by observing the graft’s serosal color, peristaltic movement, pulsation of the vasa recti, and Doppler ultrasound of mesenteric arteries. However, none of these techniques are sufficient to assess the FJG blood flow accurately [3]. Recently, tissue blood flow has been intraoperatively visualized by using indocyanine green (ICG) fluorescence angiography in various surgical fields, such as cardiac surgery [5e7], and transplantation [8]. This technique has also been applied to esophageal reconstruction, including FJG transplantation, but it has failed to reduce the incidence of anastomotic leakage [9,10]. Intraoperative assessment of arterial blood flow is relatively easy using the techniques described previously, but it is difficult to identify venous malperfusion of the graft caused by the failure of venous drainage. A previous study of ICG fluorescence angiography in microsurgical breast reconstruction could not detect the graft’s venous congestion because the ICG fluorescence signal was detected as a result of arterial perfusion [11]. To detect venous malperfusion in FJGs after pharyngolaryngoesophagectomy, we used newly developed software that can quantify the fluorescence intensity in the desired area of the surgical field. With this program, we assessed changes in ICG fluorescence intensity and created a time-florescence intensity curve of the ICG fluorescence angiography using archived video files. In this study, we retrospectively analyzed the data of our surgical cases with FJG, seeking a pharmacokinetic parameter that can predict FJG venous malperfusion intraoperatively.
2.
Material and methods
2.1.
ICG fluorescence angiography
underwent FJG transfer after pharyngolaryngoesophagectomy for hypopharyngeal cancer, cervical esophageal cancer, or thyroidal cancer. The tumors were located in the hypopharynx in 22 patients, the cervical esophagus in 2 patients, the middle thoracic esophagus in 1 patient, and the thyroid in 1 patient (Table). The anastomotic vessels are shown in Table. Figure 1C shows an intraoperative view of ICG fluorescence angiography of FJG. A surgeon directly handled the camera unit and observed the real-time image on a laptop computer (Fig. 1A). After the pharyngolaryngoesophagectomy, reconstruction with an FJG was performed. The superior thyroid artery was used as the feeding artery with end-to-end anastomosis, whereas the jugular vein was used as the drainage vein with end-to-side anastomosis. Esophago-jejunal anastomosis was performed after the vessel anastomoses (Fig. 1B and D). The video files of the ICG fluorescence angiography were stored on a computer hard drive and retrospectively analyzed with the newly developed ROIs software (Hamamatsu Photonics K. K.). In the quantitative analysis of ICG fluorescence angiography, a time curve of fluorescence intensity at the serosae of the middle portion of the FJG was created and retrospectively analyzed in each case. The maximum fluorescence intensity in thee serosal surface in the FJG was recorded as FIMAX. T1/ 2max was defined as the duration between when the intensity began rising and when it reached half of FIMAX (Fig. 2). FIMAX and T1/2max were calculated as discussed previously, and we compared the differences in either FIMAX and T1/2max between successful cases and venous malperfusion cases.
2.3.
Statistical analysis
The data are expressed as the mean standard deviation. Statistical significance was assessed using the two-sided Student t-test. Statistical analyses were performed using StatView 5.0 (SAS Institute, Tokyo, Japan).
Table e Patients characteristics and anastomotic vessels. ICG fluorescence angiography was performed using a near-infrared camera system (PDE; Hamamatsu Photonics K. K., Hamamatsu, Japan) that activates ICG with emitted light (wavelength: 760 nm) [12]. ICG (1 mL, Diagnogreen 0.5%; Daiichi-Sankyo Pharmaceutical, Tokyo, Japan) was intravenously injected, after which it instantly bound to globulins in the plasma. ICG absorbs light in the nearinfrared range, with a maximum wavelength of 805 nm; it fluoresces with a maximum wavelength of 840 nm in plasma [13].
2.2. Intraoperative monitoring of ICG fluorescence angiography in patients All procedures used in this study were approved by the Ethics Committee of Clinical Research of the Hamamatsu University School of Medicine and with written consent was obtained from each patient. Between February 2007 and November 2011, 26 consecutive patients (24 male and 2 female)
Characteristics and anastomotic vessels Age (range) Sex Male Female Location Ph Ce Mt Thyroid Operative procedure FJG Gastric pull-up and FJG Feeding artery Superior thyroidal artery Transverse cervical artery Carotid artery Drainage vein Internal jugular vein External jugular vein
n 63.1 (49e75) 24 2 22 2 1 1 24 2 15 9 2 22 4
396
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Fig. 1 e Intraoperative view of ICG fluorescence angiography. (A) A surgeon handles a near-infrared camera probe to capture the images of an FJG. (B) Macroscopic image of an FJG. (C) ICG fluorescence angiography of an FJG. (D) A pictorial of an FJG. The right (Rt.) superior thyroid artery was used as the feeding artery with end-to-end anastomosis, whereas the Rt. jugular vein was used as the drainage vein with end-to-side anastomosis after completion of pharyngo-jejunal anastomosis. Esophago-jejunal anastomosis has not yet performed in the illustration. (E) Clinical courses of 26 patients who underwent FJG transfer.
3.
Results
3.1.
Results of FJG surgery
During the study period, 26 patients underwent FJG transfer after pharyngolaryngoesophagectomy (Fig. 1D). Among them, 19 patients had no events regarding blood perfusion of the FJG. There were no perioperative deaths. All patients started oral intake at their discharge from the hospital. In two patients, occlusion of the arterial anastomosis of the FJG was identified intraoperatively when the malperfusion of the grafts was detected by either lack of Doppler ultrasound signal at the marginal arteries or lack of ICG fluorescence signals in the serosae of the FJGs. The arterial anastomoses were immediately fixed by the surgeons, and the recovery of perfusion in the FJGs was confirmed by both
Doppler ultrasound and a second ICG fluorescence angiography. Five patients exhibited occlusion of the venous anastomosis. In three of these cases, venous malperfusion was detected intraoperatively when the surgeons noticed unusually slow fluorescence signals on the FJG serosae. Immediate revisions of the venous anastomoses provided recovery of good blood perfusion, which was confirmed with a second ICG fluorescence angiography. The other two patients were identified as having FJG necrosis at 1 d and 2 d after the operation. Surgeons did not notice the FJG malperfusion because they obtained audible Doppler ultrasound and positive ICG fluorescence signals during the initial surgery. In both patients, although the arterial anastomoses in the necrotized FJGs were confirmed to be patent at the second operation, the venous anastomoses were
j o u r n a l o f s u r g i c a l r e s e a r c h 1 9 4 ( 2 0 1 5 ) 3 9 4 e3 9 9
397
Fig. 3 e The receiver operating characteristics curve of T1/ 2max. The area under the curve was 0.82. A cutoff value of T1/2max of <9.6 s showed sensitivity of 80%, and a specificity of 92% for prediction of venous malperfusion of an FJG. (Color version of figure is available online.)
Fig. 2 e (A) Comparison of the time-fluorescence intensity curves of ICG fluorescence angiography in the FJG serosae of a patient with good FJG perfusion and a patient with venous congestion as a result of venous obstruction. (FIMAX: maximum fluorescence intensity; T1/2max: the duration between when the intensity began rising and when it reached half of the an uprising point and a point to reach the half of the FIMAX.) (B) Comparison of T1/2max between successful cases (n [ 25) and cases with failed venous drainage (n [ 5) *P < 0.01.
3.3.
The receiver operating characteristics analysis demonstrated that T1/2max was a significant predictor of venous malperfusion in FJG. With a cutoff T1/2max value of <9.6 s, the sensitivity and specificity for prediction of venous malperfusion of FJG were 80% and 92%, respectively, and the area under the curve was 0.82 (Fig. 3).
4. thrombosed. The patients underwent a second laparotomy, and new FJGs were transferred after removal of the necrotized FJG. The vascular anastomotic patency was confirmed with ICG fluorescence angiography. After the successful transfer of FJGs, both patients’ postoperative courses were uneventful.
3.2. Analysis of time-fluorescence intensity curve in patients Retrospective analysis of the time-fluorescence intensity curve of ICG fluorescence angiography at FJG serosae identified that all five cases of venous anastomotic failure showed a delayed increase of fluorescence signals (Fig. 2A). The mean T1/2max in successful cases was 5.8 4.3 s, whereas the mean T1/2max in cases with failed venous drainage was 16.2 10.6 s (P < 0.01; Fig. 2B). By contrast, the maximum fluorescence intensity of the serosae at the plateau phase (FIMAX) showed no significant differences between the two groups (data not shown).
Predicting venous malperfusion in FJG
Discussion
Since Seidenberg et al. introduced reconstruction with an FJG in 1959 [14] the procedure has become popular for treating hypopharyngeal carcinoma and some cases of cervical esophageal carcinoma [2,4]. Reconstruction with an FJG is considered superior to reconstruction with a muscle or skin flap [4] because non-digestive conduits lacks peristaltic function and a mucous lining, which may be associated with difficulty swallowing or passing food. However, the procedure is technically demanding. Although microvascular reconstruction has greatly improved, there remains much room for improvement and further study. Particularly, the rate of graft failure mainly as a result of graft malperfusion is between 3% and 24% [3,4,15]. A necrotic FJG transferred to the neck is a life-threatening complication because it is adjacent to major vessels, such as the carotid arteries and the jugular veins, that can become infected by necrotic tissue. Venous anastomosis is the most common cause of FJG failure [3,16]. As in the present study, the failure of arterial anastomosis in FJG can be detected intraoperatively with relatively ease. Arterial occlusion causes loss of peristaltic
398
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movement, audible Doppler ultrasound at the mesenteric arteries, and loss of ICG fluorescence signals in the FJG, which help surgeons to notice an arterial occlusion before skin closure and avoid catastrophe. By contrast, it is more difficult for surgeons to notice venous malperfusion in an FJG because blood feeding via the arterial anastomosis facilitates color changes of the serosae, peristalsis movement, and audible Doppler ultrasound at the mesenteric vessels. Even ICG fluorescence angiography shows bright fluorescence signals in the FJG serosae in cases of venous malperfusion. For these reasons, we missed two cases of venous malperfusion in which we should have corrected the venous anastomosis in the initial surgery and could have avoided FJG necrosis. These experiences motivated us to seek out a new parameter to detect venous malperfusion of the FJG intraoperatively. In this case series, surgeons noticed FJG venous malperfusion in three cases because of an unusual slow fluorescence signals in the FJG serosae during ICG fluorescence angiography. This encouraged us to analyze the ICG fluorescence angiography quantitatively. Intraoperative ICG fluorescence angiography is an emerging technique. Using a near-infrared camera system, surgeons can obtain real-time images of blood flow in the desired surgical field. Previously, ICG fluorescence imaging has been applied as a lymphography for diagnosis of lymphedema [12], and the sentinel lymph nodes of breast cancer [17], and as an angiography for peripheral, cardiac, and neurovascular surgery [5,18,19]. Fluorescence images have traditionally been visually interpreted based on the surgeons’ experience. Quantification of fluorescence images has been difficult because the absolute values of fluorescence intensity are seriously affected by room lighting, fluid in the operative field, and fat. The background fluorescence level is different for each surgery. In this study, we switched from assessing the images visually to plotting to chronological changes in the fluorescence intensity at any desired region. The newly developed ROIs software enabled us to trace the fluorescence change over time not only in real-time images but also in archived video files. We retrospectively assessed the time-fluorescence intensity curves in video files of 26 cases using the ROIs software to assess changes in the curve. The 5 cases with venous malperfusion showed a longer T1/2max than the cases with successful FJG perfusion. According to the receiver operating characteristics analysis, a T1/2max >9.6 s may be indicative of venous malperfusion. In venous congestion resulting from a failure of venous anastomosis, arterial flow continues causing increased intravascular pressure and interstitial edema. The increased extravascular pressure causes external compression and collapse of the vessels, which further elevates microvascular resistance [20e22]. These mechanisms may explain the delayed increase in fluorescence intensity in cases of venous malperfusion. By combining the T1/2max parameter with conventional observations of Doppler ultrasound at the mesenteric vessels, peristalsis movement, and color changes of the serosa, we could close the skin without concern about FJG perfusion failure. Prospective studies are needed to demonstrate the usefulness of the intraoperative quantitative analysis of ICG fluorescence angiography to reduce vascular problems in FJGs.
Even when FJG perfusion is properly assessed intraoperatively with ICG fluorescence angiography, postoperative monitoring of graft viability remains important to improving the overall success rate of FJG surgery. Most of patients undergo preoperative chemoradiotherapy, which might affect the cervical blood vessels for the anastomosis possibly leading to postoperative anastomotic stenosis or thromboembolic occlusion. Therefore, significant efforts have been made to establish a reliable postoperative monitoring method, such as monitoring of intramucosal pH by tonometer [23], endoscopic observation [24], and Doppler ultrasound monitoring of FJG [24]. Some surgeons prefer to monitor flaps through the small window of the neck incision until the second or third postoperative day [4,25]. Using the monitor flap technique in which a portion of FJG is brought out, ICG fluorescence angiography can be applied postoperatively in the intensive care unit to check the perfusion status of the flaps. Furthermore, venous congestion resulting from failure of venous anastomosis is a common problem in other organ transplantation procedures, such as liver transplantation from living donor [26] or skin flap transfers [27]. Fluorescence angiography with chronological quantification of fluorescence intensity may also be useful to assess venous perfusion in various tissue transfers.
5.
Conclusions
In conclusion, we assessed the utility of ICG fluorescence angiography in FJG surgery. In this retrospective study, T1/ 2max was identified as a useful parameter for detecting intestinal venous malperfusion. Our review of archived video files of ICG fluorescence angiography in FJG patients revealed that 9.6 s may be a reliable T1/2max cutoff value to predict venous malperfusion of FJGs.
Acknowledgment Authors’ contributions: K.K., N.U., and S.M. wrote the article. K.K. did the data analysis. K.K. and N.U. obtaining the funding. N.U. contributed to the conception and design. S.M., M.S., H.K., Y.H., M.O., and T.Y. did the data collection and interpretation. H.M. and H.K. did the critical revision of the article. Each author certifies that he has made substantial contribution as mentioned previously to the work reported in the article. This work was supported by Grant-in-Aid for Scientific Research (C) (24591938) (K.K.) and Grant-in-Aid for Scientific Research (B) (20291958) (N.U.).
Disclosure The authors report no propriety or commercial interest in any product mentioned or concept discussed in this article.
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references
[1] Disa JJ, Pusic AL, Hidalgo DA, Cordeiro PG. Microvascular reconstruction of the hypopharynx: defect classification, treatment algorithm, and functional outcome based on 165 consecutive cases. Plast Reconstr Surg 2003;111:652. [2] Sarukawa S, Asato H, Okazaki M, Nakatsuka T, Takushima A, Harii K. Clinical evaluation and morbidity of 201 free jejunal transfers for oesophagopharyngeal reconstruction during the 20 years 1984-2003. Scand J Plast Reconstr Surg Hand Surg 2006;40:148. [3] Ott K, Lordick F, Molls M, Bartels H, Biemer E, Siewert JR. Limited resection and free jejunal graft interposition for squamous cell carcinoma of the cervical oesophagus. Br J Surg 2009;96:258. [4] Perez-Smith D, Wagels M, Theile DR. Jejunal free flap reconstruction of the pharyngolaryngectomy defect: 368 consecutive cases. J Plast Reconstr Aesthet Surg 2013;66:9. [5] Taggart DP, Choudhary B, Anastasiadis K, Abu-Omar Y, Balacumaraswami L, Pigott DW. Preliminary experience with a novel intraoperative fluorescence imaging technique to evaluate the patency of bypass grafts in total arterial revascularization. Ann Thorac Surg 2003;75:870. [6] Balacumaraswami L, Abu-Omar Y, Choudhary B, Pigott D, Taggart DP. A comparison of transit-time flowmetry and intraoperative fluorescence imaging for assessing coronary artery bypass graft patency. J Thorac Cardiovasc Surg 2005; 130:315. [7] Unno N, Nishiyama M, Suzuki M, et al. Quantitative lymph imaging for assessment of lymph function using indocyanine green fluorescence lymphography. Eur J Vasc Endovasc Surg 2008;36:230. [8] Sekijima M, Tojimbara T, Sato S, et al. An intraoperative fluorescent imaging system in organ transplantation. Transplant Proc 2004;36:2188. [9] Shimada Y, Okumura T, Nagata T, et al. Usefulness of blood supply visualization by indocyanine green fluorescence for reconstruction during esophagectomy. Esophagus 2011;8:259. [10] Pacheco PE, Hill SM, Henriques SM, Paulsen JK, Anderson RC. The novel use of intraoperative laser-induced fluorescence of indocyanine green tissue angiography for evaluation of the gastric conduit in esophageal reconstructive surgery. Am J Surg 2013;205:349. [11] Newman MI, Samson MC. The application of laser-assisted indocyanine green fluorescent dye angiography in microsurgical breast reconstruction. J Reconstr Microsurg 2009;25:21. [12] Unno N, Inuzuka K, Suzuki M, et al. Preliminary experience with a novel fluorescence lymphography using indocyanine green in patients with secondary lymphedema. J Vasc Surg 2007;45:1016.
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[13] Benson RC, Kues HA. Fluorescence properties of indocyanine green as related to angiography. Phys Med Biol 1978;23:159. [14] Seidenberg B, Rosenak SS, Hurwitt ES, Som ML. Immediate reconstruction of the cervical esophagus by a revascularized isolated jejunal segment. Ann Surg 1959;149:162. [15] Yamana I, Shiraishi T, Shiroshita T, et al. Free jejunal graft repair after pharyngolaryngo-esophagectomy-risk factor analysis for postoperative dysphagia. Ann Thorac Cardiovasc Surg 2014;20:1. [16] Shirakawa Y, Naomoto Y, Noma K, et al. Free jejunal graft for hypopharyngeal and esophageal reconstruction. Langenbecks Arch Surg 2004;389:387. [17] Kitai T, Inomoto T, Miwa M, Shikayama T. Fluorescence navigation with indocyanine green for detecting sentinel lymph nodes in breast cancer. Breast Cancer 2005;12:211. [18] Unno N, Suzuki M, Yamamoto N, et al. Indocyanine green fluorescence angiography for intraoperative assessment of blood flow: a feasibility study. Eur J Vasc Endovasc Surg 2008; 35:205. [19] Raabe A, Nakaji P, Beck J, et al. Prospective evaluation of surgical microscope-integrated intraoperative near-infrared indocyanine green videoangiography during aneurysm surgery. J Neurosurg 2005;103:982. [20] Angel MF, Mellow CG, Knight KR, O’Brien BM. Secondary ischemia time in rodents: contrasting complete pedicle interruption with venous obstruction. Plast Reconstr Surg 1990;85:789. discussion 94e5. [21] Hjortdal VE, Sinclair T, Kerrigan CL, Solymoss S. Venous ischemia in skin flaps: microcirculatory intravascular thrombosis. Plast Reconstr Surg 1994;93:366. [22] Hjortdal VE, Hansen ES, Hauge E. Myocutaneous flap ischemia: flow dynamics following venous and arterial obstruction. Plast Reconstr Surg 1992;89:1083. [23] Kamiya K, Suzuki S, Mineta H, Konno H. Tonometer pHi monitoring of free jejunal grafts following pharyngolaryngoesophagectomy for hypopharyngeal or cervical esophageal cancer. Dig Surg 2007;24:214. [24] Haughey BH. The jejunal free flap in oral cavity and pharyngeal reconstruction. Otolaryngol Clin North Am 1994; 27:1159. [25] Cho BC, Shin DP, Byun JS, Park JW, Baik BS. Monitoring flap for buried free tissue transfer: its importance and reliability. Plast Reconstr Surg 2002;110:1249. [26] Kim KW, Kim TK, Kim SY, et al. Doppler sonographic abnormalities suggestive of venous congestion in the right lobe graft of living donor liver transplant recipients. AJR Am J Roentgenol 2007;188:W239. [27] Mirzabeigi MN, Wang T, Kovach SJ, Taylor JA, Serletti JM, Wu LC. Free flap take-back following postoperative microvascular compromise: predicting salvage versus failure. Plast Reconstr Surg 2012;130:579.
Available online at www.sciencedirect.com
ScienceDirect journal homepage: www.JournalofSurgicalResearch.com
Quantitative assessment of the free jejunal graft perfusion Kinji Kamiya, MD, PhD,a Naoki Unno, MD, PhD, FACS,a,* Shinichiro Miyazaki, MD, PhD,a Masaki Sano, MD, PhD,a Hirotoshi Kikuchi, MD, PhD,a Yoshihiro Hiramatsu, MD, PhD,a Manabu Ohta, MD, PhD,a Takashi Yamatodani, MD, PhD,b Hiroyuki Mineta, MD, PhD,b and Hiroyuki Konno, MD, PhD, FACSa a b
Second Department of Surgery, Hamamatsu University School of Medicine, Hamamatsu, Japan Department of Otolaryngology/Head and Neck Surgery, Hamamatsu University School of Medicine, Hamamatsu, Japan
article info
abstract
Article history:
Background: Reconstruction with free jejunal graft (FJG) is often performed for patients with
Received 12 May 2014
hypopharyngeal or cervical esophageal cancer. During reconstruction with an FJG after
Received in revised form
pharyngoesophagectomy, it is critical to intraoperatively detect venous anastomotic failure
16 October 2014
and subsequent venous malperfusion to avoid postoperative FJG necrosis. This study in-
Accepted 30 October 2014
troduces a novel method for assessing blood perfusion in FJGs by using indocyanine green
Available online 5 November 2014
(ICG) fluorescence angiography. Methods: We used ICG fluorescence angiography to quantitatively assess FJG blood perfusion in
Keywords:
archived fluorescence video files from 26 patients who had undergone FJG transfer. A software
Indocyanine green
program “ROIs”, was used to create a time-fluorescence intensity curve. We retrospectively
Fluorescence angiography
measured the maximum fluorescence intensity at the terminal ileum and the duration (T1/
Free jejunal graft
2max) between when the intensity began rising and when it reached half of the maximum.
Pharyngoesophagectomy
Results: Among the 26 patients, 5 patients suffered venous anastomotic failure. In three of
Esophageal cancer
these cases, anastomosis was corrected intraoperatively; the other two patients underwent a second FJG transfer. Retrospective assessment showed that the mean T1/2max at the FJG serosae was significantly longer in these five patients than that in FJGs with good blood perfusion. Our analysis revealed that a T1/2max >9.6 s may be a good indicator of FJG venous malperfusion. Conclusions: Quantitative analysis of ICG fluorescence angiography proved useful for detecting venous anastomotic failure of FJG, and may help to reduce vascular problems in FJG reconstruction. ª 2015 Elsevier Inc. All rights reserved.
1.
Introduction
In radical surgery for hypopharyngeal and cervical esophageal cancer, reconstruction after pharyngolaryngoesophagectomy
is performed using a skin flap, colon, or jejunal graft. Of these methods, free jejunal graft (FJG) transplantation is most widely performed [1e4]. However, the procedure is complex, requiring both microvascular and intestinal anastomoses, and
* Corresponding author. Second Department of Surgery, Hamamatsu University School of Medicine, 1-20-1, Handayama, Higashi-ku, Hamamatsu 431 3192, Japan. Tel.: þ81 53 435 2279; fax: þ81 53 435 2273. E-mail address: [email protected] (N. Unno). 0022-4804/$ e see front matter ª 2015 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.jss.2014.10.049
395
j o u r n a l o f s u r g i c a l r e s e a r c h 1 9 4 ( 2 0 1 5 ) 3 9 4 e3 9 9
the success of the reconstruction is primarily dependent on the FJG blood flow. Although microvascular techniques are becoming more advanced, the anastomoses of the jejunal blood vessels to the cervical vessels are often challenging. Failure of vascular anastomosis causes FJG necrosis. To avoid this, FJG blood flow should be intraoperatively assessed. Conventionally, surgeons judge the FJG blood flow by observing the graft’s serosal color, peristaltic movement, pulsation of the vasa recti, and Doppler ultrasound of mesenteric arteries. However, none of these techniques are sufficient to assess the FJG blood flow accurately [3]. Recently, tissue blood flow has been intraoperatively visualized by using indocyanine green (ICG) fluorescence angiography in various surgical fields, such as cardiac surgery [5e7], and transplantation [8]. This technique has also been applied to esophageal reconstruction, including FJG transplantation, but it has failed to reduce the incidence of anastomotic leakage [9,10]. Intraoperative assessment of arterial blood flow is relatively easy using the techniques described previously, but it is difficult to identify venous malperfusion of the graft caused by the failure of venous drainage. A previous study of ICG fluorescence angiography in microsurgical breast reconstruction could not detect the graft’s venous congestion because the ICG fluorescence signal was detected as a result of arterial perfusion [11]. To detect venous malperfusion in FJGs after pharyngolaryngoesophagectomy, we used newly developed software that can quantify the fluorescence intensity in the desired area of the surgical field. With this program, we assessed changes in ICG fluorescence intensity and created a time-florescence intensity curve of the ICG fluorescence angiography using archived video files. In this study, we retrospectively analyzed the data of our surgical cases with FJG, seeking a pharmacokinetic parameter that can predict FJG venous malperfusion intraoperatively.
2.
Material and methods
2.1.
ICG fluorescence angiography
underwent FJG transfer after pharyngolaryngoesophagectomy for hypopharyngeal cancer, cervical esophageal cancer, or thyroidal cancer. The tumors were located in the hypopharynx in 22 patients, the cervical esophagus in 2 patients, the middle thoracic esophagus in 1 patient, and the thyroid in 1 patient (Table). The anastomotic vessels are shown in Table. Figure 1C shows an intraoperative view of ICG fluorescence angiography of FJG. A surgeon directly handled the camera unit and observed the real-time image on a laptop computer (Fig. 1A). After the pharyngolaryngoesophagectomy, reconstruction with an FJG was performed. The superior thyroid artery was used as the feeding artery with end-to-end anastomosis, whereas the jugular vein was used as the drainage vein with end-to-side anastomosis. Esophago-jejunal anastomosis was performed after the vessel anastomoses (Fig. 1B and D). The video files of the ICG fluorescence angiography were stored on a computer hard drive and retrospectively analyzed with the newly developed ROIs software (Hamamatsu Photonics K. K.). In the quantitative analysis of ICG fluorescence angiography, a time curve of fluorescence intensity at the serosae of the middle portion of the FJG was created and retrospectively analyzed in each case. The maximum fluorescence intensity in thee serosal surface in the FJG was recorded as FIMAX. T1/ 2max was defined as the duration between when the intensity began rising and when it reached half of FIMAX (Fig. 2). FIMAX and T1/2max were calculated as discussed previously, and we compared the differences in either FIMAX and T1/2max between successful cases and venous malperfusion cases.
2.3.
Statistical analysis
The data are expressed as the mean standard deviation. Statistical significance was assessed using the two-sided Student t-test. Statistical analyses were performed using StatView 5.0 (SAS Institute, Tokyo, Japan).
Table e Patients characteristics and anastomotic vessels. ICG fluorescence angiography was performed using a near-infrared camera system (PDE; Hamamatsu Photonics K. K., Hamamatsu, Japan) that activates ICG with emitted light (wavelength: 760 nm) [12]. ICG (1 mL, Diagnogreen 0.5%; Daiichi-Sankyo Pharmaceutical, Tokyo, Japan) was intravenously injected, after which it instantly bound to globulins in the plasma. ICG absorbs light in the nearinfrared range, with a maximum wavelength of 805 nm; it fluoresces with a maximum wavelength of 840 nm in plasma [13].
2.2. Intraoperative monitoring of ICG fluorescence angiography in patients All procedures used in this study were approved by the Ethics Committee of Clinical Research of the Hamamatsu University School of Medicine and with written consent was obtained from each patient. Between February 2007 and November 2011, 26 consecutive patients (24 male and 2 female)
Characteristics and anastomotic vessels Age (range) Sex Male Female Location Ph Ce Mt Thyroid Operative procedure FJG Gastric pull-up and FJG Feeding artery Superior thyroidal artery Transverse cervical artery Carotid artery Drainage vein Internal jugular vein External jugular vein
n 63.1 (49e75) 24 2 22 2 1 1 24 2 15 9 2 22 4
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Fig. 1 e Intraoperative view of ICG fluorescence angiography. (A) A surgeon handles a near-infrared camera probe to capture the images of an FJG. (B) Macroscopic image of an FJG. (C) ICG fluorescence angiography of an FJG. (D) A pictorial of an FJG. The right (Rt.) superior thyroid artery was used as the feeding artery with end-to-end anastomosis, whereas the Rt. jugular vein was used as the drainage vein with end-to-side anastomosis after completion of pharyngo-jejunal anastomosis. Esophago-jejunal anastomosis has not yet performed in the illustration. (E) Clinical courses of 26 patients who underwent FJG transfer.
3.
Results
3.1.
Results of FJG surgery
During the study period, 26 patients underwent FJG transfer after pharyngolaryngoesophagectomy (Fig. 1D). Among them, 19 patients had no events regarding blood perfusion of the FJG. There were no perioperative deaths. All patients started oral intake at their discharge from the hospital. In two patients, occlusion of the arterial anastomosis of the FJG was identified intraoperatively when the malperfusion of the grafts was detected by either lack of Doppler ultrasound signal at the marginal arteries or lack of ICG fluorescence signals in the serosae of the FJGs. The arterial anastomoses were immediately fixed by the surgeons, and the recovery of perfusion in the FJGs was confirmed by both
Doppler ultrasound and a second ICG fluorescence angiography. Five patients exhibited occlusion of the venous anastomosis. In three of these cases, venous malperfusion was detected intraoperatively when the surgeons noticed unusually slow fluorescence signals on the FJG serosae. Immediate revisions of the venous anastomoses provided recovery of good blood perfusion, which was confirmed with a second ICG fluorescence angiography. The other two patients were identified as having FJG necrosis at 1 d and 2 d after the operation. Surgeons did not notice the FJG malperfusion because they obtained audible Doppler ultrasound and positive ICG fluorescence signals during the initial surgery. In both patients, although the arterial anastomoses in the necrotized FJGs were confirmed to be patent at the second operation, the venous anastomoses were
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Fig. 3 e The receiver operating characteristics curve of T1/ 2max. The area under the curve was 0.82. A cutoff value of T1/2max of <9.6 s showed sensitivity of 80%, and a specificity of 92% for prediction of venous malperfusion of an FJG. (Color version of figure is available online.)
Fig. 2 e (A) Comparison of the time-fluorescence intensity curves of ICG fluorescence angiography in the FJG serosae of a patient with good FJG perfusion and a patient with venous congestion as a result of venous obstruction. (FIMAX: maximum fluorescence intensity; T1/2max: the duration between when the intensity began rising and when it reached half of the an uprising point and a point to reach the half of the FIMAX.) (B) Comparison of T1/2max between successful cases (n [ 25) and cases with failed venous drainage (n [ 5) *P < 0.01.
3.3.
The receiver operating characteristics analysis demonstrated that T1/2max was a significant predictor of venous malperfusion in FJG. With a cutoff T1/2max value of <9.6 s, the sensitivity and specificity for prediction of venous malperfusion of FJG were 80% and 92%, respectively, and the area under the curve was 0.82 (Fig. 3).
4. thrombosed. The patients underwent a second laparotomy, and new FJGs were transferred after removal of the necrotized FJG. The vascular anastomotic patency was confirmed with ICG fluorescence angiography. After the successful transfer of FJGs, both patients’ postoperative courses were uneventful.
3.2. Analysis of time-fluorescence intensity curve in patients Retrospective analysis of the time-fluorescence intensity curve of ICG fluorescence angiography at FJG serosae identified that all five cases of venous anastomotic failure showed a delayed increase of fluorescence signals (Fig. 2A). The mean T1/2max in successful cases was 5.8 4.3 s, whereas the mean T1/2max in cases with failed venous drainage was 16.2 10.6 s (P < 0.01; Fig. 2B). By contrast, the maximum fluorescence intensity of the serosae at the plateau phase (FIMAX) showed no significant differences between the two groups (data not shown).
Predicting venous malperfusion in FJG
Discussion
Since Seidenberg et al. introduced reconstruction with an FJG in 1959 [14] the procedure has become popular for treating hypopharyngeal carcinoma and some cases of cervical esophageal carcinoma [2,4]. Reconstruction with an FJG is considered superior to reconstruction with a muscle or skin flap [4] because non-digestive conduits lacks peristaltic function and a mucous lining, which may be associated with difficulty swallowing or passing food. However, the procedure is technically demanding. Although microvascular reconstruction has greatly improved, there remains much room for improvement and further study. Particularly, the rate of graft failure mainly as a result of graft malperfusion is between 3% and 24% [3,4,15]. A necrotic FJG transferred to the neck is a life-threatening complication because it is adjacent to major vessels, such as the carotid arteries and the jugular veins, that can become infected by necrotic tissue. Venous anastomosis is the most common cause of FJG failure [3,16]. As in the present study, the failure of arterial anastomosis in FJG can be detected intraoperatively with relatively ease. Arterial occlusion causes loss of peristaltic
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movement, audible Doppler ultrasound at the mesenteric arteries, and loss of ICG fluorescence signals in the FJG, which help surgeons to notice an arterial occlusion before skin closure and avoid catastrophe. By contrast, it is more difficult for surgeons to notice venous malperfusion in an FJG because blood feeding via the arterial anastomosis facilitates color changes of the serosae, peristalsis movement, and audible Doppler ultrasound at the mesenteric vessels. Even ICG fluorescence angiography shows bright fluorescence signals in the FJG serosae in cases of venous malperfusion. For these reasons, we missed two cases of venous malperfusion in which we should have corrected the venous anastomosis in the initial surgery and could have avoided FJG necrosis. These experiences motivated us to seek out a new parameter to detect venous malperfusion of the FJG intraoperatively. In this case series, surgeons noticed FJG venous malperfusion in three cases because of an unusual slow fluorescence signals in the FJG serosae during ICG fluorescence angiography. This encouraged us to analyze the ICG fluorescence angiography quantitatively. Intraoperative ICG fluorescence angiography is an emerging technique. Using a near-infrared camera system, surgeons can obtain real-time images of blood flow in the desired surgical field. Previously, ICG fluorescence imaging has been applied as a lymphography for diagnosis of lymphedema [12], and the sentinel lymph nodes of breast cancer [17], and as an angiography for peripheral, cardiac, and neurovascular surgery [5,18,19]. Fluorescence images have traditionally been visually interpreted based on the surgeons’ experience. Quantification of fluorescence images has been difficult because the absolute values of fluorescence intensity are seriously affected by room lighting, fluid in the operative field, and fat. The background fluorescence level is different for each surgery. In this study, we switched from assessing the images visually to plotting to chronological changes in the fluorescence intensity at any desired region. The newly developed ROIs software enabled us to trace the fluorescence change over time not only in real-time images but also in archived video files. We retrospectively assessed the time-fluorescence intensity curves in video files of 26 cases using the ROIs software to assess changes in the curve. The 5 cases with venous malperfusion showed a longer T1/2max than the cases with successful FJG perfusion. According to the receiver operating characteristics analysis, a T1/2max >9.6 s may be indicative of venous malperfusion. In venous congestion resulting from a failure of venous anastomosis, arterial flow continues causing increased intravascular pressure and interstitial edema. The increased extravascular pressure causes external compression and collapse of the vessels, which further elevates microvascular resistance [20e22]. These mechanisms may explain the delayed increase in fluorescence intensity in cases of venous malperfusion. By combining the T1/2max parameter with conventional observations of Doppler ultrasound at the mesenteric vessels, peristalsis movement, and color changes of the serosa, we could close the skin without concern about FJG perfusion failure. Prospective studies are needed to demonstrate the usefulness of the intraoperative quantitative analysis of ICG fluorescence angiography to reduce vascular problems in FJGs.
Even when FJG perfusion is properly assessed intraoperatively with ICG fluorescence angiography, postoperative monitoring of graft viability remains important to improving the overall success rate of FJG surgery. Most of patients undergo preoperative chemoradiotherapy, which might affect the cervical blood vessels for the anastomosis possibly leading to postoperative anastomotic stenosis or thromboembolic occlusion. Therefore, significant efforts have been made to establish a reliable postoperative monitoring method, such as monitoring of intramucosal pH by tonometer [23], endoscopic observation [24], and Doppler ultrasound monitoring of FJG [24]. Some surgeons prefer to monitor flaps through the small window of the neck incision until the second or third postoperative day [4,25]. Using the monitor flap technique in which a portion of FJG is brought out, ICG fluorescence angiography can be applied postoperatively in the intensive care unit to check the perfusion status of the flaps. Furthermore, venous congestion resulting from failure of venous anastomosis is a common problem in other organ transplantation procedures, such as liver transplantation from living donor [26] or skin flap transfers [27]. Fluorescence angiography with chronological quantification of fluorescence intensity may also be useful to assess venous perfusion in various tissue transfers.
5.
Conclusions
In conclusion, we assessed the utility of ICG fluorescence angiography in FJG surgery. In this retrospective study, T1/ 2max was identified as a useful parameter for detecting intestinal venous malperfusion. Our review of archived video files of ICG fluorescence angiography in FJG patients revealed that 9.6 s may be a reliable T1/2max cutoff value to predict venous malperfusion of FJGs.
Acknowledgment Authors’ contributions: K.K., N.U., and S.M. wrote the article. K.K. did the data analysis. K.K. and N.U. obtaining the funding. N.U. contributed to the conception and design. S.M., M.S., H.K., Y.H., M.O., and T.Y. did the data collection and interpretation. H.M. and H.K. did the critical revision of the article. Each author certifies that he has made substantial contribution as mentioned previously to the work reported in the article. This work was supported by Grant-in-Aid for Scientific Research (C) (24591938) (K.K.) and Grant-in-Aid for Scientific Research (B) (20291958) (N.U.).
Disclosure The authors report no propriety or commercial interest in any product mentioned or concept discussed in this article.
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