Improved Outcomes in Colon and Rectal Surgery part 31 pptx

 improved outcomes in colon and rectal surgery differentiate fibrosis from tumor. If there is suspicion clinically of involvement, we will treat with IORT. Sacrectomy is preserved for those who are fit for surgery with clear cortical destruction or marrow involvement by CT/MRI below S1-2. Our initial experience with this approach is encouraging.(27) Postoperative chemotherapy is usually recommended in our institution, but has been variably administered in the literature. OPERATIVE APPROACH The patient is placed in modified lithotomy position. Initial explo- ration is undertaken to carefully assess for extrapelvic metastatic disease. Careful attention is paid to the liver and the abdomen is assessed for carcinomatous implants. All adhesions are lysed and the ureters are identified. Ureteric catheters are typically used. The left colon is mobilized as is the splenic flexure and attention is focused on the IMA root. If it has not been taken it is mobilized. An assessment for resectablity is made and if the tumor is deemed resectable, the IMA, if not previously ligated, is taken high. The neorectum is mobilized posteriorly initially, laterally, then anteriorly. The areas free from tumor involvement are most easily mobilized and are approached first. As much easy dissection should be done, as can be done, to identify landmarks initially. If anterior structures are clinically involved they are taken en bloc with the neorectum. It is much easier to take the bladder, seminal vesicles and prostate en bloc with the neorectum than to try to separate them. If there is firm adherence to the posterior aspect of the bladder, seminal vesicles or prostate, they should be taken en bloc. If the lesion is quite low in the rectum and adherent to the prostate or vesicles alone, the posterior portion of the prostate and/or the seminal vesicles may be taken without the bladder, but this is much more challenging technically than proceeding with en bloc cystoprostatectomy. In a female en bloc posterior vaginectomy and hysterectomy should be performed with any adherence. Pelvic sidewall involvement is technically difficult to resect secondary to the associated desmoplastic reaction and loss of planes. The nervi erigentes and internal iliac arterial and venous branches can be taken. However, back bleeding from distal venous branches can be torrential and difficult to control despite proximal ligation. The dissection is completed to the pelvic floor circumferentially and a decision is made as to whether sphincter preservation is possible. It is sometimes feasible to preserve the sphincters even if cystoprostatectomy is performed and a coloanal anastomosis may be possible. A double stapled technique, transabdominal-transanal hand sewn technique, low Hartmann, or APR may be necessary. Any suspicious areas for microscopic involvement are treated with IORT after specimen removal. IORT for posteriorly based or pelvic sidewall based areas is relatively easily technically performed with appropriate positioning of a shielding cone. However, it is technically challenging to dose anteriorly unless APR is performed and the patient is moved to the prone position. This allows dose deliv- ery via a cone placed through the perineal wound. If there is gross tumor left behind, we typically will not perform an anastomosis. However, if there is a suspicion of potential microscopic disease only, and this is treated with IORT, we will consider reanastomosis, assuming adequate sphincters and an appropriate margin. All coloanal anastomoses are covered with a proximal diverting loop ileosotomy. As noted above in the case of adherence only posteriorly, IORT is usually performed after the specimen is withdrawn. If the sacrum is clearly involved with tumor, sacrectomy is considered. The dissection for sacrectomy begins posteriorly, typically with internal iliac artery and vein ligation abdominally. The remainder of the dissection is completed, laterally then anteriorly. An osteotomy may be started, typically with the help of an orthope- dic consultant. The ostomy is created, the abdomen closed and the stoma matured. A plastic surgeon may be involved prior to ostomy creation if a rectus abdominus myocutaneous flap for perineal defect reconstruction is considered. The remainder of the sacrectomy is performed after turning the patient to the prone position. Reconstruction is completed frequently with the aid of the plastics consultant. Other flaps such as a gluteus myocutaneous flap may be considered.(10) Expected Outcomes Local recurrence after proctectomy occurs in 2.6 to 32% of patients.(2, 28, 29) Chemotherapy and radiation offer palliation only with median survivals reported between 10 and 17 months. (2, 28, 30) It is estimated that ~50% of patients will present with local recurrence only, without distant metastasis.(2, 31–33) The concept of radical excision for potential cure of recurrent rectal cancer is not new and was reported by Dunphy in 1947.(2, 34) The literature has expanded in recent years with multiple larger series reported with 5 year survivals ranging from 14 to 44% (see table).(2, 5, 10, 11, 13, 35–44) In fact in a subset of patients with R0 resections reported by Valentini a 67% 5 year survival was noted.(15) Long-term outcome is directly related to ability to clear local tumor in the pelvis and the absence of metastatic disease. Surgical intervention alone typically does not suffice. It is clear that a multidisciplinary approach is essential in these complex patients. Case controlled data suggests IORT can decrease local recurrence and play a role in a potentially curative treatment algorithm even in the presence of a microscopically positive margin.(45–48) In the presence of gross persistent disease it does not appear as effective, but may be useful in a multidisciplinary approach with pre and/or postop chemo-radiotherapy. (27) Preop chemo-radiotherapy and postop chemotherapy are typically employed as outlined previously. Heriot et al. hypothesize that a significant number of patients that could be candidates for resection likely are not operated secondary to perceived excessive morbidity and mortality associated with these difficult cases.(2) They argue, however, that in carefully selected patients, resection is not only safe and reason- able, but indeed offers the only chance of cure. They advocate an extended radical en bloc resection of all involved or potentially involved structures in the pelvis. The extent of resection involves all involved areas of tumor/desmoplastic reaction. This radical en bloc extended resection is to include involved common or exter- nal iliac vessels with reconstruction, wide resection of the pelvic sidewall, sacrectomy, and or partial resection of the bony pelvis if clinically involved.(2) In their series IORT was utilized selectively and chemo-radiotherapy was typically employed. In this excep- tional series of 160 patients, only 7 were found to be unresectable. Overall 5 year survival was 36.6% and cancer specific survival was 41.5% with a mean follow-up of 32 months. Unfavorable factors  indications and outcomes for treatment of recurrent rectal cancer associated with impaired survival included a lymph node positive primary tumor, margin involvement, use of IORT (likely secondary to use only in more difficult tumors), and lateral recurrence (sidewall involvement). Perioperative mortality was 0.6% (1/160) secondary to hemorrhage, morbidity was 27%.(2) They note the need for extensive multidisciplinary involvement and plan- ning, and comment that this surgery is not for the “occasional participant”.(2) These data and others confirm that the overriding principle of this challenging surgery is to attempt to obtain clear surgical margins.(2, 11, 49, 50) Others have pointed out that the pattern of pelvic invasion and the numbers of points of fixation have adverse prognostic implications.(9, 51, 52) Heriot et al’s data points to the difficulty in obtaining a clear margin when the pelvic sidewall is involved which was noted by Moore et al. in the Memorial Sloan Kettering experience.(2, 9) They noted that axial (anastomotic or perineal recurrences) or anterior based recurrences were more easily resected and had better prognosis than lateral recurrences. This was felt secondary to the difficulty in obtaining a clear margin with lateral recurrences secondary to the confines of the bony pelvis and the difficult vascular problems encountered with the iliac branches along the pelvic sidewall. See (Table 28.1).(9) Other factors associated with low likelihood of R0 resection include presentation with pelvic pain, radicular pain, or hydronephrosis.(5, 9) The use of additional preop radiation therapy in those already radiated has been questioned for fear of introducing excessive morbidity. Vermaas et al. note that the addition of a 50 Gy preop dose was associated with a statistically significant improvement in local control without increased morbidity in those eventually undergoing resection compared to a historical group which did not receive additional preop radiation.(53) Those that had a complete response (10%) had an improvement in survival as well. No chemotherapy was used with the preop radiation.(53) Dresen’s data also suggests that reirradiation is safe if the interval to reirradiation is >6 months and the small bowel can be excluded from the field.(11) They recommend a 30–40 Gy preop boost in combination with chemotherapy and introperative radiation if necessary. They noted an increased ability to perform an R0 resection in those reirradiated versus those who were not (64.9% vs. 29.2%, p = 0.004) and an improvement in metastasis free survival at three years (58.7 vs. 17.8%, p < 0.001). As noted previously, others have confirmed similar results.(13) It has been our practice to offer most patients a preop radiation boost combined with 5 FU based chemotherapy in those presenting with recurrent tumors as well, although our numbers do not allow meaningful outcome comparisons.(27) Table 28.2 compares outcomes reported in several larger series. The interpretation of the data from these series is difficult as they represent a diverse mix of presentations and treatment algorithms. Some included combinations of patients with locally advanced primary tumors as well as recurrent tumors. Some used extended exenterative resections with en bloc resection of adja- cent bony and vascular structures and some did not. Some had preoperative radiation boosts, some did not. Some utilized IORT and some did not. The five year survivals in the series outlined ranged from 12 to 44%. The small numbers and mix of patients makes comparisons of different approaches to the close surgical margin impossible. It is not clear from the data whether extended en bloc resection of bony or vascular structures should be performed or IORT should be preferred in these cases. However, although morbidity (27 to 78%) and mortality (0–13%) is significant regardless of approach, the overriding theme in these series remains that a multimodality approach including surgery offers the only opportunity for cure, and that those patients having the longest survival undergo R0 resection. There is a suggestion that similar long term survivals and rates of local control can be obtained when IORT is utilized in patients with a microscopically involved or close margin.(5, 27) TREATMENT OF COLORECTAL LIVER METASTASIS Liver resection for the treatment of metastatic colon cancer was first described by Lortat- Jacob in 1952 (54–56) and in the US by Woodington in 1963.(57) Fifteen years later, Attiyeh (58) described a series of 25 patients who had undergone liver resection for metastatic colon cancer with a 40% five year and a 28% ten year survival. Although these early series were highly selected patients, no other therapy to date provides a better therapeutic benefit than complete resection of isolated metastatic colon cancer to the liver. Historically, treatment with 5 fluorouracil and leucovorin for metastatic colon cancer resulted in 5 year survival rates of less than 5%.(59, 60) The addition of Oxaliplatin and Irinotecan based regimens have improved the median survival for patients with stage IV disease to over two years (61), however 5 year survival rates have Table 28.1 Site of involvement and likelihood of R0 Resection. Anastomotic or perineal wound R0 90% Anastomotic or perineal and anterior R0 72% Lateral and/or posterior component R0 43% Iliac vessels R0 17% N=119 patients with pelvic recurrence of colorectal cancer. Source: Moore et al. (9). Table 28.2 Outcomes in Recurrent Rectal Cancer. Author N 5 year Survival Morbidity Mortality Dresen (11) 147 31.5 59 4.8 Heriot (2) 160 36.6 27 0.1 Maetani (35) 36 28 – – Wiig (36) 47 18 38 4 Yamada (37) 64 23 50 2 Jiménez (38) 55 28 78 5 Kecmanovic (38) 28 17 43 10 Ike (40) 45 14 77 13 Lopez (41) 19 44 67 0 Kakuda (42) 22 12 68 5 Moriya (43) 57 36 58 4 Vermaas (44) 35 16 70 3 Mohiuddin (12) 34 22 – 0 Wanebo (10) 61 31 38 8 Valentín (11) 59 39 – – Source: Adopted from de Wilt et al.(5)  improved outcomes in colon and rectal surgery remained below 10% (62). Interestingly in stage 3 disease, analysis of patient survival reveals three groups with markedly different survival rates. The difference in survival rates for the groups was found to be dependent on extent of nodal involvement with survival ranging from 44% for stage IIIc patients, that is four or more positive lymph nodes to 83% for stage IIIa, 1–3 positive lymph nodes.(63, 64) The ability to identify a subpopulation within a cancer stage which has a potential for improved survival also holds true for patients with stage IV colon cancer patients. Patients with isolated liver metastasis from their colon cancer treated with multimodality therapy including surgery have a significantly improved 5 year survival when compared to patients with isolated liver metastasis treated with chemotherapy alone (65–67) or patients with nonresectable stage IV disease.(68) Approximately, 150,000 new cases of colon cancer were diagnosed in 2007.(69, 70) It has been estimated that almost 20% will have isolated liver metastasis at time of presentation and for patients presenting with local disease, 25% will eventually develop isolated liver metastasis and be eligible for resection.(69, 71) Because of the marked improvement in survival for patients with metastatic colon cancer to the liver treated with resection, identification of patients who are candidates for surgical therapy and appropriate management is of paramount importance. Assessing Resectability Evaluation to determine whether a patient with colon cancer metastatic to the liver is a candidate for hepatic resection depends on 1) medical comorbidities of the patient, 2) anatomic extent of disease in the liver and 3) the presence or extent of extrahepatic disease. Before deciding whether a patient is a nonoperative candidate, thought should be given to downstaging with systemic or hepatic artery infusional chemotherapy (72–74), combined resection and radiofrequency ablation (75, 76), staged resection (77) and in the case of extended resections, portal vein embolization (78, 79). While prior dogma limited candidates for resection based on tumor margins, tumor number or extent of extrahepatic disease (80), the current National Comprehensive Cancer Network (NCCN) guidelines describe outcome objectives to determine if a patient may benefit from resection. The goals currently included in the current NCCN guidelines focus on these ten points: 1) resection must be feasible based on adequate liver reserve after resection and anatomic extent of disease 2) debulking is not recommended, 3) there should be no unresectable extrahepatic sites, 4) if tumors are downstaged, than all original sites must be resectable, 5) resection should be the treatment of choice, 6) ablations can be considered if all disease is treatable, 7) solitary lesions have a better prognosis than multiple lesions, 8) arterial embolizations should be performed only on a clinical trial, 9) the primary tumor must have been resected for cure, and 10) reresec- tions are possible in selected candidates (81). Before surgical resection of liver metastasis, the patient requires a full staging evaluation and risk stratification to determine operative risk. Staging evaluations include a CT scan of the chest, abdomen, and pelvis obtained with oral and intravenous contrast if possible. If poor renal function precludes IV contrast administration for CT scanning then staging can be performed with a noncontrasted CT scan of the chest and other imaging of the abdomen. If the patient has mild, chronic kidney disease stage 1–3 (glomerular filtration rate > 30) than MRI scanning can be helpful to fully evaluate the extent of disease in the liver.(82, 83) Patients with advanced renal dysfunction, in which gadolinium poses a significant risk, may require hepatic evaluation with either transabdominal or laparoscopic ultrasound. While prior studies have suggested precluding patients with greater then three liver metastasis from consideration, outcomes data would suggest that overall tumor burden, vascular involvement and extrahepatic spread may be more important in the decision algorithm.(84) The addition of (18F) fluoro-2-deoxy- D-glucose (FDG) PET scanning to CT or MRI staging has assisted in identifying patients with occult extrahepatic metastasis who may not benefit from surgery.(85–87) In these studies, the addition of FDG-PET was useful in identifying 12% of patients who were not surgical candidates, and altered surgical therapy in an additional 23% who underwent operation. Interestingly, the ability to detect lesions less than one centimeter in the liver was only 25% in the data by Fong et al. and the recurrence within the first year was 40% indicating even with PET scanning that a significant number of liver lesions were missed on imaging. Other investiga- tors have demonstrated that addition of FDG-PET has increased both overall and disease free survival at 5 years with overall actu- arial five year survival of 58% for patients which demonstrated no extrahepatic PET positive lesions on preoperative imaging. More recent reports have demonstrated the ability of recent chemotherapy to affect the ability of FDG-PET to identify viable tumor.(88–91) In a study by Akhurst et al. evaluating the sensitivity of FDG-PET, patients undergoing surgery for resection of metastatic colon cancer were evaluated by PET imaging. Thirteen of 42 patients had received chemotherapy within three months of surgery and 29 /42 had not. In the group which had received chemotherapy 37% of lesions were PET negative as compared to 27% of the lesions in the no chemotherapy group. Interestingly, no tumor >1.2 cm was missed in the group without chemotherapy while some tumors as large as 3.2 cm were PET negative after chemotherapy. In this study, 92% of all tumors smaller than 1 cm were undetected by PET imaging. In a study by Carnaghi et al. PET imaging sensitivity dropped to 62% after chemotherapy and was as low as 18% for lesions under 1 cm in size. Taken together, these data would support use of PET imaging prior to chemotherapy to fully stage the extent of disease and nonreliance on conversion of intrahepatic lesion to PET negative on decision making con- cerning hepatic resection. Extrahepatic disease remains a relative contraindication for liver resection although published studies would support resection in limited cases if all extrahepatic disease can be resected (92). Several studies have demonstrated decreased survival rates for patients resected with positive portal or hepatic artery lymph node metastasis (93, 94). Unfortunately, these studies do not comment on the use of adjuvant therapies after surgery or whether patients had chemotherapy sensitive disease prior to resection. In our practice we will offer resection to patients with extrahepatic lymph node metastasis if the disease is localized to the porta hepatis, is completely resectable at the time of surgery, and had a favorable response to medical therapy. In addition to staging studies, a medical workup would obviously include cardiac evaluations for those displaying cardiac risk factors and pulmonary  indications and outcomes for treatment of recurrent rectal cancer function testing for those with significant lung disease or smoking history. Cardiac stress echo testing can be performed for patients with significant cardiac risk factors. Because there is considerable variability between patients, decisions as to whether a patient is a candidate for resection must take into account the patients overall medical status and the type of procedure being planned. Decision making regarding operative timing can be com- plicated by presentation of the disease. For patients who present with synchronous asymptomatic colon and liver disease, no single treatment algorithm has been established in the field. Acceptable treatment protocols range from complete resection of the colon and liver disease at one operation (95–97) to neoadjuvant chemotherapy followed by synchronous or staged colon and liver resection (98–102). Outcomes from studies evaluating simultaneous liver and colon resections have suggested higher incidences of recurrence and lower overall 5 year survival rates in patients undergoing combined resection. Other authors have recommended a waiting period of 3 months between colon resection and liver resection in order to better select patients for surgery (103, 104). Regardless of the manner in which patients undergo resection, the efficacy of post operative chemotherapy has recently been shown to provide a small survival advantage.(105, 106) Treatment algorithms for resection of metachronous lesions have suggested resection followed by either chemotherapy or hepatic artery infusional (HAI) therapy.(81) Several studies have demonstrated a improvement in disease free and overall survival with the use of HAI (72, 74, 107–109), however, prior studies demonstrating lack of efficacy, introduction of newer chemotherapeutic regimens and high rates of mechanical problems with the pumps (110), have limited there widespread use. Patients who are candidates for liver resection and are on chemotherapy regimens including irinotecan, oxaliplatin, or bevacizumab should be evaluated for hepatic dysfunction prior to surgery.(111) Recent reports have associated the use of irintotecan-based chemotherapy regimens with hepatic steatosis and oxaliplatin based regimens with sinusoidal dilatation.(112, 113) These may occur in 20–30% of patients on therapy. There has been concern that Bevacizumab may potentially increase postoperative complications and mortality due to its effect on vascular endothelial growth factor. In a recent study evaluating 81 patients receiving chemotherapy with Bevacizumab to 44 patients receiving chemotherapy alone, no significant increase in complications were seen after liver resection (114), although increased morbidity and mortality has been reported with patients having increased steatosis at time of resection (113, 115). Preoperative preparation often is related to the extent of liver resection planned. For patients with bilobar disease treatment plans need to be formulated to determine if the tumor can be treated all in one operation or whether sequential procedures will be needed to treat the full extent of the disease.(78, 99) In cases of bilobar disease preference should be given to resection if possible. Occasionally, treatment will involve a combination of resection with the possibility of radiofrequency ablation of remaining contralobar lesions. If the tumors are located near or on the middle vein, and resection will involve removal of more than 70% of the liver, then thought should be given to preoperative portal vein embolization to allow for hypertrophy of the remaining segments prior to tumor removal. Studies have shown decreased morbidity and mortality in patients undergoing preoperative portal embolization before major surgical resection.(79, 116–119) In order to determine the resectability of the patient, factors such as extent of disease, number and location of lesions, synchronous or metachronous presentation, and exposure to previous therapy should all be taken into account. Special consideration should be given for patients with rectal cancer with synchronous liver metastasis. Current standard of care for primary rectal cancers remains combined chemotherapy with rectal and pelvic radiation. The most common regimen would use 5-fluorouracil for radiation sensitization. The poor response rates of metastatic lesions from this chemotherapeutic regimen have led some inves- tigators to suggest initial treatment with oxaliplatin or irinotecan containing regimens, yet local recurrence rates for rectal prima- ries treated with this regimen followed by resection have not been well defined. Currently there is no defined standard of care and the treatment of these patients should be individualized. Adjuvant Therapies In addition to surgical resection and systemic chemotherapy, a significant number of alternative liver directed therapies exist. Treatments including radiofrequency ablation, cryotherapy, microwave ablation, chemoembolization, yttrium-90 and stereotatic high dose radiation are alternate tools for site directed therapy. Cryotherapy has been shown to be an effective treatment for liver metastasis with or without resection.(120–124) When initially introduced, complications including liver fracture, bleeding, systemic cytokine induced lung injury, myoglobinuria and pleural effusion reduced its overall popularity and widespread use. Radiofrequency ablation was initially described in the treatment of metastatic colon cancer in 1996.(125) While a much less morbid procedure than resection or cryotherapy, limits to the size of treatable tumors and higher incidence of recurrence as well as lower overall survival when compared to resection have prevented this from replacing surgery as the gold standard for therapy.(126, 127) Microwave ablation, chemoembolization and stereotatic body radiotherapy remain investigational in the US at this time. Injection of yttium-90 labeled beads into the hepatic artery of tumor containing segments of liver has received approval by the Federal Drug administration for the treatment of unresectable colon cancer metastasis to the liver. Current trials are underway to determine the role of this therapy in downstaging liver metastasis and as primary therapy with chemotherapy in the adjuvant setting. Operative Approach Laparoscopy Patients who have single or peripherally located metastatic lesions may be candidates for laparoscopic liver resection. Anteriorly located lesions in either the right or left lobes can often be approached in the supine position. A full explanation of all the techniques and equip- ment available for resection are beyond the scope of this chapter but have been summarized recently in a review.(128–130) In our practice, we find the LigaSure™ Vessel Sealing System (Valley Lab, Boulder, CO) and the TissueLink Endo SH2.0™ Sealing Hook (SH) (TissueLink Medical Inc., Dover, NH). to be the most useful for laparoscopic resections. Port placement often varies significantly  improved outcomes in colon and rectal surgery depending on the location of the lesion to be removed. Addition of the hand port has been described to assist with right lobe liver resection and may be useful depending on the body habitus of the patient, the location of the tumor and the characteristics of the liver, i.e, underlying fibrosis, steatosis, etc. In general, a 5–15 mm port is often placed in the plane of the liver dissection to facilitate stapling of the liver. The initial step of the procedure involves localization of the tumor and demarcation of the liver division plane. Laparoscopic ultrasound is needed to define the location and extent of the tumor and to map the appropriate vascular structures. The surface of the liver is marked in the division plane often with electrocautery. The margin status for resection has been a topic of considerable debate in the literature. Several studies have suggested that no significant margin is necessary as long as the cap- sule of the tumor has not been violated during the resection. Other studies have suggested higher local recurrence rates when tumor was present at the resection margin, regardless of the method of resection.(131, 132) Resection can be performed with or without hilar control. Vascular clamping before resection is not necessar- ily needed. Parenchmal dissection can be performed with various energy sources. Venous bleeding is controlled by adjusting the pressure of the pnuemoperitoneum and the central venous pressure. The portal vein and the hepatic vein are taken with a laparoscopic GIA stapler using 2.5 mm staples. The approach to posterior lesions can be more difficult. Descriptions on resection techniques utilizing anterior and lateral approaches to these lesions have been described (133, 134). Resection principles are similar. Open Resection The majority of resections are performed using an open technique. Open approaches may be more appropriate if there are multiple lesions, if the lesions involve or abut the major portal structures or if obtaining a margin on or near a hepatic vein may be difficult. For patients with bilobar disease or larger primary tumors, laparoscopy at the time of, but prior to open resection may help differentiate resectable from nonresectable patients. Laparoscopic ultrasound is an invaluable aid in determining the number and extent of hepatic metastases. Laparoscopy before laparotomy in patients at high risk to have unresectable disease is helpful to limit the patient morbidity and recovery time. The approach to open resection differs from laparoscopic in that vascular control is often mandatory in limiting operative blood loss. Exposure is obtained with either a Mercedes incision or via a Chevron approach. Use of the Bookwalter, Thompson or upper hand retractor often aids in exposure. Again, full descriptions of resection techniques are beyond the scope of this chapter (reviewed in (135–137)) but in general formal resections do not confer survival advantage. Studies which have evaluated long term survival would suggest that liver conservation during the resection of metasatic disease does not increase the overall recurrence rates and may confer a better long-term outcome.(138) Expected Outcomes Early series looking at survival of patients undergoing liver resection have demonstrated 5 year survival rates of 25–37%.(139, 140) Further screening patients with FDG - PET imaging has resulted in increasing the sensitivity of identifying patients with extrahepatic disease. Better patient selection has resulted in five year survival rates of almost 60%. Even with better imaging most patients will develop recurrent disease of which half will have liver only recurrence. These patients can safely undergo repeat resections with equivalent outcomes.(141– 143) Addition of adjuvant chemotherapy after resection has been recommended as part of the NCCN treatment recommendations based on improvement in survival for patients treated with 5-flour- ouracil or oxaliplatin based regimens.(61, 105, 106) Treatment of patients with synchronous colon and liver lesions with simultaneous liver and colon resection have demonstrated increased risk of early recurrence and lower overall disease free survival. These data were from studies conducted before treatment with current chemotherapy based adjuvant therapies. Treatment of patients with adjuvant therapy prior to liver resection has been advocated by several different authors as a way to identify favorable, chemotherapy sensitive tumors. Other authors have argued that resistance to chemotherapy is a poor prognostic sign even in resectable disease. (144) Multiple studies have demonstrated the ability to downstage metastatic tumor burden in the liver by neoadjuvant therapy either given systemically or by hepatic artery infusion. Rates of converting unresectable colorectal liver metastasis to resectable disease vary from 16% to 51%.(101, 145) One inherent problem with current studies evaluating the efficacy of various treatments for patients with stage IV disease is the ability to control for the extent of disease in the treatment group. Similar to the patients with stage III disease who can be divided into three separate categories based on extent of nodal involvement, stage IV patients represent a spectrum of disease burden requiring a more complex substaging to accurately identify and evaluate different treatment options. Unfortunately, this currently does not exist. Several authors have reported risk factors which cor- relate with patient outcome. In 1997, Fong et al. reported on scoring system which included points awarded for size of the tumor, disease free survival<12 months, number of tumors >1, node positive disease, and a CEA greater the 200. For patients with 0–1 point, 2–3 points, and 4–5 points, five years survival was 50%, 20% and 10% (146). Studies to evaluate the use of this and other scoring sys- tems when applied to an independent population proved unsuc- cessful and have led to the development of other nomograms for predicting disease-specific survival.(147, 148) Although predicting outcome is useful, a staging system is needed to be able to evaluate treatment outcome in similarly controlled groups. One such system has been recently proposed.(149) Significant progress continues to be made in the treatment of metastatic colon cancer to the liver. An aggressive multimodal approach between surgical, medical and radiologic specialties is required for optimizing outcome. While treatment algorithms con- tinue to evolve, there is one tenet that remains constant: patients need to be constantly reevaluated for the appropriate medical or surgical care and that aggressive intervention can significantly improve disease free and overall survival. COLORECTAL LUNG METASTASIS When colorectal cancer (CRC) is confined to the bowel, the workup and management are usually fairly straight forward. When  indications and outcomes for treatment of recurrent rectal cancer there is disease (suggested or proven) outside the bowel, the management becomes debatable. As early as the 1980s and 1990s, CRC which had spread to the liver or lung was considered unresectable at most hospitals, and therefore incurable. There are reports of metastectomies going back to the 1940’s (150), but this approach was not widely accepted. As new technologies developed, such as chemoembolization, cryotherapy, radiofrequency ablation, and safe techniques for metastectomies, aggressive medical centers began resecting or ablating metastatic foci once the primary site was controlled. These centers then began finding that in some sit- uations metastectomy offered a chance at cure and long term cancer free survival. Those surgeons who pushed the envelope even further began finding that repeat lung resections for second and third recurrences can still offer chances at cure.(151–154) Cure rates for metastectomies were not high, and most patients eventually developed further metastatic deposits and succumbed to their disease, but a noticeable percentage maintained their disease free state and lived normal life spans. From the patient’s perspec- tive, this was a tremendous leap. Imagine the difference between being told you have almost no chance of cure and will probably die of cancer in the next few years, to being told that with some extra surgery you may have a 25% chance of cure. Suddenly 25% sounds like a wonderful number. In a day when cancer still is a major cause of pain and suffering, we applaud those who work to give us further means of saving patients, and will review some of their work, as well as explain our approach to managing known CRC with known or suspected lung metastases. Assessing Resectability The first step is finding and working up lung nodules. Suspected lung mets can be found before or after the CRC is found. Most commonly the bowel cancer is found first. Preoperative chest x-rays may show an asymptomatic lung mass, or staging CT chest/ abdomen/pelvis +/- PET scan may show the suspected lung mass. If the lung mass is seen on preoperative chest x-ray, then CT/PET is recommended. Although biopsy and pathologic examination of tumors is the gold standard for differentiating malignant nodules from benign nodules, the radiographic characteristics can help. Primary lung cancers tend to have irregular, spiculated borders, and if >8 mm in diameter, most state-of–the-art PET scanners should start to show PET activity. There are, of course exceptions to this. Primary carcinoid tumors of the lung have smooth borders and have low to no PET activity. Luckily these tend to be slow growing, and if not biopsied right away, can be followed with serial scans until growth is confirmed. Bronchoalveolar lung cancer (a variant of adenocarcinoma) can present as a mass, but can also appear with an infiltrative pattern which is often read as pneumonia, initially. Failure to improve after a course of antibiotics, or lack of any recent or current infectious symptoms in the patient should increase your suspicion for cancer. Multiple smooth bordered nodules of varying sizes, especially in a patient with a known CRC, tend to be metastases. PET activity should start to show in colorectal metastases greater than 10 mm. Large (>10 mm) lung nodules without PET activity in the presence of a PET avid colorectal cancer are still con- cerning, but could very well be non-malignant processes such as rounded atelectasis, scar, or granulomatous disease. If old radio- graphs, especially CTs, are available, then these should be viewed. If the suspected nodules are not new, and have been present for more than 2 years without increasing in number or size, then the likelihood of metastatic disease or primary lung cancer is extremely low. Any nodules that are new or increasing in size are suspect. Once the lung nodules are found, the next step is deciding what to do with them. Most CRC patients are middle aged to elderly and a good proportion have smoking histories. We need to be just as concerned about a second primary lung cancer as we are about metastatic disease. Once again, the radiographic characteristics can help. As stated before, multiple, smooth bordered, PET avid nodules are probably metastatic CRC, but intrapulmonary metastases from a lung cancer are still possible. A solitary PET avid lung mass several centimeters in size, without any other suspicious metastatic deposits either intra or extra-thoracic would be suspicious for a primary lung cancer. While CRC can spread to the hilar, internal mammary, and mediastinal lymph nodes, the presence of nodal enlargement >10 mm would also make us suspect lung cancer more than CRC. Differentiating lung cancer from CRC is important because the survival of the cancers is different, and knowing the patient’s prognosis may affect the aggressiveness of treatment for the other cancer. For example, let us imagine that two nodules are found in different lobes, with no other suspected sites of metastases, in a patient with proven CRC. If both of these nodules are resected and proven to be metastatic CRC, then aggressive management of the primary cancer is warranted, since long term survival may be 25–40%. On the other hand, if biopsies of the lung nodules show primary lung cancer with an interlobar metastasis, then the patient has stage IV lung cancer, and overall survival is usually measured in months to a couple of years, and less aggressive CRC management might be appropriate. If the PET scan shows suspected disease in other extra-thoracic and extra-abdominal sites, such as bone lesions, then these areas need to be biopsied before embarking on lung resections. Usually CT guided biopsies of suspected bone mets are safer and easier than lung resections. Who to operate on, and in which order to operate (bowel or lung first) can be tricky. Patient selection for lung surgery involves several factors. These include 1) exclusion of other sites of metastatic disease 2) adequate lung function for resection based on pulmonary function tests and clinical exam 3) ability to control intra abdominal disease. Excluding extra-thoracic and extra-colonic metastases is critical. Spread of CRC to sites other than the liver and lung, such as the bone, would preclude performing thoracic resections. If the only sites of disease are the bowel, liver, and lung, and the abdominal surgeons feel that curative resections can be performed on these two organs, then curative lung surgery is considered.(152, 153) In order to resect portions of the lung, the patient must have enough residual lung function not only to support life, but also allow for a quality of life acceptable to the patient. Pulmonary function tests are usually easy to obtain. We base our decision for resection on the FEV1 (forced expired volume in 1 second), the diffusion of carbon monoxide (DLCO), and the clinical exam. If after viewing the CT chest and deciding on the extent of resection, the predicted postoperative (ppo) FEV1 is > 0.8 L, then surgery is considered. If the predicted postoperative DLCO is >40% of predicted, then surgery is considered.(155) These formulas should by no means be followed blindly. Just, if not more, important is the clinical evaluation of the patient. As a general rule, if the patient can climb three flights of  improved outcomes in colon and rectal surgery stairs without having to stop due to shortness of breath, then they should be able to tolerate a pneumonectomy or equivalent resection. I also ask if they can walk around the block without stopping. Usually the PFT numbers will support the patient’s answers on the clinical exam. Sometimes they don’t, and I tend to trust the clinical exam over the numbers. For example, we had a patient whose FEV1 and diffusion capacity were >100% of predicted. Based on those numbers a pneumonectomy should have been possible. When seen in clinic he could barely walk from the waiting room to the exam room due to dyspnea and desaturation. Conversely, one patient had a PFT FEV1 of 0.7 L, but biked 5 miles a day with her husband without oxygen. I based my decisions on the clinical evaluation, did not operate on the first patient, and successfully performed a lobectomy on the second patient. Some patients will be borderline resectable based on PFTs and clinical exam. A split perfusion V/Q scan can then be performed. With this test the nuclear medicine doctors can estimate which parts of the lungs are performing what percentage of the work. This allows for a more exact calculation of ppoFEV1. For example, if a tumor is obstructing a lobar bron- chus, then the V/Q scan should show that that lobe is contributing almost nothing to the overall lung function, and resection can be performed with no decrease in PFTs. Operative Approach As mentioned above, part of the decision is how much lung needs to be taken out. Obviously, if we are aiming for cure, then all sites of pulmonary metastases need to be addressed. Metastatic disease is different than primary lung cancer. For lung cancer, anatomic resection is the gold standard (156), with lobectomy being preferred (unless pneumonectomy is required) over segmentectomy, and segmentectomy preferred over wedge resection. Metastectomies are the converse. Lung sparing is very important, especially since the chance for future metastases is high. Also, larger anatomic resections of metastases offer no survival advantage, so wedge resections with negative margins are adequate. Anatomic resections are considered when the size or position of the cancer precludes a wedge resection. Tumors on the periphery of the lung <3 cm in size can usually be excised by a wedge. Larger masses can sometimes be resected by a wedge, especially if in the inferior lingula. Large tumors, those positioned several centimeters deep to the visceral pleura, mid basilar tumors, or those near the hilum will probably require a segmentectomy, multiple segmentectomy (ex. basilar segmentectomy, lingular sparing left upper lobectomy), or lobectomy. Pneumonectomy will be described later. With this information a thoracic surgeon can estimate the percentage of overall lung to be resected, and calculate the ppoFEV1 and ppoDLCO. Once it has been decided that the patient could undergo lung surgery, the order of surgery is decided upon after discussion between the colon, hepatic, and lung surgeons. If the thoracic metastectomies can be performed with quick wedge resections with low morbidity, then I would operate first if my finding will change the other surgeons’ resections. If larger, more risky thoracic resections are needed (especially pneumonectomy), then I would prefer the abdominal surgeons to proceed and make sure that the primary tumor and intraabdominal metastases can be controlled first. If the resection pathology is favorable and the patient has recovered, then definitive lung resection is done. It is nice for the patient if combined surgery can be performed. For video-assisted thoracoscopic surgery (VATS) wedge resections I feel comfortable removing the thoracic disease and then letting the abdominal surgeons proceed at the same setting. The VATS approach allows for less pain and earlier mobility, and usually doesn’t hinder patient recovery from the laparotomy. If the lung surgery requires a thoracotomy, lobectomy, or pneumonectomy, I prefer not to operate at the same setting, as postoperative recovery becomes much more difficult for the patient. Video Assisted Thoracoscopic Surgery (VATS) A relatively new factor that has changed our approach to metastectomies is the VATS, or video assisted thoracoscopic surgery, technique. Traditionally lung resection required a lateral or posterolateral thoracotomy. These incisions are painful, usually involve transecting the latissimus muscle, require several days of hospital stay to recover and several weeks or months as an outpatient to recover, and frequently require epidural placement preoperatively for pain control. As the size of the thoracotomy increases, the chance for chronic pain increases as well. If the patient recurs on the ipsilateral side, then repeat thoracotomies are needed. The amount of scar tissue in the thorax increases after larger dissections, and any redo operation runs the risk of having to deal with this. Sometimes the lung is so scarred in that exposure and resection are not possible. Usually, however, the surgery just takes longer as the scar tissue is dealt with, and may require even further extension of the old incision to facilitate exposure. Just like surgery in other areas of the body, the longer and more difficult the dissection, the greater the risk of complications. With VATS, wedge resections require only three incisions 10 mm or less in length. Pain is managed more easily and discharge is usually anticipated in 1 to 2 days postop. Changing to lobectomy only needs one of those incisions to be lengthened to a 3–4 cm utility incision. The latissimus and serratus muscles are spared, and no rib notching is needed. We no longer use epidurals, and instead leave a PCA (patient controlled analgesia) for one day as well as placing a marcaine infuser catheter in the intercostal space and subcutaneous tissue of the utility incision. The marcaine pump we use will last for about three days. On post op day 1 the PCA is discontinued and oral pain meds are started. Discharge is anticipated on postop day 4–5 to home without any chest tubes. Since the amount of intercostal muscle being transected during VATS surgery is minimal, chest wall adhesions with redo operations is usually minimal, especially after wedge resections. Even multiple surgeries on the same side can be managed with only a short increase in operative time to take down adhesions, and often the same incisions can be used. Expected Outcomes Now that we know how to work up a patient for lung surgery, decide if they can tolerate lung surgery, and understand the latest approach to lung resections, we need to review our chances for helping these people survive metastatic CRC. We will review a select number of studies. The Mayo Clinic, Rochester, reported in 1992 their experience with 139 consecutive lung resections for metastatic CRC.(154) Resections were performed via wedge resection in 68, lobectomy in 53, and more extensive resections including pneumonectomy in 18. During follow up, 19 patients recurred in the lung and needed repeat resections. Median follow up was 7 years (range 1–20.4). Overall  indications and outcomes for treatment of recurrent rectal cancer 5- and 20- year survival was 30.5% and 16.2%, respectively. Five year survival for solitary metastases was 36.9% compared to 19.3% for patients with two lesions. For those who recurred and required repeat resection, 5- year survival after the second resection was just over 30%. Twenty patients had extrapulmonary metastases as well as lung lesions. Survival after resection for these patients was also 30%. Interestingly, they noted that patients with prethoracotomy CEA levels >5 ng/ml had much poorer survival at 5 years compared to lower CEA level patients (16% vs. 46.8%). This same poor prognostic indicator has been realized by others.(151, 157) Based on their experience, they supported resection of intra- and extrapulmonary metastases, even if they recur. Irshad et al. reported on a 25 year experience, from 1975 to 1999, in which 49 patients underwent curative colorectal surgery followed by curative thoracic metastectomies. Overall survivals at 5, 10, and 15 years were 55%, 40%, and 25%. Patients with solitary metastases did better, but multiple metastectomies still had a survival advantage.(158) One area of debate is how aggressive of a resection should be performed. More precisely, should a patient undergo pneumonectomy for stage IV colorectal cancer? Pneumonectomy alone carries a higher mortality than lesser resections, with an operative mortality around 7%. In centers accustomed to taking care of these patients, and surgeons who specialize in this procedure, the mortality is lower. Hendricks et al. looked at 10 cases of pneumonectomy for metastectomy and found 5 year survival of around 45%.(159) Koong et al. reviewed 133 patients who underwent pneumonectomy or comple- tion pneumonectomy for metastases. 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Arch Surg 2000; 135(4): 473–9. . 3 Mohiuddin (12) 34 22 – 0 Wanebo (10) 61 31 38 8 Valentín (11) 59 39 – – Source: Adopted from de Wilt et al.(5)  improved outcomes in colon and rectal surgery remained below 10% (62). Interestingly. multidisciplinary involvement and plan- ning, and comment that this surgery is not for the “occasional participant”.(2) These data and others confirm that the overriding principle of this challenging. When initially introduced, complications including liver fracture, bleeding, systemic cytokine induced lung injury, myoglobinuria and pleural effusion reduced its overall popularity and widespread

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