Scanned Medical Document About Cancer

1

J.-L. Koh et al.

evaluate the mXwy of preoperative CT in estimating PCI as part of the patient selection process. PATIENTS AND METHODS Preoperative abdominopelvic CT scans of patients with CRPC who were planning to undergo exploratory laparotomy with or without proceeding with CRS were prospectively reviewed. Appendiceal adenocarcinomas were excluded from this study. These findings were then compared to the operative records of peritoneal cancer assessment. From February 2006 to July 2008, 19 patients were prospectively entered into this study. , CT scans were performed using multislice CT scanner t tp >t with oral and intravenous contract enhancement. There were Vvw^tj no standard CT acquisition parameters because the vast majority of our patients were referred from other institutions. The scans were reviewed on hardcopy films. Localization and size of peritoneal implants on CT scans were evaluated and scored by a single experienced radiologist preoperatively at a weekly multidisciplinary team meeting. Intraoperative PCI scores were obtained and documented at the time of surgical exploration by a single surgeon. Surgical intervention for CRPC was performed within 1 month of diagnosis. The size and distribution of peritoneal deposits were recorded using the PCI system as described by Sugarbaker (Fig. 1).'' The abdomen is divided into nine regions and the small bowel into four: each assigned a lesion-size

J

(LS) score of 0 to 3, which would be representative of the largest implant visualized. LS-0 denotes the absence of implants, LS-1 indicates implants <0.25 cm, LS-2 between 0.25 and 5 cm, and LS-3 >5 cm or a confluence of disease. These figures amount to a final numerical score of 0-39. Statistical Analysis Tumor distribution in each abdominopelvic region was assessed as tumor present versus absent. The sensitivity, specificity, positive predictive value, and negative predictive value were calculated for each abdominopelvic region. These were based on the presence versus absence of peritoneal implants regardless of size. The impact of lesion size on the sensitivity of CT in detecting a tumor nodule also was analyzed. The efficacy of CT in demonstrating the volume of peritoneal disease was evaluated by comparing the radiological and intraoperative lesion size and PCI scores using the Wilcoxon signed-rank test.

Sensitivity

True-positive results True-positive+False-negative results

Specificity

True-negative results _______________ True-negative+False-positive results

Positive

predictive

Negative predictive value

value

True-positive results _______________ True-positive+False-positive results True-negative results _______________ True-negative+False-negative results

Peritoneal Cancer Index Lesion Size Regions 0 Central Right Upper Epigastrium Left Upper Left Flank Left Lower Pelvis Right Lower Right Flank 9 10 11 12

Upper Jejunum Lower Jejunum Upper Ileum Lower Ileum

PCI

FIG. 1 Sugarbaker's Peritoneal Cancer Index (PCI) system''

Lesión Size Score LS O No tumor seen LS 1 Tumor up to 0.5 cm L S 2 Tumor up to 5.0 cm L S 3 Tumor > 5.0 cm or confluence

CT Colorectal Peritoneal Carcinomatosis

RESULTS Clinical and Intraoperative Data There were 11 female patients. The mean age of this group of patients was 57 years (standard deviation 13). All patients had previously been operated on for their primary mmor. The primary was located in the rectosigmoid area in five cases, sigmoid in four, left colon in three, right colon in three, rectum in three, and cecum in one. Twelve patients were classified as stage III and seven patients as stage IV for their primary tumor. There were 18 patients with moderately differentiated and 1 with poorly differentiated disease. With exploratory laparotomy, all 19 patients were found to have peritoneal dissemination from colorectal cancer. Nine patients were identified to have mucinous adenocarcinoma and the remaining ten patients had the intestinal subtype. The median PCI was 10 (range 2-35). Five patients had extensive peritoneal involvement, with PCI > 15 and 14 patients had PCI <15. All cases with extensive peritoneal carcinomatosis were of the mucinous subtype. The distribution of peritoneal implants by LS as visualized during surgical exploration is demonstrated in Fig. 2 according to abdominopelvic regions. The most frequent sites for peritoneal involvement were the pelvis and right lower region, closely followed by the central, right upper, and left lower regions. There was a predilection for the right side, with spread to the right upper and right flank regions approximately twice as common as to the left. With exception of the distal ileum, the small bowel segments were the least commonly affected. CT Analysis by Abdominopelvic Regions ' Sensitivity CT detection of peritoneal implants was 67% in the epigastrium. Two other regions yielded a sensitivity >50%: right upper and pelvis (54% and 60%, respectively). The depiction of small-bowel involvement had the lowest sensitivities of all regions examined (817%). f.

Specificity The specificity of CT for detection of peritoneal nodules exceeded 80% in all regions except the pelvis (75%). In particular, specificity was 100% in the right upper, epigastric, right lower, and right flank regions and the entire small-bowel segment.

^■Positive Predictive Value The positive predictive value of CT in detecting CRPC was 100% in 8 of 13 regions. It

329

J.-L. Koh et aL

3

was lowest in the left upper region (50%), where there were two false-positive results. Both were reported as lesions >5 cm on preoperative CT but were not found during subsequent surgical exploration. Negative Predictive Value The negative predictive value was not reliable throughout the abdominopelvic regions except the epigastrium (87%), left upper (80%), and left flank (80%) regions. The values were lowest in the right lower (31%) and right flank (33%) regions. Further details on the CT findings according to regional components that constitute the PCI system are illustrated in Fig. 3.

FIG. 3 Relationship between radiological and intraoperative lesion size (LS) score (LSCT & LSQ, respectively) by abdominopelvic regions of PCI scoring system. Each dot in the first column represents the radiological LS for each patient. The second column represents the corresponding intraoperative LS. The line connecting the two demonstrates the degree of difference between the scores, which has been calculated for the group using the Wilcoxon Signed-rank test. -I-PV = positive predictive value; -PV = negative predictive value. The sensitivity, specificity, -t-PV and —PV indicate the presence versus absence of peritoneal nodules regardless of lesion size

Analysis by Lesion Size Overall, where CT identifies the presence of disease, it portrayed lesion size accurately in 60%, underestimated in 33%, and overestimated in 7% of cases. Analysis of individual abdominopelvic regions demonstrated a statistically significant difference between radiologically and intraoperatively visualized lesion sizes ( P < 0.05) except in the epigastrium, left upper, and left flank regions. The mean intraoperative LS score was greater than that recorded radiologically in all regions except the left upper quadrant (Fig. 3).

331

FIG. 4 Impact of lesion size on sensitivity of CT scan

The sensitivity of CT in detecting peritoneal implants was influenced by lesion size. The false-negative rate significantly decreased with increased lesion size (Fig. 4). Small nodules (<0.5 cm) were visualized on CT with only a sensitivity of 11%, which is in contrast to 94% with nodules exceeding 5 cm. Comparison of CT with Intraoperative PCI Comparison of overall PCI scores as established during surgical exploration and its CT depiction revealed a significant difference ( P < 0.001, XQ = 12.47, XR = 6.68), in that radiological PCI underestimated intraoperative PCI. DISCUSSION It must be emphasized that a stringent patient selection process is necessary to identify those who will benefit from CRS. The PCI score denotes the extent of peritoneal disease and predicts survival.'"'''^""' Hence, it may influence the direction of therapeutic management: cytoreduction with intraperitoneal chemotherapy or a more conservative approach with systemic chemotherapy. This would be better assessed as part of the preoperative workup if possible rather than during surgical exploration. In clinical practice, CT is the standard preoperative imaging modality used for this purpose.'"* However, data are limited on its utility in estimating PCI for peritoneal dissemination of CRPC. Available studies have largely been conducted on ovarian cancer.Also, most papers on peritoneal dissemination of gastrointestinal malignancies have been published more than a decade ago; more current data are desirable.'"'-"' The present study is the first to focus exclusively on CRPC, where PCI is recognized as being most prognostic. Our results showed that CT underestimates extent of peritoneal carcinomatosis from colorectal cancer. The detection rates ranged from 8-67%, depending on the

region involved; only the epigastrium exceeded the 60% mark. Jacquet et al. recorded considerably higher rates, witii the right flank, left flank, right lower, and left lower abdominal regions all with sensitivities >80%.The pelvis had the lowest sensitivity, with 60%. The large proportion of cystadenocarcinomas of appendiceal origin that constituted their study may account for this difference.''^ Small-bowel disease was the most poorly visualized in our series (8-14%). In a recent study by de Bree et al., statistically significant interobserver differences were demonstrated, particularly in regards to the small bowel."'' These are noteworthy findings, because small-bowel involvement entails major implications on outcome. In another study Jacquet et al. evaluated the interpretative CT findings that impact on the likelihood of complete cytoreduction."'' They described the presence of small-bowel implants >0.5 cm (discounting the terminal ileum) and obstruction of bowel segments as 88% predictive of an incomplete resection. Without these two features, the probability of complete cytoreduction was 92%. The distribution of spread is consistently reported in the literature. The greater omentum, pelvis, small bowel, and its mesentery seem to be the favored sites for metastases.'^'"''"'' This is presumed to be associated with the natural flow of intraperitoneal fluid. Our findings parallel those published, with the exception of the small bowel segments—they were amongst the least frequently involved sites in our study. This relative sparing of the small bowel may be a result of their active peristaltic movement, as proposed by Schwartz et al."^ Studies are unanimous in the conclusion that CT sensitivity increases remarkably with larger implants.'"'■"'' Our study confirms these findings (Fig. 4). The results by Jacquet et al. are comparable to the present study: 28% for nodules <0.5 cm in diameter compared with 90% for ones >5 cm.''' Additionally, as observed by de Bree et al., CT representation of the actual size of peritoneal nodules was considerably inaccurate."'' We were unable to draw conclusions regarding the CT depiction between the two histological subtypes, jijtestinal and m^eyjous, because of the small sample size. The aforementioned studies found that mucinous adenocarcinomas are more accurately represented on CT."''"'^ Additionally, these tumors also demonstrate the tendency to be more widespread. The prognostic significance of intestinal versus mucinous type disease is not well-established. Some studies suggest an association between mucinous histology and reduced survival. Yan et al. reported a 2-year survival of 26% and 80% in the mucinous and intestinal group respectively." However, whether this

J.-L. Koh et al.

is related to the greater volume of disease or true biological differences is unknown. The present study suggests that radiologically determined PCI underestimates the true extent of peritoneal disease in the context of CRPC. In fact, in our series, the mean operative PCI nearly doubles that approximated by CT { P < 0.001). Numerous studies have demonstrated a survival benefit with a low PCI score, although the cutoff point is not well established.'''*''''^"^ The question remains: is it reasonable to exclude patients based on a preoperative PCI? It may be reasonable to suggest that patients with a preoperative CT PCI >15 should be considered inappropriate for the combined treatment, because the clinical PCI may be much higher. In addition, some caveats of the PCI system should be considered. Certain factors may supersede a favorable PCI; the presence of disease at crucial anatomic sites, such as extensive small-bowel involvement, prevents the attainment of a complete cytoreduction." '"' Disease infiltration of anatomic sites, such as the omentum, pelvis, and diaphragms (all frequently involved structures), can be adequately managed with peritonectomy procedures, as described by Sugarbaker."'* Ileocecal involvement is amenable to intestinal resection. In such cases, complete eradication of macroscopic disease may be achievable despite a high PCI. Other imaging modalities have been utilized to profile peritoneal disease preoperatively. Magnetic resonance imaging (MRI), with its superior contrast resolution and capacity for multiple imaging types, may seem like the obvious alternative to CT. However, it requires longer scanning time and is easily influenced by motion artefacts related to respiration and bowel peristalsis. Like CT, it is limited by low sensitivity for small-nodule detection."" Positron emission tomography (PET) with 2-(fluorine 18) fluoro-2-deoxy-D-glucose (FDG) localizes malignant tissues by their increased FDG tracer uptake relative to metabolically normal cells and offers greater sensitivity compared with anatomic imaging techniques.""* The major pitfall of PET is its low specificity. Integration of the functional data provided by PET and the structural imaging from CT to produce the PET-CT system presents an attractive option. However, this is not surprisingly limited by high cost and availability. Because peritoneal deposits usually have low-volume density, all imaging modalities have major limitations in the assessment of low-volume disseminated peritoneal disease and may fail to detect early localized disease at a stage where treatment is most likely to be beneficial. Diagnostic laparoscopy allows direct visualization of peritoneal involvement and may be a valuable supplementary tool. However, technical difficulties arise in the presence of adhesions due to extensive previous surgery. It also is limited in its risk of port-tract metastasis and visualization of the retroperitoneal space. Evidence for the use of staging laparoscopy in ovarian cancer has been encouraging; however, its utility in CRPC has not been established.The value of laparoscopy

staging is being explored in the prospective, multi-institutional registry study.'" To our knowledge, there has been no description for the use of CT-enhancing techniques, such as three-dimensional reconstruction and rectal contrast for this purpose. We must encourage the general surgeons to record intraoperative PCI at the time of primary colon resection, if there is evidence of synchronous peritoneal carcinomatosis. In conclusion, this study demonstrated that the sensitivity of CT in detecting peritoneal implants was influenced by lesion size and CT PCI significantly underestimated clinical PCI. The role of CT in refining patient selection and improving prognosis needs to be closely evaluated. REFERENCES 1. Chu DZJ, Lang NP, Thompson C, Osteen PK, Westbrook KC. Peritoneal carcinomatosis in nongynecologic malignancy. A prospective study of prognostic factors. Cancer. 1989;63:364-7. 2. Jayne DG, Fook S, Loi C, Seow-Choen F. Peritoneal carcinomatosis from colorectal cancer. Br J Surg. 2002;89:1545-50. 3. Sadeghi B, Arvieux C, Glehen O, et al. Peritoneal carcinomatosis from non-gynecologic malignancies. Results of EVOCAPE 1 multicentric prospective study. Cancer. 2000;88:358-63. 4. "Verwaal VJ, van Ruth S, de Bree E, van Slooten GW, van Tinieren H, Boot H, et al. Randomized trial of cytoreduction and hyperthermic intraperitoneal chemotherapy versus systemic chemotherapy and palliative surgery in patients with peritoneal carcinomatosis of colorectal cancer. J Clin Oncol. 2003;21:373743. 5. Glehen O, Kwiatkowski F, Sugarbaker PH, et al. Cytoreductive surgery combined with perioperative intraperitoneal chemotherapy for the management of peritoneal carcinomatosis from colorectal cancer: a multi-institutional study. J Clin Oncol. 2004;22:3284-92. 6. Witkamp AJ, de Bree E, Kaag MM, et al. Extensive cytoreductive surgery followed by intra-operative hyperthermic intraperitoneal chemotherapy with mitomycin-C in patients with peritonea! carcinomatosis of colorectal origin. Eur J Cancer. 2001;37:979-84. 7. Shen P, Hawksworth J, Lovato J, Loggie BW, Geisinger KR, Heming RA, et al. Cytoreductive surgery and intraperitoneal hyperthermic chemotherapy with mitomycin C for peritoneal carcinomatosis from nonappendiceal colorectal carcinoma. Ann Surg Oncol. 2004;!!:278-86. 8. Kusamura S, Younan R, Baratti D, Costanzo P, Favaro M, Gavazzi C, et al. Cytoreductive surgery followed by intraperitoneal hyperthermic perfusion. Analysis of morbidity and mortality in 209 peritoneal surface malignancies treated with closed abdomen technique. Cancer. 2006;106:1144-53. 9. Yan TD, Edwards G, Alderman R, Marquardt CE, Sugarbaker PH. Morbidity and mortality assessment of cytoreductive surgery and perioperative intraperitoneal chemotherapy for diffuse malignant peritoneal mesothelioma: a prospective study of 70 consecutive cases, Ann Surg Oncol. 2007;14:515-25. 10. Yan TD, Links M, Fransi S, Jacques T, Black D, Saunders V, et al. Learning curve for cytoreductive surgery and perioperative intraperitoneal chemotherapy for peritoneal surface malignancy:

CT Colorectal Peritoneal Carcinomatosis

11.

12.

13.

14.

15.

16.

17.

18.

19.

20.

21.

a journey to becoming a nationally funded peritonectomy center. Ann Surg Oncol. 2007;14:2270-80. da Silva RG, Sugarbaker PH. Analysis of prognostic factors in seventy patients having a complete cytoreduction plus perioperative intraperitoneal chemotherapy for carcinomatosis from colorectal cancer. J Am Coll Surg. 2006;206:878-86. Elias D, Blot F, El Otmany A, et al. Curative treatment of peritoneal carcinomatosis arising from colorectal cancer by complete resection and intraperitoneal chemotherapy. Cancer 2001 ;92: 71-6. Yan TD, Chu F, Links M, Kam PC, Glenn D, Morris DL. Cytoreductive surgery and perioperative intraperitoneal chemotherapy for peritoneal carcinomatosis from colorectal carcinoma: non-mucinous tumor associated with an improved survival. Eur J Surg Oncol. 2006;32:1119-24. Yan TD, Morris DL, Shigeki K, Dario B, Deraco M. Preoperative Investigations in the management of peritoneal surface malignancy with cytoreductive surgery and perioperative intraperitoneal chemotherapy: expert consensus statement. J Surg Oncol. 2008;98;224-7. Jacquet P, Jelinek JS, Steves MA, Sugarbaker PH. Evaluation of computed tomography in patients with peritoneal carcinomatosis. Cancer 1993;72:1631-6. Nelson RC, Chezmar JL, Hoe! MJ, Buck DR, Sugarbaker PH. Peritoneal carcinomatosis: preoperative CT with intraperitoneal contrast material. Radiology. 1992;182:133-8. De Rosa V, Mangoni di Stefano ML, Brunetti A, Caraco C, Graziano R, Gallo MS, Maffeo A. Computed tomography and second-look surgery in ovarian cancer patients. Correlation, actual role, and limitations of CT scan. Eur J Gynaecol Oncol. 1995;16:123-9. Coakley FV, Choi PH, Gougoutas CA, et al. Peritoneal metastases: detection with spiral CT in patients with ovarian cancer. Radiology. 2002;223:495-9. Shehata M, Chu F, Saunders V, Kam PC, Links M, Morris DL. Peritoneal carcinomatosis from colorectal cancer and small bowel cancer treated with peritonectomy. ANZ J Surg. 2006;76:467-71. Yan TD, Sim J, Morris DL. Selection of patients with colorectal peritoneal carcinomatosis for cytoreductive surgery and perioperative intraperitoneal chemotherapy. Ann Surg Oncol. 2006; 14: 1807-17. Pestieau SR, Sugarbaker PH. Treatment of primary colon cancer with peritoneal carcinomatosis. Dis Colon Rectum. 2000;43: 1341-6.

333

22. Tempany CM, Zou KH, Siverman SG, Brown DL, Kurtz AB, McNeil BJ. Staging of advanced ovarian cancer: comparison of imaging modalities: report from the Radiological Diagnostic Oncology Group. Radiology. 2000;215:761-7. 23. Prayer L, Kainz C, Kramer J. CT and MR accuracy in the detection of tumor recurrence in patients treated for ovarian cancer. J Comput Assist Tomogr. 1993;17:626-632. 24. de Bree E, Koops W, Kroger R, van Ruth S, Witkamp AJ, Zoetmulder FAN. Peritoneal carcinomatosis from colorectal or appendiceal origin: correlation of preoperative CT in intraoperative findings and evaluation of interobserver agreement. J Surg Oncol. 2004;86:64-73. 25. Jacquet P, Jelinek JS, Chang D, Koslowe P, Sugarbaker PH. Abdominal computed tomographic scan in the selection of patients with mucinous peritoneal carcinomatosis for cytoreductive surgery. J Am Coll Surg. 1995;181:530-8. 26. Schwartz B, Bresalier RS, Kim YS. The role of mucin in coloncancer metastasis. Int J Cancer. 1992;52:60-5. 27. Sugarbaker PH, Jablonski KA. Prognostic features of 51 colorectal and 130 appendiceal cancer patients with peritoneal carcinomatosis treated by cytoreductive surgery and intraperitoneal chemotherapy. Ann Surg. 1995;221:134-2. 28. Harmon RL, Sugarbaker PH. Prognostic indicators in peritoneal carcinomatosis from gastrointestinal cancer. Int Semin Surg Oncol. 2005;2:3. 29. Sugarbaker PH. Peritonectomy procedures. Ann Surg. I993;221: 29-42. 30. Huebner RH, Park KC, Shepherd JE, Schwimmer J, Czemin J, Phelps ME, et al. A meta-analysis of the literature for wholebody FDG PET detection of recurrent colorectal cancer. J Nucl Med. 2000;41:1177-89, 31. Deffieux X, Castaigne D, Pome! C. Role of laparoscopy to evaluate candidates for complete cytoreduction in advanced stages of epithelial ovarian cancer. Int J Gynecol Cancer. 2006; 16:35-40. 32. Esquivel J, Sticca R, Sugarbaker P. Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in the management of peritoneal surface malignancies of colonic origin: a consensus statement. Society of Surgical Oncology. Ann Surg Oncol. 2007;14:128-33.