Improved prognosis following peritonectomy procedures and hyperthermic intraperitoneal chemotherapy for peritoneal carcinomatosis from appendiceal carcinoma.

AIMS: The prognosis of patients with peritoneal carcinomatosis from gastrointestinal malignancies is poor. The aim of this study was to analyse the results of multimodality treatment for peritoneal carcinomatosis of appendiceal carcinoma. PATIENTS AND METHODS: From 07/95 to 01/00, 17 patients (13 males, 4 female, median age 58 years) underwent peritonectomy procedures in combination with intraperitoneal hyperthermic chemotherapy. Surgical, pathological and survival data were analysed retrospectively. RESULTS: All patients had undergone previous surgical treatment and one patient had received chemotherapy. In all patients peritonectomy procedures, as described by Sugarbaker, were performed with the aim of achieving a macroscopically complete cytoreduction (range 2-6, median 4 procedures per patient). Following resection, open hyperthermic intraperitoneal chemotherapy with cisplatin was performed. Eleven patients had postoperative complications (predominantly "non-surgical") and two patients died postoperatively. The 4-year survival rate was 75%. Complete cytoreducion had a statistically significant positive influence on long-term survival. CONCLUSIONS: In selected patients (WHO status 0/1, minimal residual disease, no distant metastases, complete cytoreduction), the prognosis for patients with peritoneal carcinomatosis of appendiceal origin can be improved by peritonectomy procedures and hyperthermic intraperitoneal chemotherapy. Postoperative morbidity may be increased due to "non-surgical" complications. Copyright Harcourt Publishers Limited.     

Predictors and survival of synchronous peritoneal carcinomatosis of colorectal origin: A population‐based study

The aim of our study was to provide population‐based data on incidence and prognosis of synchronous peritoneal carcinomatosis and to evaluate predictors for its development. Diagnosed in 1995–2008, 18,738 cases of primary colorectal cancer were included. Predictors of peritoneal carcinomatosis were analysed by multivariable logistic regression analysis. Median survival in months was calculated by site of metastasis. In the study period, 904 patients were diagnosed with synchronous peritoneal carcinomatosis (4.8% of total, constituting 24% of patients presenting with M1 disease). The risk of peritoneal carcinomatosis was increased in case of advanced T stage [T4 vs. T1,2: odds ratio (OR) 4.7, confidence limits 4.0–5.6), advanced N stage [N0 vs. N1,2: OR 0.2 (0.1–0.2)], poor differentiation grade [OR 2.1 (1.8–2.5)], younger age [<60 years vs. 70–79 years: OR 1.4 (1.1–1.7)], mucinous adenocarcinoma [OR 2.0 (1.6–2.4)] and right‐sided localisation of primary tumour [left vs. right: OR 0.6 (0.5–0.7)]. Median survival of patients with peritoneum as single site of metastasis remained dismal [1995–2001: 7 (6–9) months; 2002–2008: 8 (6–11) months], contrasting the improvement among patients with liver metastases [1995–2001: 8 (7–9) months; 2002–2008: 12 (11–14) months]. To conclude, synchronous peritoneal metastases from colorectal cancer are more frequent among younger patients and among patients with advanced T stage, mucinous adenocarcinoma, right‐sided tumours and tumours that are poorly differentiated. The prognosis of synchronous peritoneal carcinomatosis remains poor with a median survival of 8 months and even worse if concomitant metastases in other organs are present.     

The management of synchronous peritoneal carcinomatosis and hematogenous metastasis from colorectal cancer.

AIMS: Combined local and distant dissemination for colorectal cancer occurs especially in younger patients. New strategies combining maximal cytoreductive surgery with intraperitoneal and systemic chemotherapy have been used in an attempt to prolong survival with an acceptable morbidity and mortality. METHODS: Twenty-seven patients with histologically proven peritoneal carcinomatosis from colorectal cancer had distant metastases in addition to peritoneal carcinomatosis. The goal for treatment in all patients was complete local and distant cytoreduction. Aggressive intraperitoneal and systemic chemotherapy was used. The endpoint for all the analysis was survival from the time of definitive treatment at our Institution. RESULTs: In addition to peritoneal carcinomatosis, 16 patients had liver metastases, six patients had lung metastases, four had liver and lung metastases and one had supraclavicular lymph-node metastases. Median survival time (MST) for the entire group was 15.2 months. Patients that received a complete cytoreductive surgery had a MST of 20.6 months and patients with incomplete cytoreduction had a MST of 9.0 months (p= 0.0471). Post-operative morbidity and mortality was 14.8 and 0%, respectively. CONCLUSION: A group of carefully selected patients with peritoneal carcinomatosis and distant metastases from colorectal cancer may benefit from cytoreductive surgery and intraperitoneal chemotherapy.     

Peritonealkarzinose bei gastrointestinalen Malignomen

Peritoneal carcinomatosis is defined as the seeding of malignant cells in the peritoneum. In primary peritoneal carcinomatosis, the cancer cells originate from the peritoneum itself, whereas they spread from another solid tumor in secondary peritoneal carcinomatosis. Amongst tumors of gastrointestinal origin, metastases from colorectal cancer are the most common, although the incidence in gastric cancer (30?%) is higher. The best method for diagnosis is computer tomography of the abdomen (with intravenous, oral, and rectal administration of contrast agent). Systemic chemotherapy is significantly less effective in patients with peritoneal metastases than in patients with metastases in solid organs (e.?g. liver). Carefully chosen patients can be treated with cytoreductive surgery (CRS) in combination with intraabdominally applied hyperthermic intraperitoneal chemotherapy (HIPEC). The prognosis is highly dependent on the histology of the primary tumor as well as the extent of peritoneal seeding; the life expectancy can be between a few months and several years.     

Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for peritoneal carcinomatosis from colorectal and gastrointestinal origin shows acceptable morbidity and high survival

Background

Peritoneal carcinomatosis from colorectal origin carries a poor prognosis. Recent clinical studies show that cytoreductive surgery (CS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) improves survival of selected patients with a colorectal carcinoma and isolated peritoneal carcinomatosis in the absence of extra-abdominal metastases. Here, we report the clinical outcomes and survival after cytoreductive surgery and HIPEC of the first cohort of patients treated in our institution.

Methods

Sixty-seven patients underwent a laparotomy. Complete cytoreduction could be performed in 49 patients, who underwent a total of 53 CS–HIPEC procedures. All had peritoneal carcinomatosis originating from primary colorectal, cecal, appendiceal, and gastric tumors.

Results

In patients who underwent CS–HIPEC, an R0 resection could be achieved in 4%, R1 in 88%, and R2 in 8%. The 30-day mortality was 0; one patient died in-hospital after 10 weeks. The median hospital stay was 12 days (range 4–56). The overall morbidity was 43%, including extended gastroparesis (11%), anastomotic failure (11%) and intra-abdominal abscess (9%). Mean time to clinical recurrence was 12 months (range 4–22). The actuarial 1-year survival was 88% and 2-year survival was 75%.

Conclusion

In well-selected patients referred to a specialized institution, CS–HIPEC has an accep table morbidity and high survival rate.     

Peritoneal carcinomatosis from non-gynecologic malignancies: results of the EVOCAPE 1 multicentric prospective study

BACKGROUND: Peritoneal carcinomatosis (PC) is a common evolution of digestive cancer, associated with a poor prognosis. Yet it is poorly documented in the literature. METHODS: Three hundred seventy patients with PC from non-gynecologic malignancies were followed prospectively: the PC was of gastric origin in 125 cases, of colorectal origin in 118 cases, of pancreatic origin in 58 cases, of unknown origin in 43 cases, and of miscellaneous origins in 26 cases. A previously reported PC staging system was used to classify these 370 patients. RESULTS: Mean and median overall survival periods were 6.0 and 3.1 months, respectively. Survival rates were mainly affected by the initial PC stage (9.8 months for Stage I with malignant peritoneal granulations less than 5 mm in greatest dimension, versus 3.7 months for Stage IV with large, malignant peritoneal masses more than 2 cm in greatest dimension). The presence of ascites was associated with poor survival of patients with gastric or pancreatic carcinoma. Differentiation of the primary tumor did not influence the prognoses of patients with PC. CONCLUSIONS: A better knowledge of the natural history of PC is needed, in view of the many Phase I, II, and III trials currently being conducted to evaluate aggressive multimodal therapeutic approaches to treating patients with PC from non-gynecologic malignancies.     

胃肠道肿瘤腹膜转移治疗进展

胃肠道肿瘤通过腹腔局部播散和种植可导致腹膜转移癌(peritoneal carcinomatosis,PC),患者常会出现肠梗阻、恶性腹水、疼痛等并发症,为肿瘤终末期,预后较差.胃肠道肿瘤腹膜转移的治疗方法包括全身化疗、腹腔化疗、减瘤手术、减瘤手术联合腹腔热灌注化疗、分子靶向治疗等,这些治疗方法给患者的生存带来不同程度的获益,使腹膜转移癌的预后取得了较大的改善.本文将近年来消化道肿瘤的发病机制及其治疗方法做一回顾总结.     

胃肠胰神经内分泌肿瘤患者预后的多因素分析

目的:分析胃肠胰神经内分泌肿瘤患者预后的危险因素,并探讨对应的干预对策,以期为临床提供借鉴。方法:回顾自2002年6月至2013年12月入院治疗的胃肠胰神经内分泌肿瘤患者的资料,对患者的一般情况如性别、年龄、肿瘤大小、肿瘤部位、肿瘤侵犯程度、淋巴结转移、血管侵犯、手术切缘、远处转移、总生存期等数据进行分析,总结胃肠胰神经内分泌肿瘤患者预后的危险因素。结果:123患者平均发病年龄56.9岁,男性平均发病年龄59.5岁,女性平均发病年龄52岁。＜60岁患者68例,≥60岁55例,从发病到明确诊断时平均时间为9.8月,中位生存时间为46.1个月,1年生存率为69%,3年生存率为37.4%, 5年生存率为29.6%。通过单因素分析,年龄、肿瘤大小、肿瘤侵犯程度、淋巴结转移、血管侵犯、手术切缘、远处转移与胃肠胰神经内分泌肿瘤患者预后显著相关,P＜0.05;性别、肿瘤部位与胃肠胰神经内分泌肿瘤患者预后无明显相关,P分别为0.784、0.988。通过多因素COX回归分析,年龄(HR=1.93,95%CI:1.06~3.50)及远处转移(HR=1.83,95%CI:1.24~2.72)为胃肠胰神经内分泌肿瘤患者预后的独立危险因素。结论:年龄、肿瘤大小、肿瘤侵犯程度、淋巴结转移、血管侵犯、手术切缘、远处转移等是胃肠胰神经内分泌肿瘤患者生存预后的危险因素,年龄大、远处转移患者生存预后最差。     

Intraperitoneal chemotherapy for colorectal cancer.

The peritoneal surface remains an important failure site for patients with colorectal cancer. Peritoneal metastases of colorectal cancer are at present considered equal to distant metastatic disease. Consequently, peritoneal carcinomatosis is treated with systemic chemotherapy and surgery only to palliate complications such as obstruction. Despite the development of new chemotherapeutic agents and combinations, the results remain disappointing with a limited impact on survival. Colorectal carcinoma cells are relatively resistant to chemotherapy. Intraperitoneal chemotherapy seems to be an attractive approach in the treatment of high-risk colorectal cancer and peritoneal carcinomatosis from colorectal origin providing high local drug concentration with limited systemic side effects. Adjuvant early postoperative intraperitoneal chemotherapy is worthwhile for consideration as treatment option after resection of high-risk colorectal cancer. In the treatment of peritoneal carcinomatosis postoperative intraperitoneal chemotherapy leads to inadequate exposure of the peritoneal surface. Only an intraoperative intraperitoneal chemotherapy performed with direct cytotoxic drugs such as MMC and cisplatin overcome this problem. The limited drug penetration in tissue implies the need for extensive cytoreductive surgery. The results of phase II studies suggest that an increased median survival can be achieved with this approach. The natural history of this disease and the heterogeneity of the patients are such that only a randomized trial design will adequately answer the question whether regional treatment of patients with peritoneal dissemination of colorectal cancer actually prolongs survival. The results of such a study are to be expected in approximately 2 years time.     

Direct surgery with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for patients with colorectal peritoneal metastases

IntroductionNeoadjuvant chemotherapy is widely used in treatment of peritoneal metastases from colorectal cancer, but there is little scientific evidence for this approach. This study aimed to study survival in patients treated with direct surgery with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS-HIPEC), i.e. without neoadjuvant chemotherapy.Material and methodsPatients with histopathologically confirmed peritoneal metastases from colorectal cancer that underwent first-time CRS-HIPEC with complete cytoreduction (CC0 or 1) at Karolinska University Hospital 2012–2019 were included. Patients with synchronous extraperitoneal metastases were excluded if not treated before end of follow-up. Factors associated with overall survival (OS) and disease-free survival (DFS) were evaluated using the Kaplan-Meier method and Cox regression models. The multivariable models were adjusted for sex, age, synchronous/metachronous peritoneal metastases, peritoneal carcinomatosis index (PCI), extraperitoneal metastases and the pathological tumor (T) and lymph node (N) stage of the primary tumor.ResultsIn all, 131 patients underwent complete CRS-HIPEC for peritoneal metastases without neoadjuvant chemotherapy. The median OS and DFS were 40.3 months and 12.5 months, respectively, in patients treated with direct surgery. In the multivariable model, PCI≥16 was the only variable associated with decreased OS, whereas elevated PCI, metachronous development of peritoneal metastases and synchronous extraperitoneal metastases were associated with decreased DFS. Age was not associated with an impaired prognosis.ConclusionPatients who underwent direct surgery with CRS-HIPEC had a good prognosis, with a median OS of more than 3 years. The results from this study question the need of neoadjuvant chemotherapy in all patients eligible for CRS-HIPEC.     

Extensive cytoreductive surgery followed by intra-operative hyperthermic intraperitoneal chemotherapy with mitomycin-C in patients with peritoneal carcinomatosis of colorectal origin

Peritoneal seeding from colorectal cancer has a very poor prognosis and is relatively resistant to systemic chemotherapy. We performed a phase I/II trial to investigate the feasibility and effectiveness of extensive cytoreductive surgery in combination with intra-operative hyperthermic intraperitoneal chemotherapy (HIPEC) in these patients. 29 patients with peritoneal carcinomatosis of colorectal origin without evidence of distant metastases underwent cytoreductive surgery and intra-operative HIPEC with mitomycin-C (MMC), followed by systemic chemotherapy with 5-fluorouracil (5-FU)/leucovorin. Surgical complications occurred in 11 patients (38%). One patient died directly related to the treatment, resulting in a mortality rate of 3%. MMC toxicity existed mainly of leucocytopenia (in 15 patients; 52%). After a median follow-up of 38 months (range 26-52 months) we found a 2- and 3-year survival rate (Kaplan-Meier) of 45 and 23%, respectively. Extensive cytoreductive surgery and HIPEC is feasible in patients with peritoneal seeding of colorectal cancer. First results suggest that a higher median survival could be achieved compared with conventional palliative surgery and systemic chemotherapy, therefore a randomised phase III study is now being conducted.     

Matrix metalloproteinase inhibition prevents colon cancer peritoneal carcinomatosis development and prolongs survival in rats.

Matrix metalloproteinases (MMP) are enzymes responsible for extracellular matrix degradation which play a role in cancer progression and metastatic spreading. We investigated the effects of the MMP inhibitor, batimastat, in vitro on the proliferation and invasiveness of the rat colon cancer cell line DHD/K12, and in vivo on the growth of an aggressive model of peritoneal carcinomatosis producing haemorrhagic ascites and metastases, obtained in the rat by i.p. injection of DHD/K12 cells. MMP production was studied in conditioned culture media, solid tumors and ascitic fluid. In vivo, after injection of tumor cells on day 0, rats received i.p. daily either batimastat (30 mg/kg) or equal volume of vehicle from day 2 until killing on day 43 (series I) or from day 13 until death (series II). The grade of peritoneal carcinomatosis, ascite volume, number and size of liver metastases were evaluated in both series, and survival in series II. MMPs-1, -2 and -9 were identified in culture media, tumors and ascites. In vitro, batimastat did not modify DHD/K12 cell proliferation and slightly reduced cell invasion. In vivo, in series I, batimastat treatment totally prevented peritoneal carcinomatosis and liver metastasis development. In series II, it significantly prolonged survival (P < 0.0002) and reduced peritoneal carcinomatosis (P < 0.001) and hepatic metastases number as compared with controls. However, batimastat-treated rats of the two series had peritoneal inflammation with marked ascites. Nevertheless, inhibition of MMP is a new therapeutic approach which may be promising in treatment of microtumors as in more advanced cancer stages.     

Clinical application of total parenteral nutrition in patients with peritoneal carcinomatosis

Cancer patients with terminal stage peritoneal carcinomatosis are often unable to eat, rendering total parenteral nutrition (TPN) as the only option to avoid starvation. In this retrospective study, we reviewed the medical records of 46 patients with peritoneal carcinomatosis and compared them to the records of 51 patients who had gastrointestinal malignancy without evidence of peritoneal carcinomatosis. The factors evaluated include demographic data, cause of primary malignancy, ascites formation, anthropometric measurements, laboratory tests, and outcome measurements as well as factors associated with greater than 90‐day survival. In‐hospital mortality was observed in 31 of the 46 patients with peritoneal carcinomatosis, with a median survival time of 40 days (4–148 days) for all 46 patients. The median duration of TPN administration in the peritoneal carcinomatosis group was 24.1 ± 27.4 days (3–68 days). Severe infection related to TPN application was seen in 5/46 (10.7%) patients with peritoneal carcinomatosis and 6/51 (9.8%) patients without peritoneal carcinomatosis. The length of survival varied widely among terminal patients with peritoneal carcinomatosis. The average survival time in peritoneal carcinomatosis patients receiving TPN was short, indicating that the nutrition support of TPN was relatively suboptimal. Ascites was not a prognostic factor for peritoneal carcinomatosis, while body mass index was a predictor for 90‐day survival.     

Cytoreductive surgery and perioperative intraperitoneal chemotherapy for peritoneal carcinomatosis from colorectal carcinoma: non-mucinous tumour associated with an improved survival

AIMS: Cytoreductive surgery combined with perioperative intraperitoneal chemotherapy has been reported as a treatment option for patients with peritoneal carcinomatosis from colorectal carcinoma. METHODS: Thirty patients with colorectal peritoneal carcinomatosis underwent cytoreductive surgery and perioperative intraperitoneal chemotherapy. All appendiceal cancers were excluded. All patients were followed until January 2006 or death. Univariate analysis was performed to evaluate significant prognostic factors for overall survival, defined from the time of surgery. RESULTS: There were 13 male patients. The mean age at the time of surgery was 54years. There was no hospital mortality. The mean duration of hospital stay was 27days. The overall median survival was 29months, with 1- and 2-year survival of 72% and 64%, respectively. Twenty-one patients had complete cytoreduction and their 1- and 2-year survival rates were 85% and 71%, respectively. Univariate analysis demonstrated that patients with non-mucinous colorectal adenocarcinoma, Peritoneal Cancer Index (PCI) < or =13, and complete cytoreduction were associated with an improved survival. CONCLUSIONS: This study reported on 30 patients who underwent cytoreductive surgery and perioperative intraperitoneal chemotherapy for colorectal peritoneal carcinomatosis. Patients with mucinous tumour had relatively more extensive intraperitoneal disease. Non-mucinous colorectal adenocarcinoma, PCI < or =13, and complete cytoreduction were associated with an improved survival.     

Hyperthermic intraperitoneal chemoperfusion in combined treatment of locally advanced and disseminated gastric cancer: Results of a single-centre retrospective study

Background: Patients with locally advanced gastric cancer (GC) and/or peritoneal metastases have a poor prognosis despite systemic chemotherapy or palliative surgery. The aim of this retrospective comparative non-randomised study was to evaluate aggressive cytoreduction in combination with hyperthermic intraperitoneal chemoperfusion (HIPEC) as a novel treatment strategy for patients with intraperitoneal disseminated and locally advanced GC.

Patients and methods: Forty-nine GC patients with serosal invasion (n?=?19), limited peritoneal metastases (n?=?20), or disseminated peritoneal metastases and tense ascites (n?=?10) underwent combination therapy with HIPEC. Three matched control groups undergoing standard therapies were retrospectively identified.

Results: Combination therapy for serosa-invasive GC reduced the level of metachronous peritoneal carcinomatosis and increased median survival from 12 months to 22.5 months (p?=?0.001). The median and 1-year survival rates for intraperitoneal disseminated GC patients undergoing therapy with the use of HIPEC were 12 months and 68.8% compared with 8 months and 25%, respectively (p?=?0.004) for control subgroup patients (palliative chemotherapy). The symptomatic use of HIPEC allows effective elimination of recurrent ascites in GC patients.

Conclusion: HIPEC is a well-tolerated and effective method of adjuvant therapy for gastric cancer with high risk of intraperitoneal progression. Cytoreduction followed by HIPEC improves survival in patients with limited peritoneal carcinomatosis of gastric origin.     

结直肠癌腹膜转移的多学科综合治疗

腹膜转移是结直肠癌常见转移部位之一,传统观念认为其预后差,没有手术治疗的价值。近年来,随着外科技术、精确控温的腹腔热灌注化疗以及多学科综合治疗的进步,对结直肠癌腹膜转移的认识和治疗策略发生很大的变化,拟就这一问题进行综述。在预后方面,如果仅行姑息性化疗,结直肠癌腹膜转移的预后差于肝、肺等非腹膜部位的转移;但对于一部分合适的患者施行完全性腹膜减瘤术联合腹腔热灌注化疗,则可能使部分患者获得长期生存;腹膜转移癌的预后因素包括腹膜播散癌指数、减瘤术完全性程度、是否合并腹膜外转移(肝脏等)、腹膜表面疾病严重程度评分和日本腹膜分期等。在治疗方面,完全性腹膜减瘤术联合腹腔热灌注化疗以及全身治疗(化疗+靶向治疗),可能是最佳的多学科综合治疗策略。     

Long-term survival and tumor 5-FU sensitivity in patients with stage IV colorectal cancer and peritoneal dissemination

Among 125 patients with peritoneal dissemination (P1-3) of colorectal cancer, including those with other synchronous metastases, the 5-year overall survival (OS) rate was 13.3% for P1 patients (n=30), 12.8% for P2 patients (n=39), and 1.8% for P3 patients (n=56) (P1 vs. P2, p=N.S.; P2 vs. P3, p=0.02; P1 vs. P3, p=0.001), while the median survival time (MST) was 12.0, 14.1, and 3.1 months, respectively. The 5-year OS rates for patients who had peritoneal dissemination without other metastases were 17.6% (n=17), 12.5% (n=19), and 3.4% (n=28) (P1 vs. P2, p=N.S.; P2 vs. P3, p=N.S.; P1 vs. P3, p=0.039), while the MST was 25.1, 15.1, and 12.5 months, respectively. In the P3 short survival group (SSG; n=13), TS expression was high in 7.7% (1/13) and low in 92.3% (12/13) of tumors, while DPD expression was high in 38.5% (5/13) and low in 61.5% (8/13) of tumors. In the P3 long survival group (LSG; n=15), the corresponding values were 80.0% (12/15), 20.0% (3/15), 33.3% (5/15), and 66.7% (10/15). High TS and low DPD expression was found in only 7.7% (1/13) of the SSG tumors vs. 46.7% (7/15) of the LSG tumors (p=0.028). These results suggest that the prognosis of stage IV colorectal cancer with P3 peritoneal dissemination is extremely poor. In addition, patients fitting the SSG criteria are unlikely to respond to treatment with 5-FU+LV, and may need combination chemotherapy using CPT-11 and/or L-OHP.     

The usefulness of pharmacokinetic modulating chemotherapy (UFT plus 5FU) in the treatment of unresectable colorectal carcinomas

This study was performed to improve the prognosis of unresectable (primary non-curative and recurrent) colorectal carcinoma by using pharmacokinetic modulating chemotherapy (PMC), a combination of oral UFT and continuous venous 5FU infusion. The subjects were 120 patients who were prospectively selected for this study. The patients selected PMC or alternative treatment. Fifty-six patients received PMC. The PMC group received 200-400 mg/body/ day UFT orally 5-7 days per week and 600 mg/m2/24 h 5FU infusion once a week. PMC markedly improved the median survival period (26.6 months vs. 9.2 months P<0.000001). This significant improvement as observed in unresectable primary colorectal carcinoma (P=0.0003), recurrent tumors (P<0.00001), local extension (P=0.01), lung metastases (P=0. 03), liver metastases (P=0.0001), and peritoneal seedings (P=0.02). One of 56 patients who received PMC developed grade 4 toxicity. PMC significantly improved the prognosis of unresectable colorectal carcinoma which has a low survival rate. PMC also indicated tolerable compliance and cost effectiveness.     

Carcinoma of unknown primary with gastrointestinal profile: immunohistochemistry and survival data for this favorable subset

Background

Carcinoma of unknown primary with a “gastrointestinal profile” is an emerging, favorable entity. Distinguishing this entity is of increasing significance given the progress in the treatment of colorectal cancer.

Patients and methods

74 carcinoma of unknown primary (CUP) patients with CDX2+ tumors were chosen from the databases at M.D. Anderson and Sarah Cannon Cancer Centers between 2004 and 2010. Data on clinical and pathological characteristics including therapy and survival were recorded.

Results

20 patients had ascites on presentation; the predominant sites of metastases included liver (30 %), carcinomatosis (50 %), and nodes (51 %). Based on immunohistochemistry, 2 cohorts were created: Cohort 1—“consistent with lower GI profile” included 34 patients [CDX-2+, CK20+, CK7?] and Cohort 2—“probable lower GI profile” included 40 patients [CDX2+, irrespective of CK7/CK20 status]. Excluding 6 outliers, Cohorts 1 and 2 had 32 and 36 patients, respectively; their median survivals were 37 and 21 months, respectively. On multivariate Cox regression analysis, only liver metastases were found to negatively influence survival.

Conclusions

Our retrospective study provides encouraging indications that CUP patients with gastrointestinal profiles benefit from site-specific therapy. We recommend all CUP patients, especially those with abdominal nodes, isolated carcinomatosis or liver metastases, to undergo optimal immunohistochemistry (IHC) to check for a gastrointestinal profile of CUP.