The desmoplastic growth pattern is associated with second-stage completion and longer survival in 2-stage hepatectomy for colorectal cancer liver metastases.

BACKGROUND: Two-stage hepatectomy for bilobar colorectal cancer liver metastases is potentially curative for selected patients. Histological growth patterns of colorectal liver metastases (desmoplastic, replacement, and pushing) have prognostic value. Our aim was to evaluate their association with pathologic response to preoperative treatment, second-stage hepatectomy completion, and survival in patients treated with a curative-intent 2-stage hepatectomy. METHODS: In 67 patients planned for 2-stage hepatectomy, colorectal liver metastases resected from the first-stage hepatectomy were retrospectively evaluated for growth patterns and pathologic response according to Tumor Regression Grading, modified Tumor Regression Grading, and Blazer grading. Tumor Regression Grading 1 to 3, modified Tumor Regression Grading 1 to 3, and Blazer 0 and 1 defined good responders. RESULTS: Desmoplastic growth patterns (GP) were more frequent among good responders (P < .001). Second-stage hepatectomy completion was associated with desmoplastic growth patterns and pathologic response on univariate analysis and multivariable analyses (P = .017 and P = .041, respectively). Median follow-up was 84 months (95% confidence interval: 53.4 [not reached]). Nondesmoplastic GP patients and nonresponders had a poorer overall survival (hazard ratio = 3.86, 95% confidence interval: 2.11-7.07, P < .001 and hazard ratio = 2.14, 95% confidence interval: 1.19-3.83, P = .009, respectively) on univariate analysis. Nondesmoplastic growth pattern was the only factor associated with a poorer overall survival on multivariable analysis (hazard ratio = 4.17, 95% confidence interval: 1.79-9.74, P < .001). Nondesmoplastic GP was also associated with a poorer recurrence-free survival (hazard ratio = 2.05, 95% confidence interval: 1.13-3.70, P = .017). CONCLUSION: Desmoplastic GP could represent a useful morphological marker for early identification of patients who might benefit from 2-stage hepatectomy completion.

The lymphatic system and sentinel lymph nodes: conduit for cancer metastasis.

The lymphatic system is a complicated system consisting of the lymphatic vessels and lymph nodes draining the extracellular fluid containing cellular debris, excess water and toxins to the circulatory system. The lymph nodes serve as a filter, thus, when the lymph fluid returns to the heart, it is completely sterile. In addition, the lymphatic system includes the mucosa-associated lymphoid tissue, such as tonsils, adenoids, Peyers patches in the small bowel and even the appendix. Taking advantage of the drainage system of the lymphatics, cancer cells enter the lymphatic vessels and then the lymph nodes. In general, the lymph nodes may serve as a gateway in the majority of cases in early cancer. Occasionally, the cancer cells may enter the blood vessels. This review article emphasizes the structural integrity of the lymphatic system through which cancer cells may spread. Using melanoma and breast cancer sentinel lymph node model systems, the spread of early cancer through the lymphatic system is progressive in a majority of cases. The lymphatic systems of the internal organs are much more complicated and difficult to study. Knowledge from melanoma and breast cancer spread to the sentinel lymph node may establish the basic principles of cancer metastasis. The goal of this review article is to emphasize the complexity of the lymphatic system. To date, the molecular mechanisms of cancer spread from the cancer microenvironment to the sentinel lymph node and distant sites are still poorly understood and their elucidation should take major priority in cancer metastasis research.

Complete pathologic response after two-stage cytoreductive surgery with HIPEC for bulky pseudomyxoma peritonei: proof of concept.

Introduction: Pseudomyxoma peritonei (PMP) is a rare disease characterized by the progressive accumulation of mucinous ascites and peritoneal implants. The optimal treatment for PMP includes the association of complete cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC). For patients with a large burdensome disease, the completeness of cytoreduction sometimes requires maximal effort surgery. The aim of this article is to provide proof of concept for two stage cytoreductive surgery (CRS) in this category of patients.Methods and materials: A two stage CRS and HIPEC with oxaliplatin was proposed for patients with bulky PMP including important involvement of the serosal surfaces of the bowel or colon who had an impaired nutritional status. The residual disease at the end of the first stage was less than 5 mm of thickness on several implants. Clinical, surgical and histopathological variables were analyzed.Results: All eight patients completed the two-stage strategy. Mortality was nil. One Clavien Dindo grade 3 event occurred in each stage. After a median follow up of 29.5 months, all patients were alive and free of recurrence. All of the patients had histopathological complete response on the specimens obtained from the residual sites during the second stage surgery.Conclusions: Two-stage surgical strategy is feasible for bulky PMP patients and it is associated with little high-grade morbidity and enhanced visceral sparing.

Two-stage hepatectomy for colorectal liver metastases: Pathologic response to preoperative chemotherapy is associated with second-stage completion and longer survival.

BACKGROUND: Two-stage hepatectomy of bilobar colorectal liver metastases is widely used and shows encouraging survival results. However, the risk of dropout after the first stage remains high and is associated with poor survival. The objective of our study was to evaluate the factors associated with long-term survival based on the pathologic response to preoperative systemic chemotherapy in colorectal liver metastases patients who underwent two-stage hepatectomy. METHODS: The pathologic response to preoperative chemotherapy and its effect on second-stage completion and survival were retrospectively evaluated in 67 patients treated between 2003 and 2013. RESULTS: A total of 56 patients underwent two-stage hepatectomy for initially nonresectable colorectal liver metastases. Chemotherapy was combined with a biotherapy in 32 cases. The tumor regression grade, modified tumor regression grade, and Blazer grade were used to classify patients as responders (tumor regression grade and modified tumor regression grade 1-3, Blazer 0-1) or nonresponders (tumor regression grade and modified tumor regression grade 4-5, Blazer 2) after the first stage. Tumor response in the three classifications was associated with second-stage completion (tumor regression grade 1-3: OR = 4.01, 95% CI: 1.12-14.36, P = .033; modified tumor regression grade 1-3: OR = 3.8, 95% CI: 1.13-12.6, P = .03; Blazer 0-1: OR = 5.45, 95% CI: 1.66-17.85, P = .005). Triple chemotherapy was also associated with responders. The median overall survival of responders was significantly higher (Blazer 0-1: 42.9 months versus Blazer 2: 20.1 months, P = .018; tumor regression grade 1-3: 42.9 months versus tumor regression grade 4-5: 25.1 months, P = .04). CONCLUSION: A pathologic response to chemotherapy is associated with second-stage completion and longer survival. Further studies are needed to achieve the early identification of patients for whom the benefit of the second surgical stage is less straightforward.

Preoperative intraperitoneal oxaliplatin for unresectable peritoneal carcinomatosis of colorectal origin: a pilot study.

BACKGROUND: Peritoneal carcinomatosis in colorectal cancer is an advanced stage of the disease where improved survival can be attained whenever the resection associated with hyperthermic intreperitoneal chemotherapy is possible. In unresectable cases, systemic chemotherapy is administered to obtain conversion to resectability but results have not yet been clearly evaluated. Local chemotherapy in this setting has been proven useful in several similar situations. The aim of the present pilot study was to evaluate the feasibility of pre-operative intraperitoneal chemotherapy with oxaliplatin in these patients. METHODS: Six patients with unresectable peritoneal disease of colorectal origin were included in the study. An intraperitoneal implantable chamber catheter was inserted during the laparotomy that evaluated the extent of the peritoneal disease (peritoneal carcinomatosis index 25 to 39). Patients then underwent intraperitoneal chemotherapy with oxaliplatin 85 mg/m2 in combination with systemic chemotherapy (FOLFIRI or simplified LV5FU) and a targeted therapy every 2 weeks. RESULTS: Two catheter perfusion incidents were reported due to the abdominal wall thickness. Two patients completed the four intraperitoneal (IP) chemotherapy cycles without major toxicity. One patient developed grade 3 or 4 diarrhea requiring a short intensive care unit (ICU) stay, though it is not clear whether the event was induced by intravenous irinotecan, IP oxaliplatin or the combination of both. Grade 3 fatigue and abdominal pain were also recorded. For one patient with aggressive disease, best supportive care was initiated after the first course of chemotherapy. CONCLUSIONS: Our study is the first to assess intraperitoneal oxaliplatin-based chemotherapy in the preoperative setting for patients with unresectable peritoneal metastases. The tolerance was acceptable for 85 mg/m2 IP oxaliplatin combined with systemic therapy in these patients. Our results justify carrying on with a phase I/II trial to determine the recommended dose of oxaliplatin in this clinical context and its efficacy.

The best surgical approach for left colectomy: a comparative study between transverse laparotomy, midline laparotomy and laparoscopy.

AIM: To compare the early and late complications after left colectomy (LC) by left transverse laparotomy (LTL), midline laparotomy (ML) and laparoscopy (La). METHODS: From 1998 to 2003, 328 patients underwent an LC by LTL, ML or La. After matching patients for age, ASA score and indication, 159 patients were divided into three groups of 53 patients each according to the surgical approach performed. The median follow-up was 8 years. Early and late complications were compared by univariate and multivariate analysis. RESULTS: Early morbidity rates after LTL, ML and La were 52%, 45% and 21%, respectively (p = 0.002). Extra digestive complication rates after LTL, ML and La were 36%, 34% and 13.2%, respectively (p = 0.02). Respiratory complication rates were 15%, 21% and 2% (p = 0.01). The rate of wound infection was higher after LTL (15% vs. 6% and 6%, p = 0.06). Length of stay was significantly shorter after La (median: LTL, 10 days; ML, 9 days; La, 6 days; p < 0.0001). At a median follow-up of 8 years, the obstruction rate was 6.3%, regardless of the surgical approach. The rates of incisional hernia after LTL, ML and La were 8%, 23% and 3% (p = 0.004), respectively, with odds ratio (OR) = 4.47 (1.2 to 16). CONCLUSION: Our study shows that although La has a significant lower rate of complications, LTL, with fewer respiratory complications and hernia than ML, should be considered as the reference incision in case of conversion or contra-indication for laparoscopy.

Laparoscopic ventral rectopexy for the treatment of outlet obstruction associated with recto-anal intussusception and rectocele: a valid alternative to STARR procedure in patients with anal sphincter weakness.

OBJECTIVE: This study was designed to assess the safety and outcomes achieved with Stapled Trans-Anal Rectal Resection (STARR) vs laparoscopic ventral rectopexy (LVR) in obstructed defecation patients. METHOD: From 2002 to 2011, 52 patients (females) had a rectocele with outlet obstruction. After clinical assessment by an Obstructed Defecation Syndrome score (ODS), an anorectal manometry, a defecography and an endoanal ultrasound, the patients underwent either a STARR (n=25) or a LVR (n=27) according to the existence of an asymptomatic anal sphincter injury. Functional results were evaluated clinically and by the preoperative and 18 months postoperative ODS score and by an 18 months postoperative score of satisfaction. RESULTS: Average ages were 56 ± 10 years in the STARR and 60 ± 9 years in LVR. The 1-month postoperative complication rates were comparable for the 2 groups (25%). Mean length of stay was shorter for STARR than for LVR (5.6 ± 2.1 vs. 7.1 ± 2.9, P=0.009). After treatment, the ODS was lowered by 56% in LVR and 59% in the STARR (P=0.0001) but with no difference between the 2 groups. Eighty percent of patients were very or moderately satisfied after LVR, versus 84% after STARR. CONCLUSIONS: The 2 surgical procedures obtain good results with 80% of satisfied patients with a length of stay a little shorter in the STARR. BRIEF SUMMARY: In our retrospective study, Stapled Trans-Anal Rectal Resection (STARR) and laparoscopic ventral rectopexy improved the outlet obstruction associated with recto-anal intussusception and rectocele.