Impact of KRAS, BRAF and PI3KCA mutations in rectal carcinomas treated with neoadjuvant radiochemotherapy and surgery.

BACKGROUND: Conventional treatment for locally advanced rectal cancer usually combines neoadjuvant radiochemotherapy and surgery. Until recently, there have been limited predictive factors (clinical or biological) for rectal tumor response to conventional treatment. KRAS, BRAF and PIK3CA mutations are commonly found in colon cancers. In this study, we aimed to determine the mutation frequencies of KRAS, BRAF and PIK3CA and to establish whether such mutations may be used as prognostic and/or predictive factors in rectal cancer patients. METHODS: We retrospectively reviewed the clinical and biological data of 98 consecutive operated patients between May 2006 and September 2009. We focused in patients who received surgery in our center after radiochemotherapy and in which tumor samples were available. RESULTS: In the 98 patients with a rectal cancer, the median follow-up time was 28.3 months (4-74). Eight out of ninety-eight patients experienced a local recurrence (8%) and 17/98 developed distant metastasis (17%). KRAS, BRAF and PIK3CA were identified respectively in 23 (23.5%), 2 (2%) and 4 (4%) patients. As described in previous studies, mutations in KRAS and BRAF were mutually exclusive. No patient with local recurrence exhibited KRAS or PIK3CA mutation and one harbored BRAF mutation (12.5%). Of the seventeen patients with distant metastasis (17%), 5 were presenting KRAS mutation (29%), one BRAF (5%) and one PIK3CA mutation (5%). No relationship was seen between PIK3CA, KRAS or BRAF mutation and local or distant recurrences. CONCLUSION: The frequencies of KRAS, BRAF and PIK3CA mutations in our study were lower than the average frequencies reported in colorectal cancers and no significant correlation was found between local/distant recurrences and KRAS, BRAF or PIK3CA mutations. Future studies with greater number of patients, longer follow-up time and greater power to predict associations are necessary to fully understand this relationship.

A comparative study of patients with and without associated digestive surgery in a two-stage hepatectomy setting.

PURPOSE: The purpose of this study was to compare the feasibility and outcomes of two-stage hepatectomy in patients with or without accompanying digestive surgery. METHODS: We analyzed prospectively data from 56 patients with colorectal liver metastases undergoing two-stage hepatectomy between 1995 and 2009. Patients undergoing associated digestive resection (group I, n = 32) were compared with patients without associated digestive surgery (group II, n = 17). RESULTS: The feasibility rate was 87.5% (49 patients). Neither the type and extent of hepatectomy nor the type of chemotherapy administered differed between the two groups. The median interval between hepatectomies was 1.79 and 2.07 months for groups I and II, respectively (not significant). One patient (group I) died of liver failure after the second hepatectomy. Postoperative morbidity rates were comparable: 37.5% (group I) vs. 35.5% (group II) after the first hepatectomy and 46.9% (group I) vs. 52.9% (group II) after the second hepatectomy. The median hospital stay after the first hepatectomy was longer in group I (13.5 days) than in group II (10 days) (P < 0.01). Median follow-up was 54 months. The median overall survival (OS) was 45.8 months, and 3- and 5-year OS were 58 and 31%, respectively. Median OS was longer for group II (58 months) than for group I (34 months) (P = 0.048). CONCLUSIONS: Digestive tract resection associated with two-stage hepatectomy does not increase postoperative mortality or morbidity nor does it lead to delay in chemotherapy or a reduction in cycles administered. The need for digestive tract surgery should not affect the surgical management of two-stage hepatectomy patients.

Retroperitoneal vascular surgery for the treatment of giant growing teratoma syndrome.

OBJECTIVE: To evaluate whether an aggressive surgical policy, which included vascular surgery with standard retroperitoneal lymph node dissection (RPLND), would be justified for managing bulky retroperitoneal growing teratoma syndrome (GTS). METHODS: Data were collected retrospectively from a series of 12 patients who, from 1992 to 2010, underwent radical RPLND for bulky GTS (retroperitoneal mass≥10 cm in diameter). For complete resection, vascular procedures and nephrectomy were performed. RESULTS: Median tumor diameter was 100 mm before and 140 mm (range 100-300) after chemotherapy. Two patients underwent iterative RPLND. In addition to RPLND, patients underwent aortic section with aortic anastomosis (n=6), inferior vena cava resection (n=3), both the latter and the former (n=1), and aortic graft with left nephrectomy (n=2). There were no operative deaths; 3 patients had complications (25%), but none were related to extended procedures. The median hospital stay was 15 days. Median follow up was 59 months (range 10-162). One patient died of metastatic cutaneous melanoma 112 months after RPLND, 10 patients survived and are disease-free, and one patient had a para-aortic recurrence. CONCLUSION: A 100% complete resection rate, long-term survival, no mortality, and acceptable morbidity were achieved when vascular surgery and left nephrectomy were combined with standard RPLND for bulky GTS.

Predictive role of preoperative lymphoscintigraphy on the status of the sentinel lymph node in clinically node-negative patients with cutaneous melanoma.

We reviewed our experience to assess the predictive role of preoperative lymphoscintigraphy with regard to the pathological status of sentinel lymph node (sN) in patients with cutaneous melanoma, to optimize the surgical treatment planning with regard to the use of intraoperative frozen section examination of sN. Eighty-eight patients with clinically node-negative cutaneous melanoma pT1b-T4 stage underwent preoperative lymphoscintigraphy for the lymphatic mapping of sN. A lymphoscintigraphic 'score' (from L1 to L5) was developed based on the ratio of radiotracer concentration within sN nodes as compared with the injection site. Our score allowed us to foresee that sN of patients with thick melanomas (T3 and T4) and a low preoperative score (L1-L2-L3) had a 90% expected likelihood (P<0.001) of harboring metastasis, whereas sN in patients with thin melanomas (T1b-T2) and high preoperative score (from L4 to L5) showed a 100% likelihood of being metastasis free. In conclusion, the sN is a reliable predictor of regional lymph node status in patients with cutaneous malignant melanoma. Moreover, we suggest that a low score (L1-L2-L3) associated with a thick melanoma is a good predictive factor of the positive sN involvement. This information could be useful in scheduling the intraoperative frozen-section examination with an expected benefit of a positive test in almost 90% of patients. Such patients might be selected for a 'one-stage' procedure with a more effective cost/benefit ratio and decreased hospitalization costs.

Primary melanoma of the esophagus with non-metastatic dark lymph nodes in a female breast cancer patient.

BACKGROUND: Primary melanoma of the esophagus is a very rare and aggressive neoplasm; only a small number of patients survive more than 1 year after initial diagnosis. CASE REPORT: We describe a case of primary melanoma of the esophagus in a woman with a history of invasive breast cancer. The patient suffered from dysphagic and dyspeptic disorders. The abdomen ultrasonography and the esophagogastroscopy showed a lesion located at the esophago-gastric junction extending to the gastric fundus. Histological and immunohistochemical studies revealed a primary esophageal infiltrating melanoma. A total gastrectomy and regional lymphadenectomy with a partial resection of the distal esophagus was performed. RESULTS: During laparotomic exploration, numerous dark lymp hnodes were found. On frozen sections, surprisingly neither malignant cells nor melanin were detected in the lymph nodes. Resection margins were not involved with the tumor. CONCLUSION: Patient is still alive with no evidence of recurrence at 24 months after surgical treatment, alone.

Primary osteosarcoma of the spermatic cord: case report and literature review.

Primary osteosarcoma of the spermatic cord is a rare tumour with few mentions in the literature. A 59-year-old man presented with a large painless left inguinal and scrotal mass. The patient underwent excision of the mass, which arose from the spermatic cord. A left high dissection of the spermatic cord and radical orchiectomy due to associated atrophy of the left testicle were performed. Pathological findings were suggestive of spermatic cord osteosarcoma. The patient died eleven years later of metastatic lung disease. Spermatic cord osteosarcoma is an uncommon neoplasm and its preoperative diagnosis is very difficult. Any palpable suspicious mass of the cord should be investigated with ultrasonography before excision; CT scan and magnetic resonance imaging may be helpful in defining preoperative diagnosis and the extension of the mass into the neighbouring tissues. Surgical treatment of spermatic cord sarcomas in adults is via a radical orchiectomy with high dissection of the spermatic cord and en bloc excision of involved neighbouring tissues; overall 5- and 10-year survival rates are reported in the literature to be 75% and 55%, respectively.

Ileal carcinoid with liver metastasis presenting after ten years with abdominal mass and right heart failure: report of a case.

A case of ileal carcinoid metastatic to the liver is reported. The diagnosis was made and treatment given ten years after the detection of a left hypervascular liver mass, which was first confounded with a hemangioma. The onset of right heart failure led to surgical replacement of the tricuspid and pulmonary valves. After cardiac surgery the patient underwent an ileal resection and left hepatectomy for a cystic left liver metastasis. Isolated right heart failure and cystic degeneration of a liver metastasis are uncommon features of metastatic carcinoid tumors; only a few cases have been described in the literature. Cardiac surgery is recommended before liver surgery to reduce venous pressure and consequent bleeding during hepatectomy. Surgical treatment of liver metastases may relieve endocrine symptoms and result in an overall five-year survival rate of 47%.

Transpleurodiaphragmatic cryosurgical ablation for recurrent unresectable colorectal liver metastases.

BACKGROUND AND OBJECTIVES: Cryosurgical ablation (CSA) allows the focal destruction of unresectable liver metastases after previous liver resection. The abdominal approach may be difficult for recurrent colorectal cancer metastases located in the upper part of the remaining liver, close to the inferior vena cava (IVC), the hepatic veins, and the diaphragm. A transpleurodiaphragmatic access was assessed for safety and efficacy. METHODS: Between September 1999 and July 2004, 13 patients with recurrent unresectable colorectal liver metastases underwent transpleurodiaphragmatic CSA via limited right thoracotomy. Seventeen lesions were treated; median diameter was 31 mm (range 13-40 mm). One to three cryoprobes were used, depending on the size and location of metastases. RESULTS: There was no operative death; three patients developed minor complications (23%). Median hospital stay was 10 days (8-14 days). After a median follow-up of 26 months (range 8-69 months), 9 patients were alive, and 5 were disease-free. Six patients had liver recurrences outside the cryolesion. Median disease free survival was 12 months with 60% 3-year survival after CSA and 58% 5-year survival after first liver surgery. CONCLUSIONS: Transpleurodiaphragmatic CSA is safe and effective in selected patients with unresectable recurrent liver metastases from colorectal cancer.

Laparoscopic treatment of Morgagni-Larrey hernia: technical details and report of a series.

Three patients with Morgagni-Larrey hernia were admitted to the surgical department between August 2000 and September 2003 with slight chest pain and dyspnea. Laparoscopic repair of the diaphragmatic hernia was performed using a tension-free closure of the defects with either Vicryl-Prolene or dual facing mesh fixed by Prolene extracorporeal knots and Endostitch devices. The patients were discharged on postoperative day 5 without complications. Mean follow-up has been 23 months (range, 15-36 months) and no recurrence or morbidity related to the procedure has been seen. Laparoscopic repair of Morgagni-Larrey hernia represents an attractive alternative to open surgery. The benefits are gentle and easy manipulation of the content of the sac, reduced surgical trauma, and rapid and uneventful recovery.

Right portal vein thrombosis after splenectomy for trauma.

Portal vein thrombosis may complicate splenectomy in patients with hemolytic anemia and myeloproliferative disease, whereas the frequency of portal vein thrombosis in case of trauma is not defined. A case of right portal vein thrombosis after splenectomy for trauma is reported in this paper. Hematologic workup did not reveal an underlying platelet or coagulation disorder. The patient was promptly anti-coagulated with complete recanalization of the portal vein. We conclude that mild symptoms, like abdominal pain and fever, after splenectomy should be investigated with a color Doppler ultrasonography to confirm or rule out a diagnosis of portal thrombosis and to anti-coagulate the patient with thrombosis, thus preventing bowel infarction and secondary portal hypertension. Routine postoperative color Doppler might also be justified in all postsplenectomy patients (without hematologic diseases) for early detection of a portal vein thrombosis.

Conservative management of a spleen trauma using radiofrequency.

AIM OF THE STUDY: Conservative operative management of a splenic injury has become more and more employed in order to preserve the immune function of the organ. CASE REPORT: A case of a rupture of the spleen successfully treated with the use of a radiofrequency thermal energy generator is eported. The parenchymal tear was coagulated by a one cooled tip needle electrode. There were no postoperative complications and the function of the spleen was preserved. CONCLUSIONS: The technique cannot be applied in case of lesion of the major vessels or in case of avulsion of the hilum. This technique integrates to the others to make the operative conservative management of a splenic injury more and more feasible.

Radiofrequency-assisted liver resection.

Radiofrequency (RF)-assisted thermal ablation has been used with increasing frequency for unresectable hepatic tumors. This new approach employs RF energy to coagulate the liver at the hepatic resection line after which hepatic resection is performed with the use of a common scalpel. This procedure was used in three patients with hepatocellular carcinoma and in five patients with colorectal metastasis to the liver. These eight patients underwent a total of two left bisegmentectomies, three segmentectomies, and seven wedge resections. Mean operative time was 220 minutes. A mean of 78 sessions of RF-assisted ablation were required for these resections. Mean blood loss was 46 ml; no device other than RF ablation was required to obtain hemostasis. None of the patients needed a blood transfusion. Preoperative hemoglobin was 12.8 gm/dl and postoperative hemoglobin was 11.3 gm/dl. There were no perioperative deaths. Postoperative complications occurred in two patients: a liver abscess in one and heart failure in the other. The mean hospital stay was 9.4 days. This new approach, integrated with other techniques, reduces blood loss and coagulates the margins of resection during liver surgery. This new technique has two limitations: (1) it cannot be applied near main portal pedicles, and (2) it requires a long operative time. The best indication for this technique is when segmentectomy is required in patients with cirrhosis. Its role in major hepatic resections has yet to be determined. Further progress in the development of thermal ablation techniques and experience gained during the learning curve should help reduce the operative time, thereby improving the safety and efficacy of this procedure.