Laparoscopic cytoreductive surgery and hyperthermic intraperitoneal chemotherapy: Long term oncologic outcomes from the international PSOGI registry.

The laparoscopic approach for cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (L-CRS + HIPEC) in highly selected patients was previously reported from the PSOGI registry with a demonstrable reduction in length of stay and post-operative morbidity. This study aims to update this international PSOGI registry with a larger cohort of patients and a longer follow-up period. METHODS: An international registry was designed through a networking database (REDCAP®). All centers performing L-CRS + HIPEC were invited through PSOGI to submit data on their cases. Variables such as demographics, clinical outcomes, and survival were analyzed. RESULTS: A total of 315 L-CRS + HIPEC cases were provided by 14 worldwide centers. A total of 215 patients were included in the L-CRS + HIPEC group. The median peritoneal cancer index (PCI) was 3 (3-5). The median length of stay was 7 days (5-10) and the major morbidity (Clavien-Dindo ≥3) was 6.1% after 30 days. The 5-year disease-free survival (DFS) per tumor origin was: 94% for PMP-LG, 85% for PMP-HG, 100% for benign multicyst peritoneal mesothelioma (MPM), 37.4% for colonic origin, and 54%(at 3 years) for ovarian origin. The 5 years overall survival (OS) per tumor origin was: 100% for PMP-LG, PMP-HG and MPM; 61% for colonic origin, and 74% (at 3 years) for ovarian origin. In addition, a total of 85 patients were analyzed in the laparoscopic risk-reducing HIPEC (L-RR + HIPEC). The median length of stay was 5 days (4-6) and the major morbidity was 6% after 30 days. The 5-year DFS per tumor origin was: 96% for perforated low grade appendiceal mucinous neoplasm (LAMN II) and 68.1% for colon origin. The 5 years OS per tumor origin was: 98% for LAMN II and 83.5% for colonic origin. CONCLUSIONS: Minimally invasive CRS + HIPEC is a safe procedure for selected patients with peritoneal carcinomatosis in specialized centers. It improves perioperative results while providing satisfactory oncologic outcomes. L-RR + HIPEC represents a promising strategy that could be evaluated in patients with high risk of developing peritoneal carcinomatosis into prospective randomized trials.

Laparoscopic cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for limited peritoneal metastasis. The PSOGI international collaborative registry.

INTRODUCTION: A laparoscopic approach for cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (L-CRS+HIPEC) in highly selected patients has been reported in small cohorts with a demonstrable reduction in length of stay and post-operative morbidity. This study aims to analyse individual patient data from these international centres collected through the Peritoneal Surface Oncology Group International (PSOGI) L-CRS+HIPEC registry. METHODS: An international registry was designed through a networking database (REDCAP®). All centres performing L-CRS+HIPEC were invited through PSOGI to submit data on their cases. Patient's characteristics, postoperative outcomes and survival were analysed. RESULTS: Ten international centres contributed a total of 143 L-CRS+HIPEC patients during the study period. The most frequent indication was low grade pseudomyxoma peritonei in 79/143 (55%). Other indications were benign multicyst mesothelioma in 21/143(14%) and peritoneal metastasis from colon carcinoma in 18/143 (12,5%) and ovarian carcinoma in 13/143 (9%). The median PCI was 3 (2-5). The median length of stay was 6 (5-10) days, with 30-day major morbidity rate of 8.3% and 30-day mortality rate of 0.7%. At a median follow-up of 37 (16-64) months 126/143 patients (88.2%) were free of disease. CONCLUSIONS: Analysis of these data demonstrates that L-CRS+HIPEC is a safe and feasible procedure in highly selected patients with limited peritoneal disease when performed at experienced centres. While short to midterm outcomes are encouraging in patients with less invasive histology, longer follow up is required before recommending it for patients with more aggressive cancers with peritoneal dissemination.

A minimally invasive approach for peritonectomy procedures and hyperthermic intraperitoneal chemotherapy (HIPEC) in limited peritoneal carcinomatosis: The American Society of Peritoneal Surface Malignancies (ASPSM) multi-institution analysis.

BACKGROUND: Minimally invasive surgery is playing an increasing role in the treatment of patients with gastrointestinal and gynaecological malignancies as the data show reduced morbidity, faster recovery and similar oncological outcome when compared to open procedures. MATERIALS AND METHODS: The American Society of Peritoneal Surface Malignancies (ASPSM) conducted a retrospective study to analyse peritonectomy procedures and HIPEC done via the laparoscopic route. A database with standard clinical and pathological parameters was set up and distributed amongst ASPSM members. Rate of relapse, morbidity and mortality were the primary endpoints of the study. RESULTS: A total of 90 patients from 7 centres around the world were identified. Sixty percent were female. Mean age was 50 years. Peritoneal carcinomatosis from appendiceal origin was the most common diagnosis in a 64.9% of patients and colon origin was diagnosed in 16.5% of patients. Mean peritoneal cancer index (PCI) was 4.1 (0-10). Forty-one percent of patients had a bowel resection. Mean operative time was 4.7 h (2.5-8). All patients had a complete cytoreduction and HIPEC. Grade 3 and 4 morbidity was 3.0 and 6.5%, respectively. The most common reason for re-operation was an internal hernia in 2 out of 5 cases. Operative mortality and re-admission rates were 0 and 5%, respectively. Mean hospital stay was 7.4 days (1-18). At a mean follow-up of 31.6 months, 15/90 patients have a disease relapse but loco-regional relapse was identified in only five patients. CONCLUSIONS: Analysis of these data suggests that minimally invasive approach for peritonectomy procedures and HIPEC is feasible, safe and should be considered as part of the armamentarium for highly selected patients with peritoneal surface malignancies with limited tumour burden, defined as PCI of 10 or less and borderline tumours as low-grade pseudomyxoma and benign multicystic mesothelioma.

Single-stage resection and microwave ablation for bilobar colorectal liver metastases.

BACKGROUND: Patients undergoing liver resection combined with microwave ablation (MWA) for bilobar colorectal metastasis may have similar overall survival to patients who undergo two-stage hepatectomy, but with less morbidity. METHODS: This was a multi-institutional evaluation of patients who underwent MWA between 2003 and 2012. Morbidity (90-day) and mortality were compared between patients who had MWA alone and those who underwent combined resection and MWA (CRA). Mortality and overall survival after CRA were compared with published data on two-stage resections. RESULTS: Some 201 patients with bilobar colorectal liver metastasis treated with MWA from four high-volume institutions were evaluated (100 MWA alone, 101 CRA). Patients who had MWA alone were older, but the groups were otherwise well matched demographically. The tumour burden was higher in the CRA group (mean number of lesions 3·9 versus 2·2; P = 0·003). Overall (31·7 versus 15·0 per cent; P = 0·006) and high-grade (13·9 versus 5·0 per cent; P = 0·030) complication rates were higher in the CRA group. Median overall survival was slightly shorter in the CRA group (38·4 versus 42·2 months; P = 0·132) but disease-free survival was similar (10·1 versus 9·3 months; P = 0·525). The morbidity and mortality of CRA compared favourably with rates in the existing literature on two-stage resection, and survival data were similar. CONCLUSION: Single-stage hepatectomy and MWA resulted in survival similar to that following two-stage hepatectomy, with less overall morbidity.

Impact of chemotherapy on survival in surgically resected retroperitoneal sarcoma.

BACKGROUND: The role of systemic chemotherapy (CT) in the multimodality treatment strategy for retroperitoneal sarcomas (RPS) remains controversial. We hypothesized that chemotherapy does not improve overall survival for patients with surgically resected RPS. METHODS: The National Cancer Database was used to identify all patients with RPS that underwent surgical resection from 1998 to 2011. Univariate and multivariable Cox proportional hazards modeling were used to assess overall survival (OS) and logistic regression was used for associations. Propensity score (PS) modeling was performed to create balanced cohorts for analysis. RESULTS: A total of 8653 patients with surgically resected RPS were identified; 1525 (17.6%) received CT; 10.6% of patients (n = 163) in the neoadjuvant setting. Factors associated with receipt of CT included moderate (OR 2.3) to poorly differentiated (OR 4.3) tumors, leiomyosarcoma (OR 1.8) or undifferentiated pleomorphic sarcoma (OR 2.3) histology, and R2 resection status (OR 2.2) (all p < 0.05). Unadjusted median OS for patients receiving CT compared to surgery alone was 40 vs 68.2 months respectively (p < 0.01). Following propensity score matching, worse median OS persisted among the CT cohort (40 vs 52 months, p = 0.002). Receipt of chemotherapy was not associated with improved long term survival in adjusted models for the raw and propensity matched cohorts (HR 1.17, 95% CI: 1.04-1.31; p = 0.009). CONCLUSION: Current available chemotherapy regimens for RPS do not confer a survival benefit. Routine use of chemotherapy for RPS should be discouraged until new effective systemic agents become available.

Patency rates of portal vein/superior mesenteric vein reconstruction after pancreatectomy for pancreatic cancer.

BACKGROUND: Pancreatectomy with venous reconstruction (VR) for pancreatic cancer (PC) is occurring more commonly. Few studies have examined the long-term patency of the superior mesenteric-portal vein confluence following reconstruction. METHODS: From 2007 to 2013, patients who underwent pancreatic resection with VR for PC were classified by type of reconstruction. Patency of VR was assessed using surveillance computed tomographic imaging obtained from date of surgery to last follow-up. RESULTS: VR was performed in 43 patients and included the following: tangential resection with primary repair (7, 16%) or saphenous vein patch (9, 21%); segmental resection with splenic vein division and either primary anastomosis (10, 23%) or internal jugular vein interposition (8, 19%); or segmental resection with splenic vein preservation and either primary anastomosis (3, 7%) or interposition grafting (6, 14%). All patients were instructed to take aspirin after surgery; low molecular weight heparin was not routinely used. An occluded VR was found in four (9%) of the 43 patients at a median follow-up of 13 months; median time to detection of thrombosis in the four patients was 72 days (range 16-238). CONCLUSIONS: Pancreatectomy with VR can be performed with high patency rates. The optimal postoperative pharmacologic therapy to prevent thrombosis requires further investigation.

Consensus guidelines from The American Society of Peritoneal Surface Malignancies on standardizing the delivery of hyperthermic intraperitoneal chemotherapy (HIPEC) in colorectal cancer patients in the United States.

BACKGROUND: The American Society of Peritoneal Surface Malignancies (ASPSM) is a consortium of cancer centers performing cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (HIPEC). This is a position paper from the ASPSM on the standardization of the delivery of HIPEC. METHODS: A survey was conducted of all cancer centers performing HIPEC in the United States. We attempted to obtain consensus by the modified method of Delphi on seven key HIPEC parameters: (1) method, (2) inflow temperature, (3) perfusate volume, (4) drug, (5) dosage, (6) timing of drug delivery, and (7) total perfusion time. Statistical analysis was performed using nonparametric tests. RESULTS: Response rates for ASPSM members (n = 45) and non-ASPSM members (n = 24) were 89 and 33 %, respectively. Of the responders from ASPSM members, 95 % agreed with implementing the proposal. Majority of the surgical oncologists favored the closed method of delivery with a standardized dual dose of mitomycin for a 90-min chemoperfusion for patients undergoing cytoreductive surgery for peritoneal carcinomatosis of colorectal origin. CONCLUSIONS: This recommendation on a standardized delivery of HIPEC in patients with colorectal cancer represents an important first step in enhancing research in this field. Studies directed at maximizing the efficacy of each of the seven key elements will need to follow.

Ciliated hepatic cyst leading to squamous cell carcinoma of the liver - A case report and review of the literature.

INTRODUCTION: Ciliated hepatic foregut cysts (CHFC) are rare, typically benign liver lesions. Primary squamous cell carcinoma (SCC) of the liver is also a rare entity with only approximately 25 reported cases in the literature. Recently, there have been four reports of malignant transformation of CHFC into primary squamous cell carcinoma of the liver. Here we report a fifth with unique presentation and review the literature. PRESENTATION OF CASE: A 34 year-old man, with a history of ulcerative colitis, was incidentally found to have a 10cm lesion in the right anterior sector plus left medial section of the liver on computerized tomography (CT) scan. The patient was asymptomatic at presentation and neoplastic markers were not elevated. Sequential transarterial chemoembolization (TACE) and portal vein embolization (PVE) allowed for left lateral section plus segment 1 hypertrophy and subsequent resection. Histology later revealed the cyst to be a CHFC and showed its malignant transformation. At 6 month follow-up, the patient has lung and abdominal recurrence. DISCUSSION: With now the fifth case of malignant transformation of CHFC being reported, approximately 5% of all reported CHFC have undergone malignant transformation. This frequency, taken together with the aggressive disease course and poor prognosis, suggests that CHFC must not be presumed benign and should be regarded with clinical suspicion. CONCLUSION: Accurate diagnosis of CHFC is mandatory given its potential malignant transformation. Even in asymptomatic CHFC, surgical excision is recommended. In addition, in cases of otherwise unresectable lesions, sequential TACE and PVE may provide optimal hypertrophy of future liver remnant.

Gastrointestinal quality of life in patients after anti reflux surgery.

A subset of patients does not report improvement of symptoms or satisfaction after antireflux surgery. The aim of this study is to assess the effect of pre-existing depression as a factor in patient satisfaction and gastrointestinal quality of life index (GIQLI) outcomes after antireflux surgery. Patients undergoing antireflux surgery who had filled a preoperative quality of life score and had more than 1 year follow-up were included in this study. Based on available history and self-reported medication use, patients were divided in two groups: with depression (group A) and without depression (group B). Fifty-four patients with completed preoperative GIQLI questionnaire were contacted for this study; 32 (59%) patients completed the postoperative questionnaire. Seven patients (22%) had psychological disorder (group A) in the form of depression The GIQLI in groups A and B increased significantly from 64.4 +/- 17.3 and 89.6 +/- 18.6 to 88.6 +/- 23.7 (P < 0.001) and 102.2 +/- 18.6 (P = 0.02), respectively, after the surgery. There was significant improvement in the quality of life in patients after antireflux surgery based on the GIQLI assessment. This improvement was also reported in patients with history of depression.

A randomized trial of the peri-operative use of COX-2 inhibitors in Lichtenstein herniorrhaphy.

INTRODUCTION: We present a randomized controlled trial to evaluate the value of the cyclo-oxygenase-2 (COX-2) inhibitor, rofecoxib, as an adjuvant for pain management for patients undergoing a conventional Lichtenstein inguinal herniorrhaphy. The drug was removed from the market coincidentally with the conclusion of the trial due to thrombotic complications. We believe that the data remains important, however, because of the imminent release of similar compounds with a better safety profile. No industry support was sought or accepted for this trial, with the exception of the study drug and an identical placebo preparation supplied by Merck in a completely unrestricted agreement. METHODS AND MATERIALS: Seventy-nine patients were recruited for the single-center randomized controlled double blinded trial, with 27 receiving placebo, 26 who received rofecoxib only in the post-operative period, and 26 who received rofecoxib both in the pre- and post-operative period. The patients were followed for 6 weeks with serial administration of the short form 36 health survey questionnaire (SF-36), visual analog scale (VAS) questionnaire, and activity restriction questionnaire. Statistical analysis was performed using multivariate generalized estimating equations in a blinded fashion. RESULTS: The mean pain over time decreased over the 6 weeks and was significantly lower in the group that received rofecoxib in the post-operative period than the other two groups (P = 0.02). The number of rescue narcotic medications taken by patients on day 1 were 3.0 (2.4) [mean (SD)] in the placebo group, 2.2 (1.7) (P < 0.001) in the post-operative only group, and 2.9 (2.3) (P = 0.37) in the peri-operative group. There was no statistical significance between the physical health composite scores or the mental health composite scores at 6 weeks. CONCLUSION: The use of post-operative rofecoxib decreases the amount of pain post-operatively after inguinal herniorrhaphy and decreases the number of rescue narcotic medications used, but it does not change the quality of life. This effect is lacking in the peri-operative group. There is no evidence to recommend the routine use of rofecoxib or similar COX-2 inhibitors after inguinal hernia surgery.

Laparoscopic re-operation for failed Heller myotomy.

Laparoscopic Heller myotomy for achalasia has a 10-20% failure rate and may require re-operation to control persistent or recurrent symptoms. We report follow-up of 15 patients who underwent laparoscopic re-operation for failed Heller myotomy. Between 1993 and 2004, 15 patients underwent laparoscopic re-operation for failed Heller myotomy at our center. The mean duration between procedures was 23 months. Follow-up was completed at a mean duration of 30 months in 14 patients (93%) via a telephone questionnaire. Our overall failure rate for primary surgery (n = 106) was 5.6%. The mechanisms of failure were incomplete myotomy (33%), myotomy fibrosis (27%), fundoplication disruption (13%), too tight fundoplication (7%) and a combination of myotomy fibrosis and incomplete myotomy (20%). Significant symptom improvement was observed with postoperative symptom resolution seen in 71% of patients with dysphagia, 89% for regurgitation, 58% for heartburn and 40% for chest pain. Fifty percent reported excellent results and 79% would recommend the procedure to a friend. Subsequent dilations were performed in four patients (29%). Two patients required conversion to open surgery (13%). Three patients (20%) failed the re-operation and required further revisional surgery. Complications included intraoperative perforation in three (none of which resulted in postoperative morbidity) and a pneumothorax in one patient. Prior endoscopic therapies (pneumatic dilation or Botulinum toxin) were not associated with poor results. Laparoscopic re-operation for failed Heller myotomy is feasible and results are encouraging.

Clinical and genetic risk factors for the development of multi-drug resistant tuberculosis in non-HIV infected patients at a tertiary care center in India: a case-control study.

Genetic susceptibility of the host to multi-drug resistant tuberculosis (MDR-TB) is not fully understood. We undertook a case-control study at a tertiary care center at New Delhi, India to identify the clinical and genetic predictors of MDR-TB as compared to the drug sensitive TB cases. Patients with multi-drug resistant tuberculosis were identified on the basis of drug sensitivity testing by the proportion method. Treatment was initiated according to standard norms and all patients were followed up during the period. Genomic DNA extracted from the peripheral blood mononuclear cell pellet was used for amplification of HLA class II region (second exon) with a set of forward (5') and reverse (3') primers. A sequence specific 5' biotinylated probes were used to determine 12 DRB1, 8 DQA1 and 13 DQB1 alleles by the PCR-SSOP method. Past history of disease, higher severity of illness, inadequacy of drug treatment and presence of HLA-DRB1*14, DQB1*0503 and DQB1*0502 alleles were found to be significant risk factors for MDR-TB. Multivariate analysis identified poor past compliance to treatment (odds ratio, OR=6.6; 95% confidence interval, CI [2.0-21.5]), higher number of cavities (OR=6; 95% CI [2.1-17.3]) in chest radiographs and the presence of the HLA-DRB1*14 allele (OR=8.2; 95% CI [2.1-31.3]) as independent predictors of MDR-TB. Our results suggest that a combination of clinical and immunogenetic parameters could provide better information on drug resistance in tuberculosis with implications in therapy.