Cytoreductive surgery with hyperthermic intraperitoneal chemotherapy for peritoneal metastasis of non-primary origin.

PURPOSE: The objective of this study was to analyze the role of cytoreductive surgery with hyperthermic intraperitoneal chemotherapy that has developed in the treatment of patients with peritoneal metastasis of non-primary origin. METHODS: Patients who underwent treatment for secondary gastrointestinal and ovarian malignancies over a 20-year period were reviewed. Survival curves were estimated by the Kaplan-Meier product limit method and the log-rank test was used to assess differences between subgroups. RESULTS: The study included 293 patients. The most common histology was ovarian cancer (56.3%). Median PCI was 16 and CC0-1 resection was obtained in 88.1% of cases. Grade III and IV complications occurred in 12 patients (4.1%) and 47 patients (16%), respectively. The 30- and 60-day mortality rate was 1.3% (4 patients) and 2.4% (7 patients). Five-year OS was 21.7%, 73.6%, 42.1%, and 0 for colorectal, appendiceal, ovarian, and gastric cancer (p = < 0.0001), respectively, whereas 5-year DFS was 12.4%, 48.4%, 24.3%, and 0 (p = < 0.0001), respectively. Survival outcomes were significantly higher for CC0 in each subgroup of patients. CONCLUSION: Despite being a complex procedure, cytoreductive surgery with hyperthermic intraperitoneal chemotherapy should be considered a safe treatment with acceptable postoperative morbidity and mortality rates, if performed in high-volume centers. Good survival outcomes have been increasingly obtained in selected patients with peritoneal metastasis of non-primary origin.

Drain after elective laparoscopic cholecystectomy. A randomized multicentre controlled trial.

BACKGROUND: Routine drainage after laparoscopic cholecystectomy is still debatable. The present study was designed to assess the role of drains in laparoscopic cholecystectomy performed for nonacutely inflamed gallbladder. METHODS: After laparoscopic gallbladder removal, 53 patients were randomized to have a suction drain positioned in the subhepatic space and 53 patients to have a sham drain. The primary outcome measure was the presence of subhepatic fluid collection at abdominal ultrasonography, performed 24 h after surgery. Secondary outcome measures were postoperative abdominal and shoulder tip pain, use of analgesics, nausea, vomiting, and morbidity. RESULTS: Subhepatic fluid collection was not found in 45 patients (84.9 %) in group A and in 46 patients (86.8 %) in group B (difference 1.9 (95 % confidence interval -11.37 to 15.17; P = 0.998). No significant difference in visual analogue scale scores with respect to abdominal and shoulder pain, use of parenteral ketorolac, nausea, and vomiting were found in either group. Two (1.9 %) significant hemorrhagic events occurred postoperatively. Wound infection was observed in three patients (5.7 %) in group A and two patients (3.8 %) in group B (difference 1.9 (95 % CI -6.19 to 9.99; P = 0.997). CONCLUSIONS: The present study was unable to prove that the drain was useful in elective, uncomplicated LC.

Feasibility of diaphragmatic interventions in cytoreductive surgery with hyperthermic intraperitoneal chemotherapy for peritoneal carcinomatosis: A 20-year experience.

INTRODUCTION: Complete cytoreductive surgery with hyperthermic intraperitoneal chemotherapy is an effective treatment for improving prognosis of selected patients with peritoneal carcinomatosis. The addiction of diaphragmatic procedures may increase the incidence of postoperative respiratory complications. Our goal was to evaluate the early postoperative results following diaphragmatic surgery. METHODS: Prospectively collected data of patients undergoing diaphragmatic surgery between January 2000 and January 2020 were retrospectively analyzed. Chest drains were routinely placed in all cases. Demographics, clinical and perioperative features were evaluated. RESULTS: The study included 222 patients. Peritoneal stripping and full-thickness resections were performed in 165 and 57 cases, respectively. Women and ovarian tumours represented the vast majority of cases. Overall postoperative mortality and morbidity rates were 1.3% (3 patients) and 43.2% (96 patients), respectively. Specific diaphragmatic surgery-related complications was 9.4% (21 patients). No pleural effusion and pneumothotrax occurred. The incidence of pneumonia was 1.8% (4 patients), each due to systemic bacterial origin, 2 (0.9%) of which required Intensive Care Unit-readmission. Postoperative bleeding was observed in 15 (6.7%) cases, 12 (5.4%) of which required reoperation. A comparison with 105 patients who operated during the same period without diaphragmatic surgery was performed and by multivariate analysis, Peritoneal Cancer Index, histology and overall morbidity resulted significantly associated with diaphragmatic surgery. CONCLUSION: Diaphragmatic surgery during cytoreductive surgery with hyperthermic intraperitoneal chemotherapy is often required in order to obtain complete resection. It may be associated with higher postoperative morbidity, especially bleeding, but routine placement of chest drains may reduce the incidence of adverse respiratory events.

Cytoreductive Surgery with Hyperthermic Intraperitoneal Chemotherapy for Peritoneal Carcinomatosis from Epithelial Ovarian Cancer: A 20-Year Single-Center Experience.

Despite improvement in treatments, the peritoneum remains the primary site of relapse in most ovarian cancer cases. Patients who underwent cytoreductive surgery with hyperthermic intraperitoneal chemotherapy for peritoneal carcinomatosis from epithelial ovarian cancer were reviewed. Kaplan-Meier curves and multivariate Cox analyses were used to identify survival rates and prognostic factors. This study included 158 patients. The procedure was mostly performed for recurrent disease (46.8%) and high-grade serous carcinoma (58.2%). The median peritoneal cancer index was 14, and complete cytoreduction was obtained in 87.9% of cases. Grade IV morbidity occurred in 15.2% of patients, mostly requiring surgical reoperation, and one patient (0.6%) died within 90 days. The median follow-up was 63.5 months. The Kaplan-Meier 5-year overall survival (OS) and disease-free survival (DFS) rates were 42.1% and 24.3%, respectively. Multiple regression logistic analyses demonstrated that the completeness of cytoreduction (CC) score (p ≤ 0.0001), pancreatic resection (p ≤ 0.0001) and number of resections (p = 0.001) were significant factors influencing OS; whereas the CC score (p ≤ 0.0001) and diaphragmatic procedures (p = 0.01) were significant for DFS. The addition of hyperthermic intraperitoneal chemotherapy to standard multimodality therapy may improve outcomes in both primary and recurrent epithelial ovarian cancer without impairing early postoperative results, but the exact timing has not yet been established. Prospective randomized studies will clarify the role and indications of this approach.

Transanal drainage tube: alternative option to defunctioning stoma in rectal cancer surgery?

BACKGROUND: Anastomotic leakage (AL) remains the most dreaded complication after rectal cancer surgery. The aim of this study was to evaluate the role of transanal drainage tube in reducing the incidence, severity and hospital costs respect to defunctioning stoma (DS). METHODS: Considering 429 patients consecutively operated for rectal adenocarcinoma, the tube was placed in 275 (Group A) and not placed in 154 (Group B) patients. A DS was created in a subgroup of 54 patients among the latter. RESULTS: The incidence of AL was significantly higher in Group B (P=0.007). In patients with DS, the incidence was higher than Group A (P=NS). Grade C complications were significantly higher in Group B (P=0.006) and Grade B complications were significantly higher in patients with DS (P=0.03). Estimated economic benefit was 4,000 Euros for each patient. CONCLUSIONS: Transanal drainage tube may be a safe and effective alternative to DS in many cases. The incidence of leakage and Grade C complications are reduced albeit not significantly but Grade B complications are significantly lower. Although the AL incidence was similar in our experience, the tube allows to avoid a stoma-related consequence and the need for reversal procedure with economic benefit.

A Distinctive microRNA (miRNA) Signature in the Blood of Colorectal Cancer (CRC) Patients at Surgery.

BACKGROUND: Liquid biopsy (LB) provides an examination of the peripheral blood of cancer patients for circulating tumor cells, cell-free nucleic acids and microRNAs (miRNAs) and is an established tool of precision medicine. Unlike most previous LB studies that focused on advanced metastatic colorectal cancer (CRC), we assessed miRNA dysregulation in blood samples obtained on the day of surgery from patients with primary CRC lesions but no clinical evidence of extra-colonic diffusion. In this study, plasma preparation included miRNAs associated to exosomes, but excluded large macrovesicles from the preparation. METHODS: The miRNA profile in plasma isolated from a cohort of 35 CRC patients at the day of surgery was analyzed by Next Generation Sequencing (NGS) and further confirmed by droplet digital RT-PCR (dd-RT-PCR). RESULTS: A miR-141-3p/miR-221-3p/miR-222-3p upregulation signature previously described in advanced CRC did not discriminate the analyzed early-CRC cohort from six tumor-free donors (Tf-D). In contrast, NGS-based miRNome analysis of a training cohort of five CRC and three tumor-free donors identified a novel, distinct nine miRNA signature comprising five up-regulated and four down-regulated miRNAs, six of which could be confirmed in the full CRC and tumor-free donor validation dataset by dd-RT-PCR. Additionally, a KRAS (Kirsten Rat Sarcoma Viral Oncogene Homolog) mutant status was correlated with the plasma content of three identified miRNAs. CONCLUSIONS: When the data obtained were comparatively evaluated, at least one of the miRNAs belonging to the signature list was found to be dysregulated in 34/35 (97.1%) of our early-CRC plasma samples. The miRNA list provides diagnostic markers as well as possible molecular targets for protocols focusing on "microRNA therapeutics".

Cross-sectional analysis of circulating tumor DNA in primary colorectal cancer at surgery and during post-surgery follow-up by liquid biopsy.

BACKGROUND: Liquid biopsy (LB) in early-stage, non-metastatic colorectal cancer (CRC) must be sensitive enough to detect extremely low circulating tumor DNA (ctDNA) levels. This challenge has been seldom and non-systematically investigated. METHODS: Next generation sequencing (NGS) and digital PCR (dPCR) were combined to test tumor DNAs (tDNAs) and paired ctDNAs collected at surgery from 39 patients, 12 of whom were also monitored during the immediate post-surgery follow up. Patients treated for metastatic disease (n = 14) were included as controls. RESULTS: NGS and dPCR concordantly (100% agreement) called at least one single nucleotide variant (SNV) in 34 tDNAs, estimated differences in allelic frequencies being negligible (±1.4%). However, despite dPCR testing, SNVs were only detectable in 15/34 (44.1%) ctDNAs from patients at surgery, as opposed to 14/14 (100%) metastatic patients. This was likely due to striking differences (average 10 times, up to 500) in ctDNA levels between groups. NGS revealed blood-only SNVs, suggesting spatial heterogeneity since pre-surgery disease stages, and raising the combined NGS/dPCR sensitivity to 58.8%. ctDNA levels at surgery correlated with neither tumor size, stage, grade, or nodal status, nor with variant abundance in paired tDNA. LB sensitivity reached 63.6% when ctDNA was combined with CEA. Finally, persistence and absence of ctDNA on the first conventional (month 3) post-surgery follow-up were associated with fast relapse and a disease-free status in 3 and 7 patients, respectively. CONCLUSIONS: A simple clinical NGS/dPCR/CEA combination effectively addresses the LB challenge in a fraction of non-metastatic CRC patients.

[Incidental thyroid microcarcinoma in benign thyroid disease. Incidence in a total of 100 consecutive thyroidectomies]. / I microcarcinoma incidentale della tiroide nelle tireopade benigne. Incidenza su 100 tiroidectomie totali consecutive.

Over the past few years, incidental thyroid microcarcinoma has become a frequent disease and its incidence in some reports is considerable. Discovering new cases depends on the extended indications for total thyroidectomy for benign disease, on progress in the field of diagnostic instruments (ultrasound, scintigram, fine needle biopsy for cytology, CT scan, MRI), and on the pathology examination of very thin slices of specimens. In spite of the high incidence reported in some autopsy series, suggesting that this tumour may have a good prognosis, some Authors report an overall incidence of up to 11% of local recurrence, metastasis or mortality. For all these reasons the surgical treatment of incidental thyroid microcarcinoma is still controversial. The aim of this study was to estimate the incidence and examine the clinical-pathological findings of incidental thyroid microcarcinoma in a series of 100 consecutive thyroidectomies and to evaluate whether complete removal of the gland should be adopted in all cases. In the present series the incidence of incidental thyroid microcarcinoma was 21.6% (19/88). Total thyroidectomy was considered the treatment of choice for diffuse benign disease and appeared to be necessary for both the diagnosis and treatment of incidental thyroid microcarcinoma.

Low-dose hepatitis B immunoglobulin given "on demand" in combination with lamivudine: a highly cost-effective approach to prevent recurrent hepatitis B virus infection in the long-term follow-up after liver transplantation.

BACKGROUND: Cost of long-term prophylaxis with high-dose human hepatitis B immune globulin (HBIg) after liver transplantation is extremely high. The aim of the present study was to assess consumption rates of high (5,000 IU) and low (2,000 IU) doses of HBIg given intravenously "on demand", and determine their cost-effectiveness compared with conventional fixed monthly schedules. METHODS: The study included 11 male patients (mean age 53 years) who received transplants for hepatitis B virus (HBV)-related cirrhosis 29 to 96 months earlier, all receiving lamivudine (100 mg/day) prophylaxis. Each patient received three consecutive intravenous infusions of 5,000 IU HBIg, followed by three 2,000 IU infusions. HBIg consumption was assessed by serial measurement of serum hepatitis B surface antibody (HBsAb) titer at 2-week intervals. HBIg was readministered only when HBsAb titers dropped below 70 IU/L (i.e., "on demand"). RESULTS: Mean HBsAb peak titers after high and low HBIg doses were 1,641 +/- 385 and 848 +/- 216 IU/L, respectively (P <0.0001). Mean time to reach an HBsAb titer less than 70 IU/L was 79.5 +/- 38.2 days versus 61.6 +/- 32.1 days, respectively (P =NS). Interindividual variation coefficients were 23 +/- 18% and 32 +/- 26% (5,000 IU and 2,000 IU, respectively). Using the on demand approach, maintenance of a protective anti-HBs titer required an average number of 4.0 (5,000 IU) and 5.6 (2,000 IU) HBIg administrations per year, respectively (P =NS). CONCLUSIONS: Individual HBIg consumption profiles are highly variable. A low-dose (2,000 IU) on demand HBIg administration schedule is highly cost-effective and provides more than 50% savings compared with conventional high-dose monthly schedules.

Major iatrogenic tracheal injury during pneumonectomy: conservative treatment.

We hereby present the case of a 55-year-old woman with an iatrogenic tracheal laceration that occurred during double lumen intubation for left pneumonectomy. Conservative treatment was performed and the patient was discharged 12 days after surgery. No major sequelae after 3 months of follow-up were observed.

Failure of a reinforced triple course of hepatitis B vaccination in patients transplanted for HBV-related cirrhosis.

Long-term immunoprophylaxis with anti-HBs immunoglobulins (HBIg) is used to prevent hepatitis B (HBV) reinfection after liver transplantation for HBV-related cirrhosis. This approach is highly expensive. A recent report proposed posttransplant HBV vaccination with a reinforced schedule as an alternative strategy to allow HBIg discontinuation. We investigated the efficacy of a reinforced triple course of HBV vaccination in 17 patients transplanted for HBsAg-positive cirrhosis 2 to 7 years earlier. The first cycle consisted of 3 double intramuscular doses (40 microg) of recombinant vaccine at month 0, 1, and 2, respectively. This was followed, in nonresponders, by a second cycle of 6 intradermal 10 microg doses every 15 days. All nonresponders then received a third cycle identical to the first one. Vaccination started 4.5 months after HBIg discontinuation, and lamivudine (100 mg/day) was given throughout the study. All patients were seronegative for HBsAg and HBV-DNA (by PCR) and positive for anti-HBe, and 7 were positive for anti-HDV. After the first cycle one patient (#5, 53 years old, male) developed an anti-HBs titer of 154 IU/L, another (#12) reached a titer of 20 IU/L and the remainder had titers <10 IU/L. At month 7, patient #5 reached a titer of 687 IU/L. After the second cycle only one additional patient (#9) had a slight response (an anti-HBs titer of 37 IU/L). After the third cycle patient #9 rose to an anti-HBs titer of 280 IU/L, patient #12 dropped to 10 IU/L, and no other patient responded. In conclusion, a highly reinforced HBV vaccination program is effective only in a few patients who had liver transplants for HBV-related cirrhosis.