Adjuvant and neoadjuvant chemotherapy for MSI early gastric cancer: a systematic review and meta-analysis.

Background: Perioperative chemotherapy (CT) is an established therapeutic approach for patients diagnosed with stage IB-III gastric cancer (GC). Objectives: This study aimed to investigate the efficacy of this approach in individuals with GC exhibiting high microsatellite instability (MSI-H). Design: A systematic review was conducted, including studies that provided data on (neo)adjuvant CT outcomes in patients with MSI-H GC. Methods: Systematic searches were conducted in PubMed, Cochrane Central of Controlled Trials, and Embase databases. Data were aggregated using hazard ratios (HRs) to compare overall survival between CT and surgery. Results: Data analysis from 23 studies, including 22,011 patients, revealed that the prevalence of MSI-H is 9.8%. Administration of adjuvant or perioperative CT did not significantly reduce the risk of death or relapse in patients with MSI-H GC (HR = 0.8, 95% CI 0.54-1.16; p = 0.24 and HR = 0.84, 95% CI 0.59-1.18; p = 0.31, respectively). Conclusion: Chemotherapy did not benefit patients diagnosed with MSI-H nonmetastatic GC but rather will be integrated with immune checkpoint inhibitors in the near future.

Hepatocellular carcinoma in patients with nonalcoholic fatty liver disease: A systematic review and meta-analysis: HCC and Steatosis or Steatohepatitis.

BACKGROUND AND AIMS: Hepatic steatosis of nonalcoholic etiology (nonalcoholic fatty liver disease; NAFLD) is an emergent condition that may lead to hepatic cirrhosis and finally to liver cancer. We evaluate the risk of developing hepatocellular carcinoma (HCC) and quantify the prognosis in terms of recurrence (DFS) as well as HCC-specific and overall survival (CSS and OS) of patients with and without NAFLD. METHODS: We searched published articles that evaluated the risk and outcomes of HCC in patients with steatosis/steatohepatitis from inception to July 2021 were identified by searching the PubMed, EMBASE, and Cochrane Library databases. Prospective cohort, case-control, or retrospective studies were selected that were published in English and provided incidence and survival rates of HCC patients with NAFLD. A random-effects model was created to estimate the pooled effect size. The primary outcome of interest was HCC incidence. The secondary endpoints were DFS, CSS, and OS. RESULTS: In total, 948 217 patients with NAFLD were analyzed, from n = 103 observational studies. NAFLD significantly increased the risk of HCC (HR = 1.88 [95% CI, 1.46-2.42]; P < .01] but not risk of recurrence (HR = 0.99 [95% CI, 0.85-1.15]; P = .9) or overall mortality (HR = 1.04 [95% CI, 0.88-1.24]; P = 0.64). Conversely, NAFLD increased HCC-related mortality risk (HR = 2.16 [95% CI, 0.85-5.5]; P = .1). Risk of HCC was increased in Western countries but not in Asian countries. CONCLUSIONS: Patients with NAFLD have an increased risk of HCC as compared to patients without NAFLD. NAFLD also increases liver cancer (HCC) mortality. These results justify applying general measures to patients with proven NAFLD and monitoring patients with NASH and fibrosis.

Time interval between neoadjuvant radio-chemotherapy and surgery in rectal cancer: is the long interval correct for all patients?

BACKGROUND: Optimal time between neoadjuvant radio-chemotherapy period and surgery remains controversial in patients with rectal cancer: an increasing number of studies show results in favor of a long interval. METHODS: We conducted a retrospective analysis of the cases of low-middle rectal adenocarcinoma undergoing neoadjuvant RT-CT and surgery: the primary endpoint was the complete pathological response rate and the secondary endpoint the rate of complications. We analyzed cases from 1/01/2003 to 31/12/2018 divided in two periods: from 2003 to 2010 (23 pts) and from 2011 to 2018 (23 pts). The two periods were characterized by two different surgical teams which use different time intervals (≤ vs. >8 weeks). RESULTS: The pCR rate is 21.7% in both groups; as regards the complications, the difference between the two groups is in grade IIIb: 8.7% in the first group and 17.4% in the second group (P=0.66). CONCLUSIONS: Although our study is based on a small number of patients, it shows the same rate of pCR with respect to two different time intervals; this suggests the need for studies based on the division of patients into subgroups and the evaluation of different time intervals in order to reach the best oncological outcomes.

Human papillomavirus (HPV) types 16 and 18 infection and esophageal squamous cell carcinoma: a systematic review and meta-analysis.

OBJECTIVE: The human papillomavirus (HPV) is implicated in the pathogenesis of several cancers among humans. The role of HPV as one of the etiological agents in esophageal carcinogenesis is partially unknown. We assessed whether the available evidence supports the association of HPV with risk and prognosis in patients with esophageal squamous cell carcinomas (ESCCs). DESIGN: For this systematic review and meta-analysis, PubMed, Embase, Cochrane Library, and SCOPUS were searched up to February 2021. The included studies were prospective or retrospective studies that evaluated the incidence, risk, and prognosis of HPV-16/18-related ESCCs in adult subjects. The primary outcome was the incidence rate of ESCC in HPV-16/18 carriers. Secondary outcomes included the risk of ESCCs compared with healthy HPV-16/18 carriers (expressed as odds ratios [ORs] with 95% confidence intervals [CIs]) and the survival of HPV + versus HPV- ESCCs. RESULTS: The search identified 1649 unique citations, of which 145 met the inclusion criteria and were included in the pooled analysis (16,484 patients). The pooled HPV prevalence in ESCCs was 18.2% (95% CI 15.2-21.6%; P < 0.001). A significantly increased ESCC risk was associated with HPV infection (OR = 3.81; 95% CI 2.84-5.11; P < 0.001). Main limitation were methods of HPV detection (DNA only), race of populations included (mainly Asiatic countries) and lack of adjustment for other prognostic factors. CONCLUSIONS: The findings suggest that HPV-16/18 is detectable in about 1 on 5 cases of ESCC with different prevalences across the world. It is moderately but significantly associated with a diagnosis of ESCC. Further epidemiological studies are needed to confirm and increase the current knowledge of the subject.

Association of Obesity With Survival Outcomes in Patients With Cancer: A Systematic Review and Meta-analysis.

Importance: Obesity, defined as a body mass index (BMI) greater than 30, is associated with a significant increase in the risk of many cancers and in overall mortality. However, various studies have suggested that patients with cancer and no obesity (ie, BMI 20-25) have worse outcomes than patients with obesity. Objective: To assess the association between obesity and outcomes after a diagnosis of cancer. Data Sources: PubMed, the Cochrane Library, and EMBASE were searched from inception to January 2020. Study Selection: Studies reporting prognosis of patients with obesity using standard BMI categories and cancer were included. Studies that used nonstandard BMI categories, that were limited to children, or that were limited to patients with hematological malignant neoplasms were excluded. Screening was performed independently by multiple reviewers. Among 1892 retrieved studies, 203 (17%) met inclusion criteria for initial evaluation. Data Extraction and Synthesis: The Meta-analysis of Observational Studies in Epidemiology (MOOSE) and Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guidelines were reporting guideline was followed. Data were extracted by multiple independent reviewers. Risk of death, cancer-specific mortality, and recurrence were pooled to provide an adjusted hazard ratio (HR) with a 95% CI . A random-effects model was used for the retrospective nature of studies. Main Outcomes and Measures: The primary outcome of the study was overall survival (OS) in patients with cancer, with and without obesity. Secondary end points were cancer-specific survival (CSS) and progression-free survival (PFS) or disease-free survival (DFS). The risk of events was reported as HRs with 95% CIs, with an HR greater than 1 associated with a worse outcome among patients with obesity vs those without. Results: A total of 203 studies with 6 320 365 participants evaluated the association of OS, CSS, and/or PFS or DFS with obesity in patients with cancer. Overall, obesity was associated with a reduced OS (HR, 1.14; 95% CI, 1.09-1.19; P < .001) and CSS (HR, 1.17; 95% CI, 1.12-1.23; P < .001). Patients were also at increased risk of recurrence (HR, 1.13; 95% CI, 1.07-1.19; P < .001). Conversely, patients with obesity and lung cancer, renal cell carcinoma, or melanoma had better survival outcomes compared with patients without obesity and the same cancer (lung: HR, 0.86; 95% CI, 0.76-0.98; P = .02; renal cell: HR, 0.74; 95% CI, 0.53-0.89; P = .02; melanoma: HR, 0.74; 95% CI, 0.57-0.96; P < .001). Conclusions and Relevance: In this study, obesity was associated with greater mortality overall in patients with cancer. However, patients with obesity and lung cancer, renal cell carcinoma, and melanoma had a lower risk of death than patients with the same cancers without obesity. Weight-reducing strategies may represent effective measures for reducing mortality in these patients.

A systematic review of salvage therapies in refractory metastatic colorectal cancer.

PURPOSE: Established that the only approved agents in previously treated metastatic colorectal cancer (CRC) are trifluoridine/tipiracil and regorafenib, we conducted a systematic review of all the published phase 2-3 trials, with the scope to evaluate the benefit of any later-line regimens in refractory metastatic CRC. METHODS: Phase 2-3 studies that enrolled patients with stage IV disease receiving salvage therapies for refractory CRC were identified using electronic databases (Pubmed, EMBASE, and Cochrane Library). Clinical outcomes were pooled using a point estimates for the weighted values of median overall survival (OS), progression-free survival (PFS), response rate (ORR), stable disease rate (SD), and 6-month and 1-year OS. RESULTS: Overall, 7556 patients were included from 67 studies (n = 70 arms). Overall, the pooled ORR and SD were 15.4% (95% CI 13-18%) and 36.9% (95% CI 33.5-40.6%). Median PFS, 6-month and 1-year OS, and median OS were 3.2 (95% CI 2.9-3.3) months, 65.4% (95% CI 61.9-68.8%), 36% (95% CI 32.3-39.9%) and 8.8 (95% CI 8.3-9.2) months. Overall survival was different in the monochemotherapy, polychemotherapy, chemotherapy + targeted therapy, and targeted therapy alone arms (7.6, 9.5, 10.3, and 7.9 months, respectively, P for difference = 0.01). Median PFS were respectively 2.3, 3.9, 3.8, and 2.6, respectively (P for difference < 0.01). CONCLUSIONS: Overall, combination therapy (polychemotherapy with or without targeted agents) is associated with a higher control of disease and better outcome than approved agents. Treatment, if possible, should be personalized according to the patients' conditions, physician preference and molecular profile of disease.

Risk of second primary tumors in GIST survivors: A systematic review and meta-analysis.

INTRODUCTION: Gastrointestinal stromal tumors (GISTs) are rare mesenchymal tumors arising in the gastrointestinal tract. Second primary tumors (SPTs) have been reported frequently, either synchronously or during follow-up, in patients diagnosed with GISTs. METHODS: We carried out an electronic search of PubMed, SCOPUS, Web of Science, EMBASE, and the Cochrane Library seeking articles investigating the incidence of SPTs in patients with concomitant GIST. All studies were evaluated for heterogeneity before meta-analysis and for publication bias. Pooled incidence rate was estimated using fixed- and random-effects models. Subsite of SPTs was also investigated. RESULTS: A total of 32 studies met the inclusion criteria, for a total of 19,627 patients with a diagnosis of GIST. The pooled prevalence of SPTs was 20%, with 14% and 3% being synchronous and metachronous tumors, respectively. We found a risk for several specific cancer sites, in particular gastrointestinal (5%) and genitourinary tract cancers (3%). The most frequently associated malignancies were: colorectal (17%), prostate (14%), gastric (9%), esophageal (5.5%), lung (5.4%), hepato-biliopancreatic (4.7%), breast (4.6%), lymphoma (4.4%), kidney (4.35%), and sarcomas (3.3%). Regression analyses revealed a significant positive association for all SPTs with follow-up and Miettinen risk. CONCLUSIONS: Our results indicate that 20% of patients with GIST experienced a SPT, primarily synchronously with a diagnosis of GIST. In particular, we observed an excess of incident gastrointestinal tumors. These findings have important implications for both pathologists, who should perform extensive molecular analysis of surgical non-GIST specimens in resected patients, and for oncologists, who should continue to follow up GIST patients.

Three-Dimensional (3D) Versus Two-Dimensional (2D) Laparoscopic Bariatric Surgery: a Single-Surgeon Prospective Randomized Comparative Study.

BACKGROUND: To address the issue whether three-dimensional (3D) offers real operative time advantages to the laparoscopic surgical procedure, we have designed a single-surgeon prospective randomized comparison of 3D versus two-dimensional (2D) imaging during two different bariatric procedures. METHODS: Forty morbidly obese patients were randomized on the day of surgery by a random computer-generated allocation list to receive either a 3D high-definition (HD) display or 2D HD imaging system laparoscopic bariatric procedure by a single experienced surgeon. Forty operations were performed with either a 3D HD display or 2D HD imaging system. After the insertion of the access ports, both surgical procedures were divided in component tasks, and the execution times were compared. RESULTS: The execution times for the entire procedure and the single tasks were not significantly different between the 2D and 3D groups during sleeve gastrectomy. The execution times for the entire procedure and the single tasks, except for the first one, were significantly different between the 2D and 3D groups during mini-gastric bypass (p < 0.05). The surgeon experienced better depth perception with the 3D system and subjectively reported less strain using 3D vision system rather than the 2D system particularly during longer procedure. CONCLUSIONS: 3D imaging seems to decrease the performance time of more difficult bariatric procedures, which involve surgical tasks as suturing and intestinal measurement. Further comparative studies are necessary to address the issue if novice surgeons could benefit from reduced learning curve requested with 3D vision and to verify with greater numbers if 3D imaging can reduce complications.

Video-assisted versus conventional total thyroidectomy and central compartment neck dissection for papillary thyroid carcinoma.

BACKGROUND: Although video-assisted (VA) thyroidectomy emerged as effective treatment for selected patients with papillary thyroid carcinoma (PTC), some concerns remain about obtaining adequate central neck node clearance. We compared patients who underwent VA and conventional total thyroidectomy (TT) and central compartment dissection (CCD) for PTC. METHODS: A total of 52 consecutive patients successfully underwent VA-TT and VA-CCD for PTC (VA group) were compared to 52 controls who underwent conventional TT and CCD (C group) for PTC. RESULTS: The two groups were matched for age (p = 0.75), sex (p = 0.07), and tumor size (p = 1.0). Operating time (p = 0.23), overall postoperative complications (p = 0.41), pT (p = 0.44), and pN (p = 0.84) were similar in the two groups. The mean number of removed nodes was similar (10.6 ± 4.6 in VA group vs. 12.2 ± 5.6 in C group) (p = 0.11).Mean postoperative serum thyroglobulin (sTg) off levothyroxine (LT4) suppressive treatment was 3.2 ± 5.0 ng/ ml in the VA group and 2.6 ± 7.4 ng/ml in the C-group (P = 0.67). Mean postoperative radioiodine uptake (RAIU) was similar in the two groups (1.5 ± 1.3 vs. 1.7 ± 1.3%) (p = 0.49). When pN1a patients alone were considered, no difference was found between the VA group (21 patients) and the controls (24 patients) concerning the mean number of removed nodes (10.3 ± 4.1 vs. 12.4 ± 5.6) (p = 0.16), the mean sTg off LT4 (4.4 ± 6.0 vs. 1.9 ± 2.7 ng/ml) (p = 0.07) and the mean RAIU (1.9 ± 1.5 vs. 1.7% ± 1.3%) (p = 0.63). CONCLUSIONS: The results of VA-TT and CCD in selected cases of PTC appear to be comparable to those of conventional surgery. A longer follow-up and larger series are necessary to draw definitive conclusions concerning longterm outcomes.