Strong impact of sarcopenia as a risk factor of survival in resected gastric cancer patients: first Italian report of a Bicentric study.

Gastric cancer (GC) accounts for 4% of all cancers in Europe. Sarcopenia is a complex syndrome characterized by a loss of muscle mass and function associated with age, often present in neoplastic patients. Recently, several studies have shown a significant association between sarcopenia and poor prognosis in various pathological conditions. The current observational retrospective study investigates the association between sarcopenia and overall survival (OS) and recurrence-free survival (RFS) in patients with GC undergoing up-front surgery with curative intent. Resected GC patients' clinical records and CT images were retrospectively assessed. The preoperative CT calculation of the skeletal muscle index (SMI) at L3 level allowed us to categorize patients as sarcopenic or not. Kaplan-Meyer and univariate and multivariate Cox regression analyses were performed to determine the difference in survival and presence of independent prognostic factors. Fifty-five patients, 28 male and 27 female, out of 298 studied for gastric cancer were enrolled in the current study from two cancer referral centers in Italy. The preoperative CT calculation of the SMI at L3 level allowed us to identify 39 patients with and 16 without sarcopenia. A statistically significant difference between the sarcopenic and non-sarcopenic groups was observed in both OS and RFS (p < 0.023; p < 0.006). Moreover, sarcopenia was strongly correlated to a higher risk of recurrence in univariate and multivariate analysis (p < 0.02). Sarcopenia can be considered a critical risk factor for survival in patients with resectable GC treated with up-front surgery. Identifying sarcopenic patients at the time of diagnosis would direct selection of patients who could benefit from early nutritional and/or physical treatments able to increase their muscle mass and possibly improve the prognosis. More extensive multicenter studies are needed to address this issue.

Chemotherapy toxicity and activity in patients with pancreatic ductal adenocarcinoma and germline BRCA1-2 pathogenic variants (gBRCA1-2pv): a multicenter survey.

BACKGROUND: Germline BRCA1-2 pathogenic variants (gBRCA1-2pv)-related pancreatic ductal adenocarcinoma (PDAC) showed increased sensitivity to DNA cross-linking agents. This study aimed at exploring safety profile, dose intensity, and activity of different chemotherapy regimens in this setting. PATIENTS AND METHODS: gBRCA1-2pv PDAC patients of any age and clinical tumor stage who completed a first course of chemotherapy were eligible. A descriptive analysis of chemotherapy toxicity, dose intensity, response, and survival outcomes was performed. RESULTS: A total of 85 gBRCA1-2pv PDAC patients treated in 21 Italian centers between December 2008 and March 2021were enrolled. Seventy-four patients were assessable for toxicity and dose intensity, 83 for outcome. Dose intensity was as follows: nab-paclitaxel 72%, gemcitabine 76% (AG); cisplatin 75%, nab-paclitaxel 73%, capecitabine 73%, and gemcitabine 65% (PAXG); fluorouracil 35%, irinotecan 58%, and oxaliplatin 64% (FOLFIRINOX). When compared with the literature, grade 3-4 neutropenia, thrombocytopenia, and diarrhea were increased with PAXG, and unmodified with AG and FOLFIRINOX. RECIST responses were numerically higher with the three- (81%) or four-drug (73%) platinum-containing regimens that outperformed AG (41%) and oxaliplatin-based doublets (56%). Carbohydrate antigen 19.9 (CA19.9) reduction >89% at nadir was reported in two-third of metastatic patients treated with triplets and quadruplets, as opposed to 33% and 45% of patients receiving oxaliplatin-based doublets or AG, respectively. All patients receiving AG experienced disease progression, with a median progression-free survival (mPFS) of 6.4 months, while patients treated with platinum-containing triplets or quadruplets had an mPFS >10.8 months. Albeit still immature, data on overall survival seemed to parallel those on PFS. CONCLUSIONS: Our data, as opposed to figures expected from the literature, highlighted that platinum-based regimens provoked an increased toxicity on proliferating cells, when dose intensity was maintained, or an as-expected toxicity, when dose intensity was reduced, while no change in toxicity and dose intensity was evident with AG. Furthermore, an apparently improved outcome of platinum-based triplets or quadruplets over other regimens was observed.

Brain metastases: an overview.

So far brain metastases represent a critical stage of a disease course and the frequency is increasing over the years. The treatment of brain metastases should be individualized for each patient: in case of single brain metastasis, surgery or radiosurgery should be considered as first options of treatment; in case of multiple lesions, whole-brain radiotherapy is the standard of care in association with systemic therapy or surgery/radiosurgery. Chemotherapy should be considered when surgery or radiation therapy are not possible. In the last decades, TKIs or monoclonal antibodies have shown increase in overall response rate and overall survival in Phase II-III trials. The aim of this paper is to make an overview of the current approaches in management of patients with brain metastases.

Cetirizine reduces the number of tryptase-positive mast cells in psoriatic patients: a double-blind controlled study.

Psoriatic plaque contains an increased number of mast cells that are thought to play an important role in the initiation and maintenance of the disease through the release of mediators such as histamine, proteoglycans, proteinases and cytokines. To verify the possible participation of these cells in the chronic inflammatory cutaneous response in psoriasis, we performed a double-blind controlled study to investigate the presence and activation of tryptase-positive mast cells in the lesional skin of 19 patients affected by active psoriasis vulgaris minima compared with five healthy, age-matched subjects. Psoriatic patients were randomized into two groups (A and B). The first group was treated with cetirizine (10 mg/three times a day for 15 days) and the second one was treated with placebo. Both groups underwent clinical staging [psoriasis area and severity index (PASI) score] and immunohistochemical evaluation [alkaline phosphatase antialkaline phosphatase (APAAP) procedure] before and after treatment. In group A, the PASI score ranged from 3.8 (SE +/- 1.00) to 1.8 (SE +/- 0.68) and in group B, from 5.0 (SE +/- 0.98) to 3.4 (SE +/- 0.47). The mean number of tryptase-positive mast cells for field, mainly distributed in the perivascular and periadnexal sites, ranged from 40.8 (SE +/- 7.15) to 21.6 (SE +/- 3.04) in group A and from 25.1 (SE +/- 3.78) to 26.3 (SE +/- 3.59) in group B (ANOVA test f = 6.95; gl = 1.16; p = 0.02). In our psoriatic patients, cetirizine significantly reduced the expression of tryptase-positive mast cells and produced a clinical improvement in erythema, suggesting a multilevel immunopharmacologic modulation of this antihistamine in psoriasis.

Correlation of Ki-67 expression in cutaneous primary melanoma with prognosis in a prospective study: different correlation according to thickness.

BACKGROUND: The proliferative activity of melanoma cells, evaluated as MIB-1 immunoreactivity against a Ki-67 epitope, has been considered an indicator of poor prognosis in thick primary melanomas. OBJECTIVE: The aim of the study was to assess the correlation between the growth fraction of primary melanomas, assessed by means of Ki-67 immunoreactivity, and metastatic relapse. METHODS: Ki-67 reactivity in primary melanomas was evaluated as at least 5% of positive neoplastic cells and was assessed on fresh specimens of 55 primary lesions at the time of excision. Such reactivity was correlated with metastatic relapse of patients in a prospective study, by means of multivariate Cox regression models (follow-up, 3-120 months). RESULTS: Ki-67 immunoreactivity was associated with increasing thickness (P =.003). Positive correlation was found between Ki-67 reactivity and metastatic dissemination in primary melanomas less than 1.5 mm thick (n = 23; mean thickness, 0.75 +/- 0.3 mm; P =.002). On the contrary, a negative correlation was found between Ki-67 reactivity and metastatic activity in primary melanomas thicker than 1.5 mm (n = 32; mean thickness, 4.0 +/- 1.6 mm; P =.019). CONCLUSION: Ki-67 proliferative activity appears to be a possible predictor of metastasis in primary melanomas, in particular, an indicator of poor prognosis in lesions less than 1.5 mm thick.

Oral carcinoma in a young man: a case of dyskeratosis congenita.

We report a 28-year-old male with a voluminous growth of the tongue, present for 6 months. The histological examination revealed a squamous cell carcinoma. The patient was also affected by oral leukoplakia, nail dystrophy, reticulated poikiloderma of the neck and hyperkeratosis of palms and soles. On the basis of clinical features and histological findings, as well as findings from the family, the diagnosis of dyskeratosis congenita (DKC) was made.

[Postoperative peritonitis. The criteria for a reintervention]. / Le peritoniti postoperatorie. I criteri di reintervento.

BACKGROUND: Postoperative peritonitis is a pathologic condition with a sometime nuclear clinical occurrence and therefore with an uncertain timing for reoperation. Aim of this paper is to identify the type and frequency of the digestive and systemic symptoms in relation to the anatomo-pathologic peroperative picture. METHODS: Between 1980 and 1996, 119 patients were reoperated for a postoperative peritonitis (PPO) in the Surgical Department of Modena University. PPO was due to a lesion situated above the mesocolon in 33 patients, from the small bowel in 18, postappendicectomy in 25 and from the colon in 40. The first operation (for benign disease in 66.4%, for malignancy in 33.6%) was performed in emergency in 47 cases (39.5%) and as elective surgery in 72 (60.5%). RESULTS: The global mortality was of 33.6% (40 patients). An attempt is made to identify, the earlier and the most important bioclinical parameters for a correct indication to surgery. Twenty symptoms have been identified that, with different frequency, are strictly related with the onset of a PPO (in average 5 symptoms were positive). A research of these parameters, each 4-6 hours, allow to identify a subclinical PPO. CONCLUSIONS: During the decisional timing, it is important to check these general and digestive symptoms, apparently not serious, in order to avoid the onset appearance of an abdominal tenderness or a multiorgan failure that make the prognosis more severe.

[The surgery of non-small-cell bronchogenic carcinoma in stage IIIA. An analysis of 150 treated cases]. / La chirurgia del carcinoma broncogeno non a piccole cellule in stadio IIIA. Analisi di 150 casi trattati.

BACKGROUND AND AIM: The authors report the findings of a retrospective study made of 150 cases of bronchogenic non-small-cell carcinoma at stage IIIA. METHODS: Of the 150 patients treated 130 were male and 20 female. The mean age of the population examined was 55, with a minimum of 28 and maximum of 76. The techniques of exeresis used were pneumonectomy in 70 cases (33.3%) (simple in 50 cases--33.3% and intrapericardial ligation of pulmonary vessels in 20--13.3%), lobectomy in 61 cases (40.6%), lobectomy with associated atypical resection in 9 cases (6%), atypical resection in 6 patients (4%) and bilobectomy in 4 (2.6%). RESULTS: The 5-year survival rate was 16.9%. It was also found that the 5-year survival rate was 20.7% higher for epidermoid carcinoma compared to other histiotypes. The technique used also influenced survival and subjects undergoing pneumonectomy presented a 5-year survival of 29.7% compared to 26.8% for lobectomies associated with atypical resection. CONCLUSION: Surgery of bronchogenic carcinoma at stage IIIA has not obtained promising results in terms of survival. However, no other alternative treatment permits an average 5-year survival rate of 15% to be achieved.

Immunohistochemical evidence of cytokine networks during progression of human melanocytic lesions.

Melanoma cells in culture express a variety of growth factors and cytokines and some of their autocrine and paracrine roles have been investigated. However, less information is available on the potential dynamic changes in expression of these molecules on cells during melanoma development and progression in situ. Using immunohistochemistry, we tested 40 nevi and primary and metastatic melanoma lesions for the expression of 10 growth factors and cytokines and the respective receptors representing 10 cell surface molecules. Nevi and thin (< 1 mm) primary melanomas showed little expression of ligands except weak reactivity of tumor necrosis factor-alpha (TNF-alpha), transforming growth factor-beta (TGF-beta), interleukin-8 (IL-8) and reactivity of TGF-betaR and c-kit. Marked up-regulation of growth factors, cytokines and receptor expression was observed in thick (> 1 mm) primary melanomas, which were stained with polyclonal or monoclonal antibodies (MAbs) for IL-1alpha, IL-1beta, IL-6, IL-8, TNF-alpha, TGF-beta, granulocyte-macrophage colony-stimulating factor (GMCSF) and stem cell factor (SCF), but not IL-2. Metastases showed similar expression patterns except that SCF was absent. Co-expression of ligand and receptor was observed for TGF-beta, GM-CSF and IL-6, suggesting an autocrine role for these ligands. TNF-alpha appears to be a marker of benign lesions; IL-6 and IL-8 expression is associated with biologically early malignancy; TGF-beta, GM-CSF and IL-1alpha are highly expressed in biologically late lesions; and TNF-beta is an apparent marker of metastatic dissemination. Our results indicate that melanoma cells utilize cascades of growth factors and cytokines for their progression.

Squamous-cell carcinoma developing within anal lichen planus: report of a case.

AIM: We present a case of squamous-cell carcinoma developing within perianal lichen planus. This is a chronic or recurrent cutaneous and/or mucosal dermatosis affecting less than 1 percent of the population. Neoplastic degeneration of cutaneous lichen planus is rare; only one case of squamous-cell carcinoma developing within perianal lichen planus has been described up until now in the international literature. CASE REPORT: Our case involved a 68-year-old woman with chronic, long-term lichen planus spreading all over the vulva and perianal region and the mucosa of the anal canal, where squamous-cell carcinoma developed within the perianal lichen planus. Treatment consisted of wide, circular excision of the perianal skin and mucosectomy of the anal canal up to as far as 1 cm above the dentate line. Reconstruction was performed by means of two V-Y bilateral subcutaneous flaps. CONCLUSION: Wide excision was performed not only to remove the squamous-cell carcinoma but also the lichen planus to prevent recurrence of metachronous or synchronous squamous-cell carcinoma. Follow-up at one year after surgery showed no local recurrence of either lichen planus or squamous-cell carcinoma, which suggests that surgical removal should be the therapy of choice for long-term, chronic perianal lichen planus that has proved to be resistant to medical therapy.

[Phantom rectum after Miles' operation]. / Il retto fantasma dopo intervento di Miles.

The authors observed symptoms relating to the existence of a phantom rectum, a phenomenon about which little is still known, in 233 cases (32.1%) in a series of 724 patients undergoing amputation of the abdomino perineal rectum due to malignant neoplasm. The genesis of this phenomenon is attributed to an abnormal reactivity of the cortical and thalamic projection areas with greater response to stimuli from the stump or aspecific visceral stimuli, or even stimuli from the adjacent cortical regions. The psychodynamic aspects linked to the patient's need to develop a different body awareness should not be underestimated; this has to integrate a new anatomic reality, such as colostomy in the place of the anorectum, entailing the relinquishment of the previous body scheme. Prevention and treatment of phantom rectum, which is painful in 27% of cases, is essential for a correct operating technique, adequate psychotherapeutic support, the patient's active participation in a reeducation programme for colostomy management. It should not be forgotten that painful phantom rectum, especially with late onset, may be diagnostically significant as an indicator of the recurrence of neoplastic pathology, sometimes allowing diagnosis to be anticipated by several months. This underlines the importance of carrying out a careful postoperative clinical, biohumoral and radiological control in these patients, including pelvic CT. In the authors' experience of 233 patients suffering from phantom rectum, it was possible to document the presence of neoplastic recidivation in 30 cases (12.8%) using pelvic CT. In these cases, symptoms appeared after a disease-free interval of 26.3 months (range 3-75 months), whereas the presence of phantom rectum without recidivation is usually described in the first 2 months after surgery.

In situ expression of transforming growth factor beta is associated with melanoma progression and correlates with Ki67, HLA-DR and beta 3 integrin expression.

Transforming growth factor-beta (TGF beta), which is secreted by cultured melanoma cells constitutively, inhibits the proliferation of normal melanocytes and of most melanoma cells in vitro, but some melanoma cells from advanced stages of the disease develop resistance to TGF beta-dependent growth inhibition, without developing any change in TGF beta cell surface binding. In vitro TGF beta also downregulates the expression of HLA-DR molecules on melanoma cells, and upregulates the expression of the beta 3 integrin subunit on some cell lines. Immunohistochemical analysis of 53 melanocytic lesions (12 naevi, 30 primary melanomas and 11 metastases) revealed a trend of increasing expression of TGF beta and TGF beta receptor type III with tumour progression, and a significantly higher expression of both TGF beta (P < 0.0001) and the receptor (P < 0.05) in metastatic and thick (> 1 mm) primary melanomas compared with thin (< 1 mm) primary melanomas. The expression of TGF beta correlated with expression of a marker of proliferation, Ki67, and with HLA-DR and beta 3 integrin subunit expression. Coexpression of the four molecules was observed in all metastases and in most thick primary melanomas. These findings argue against an inhibitory effect of TGF beta on cell proliferation or HLA-DR antigen expression in melanoma, and suggest the upregulation of the beta 3 subunit. TGF beta protein appears to be a biological marker of melanoma progression in situ.

[Surgery of anal fistulas]. / La chirurgia delle fistole anali.

The authors report a study on 120 patients with anal fistula (111 males and 9 females). The average age was 44.3 years (median 44, SD +/- 14.807). 64.1% of patients had an intersphincteric fistula, 23.3% hanal transphincteric fistula, 1.6% a suprasphincteric fistula, 7.5% a horseshoe fistula and the 3.3% an extrasphincteric fistula. We treated 14 patients (11.66%) with direct surgical treatment. The other 106 had various types of treatment depending on the localisation and the involvement of the anorectal sphincter. We had 11 cases (9.1%) of complications, such as recurrence in 5 patients (4.1%) transitory incontinence in 2 cases (1.6%) and finally postoperative bleeding in 3 patients (2.5%).

Fibrogenic cytokines in vulvar lichen sclerosus. An immunohistochemical study.

OBJECTIVE: To evaluate the expression of fibrogenic cytokines in lichen sclerosus (LS) infiltrate as compared with lichen planus (LP) infiltrate. STUDY DESIGN: Eight cases of vulvar LS (early stage, n = 3; well developed or old, n = 5) and 4 of vulvar LP were studied. Monoclonal antibodies directed against some of the major fibrogenic cytokines (IL-4, TGF-beta, IL-6) and against IFN-gamma, which inhibits collagen synthesis, were used per the alkaline phosphatase/anti-alkaline phosphatase technique on frozen sections. RESULTS: Staining for IL-4 revealed higher expression of fibrogenic cytokines (more than 50% infiltrating cells) in the LS infiltrate, mainly in early lesions, than in LP. Conversely, staining for IFN-gamma in LS was poor (less than 10% infiltrating cells), while strong positivity (more than 60% infiltrating cells) was found in LP. Staining for TGF-beta, a mediator of fibrosis in scleroderma, was similar in both LS and LP dermis. CONCLUSION: This study showed the immunohistochemical expression of fibrogenic cytokines in vulvar LS, with a different pattern as compared to that of LP. It is conceivable that dermal infiltrating cells actively participate, via cytokine production, in the pathogenesis of fibrosis in LS.

[Rubber band ligation of hemorrhoids. Our experience]. / La legatura elastica delle emorroidi. Nostra esperienza.

The authors present their series of rubber band ligation of hemorrhoids performed from 1991 to 1994 in the Unità di Colon Proctologia of Modena, that is located in the Second Division of Surgery of the Surgical Department of Modena University. In that period 158 patients were treated. Age range was between 17 and 93 years old, and patients were affected by II and III degree of hemorrhoids. The complications verified were: 14 cases of recurrence (8.8%), 2 cases of severe bleeding, no case of perineal sepsis or urinary retention. Other complications of less importance were 89 cases of pain (56.3%), not severe bleeding in 23.41% of patients. Results show that this method of treatment of hemorrhoids, used by experts, is the first choice treatment of this pathology.

Vertical subcutaneous pedicle flaps for posterior perineal reconstruction. Report of three cases.

PURPOSE: Loss of a certain amount of cutaneous tissue of the perineal region may be remedied by first intention with creation of cutaneous flaps, thus preventing second intention healing. METHODS: We present three emblematic cases in which the posterior perineal region was reconstructed by means of vertical subcutaneous pedicle flaps, subsequent to cutaneous tissue loss after surgery for extensive condilomas or neoplastic pathologies. RESULTS: Tissue loss was repaired by means of a V-Y type vertical subcutaneous pedicle flap, constructed laterally of the extirpation zone and advanced in a median direction. In all cases, no ischemia or infection of flaps occurred; sphincteral continence and long-term aesthetic results have proved to be satisfactory. CONCLUSIONS: Vertical pedicle subcutaneous flaps are well vascularized, extremely mobile, and easy to perform and have no serious postoperative complications.