Tumor regression grade and survival after neoadjuvant treatment in gastro-esophageal cancer: A meta-analysis of 17 published studies.

INTRODUCTION: Major pathologic regression after neoadjuvant therapy is a strong and favorable prognostic factor in several types of cancer (breast, rectal and bladder). This information is less clear and has yet to be systematically evaluated in upper gastrointestinal tumors. We performed a meta-analysis to evaluate the prognostic impact of tumor regression after preoperative therapy on disease-free survival (DFS) and overall survival (OS) in gastro-esophageal cancer patients. METHODS: we searched for relevant articles in PubMed, SCOPUS, Web of Science, CINAHL, LILACS, Ovid, Cochrane Library, Google Scholar and Embase up to June 2, 2016. Data of tumor regression (complete or near-complete pathologic response) that independently correlated with OS and DFS in multivariate analysis were extracted, and the proper hazard ratios (HRs) with corresponding 95% confidence intervals (95% CIs) were pooled according to the random effect model. RESULTS: a total of 17 studies-which included 3145 patients-were considered in the final analysis. Major pathologic response was significantly related with better OS (HR 0.46, 95% CI 0.32-0.66, P < 0.001) and DFS (HR = 0.40, 95% CI 0.26-0.62, P < 0.001). Pathologic complete response (pCR) or major tumor regression were associated with the same degree of benefit in outcome compared to no or minimal pathologic regression, regardless of histology. CONCLUSION: major pathologic response is associated with a significant improvement in OS compared to no response or minor pathologic changes after neoadjuvant therapy in gastro-esophageal cancers. This should be considered a robust prognostic factor to guide postoperative treatment and follow-up.

Tumour Budding and Survival in Stage II Colorectal Cancer: a Systematic Review and Pooled Analysis.

PURPOSE: Tumour budding is defined as the presence of isolated or small clusters of malignant cells at the invasive edge of the tumour. It is considered a negative prognostic factor in colorectal cancer (CRC) and is associated with a poor outcome and adverse pathological features. Here, we report a meta-analysis of the association of tumour budding and survival in stage II CRC patients. METHODS: PubMed, EMBASE, Web of Science and SCOPUS were searched for studies that assessed the relationship between tumour budding and 5-year overall survival (OS) in stage II CRC patients. Published data were extracted and used to compute odds ratios (ORs) for death at 5 years and hazard ratios (HRs) for survival amongst patients with respect to the extent of tumour budding, using multivariate analysis. Data were pooled using the Mantel-Haenszel random effect model. RESULTS: We analysed 12 studies that included a total of 1652 patients. High-grade budding was associated with worse OS at 5 years (OR for death, 6.25; 95 % confidence interval [CI], 4.04-9.67; P < 0.00001). The absolute difference in 5-year OS was -25 % (95 % CI, -18- - 33 %, P < 0.00001). It was particularly noteworthy that the presence of high-grade budding was associated with an increased risk of death (HR for death, 3.68; 95 % CI, 2.16-6.28, P < 0.00001). CONCLUSIONS: Tumour budding is associated with worse survival in stage II CRC, in particular in pT3N0M0 patients. It could therefore potentially be used when deciding whether to administer adjuvant chemotherapy in high-risk node negative CRC patients.

[Neuroendocrine small-cell bladder cancer: our experience]. / Carcinoma neuroendocrino a piccole cellule della vescica; nostra esperienza.

INTRODUCTION: Neuroendocrine bladder cancer is extremely rare, with an estimated incidence of 0.35-0.70% of all bladder tumors. The small-cell carcinoma represents the most frequent histologic variant described. Small-cell carcinoma is an epithelial tumor associated with a more aggressive behavior and poorer prognosis than transitional cell bladder carcinoma. The overall survival rate at 5 years does not exceed 8%. At the time of presentation 59% of patients have clinical stage >T2 and 56% show metastatic disease. In 50% of the patients, fatal progression occurs within 6 months. Local recurrence after radical surgery occurred in 50-70% of cases. PATIENTS AND METHODS: We report three cases of pure neuroendocrine small-cell bladder cancer. Hematuria was the most common presenting symptom. Local advanced disease was present in all the cases with stage >T2, metastatic disease in 1 case, lymph node involvement and ureteral bilateral obstruction in 2. Two patients were treated by radical cystectomy, bilateral pelvic limph node resections and urinary derivation. Platinum-based adjuvant chemotherapy was proposed but only two patients received the treatment. One patient with liver metastasis was managed only by extensive TUR and support regimen. RESULTS: In 2 patients residual or relapsed cancer reappered within 2 months after surgery. All of the three patients died of metastatic disease at 5, 7, and 13 months. Median overall survival was 7 months. The most common site of relapse and spread of disease was the peritoneum and intestinal tract, and the reason of death was uncontrolled acute hemorrhage from gastro-intestinal district. CONCLUSIONS: In the absence of a prospective study, and because of the rarity of the disease, the best treatment for small-cell bladder cancer remains uncertain. Neoadjuvant chemotherapy with platinum regimen plus aggressive surgical approach will be the treatment of choice. The association of chemotherapy and radiotherapy should also be considered.

Malignant transformation of biliary cystadenoma: a difficult diagnosis.

The case is described of a 63-year-old female with a multilocular liver cyst diagnosed as cystadenoma after imaging and fine needle aspiration. The lesion, however, proved to be an invasive cystadenocarcinoma at surgery. Cystadenoma cannot be differentiated, preoperatively, from cystadenocarcinoma and should always be considered for surgical resection.

Pulmonary hyalinizing granuloma. A limited form of Wegener's granulomatosis?

Pulmonary hyalinizing granuloma is an uncommon disease that consists of slowly enlarging nodules in the pulmonary parenchyma. It occurs rarely: in fact, fewer than 70 case reports have been published in the past 20 years. It is important however in the differential diagnosis of lung diseases manifesting multiple pulmonary nodules. The etiology and pathogenesis of this disorder are unknown. Evidence suggests that the nodules could be the result of a chronic exaggerated immune response to infectious agents or to any other process in which antigen-antibody complexes are involved. More than 50% of the patients reported have evidence of autoimmune phenomena, e.g. positive antinuclear antibodies, a positive rheumatoid factor, or circulating immune complexes. The present report describes, for the first time, a case of pulmonary hyalinizing granuloma in which the patient had antineutrophil cytoplasmic autoantibodies with a granular cytoplasmatic pattern with typical central accentuation of fluorescence intensity and negative nuclei. The presence of antineutrophil cytoplasmic autoantibodies suggests that pulmonary hyalinizing granuloma could be regarded as a localized, non-evolving, form of Wegener's granulomatosis or a purely granulomatous Wegener's granulomatosis.

[Plasma-cell granuloma of the sigmoid colon concomitant with adenocarcinoma of the cecum. Viewpoint for debate, literature review on pseudotumors, idiopathic colitis and cancer]. / Concomitanza di granuloma plasmacellulare del sigma e adenocarcinoma del cieco. Spunto per una discussione ed una revisione della letteratura in tema di pseudotumori, coliti idiopatiche e cancro.

A case of colonic pseudotumor, causing intestinal occlusion, concomitant with a caecum neoplasia is reported. A male 69 years old was referred to our Institution for colic abdominal pain: colonoscopy aborted because of an insuperable sigma stenosis; diagnostic enema confirmed the sigmoid stenosis, originally advised as neoplastic. As operation, the sigmoid tumor appeared accompanied with enlarged draining lymph nodes and peritoneal sac was disseminated of miliary-like whity granules. Hystological examination showed a plasma-cell granuloma with nodular and peritoneal chronic inflammatory reaction. A pancolonoscopy, performed fourty days later, discovered an unsuspected adenocarcinoma neoplasia of the caecum, that was resected with a second operation. Regional nodes were not involved. The authors make a review of international literature about of plasma-cell granuloma, pseudotumor and inflammatory chronic bowel diseases in order to identify possible correlations between pseudotumor and neoplasms. The extremely low incidence of plasma-cell granulomas in the alimentary tract (17 case since 1970 to 1994) and the reported association with concomitant neoplasms (29%) suggest to consider extremely useful an accurate study of patients with intestinal pseudotumors in order to identify neoplasms of the gastrointestinal tract as well as of other organs.

[Carcinoid tumors of the cecal appendix]. / Tumori carcinoidi dell'appendice cecale.

The authors evaluate the incidence of carcinoid tumours out of a total of 2478 appendectomies performed between January 1984 and December 1991 at Treviglio Hospital. Histological tests, routinely performed on all appendixes removed, have revealed an incidence of 0.56% of this disease. Lesions are clinically silent in all cases. In fact, the finding of a carcinoid tumour was coincidental in 12 patients undergoing appendectomy for symptoms of appendicitis, and in two cases in which appendectomy was initially performed during the course of hysterectomy. Eleven cases were histologically of the classical type, including one with a "balloon cell" variant. Lastly, three cases were tubular type adenocarcinoids. In all cases treatment took the form of simple appendectomy. Follow-up studies are still in progress which have enabled the recidivation of neoplasia to be excluded in all patients, even 11 years after treatment.

Aortoesophageal fistula. Report of one case complicating foreing body ingestion with considerations about pathogenesis.

Aorto-esophageal fistula is a very rare disease and few cases are reported. The most frequent ethiological factors are foreign body ingestion primary disease of esophagus or aorta and iatrogenic damages in particular endoscopical investigations. In this report a new case is described and a pathogenic explanation for the development of the disease is proposed.

[Metastatic malignant melanoma of the ovary]. / Melanoma maligno metastatico dell'ovaio.

We report 2 cases of ovarian metastases of malignant melanoma arisen 4 and 6 years after the removal of the primitive epithelial neoplasia. In both cases the ovarian neoplasia was unilateral. Both the macroscopic and the histological aspects of the malignant melanoma were examined. From both cases it was clear that it was a solid neoplasia with histological aspect of wide epithelioid cells with abundant cytoplasm and intracytoplasmatic melanotic pigment. The immunohistochemical results supported positivity for protein S100, vimentine and HMB45, negativity for cytokeratine.

[A mucinous ovarian tumor with foci of anaplastic carcinoma]. / Tumore ovarico mucinoso con foci di carcinoma anaplastico.

One ovarian mucinous cystic tumor that contained a mural solid nodule of anaplastic carcinoma is described in a 35-year-old woman. The epithelial elements consisted of invasive well differentiated mucinous carcinoma. The anaplastic nodule showed some similarities with the cells described in sarcoma and sarcoma-like mural nodules. In favor of a diagnosis of anaplastic carcinoma there are poor circumscription of the nodules, vascular invasion and absence of a prominent inflammatory reaction.

[Epithelial changes associated with invasive epidermoid carcinoma of the vulva]. / Alterazioni epiteliali associate al carcinoma epidermoide invasivo della vulva.

The frequency and meaning of epithelial alterations adjacent to a vulvar invasive carcinoma are examined. In the period from 1986 to 1989, 37 cases of vulvar invasive carcinoma were observed in the Bergamo Hospital (Anatomopathology Institute of Bergamo) in women aged between 54-95 years operated for vulvectomy. The vulvar epithelium adjacent to the invasive carcinoma was studied in order to determine the frequency and the type of associated lesions. Two lesions seem to be meaningfully correlated to the vulvar carcinoma: the lichen sclerosus in 59% of cases and the VIN3 of differentiated type in 35%. The identification of these epithelial lesions can serve to select the cases with increased risk to develop invasive carcinoma.

[Blue nevus of the uterine cervix]. / Il nevo blu della cervice uterina.

Seven cases of blue nevus of the endocervix were examined macroscopically and histologically. The endocervical blue nevus is a rare lesion which can be incidentally found in surgical pieces after hysterectomy in middle-aged women. It looks like a blue-blackish little lesion, located superficially in the submucosa of the endocervix. The immunohistochemical results are positive for Protein S100 of the nevus cells. Due of its localization in the cervical duct the lesion can be hardly identified through colposcopy. Histogenetical hypotheses are finally discussed.

Primary mediastinal seminoma.

We describe three cases of primary mediastinal seminoma, a rare neoplasm histologically similar to the testicular form, which mainly affects men between 30-60 yrs of age. Case No. 1--a 45 year old patient was treated with a combination of radiotherapy and chemotherapy. Twenty six months after the diagnosis, the patient shows a limited residual lesion, a good general health status and was asymptomatic. Case No. 2--a 56 year old patient was admitted for suspected epithelial lung cancer, with subsequent histological diagnosis of seminoma on surgical sample. The exeresis of the lesion was followed by radiotherapy and chemotherapy, the latter interrupted owing to the onset of thrombotic complications resulting in the patient's death. Case No. 3--a 35 year old patient was subjected to diagnostic and therapeutic thoracotomy, with diagnosis of primary mediastinal seminoma. The surgical therapy was followed by a cycle of radiotherapy. Five years later, the general health of the patient is good and he is still asymptomatic. In the discussion we consider the embryogenesis, clinical picture, radiological and anatomicopathological aspects, typical biomarkers of cancer, diagnostic procedures and therapeutic protocols currently followed.

Combined Clark's nevus.

We report five cases of combined Clark's nevi. Like all melanocytic nevi, Clark's nevus can combine with other nevi to produce lesions that are hard to interpret clinically and histologically. The morphology of combined Clark's nevus can resemble that of a melanoma associated with a nevus.

[Transcervical electric resection in submucous myomas]. / Elettroresezione transcervicale dei miomi sottomucosi.

Twenty-five patients underwent hysteroscopic resection of large symptomatic intrauterine fibroids. Patients were divided into one of three groups: those with pedunculated myomas (G0), those with intramural extension less than 50% (G1), and those with fibroids with intramural extension more than 50% (G2). In the first group (7 patients) the age ranged from 42-52 years (mean age 48 years), the operating time ranged from 15-60 min. (mean time 27 minutes), and the amount of fluid used for irrigation ranged from 1000-10000 ml (mean fluid 4400 ml). Four of the seven patients had concomitant endometrial polyps. Follow-up ranged from 3-32 months (mean 21 months), one patient was lost, and the success rate in 6 was 100%. In the second group (9 patients) the age ranged from 30-54 years (mean age 43.5 years), the operating time ranged from 35-90 minutes (mean time 62 minutes), and the amount of fluid used ranged from 2800-12500 ml (mean fluid 7150 ml). In one case endometrial ablation was associated. Two patients (45 and 54 years) had histopathological diagnosis of malignancy (endometrial stromal nodule and stromal myoma) and required hysterectomy. No residual stromal nodule was found in the uterus following hysteroscopy resection in one case. Follow-up ranged from 6-38 months (mean 20 months), two patients was lost and one had repeat hysteroscopic procedure. Four of the nine patients had a successful outcome.(ABSTRACT TRUNCATED AT 250 WORDS)

[An adenomatoid tumor of the uterus]. / Tumore adenomatoide dell'utero.

Three adenomatoid tumors of the uterus were examined. These tumors arising in the uterus are often regarded as incidental findings at operation, and are sometimes not well recognized at the time of diagnosis. They are small nodular lesions in the wall of the myometrium. Microscopically they presented with four distinctive histologic types, and immunohistochemically gave positive staining for keratin and for the mesothelial marker. The immunohistochemical results support the theories of histogenesis of the adenomatoid tumor as a type of benign mesothelioma.

Endometrioid carcinoma in pelvic endometriosis in a postmenopausal woman with tamoxifen adjuvant therapy for breast cancer. A case report.

This concerns a 57 year old woman operated on in 1988 for a left radical mastectomy due to ductal breast carcinoma and subsequently treated with chemotherapy and Tamoxifen adjuvant. In 1990 a laparo-hystero-oophorectomy was carried out due to uterine fibromas. The woman continued taking Tamoxifen. Two years later a pelvic regeneration appeared, resulting in endometriosis, site of adenomatose hyperplasia and of endometrioid carcinoma GI. This furthermore confirms the importance of a gynecological follow-up for all women treated with Tamoxifen adjuvant therapy.

[Prostatic tissue in a cystic teratoma of the ovary]. / Tessuto prostatico in un teratoma cistico dell'ovaio.

We report one example of mature cystic teratoma of the ovary containing prostatic tissue, in a 73 year-old female. The tumor is typical and it is composed of well-differentiated derivatives of the three germ layers. Prostatic tissue was an incidental finding in teratoma. This tissue contained ducts and acini in a simple branching pattern similar to that seen in the peripheral zone of the prostatic gland. The immunohistochemical stainings for PSA and PSAP throughout the glandular cells were similar to those present in normal prostate.

Ovarian carcinomas with choriocarcinomatous differentiation.

BACKGROUND: Ovarian carcinomas may produce human chorionic gonadotropin (HCG) or HCG-like substances and may even contain syncytiotrophoblast cells, but a true choriocarcinomatous component has not been described in these tumors. METHODS: Two cases of poorly differentiated ovarian carcinoma with choriocarcinomatous components are reported. Pathologic findings were correlated with immunohistochemical stains, hormonal effects, and clinical behavior. RESULTS: Each tumor contained a circumscribed, extensively necrotic and hemorrhagic brown nodule. Microscopically, the nodules exhibited a mixture of cytotrophoblast and syncytiotrophoblast. The syncytiotrophoblast capped cytotrophoblast and was strongly positive for beta-HCG. In one of the cases, a transformation zone composed of poorly differentiated carcinoma with occasional beta-HCG-positive cells was observed between a mucinous cystadenoma and the choriocarcinomatous elements. The two cases exhibited activation of the ovarian stroma in the form of condensation and luteinization. Extra-abdominal metastases developed early in both patients and, despite multiagent chemotherapy, they died shortly postoperatively. CONCLUSIONS: Choriocarcinoma may rarely develop as a result of dedifferentiation of common epithelial ovarian tumors. Recognition of choriocarcinomatous components in ovarian carcinomas is important because of its association with aggressive behavior.

[Giant-cell arteritis of the female genital tract]. / Arterite a cellule giganti del tratto genitale femminile.

One case of giant-cell arteritis involving the female genital tract of a post-menopausal woman is reported. The patient was a 75 year-old female, who presented anemia, fatigue, weight loss and a palpable abdominal mass. A hysterectomy and bilateral salpingo-oophorectomy proved multiple uterine leiomyomas. The uterus, ovaries and tubes unexpectedly revealed extensive giant-cell arteritis of small and medium sized vessels. Giant-cell arteritis of the female genital tract is a rare finding that may occur as an isolated form or as part of generalized giant cell arteritis.